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  • 1
    Publication Date: 2018-07-20
    Description: Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor B activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC.
    Keywords: Cell Biology, Medicine, Diseases
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-10-17
    Description: Neural stem cells show age-dependent developmental potentials, as evidenced by their production of distinct neuron types at different developmental times. Drosophila neuroblasts produce long, stereotyped lineages of neurons. We searched for factors that could regulate neural temporal fate by RNA-sequencing lineage-specific neuroblasts at various developmental times. We found that two RNA-binding proteins, IGF-II mRNA-binding protein (Imp) and Syncrip (Syp), display opposing high-to-low and low-to-high temporal gradients with lineage-specific temporal dynamics. Imp and Syp promote early and late fates, respectively, in both a slowly progressing and a rapidly changing lineage. Imp and Syp control neuronal fates in the mushroom body lineages by regulating the temporal transcription factor Chinmo translation. Together, the opposing Imp/Syp gradients encode stem cell age, specifying multiple cell fates within a lineage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Zhiyong -- Yang, Ching-Po -- Sugino, Ken -- Fu, Chi-Cheng -- Liu, Ling-Yu -- Yao, Xiaohao -- Lee, Luke P -- Lee, Tzumin -- R01-GM084947/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):317-20. doi: 10.1126/science.aad1886.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA, USA. ; Howard Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA, USA. Departments of Bioengineering, Electrical Engineering, and Computer Science, and Biophysics Graduate Program, University of California Berkeley, 408C Stanley Hall, Berkeley, CA, USA. ; Departments of Bioengineering, Electrical Engineering, and Computer Science, and Biophysics Graduate Program, University of California Berkeley, 408C Stanley Hall, Berkeley, CA, USA. ; Howard Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA, USA. leet@janelia.hhmi.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472907" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Lineage ; Drosophila Proteins/genetics/metabolism/*physiology ; Drosophila melanogaster/genetics/*growth & development ; Mushroom Bodies/cytology/growth & development ; Nerve Tissue Proteins/metabolism ; Neural Stem Cells/*cytology ; Neurogenesis/genetics/*physiology ; Neurons/*cytology ; RNA-Binding Proteins/genetics/*physiology ; Sequence Analysis, RNA
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2018-06-02
    Description: Objective Although the role of microRNA-17 (miR-17) has been identified as a tumour biomarker in various studies, its prognostic value in cancers remains unclear. Therefore, we performed a systematic review and meta-analysis to analyse and summarise the relationship between the miR-17 status and clinical outcome in a variety of human cancers. Design Systematic review and meta-analysis. Data sources PubMed, Web of Science and Embase from the first year of records to 15 May 2017. Outcomes The patients’ survival results were pooled, and pooled HRs with 95% CIs were calculated and used for measuring the strength of association between miR-17 and the prognosis of cancers, including hepatocellular carcinoma, lung cancer, osteosarcoma, glioma, T-cell lymphoblastic lymphoma and colon cancer. Heterogeneity, publication bias and subgroup analysis were also conducted. Results A total of 1096 patients were included in this meta-analysis from 12 articles. The results indicated that the increased expression of miR-17 played an unfavourable role in overall survival in various human carcinomas with the HR of 1.342 taking into account the publication bias. In subgroup analysis, HR of ethnicity (Caucasian HR=1.48 and Asian HR=1.40), disease (digestive system HR=1.36 and blood system cancer (HR=2.38), detection method (quantitative real-time PCR HR=1.40 and in situ hybridisation, HR=2.59) and detection sample (tissue HR=1.45 and serum HR=1.32) were significant with p〈0.05. For the analysis of disease-free survival and recurrence-free survival, the increased expression of miR-17 was associated with unfavourable prognosis (HR=1.40). Conclusions miR-17 may be a useful biomarker in predicting the clinical outcome of human cancers, but due to the limitations of the current studies, further verification of the role of miR-17 in human malignancies is urgently needed. PROSPERO registration number CRD42017065749
    Keywords: Open access, Genetics and genomics
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 4
    Publication Date: 2018-02-16
    Description: Objectives To describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China. Design This was a multicentre, retrospective, observational study. Setting 13 teaching hospitals in northern, central and southern China from 1 January 2014 to 31 December 2014 Participants Information on hospitalised patients aged ≥14 years with radiographically confirmed pneumonia with illness onset in the community was collected using standard case report forms. Primary and secondary outcome measures Resource use for CAP management. Results Of 14 793 patients screened, 5828 with radiographically confirmed CAP were included in the final analysis. Low mortality risk patients with a CURB-65 score 0–1 and Pneumonia Severity Index risk class I–II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients, respectively. 21.7% (1111/5130) patients had already achieved clinical stability on admission. A definite or probable pathogen was identified only in 12.7% (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection risk factors received antimicrobial overtreatment regimens. The median duration between clinical stability to discharge was 5.0 days with 30-day mortality of 4.2%. Conclusions These data demonstrated the overuse of health resources in CAP management, indicating that there is potential for improvement and substantial savings to healthcare systems in China. Trial registration number NCT02489578 ; Results.
    Keywords: Open access, Infectious diseases
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 5
    Publication Date: 2018-01-06
    Description: The origin of the pseudogap region below a temperature T * is at the heart of the mysteries of cuprate high-temperature superconductors. Unusual properties of the pseudogap phase, such as broken time-reversal and inversion symmetry are observed in several symmetry-sensitive experiments: polarized neutron diffraction, optical birefringence, dichroic angle-resolved photoemission spectroscopy, second harmonic generation, and polar Kerr effect. These properties suggest that the pseudogap region is a genuine thermodynamic phase and are predicted by theories invoking ordered loop currents or other forms of intra-unit-cell (IUC) magnetic order. However, muon spin rotation (μSR) and nuclear magnetic resonance (NMR) experiments do not see the static local fields expected for magnetic order, leaving room for skepticism. The magnetic resonance probes have much longer time scales, however, over which local fields could be averaged by fluctuations. The observable effect of the fluctuations in magnetic resonance is then dynamic relaxation. We have measured dynamic muon spin relaxation rates in single crystals of YBa 2 Cu 3 O y (6.72 〈 y 〈 6.95) and have discovered "slow" fluctuating magnetic fields with magnitudes and fluctuation rates of the expected orders of magnitude that set in consistently at temperatures T mag T *. The absence of any static field (to which μSR would be linearly sensitive) is consistent with the finite correlation length from neutron diffraction. Equally important, these fluctuations exhibit the critical slowing down at T mag expected near a time-reversal symmetry breaking transition. Our results explain the absence of static magnetism and provide support for the existence of IUC magnetic order in the pseudogap phase.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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