1,255 research outputs found

    Data based reconstruction of complex geospatial networks, nodal positioning, and detection of hidden node

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    Funding This work was supported by ARO under grant no. W911NF-14-1-0504.Peer reviewedPublisher PD

    The contribution of methionine to the stability of the Escherichia coli MetNIQ ABC transporter-substrate binding protein complex

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    Despite the ubiquitous role of ATP-binding cassette (ABC) importers in nutrient uptake, only the Escherichia coli maltose and vitamin B_(12) ABC transporters have been structurally characterized in multiple conformations relevant to the alternating access transport mechanism. To complement our previous structure determination of the E. coli MetNI methionine importer in the inward facing conformation (Kadaba et al. (2008) Science 321, 250-253), we have explored conditions stabilizing the outward facing conformation. Using two variants, the Walker B E166Q mutation with ATP+EDTA to stabilize MetNI in the ATPbound conformation and the N229A variant of the binding protein MetQ, shown in this work to disrupt methionine binding, a high affinity MetNIQ complex was formed with a dissociation constant measured to be 27 nm. Using wild type MetQ containing a co-purified methionine (for which the crystal structure is reported at 1.6 Å resolution), the dissociation constant for complex formation with MetNI is measured to be ~40-fold weaker, indicating that complex formation lowers the affinity of MetQ for methionine by this amount. Preparation of a stable MetNIQ complex is an essential step towards the crystallographic analysis of the outward facing conformation, a key intermediate in the uptake of methionine by this transport system

    A geometrical approach to control and controllability of nonlinear dynamical networks

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    Acknowledgements This work was supported by the ARO under Grant No. W911NF-14-1-0504. X.W. was supported by the NIH under Grant No. GM106081.Peer reviewedPublisher PD

    PinX1 regulation of telomerase activity and apoptosis in nasopharyngeal carcinoma cells

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    <p>Abstract</p> <p>Background</p> <p>Human interacting protein X1 (PinX1) has been identified as a critical telomerase inhibitor and proposed to be a putative tumor suppressor gene. Loss of PinX1 has been found in a large variety of malignancies, however, its function in inhibiting telomerase activity of tumor cells is not well documented. Here we show that PinX1 is essential for down-regulation telomerase activity of nasopharyngeal carcinoma.</p> <p>Methods</p> <p>Expression vectors of human PinX1 (pEGFP-C3-PinX1) and its small interfering RNA (PinX1-FAM-siRNA) were constructed and transfected into NPC. Their effects on mRNA of telomerase catalytic subunit (hTERT), telomerase activity, cell proliferation, cell migration, wound healing, cell cycles and apoptosis were examined using semi-quantitative RT-PCR, stretch PCR, MTT assay, Transwell, scratch assay and flow cytometry, respectively.</p> <p>Results</p> <p>Transfection of pEGFP-C3-PinX1 and PinX1-FAM-siRNA increased and reduced PinX1 mRNA by 1.6-fold and 70%, respectively. Over-expression of PinX1 decreased hTERT mRNA by 21%, reduced telomerase activity, inhibited cell growth, migration and wound healing ability, arrested cells in G0/G1 phase, and increased apoptotic index. In contrast, down-regulation of PinX1 did not alter the above characteristics.</p> <p>Conclusions</p> <p>PinX1 may play important roles in NPC proliferation, migration and apoptosis and has application potential in tumor-targeted gene therapy.</p

    Direct synthesis of ultrafine tetragonal BaTiO3 nanoparticles at room temperature

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    A large quantity of ultrafine tetragonal barium titanate (BaTiO3) nanoparticles is directly synthesized at room temperature. The crystalline form and grain size are checked by both X-ray diffraction and transmission electron microscopy. The results revealed that the perovskite nanoparticles as fine as 7 nm have been synthesized. The phase transition of the as-prepared nanoparticles is investigated by the temperature-dependent Raman spectrum and shows the similar tendency to that of bulk BaTiO3 materials. It is confirmed that the nanoparticles have tetragonal phase at room temperature

    Comparative evaluation of the diagnosis, reporting and investigation of malaria cases in China, 2005-2014: transition from control to elimination for the national malaria programme

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    Background: The elimination of malaria requires high-quality surveillance data to enable rapid detection and response to individual cases. Evaluation of the performance of a national malaria surveillance system could identify shortcomings which, if addressed, will improve the surveillance program for malaria elimination.Methods: Case-level data for the period 2005–2014 were extracted from the China National Notifiable Infectious Disease Reporting Information System and Malaria Enhanced Surveillance Information System. The occurrence of cases, accuracy and timeliness of case diagnosis, reporting and investigation, were assessed and compared between the malaria control stage (2005–2010) and elimination stage (2011–2014) in mainland China.Results: A total of 210 730 malaria cases were reported in mainland China in 2005–2014. The average annual incidence declined dramatically from 2.5 per 100 000 people at the control stage to 0.2 per 100 000 at the elimination stage, but the proportion of migrant cases increased from 9.8 % to 41.0 %. Since the initiation of the National Malaria Elimination Programme in 2010, the overall proportion of cases diagnosed by laboratory testing consistently improved, with the highest of 99.0 % in 2014. However, this proportion was significantly lower in non-endemic provinces (79.0 %) than that in endemic provinces (91.4 %) during 2011–2014. The median interval from illness onset to diagnosis was 3 days at the elimination stage, with one day earlier than that at the control stage. Since 2011, more than 99 % cases were reported within 1 day after being diagnosed, while the proportion of cases that were reported within one day after diagnosis was lowest in Tibet (37.5 %). The predominant source of cases reporting shifted from town-level hospitals at the control stage (67.9 % cases) to city-level hospitals and public health institutes at the eliminate stage (69.4 % cases). The proportion of investigation within 3 days after case reporting has improved, from 74.6 % in 2010 to 98.5 % in 2014.Conclusions: The individual case-based malaria surveillance system in China operated well during the malaria elimination stage. This ensured that malaria cases could be diagnosed, reported and timely investigated at local level. However, domestic migrants and overseas populations, as well as cases in the historically malarial non-endemic areas and hard-to-reach area are new challenges in the surveillance for malaria elimination.<br/

    BEN-solo factors partition active chromatin to ensure proper gene activation in Drosophila

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    The Drosophila genome encodes three BEN-solo proteins including Insensitive (Insv), Elba1 and Elba2 that possess activities in transcriptional repression and chromatin insulation. A fourth protein—Elba3—bridges Elba1 and Elba2 to form an ELBA complex. Here, we report comprehensive investigation of these proteins in Drosophila embryos. We assess common and distinct binding sites for Insv and ELBA and their genetic interdependencies. While Elba1 and Elba2 binding generally requires the ELBA complex, Elba3 can associate with chromatin independently of Elba1 and Elba2. We further demonstrate that ELBA collaborates with other insulators to regulate developmental patterning. Finally, we find that adjacent gene pairs separated by an ELBA bound sequence become less differentially expressed in ELBA mutants. Transgenic reporters confirm the insulating activity of ELBA- and Insv-bound sites. These findings define ELBA and Insv as general insulator proteins in Drosophila and demonstrate the functional importance of insulators to partition transcription units

    A novel scoring system for the quantitative prediction of prognosis in acute myeloid leukemia

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    BackgroundAcute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy. Patient prognosis cannot be accurately assessed in National Comprehensive Cancer Network (NCCN) risk stratification subgroups based on the current criteria. This study aimed to develop a novel prognostic score model for the quantitative prediction of prognosis in AML.ResultsWe developed a prognostic risk scoring model of AML using differentially expressed genes to predict prognosis in patients with AML. Furthermore, we evaluated the effectiveness and clinical significance of this prognostic model in 4 AML cohorts and 905 patients with AML. A prognostic risk scoring model of AML containing eight prognosis-related genes was constructed using a multivariate Cox regression model. The model had a higher predictive value for the prognosis of AML in the training and validation sets. In addition, patients with lower scores had significantly better overall survival (OS) and even-free survival (EFS) than those with higher scores among patients with intermediate-risk AML according to the NCCN guidelines, indicating that the model could be used to further predict the prognosis of the intermediate-risk AML populations. Similarly, patients with high scores had remarkably poor OS and EFS in the normal-karyotype populations, indicating that the scoring model had an excellent predictive performance for patients with AML having normal karyotype.ConclusionsOur study provided an individualized prognostic risk score model that could predict the prognosis of patients with AML

    Voluntary Wheel Running Reverses Deficits in Social Behavior Induced by Chronic Social Defeat Stress in Mice: Involvement of the Dopamine System

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    Voluntary exercise has been reported to have a therapeutic effect on many psychiatric disorders and social stress is known to impair social interaction. However, whether voluntary exercise could reverse deficits in social behaviors induced by chronic social defeat stress (CSDS) and the underlying mechanism remain unclear. The present study shows CSDS impaired social preference and induced social interaction deficiency in susceptible mice. Voluntary wheel running (VWR) reversed these effects. In addition, CSDS decreased the levels of tyrosine hydroxylase in the ventral tegmental area and the D2 receptor (D2R) in the nucleus accumbens (NAc) shell. These changes can be recovered by VWR. Furthermore, the recovery effect of VWR on deficits in social behaviors in CSDS mice was blocked by the microinjection of D2R antagonist raclopride into the NAc shell. Thus, these results suggest that the mechanism underlying CSDS-induced social interaction disorder might be caused by an alteration of the dopamine system. VWR may be a novel means to treat CSDS-induced deficits in social behaviors via modifying the dopamine system

    ABSCISIC ACID-INSENSITIVE 5-KIP-RELATED PROTEIN 1-SHOOT MERISTEMLESS modulates reproductive development of Arabidopsis

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    Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5–KRP1–STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency
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