214 research outputs found

    Neuronal functions of ahr-1, the Caenorhabditis elegans homolog of the aryl hydrocarbon receptor

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    The mammalian aryl hydrocarbon receptor (AHR) mediates the toxic effects of dioxins and related compounds. Toxicological and genetic studies have shown that AHR regulates important development events and physiological functions. Interestingly, AHR homologs are found in most metazoans, and studies of AHR regulation and function in invertebrate model systems may provide insight to the ancient functions of AHR. In this thesis, I analyze the endogenous functions of the ahr-1 gene in the nematode Caenorhabditis elegans. ahr-1:GFP is expressed in a subset of neurons. ahr-1 regulates the development of diverse neuronal cell types, including the AVM and PLM touch receptor neurons and the SDQR interneuron. Dorsal migration of the SDQR neuron requires the normal functions of both ahr-1 and its transcription factor dimerization partner ahr-1. Further, I show that UNC-6/Netrin, SAX-3/Robo, and UNC-129/TGFbeta also have roles in this migration event. In the URXL and URXR neurons, the UNC-86 transcription factor promotes expression of ahr-1, and the AHR-1 transcriptional complex then activates the expression of certain cell type specific markers, including gcy-32:GFP and npr-1:GFP. These data show that the AHR-1 transcriptional complex acts in combination with other intrinsic and extracellular factors to direct the differentiation of distinct neuronal subtypes;In addition to its roles in neural development, ahr-1 also functions acutely to regulate a specific behavior: the aggregation of C. elegans on lawns of bacterial food. Loss-of-function mutations in ahr-1 or aha-1 suppress aggregation behavior in npr-1-deficient animals. Expression of ahr-1 in only 4 neurons, including URXR and URXL, restores aggregation behavior to ahr-1 mutant animals. Aggregation behavior can be restored to ahr-1-deficient animals by heat-shock induction of ahr-1 expression several hours after development of the URX neurons is normally complete. Mutants defective in ahr-1 or aha-1 express the gcy-32, gcy-34, and gcy-35 soluble guanylate cyclase (sGC) reporter genes at markedly reduced levels. These genes have been shown to have key roles in regulating aggregation behavior. Collectively, these data support a model in which the AHR-1:AHA-1 transcription complex regulates the expression of sGCs and other unidentified genes that act acutely in the URX neurons to promote aggregation behavior

    Origin of the high sensitivity of Chinese red clay soils to drought: significance of the clay characteristics

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    International audienceThe red clay soils which are widespread in China are known to be highly sensitive to drought during the dry season but the origin of this high sensitivity to drought remains unclear. Several red clay soils were selected in the Hunan province for study. We studied their basic physico-chemical properties and clay mineralogy, their structure and shrinkage properties, as well as their water retention properties. Results show that the amount of water available between -330 and -15 000 hPa water potential is consistent with that recorded in many other clay soils from different parts of the world and thus cannot explain the high sensitivity of the red clay soils to drought. This high sensitivity to drought might be related to the high proportion of poorly available water which was characterized by the amount of available water between -3300 and -15 000 hPa water potential. Comparison with clay soils located in different parts of the world and for which the sensitivity to drought was not identified, showed that this proportion of poorly available water is indeed much higher in the red clay soils studied than in clay soils representing a large range of both clay content and mineralogy. This specific behaviour of the red clay soils studied is thought to be related to the history of their parent materials: these materials are continental sediments which may have been submitted to great hydric stress, thus leading to strongly consolidated soils with consequences such as a high proportion of poorly available water, strong aggregation and weak shrinkage properties

    Twofold Symmetry Observed in Bi2_{2}Te3_{3}/FeTe Interfacial Superconductor

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    Superconducting pairing symmetry are crucial in understanding the microscopic superconducting mechanism of a superconductor. Here we report the observation of a twofold superconducting gap symmetry in an interfacial superconductor Bi2_{2}Te3_{3}/FeTe, by employing quasiparticle interference (QPI) technique in scanning tunneling microscopy and macroscopic magnetoresistance measurements. The QPI patterns corresponding to energies inside and outside the gap reveal a clear anisotropic superconducting gap. Furthermore, both the in-plane angle-dependent magnetoresistance and in-plane upper critical field exhibit a clear twofold symmetry. This twofold symmetry align with the Te-Te direction in FeTe, which weakens the possible generation by bi-collinear antiferromagnetism order. Our finding provides key information in further understanding of the topological properties in Bi2_{2}Te3_{3}/FeTe superconducting system and propels further theoretical interests in the paring mechanism in the system

    Soybean Breeding on Seed Composition Trait

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    Soybean is a most important crop providing edible oil and plant protein source for human beings, in addition to animal feed because of high protein and oil content. This review summarized the progresses in the QTL mapping, candidate gene cloning and functional analysis and also the regulation of soybean oil and seed storage protein accumulation. Furthermore, as soybean genome has been sequenced and released, prospects of multiple omics and advanced biotechnology should be combined and applied for further refine research and high-quality breeding

    Non-contrast computed tomography-based radiomics for staging of connective tissue disease-associated interstitial lung disease

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    Rationale and introductionIt is of significance to assess the severity and predict the mortality of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). In this double-center retrospective study, we developed and validated a radiomics nomogram for clinical management by using the ILD-GAP (gender, age, and pulmonary physiology) index system.Materials and methodsPatients with CTD-ILD were staged using the ILD-GAP index system. A clinical factor model was built by demographics and CT features, and a radiomics signature was developed using radiomics features extracted from CT images. Combined with the radiomics signature and independent clinical factors, a radiomics nomogram was constructed and evaluated by the area under the curve (AUC) from receiver operating characteristic (ROC) analyses. The models were externally validated in dataset 2 to evaluate the model generalization ability using ROC analysis.ResultsA total of 245 patients from two clinical centers (dataset 1, n = 202; dataset 2, n = 43) were screened. Pack-years of smoking, traction bronchiectasis, and nine radiomics features were used to build the radiomics nomogram, which showed favorable calibration and discrimination in the training cohort {AUC, 0.887 [95% confidence interval (CI): 0.827–0.940]}, the internal validation cohort [AUC, 0.885 (95% CI: 0.816–0.922)], and the external validation cohort [AUC, 0.85 (95% CI: 0.720–0.919)]. Decision curve analysis demonstrated that the nomogram outperformed the clinical factor model and radiomics signature in terms of clinical usefulness.ConclusionThe CT-based radiomics nomogram showed favorable efficacy in predicting individual ILD-GAP stages

    Anti-tumor activity against multiple myeloma by combination of KW-2478, an Hsp90 inhibitor, with bortezomib

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    Heat shock protein 90 (Hsp90) is a promising target for anti-tumor therapy. We previously reported the anti-tumor activity of a novel Hsp90 inhibitor, KW-2478, in multiple myeloma (MM) as a single agent. In this study, we examined the combinational effect of KW-2478 and bortezomib, a proteasome inhibitor, in vitro and in vivo. In vitro, KW-2478 enhanced bortezomib-induced cell growth inhibition, both in MM cell lines and primary patient MM cells. The combination of KW-2478 and bortezomib also induced caspase activation in MM cell lines. Interestingly, the combination synergistically enhanced the expression of Hsp70B, a homolog of Hsp70, in human MM cells and peripheral blood mononuclear cells, indicating Hsp70B could be a surrogate biomarker for the combination of Hsp90 and proteasome inhibitors. In vivo, the combination of KW-2478 with bortezomib showed synergistic anti-tumor activity without significant body weight loss in a subcutaneously inoculated human myeloma model. Furthermore, the combination also showed synergistic reduction of tumor burden in bone marrow in an orthotopic myeloma model. Our results strongly suggest that combination of KW-2478 with bortezomib could exhibit enhanced anti-tumor activity against human myeloma
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