Sex differences in emotional behaviors and affective disorders have been widely noted, of which sexually dimorphic secretion of gonadal steroid hormones such as estrogen is suspected to play a role. ...However, the underlying neural mechanisms remain poorly understood. We noted that the expression of estrogen receptor 2 (Esr2, or ERβ), a key mediator of estrogen signaling in the brain, was enriched in the dorsal raphe nucleus (DRN), a region involved in emotion regulation. To investigate whether DRN Esr2 expression confers sex‐specific susceptibility or vulnerability in emotional behaviors, we generated a conditional allele of Esr2 that allowed for site‐specific deletion of Esr2 in the DRN via local injection of Cre‐expressing viruses. DRN‐specific Esr2 deletion mildly increased anxiety behaviors in females, as shown by decreased time spent in the center zone of an open field in knockout females. By contrast, DRN Esr2 deletion had no effects on anxiety levels in males, as demonstrated by knockout males spending comparable time in the center zone of an open field and open arms of an elevated‐plus maze. Furthermore, in the tail suspension test, DRN Esr2 deletion reduced immobility, a depression‐like behavior, in a male‐biased manner. Together, these results reveal sex‐specific functions of DRN Esr2 in regulating emotional behaviors and suggest targeted manipulation of DRN Esr2 signaling as a potential therapeutic strategy to treat sex‐biased affective disorders.
A subset of 5‐HT+ neurons in the dorsal raphe nucleus (DRN) expresses the estrogen receptor 2 (Esr2). Cre‐mediated deletion of Esr2 expression in a newly generated conditional mouse line (Esr2fl/fl) led to sexually dimorphic effects on emotional behaviors in mice, increasing anxiety in females and reducing despair‐like behavior in males.
In this paper, analytical equation-based solutions are derived to allow quick and accurate calculations directly from the physical parameters of coupled, asymmetrical, lossy, and nonuniform ...microstrip lines with interdigital trapezoidal tabs incorporated, resulting in their corresponding scattering parameters. Capacitance and inductance matrices under a quasi-static condition are derived from the cross-sectional dimensions of asymmetrical coupled microstrip lines with unequal widths. They are converted into a frequency-dependent resistance-inductance-conductance-capacitance model, allowing complete equation-based solutions to their four-port Z-matrix, S-matrix, and ABCD-matrix. As an application example of tackling the complexity of transmission lines, the derived analytical method is applied to a transitional structure with linearly varying trace width in tabbed microstrip lines by the method of segmentation. In addition, a new concept of tab-coupling fringing capacitance is specifically introduced to compensate for underestimated mutual capacitance at tab positions, which will improve the accuracy of the proposed approach. Numerical modeling results from commercial simulation tools are compared for validation purposes. As a conclusion, the proposed method and its versatility are demonstrated with applications to practical high-speed and high-density printed circuit board designs, which renders itself effective and efficient in an optimization process.
The plant‐parasitic nematode Bursaphelenchus xylophilus, the causal agent of pine wilt disease (PWD), causes enormous economic loss every year. Currently, little is known about the pathogenic ...mechanisms of PWD. Several effectors have been identified in B. xylophilus, but their functions and host targets have yet to be elucidated. Here, we demonstrated that BxSCD1 suppresses cell death and inhibits B. xylophilus PAMP BxCDP1‐triggered immunity in Nicotiana benthamiana and Pinus thunbergii. BxSCD1 was transcriptionally upregulated in the early stage of B. xylophilus infection. In situ hybridization experiments showed that BxSCD1 was specifically expressed in the dorsal glands and intestine. Cysteine residues are essential for the function of BxSCD1. Transient expression of BxSCD1 in N. benthamiana revealed that it was primarily targeted to the cytoplasm and nucleus. The morbidity was significantly reduced in P. thunbergii infected with B. xylophilus when BxSCD1 was silenced. We identified 1‐aminocyclopropane‐1‐carboxylate oxidase 1, the actual ethylene‐forming enzyme, as a host target of BxSCD1 by yeast two‐hybrid and coimmunoprecipitation. Overall, this study illustrated that BxSCD1 played a critical role in the B. xylophilus–plant interaction.
BxSCD1 suppressed plant immunity in Nicotiana benthamiana and Pinus thunbergii. We report for the first time that BxSCD1 interacts with an ethylene‐forming enzyme in pine.
PurposeWhile prior research provides interesting insights into the effect of social media use in enterprises, there is limited research on how use of different social media platforms affects employee ...job satisfaction and work efficiency. This study developed a research model to investigate how public and private social media platforms used for different motivations affect employee job satisfaction and work efficiency.Design/methodology/approachOnline surveys were conducted in China, generating 453 valid responses for analysis. Structural equation modeling is performed to test the research model and hypotheses.FindingsThe results suggest that (1) public social media used for both work- and social-related motivations positively affects employee job satisfaction, while private social media only used for social-related motivations can contribute to employee job satisfaction. (2) Public and private social media used for work-related motivations can contribute to employee work efficiency, while social-related motivations for use of public and private social media and employee work efficiency are not significant. (3) In the process of social media usage influencing employee job satisfaction and work efficiency, employees of different genders show significant differences.Originality/valueFirst, this paper contributes to information systems social media research by examining the joint effects of different motivations for public and private social media usage on employee job satisfaction and work efficiency in organizations. Second, it contributes to uses and gratification theory by clarifying the relationship between different motivations for enterprise social media use and its needs.
Giant cell tumor stromal cell (GCTSC) is the tumor cell of giant cell tumor of bone (GCTB). The biomarkers characterization of GCTSC is critical for the selection of GCTB targeting drugs. We believe ...the main functions of GCTSC in different part of tumor should be different for different environment. Then the biological behavior and molecular biomarkers of GCTSC should be different as well. Based on this idea, we focused on GCTSC which located in central tissue, peripheral tissue and took MMP‐9 as the breakthrough point to carry out research. The results showed MMP‐9 staining grade of GCTSC which located in central tissue was slight, whereas multinucleated giant cell staining grade was high. The peripheral tissue was consisted by almost GCTSC with high MMP‐9 staining degree and mRNA expression. This study also provided clues and inspiration for reducing GCTB recurrence rate after intralesional curettage with MMP‐9 targeted therapy which were aimed at the residual peripheral tissue.
MMP‐9 expression of GCTCS is different in different part of tumor. MMP‐9 targeted therapy which was aimed at the GCTB residual peripheral tissue might be a good way to further reduce the recurrence rate of GCTB after intralesional curettage.
The year 2016 marks the 200th birth anniversary of Carl Friedrich Wilhelm Ludwig (1816-1895). As one of the most remarkable scientists, Ludwig invented the kymograph, which for the first time enabled ...the recording of continuous blood pressure (BP), opening the door to the modern study of physiology. Almost a century later, intraarterial BP monitoring through an arterial line has been used clinically. Subsequently, arterial tonometry and volume clamp method were developed and applied in continuous BP measurement in a noninvasive way. In the last two decades, additional efforts have been made to transform the method of unobtrusive continuous BP monitoring without the use of a cuff. This review summarizes the key milestones in continuous BP measurement; that is, kymograph, intraarterial BP monitoring, arterial tonometry, volume clamp method, and cuffless BP technologies. Our emphasis is on recent studies of unobtrusive BP measurements as well as on challenges and future directions.
Familial risk for lung cancer Kanwal, Madiha; Ding, Xiao-Ji; Cao, Yi
Oncology letters,
02/2017, Letnik:
13, Številka:
2
Journal Article
Odprti dostop
Lung cancer, which has a low survival rate, is a leading cause of cancer-associated mortality worldwide. Smoking and air pollution are the major causes of lung cancer; however, numerous studies have ...demonstrated that genetic factors also contribute to the development of lung cancer. A family history of lung cancer increases the risk for the disease in both smokers and never-smokers. This review focuses on familial lung cancer, in particular on the familial aggregation of lung cancer. The development of familial lung cancer involves shared environmental and genetic factors among family members. Familial lung cancer represents a good model for investigating the association between environmental and genetic factors, as well as for identifying susceptibility genes for lung cancer. In addition, studies on familial lung cancer may help to elucidate the etiology and mechanism of lung cancer, and may identify novel biomarkers for early detection and diagnosis, targeted therapy and improved prevention strategies. This review presents the aetiology and molecular biology of lung cancer and then systematically introduces and discusses several aspects of familial lung cancer, including the characteristics of familial lung cancer, population-based studies on familial lung cancer and the genetics of familial lung cancer.
Lysophosphatidic acid receptor 5 (LPAR5) is involved in mediating thyroid cancer progression, but the underlying mechanism needs to be further revealed. In this study, we confirmed that LPAR5 is ...upregulated in papillary thyroid carcinoma (PTC), especially in BRAF‐like PTC, by analyzing The Cancer Genome Atlas (TCGA) database and performing immunohistochemistry assay in human thyroid cancer tissues. LPAR5‐specific antagonist TC LPA5 4 treatment inhibited CGTH‐W3, TPC‐1, B‐CPAP, and BHT‐101 cell proliferation, CGTH‐W3 and TPC‐1 cell migration significantly. In vivo, TC LPA5 4 treatment could delay CGTH‐W3 xenograft growth in nude mice. We also found that LPAR5‐specific antagonist TC LPA5 4, PI3K inhibitor wortmannin, or mTOR inhibitor rapamycin pretreatment abrogated phosphorylation of Akt and p70S6K1 stimulated by LPA in CGTH‐W3 and TPC‐1 cells. Stimulating CGTH‐W3 cells transfected with pEGFPC1‐Grp1‐PH fusion protein with LPA resulted in the generation of phosphatidylinositol (3,4,5)‐triphosphate, which indicates that PI3K was activated by LPA directly. The p110β‐siRNA instead of p110α‐siRNA transfection abrogated the increase of levels of phosphorylated Akt and S6K1 stimulated by LPA. Furthermore, immunoprecipitation assay confirmed an interaction between LPAR5 and p110β. Overall, we provide new insights that the downregulation of LPAR5 decreased the proliferation and migration phenotype via the PI3K/Akt pathway. Inhibition of LPAR5 or the PI3K/Akt signal may be a novel therapeutic strategy for treating thyroid cancer.
Lysophosphatidic acid receptor 5 (LPAR5) is upregulated in thyroid cancer and plays important roles in thyroid cancer proliferation and migration through activating PI3K kinase directly. Inhibition of LPAR5 or the PI3K/Akt pathway may be used for the therapy of metastatic and recurrent thyroid cancer expressing high levels of LPAR5.
The sodium-glucose transporter 2 (SGLT2) inhibitors Canagliflozin and Dapagliflozin are recently approved medications for type 2 diabetes. Recent studies indicate the potential ability of SGLT2 ...inhibitors to attenuate cancer growth of SGLT2-expressing cancer cells, but there is little known about the effects of SGLT2 inhibitors on breast cancer. The goal in this research was to assess the anticancer activity of SGLT2 inhibitors in breast cancerin vitro and in vivo.
We test the SGLT2 expression in breast cancer using immunohistochemistry and immunoblot assay. MTT cytotoxicity assay, colony formation assay and human breast cancer cells nude mice xenograft model were performed to detect the effects of SGLT2 inhibitors on cancer cell proliferation and growth. Flow Cytometry assay was performed to determine if the SGLT2 inhibitors induced cell cycle arrest and apoptosis.
We proved that SGLT2 expresses in breast cancer cell lines and human breast tumor tissue samples. SGLT2 inhibitors Dapagliflozin and Canagliflozin exhibited a potent anti-proliferative effect in breast cancer cells as demonstrated by MTT, clonogenic survival assay in vitro and xenograft growth model in vivo. Furthermore, we found that SGLT2 inhibitors arrested cell cycle in G1/G0 phase and induced cell apoptosis. Western blot analysis demonstrated that treatment with SGLT2 inhibitors increased the phosphorylation of Amp-activated protein kinase (AMPK) and decreased the phosphorylation of 70 kDa ribosomal protein S6 kinase 1 (p70S6K1) in breast cancer cells.
These findings indicate that SGLT2 inhibitor-therapy induced AMPK-mediated cell cycle arrest and apoptosis, which is a potential novel strategy for the treatment of breast cancer.
The aging population, prevalence of chronic diseases, and outbreaks of infectious diseases are some of the major challenges of our present-day society. To address these unmet healthcare needs, ...especially for the early prediction and treatment of major diseases, health informatics, which deals with the acquisition, transmission, processing, storage, retrieval, and use of health information, has emerged as an active area of interdisciplinary research. In particular, acquisition of health-related information by unobtrusive sensing and wearable technologies is considered as a cornerstone in health informatics. Sensors can be weaved or integrated into clothing, accessories, and the living environment, such that health information can be acquired seamlessly and pervasively in daily living. Sensors can even be designed as stick-on electronic tattoos or directly printed onto human skin to enable long-term health monitoring. This paper aims to provide an overview of four emerging unobtrusive and wearable technologies, which are essential to the realization of pervasive health information acquisition, including: 1) unobtrusive sensing methods, 2) smart textile technology, 3) flexible-stretchable-printable electronics, and 4) sensor fusion, and then to identify some future directions of research.
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