Differential Inductive Signaling of CD90+ Prostate Cancer-Associated Fibroblasts Compared to Normal Tissue Stromal Mesenchyme Cells

Prostate carcinomas are surrounded by a layer of stromal fibroblastic cells that are characterized by increased expression of CD90. These CD90+ cancer-associated stromal fibroblastic cells differ in gene expression from their normal counterpart, CD49a+CD90lo stromal smooth muscle cells; and were postulated to represent a less differentiated cell type with altered inductive properties. CD90+ stromal cells were isolated from tumor tissue specimens and co-cultured with the pluripotent embryonal carcinoma cell line NCCIT in order to elucidate the impact of tumor-associated stroma on stem cells, and the ‘cancer stem cell.’ Transcriptome analysis identified a notable decreased induction of smooth muscle and prostate stromal genes such as PENK, BMP2 and ChGn compared to previously determined NCCIT response to normal prostate stromal cell induction. CD90+ stromal cell secreted factors induced an increased expression of CD90 and differential induction of genes involved in extracellular matrix remodeling and the RECK pathway in NCCIT. These results suggest that, compared to normal tissue stromal cells, signaling from cancer-associated stromal cells has a markedly different effect on stem cells as represented by NCCIT. Given that stromal cells are important in directing organ-specific differentiation, stromal cells in tumors appear to be defective in this function, which may contribute to abnormal differentiation found in diseases such as cancer

HIV-1 superinfection results in broad polyclonal neutralizing antibodies

<div><p>HIV-1 vaccines designed to date have failed to elicit neutralizing antibodies (Nabs) that are capable of protecting against globally diverse HIV-1 subtypes. One relevant setting to study the development of a strong, cross-reactive Nab response is HIV-1 superinfection (SI), defined as sequential infections from different source partners. SI has previously been shown to lead to a broader and more potent Nab response when compared to single infection, but it is unclear whether SI also impacts epitope specificity and if the epitopes targeted after SI differ from those targeted after single infection. Here the post-SI Nab responses were examined from 21 Kenyan women collectively exposed to subtypes A, C, and D and superinfected after a median time of ~1.07 years following initial infection. Plasma samples chosen for analysis were collected at a median time point ~2.72 years post-SI. Because previous studies of singly infected populations with broad and potent Nab responses have shown that the majority of their neutralizing activity can be mapped to 4 main epitopes on the HIV-1 Envelope, we focused on these targets, which include the CD4-binding site, a V1/V2 glycan, the N332 supersite in V3, and the membrane proximal external region of gp41. Using standard epitope mapping techniques that were applied to the previous cohorts, the present study demonstrates that SI did not induce a dominant Nab response to any one of these epitopes in the 21 women. Computational sera delineation analyses also suggested that 20 of the 21 superinfected women’s Nab responses could not be ascribed a single specificity with high confidence. These data are consistent with a model in which SI with diverse subtypes promotes the development of a broad polyclonal Nab response, and thus would provide support for vaccine designs using multivalent HIV immunogens to elicit a diverse repertoire of Nabs.</p></div

Characterization of Near-Interface Oxide Trap Density in Nitrided Oxides for Nano-Scale MOSFET Applications

This paper presents the depth profile of oxide trap density, extracted from the dual gate processed thermally grown oxide in NO ambient and remote plasma nitrided oxides by using multifrequency and multitemperature charge pumping technique in conjunction with the tunneling model of trapped charges. Ni-trided oxide is widely used to improve the reliability of nanoscale MOSFETs because it can decrease the degradation of gate oxide due to the generation of traps therein. Based on the measurement, the optimum nitrogen concentration in such typical nitrided process is discussed in correlation with the gate oxide thickness for nanoscale CMOSFETs.X1122sciescopu

Development and validation of a serum microRNA biomarker panel for detecting gastric cancer in a high-risk population

10.1136/gutjnl-2020-322065GUT705829-83