Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on the differential single-cell gene expression ...analysis of mesenchymal osteolineage cells close to, and further removed from, hematopoietic stem/progenitor cells (HSPCs) to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location. We functionally examined, among the genes that were preferentially expressed in proximal cells, three secreted or cell-surface molecules not previously connected to HSPC biology—the secreted RNase angiogenin, the cytokine IL18, and the adhesion molecule Embigin—and discovered that all of these factors are HSPC quiescence regulators. Therefore, our proximity-based differential single-cell approach reveals molecular heterogeneity within niche cells and can be used to identify novel extrinsic stem/progenitor cell regulators. Similar approaches could also be applied to other stem cell/niche pairs to advance the understanding of microenvironmental regulation of stem cell function.
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•Single-cell RNA-seq of HSPC-proximal stromal cells identifies niche cells•HSPC-proximal cells have a distinct RNA-seq profile compared to HSPC-distal cells•Proximal cell signature identifies niche regulators of stem/progenitor function•Three representative niche factors regulate HSPC quiescence in vivo
Silberstein et al. describe an approach combining micro-anatomical proximity between stem/progenitor cells and stromal cells and differential single-cell gene expression to identify niche cells and factors regulating HSPC function. With adaptation, this approach could be applied to discover regulatory niche factors for other stem cell populations.
•We propose two complex model equations starting from the first negative flow equations of AKNS hierarchy.•We show the integrability of complex systems by providing the Lax pairs.•We present ...multi-soliton solutions by Hirota’s bilinear method and N-soliton solutions in pfaffians form.•Dynamics of one- and two-soliton solutions are investigated in details.
In this paper, we propose a complex negative order AKNS equation and a coupled complex negative order AKNS equation. They are integrable due to the existence of Lax pairs. Furthermore, we find their multi-soliton solutions in terms of Pfaffians by virtue of Hirota’s bilinear method. One- and two-soliton solutions are investigated in detail exhibiting favorable evolution properties. Especially, the same as the coupled nonlinear Schrödinger equation, inelastic interactions and energy re-distribution happen between two solitons, that has potential applications and deserve further study.
In this paper, we study the correspondence between the Coupled Dispersionless (CD)-type equations and the Short Pulse (SP)-type equations. From the real and complex modified CD equations, we ...construct the real and complex Modified Short Pulse (mSP) equations geometrically and algebraically. From the geometric point of view, we establish the link of the motions of space curves to the real and complex modified CD equations, then to the real and complex mSP equations via hodograph transformations. The integrability of these equations are confirmed by constructing their Lax pairs geometrically. By using hodograph transformation, we construct the two-component SP equation from the CD-type equations, the multi-component real and complex SP and mSP equations from the multi-component CD equations. The multi-soliton solutions in the determinant form for the mSP and two-component SP equations are provided.
SOX9 is a transcription factor that plays a critical role in the development of multiple tissues. We previously reported that SOX9 in normal human adult prostate was restricted to basal epithelium. ...SOX9 was also expressed in a subset of prostate cancer (PCa) cells and was increased in relapsed hormone-refractory PCa. Moreover, SOX9 expression in PCa cell lines enhanced tumor cell proliferation and was beta-catenin regulated. Here we report additional in vivo results showing that SOX9 is highly expressed during fetal prostate development by epithelial cells expanding into the mesenchyme, suggesting it may contribute to invasive growth in PCa. Indeed, SOX9 overexpression in LNCaP PCa xenografts enhanced growth, angiogenesis, and invasion. Conversely, short hairpin RNA-mediated SOX9 suppression inhibited the growth of CWR22Rv1 PCa xenografts. These results support important functions of SOX9 in both the development and maintenance of normal prostate, and indicate that these functions contribute to PCa tumor growth and invasion.
The autonomic nervous system is critically involved in mediating the control by leptin of many physiological processes. Here, we examined the role of the leptin receptor (LepR) in proopiomelanocortin ...(POMC) and agouti-related peptide (AgRP) neurons in mediating the effects of leptin on regional sympathetic and parasympathetic nerve activity.
We analyzed how deletion of the LepR in POMC neurons (POMC
/LepR
mice) or AgRP neurons (AgRP
/LepR
mice) affects the ability of leptin to increase sympathetic and parasympathetic nerve activity. We also studied mice lacking the catalytic p110α or p110β subunits of phosphatidylinositol-3 kinase (PI3K) in POMC neurons.
Leptin-evoked increase in sympathetic nerve activity subserving thermogenic brown adipose tissue was partially blunted in mice lacking the LepR in either POMC or AgRP neurons. On the other hand, loss of the LepR in AgRP, but not POMC, neurons interfered with leptin-induced sympathetic nerve activation to the inguinal fat depot. The increase in hepatic sympathetic traffic induced by leptin was also reduced in mice lacking the LepR in AgRP, but not POMC, neurons whereas LepR deletion in either AgRP or POMC neurons attenuated the hepatic parasympathetic nerve activation evoked by leptin. Interestingly, the renal, lumbar and splanchnic sympathetic nerve activation caused by leptin were significantly blunted in POMC
/LepR
mice, but not in AgRP
/LepR
mice. However, loss of the LepR in POMC or AgRP neurons did not interfere with the ability of leptin to increase sympathetic traffic to the adrenal gland. Furthermore, ablation of the p110α, but not the p110β, isoform of PI3K from POMC neurons eliminated the leptin-elicited renal sympathetic nerve activation. Finally, we show trans-synaptic retrograde tracing of both POMC and AgRP neurons from the kidneys.
POMC and AgRP neurons are differentially involved in mediating the effects of leptin on autonomic nerve activity subserving various tissues and organs.
Background. Large scalp defects, especially those complicated by calvarial defects, titanium mesh exposure, or cerebrospinal fluid (CSF) leak, pose a challenge for the neurosurgeon and plastic ...surgeon. Here, we describe our experience of reconstructing the complex scalp defect with free flap transfer. Methods. From October 2012 to September 2017, 8 patients underwent free flap transfer for the reconstruction of the scalp or complicated scalp and calvarial defects. Five patients presented with scalp tumor and the other 3 patients with scalp necrosis or ulceration (2 patients with titanium plate exposure). Seven anterolateral thigh flaps and one radial forearm flap were harvested and employed. The clinical data, including defect characteristics, flap type, complications, and outcomes, were recorded and analyzed. Results. Five patients were pathologically diagnosed with malignant tumor, and 3 of them were given further radiotherapy. For the 2 patients with exposure of titanium plate, no titanium plate was removed. For the patient with scalp necrosis after decompressive craniectomy accompanied by CSF leakage, the CSF leak was stopped after reconstruction. The size of the flaps ranged from 3 to 14 cm in width and 4 to 18 cm in length. No flap failure occurred in these cases. From follow-up to the present, no ulceration or necrosis occurred. Conclusions. Free flap transfer is an ideal method for the reconstruction of large, complicated scalp defects with a one-stage operation. The anterolateral thigh flap is favored because of its durability, adjustability, water tightness, and infection prevention.
Transparent conductive tin-doped indium oxide (In
2
O
3
:Sn, ITO) thin films with various Sn-doping concentrations have been prepared using the low cost reactive thermal evaporation (RTE) technique ...at a low growth temperature of ~160 °C. The structural characteristics, optical and electrical properties of the ITO thin films were investigated. These polycrystalline ITO films exhibited preferential orientation along (222) plane and possessed low resistivities ranging from 3.51 to 5.71 × 10
−4
Ω cm. The decreased mobility was attributed to the scattering by ionized and neutral impurities at high doping concentrations. The optimized ITO thin film deposited with 6.0 wt% Sn-doping concentration exhibited a high average transparency of 87 % in the wavelength range of 380–900 nm and a low resistivity of 3.74 × 10
−4
Ω cm with a high Hall mobility of 47 cm
2
V
−1
s
−1
. A hydrogenated amorphous silicon and silicon–germanium (a-Si:H/a-SiGe:H) double-junction solar cell fabricated with the RTE-grown ITO electrodes presented a conversion efficiency of 10.51 %.
Abstract
Prostate specific antigen screening has resulted in a decrease in prostate cancer-related deaths. However, it also has led to over-treatment affecting the quality of life of many patients. ...New biomarkers are needed to distinguish prostate cancer from benign prostate hyperplasia (BPH) and to predict aggressiveness of the disease. Here, we report that ribonuclease 4 (RNASE4) serves as such a biomarker as well as a therapeutic target. RNASE4 protein level in the plasma is elevated in prostate cancer patients and is positively correlated with disease stage, grade, and Gleason score. Plasma RNASE4 level can be used to predict biopsy outcome and to enhance diagnosis accuracy. RNASE4 protein in prostate cancer tissues is enhanced and can differentiate prostate cancer and BPH. RNASE4 stimulates prostate cancer cell proliferation, induces tumor angiogenesis, and activates receptor tyrosine kinase AXL as well as AKT and S6K. An RNASE4-specific monoclonal antibody inhibits the growth of xenograft human prostate cancer cell tumors in athymic mice.
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