The Formation of a Magnetic Channel by the Emergence of Current-carrying Magnetic Fields

A magnetic channel - a series of polarity reversals separating elongated flux threads with opposite polarities - may be a manifestation of a highly non-potential magnetic configuration in active regions. To understand its formation we have carried out a detailed analysis of the magnetic channel in AR 10930 using data taken by the Solar Optical Telescope/Hinode. As a result, we found upflows (-0.5 to -1.0 km/s) and downflows (+1.5 to +2.0 km/s) inside and at both tips of the thread respectively, and a pair of strong vertical currents of opposite polarity along the channel. Moreover, our analysis of the nonlinear force-free fields constructed from the photospheric magnetic field indicates that the current density in the lower corona may have gradually increased as a result of the continuous emergence of the highly sheared flux along the channel. With these results, we suggest that the magnetic channel originates from the emergence of the twisted flux tube that has formed below the surface before the emergence.Comment: 11 figures, accepted for Astrophysical journa

Multi-dimensional histone methylations for coordinated regulation of gene expression under hypoxia

Hypoxia increases both active and repressive histone methylation levels via decreased activity of histone demethylases. However, how such increases coordinately regulate induction or repression of hypoxia-responsive genes is largely unknown. Here, we profiled active and repressive histone tri-methylations (H3K4me3, H3K9me3, and H3K27me3) and analyzed gene expression profiles in human adipocyte-derived stem cells under hypoxia. We identified differentially expressed genes (DEGs) and differentially methylated genes (DMGs) by hypoxia and clustered the DEGs and DMGs into four major groups. We found that each group of DEGs was predominantly associated with alterations in only one type among the three histone tri-methylations. Moreover, the four groups of DEGs were associated with different TFs and localization patterns of their predominant types of H3K4me3, H3K9me3 and H3K27me3. Our results suggest that the association of altered gene expression with prominent single-type histone tri-methylations characterized by different localization patterns and with different sets of TFs contributes to regulation of particular sets of genes, which can serve as a model for coordinated epigenetic regulation of gene expression under hypoxia.111Ysciescopu

Clinical Significance of Extraluminal Compressions according to the Site of the Duodenum

Background/Aims Differentiating extraluminal compressions from true subepithelial tumors in the duodenum by endoscopy alone is difficult. Endoscopic ultrasonography (EUS) is one of the most useful diagnostic modalities for this purpose. Extraluminal compression in the duodenum is occasionally observed, but its clinical significance has not been reported. Therefore, the aim of this study was to evaluate the clinical significance of extraluminal compression in the duodenum according to lesion location.Materials and Methods We retrospectively evaluated 22 patients diagnosed as having extraluminal compression in the duodenum based on EUS findings between January 2006 and December 2017. Some patients underwent abdominal computed tomography for accurate diagnosis. Results The location of the extraluminal compression was the duodenal bulb in 10 cases, the superior duodenal angle in 10 cases, and the second portion of the duodenum in 2 cases. Of the 22 cases, 12 were caused by normal structures, including vessels, the right kidney, the gallbladder, and the pancreas, and 10 were caused by pathological lesions, including the hepatic cyst, remnant cystic duct and dilated common bile duct after cholecystectomy; gallstones, gallbladder polyps, remnant cystic duct cancer, and pseudomyxoma peritoneii. The anterior wall of the duodenum was the most frequent location of extraluminal compression. However, the lesions in the anterior wall of the duodenal bulb and superior duodenal angle showed a high frequency of pathologic lesions, including malignancy. Conclusions If the extraluminal compression is found in the anterior wall of the duodenum, EUS is needed because of the high frequency of pathological lesions

The determination of dark adaptation time using electroretinography in conscious Miniature Schnauzer dogs

The optimal dark adaptation time of electroretinograms (ERG's) performed on conscious dogs were determined using a commercially available ERG unit with a contact lens electrode and a built-in light source (LED-electrode). The ERG recordings were performed on nine healthy Miniature Schnauzer dogs. The bilateral ERG's at seven different dark adaptation times at an intensity of 2.5 cd·s/m2 was performed. Signal averaging (4 flashes of light stimuli) was adopted to reduce electrophysiologic noise. As the dark adaptation time increased, a significant increase in the mean a-wave amplitudes was observed in comparison to base-line levels up to 10 min (p < 0.05). Thereafter, no significant differences in amplitude occured over the dark adaptation time. Moreover, at this time the mean amplitude was 60.30 ± 18.47 µV. However, no significant changes were observed for the implicit times of the a-wave. The implicit times and amplitude of the b-wave increased significantly up to 20 min of dark adaptation (p < 0.05). Beyond this time, the mean b-wave amplitudes was 132.92 ± 17.79 µV. The results of the present study demonstrate that, the optimal dark adaptation time when performing ERG's, should be at least 20 min in conscious Miniature Schnauzer dogs

A Role of Canonical Transient Receptor Potential 5 Channel in Neuronal Differentiation from A2B5 Neural Progenitor Cells

Store-operated Ca2+ entry (SOCE) channels are the main pathway of Ca2+ entry in non-excitable cells such as neural progenitor cells (NPCs). However, the role of SOCE channels has not been defined in the neuronal differentiation from NPCs. Here, we show that canonical transient receptor potential channel (TRPC) as SOCE channel influences the induction of the neuronal differentiation of A2B5+ NPCs isolated from postnatal-12-day rat cerebrums. The amplitudes of SOCE were significantly higher in neural cells differentiated from proliferating A2B5+ NPCs and applications of SOCE blockers, 2-aminoethoxy-diphenylborane (2-APB), and ruthenium red (RR), inhibited their rise of SOCE. Among TRPC subtypes (TRPC1-7), marked expression of TRPC5 and TRPC6 with turned-off TRPC1 expression was observed in neuronal cells differentiated from proliferating A2B5+ NPCs. TRPC5 small interfering RNA (siRNA) blocked the neuronal differentiation from A2B5+ NPCs and reduced the rise of SOCE. In contrast, TRPC6 siRNA had no significant effect on the neuronal differentiation from A2B5+ NPCs. These results indicate that calcium regulation by TRPC5 would play a key role as a switch between proliferation and neuronal differentiation from NPCs

Circulating Tumor Cells and TWIST Expression in Patients with Metastatic Gastric Cancer: A Preliminary Study

Background and Aims: The clinical significance of circulating tumor cells (CTCs) and TWIST expression in CTCs remains unelucidated in patients with gastric cancer (GC). Here, we evaluated CTCs and TWIST expression in CTCs and explored their correlation with prognosis in patients with metastatic GC. Methods: Peripheral blood samples were prospectively obtained from 31 patients with metastatic GC between September 2017 and December 2018, prior to treatment. CTCs were detected using a centrifugal microfluidic system and CTCs positive for TWIST immunostaining were defined as TWIST (+) CTCs. Results: CTCs and TWIST (+) CTCs were detected in 25 (80.6%) and 24 (77.4%) of the 31 patients, respectively. CTC count in patients with first diagnosis of metastatic cancer tended to be higher than that in those with recurrent metastatic cancer, but TWIST (+) CTC count was not different between the two groups. There was no difference in CTC and TWIST (+) CTC counts according to histopathologic type, peritoneal dissemination, hematogenous metastasis, serum tumor makers, or response to first-line chemotherapy. Patients with CTCs &gt; 7.5/7.5 mL of blood showed shorter overall survival (OS) than those with CTCs &amp; LE; 7.5/7.5 mL of blood (p = 0.049). Additionally, patients with TWIST (+) CTCs &gt; 2.5/7.5 mL of blood tended to show shorter OS than those with TWIST (+) CTCs &amp; LE; 2.5/7.5 mL of blood (p = 0.105). Conclusions: Our study demonstrated that high levels of CTCs and TWIST (+) CTCs were associated with worse OS

Limitations of Conventional Contrast-enhanced MRI in Selecting Sentinel Node Biopsy Candidates among DCIS Patients

Purpose: A better predictive model for occult invasive disease in ductal carcinoma in situ (DCIS) patients is essential to guide the tailored use of sentinel node biopsies. We hypothesized that recent improvement of contrast-enhanced breast magnetic resonance imaging (MRI) could provide more accurate information on the presence of occult invasion in DCIS patients. Methods: From a prospectively maintained database, we identified 143 DCIS patients diagnosed with needle biopsies in whom MRI images were available. Results: Sixty-five patients (45.5%) were upstaged to invasive carcinoma after curative surgery. Ultrasonographic lesion size, mass-appearance on mammography, type of needle used, and the presence of suspicious microinvasive foci were associated with increased likelihood of upstaging. Among the features of MRI, only mass-appearance was significantly associated with the presence of invasive disease (p=0.002). However, up to 50% of masses in MRI cases had mass-appearance on mammography as well. Other morphologic and pharmacokinetic features of MRI, such as shape, margin, and patterns of enhancement and washout, did not have a significant association. Conclusion: Among various morphologic and pharmacokinetic parameters of contrast-enhanced MRI, only mass-appearance was associated with occult invasive disease. Our results show the limitations of current contrast-enhanced MRI in predicting invasive disease in patients with preoperative diagnoses of DCIS.Moon HG, 2009, ANN ONCOL, V20, P636, DOI 10.1093/annonc/mdn683Kuerer HM, 2009, J CLIN ONCOL, V27, P279, DOI 10.1200/JCO.2008.18.3103HU M, 2009, P NATL ACAD SCI USA, V106, P3372Gadre SA, 2008, HISTOPATHOLOGY, V53, P545, DOI 10.1111/j.1365-2559.2008.03152.xOkumura Y, 2008, BMC CANCER, V8, DOI 10.1186/1471-2407-8-287Sakorafas GH, 2008, CANCER TREAT REV, V34, P483, DOI 10.1016/j.ctrv.2008.03.001Morrow M, 2008, ANN SURG ONCOL, V15, P2641, DOI 10.1245/s10434-008-0083-zPorembka MR, 2008, ANN SURG ONCOL, V15, P2709, DOI 10.1245/s10434-008-9947-5Lee JW, 2008, J SURG ONCOL, V98, P15, DOI 10.1002/jso.21077Hu M, 2008, CANCER CELL, V13, P394, DOI 10.1016/j.ccr.2008.03.007Ansari B, 2008, BRIT J SURG, V95, P547, DOI 10.1002/bjs.6162Orel S, 2008, J CLIN ONCOL, V26, P703, DOI 10.1200/JCO.2007.14.3594Facius M, 2007, CLIN IMAG, V31, P394, DOI 10.1016/j.clinimag.2007.04.030Kuhl CK, 2007, LANCET, V370, P485Jung EJ, 2007, INT J CANCER, V120, P2331, DOI 10.1002/ijc.22434Nielsen BS, 2007, INT J CANCER, V120, P2086, DOI 10.1002/ijc.22340van der Velden APS, 2006, AM J SURG, V192, P172, DOI 10.1016/j.amjsurg.2006.02.026Goyal A, 2006, BREAST CANCER RES TR, V98, P311, DOI 10.1007/s10549-006-9167-2Mansel RE, 2006, J NATL CANCER I, V98, P599, DOI 10.1093/jnci/djj158Lyman GH, 2005, J CLIN ONCOL, V23, P7703, DOI 10.1200/JCO.2005.08.001Wilkie C, 2005, AM J SURG, V190, P563, DOI 10.1016/j.amjsurg.2005.06.011Groves AM, 2005, MAGN RESON IMAGING, V23, P733, DOI 10.1016/j.mri.2005.06.003Hylton N, 2005, J CLIN ONCOL, V23, P1678, DOI 10.1200/JCO.2005.12.002Leonard GD, 2004, J NATL CANCER I, V96, P906, DOI 10.1093/jnci/djh164Hata T, 2004, J AM COLL SURGEONS, V198, P190, DOI 10.1016/j.jamcollsurg.2003.10.008Hwang EW, 2003, ANN SURG ONCOL, V10, P381, DOI 10.1245/ASO.2003.03.085*AM COLL RAD, 2003, ACR BI RADS BREAST IMorrow M, 2002, CA-CANCER J CLIN, V52, P277Jackman RJ, 2001, RADIOLOGY, V218, P497Brown LF, 1999, CLIN CANCER RES, V5, P1041

An integrative approach for exploring the nature of fibroepithelial neoplasms.

BACKGROUND: Malignant phyllodes tumour (MPT) is a rare breast malignancy with epithelial and mesenchymal features. Currently, there are no appropriate research models or effective targeted therapeutic approaches for MPT. METHODS: We collected fresh frozen tissues from nine patients with MPT and performed whole-exome and RNA sequencing. Additionally, we established patient-derived xenograft (PDX) models from patients with MPT and tested the efficacy of targeting dysregulated pathways in MPT using the PDX model from one MPT. RESULTS: MPT has unique molecular characteristics when compared to breast cancers of epithelial origin and can be classified into two groups. The PDX model derived from one patient with MPT showed that the mouse epithelial component increased during tumour growth. Moreover, targeted inhibition of platelet-derived growth factor receptor (PDGFR) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) by imatinib mesylate and PKI-587 showed in vivo tumour suppression effects. CONCLUSIONS: This study revealed the molecular profiles of MPT that can lead to molecular classification and potential targeted therapy, and suggested that the MPT PDX model can be a useful tool for studying the pathogenesis of fibroepithelial neoplasms and for preclinical drug screening to find new therapeutic strategies for MPT