Giant Superfluorescent Bursts from a Semiconductor Magnetoplasma

Currently, considerable resurgent interest exists in the concept of superradiance (SR), i.e., accelerated relaxation of excited dipoles due to cooperative spontaneous emission, first proposed by Dicke in 1954. Recent authors have discussed SR in diverse contexts, including cavity quantum electrodynamics, quantum phase transitions, and plasmonics. At the heart of these various experiments lies the coherent coupling of constituent particles to each other via their radiation field that cooperatively governs the dynamics of the whole system. In the most exciting form of SR, called superfluorescence (SF), macroscopic coherence spontaneously builds up out of an initially incoherent ensemble of excited dipoles and then decays abruptly. Here, we demonstrate the emergence of this photon-mediated, cooperative, many-body state in a very unlikely system: an ultradense electron-hole plasma in a semiconductor. We observe intense, delayed pulses, or bursts, of coherent radiation from highly photo-excited semiconductor quantum wells with a concomitant sudden decrease in population from total inversion to zero. Unlike previously reported SF in atomic and molecular systems that occur on nanosecond time scales, these intense SF bursts have picosecond pulse-widths and are delayed in time by tens of picoseconds with respect to the excitation pulse. They appear only at sufficiently high excitation powers and magnetic fields and sufficiently low temperatures - where various interactions causing decoherence are suppressed. We present theoretical simulations based on the relaxation and recombination dynamics of ultrahigh-density electron-hole pairs in a quantizing magnetic field, which successfully capture the salient features of the experimental observations.Comment: 21 pages, 4 figure

Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series

© 2020 BACKGROUND: Chemotherapy-resistant cancer stem cells (CSC) may lead to tumor recurrence in glioblastoma (GBM). The poor prognosis of this disease emphasizes the critical need for developing a treatment stratification system to improve outcomes through personalized medicine. METHODS: We present a case series of 12 GBM and 2 progressive anaplastic glioma cases from a single Institution prospectively treated utilizing a CSC chemotherapeutics assay (ChemoID) guided report. All patients were eligible to receive a stereotactic biopsy and thus undergo ChemoID testing. We selected one of the most effective treatments based on the ChemoID assay report from a panel of FDA approved chemotherapy as monotherapy or their combinations for our patients. Patients were evaluated by MRI scans and response was assessed according to RANO 1.1 criteria. RESULTS: Of the 14 cases reviewed, the median age of our patient cohort was 49 years (21–63). We observed 6 complete responses (CR) 43%, 6 partial responses (PR) 43%, and 2 progressive diseases (PD) 14%. Patients treated with ChemoID assay-directed therapy, in combination with other modality of treatment (RT, LITT), had a longer median overall survival (OS) of 13.3 months (5.4-NA), compared to the historical median OS of 9.0 months (8.0–10.8 months) previously reported. Notably, patients with recurrent GBM or progressive high-grade glioma treated with assay-guided therapy had a 57% probability to survive at 12 months, compared to the 27% historical probability of survival observed in previous studies. CONCLUSIONS: The results presented here suggest that the ChemoID Assay has the potential to stratify individualized chemotherapy choices to improve recurrent and progressive high-grade glioma patient survival. Importance of the Study: Glioblastoma (GBM) and progressive anaplastic glioma are the most aggressive brain tumor in adults and their prognosis is very poor even if treated with the standard of care chemoradiation Stupp\u27s protocol. Recent knowledge pointed out that current treatments often fail to successfully target cancer stem cells (CSCs) that are responsible for therapy resistance and recurrence of these malignant tumors. ChemoID is the first and only CLIA (clinical laboratory improvements amendment) -certified and CAP (College of American Pathologists) -accredited chemotherapeutic assay currently available in oncology clinics that examines patient\u27s derived CSCs susceptibility to conventional FDA (Food and Drugs Administration) -approved drugs. In this study we observed that although the majority of our patients (71.5%) presented with unfavorable prognostic predictors (wild type IDH-1/2 and unmethylated MGMT promoter), patients treated with ChemoID assay-directed therapy had an overall response rate of 86% and increased median OS of 13.3 months compared to the historical median OS of 9.1 months (8.1–10.1 months) previously reported [1] suggesting that the ChemoID assay may be beneficial in personalizing treatment strategies

Ubiquitin Ligase RNF146 Regulates Tankyrase and Axin to Promote Wnt Signaling

Canonical Wnt signaling is controlled intracellularly by the level of β-catenin protein, which is dependent on Axin scaffolding of a complex that phosphorylates β-catenin to target it for ubiquitylation and proteasomal degradation. This function of Axin is counteracted through relocalization of Axin protein to the Wnt receptor complex to allow for ligand-activated Wnt signaling. AXIN1 and AXIN2 protein levels are regulated by tankyrase-mediated poly(ADP-ribosyl)ation (PARsylation), which destabilizes Axin and promotes signaling. Mechanistically, how tankyrase limits Axin protein accumulation, and how tankyrase levels and activity are regulated for this function, are currently under investigation. By RNAi screening, we identified the RNF146 RING-type ubiquitin E3 ligase as a positive regulator of Wnt signaling that operates with tankyrase to maintain low steady-state levels of Axin proteins. RNF146 also destabilizes tankyrases TNKS1 and TNKS2 proteins and, in a reciprocal relationship, tankyrase activity reduces RNF146 protein levels. We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation. RNF146 is a cytoplasmic protein that also prevents tankyrase protein aggregation at a centrosomal location. Tankyrase auto-PARsylation and PARsylation of Axin is known to lead to proteasome-mediated degradation of these proteins, and we demonstrate that, through ubiquitylation, RNF146 mediates this process to regulate Wnt signaling

Gata3 Acts Downstream of β-Catenin Signaling to Prevent Ectopic Metanephric Kidney Induction

Metanephric kidney induction critically depends on mesenchymal–epithelial interactions in the caudal region of the nephric (or Wolffian) duct. Central to this process, GDNF secreted from the metanephric mesenchyme induces ureter budding by activating the Ret receptor expressed in the nephric duct epithelium. A failure to regulate this pathway is believed to be responsible for a large proportion of the developmental anomalies affecting the urogenital system. Here, we show that the nephric duct-specific inactivation of the transcription factor gene Gata3 leads to massive ectopic ureter budding. This results in a spectrum of urogenital malformations including kidney adysplasia, duplex systems, and hydroureter, as well as vas deferens hyperplasia and uterine agenesis. The variability of developmental defects is reminiscent of the congenital anomalies of the kidney and urinary tract (CAKUT) observed in human. We show that Gata3 inactivation causes premature nephric duct cell differentiation and loss of Ret receptor gene expression. These changes ultimately affect nephric duct epithelium homeostasis, leading to ectopic budding of interspersed cells still expressing the Ret receptor. Importantly, the formation of these ectopic buds requires both GDNF/Ret and Fgf signaling activities. We further identify Gata3 as a central mediator of β-catenin function in the nephric duct and demonstrate that the β-catenin/Gata3 pathway prevents premature cell differentiation independently of its role in regulating Ret expression. Together, these results establish a genetic cascade in which Gata3 acts downstream of β-catenin, but upstream of Ret, to prevent ectopic ureter budding and premature cell differentiation in the nephric duct

SP8 transcriptional regulation of Cyclin D1 during mouse early corticogenesis

Multiple signals control the balance between proliferation and differentiation of neural progenitor cells during corticogenesis. A key point of this regulation is the control of G1 phase length, which is regulated by the Cyclin/Cdks complexes. Using genome-wide chromatin immunoprecipitation assay and mouse genetics, we have explored the transcriptional regulation of Cyclin D1 (Ccnd1) during the early developmental stages of the mouse cerebral cortex. We found evidence that SP8 binds to the Ccnd1 locus on exon regions. In vitro experiments show SP8 binding activity on Ccnd1 gene 3′-end, and point to a putative role for SP8 in modulating PAX6-mediated repression of Ccnd1 along the dorso-ventral axis of the developing pallium, creating a medialLow-lateralHigh gradient of neuronal differentiation. Activation of Ccnd1 through the promoter/5′-end of the gene does not depend on SP8, but on βcatenin (CTNNB1). Importantly, alteration of the Sp8 level of expression in vivo affects Ccnd1 expression during early corticogenesis. Our results indicate that Ccnd1 regulation is the result of multiple signals and that SP8 is a player in this regulation, revealing an unexpected and potentially novel mechanism of transcriptional activation

The molecular and cellular signatures of the mouse eminentia thalami support its role as a signalling centre in the developing forebrain

The mammalian eminentia thalami (EmT) (or thalamic eminence) is an embryonic forebrain structure of unknown function. Here, we examined the molecular and cellular properties of the mouse EmT. We first studied mRNA expression of signalling molecules and found that the EmT is a structure, rich in expression of secreted factors, with Wnts being the most abundantly detected. We then examined whether EmT tissue could induce cell fate changes when grafted ectopically. For this, we transplanted EmT tissue from a tau-GFP mouse to the ventral telencephalon of a wild type host, a telencephalic region where Wnt signalling is not normally active but which we showed in culture experiments is competent to respond to Wnts. We observed that the EmT was able to induce in adjacent ventral telencephalic cells ectopic expression of Lef1, a transcriptional activator and a target gene of the Wnt/β-catenin pathway. These Lef1-positive;GFP-negative cells expressed the telencephalic marker Foxg1 but not Ascl1, which is normally expressed by ventral telencephalic cells. These results suggest that the EmT has the capacity to activate Wnt/β-catenin signalling in the ventral telencephalon and to suppress ventral telencephalic gene expression. Altogether, our data support a role of the EmT as a signalling centre in the developing mouse forebrain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00429-015-1127-3) contains supplementary material, which is available to authorized users

Regulation of endothelial permeability by angiopoietin-1 and vascular endothelial growth factor.

Regulation of endothelial permeability by angiopoietin-1 and vascular endothelial growth factor