The relation between the two-point and the three-point correlation functions in the non-linear gravitational clustering regime

The connection between the two-point and the three-point correlation functions in the non-linear gravitational clustering regime is studied. Under a scaling hypothesis, we find that the three-point correlation function, $\zeta$, obeys the scaling law $\zeta\propto \xi^{\frac{3m+4w-2\epsilon}{2m+2w}}$ in the nonlinear regime, where $\xi$, $m$, $w$, and $\epsilon$ are the two-point correlation function, the power index of the power spectrum in the nonlinear regime, the number of spatial dimensions, and the power index of the phase correlations, respectively. The new formula reveals the origin of the power index of the three-point correlation function. We also obtain the theoretical condition for which the ``hierarchical form'' $\zeta\propto\xi^2$ is reproduced.Comment: 16 pages, 4 figures. Accepted for publication in APJ. Some sentences and figures are revise

Rhabdomyolysis with Multiple Electrolyte Imbalances under Proton Pump Inhibitor Treatment after Total Thyroidectomy

A 90-year-old man presented with muscle weakness, difficulty concentrating, and dysphagia. About eighteen months prior to presentation, lansoprazole had been initiated to prevent stress ulcers; he also had a history of total thyroidectomy due to papillary thyroid cancer ten years prior. Laboratory findings were as follows: K 2.4 mEq/L, Ca 3.7 mg/dL, Mg 1.3 mg/dL, CK 5386 U/L, and intact PTH (iPTH) 14 pg/mL. Rhabdomyolysis with multiple electrolyte imbalances under proton pump inhibitor (PPI) treatment was diagnosed. We initiated intravenous hydration and electrolyte supplementation with discontinuation of PPI. After discontinuing PPI, the patient’s serum magnesium, potassium, and calcium levels normalised with oral vitamin D and calcium supplementation. PPIs can cause hypocalcaemia and hypokalaemia via hypomagnesemia; hypocalcaemia is also a common postoperative complication of thyroidectomy. Careful monitoring of electrolyte levels is required in patients with long-term PPI treatment, especially in post-thyroidectomy cases

The function of histone methylation and acetylation regulators in GBM pathophysiology

Glioblastoma (GBM) is the most common and lethal primary brain malignancy and is characterized by a high degree of intra and intertumor cellular heterogeneity, a starkly immunosuppressive tumor microenvironment, and nearly universal recurrence. The application of various genomic approaches has allowed us to understand the core molecular signatures, transcriptional states, and DNA methylation patterns that define GBM. Histone posttranslational modifications (PTMs) have been shown to influence oncogenesis in a variety of malignancies, including other forms of glioma, yet comparatively less effort has been placed on understanding the transcriptional impact and regulation of histone PTMs in the context of GBM. In this review we discuss work that investigates the role of histone acetylating and methylating enzymes in GBM pathogenesis, as well as the effects of targeted inhibition of these enzymes. We then synthesize broader genomic and epigenomic approaches to understand the influence of histone PTMs on chromatin architecture and transcription within GBM and finally, explore the limitations of current research in this field before proposing future directions for this area of research

Universality in the distribution of caustics in the expanding Universe

We numerically investigate the long--time evolution of density perturbations after the first appearance of caustics in an expanding cosmological model with one--dimensional `single--wave' initial conditions. Focussing on the time--intervals of caustic appearances and the spatial distribution of caustics at subsequent times, we find that the time--intervals of caustic appearances approach a constant, i.e., their time--subsequent ratio converges to 1; it is also found that the spatial distribution of caustics at a given time features some universality rules, e.g., the ratio between the position of the nearest caustic from the center and that of the second nearest caustic from the center approaches a constant. Furthermore we find some rules for the mass distribution for each caustic. Using these universality constants we are in the position to predict the spatial distribution of caustics at an arbitrary time in order to give an estimate for the power spectral index in the fully--developed non--dissipative turbulent (`virialized') regime.Comment: 23 pages, 19 figure

Transcriptome map of plant mitochondria reveals islands of unexpected transcribed regions

<p>Abstract</p> <p>Background</p> <p>Plant mitochondria contain a relatively large amount of genetic information, suggesting that their functional regulation may not be as straightforward as that of metazoans. We used a genomic tiling array to draw a transcriptomic atlas of <it>Oryza sativa japonica </it>(rice) mitochondria, which was predicted to be approximately 490-kb long.</p> <p>Results</p> <p>Whereas statistical analysis verified the transcription of all previously known functional genes such as the ones related to oxidative phosphorylation, a similar extent of RNA expression was frequently observed in the inter-genic regions where none of the previously annotated genes are located. The newly identified open reading frames (ORFs) predicted in these transcribed inter-genic regions were generally not conserved among flowering plant species, suggesting that these ORFs did not play a role in mitochondrial principal functions. We also identified two partial fragments of retrotransposon sequences as being transcribed in rice mitochondria.</p> <p>Conclusion</p> <p>The present study indicated the previously unexpected complexity of plant mitochondrial RNA metabolism. Our transcriptomic data (<it>Oryza sativa </it>Mitochondrial rna Expression Server: OsMES) is publicly accessible at [<url>http://bioinf.mind.meiji.ac.jp/cgi-bin/gbrowse/OsMes/#search</url>].</p

Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma

The pluripotency transcription factor SOX2 is essential for the maintenance of glioblastoma stem cells (GSC), which are thought to underlie tumor growth, treatment resistance, and recurrence. To understand how SOX2 is regulated in GSCs, we utilized a proteomic approach and identified the E3 ubiquitin ligase TRIM26 as a direct SOX2-interacting protein. Unexpectedly, we found TRIM26 depletion decreased SOX2 protein levels and increased SOX2 polyubiquitination in patient-derived GSCs, suggesting TRIM26 promotes SOX2 protein stability. Accordingly, TRIM26 knockdown disrupted the SOX2 gene network and inhibited both self-renewal capacity as well as in vivo tumorigenicity in multiple GSC lines. Mechanistically, we found TRIM26, via its C-terminal PRYSPRY domain, but independent of its RING domain, stabilizes SOX2 protein by directly inhibiting the interaction of SOX2 with WWP2, which we identify as a bona fide SOX2 E3 ligase in GSCs. Our work identifies E3 ligase competition as a critical mechanism of SOX2 regulation, with functional consequences for GSC identity and maintenance

Inhibition of DNA methyltransferases blocks mutant huntingtin-induced neurotoxicity

Although epigenetic abnormalities have been described in Huntington’s disease (HD), the causal epigenetic mechanisms driving neurodegeneration in HD cortex and striatum remain undefined. Using an epigenetic pathway-targeted drug screen, we report that inhibitors of DNA methyltransferases (DNMTs), decitabine and FdCyd, block mutant huntingtin (Htt)-induced toxicity in primary cortical and striatal neurons. In addition, knockdown of DNMT3A or DNMT1 protected neurons against mutant Htt-induced toxicity, together demonstrating a requirement for DNMTs in mutant Htt-triggered neuronal death and suggesting a neurodegenerative mechanism based on DNA methylation-mediated transcriptional repression. Inhibition of DNMTs in HD model primary cortical or striatal neurons restored the expression of several key genes, including Bdnf, an important neurotrophic factor implicated in HD. Accordingly, the Bdnf promoter exhibited aberrant cytosine methylation in mutant Htt-expressing cortical neurons. In vivo, pharmacological inhibition of DNMTs in HD mouse brains restored the mRNA levels of key striatal genes known to be downregulated in HD. Thus, disturbances in DNA methylation play a critical role in mutant Htt-induced neuronal dysfunction and death, raising the possibility that epigenetic strategies targeting abnormal DNA methylation may have therapeutic utility in HD

A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells

SummaryGlioblastoma harbors a dynamic subpopulation of glioblastoma stem-like cells (GSCs) that can propagate tumors in vivo and is resistant to standard chemoradiation. Identification of the cell-intrinsic mechanisms governing this clinically important cell state may lead to the discovery of therapeutic strategies for this challenging malignancy. Here, we demonstrate that the mitotic E3 ubiquitin ligase CDC20-anaphase-promoting complex (CDC20-APC) drives invasiveness and self-renewal in patient tumor-derived GSCs. Moreover, CDC20 knockdown inhibited and CDC20 overexpression increased the ability of human GSCs to generate brain tumors in an orthotopic xenograft model in vivo. CDC20-APC control of GSC invasion and self-renewal operates through pluripotency-related transcription factor SOX2. Our results identify a CDC20-APC/SOX2 signaling axis that controls key biological properties of GSCs, with implications for CDC20-APC-targeted strategies in the treatment of glioblastoma