Dark Quest. I. Fast and Accurate Emulation of Halo Clustering Statistics and Its Application to Galaxy Clustering

We perform an ensemble of $N$-body simulations with $2048^3$ particles for 101 flat $w$CDM cosmological models sampled based on a maximin-distance Sliced Latin Hypercube Design. By using the halo catalogs extracted at multiple redshifts in the range of $z=[0,1.48]$, we develop Dark Emulator, which enables fast and accurate computations of the halo mass function, halo-matter cross-correlation, and halo auto-correlation as a function of halo masses, redshift, separations and cosmological models, based on the Principal Component Analysis and the Gaussian Process Regression for the large-dimensional input and output data vector. We assess the performance of the emulator using a validation set of $N$-body simulations that are not used in training the emulator. We show that, for typical halos hosting CMASS galaxies in the Sloan Digital Sky Survey, the emulator predicts the halo-matter cross correlation, relevant for galaxy-galaxy weak lensing, with an accuracy better than $2\%$ and the halo auto-correlation, relevant for galaxy clustering correlation, with an accuracy better than $4\%$. We give several demonstrations of the emulator. It can be used to study properties of halo mass density profiles such as the mass-concentration relation and splashback radius for different cosmologies. The emulator outputs can be combined with an analytical prescription of halo-galaxy connection such as the halo occupation distribution at the equation level, instead of using the mock catalogs, to make accurate predictions of galaxy clustering statistics such as the galaxy-galaxy weak lensing and the projected correlation function for any model within the $w$CDM cosmologies, in a few CPU seconds.Comment: 46 pages, 47 figures; version accepted for publication in Ap

シコク チュウオウブ イノ チイキ ニオケル チチブタイ ホクタイ ノ ナノカワ ショウジョウ ダンソウ シュウヘン ノ チシツ コウゾウ

The Nanokawa thrust occurs in the Jurassic accretionary complexes of the Northern Chichibu Terrain in the Ino Area， Central Shikoku. Along the thrust，greenstones and pelitic semi-schists are thrust over chaotic formations，sandstones and greenstones. The strata of the hanging wall of the thrust dip gently and are slightly folded，whereas those of the footwall dip steeply to the north. Metamorphic minerals of the greenstones of the hanging wall and footwall of the Nanokawa thrust are examined. The greenstones of the hanging wall contain alkali amphibole， alkali pyroxene， stilpnomelane and pumpellyite， and have undergone the pumpellyite-actinolite facies metamorphism. On the other hand， those of the footwall contain prehnite and pumpellyite， and have undergone the prehnite-pumpellyite facies metamorphism. The Nanokawa thrust is a large overthrust， which has a different metamorphic grade between the hanging wall and footwall. The Nanokawa thrust， which runs to the north of Shirakidani limestone body in Central Shikoku， and to the north of the Torigatayama limestone body in Middle West Shikoku， is probably a southern boundary of the Jurassic accretionary deposits which have undergone the Sambagawa Metamorphism

The Sarin-like Organophosphorus Agent bis(isopropyl methyl)phosphonate Induces Apoptotic Cell Death and COX-2 Expression in SK-N-SH Cells

Organophosphorus compounds, such as sarin, are highly toxic nerve agents that inhibit acetylcholinesterase (AChE), but not cholinesterase, via multiple mechanisms. Recent studies have shown that organophosphorus compounds increase cyclooxygenase-2 (COX-2) expression and induce neurotoxicity. In this study, we examined the toxicity of the sarin-like organophosphorus agent bis(isopropyl methyl)phosphonate (BIMP) and the effects of BIMP on COX-2 expression in SK-N-SH human neuroblastoma cells. Exposure to BIMP changed cell morphology and induced caspase-dependent apoptotic cell death accompanied by cleavage of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). It also increased COX-2 expression, while pretreatment with a COX inhibitor, ibuprofen, decreased BIMP-dependent cell death and COX-2 expression in SK-N-SH cells. Thus, our findings suggest that BIMP induces apoptotic cell death and upregulates COX-2 expression

A Lin28 homologue reprograms differentiated cells to stem cells in the moss Physcomitrella patens

Both land plants and metazoa have the capacity to reprogram differentiated cells to stem cells. Here we show that the moss Physcomitrella patens Cold-Shock Domain Protein 1 (PpCSP1) regulates reprogramming of differentiated leaf cells to chloronema apical stem cells and shares conserved domains with the induced pluripotent stem cell factor Lin28 in mammals. PpCSP1 accumulates in the reprogramming cells and is maintained throughout the reprogramming process and in the resultant stem cells. Expression of PpCSP1 is negatively regulated by its 3′-untranslated region (3′-UTR). Removal of the 3′-UTR stabilizes PpCSP1 transcripts, results in accumulation of PpCSP1 protein and enhances reprogramming. A quadruple deletion mutant of PpCSP1 and three closely related PpCSPgenes exhibits attenuated reprogramming indicating that the PpCSP genes function redundantly in cellular reprogramming. Taken together, these data demonstrate a positive role of PpCSP1 in reprogramming, which is similar to the function of mammalian Lin28

Trans-omics Impact of Thymoproteasome in Cortical Thymic Epithelial Cells

The thymic function to produce self-protective and self-tolerant T cells is chiefly mediated by cortical thymic epithelial cells (cTECs) and medullary TECs (mTECs). Recent studies including single-cell transcriptomic analyses have highlighted a rich diversity in functional mTEC subpopulations. Because of their limited cellularity, however, the biochemical characterization of TECs, including the proteomic profiling of cTECs and mTECs, has remained unestablished. Utilizing genetically modified mice that carry enlarged but functional thymuses, here we show a combination of proteomic and transcriptomic profiles for cTECs and mTECs, which identified signature molecules that characterize a developmental and functional contrast between cTECs and mTECs. Our results reveal a highly specific impact of the thymoproteasome on proteasome subunit composition in cTECs and provide an integrated trans-omics platform for further exploration of thymus biology

Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness

Metastatic breast cancer is the leading cause of cancer-associated death in women. The progression of this fatal disease is associated with inflammatory responses that promote cancer cell growth and dissemination, eventually leading to a reduction of overall survival. However, the mechanism(s) of the inflammation-boosted cancer progression remains unclear. In this study, we found for the first time that an extracellular cytokine, S100A8/A9, accelerates breast cancer growth and metastasis upon binding to a cell surface receptor, melanoma cell adhesion molecule (MCAM). Our molecular analyses revealed an important role of ETS translocation variant 4 (ETV4), which is significantly activated in the region downstream of MCAM upon S100A8/A9 stimulation, in breast cancer progression in vitro as well as in vivo. The MCAM-mediated activation of ETV4 induced a mobile phenotype called epithelial-mesenchymal transition (EMT) in cells, since we found that ETV4 transcriptionally upregulates ZEB1, a strong EMT inducer, at a very high level. In contrast, downregulation of either MCAM or ETV4 repressed EMT, resulting in greatly weakened tumor growth and lung metastasis. Overall, our results revealed that ETV4 is a novel transcription factor regulated by the S100A8/A9-MCAM axis, which leads to EMT through ZEB1 and thereby to metastasis in breast cancer cells. Thus, therapeutic strategies based on our findings might improve patient outcomes

A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell production

The Psmb11-encoded β5t subunit of the thymoproteasome, which is specifically expressed in cortical thymic epithelial cells (cTECs), is essential for the optimal positive selection of functionally competent CD8+ T cells in mice. Here, we report that a human genomic PSMB11 variation, which is detectable at an appreciable allele frequency in human populations, alters the β5t amino acid sequence that affects the processing of catalytically active β5t proteins. The introduction of this variation in the mouse genome revealed that the heterozygotes showed reduced β5t expression in cTECs and the homozygotes further exhibited reduction in the cellularity of CD8+ T cells. No severe health problems were noticed in many heterozygous and 5 homozygous human individuals. Long-term analysis of health status, particularly in the homozygotes, is expected to improve our understanding of the role of the thymoproteasome-dependent positive selection of CD8+ T cells in humans

FungalTraits:A user-friendly traits database of fungi and fungus-like stramenopiles

The cryptic lifestyle of most fungi necessitates molecular identification of the guild in environmental studies. Over the past decades, rapid development and affordability of molecular tools have tremendously improved insights of the fungal diversity in all ecosystems and habitats. Yet, in spite of the progress of molecular methods, knowledge about functional properties of the fungal taxa is vague and interpretation of environmental studies in an ecologically meaningful manner remains challenging. In order to facilitate functional assignments and ecological interpretation of environmental studies we introduce a user friendly traits and character database FungalTraits operating at genus and species hypothesis levels. Combining the information from previous efforts such as FUNGuild and Fun(Fun) together with involvement of expert knowledge, we reannotated 10,210 and 151 fungal and Stramenopila genera, respectively. This resulted in a stand-alone spreadsheet dataset covering 17 lifestyle related traits of fungal and Stramenopila genera, designed for rapid functional assignments of environmental studies. In order to assign the trait states to fungal species hypotheses, the scientific community of experts manually categorised and assigned available trait information to 697,413 fungal ITS sequences. On the basis of those sequences we were able to summarise trait and host information into 92,623 fungal species hypotheses at 1% dissimilarity threshold