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This analysis predicted that Sox2 targeted a large number of ethanol-dysregulated genes. A gene regulatory network analysis showed that many of the dysregulated genes are targeted by multiple transcription factors. Injection of sox2 mRNA partially rescued ethanol-induced gene expression, epiboly and gastrulation defects. Additional studies of this ethanol dysregulated network may identify therapeutic targets that coordinately regulate early development.A new bacterial strain, designated HM134T, was isolated from a sample of soil collected from a Chinese mangrove Avicennia marina forest. Assessed by a polyphasic approach, the taxonomy of strain HM134T was found to be associated with a range of phylogenetic and chemotaxonomic properties consistent with the genus Micromonospora. Phylogenetic analysis based on the 16s rRNA gene sequence indicated that strain HM134T formed a distinct lineage with the most closely related species, including M. rifamycinica AM105T, M. wenchangensis CCTCC AA 2012002T and M. mangrovi 2803GPT1-18T. The ANI values between strain HM134T and the reference strains ranged from 82.6% to 95.2%, which was below the standard criteria for classifying strains as the same species (96.5%). Strain HM134T and related species shared in silico dDDH similarities values below the recommended 70% cut-off for the delineation of species (range from 25.7-62.6%). The DNA G+C content of strain HM134T was 73.2 mol%. Analysis of phylogenetic, genomic, phenotypic and chemotaxonomic characteristics revealed that strain HM134T is considered to represent a novel species of the genus Micromonospora, for which the name M. zhangzhouensis sp. nov. is proposed. The extract of strain HM134T was demonstrated to exhibit cytotoxic activity against the human cancer cell lines HepG2, HCT-116 and A549. Active substance presented in the fermentation broth of strain HM134T was isolated by bioassay-guided analysis and purified afterwards. A new derivative of diterpenoid was identified through electrospray ionizing mass spectrometry (MS) and nuclear magnetic resonance (NMR). The compound showed different cytotoxic activities against cancer cells, with the highest cytotoxicity against HCT-116, corresponding to IC50 value of 38.4 μg/mL.In this report we offer the widest comparison of links removal (attack) strategies efficacy in impairing the robustness of six real-world complex weighted networks. We test eleven different link removal strategies by computing their impact on network robustness by means of using three different measures, i.e. the largest connected cluster (LCC), the efficiency (Eff) and the total flow (TF). We find that, in most of cases, the removal strategy based on the binary betweenness centrality of the links is the most efficient to disrupt the LCC. The link removal strategies based on binary-topological network features are less efficient in decreasing the weighted measures of the network robustness (e.g. Eff and TF). Removing highest weight links first is the best strategy to decrease the efficiency (Eff) in most of the networks. Last, we found that the removal of a very small fraction of links connecting higher strength nodes or of highest weight does not affect the LCC but it determines a rapid collapse of the network efficiency Eff and the total flow TF. This last outcome raises the importance of both to adopt weighted measures of network robustness and to focus the analyses on network response to few link removals.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Hypoxia-inducible factor 1 (HIF1) is a heterodimeric transcription factor, consisting of a constitutively expressed β-subunit (HIF1B) and a regulated α-subunit (HIF1A). In the present study, we analyzed the HIF1 driven transcriptional activity in bovine granulosa cells (GC). Treatment of GC with FSH (follicle stimulating hormone) and IGF1 (insulin-like growth factor 1) resulted in the upregulation of HIF1A mRNA expression under normoxia. Immunohistochemistry of bovine ovarian sections showed distinct staining of HIF1A in the GC layer of different staged ovarian follicles. Suppression of HIF1 using echinomycin and gene knockdown procedures revealed that HIF1 transcriptionally regulates the genes associated with steroidogenesis (STAR, HSD3B and CYP19A1) and proliferation (CCND2 and PCNA) of GC. Further, our data suggest that CYP19A1, the key gene of estradiol production, is one of the plausible downstream targets of HIF1 in bovine GC as shown by gene expression, radioimmunoassay, and chromatin precipitation analysis. Based on these results, we propose that HIF1 driven transcriptional activity plays a crucial role in GC functionality, especially steroidogenesis and proliferation in developing bovine ovarian follicles.Mitochondria play an essential role in bioenergetics and cellular Ca[Formula see text] handling. The mitochondrial permeability transition pore (mPTP) is a non-specific channel located in the inner mitochondrial membrane. Long-lasting openings of the pore allow the rapid passage of ions and large molecules, which can result in cell death. The mPTP also exhibits transient, low conductance openings that contribute to Ca[Formula see text] homeostasis. Although many regulators of the pore have been identified, none of them uniquely governs the passage between the two operating modes, which thus probably relies on a still unidentified network of interactions. By developing a core computational model for mPTP opening under the control of mitochondrial voltage and Ca[Formula see text], we uncovered the existence of a positive feedback loop leading to bistability. The characteristics of the two stable steady-states correspond to those of the two opening states. When inserted in a full model of Ca[Formula see text] handling by mitochondria, our description of the pore reproduces observations in mitochondrial suspensions. selleck chemicals Moreover, the model predicted the occurrence of hysteresis in the switching between the two modes, upon addition and removal of free Ca[Formula see text] in the extra-mitochondrial medium. Stochastic simulations then confirmed that the pore can undergo transient openings resembling those observed in intact cells.The reaction-diffusion system is naturally used in chemistry to represent substances reacting and diffusing over the spatial domain. Its solution illustrates the underlying process of a chemical reaction and displays diverse spatial patterns of the substances. Numerical methods like finite element method (FEM) are widely used to derive the approximate solution for the reaction-diffusion system. However, these methods require long computation time and huge computation resources when the system becomes complex. In this paper, we study the physics of a two-dimensional one-component reaction-diffusion system by using machine learning. An encoder-decoder based convolutional neural network (CNN) is designed and trained to directly predict the concentration distribution, bypassing the expensive FEM calculation process. Different simulation parameters, boundary conditions, geometry configurations and time are considered as the input features of the proposed learning model. In particular, the trained CNN model manages to learn the time-dependent behaviour of the reaction-diffusion system through the input time feature. Thus, the model is capable of providing concentration prediction at certain time directly with high test accuracy (mean relative error less then 3.04%) and 300 times faster than the traditional FEM. Our CNN-based learning model provides a rapid and accurate tool for predicting the concentration distribution of the reaction-diffusion system.The use of Trastuzumab (Herceptin), a monoclonal antibody (mAb) targeting HER2/neu, results in an increased median survival in Her2+ breast cancer patients. The tumour mutational burden and the presence of tumour infiltrating lymphocytes (TILs) clearly correlate with response to trastuzumab. Here, we investigated if the immunogenicity of the transplantable rat-neu+ tumour cell line (TUBO) derived from a BALB/c-NeuT primary tumour is associated with the response to anti-neu mAb therapy. We compared the TUBO tumour outgrowth and tumour infiltrating T cells in isogenic (BALB/c-NeuT) and non-isogenic (WT BALB/c) recipient mice. Furthermore, therapeutic efficacy of anti-neu mAb and the contribution of T cells were examined in both mouse strains. The outgrowth of untreated tumours was significantly better in BALB/c-NeuT than WT BALB/c mice. Moreover, tumour infiltrating T cells were more abundantly present in WT BALB/c than BALB/c-NeuT mice, showing that the TUBO tumour was more immunogenic in WT BALB/c mice. In TUBO tumour bearing WT BALB/c mice, anti-neu mAb therapy resulted in an increase of tumour infiltrating T cells and long-term survival. When T cells were depleted, this strong anti-tumour effect was reduced to an outgrowth delay. In contrast, in TUBO tumour bearing BALB/c-NeuT mice, treatment with anti-neu mAb resulted only in tumour outgrowth delay, both in the presence and absence of T cells. We concluded that in immunogenic tumours the response to anti-neu mAb therapy is enhanced by additional T cell involvement compared to the response to anti-neu mAb in non-immunogenic tumours.Invasions by shell-boring polychaetes such as Polydora websteri Hartman have resulted in the collapse of oyster aquaculture industries in Australia, New Zealand, and Hawaii. These worms burrow into bivalve shells, creating unsightly mud blisters that are unappealing to consumers and, when nicked during shucking, release mud and detritus that can foul oyster meats. Recent findings of mud blisters on the shells of Pacific oysters (Crassostrea gigas Thunberg) in Washington State suggest a new spionid polychaete outbreak. To determine the identity of the polychaete causing these blisters, we obtained Pacific oysters from two locations in Puget Sound and examined them for blisters and burrows caused by polychaete worms. Specimens were also obtained from eastern oysters (Crassostrea virginica Gmelin) collected in New York for morphological and molecular comparison. We compared polychaete morphology to original descriptions, extracted DNA and sequenced mitochondrial (cytochrome c oxidase I [mtCOI]) and nuclear (small subunit 18S rRNA [18S rRNA]) genes to determine a species-level molecular identification for these worms. Our data show that Polydora websteri are present in the mud blisters from oysters grown in Puget Sound, constituting the first confirmed record of this species in Washington State. The presence of this notorious invader could threaten the sustainability of oyster aquaculture in Washington, which currently produces more farmed bivalves than any other US state.Collagenase products are crucial to isolate primary cells in basic research and clinical therapies, where their stability in collagenolytic activity is required. However, currently standard collagenase products from Clostridium histolyticum lack such stability. Previously, we produced a recombinant 74-kDa collagenase from Grimontia hollisae, which spontaneously became truncated to ~60 kDa and possessed no stability. In this study, to generate G. hollisae collagenase useful as a collagenase product, we designed recombinant 62-kDa collagenase consisting only of the catalytic domain, which exhibits high production efficiency. We demonstrated that this recombinant collagenase is stable and active under physiological conditions. Moreover, it possesses higher specific activity against collagen and cleaves a wider variety of collagens than a standard collagenase product from C. histolyticum. Furthermore, it dissociated murine pancreata by digesting the collagens within the pancreata in a dose-dependent manner, and this dissociation facilitated isolation of pancreatic islets with masses and numbers comparable to those isolated using the standard collagenase from C.