Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo

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Pan‐Cancer analyses of Necroptosis‐Related genes as a potential target to predict immunotherapeutic outcome

Necroptosis is a unique programmed death mechanism of necrotic cells. However, its role and specific mechanism in cancer remain unclear, and a systematic pan‐cancer analysis of necroptosis is yet to be conducted. Thus, we performed a specific pan‐cancer analysis using The Cancer Genome Atlas and Genotype‐Tissue Expression databases to analyse necroptosis expression in terms of cancer prognosis, DNA methylation status, tumour mutative burden, microsatellite instability, immune cell infiltration in different types of cancer and molecular mechanisms. For the first time, we explored the correlation between necroptosis and immunotherapy prognosis. Thus, our study provides a relatively comprehensive understanding of the carcinogenicity of necroptosis in different types of cancer. It is suggested that necroptosis can be used to evaluate the sensitivity of different patients to immunotherapy and may become a potential target for tumour immunotherapy.     

Robust stability analysis of delayed Takagi-Sugeno fuzzy Hopfield neural networks with discontinuous activation functions

In this paper, the global robust stability problem of delayed Takagi–Sugeno fuzzy Hopfield neural networks with discontinuous activation functions (TSFHNNs) is considered. Based on Lyapunov stability theory and M-matrices theory, we derive a stability criterion to guarantee the global robust stability of TSFHNNs. Compared with the existing literature, we remove the assumptions on the neuron activations such as Lipschitz conditions, bounded, monotonic increasing property or the assumption that the right-limit value is bigger than the left one at the discontinuous point. Finally, two numerical examples are given to show the effectiveness of the proposed stability results.     

Enhanced control of pathogenic Simian immunodeficiency virus SIVmac239 replication in macaques immunized with an interleukin-12 plasmid and a DNA prime-viral vector boost vaccine regimen

DNA priming has previously been shown to elicit augmented immune responses when administered by electroporation (EP) or codelivered with a plasmid encoding interleukin-12 (pIL-12). We hypothesized that the efficacy of a DNA prime and recombinant adenovirus 5 boost vaccination regimen (DNA/rAd5) would be improved when incorporating these vaccination strategies into the DNA priming phase, as determined by pathogenic simian immunodeficiency virus SIVmac239 challenge outcome. The whole SIVmac239 proteome was delivered in 5 separate DNA plasmids (pDNA-SIV) by EP with or without pIL-12, followed by boosting 4 months later with corresponding rAd5-SIV vaccine vectors. Remarkably, after repeated low-dose SIVmac239 mucosal challenge, we demonstrate 2.6 and 4.4 log reductions of the median SIV peak and set point viral loads in rhesus macaques (RMs) that received pDNA-SIV by EP with pIL-12 compared to the median peak and set point viral loads in mock-immunized controls (P < 0.01). In 5 out of 6 infected RMs, strong suppression of viremia was observed, with intermittent "blips" in virus replication. In 2 RMs, we could not detect the presence of SIV RNA in tissue and lymph nodes, even after 13 viral challenges. RMs immunized without pIL-12 demonstrated a typical maximum of 1.5 log reduction in virus load. There was no significant difference in the overall magnitude of SIV-specific antibodies or CD8 T-cell responses between groups; however, pDNA delivery by EP with pIL-12 induced a greater magnitude of SIV-specific CD4 T cells that produced multiple cytokines. This vaccine strategy is relevant for existing vaccine candidates entering clinical evaluation, and this model may provide insights into control of retrovirus replication.     

Essential oil variations in different Perilla L. accessions: chemotaxonomic implications

Three processes play an important role in plant speciation: isolation, hybridization and polyploidization. Galapagos endemic Opuntia display putatively all of these processes. On this archipelago most islands are inhabited by a single Opuntia taxon. Santa Cruz, however, houses two morphologically distinct O. echios varieties (echios and gigantea). Morphological intermediates are found where these two geographically isolated varieties meet. Here we used ten microsatellite loci to reveal the population genetic structure of this system. In contrast to earlier studies, we found high genetic variability within localities. Genetic structuring was weak and no evidence for the existence of hybrids was found. The reasons for this weak genetic structure may include: the species’ hexaploid nature, high levels of gene flow, recent colonization, and the lack of geographic barriers. This first detailed genetic study on these threatened species will be important for further conservation planning.     

Paradoxical effects of a stress signal on pro- and anti-apoptotic machinery in HTLV-1 tax expressing cells

Adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) are associated with Human T-cell lymphotropic virus type 1 (HTLV-1) infection. The viral transactivator, Tax is able to mediate the cell cycle progression by targeting key regulators of the cell cycle such as p21/waf1, p16/ink4a, p53, cyclins D1-3/cdk complexes, and the mitotic spindle checkpoint MAD apparatus, thereby deregulating cellular DNA damage and checkpoint control. Genome expression profiling of infected cells exemplified by the development of DNA microarrays represents a major advance in genome-wide functional analysis. Utilizing cDNA microarray analysis, we have observed an apparent opposing and paradoxical regulatory network of host cell gene expression upon the introduction of DNA damage stress signal. We find the apparent induction of cell cycle inhibitors, and pro- as well as anti-apoptotic gene expression is directly linked to whether cells are at either G1, S, or G2/M phases of the cell cycle. Specifically, a G1/S block is induced by p21/waf1 and p16/ink4a, while pro-apoptotic expression at S, and G2/M is associated with caspase activation, and anti-apoptotic gene expression is associated with up regulation of Bcl-2 family member, namely bfl-1 gene. Therefore, the microarray results indicating expression of both pro- and anti-apoptotic genes could easily be explained by the particular stage of the cell cycle. Mechanism and the functional outcome of induction for both pathways are discussed.     

Contrasting effects of clipping and nutrient addition on reproductive traits of Heteropappus altaicus at the individual and population levels

This study was conducted to examine the effects of clipping and nutrient addition on plant traits of a dominant perennial forb species, Heteropappus altaicus (Willd.) Novopokr. (Compositae), at both the individual and population levels in a temperate steppe in northern China. A nested experimental design was used with clipping as the main factor and nutrient, including nitrogen (N), phosphorus (P) and both, addition as the second factor. The main effect of clipping reduced plant height, aboveground biomass (AGB) per plant, and pollen production per floret by 15.8, 34.3, 28.0% (all p < 0.05), respectively, but enhanced reproductive allocation and population density by 8 and 28.2% (both p < 0.05), respectively, suggesting contrary effects of clipping on H. altaicus traits at the individual and population levels. N addition significantly stimulated plant height, AGB per plant, reproductive allocation, pollen diameter, and pistil length, but decreased population density. The main effects of P addition also stimulated the plant traits at individual level, but did not change population traits. The significant interactions of clipping and nitrogen addition were observed on AGB per plant, pollen production, and population density. The differential responses of H. altaicus at the individual and population levels to clipping and nutrient addition indicate that the future dynamics of H. altaicus in the temperate steppe are uncertain and need long-term research to demonstrate.