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The hypothalamus-pituitary-adrenal (HPA) axis is a key neuroendocrine system implicated in stress response, major depression disorder, and post-traumatic stress disorder. We present a new, compact dynamical systems model for the response of the HPA axis to external stimuli, representing stressors or therapeutic intervention, in the presence of a circadian input. Our work builds upon previous HPA axis models where hormonal dynamics are separated into slow and fast components. Several simplifications allow us to derive an effective model of two equations, similar to a multiplicative-input FitzHugh-Nagumo system, where two stable states, a healthy and a diseased one, arise. We analyze the effective model in the context of state transitions driven by external shocks to the hypothalamus, but also modulated by circadian rhythms. Our analyses provide mechanistic insight into the effects of the circadian cycle on input driven transitions of the HPA axis and suggest a circadian influence on exposure or cognitive behavioral therapy in depression, or post-traumatic stress disorder treatment.Candidiasis, aspergillosis, and mucormycosis cause the majority of nosocomial fungal infections in immunocompromised patients. Using an unbiased transcriptional profiling in PBMCs exposed to the fungal species causing these infections, we found a core host response in healthy individuals that may govern effective fungal clearance it consists of 156 transcripts, involving canonical and non-canonical immune pathways. Systematic investigation of key steps in antifungal host defense revealed fungal-specific signatures. As previously demonstrated, Candida albicans induced type I and Type II interferon-related pathways. In contrast, central pattern recognition receptor, reactive oxygen species production, and host glycolytic pathways were down-regulated in response to Rhizopus oryzae, which was associated with an ER-stress response. TLR5 was identified to be uniquely regulated by Aspergillus fumigatus and to control cytokine release in response to this fungus. In conclusion, our data reveals the transcriptional profiles induced by C. albicans, A. fumigatus, and R. oryzae, and describes both the common and specific antifungal host responses that could be exploited for novel therapeutic strategies.Smad transcription factors are the main downstream effectors of the Transforming growth factor β superfamily (TGFβ) signalling network. The DNA complexes determined here by X-ray crystallography for the Bone Morphogenetic Proteins (BMP) activated Smad5 and Smad8 proteins reveal that all MH1 domains bind [GGC(GC)|(CG)] motifs similarly, although TGFβ-activated Smad2/3 and Smad4 MH1 domains bind as monomers whereas Smad1/5/8 form helix-swapped dimers. Dimers and monomers are also present in solution, as revealed by NMR. To decipher the characteristics that defined these dimers, we designed chimeric MH1 domains and characterized them using X-ray crystallography. We found that swapping the loop1 between TGFβ- and BMP- activated MH1 domains switches the dimer/monomer propensities. When we scanned the distribution of Smad-bound motifs in ChIP-Seq peaks (Chromatin immunoprecipitation followed by high-throughput sequencing) in Smad-responsive genes, we observed specific site clustering and spacing depending on whether the peaks correspond to BMP- or TGFβ-responsive genes. We also identified significant correlations between site distribution and monomer or dimer propensities. We propose that the MH1 monomer or dimer propensity of Smads contributes to the distinct motif selection genome-wide and together with the MH2 domain association, help define the composition of R-Smad/Smad4 trimeric complexes.Many skin conditions are associated with an imbalance in the skin microbiome. In recent years, the skin microbiome has become a hot topic, for both therapeutic and cosmetic purposes. The possibility of manipulating the human skin microbiome to address skin conditions has opened exciting new paths for therapy. Here we review the skin microbiome manipulation strategies, ranging from skin microbiome transplantation, over skin bacteriotherapy to the use of prebiotics, probiotics and postbiotics. We summarize all efforts undertaken to exchange, manipulate, transplant or selectively apply the skin microbiome to date. Multiple microbial groups have been targeted, since they have been proven to be beneficial for skin health. We focus on the most common skin disorders and their associated skin microbiome dysbiosis and we review the existing scientific data and clinical trials undertaken to combat these skin conditions. Selleckchem Vorinostat The skin microbiome represents a novel platform for therapy. Transplantation of a complete microbiome or application of single strains has demonstrated beneficial therapeutic application.Retroduplication variation (RDV), a type of retrocopy polymorphism, is considered to have essential biological significance, but its effect on gene function and species phenotype is still poorly understood. To this end, we analyzed the retrocopies and RDVs in 3,010 rice genomes. We calculated the RDV frequencies in the genome of each rice population; detected the mutated, ancestral and expressed retrogenes in rice genomes; and analyzed their RDV influence on rice phenotypic traits. Collectively, 73 RDVs were identified, and 14 RDVs in ancestral retrogenes can significantly affect rice phenotypes. Our research reveals that RDV plays an important role in rice migration, domestication and evolution. We think that RDV is a good molecular breeding marker candidate. To our knowledge, this is the first study on the relationship between retrogene function, expression, RDV and species phenotype.Many antibiotic resistance genes are associated with plasmids. The ecological success of these mobile genetic elements within microbial communities depends on varying mechanisms to secure their own propagation, not only on environmental selection. Among the most important are the cost of plasmids and their ability to be transferred to new hosts through mechanisms such as conjugation. These are regulated by dynamic control systems of the conjugation machinery and genetic adaptations that plasmid-host pairs can acquire in coevolution. However, in complex communities, these processes and mechanisms are subject to a variety of interactions with other bacterial species and other plasmid types. This article summarizes basic plasmid properties and ecological principles particularly important for understanding the persistence of plasmid-coded antibiotic resistance in aquatic environments. Through selected examples, it further introduces to the features of different types of simulation models such as systems of ordinary differential equations and individual-based models, which are considered to be important tools to understand these complex systems.
Website: https://www.selleckchem.com/products/Vorinostat-saha.html
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