Biology subjects

Chen, P.

Publications and source records attributed to Chen, P..

239 records · Page 14Linked to original sources

bioRxiv2018

Fungal polysaccharopeptides reduce obesity by richness of specific microbiota and modulation of lipid metabolism

The prevalence of obesity and related disorders has vastly increased throughout the world and prevention of such circumstances thus represents a major challenge. Here, we show that protein-bound {beta}-glucan (PBG), one representative of Coriolus versicolor polysaccharopeptides which are broadly used as immune boosters and clinically implicated in treatment of cancers and chronic hepatitis, could be a potent anti-obesity agent. PBG could reduce obesity and metabolic inflammation in mice fed with a high-fat diet (HFD). Gut microbiota analysis revealed that PBG markedly increased the abundance of Akkermansia muciniphila although it didnt rescue HFD-induced change in the Firmicutes to Bacteroidetes ratio. It appeared that PBG altered host physiology and created an intestinal microenvironment favorable for A. muciniphila colonization. Fecal transplants from PBG-treated animals in part reduced obesity in recipient HFD-fed mice. Further, PBG was shown to promote lipid metabolism in microbiota-depleted mice. Thus, our data highlights that PBG might exert its anti-obesity effects through a mirobiota-dependent (richness of specific microbiota) and -independent (modulation of lipid metabolism) manner. The fact that Coriolus versicolor polysaccharopeptides are approved oral immune boosters in cancers and chronic hepatitis with well-established safety profiles may accelerate the development of PBG as a novel drug for obesity treatment.

microbiology↗

bioRxiv2018

Nucleo-cytoplasmic trafficking regulates nuclear surface area during nuclear organogenesis

Throughout development, nuclei must be assembled following every cell division to establish a functional organelle from compact, mitotic chromatin. During nuclear organogenesis, chromatin expands to establish a nucleus of a given size seperate from the cytoplasm. Determining how nuclear organogenesis is regulated is particularly significant in the context of certain cancers in which scaling relationships between cell and nuclear sizes are not maintained. Controlling cell size in vitro using a microfluidics approach, we determined that neither nuclear volume nor surface area scale directly with cell size. Looking to explain differential nuclear scaling relationships, we developed a simple mechano-chemical mathematical model. In simulating biological perturbations in silico, our model predicted crucial roles for nucleo-cytoplasmic trafficking in regulating nuclear expansion and in restricting the recruitment of a potential nuclear surface area factor. In mammalian tissue culture, inhibiting nuclear export increased nuclear expansion rates and reduced the amount of nuclear lamin, a candidate surface area factor, being recruited to assembling nuclei, supporting our models predictions. Targeting the principal nuclear export component in the Drosophila syncytial embryo, Embargoed, we show that nuclear expansion rates are also increased in this developmental context, consistent with our model. Using the MS2-reporter system in fly embryos, we demonstrate a role for nuclear export in regulating transcription activation timing and dynamics, suggesting that regulating nuclear assembly is crucial for downstream nuclear function. Taken together, we propose a simple model through which nuclear organogenesis is achieved and demonstrate a role for nuclear export in regulating nuclear assembly.

cell biology↗

bioRxiv2018

Non-canonical Wnt signalling initiates scarring in biliary disease

Cholangiopathies, or biliary diseases, account for a significant proportion of adult and paediatric liver disease. In these pathologies, iterative cycles of damage and repair result in the development of a regenerative microenvironment surrounding the bile ducts, which orchestrates both epithelial proliferation and also biliary fibrosis. Ultimately, fibrosis at the cost of repair results in cholestasis and liver failure, necessitating liver transplantation. Whilst the fibrogenic mechanisms in hepatocellular disease have been widely studied, little is known about the processes that regulate biliary scarring. We sought to determine how the injured biliary epithelium communicates to adjacent stromal cells to regulate scar formation, and to identify therapeutically targetable pathways that could be inhibited to reduce biliary scarring, whilst maintaining the pro-regenerative stroma. Using human tissue, bile duct organoids and animal models of biliary disease, we show that non-canonical Wnt signalling is important in initiating biliary scarring. This process is driven by myeloid Wnt5a and acts through epithelial Vangl2, which is upstream of Jnk/cJun signalling. Activation of this pathway drives a pro-fibrotic signalling process which instructs portal fibroblasts to synthesise collagen. Finally, we determine that therapeutic Wnt ligand inhibition reduces biliary scarring, identifying non-canonical Wnt signalling as a novel target for anti-fibrotic therapy in cholestatic biliary disease.

physiology↗

bioRxiv2017

Mitochondrial genomes infer phylogenetic relationships among the oldest extant winged insects (Palaeoptera)

Phylogenetic relationships among the basal orders of winged insects remain unclear, in particular the relationship of the Ephemeroptera (mayflies) and the Odonata (dragonflies and damselflies) with the Neoptera. Insect evolution is thought to have followed rapid divergence in the distant past and phylogenetic reconstruction may therefore be susceptible to problems of taxon sampling, choice of outgroup, marker selection, and tree reconstruction method. Here we newly sequenced three mitochondrial genomes representing the two most diverse families of the Ephemeroptera, one of which is a basal lineage of the order. We then used an additional 90 insect mitochondrial genomes to reconstruct their phylogeny using Bayesian and maximum likelihood approaches. Bayesian analysis supported a basal Odonata hypothesis, with Ephemeroptera as sister group to the remaining insects. This was only supported when using an optimized data matrix from which rogue taxa and terminals affected by long-branch attraction were removed. None of our analyses supported a basal Ephemeroptera hypothesis or Ephemeroptera + Odonata as monophyletic clade sister to other insects (i.e., the Palaeoptera hypothesis). Our newly sequenced mitochondrial genomes of Baetis rutilocylindratus, Cloeon dipterum, and Habrophlebiodes zijinensis had a complete set of protein coding genes and a conserved orientation except for two inverted tRNAs in H. zijinensis. Increased mayfly sampling, removal of problematic taxa, and a Bayesian phylogenetic framework were needed to infer phylogenetic relationships within the three ancient insect lineages of Odonata, Ephemeroptera, and Neoptera. Pruning of rogue taxa improved the number of supported nodes in all phylogenetic trees. Our results add to previous evidence for the Odonata hypothesis and indicate that the phylogenetic resolution of the basal insects can be resolved with more data and sampling effort.

evolutionary biology↗

bioRxiv2017

Two stochastic processes shape diverse senescence patterns in a single-cell organism

Despite advances in aging research, a multitude of aging models, and empirical evidence for diverse senescence patterns, understanding is lacking of the biological processes that shape senescence, both for simple and complex organisms. We show that for a isogenic Escherichia coli bacterial population senescence results from two stochastic processes. A primary random deterioration process within the cell, such as generated by random accumulation of damage, leads to an exponential increase in mortality early in life followed by a late age mortality plateau; a secondary process of stochastic asymmetric transmission of an unknown factor at cell fission influences mortality. This second process is required to explain the difference between the classical mortality plateaus detected for young mothers offspring and the near non-senescence of old mothers offspring as well as the lack of a mother offspring correlation in age at death. We observed that life span is predominantly determined by underlying stochastic stage dynamics. Our findings support models based on stage-specific actions of alleles for the evolution of senescence. This support might be surprising since these models that have not specifically been developed in the context of simple, single cell organisms. We call for exploration of similar stochastic influences beyond simple organisms.

systems biology↗