Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an animal model

Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration(PPC)and is often clinically complicated by malignant diseases or severe infections.At present,however,research on the molecular mechanism underlying high PPC(HPPC)is scant.Here,an animal model of primary hyperproteinemia was constructed in an invertebrate(Bombyx mori)to investigate the effects of HPPC on circulating blood cells.Results showed that HPPC affected blood cell homeostasis,leading to increased reactive oxygen species levels,and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway.HPPC induced the proliferation of blood cells,mainly granulocytes,by activating the Janus kinase/signal transducer and activator of transcription(JAK/STAT)signaling pathway.Supplementation with the endocrine hormone active substance 20 E significantly reduced the impact of HPPC on blood cell homeostasis.Thus,we identified a novel signaling pathway by which HPPC affects blood cell homeostasis,which differs from hyperglycemia,hyperlipidemia,and hypercholesterolemia.In addition,we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.

BMP-IHH-mediated interplay between mesenchymal stem cells and osteoclasts supports calvarial bone homeostasis and repair

Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells(MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and repair. Abnormal function of osteogenic cells or diminished MSCs within the cranial suture can lead to skull defects, such as craniosynostosis. Despite the important function of each of these cell types within the cranial suture, we have limited knowledge about the role that crosstalk between them may play in regulating calvarial bone homeostasis and injury repair. Here we show that suture MSCs give rise to osteoprogenitors that show active bone morphogenetic protein(BMP) signalling and depend on BMP-mediated Indian hedgehog(IHH) signalling to balance osteogenesis and osteoclastogenesis activity. IHH signalling and receptor activator of nuclear factor kappa-Β ligand(RANKL) may function synergistically to promote the differentiation and resorption activity of osteoclasts. Loss of Bmpr1a in MSCs leads to downregulation of hedgehog(Hh) signalling and diminished cranial sutures. Significantly, activation of Hh signalling partially restores suture morphology in Bmpr1a mutant mice, suggesting the functional importance of BMP-mediated Hh signalling in regulating suture tissue homeostasis. Furthermore, there is an increased number of CD200+ cells in Bmpr1a mutant mice, which may also contribute to the inhibited osteoclast activity in the sutures of mutant mice. Finally, suture MSCs require BMPmediated Hh signalling during the repair of calvarial bone defects after injury. Collectively, our studies reveal the molecular and cellular mechanisms governing cell–cell interactions within the cranial suture that regulate calvarial bone homeostasis and repair.

Invariance and Noises of Shannon Entropy for Information on Oxidative Activity of DNA in All Living Cells for Medical Diagnostics

We analyze oxidative activity of DNA due to fluorescence of chromosomes inside cells, using flow cytometry method with nanometer spatial resolution. Statistics of fluorescence is presented in histogram as frequency distributions of flashes in the dependence on their intensity and in distributions of Shannon entropy, which was defined on the base of normalized distribution of information in original histogram for frequency of flashes. We show that overall sum of entropy, i.e. total entropy E , for any histogram is invariant and has identical trends of changes all values of E(r) = lnr at reduction of histogram’ rank r. This invariance reflects informational homeostasis of chromosomes activity in multi-scale networks of entropy inside all cells in various samples of blood for DNA inside neutrophils, lymphocytes, inside all leukocytes of human and inside chicken erythrocytes for various dyes, colors and various excitations of fluorescence. Informational homeostasis of oxidative activity of 3D DNA in the full set of chromosomes inside living cells exists for any Shannon-Weaver index of biodiversity of cells, at any state of health different beings. Regulation perturbations in information activity DNA provides informational adaptability and vitality of cells at homeostasis support. Noises of entropy, during regulation of informational homeostasis, depend on the states of health in real time. The main structural reconstructions of chromosomal correlations, corresponding to self-regulation of homeostasis, occur in the most large-scale networks of entropy, for rank r<32. We show that stability of homeostasis is supported by activity of all 46 chromosomes inside cells. Patterns, hidden switching and branching in sequences of averages of H?lder and central moments for noises in regulation of homeostasis define new opportunities in diagnostics of health and immunity. All people and all aerobic beings have one overall homeostatic level for countdown of information activity of DNA inside cells. We noted very bad and dangerous properties of artificial cells with other levels of informational homeostasis for all aerobic beings in foods, medical treatment and in biotechnologies.

Molecular Framework for Auxin-Controlled Hlomeostasis-of Shoot Stem Cells in Arabidopsis

The classic phytohormone auxin plays an essential role in priming meristematic cell differentiation in the shoot apical meristem to promote lateral organ initiation. Recently, several lines of evidence have suggested that auxin is not only transported to new primordia but also descends to the stem cells in the central zone. However, the function of auxin in stem cell regulation has remained elusive. Here, we show that auxin signaling in stem cells is mediated, at least in part, byAUXIN RESPONSE FACTOR 5/MONOPTEROS （ARF5/MP）, which directly represses the transcription of DORNROSCHEN /ENHANCER OF SHO0 T REGENERA TION 1 （DRN/ESR 1）. DRN expressed in stem cells positively regulates CLAVATA3 （CLV3） expression and has important meristematic functions. Our results provide a mechanistic framework for auxin control of shoot stem cell homeostasis and demonstrate how auxin differentially controls plant stem cell maintenance and differentiation.

Balanced biosynthesis and trigger threshold resulting in a double adder mechanism of cell size control

How cells accomplish cell size homeostasis is a fascinating topic, and several cell size regulation mechanisms were proposed: timer, sizer, and adder. Recently the adder model has received a great deal of attention. Adder property was also found in the DNA replication cycle. This paper aims to explain the adder phenomenon both in the division-centric picture and replication-centric picture at the molecular level. We established a self-replication model, and the system reached a steady state quickly based on evolution rules. We collected tens of thousands of cells in the same trajectory and calculated the Pearson correlation coefficient between biological variables to decide which regulatory mechanism was adopted by cells. Our simulation results confirmed the double-adder mechanism. Chromosome replication initiation and cell division control are independent and regulated by respective proteins.Cell size homeostasis originates from division control and has nothing to do with replication initiation control. At a slow growth rate, the deviation from adder toward sizer comes from a significant division protein degradation rate when division protein is auto-inhibited. Our results indicated the two necessary conditions in the double-adder mechanism: one is balanced biosynthesis, and the other is that there is a protein trigger threshold to inspire DNA replication initiation and cell division. Our results give insight to the regulatory mechanism of cell size and instructive to synthetic biology.