Non-Linear Kinetic Analysis of Protein Assembly Based on Center Manifold Theory

This review introduces a novel mathematical description of protein assembly. Protein assembly occurs in a substantially open non-equilibrium and non-linear kinetic system. The goal of systems biology is to make predictions about such complicated systems, but few have conducted stability analysis for given systems. Particularly, simulated dynamic behaviors have not been sufficiently verified by kinetic analysis in predicting macromolecular protein interactions and assembly. The non-linearity of protein assembly kinetics is complex, and it is very difficult to determine a model of multi-protein interactions based on numerical calculation. We studied the non-linear kinetics involved in the diffusion process of proteins consisting of two or three species of macromolecules and set a novel model in which non-linearity is given by the diffusion coefficient that depends on the protein concentration. By making the diffusion coefficient concentration-dependent, non-linearity leads to a simple system model. Protein assembly is initiated by monomeric protein interactions and regulated by cofactors such as guanidine triphosphate (GTP) or adenosine triphosphate (ATP) binding to the monomer. This cofactor concentration promotes the dynamic behavior of protein assembly and can be treated as an order parameter. Further, kinetic stability analysis in the center manifold theory (CMT) is introduced for analyzing the behavior of the system around the critical state. Although CMT has not been sufficiently applied for stability analysis of protein assembly systems, this theory predicts the dynamic behavior of the assembly system around the critical point using concentration as a cofactor. Protein assembly theory will provide a novel framework for nonlinear multi-parametric analysis

Cytopathology of MDS/MPN and AML by H&E Staining

Bone marrow (BM) clots are routinely sampled in aspiration tests, and their sections are prepared for histological observation by hematoxylin and eosin (H&E) staining. However, H&E-stained sections are considered less informative than those stained by the May-Grünwald Giemsa (M-G) stain; thus, diagnosis using H&E-stained clot samples is challenging for pathologists. In fact, the diagnostic evaluation is limited to the observation of cellular morphology and the myeloid-erythroid cell ratio. Pathologists leave cellular observation to laboratory hematologists, who generally use M-G staining. In this chapter, the utility of bone marrow clot specimens for diagnosis by H&E staining is reviewed. Specifically, the review provides a descriptive and illustrative explanation of the diagnosis of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myelodysplastic syndrome/myelocytic proliferative neoplasm (MDS/MPN) and demonstrates the possibility of diagnosis on the basis of the characteristic features of blast cells. Clot specimens appear to be useful for the diagnosis of hematopoietic dysplasia by pathologists, and this approach can provide more informative findings for hematologists

Information Thermodynamics of Cell Signal Transduction

Intracellular signal transduction is the most important research topic in cell biology, and for many years, model research by system biology based on network theory has long been in progress. This article reviews cell signaling from the viewpoint of information thermodynamics and describes a method for quantitatively describing signaling. In particular, a theoretical basis for evaluating the efficiency of intracellular signal transduction is presented in which information transmission in intracellular signal transduction is maximized by using entropy coding and the fluctuation theorem. An important conclusion is obtained: the average entropy production rate is constant through the signal cascade

Signaling Pathway for the Development of Pre-B Cells

Pre-B cells represent the immature stage of the B cell lineage and express genes for the pre-B cell receptor (preBCR). PreBCR consists of lambda 5 and VpreB and its expression elicits a rearrangement of the immunoglobulin heavy chain prior to rearrangement of the immunoglobulin light chain. The lambda 5 and VpreB form a surrogate light chain, which is a premature type of light chain immunoglobulin. PreBCR may cooperate or interact with the IL-7 receptor, which contributes to pre-B cell development. The preBCR distal signaling pathway recruits several adaptor proteins and protein kinases. This review aims to illustrate the framework of the signaling pathway that contributes to B cell lineage development and reconsiders the relationship between the preBCR and IL-7 receptors

Telomeres in Liver Transplantation Allografts

Living-donor liver transplant is a life-saving procedure for people with end-stage liver disease that has increased the number of organs available for people on the liver transplant waiting list. Patients often receive grafts from their relatives in living-donor liver transplantation. Maintenance of long-term graft function is important in liver transplant recipients. Livers from older donors have worse graft survival rates in human liver transplantation, and therefore, accurate evaluation of graft aging and senescence is expected to provide critical data for therapeutic intervention in long-term grafts. Many insults, including rejection, can contribute to post-transplant damage. Late post-transplant biopsies frequently show chronic hepatitis of unknown cause, and this can cause late graft dysfunction leading to cirrhosis. Telomere length in chronic hepatitis or cirrhosis is significantly lower than that in normal livers of the same age. Sustained cellular turnover in chronic liver disease accelerates cellular senescence or a crisis because of telomere shortening. Here, we review the mechanisms involved in post-transplant complications including acute cellular rejection, chronic rejection, and chronic hepatitis of unknown cause by ageing and senescence due to telomere shortening