Epigenome-Metabolome-Epigenome signaling cascade in cell biological processes

Cell fate determination as a fundamental question in cell biology has been extensively studied at different regulatory levels for many years.However,the mechanisms of multilevel regulation of cell fate determination remain unclear.Recently,we have proposed an Epigenome-Metabolome-Epigenome(E-M-E)signaling cascade model to describe the cross-over cooperation during mouse somatic cell reprogramming.In this review,we summarize the broad roles of E-M-E signaling cascade in different cell biological processes,including cell differentiation and dedifferentiation,cell specialization,cell proliferation,and cell pathologic processes.Precise E-M-E signaling cascades are critical in these cell biological processes,and it is of worth to explore each step of E-M-E signaling cascade.E-M-E signaling cascade model sheds light on and may open a window to explore the mechanisms of multilevel regulation of cell biological processes.

Synergy and Redundancy in a Signaling Cascade with Different Feedback Mechanisms

Feedback plays an important role in various biological signal transmission systems. In this paper, a signaling cascade system(including three layers: input(S), intermediate(V), output(X) components) is employed to study the fluctuations and net synergy in information transmission, in which the V component is regulated by itself or the X component, and each feedback on V is either positive or negative. The Fano factor, the net synergy, and the signalto-noise ratio(SNR) of signaling cascade with the four possible feedback types are theoretically derived by using linear noise approximation of the master equation, and the ability of information transmission through the signaling cascade is characterized by using the partial information decomposition of information theory. It is found that the signaling cascade exhibits different responses to the four feedback mechanisms, which depend on the relationships between degradation rates of components. Our results not only clarify the dependence of the Fano factor, net synergy, and SNR on the feedback regulations with the varying of degradation rates of components, but also imply that living cells could utilize different feedback mechanisms to adapt to the external fluctuating environments.

Optical Nonlinearity in a Novel Optical Signal Regeneration System Based on Cross-Gain Modulation Using Cascaded Semiconductor Optical Amplifiers

We propose a novel optical signal regeneration system based on wavelength converters by use of cross gain modulation in cascaded semiconductor optical amplifiers. The nonlinearity in optical input/output characteristics and eye opening using NRZ signal were archived.

Molecular basis of fluoride toxicities:Beyond benefits and implications in human disorders

Detrimental impacts of fluoride have become a global concern for several decades.Despite its beneficial role which is restricted only in skeletal tissues,deleterious effects are also observed in soft tissues and systems.The generation of enhanced oxidative stress is the commencement of excess fluoride exposure which may lead to cell death.Fluoride causes cell death through autophagy via Beclin 1 and mTOR signaling pathways.Beside these,several or-gan specific anomalies through different signaling pathways have been documented.Mitochon-drial dysfunction,DNA damage,autophagy and apoptosis are the damaging outcomes in case of hepatic disorders.Urinary concentration defects and cell cycle arrest have been reported in renal tissues.Abnormal immune response has been characterized in the cardiac system.Cogni-tive dysfunction,neurodegenerative condition and learning impairment have also been observed.Altered steroidogenesis,gametogenic abnormalities,epigenetic alterations and birth defect are the major reprotoxic conclusions.Abnormal immune responses,altered immu-nogenic proliferation,differentiation as well as altered ratio of immune cells are well-defined anomalies in the immune system.Though the mechanistic approach of fluoride toxicity in phys-iological systems is common,it follows different signaling cascades.This review emphasizes diverse signaling pathways which are the targets of overexposed fluoride.

Leveraging Metabolomics to Assess the Next Generation of Temozolomide-based Therapeutic Approaches for Glioblastomas

Glioblastoma multiforme （GBM） is the most common adult primary tumor of the cen- tral nervous system. The current standard of care for glioblastoma patients involves a combination of surgery, radiotherapy and chemotherapy with the alkylating agent temozolomide. Several mech- anisms underlying the inherent and acquired temozolomide resistance have been identified and con- tribute to treatment failure. Early identification of temozolomide-resistant GBM patients and improvement of the therapeutic strategies available to treat this malignancy are of uttermost impor- tance. This review initially looks at the molecular pathways underlying GBM formation and devel- opment with a particular emphasis placed on recent therapeutic advances made in the field. Our focus will next be directed toward the molecular mechanisms modulating temozolomide resistance in GBM patients and the strategies envisioned to circumvent this resistance. Finallyl we highlight the diagnostic and prognostic value of metabolomics in cancers and assess its potential usefulness in improving the current standard of care for GBM patients.