Interference of Hepatitis B Virus with Cellular Signaling

The presence of hepatitis B virus (HBV) proteins leads to changes in the cellular gene expression. As a consequence, the cellular signaling processes are influenced by the actions of HBV proteins. It has been shown that HBV nucleocapsid protein and the amino-terminal part of polymerase termed as terminal protein (TP) could inhibit interferon signaling. Further, the global gene expression profiles differ in hepatoma cells with and without HBV gene expression and replication. The expression of interferon (IFN) stimulated genes (ISGs) was differently regulated in cells with HBV replication and could be modulated by antiviral treatments. The HBV TP has been found to modulate the ISG expression and enhance the HBV replication. The modulation of the cellular signaling processes by HBV may have significant implications for pathogenesis.

Cellular signaling pathways of T cells in giant cell arteritis

Giant cell arteritis(GCA)is a commonly occurring large vacuities characterized by angiopathy of medium and large-sized vessels.GCA granulomatous formation plays an important role in the pathogenesis of GCA.Analysis of T cell lineages and signaling pathways in GCA have revealed the essential role of T cells in the pathology of GCA.T cells are the dominant population present in GCA lesions.CD4+T cell subtypes that are present include Th1,Th2,Th9,Th17,follicular helper T(Tfh)cells,and regulatory T(Treg)cells.CD8 T cells can primarily differentiate into cytotoxic CD8+T lymphocytes and Treg cells.The instrumental part of GCA is the interplay between dendritic cells,macrophages and endothelial cells,which can result in the vascular injury and the characteristics granulomatous infiltrates formation.During the inflammatory loop of GCA,several signaling pathways have been reported to play an essential role in recruiting,activating and differentiating T cells,including T-cell receptor(TCR)signaling,vascular endothelial growth factor(VEGF)-Jagged-Notch signaling and the Janus kinase and signal transducer and activator of transcription(STAT)pathway(JAK-STAT)pathway.In this review,we have focused on the role of T cells and their potential signaling mechanism(s)that are involved in the pathogenesis of GCA.A better understanding of the role of T cells mediated complicated orchestration during the homeostasis and the changes could possibly favor developments of novel treatment strategies against immunological disorders associated with GCA.

SELF-ADAPTIVE CONTROLS OF A COMPLEX CELLULAR SIGNALING TRANSDUCTION SYSTEM

In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to the changes (emergency) of kinetic behaviors of signaling system compared with single molecule or pathway. Depending on the known experimental data, we have constructed a model for complex cellular signaling transduction system, which is derived from signaling transduction of epidermal growth factor receptor in neuron. By the computational simulating methods, the self-adaptive controls of this system have been investigated. We find that this model exhibits a relatively stable selfadaptive system, especially to over-stimulation of agonist, and the amplitude and duration of signaling intermediates in it could be controlled by multiple self-adaptive effects, such as 'signal scattering', 'positive feedback', 'negative feedback' and 'B-Raf shunt'. Our results provide an approach to understanding the dynamic behaviors of complex biological systems.

Small Peptide Interacting with Pollen Calmodulinand their Effects on Cellular Functions

The interaction between dansyl-labeled pollen calmodulin (D-pCaM) and synthesized peptides was studied in the presence of Ca2+ by fluorescence spectra. It is Found that Gly/L-Ala --> D-Ala substitution in peptide chains caused great changes in their affinity for pCaM. Besides. our data provided evidence on the dissimilarity of different CaMs although they have highly-conserved structures. A preliminary study was carried out on the effects of CaM-binding peptides on cellular signal transduction, cell proliferation, showing the participation of CaM in cell functions mentioned above.

FUNDAMENTAL COMMUNICATIONS THEORIES AND SIGNAL PROCESSING TECHNIQUES FOR AMORPHOUS CELLULAR SYSTEMS

The rapid developing of the fourth generation(4G)wireless communications has aroused tremendous demands for high speed data transmission due to the dissemination of various types of the intelligent user terminals as well as the wireless multi-media services.It is predicted that the network throughput will increase

Transcriptional factor RUNX1:A potential therapeutic target for fibrotic pulmonary disease

Runt-related transcription factor-1(RUNX1),also known as the core-binding factor alpha 2 subunit,is closely related to human leukemia.The functions of RUNX1 in modulating cell proliferation,differentiation,and survival in multiple systems have been gradually discovered with the emergence of transgenic mice.RUNX1 is a powerful transcription factor implicated in diverse signaling pathways and cellular mechanisms that participate in lung development and pulmonary diseases.RUNX1 has recently been identified as a target regulator of fibrotic remodeling diseases,particularly in the kidney.However,the role of RUNX1 in pulmonary fibrosis is unclear.Pulmonary fibrosis is characterized by obscure nosogenesis,limited therapy,and poor prognosis.Moreover,the population of patients with pulmonary fibrosis is gradually increasing.Thus,there is an unmet need for therapeutic targets.In this review,we retrospectively discuss the alteration in RUNX1 mRNA expression in the RNA sequencing data of human fibrotic lungs and the protein levels in mouse pulmonary fibrosis.Subsequently,we focused on the interaction between RUNX1 and several signaling pathways involved in pulmonary fibrosis.Finally,this review highlights the therapeutic potential of RUNX1 as a target for slowing the progression of fibrotic lung disease.

Computational Cellular Dynamics Based on the Chemical Master Equation: A Challenge for Understanding Complexity

Modern molecular biology has always been a great source of inspiration for computational science. Half a century ago, the challenge from understanding macromolecular dynamics has led the way for computations to be part of the tool set to study molecular biology. Twenty-five years ago, the demand from genome science has inspired an entire generation of computer scientists with an interest in discrete mathematics to join the field that is now called bioinformatics. In this paper, we shall lay out a new mathematical theory for dynamics of biochemical reaction systems in a small volume （i.e., mesoscopic） in terms of a stochastic, discrete-state continuous-time formulation, called the chemical master equation （CME）. Similar to the wavefnnction in quantum mechanics, the dynamically changing probability landscape associated with the state space provides a fundamental characterization of the biochemical reaction system. The stochastic trajectories of the dynamics are best known through the simulations using the Gillespie algorithm. In contrast to the Metropolis algorithm, this Monte Carlo sampling technique does not follow a process with detailed balance. We shall show several examples how CMEs are used to model cellular biochemical systems. We shall also illustrate the computational challenges involved： multiscale phenomena, the interplay between stochasticity and nonlinearity, and how macroscopic determinism arises from mesoscopic dynamics. We point out recent advances in computing solutions to the CME, including exact solution of the steady state landscape and stochastic differential equations that offer alternatives to the Gilespie algorithm. We argue that the CME is an ideal system from which one can learn to understand “complex behavior” and complexity theory, and from which important biological insight can be gained.

Cell type specificity of signaling:view from membrane receptors distribution and their downstream transduction networks

Studies on cell signaling pay more attention to spatial dynamics and how such diverse organization can relate to high order of cellular capabilities.To overview the specificity of cell signaling,we integrated human receptome data with proteome spatial expression profiles to systematically investigate the specificity of receptors and receptor-triggered transduction networks across 62 normal cell types and 14 cancer types.Six percent receptors showed cell-type-specific expression,and 4% signaling networks presented enriched cell-specific proteins induced by the receptors.We introduced a concept of“response context”to annotate the cell-type dependent signaling networks.We found that most cells respond similarly to the same stimulus,as the“response contexts”presented high functional similarity.Despite this,the subtle spatial diversity can be observed from the difference in network architectures.The architecture of the signaling networks in nerve cells displayed less completeness than that in glandular cells,which indicated cellular-context dependent signaling patterns are elaborately spatially organized.Likewise,in cancer cells most signaling networks were generally dysfunctional and less complete than that in normal cells.However,glioma emerged hyper-activated transduction mechanism in malignant state.Receptor ATP6AP2 and TNFRSF21 induced rennin-angiotensin and apoptosis signaling were found likely to explain the glioma-specific mechanism.This work represents an effort to decipher context-specific signaling network from spatial dimension.Our results indicated that although a majority of cells engage general signaling response with subtle differences,the spatial dynamics of cell signaling can not only deepen our insights into different signaling mechanisms,but also help understand cell signaling in disease.

Interplay between ethylene and nitrogen nutrition:How ethylene orchestrates nitrogen responses in plants

The stress hormone ethylene plays a key role in plant adaptation to adverse environmental conditions.Nitrogen(N)is the most quantitatively required mineral nutrient for plants,and its availability is a major determinant for crop production.Changes in N availability or N forms can alter ethylene biosynthesis and/or signaling.Ethylene serves as an important cellular signal to mediate root system architecture adaptation,N uptake and translocation,ammonium toxicity,anthocyanin accumulation,and premature senescence,thereby adapting plant growth and development to external N status.Here,we review the ethylenemediated morphological and physiological responses and highlight how ethylene transduces the N signals to the adaptive responses.We specifically discuss the N-ethylene relations in rice,an important cereal crop in which ethylene is essential for its hypoxia survival.

Metropolitan spatial structure analysis based on the identification of commuting zones with Nanjing City as an example

Commuting zone research is critical to the understanding of the operational rules of the metropolitan spatial structure and improving spatial performance.This study aims to identify the main commuting centers and zones by using cellular data with Nanjing City as the example.This study analyzes the operational features of the internal spatial structures of the city from two dimensions by merging multi-source data,namely,commuting centers and zones,thus achieving an understanding of the existing problems with the urban spatial structures and their internal causes.Results showed that the commuting zones of Nanjing are distributed in a pattern of“multiple commuting centers”,with XinjiekoueHunan Road and Hongwu RoadeChaotiangongeShuangtang as the core,Mochou Lake as the main commuting area,and Dongshan and Jiangpu as the secondary commuting zones.Significant differences and similarities are discovered in our comparisons along the two dimensions of commuting zones and centers in terms of spatial structural factors,such as land use,transportation,and commuting in the city.The similarity is shown as a common declining trend in the values of all our indicators with the increase in the distance of commuting zones from the city center.However,the differences are significant in terms of the clustering features of the various parameters concerning commuting centers and zones.Specifically,four clustering patterns are discovered,namely,“monocentric clustering”,“circular monocentric clustering”,“polycentric clustering”,and“sparsely dotted distribution”.This study sheds light on the existing problems with the city’s spatial structure and proposes some overall suggestions toward urban spatial structure improvement on the basis of these findings.

Low-intensity pulsed ultrasound for regenerating peripheral nerves:potential for penile nerve

Peripheral nerve damage,such as that found after surgery or trauma,is a substantial clinical challenge.Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair after injury.In recent years,low-intensity pulsed ultrasound(LIPUS)has been studied as a potential method of stimulating peripheral nerve regeneration.In this review,the physiology of peripheral nerve regeneration is reviewed,and the experiments employing LIPUS to improve peripheral nerve regeneration are discussed.Application of LIPUS following nerve surgery may promote nerve regeneration and improve functional outcomes through a variety of proposed mechanisms.These include an increase of neurotrophic factors,Schwann cell(SC)activation,cellular signaling activations,and induction of mitosis.We searched PubMed for articles related to these topics in both in vitro and in vivo animal research models.We found numerous studies,suggesting that LIPUS following nerve surgery promotes nerve regeneration and improves functional outcomes.Based on these findings,LIPUS could be a novel and valuable treatment for nerve injury-induced erectile dysfunction.

Low-intensity pulsed ultrasound stimulates proliferation of stem/progenitor cells: what we need to know to translate basic science research into clinical applications

Low-intensity pulsed ultrasound (LIPUS) is a promising therapy that has been increasingly explored in basic research and clinical applications. LIPUS is an appealing therapeutic option as it is a noninvasive treatment that has many advantages, including no risk of infection or tissue damage and no known adverse reactions. LIPUS has been shown to have many benefits including promotion of tissue healing, angiogenesis, and tissue regeneration;inhibition of inflammation and pain relief;and stimulation of cell proliferation and differentiation. The biophysical mechanisms of LIPUS remain unclear and the studies are ongoing. In recent years, more and more research has focused on the relationship between LIPUS and stem/progenitor cells. A comprehensive search of the PubMed and Embase databases to July 2020 was performed. LIPUS has many effects on stem cells. Studies show that LIPUS can stimulate stem cells in vitro;promote stem cell proliferation, differentiation, and migration;maintain stem cell activity;alleviate the problems of insufficient seed cell source, differentiation, and maturation;and circumvent the low efficiency of stem cell transplantation. The mechanisms involved in the effects of LIPUS are not fully understood, but the effects demonstrated in studies thus far have been favorable. Much additional research is needed before LIPUS can progress from basic science research to large-scale clinical dissemination and application.

Na,K-ATPase as a target for endogenous cardiotonic steroids:What’s the evidence?

With an exception of few reports,the plasma concentration of ouabain and mari-nobufagenin,mostly studied cardiotonic steroids(CTS)assessed by immunoassay techniques,is less than 1 nM.During the last 3 decades,the implication of these endogenous CTS in the path-ogenesis of hypertension and other volume-expanded disorders is widely disputed.The threshold for inhibition by CTS of human and rodent a1-Na,K-ATPase is~1 and 1000 nM,respectively,that rules out the functioning of endogenous CTS(ECTS)as natriuretic hormones and regulators of cell adhesion,cell-to-cell communication,gene transcription and transla-tion,which are mediated by dissipation of the transmembrane gradients of monovalent cat-ions.In several types of cells ouabain and marinobufagenin at concentrations corresponding to its plasma level activate Na,K-ATPase,decrease the[Na^(+)]i;/[K^(+)]i;-ratio and increase cell pro-liferation.Possible physiological significance and mechanism of non-canonical Na^(+)/K^(+)-depen-dent and Nai^(+)/Ki^(+)independent cell responses to CTS are discussed.

A review of microfluidic approaches for investigating cancer extravasation during metastasis

Metastases,or migration of cancers,are common and severe cancer complications.Although the 5-year survival rates of primary tumors have greatly improved,those of metastasis remain below 30%,highlighting the importance of investigating specific mechanisms and therapeutic approaches for metastasis.Microfluidic devices have emerged as a powerful platform for drug target identification and drug response screening and allow incorporation of complex interactions in the metastatic microenvironment as well as manipulation of individual factors.In this work,we review microfluidic devices that have been developed to study cancer cell migration and extravasation in response to mechanical(section‘Microfluidic investigation of mechanical factors in cancer cell migration’),biochemical(section‘Microfluidic investigation of biochemical signals in cancer cell invasion’),and cellular(section‘Microfluidic metastasis-on-a-chip models for investigation of cancer extravasation’)signals.We highlight the device characteristics,discuss the discoveries enabled by these devices,and offer perspectives on future directions for microfluidic investigations of cancer metastasis,with the ultimate aim of identifying the essential factors for a‘metastasis-on-a-chip’platform to pursue more efficacious treatment approaches for cancer metastasis.

Structure-activity relationship of cyclic ADP-ribose, an update

Cyclic ADP-ribose (cADPR) is a universal Ca2+ mobilizing second messenger in many different cell types and organisms. cADPR activates Ca2+ release from endo/sarcoplasmic reticulum via ryanodine receptors. In addition, Ca2+ entry secondary to Ca2+ depletion is at least one of the mechanisms in which cADPR triggers Ca2+ inflow, too. Analogues of cADPR have been prepared by chemical and chemo-enzymatic routes. Most of the analogues were analyzed for biological activity in intact or permeabilized Jurkat T cells (a human T-lymphoma cell line). As a systematic approach, analogues were grouped according to alterations in the base, the northern ribose, the southern ribose, the pyrophosphate backbone, or in complex modifications, comprising more than one part of the molecule. Biological activity of the analogues is reviewed, with special emphasis on Jurkat T cells.