Enhancing the synchronizability of networks by rewiring based on tabu search and a local greedy algorithm

By considering the eigenratio of the Laplacian matrix as the synchronizability measure, this paper presents an efficient method to enhance the synchronizability of undirected and unweighted networks via rewiring. The rewiring method combines the use of tabu search and a local greedy algorithm so that an effective search of solutions can be achieved. As demonstrated in the simulation results, the performance of the proposed approach outperforms the existing methods for a large variety of initial networks, both in terms of speed and quality of solutions.

Smart Rewiring:Improving Network Robustness Faster

Previous work puts forward a random edge rewiring method which is capable of improving the network robustness noticeably, while it lacks further discussions about how to improve the robustness faster. In this study, the detailed analysis of the structures of improved networks show that regenerating the edges between high-degree nodes can enhance the robustness against a targeted attack. Therefore, we propose a novel rewiring strategy based on regenerating more edges between high-degree nodes, called smart rewiring, which could speed up the increase of the robustness index effectively. The smart rewiring method also explains why positive degree-degree correlation could enhance network robustness.

Contagion dynamics on adaptive multiplex networks with awareness-dependent rewiring

Over the last few years,the interplay between contagion dynamics of social influences(e.g.,human awareness,risk perception,and information dissemination)and biological infections has been extensively investigated within the framework of multiplex networks.The vast majority of existing multiplex network spreading models typically resort to heterogeneous mean-field approximation and microscopic Markov chain approaches.Such approaches usually manifest richer dynamical properties on multiplex networks than those on simplex networks;however,they fall short of a subtle analysis of the variations in connections between nodes of the network and fail to account for the adaptive behavioral changes among individuals in response to epidemic outbreaks.To transcend these limitations,in this paper we develop a highly integrated effective degree approach to modeling epidemic and awareness spreading processes on multiplex networks coupled with awareness-dependent adaptive rewiring.This approach keeps track of the number of nearest neighbors in each state of an individual;consequently,it allows for the integration of changes in local contacts into the multiplex network model.We derive a formula for the threshold condition of contagion outbreak.Also,we provide a lower bound for the threshold parameter to indicate the effect of adaptive rewiring.The threshold analysis is confirmed by extensive simulations.Our results show that awareness-dependent link rewiring plays an important role in enhancing the transmission threshold as well as lowering the epidemic prevalence.Moreover,it is revealed that intensified awareness diffusion in conjunction with enhanced link rewiring makes a greater contribution to disease prevention and control.In addition,the critical phenomenon is observed in the dependence of the epidemic threshold on the awareness diffusion rate,supporting the metacritical point previously reported in literature.This work may shed light on understanding of the interplay between epidemic dynamics and social contagion on adaptive networks.

Enhancing synchronizability by rewiring networks

According to different forms of synchronized region, complex networks are divided into type Ⅰ （unbounded synchronization region） and type Ⅱ （bounded synchronization region） networks. This paper presents a rewiring algorithm to enhance the synchronizability of type Ⅰ and type Ⅱ networks. By utilizing the algorithm for an unweighted and undirected network, a better synchronizability of network with the same number of nodes and edges can be obtained. Numerical simulations on several different network models are used to support the proposed procedure. The relationship between different topological properties of the networks and the number of rewirings are shown. It finds that the final optimized network is independent of the initial network, and becomes homogeneous. In addition the optimized networks have similar structural properties in the sense of degree, and node and edge betweenness centralities. However, they do not have similar cluster coefficients for type Ⅱ networks. The research may be useful for designing more synchronizable networks and understanding the synchronization behaviour of networks.

Network rewiring,adaptive resistance and combating strategies in breast cancer

Resistance to targeted anti-cancer drugs is a complex phenomenon and a major challenge in cancer treatment.It is becoming increasingly evident that a form of acquired drug resistance known as“adaptive resistance”is a common cause of treatment failure and patient relapse in many cancers.Unlike classical resistance mechanisms that are acquired via genomic alterations,adaptive resistance is instead driven by non-genomic changes involving rapid and dynamic rewiring of signalling and/or transcriptional networks following therapy,enabled by complex pathway crosstalk and feedback regulation.Such network rewiring allows tumour cells to adapt to the drug treatment,circumvent the initial drug challenge and continue to survive in the presence of the drug.Despite its great clinical importance,adaptive resistance remains largely under-studied and poorly defined.This review is focused on recent findings which provide new insights into the mechanisms underlying adaptive resistance in breast cancer,highlighting how breast tumour cells rewire intracellular signalling pathways to overcome the stress of initial targeted therapy.In particular,we investigate adaptive resistance to targeted inhibition of two major oncogenic signalling axes frequently dysregulated in breast cancer,the PI3K-AKT-mTOR and RAS-MAPK signalling pathways;and discuss potential combination treatment strategies that overcome such resistance.In addition,we highlight application of quantitative and computational modelling as a novel integrative and powerful approach to gain network-level understanding of network rewiring,and rationally identify and prioritise effective drug combinations.

Evolutionary rewiring and reprogramming of bacterial transcription regulation

Rewiring and reprogramming of transcriptional regulation took place during bacterial speciation. The mechanistic alterations among tran- scription factors, cis-regulatory elements and target genes confer bacteria novel ability to adapt to stochastic environmental changes. This process is critical to their survival, especially for bacterial pathogens subjected to accelerated evolution. In the past two decades, the investigators not only completed the sequences of numerous bacterial genomes, but also made great progress in understanding the molecular basis of evolution. Here we briefly reviewed the current knowledge on the mechanistic changes among orthologous, paralogous and xenogenic regulatory circuits, which were caused by genetic recombinations such as gene duplication, horizontal gene transfer, transposable elements and different genetic contexts. We also discussed the potential impact of this area on theoretical and applied studies of microbes.

Semaphorin7A:its role in the control of serotonergic circuits and functional recovery following spinal cord injury

Serotonin is a monoamine neurotransmitter synthetized in various populations of brainstem neurons.In the spinal cord,descending serotonergic projections regulate postural muscle tone,locomotion and rhythm and coordination of movements via the Central Pattern Generator.Following a spinal cord injury,serotonergic projections to the lumbar spinal cord,where the Central Pattern Generators are located,are interrupted resulting in devastating locomotor impairments and changes in the expression and activation of serotonin and its spinal receptors.The molecular cues that control the precise patterning and targeting of serotonergic inputs onto Central Pattern Generator networks in healthy animals or after injury are still unknown.In our recent research work,we have been particularly interested in Semaphorin7A,which belongs to the Semaphorins family involved in guiding growing axons and controlling plasticity of synaptic connections.In this review,we discuss the role of Semaphorin7A signaling as an important molecular actor that instructs the patterning of serotonin inputs to spinal Central Pattern Generator networks.We show that Semaphorin7A controls the wiring of descending serotonin axons in the spinal cord.Our results reveal that mistargetting of serotonin fibers in the spinal cord is compensated in healthy uninjured Semaphorin7A deficient mice so that their gross locomotion proceeds accurately.We also demonstrate that when the system is challenged with a spinal lesion,the pattern of post-injury serotonin expression is significantly altered in Semaphorin7A deficient mice with specific ectopic targeting of serotonin fibers in the lumbar spinal cord.Compensatory mechanisms in place in uninjured Semaphorin7A deficient mice are lost and injured Semaphorin7A deficient mice exhibit a worsening of their post-injury locomotor abilities.Our findings identify Semaphorin7A as a critical determinant of serotonergic circuit formation in healthy or spinal cord injured mice.

Exosomes rewire the cartilage microenvironment in osteoarthritis:from intercellular communication to therapeutic strategies

Osteoarthritis(OA)is a prevalent degenerative joint disease characterized by cartilage loss and accounts for a major source of pain and disability worldwide.However,effective strategies for cartilage repair are lacking,and patients with advanced OA usually need joint replacement.Better comprehending OA pathogenesis may lead to transformative therapeutics.Recently studies have reported that exosomes act as a new means of cell-to-cell communication by delivering multiple bioactive molecules to create a particular microenvironment that tunes cartilage behavior.Specifically,exosome cargos,such as noncoding RNAs(ncRNAs)and proteins,play a crucial role in OA progression by regulating the proliferation,apoptosis,autophagy,and inflammatory response of joint cells,rendering them promising candidates for OA monitoring and treatment.This review systematically summarizes the current insight regarding the biogenesis and function of exosomes and their potential as therapeutic tools targeting cell-to-cell communication in OA,suggesting new realms to improve OA management.

How the brain can rewire itself after an injury: the lesson from hemispherectomy

Does a post-lesional rewiring exist in the central nervous system （CNS）？ Whereas neuroimaging and neuromodulation techniques illustrate the extensive cortical reshaping after a brain injury, the remodeling of ascending and descending neuronal pathway is more difficult to be investigated. Here, we discuss how the studies dealing with hemispherectomy （HS） can provide interesting information about the functional and anatomical reorganization which take place after an extensive unilateral lesion. Indeed, studies in humans and animal models of HS clearly illustrate that the brain is capable of a widespread rewiring between the contralesional cortices and the subcortical structures as well as the medullary segments linked to the affected side of the body.

Does burning fat make tumor immune hot? Discovery of cD47 overexpression by radiation induced fatty acid oxidation

Although extensively studied,it is unknown what is the major cellular energy driving tumor metastasis after anti-cancer radiotherapy.Metabolic reprogramming is one of the fundamental hallmarks in carcinogenesis and tumor progression featured with the increased glycolysis in solid tumors.However,accumulating evidence indicates that in addition to the rudimentary glycolytic pathway,tumor cells are capable of reactivating mitochondrial OxPHOS under genotoxic stress condition to meet the increasing cellular fuel demand for repairing and surviving anti-cancer radiation.Such dynamic metabolic rewiring may play a key role in cancer therapy resistance and metastasis.Interestingly,data from our group and others have demonstrated that cancer cells can re-activate mitochondrial oxidative respiration to boost an annexing energy to meet the increasing cellular fuel demand for tumor cells surviving genotoxic anti-cancer therapy with metastatic potential.

Targeting metabolic vulnerability in mitochondria conquers MEK inhibitor resistance in KRAS-mutant lung cancer

MEK is a canonical effector of mutant KRAS;however,MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers.Here,we identified mitochondrial oxidative phosphorylation(OXPHOS)induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer(NSCLC)resistance to the clinical MEK inhibitor trametinib.Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment,satisfying their energy demand and protecting them from apoptosis.As molecular events in this process,the pyruvate dehydrogenase complex(PDHc)and carnitine palmitoyl transferase IA(CPTIA),two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation.Importantly,the co-administration of trametinib and IACS-010759,a clinical mitochondrial complex I inhibitor that blocks OXPHOS,significantly impeded tumor growth and prolonged mouse survival.Overall,our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.

Transcriptome shock in an interspecific F1 triploid hybrid of Oryza revealed by RNA sequencing

Interspecific hybridization is a driving force in evolution and speciation of higher plants. Interspecific hybridization often induces immediate and saltational changes in gene expression, a phenomenon collectively termed ＂transcriptome shock＂. Although transcriptome shock has been reported in various plant and animal taxa, the extent and pattern of shock-induced expression changes are often highly idiosyncratic, and hence entails additional investigations. Here, we produced a set of interspecific F1 triploid hybrid plants between Oryza sativa, ssp. japonica （2n=2x=24, genome AA） and the tetraploid form of O. punctata （2n=4x =48, genome, BBCC）, and conducted RNA-seq transcriptome profiling of the hybrids and their exact parental plants. We analyzed both homeolog expression bias and overall gene expression level difference in the hybrids relative to the in silico ＂hybrids＂ （parental mixtures）. We found that approximately 16% （2,541） of the 16,112 expressed genes in leaf tissue of the F1 hybrids showed nonadditive expression, which were specifically enriched in photosynthesis-related pathways. Interestingly, changes in the maternal homeolog expression, including non-stochastic silencing, were the major causes for altered homeolog expression partitioning in the F1 hybrids. Our findings have provided further insights into the tran- scriptome response to interspecific hybridization and heterosis.

Reprogramming the metabolism of Synechocystis PCC 6803 by regulating the plastoquinone biosynthesis

Cyanobacteria can utilize CO2 or even N2 to produce a variety of high value-added products efficiently.Plastoquinone(PQ)is an important electron carrier in both of the photosynthetic and respiratory electron transport chain.Although the content of PQ,as well as their redox state,have an important effect on physiology and metabolism,there are relatively few studies on the synthesis of PQ and its related metabolic regulation mechanism in photosynthetic microorganisms.In this study,the strategies of overexpression of Geranyl diphosphate:4-hydroxybenzoate geranyltransferase(lepgt)and addition of 4-hydroxybenzoate(4-HB)as the quinone ring precursor were adopted to regulate the biosynthesis of PQ in Synechocystis PCC 6803.Combined with the analysis the photosystem activity,respiration rate and metabolic components,we found the changes of intracellular PQ reprogrammed the metabolism of Synechocystis PCC 6803.The results showed that the overexpression of lepgt reduced PQ content dramatically,by 22.18%.Interestingly,both of the photosynthesis and respiration rate were enhanced.In addition,the intracellular lipid and protein contents were significantly increased.Whereas,the addition of low concentrations of 4-HB enhanced the biosynthesis of PQ,and the intracellular PQ contents were increased by 14.76%-70.86%in different conditions.Addition of 4-HB can regulate the photosystem efficiency and respiration and reprogram the metabolism of Synechocystis PCC 6803 efficiently.In a word,regulating the PQ biosynthesis provided a novel idea for promoting the reprogramming the physiology and metabolism of Synechocystis.