scholarly journals Network controllability: viruses are driver agents in dynamic molecular systems

2018 ◽  
Author(s):  
Vandana Ravindran ◽  
Jose Carlos Nacher ◽  
Tatsuya Akutsu ◽  
Masayuki Ishitsuka ◽  
Adrian Osadcenco ◽  
...  
Keyword(s):  
Control Theory ◽  
Viral Infection ◽  
Dominating Set ◽  
Network Control ◽  
Biological Information ◽  
Maximum Matching ◽  
Effective Control ◽  
Model Control ◽  
Hiv 1 ◽  
Network Controllability

ABSTRACTIn recent years control theory has been applied to biological systems with the aim of identifying the minimum set of molecular interactions that can drive the network to a required state. However in an intra-cellular network it is unclear what ‘control’ means. To address this limitation we use viral infection, specifically HIV-1 and HCV, as a paradigm to model control of an infected cell. Using a large human signalling network comprised of over 6000 human proteins and more than 34000 directed interactions, we compared two dynamic states: normal/uninfected and infected. Our network controllability analysis demonstrates how a virus efficiently brings the dynamic host system into its control by mostly targeting existing critical control nodes, requiring fewer nodes than in the uninfected network. The driver nodes used by the virus are distributed throughout the pathways in specific locations enabling effective control of the cell via the high ‘control centrality’ of the viral and targeted host nodes. Furthermore, this viral infection of the human system permits discrimination between available network-control models, and demonstrates the minimum-dominating set (MDS) method better accounts for how biological information and signals are transferred than the maximum matching (MM) method as it identified most of the HIV-1 proteins as critical driver nodes and goes beyond identifying receptors as the only critical driver nodes. This is because MDS, unlike MM, accounts for the inherent non-linearity of signalling pathways. Our results demonstrate control-theory gives a more complete and dynamic understanding of the viral hijack mechanism when compared with previous analyses limited to static single-state networks.

scholarly journals Network controllability in transmodal cortex predicts psychosis spectrum symptoms

2020 ◽  
Author(s):  
Linden Parkes ◽  
Tyler M. Moore ◽  
Monica E. Calkins ◽  
Matthew Cieslak ◽  
David R. Roalf ◽  
...  
Keyword(s):  
Control Theory ◽  
Structural Connectivity ◽  
Prediction Performance ◽  
Network Control ◽  
Association Cortex ◽  
Out Of Sample ◽  
Sample Testing ◽  
Functional Hierarchy ◽  
Structural Connections ◽  
Network Controllability

ABSTRACTBackgroundThe psychosis spectrum is associated with structural dysconnectivity concentrated in transmodal association cortex. However, understanding of this pathophysiology has been limited by an exclusive focus on the direct connections to a region. Using Network Control Theory, we measured variation in both direct and indirect structural connections to a region to gain new insights into the pathophysiology of the psychosis spectrum.MethodsWe used psychosis symptom data and structural connectivity in 1,068 youths aged 8 to 22 years from the Philadelphia Neurodevelopmental Cohort. Applying a Network Control Theory metric called average controllability, we estimated each brain region’s capacity to leverage its direct and indirect structural connections to control linear brain dynamics. Next, using non-linear regression, we determined the accuracy with which average controllability could predict negative and positive psychosis spectrum symptoms in out-of-sample testing. We also compared prediction performance for average controllability versus strength, which indexes only direct connections to a region. Finally, we assessed how the prediction performance for psychosis spectrum symptoms varied over the functional hierarchy spanning unimodal to transmodal cortex.ResultsAverage controllability outperformed strength at predicting positive psychosis spectrum symptoms, demonstrating that indexing indirect structural connections to a region improved prediction performance. Critically, improved prediction was concentrated in association cortex for average controllability, whereas prediction performance for strength was uniform across the cortex, suggesting that indexing indirect connections is crucial in association cortex.ConclusionsExamining inter-individual variation in direct and indirect structural connections to association cortex is crucial for accurate prediction of positive psychosis spectrum symptoms.

scholarly journals Age-associated network controllability changes in first episode drug-naïve schizophrenia

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Biqiu Tang ◽  
Wenjing Zhang ◽  
Shikuang Deng ◽  
Jiang Liu ◽  
Na Hu ◽  
...  
Keyword(s):  
White Matter ◽  
Control Theory ◽  
Structural Connectivity ◽  
Network Control ◽  
First Episode ◽  
Theory Approach ◽  
Functional Connections ◽  
Age Related ◽  
Drug Naïve ◽  
Network Controllability

Abstract Background Recent neuroimaging studies revealed dysregulated neurodevelopmental, or/and neurodegenerative trajectories of both structural and functional connections in schizophrenia. However, how the alterations in the brain’s structural connectivity lead to dynamic function changes in schizophrenia with age remains poorly understood. Methods Combining structural magnetic resonance imaging and a network control theory approach, the white matter network controllability metric (average controllability) was mapped from age 16 to 60 years in 175 drug-naïve schizophrenia patients and 155 matched healthy controls. Results Compared with controls, the schizophrenia patients demonstrated the lack of age-related decrease on average controllability of default mode network (DMN), as well as the right precuneus (a hub region of DMN), suggesting abnormal maturational development process in schizophrenia. Interestingly, the schizophrenia patients demonstrated an accelerated age-related decline of average controllability in the subcortical network, supporting the neurodegenerative model. In addition, compared with controls, the lack of age-related increase on average controllability of the left inferior parietal gyrus in schizophrenia patients also suggested a different pathway of brain development. Conclusions By applying the control theory approach, the present study revealed age-related changes in the ability of white matter pathways to control functional activity states in schizophrenia. The findings supported both the developmental and degenerative hypotheses of schizophrenia, and suggested a particularly high vulnerability of the DMN and subcortical network possibly reflecting an illness-related early marker for the disorder.

scholarly journals Robustness Analysis of Structural Controllability for Directed Networks Against Single Edge Attacks

2020 ◽  
Vol 9 (8) ◽  
pp. 944-951
Keyword(s):  
Critical Infrastructure ◽  
Dominating Set ◽  
Robustness Analysis ◽  
Network Control ◽  
Single Edge ◽  
Infrastructure Systems ◽  
Malicious Attack ◽  
Graph Classes ◽  
Structural Controllability ◽  
Network Controllability

Infrastructure systems are an essential component, evolving with greater interconnectivity and interdependence at varying degrees. The control robustness of a network against malicious attack and random failure also becomes a further considerable problem in network controllability and its robustness. An adversary who is adequately knowledgeable about the control system can take control of aspects of the network as it can compromise the control network’s subset of critical nodes and/or disconnect parts of the control network resulting in low observability. Therefore, safeguarding critical infrastructure systems from different disruptions is primarily significant. This paper focuses the POWER DOMINATING SET (PDS) problem, originally introduced by Haynes to study the structure of electric power network control systems and their efficient control, as an alternate framework for the examination of the structural controllability of networks. However, PDS is generally known to be NP-complete with low approximability with recent work focusing on studying properties of restricted graph classes. Based on the PDS problem, this paper also is dedicated to studying the different edge attack strategies, as well as the robustness of network controllability of Erd s-Re ́nyi networks with directed control links under single edge attacks. MATLAB will be utilised in order to produce a simulative evaluation for more realistic critical infrastructure networks such as real power networks.

Possible Targets and Therapies of SARS-CoV-2 Infection

2020 ◽  
Vol 20 (18) ◽  
pp. 1900-1907
Author(s):  
Kasturi Sarkar ◽  
Parames C. Sil ◽  
Seyed Fazel Nabavi ◽  
Ioana Berindan-Neagoe ◽  
Cosmin Andrei Cismaru ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Replication ◽  
Viral Infection ◽  
Human Activity ◽  
Viral Proteins ◽  
Therapeutic Agents ◽  
Effective Control ◽  
Human Society ◽  
Global Spread ◽  
Repurposed Drugs

The global spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes COVID-19 has become a source of grave medical and socioeconomic concern to human society. Since its first appearance in the Wuhan region of China in December 2019, the most effective measures of managing the spread of SARS-CoV-2 infection have been social distancing and lockdown of human activity; the level of which has not been seen in our generations. Effective control of the viral infection and COVID-19 will ultimately depend on the development of either a vaccine or therapeutic agents. This article highlights the progresses made so far in these strategies by assessing key targets associated with the viral replication cycle. The key viral proteins and enzymes that could be targeted by new and repurposed drugs are discussed.

scholarly journals Limited Sustained Local Transmission of HIV-1 CRF01_AE in New South Wales, Australia

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 482 ◽  
Author(s):  
Francesca Di Giallonardo ◽  
Angie N. Pinto ◽  
Phillip Keen ◽  
Ansari Shaik ◽  
Alex Carrera ◽  
...  
Keyword(s):  
Hiv Transmission ◽  
New South ◽  
New South Wales ◽  
Incidence Rates ◽  
Effective Control ◽  
South Wales ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Local Transmission

Australia’s response to the human immunodeficiency virus type 1 (HIV-1) pandemic led to effective control of HIV transmission and one of the world’s lowest HIV incidence rates—0.14%. Although there has been a recent decline in new HIV diagnoses in New South Wales (NSW), the most populous state in Australia, there has been a concomitant increase with non-B subtype infections, particularly for the HIV-1 circulating recombinant form CRF01_AE. This aforementioned CRF01_AE sampled in NSW, were combined with those sampled globally to identify NSW-specific viral clades. The population growth of these clades was assessed in two-year period intervals from 2009 to 2017. Overall, 109 NSW-specific clades were identified, most comprising pairs of sequences; however, five large clades comprising ≥10 sequences were also found. Forty-four clades grew over time with one or two sequences added to each in different two-year periods. Importantly, while 10 of these clades have seemingly discontinued, the remaining 34 were still active in 2016/2017. Seven such clades each comprised ≥10 sequences, and are representative of individual sub-epidemics in NSW. Thus, although the majority of new CRF01_AE infections were associated with small clades that rarely establish ongoing chains of local transmission, individual sub-epidemics are present and should be closely monitored.

scholarly journals Actin-binding Protein Drebrin Regulates HIV-1-triggered Actin Polymerization and Viral Infection

2013 ◽  
Vol 288 (39) ◽  
pp. 28382-28397 ◽  
Author(s):  
Mónica Gordón-Alonso ◽  
Vera Rocha-Perugini ◽  
Susana Álvarez ◽  
Ángeles Ursa ◽  
Nuria Izquierdo-Useros ◽  
...  
Keyword(s):  
Viral Infection ◽  
Actin Polymerization ◽  
Binding Protein ◽  
Actin Binding ◽  
Actin Binding Protein ◽  
Hiv 1

scholarly journals A Computational Network Control Theory Analysis of Depression Symptoms

2018 ◽  
Vol 1 ◽  
Author(s):  
Yoed N. Kenett ◽  
Roger E. Beaty ◽  
John D. Medaglia
Keyword(s):  
Control Theory ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Brain Network ◽  
Network Control ◽  
Depression Symptoms ◽  
Theory Approach ◽  
Imaging Data ◽  
The Brain ◽  
Subclinical Depression

AbstractRumination and impaired inhibition are considered core characteristics of depression. However, the neurocognitive mechanisms that contribute to these atypical cognitive processes remain unclear. To address this question, we apply a computational network control theory approach to structural brain imaging data acquired via diffusion tensor imaging in a large sample of participants, to examine how network control theory relates to individual differences in subclinical depression. Recent application of this theory at the neural level is built on a model of brain dynamics, which mathematically models patterns of inter-region activity propagated along the structure of an underlying network. The strength of this approach is its ability to characterize the potential role of each brain region in regulating whole-brain network function based on its anatomical fingerprint and a simplified model of node dynamics. We find that subclinical depression is negatively related to higher integration abilities in the right anterior insula, replicating and extending previous studies implicating atypical switching between the default mode and Executive Control Networks in depression. We also find that subclinical depression is related to the ability to “drive” the brain system into easy to reach neural states in several brain regions, including the bilateral lingual gyrus and lateral occipital gyrus. These findings highlight brain regions less known in their role in depression, and clarify their roles in driving the brain into different neural states related to depression symptoms.

scholarly journals ADS-J1 Inhibits Semen-Derived Amyloid Fibril Formation and Blocks Fibril-Mediated Enhancement of HIV-1 Infection

2015 ◽  
Vol 59 (9) ◽  
pp. 5123-5134 ◽  
Author(s):  
Tianrong Xun ◽  
Wenjuan Li ◽  
Jinquan Chen ◽  
Fei Yu ◽  
Wei Xu ◽  
...  
Keyword(s):  
Viral Infection ◽  
Amyloid Fibrils ◽  
Synergistic Effects ◽  
Sexual Transmission ◽  
Prostatic Acid Phosphatase ◽  
Fibril Formation ◽  
Antiretroviral Drugs ◽  
Target Cells ◽  
Additional Function ◽  
Hiv 1

ABSTRACTSemen-derived enhancer of viral infection (SEVI) is composed of amyloid fibrils that can greatly enhance HIV-1 infectivity. By its cationic property, SEVI promotes viral sexual transmission by facilitating the attachment and internalization of HIV-1 to target cells. Therefore, semen-derived amyloid fibrils are potential targets for microbicide design. ADS-J1 is an anionic HIV-1 entry inhibitor. In this study, we explored an additional function of ADS-J1: inhibition of SEVI fibril formation and blockage of SEVI-mediated enhancement of viral infection. We found that ADS-J1 bound to an amyloidogenic peptide fragment (PAP248–286, comprising amino acids 248 to 286 of the enzyme prostatic acid phosphatase), thereby inhibiting peptide assembly into amyloid fibrils. In addition, ADS-J1 binds to mature amyloid fibrils and antagonizes fibril-mediated enhancement of viral infection. Unlike cellulose sulfate, a polyanion that failed in clinical trial to prevent HIV-1 sexual transmission, ADS-J1 shows no ability to facilitate fibril formation. More importantly, the combination of ADS-J1 with several antiretroviral drugs exhibited synergistic effects against HIV-1 infection in semen, with little cytotoxicity to vaginal epithelial cells. Our results suggest that ADS-J1 or a derivative may be incorporated into a combination microbicide for prevention of the sexual transmission of HIV-1.

scholarly journals Mononuclear Phagocyte Differentiation, Activation, and Viral Infection Regulate Matrix Metalloproteinase Expression: Implications for Human Immunodeficiency Virus Type 1-Associated Dementia

2001 ◽  
Vol 75 (14) ◽  
pp. 6572-6583 ◽  
Author(s):  
Anuja Ghorpade ◽  
Raisa Persidskaia ◽  
Radhika Suryadevara ◽  
Myhanh Che ◽  
Xiao Juan Liu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Infection ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
De Novo ◽  
Mononuclear Phagocyte ◽  
Monocyte Migration ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The pathogenesis of human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is mediated mainly by mononuclear phagocyte (MP) secretory products and their interactions with neural cells. Viral infection and MP immune activation may affect leukocyte entry into the brain. One factor that influences central nervous system (CNS) monocyte migration is matrix metalloproteinases (MMPs). In the CNS, MMPs are synthesized by resident glial cells and affect the integrity of the neuropil extracellular matrix (ECM). To ascertain how MMPs influence HAD pathogenesis, we studied their secretion following MP differentiation, viral infection, and cellular activation. HIV-1-infected and/or immune-activated monocyte-derived macrophages (MDM) and human fetal microglia were examined for production of MMP-1, -2, -3, and -9. MMP expression increased significantly with MP differentiation. Microglia secreted high levels of MMPs de novo that were further elevated following CD40 ligand-mediated cell activation. Surprisingly, HIV-1 infection of MDM led to the down-regulation of MMP-9. In encephalitic brain tissue, MMPs were expressed within perivascular and parenchymal MP, multinucleated giant cells, and microglial nodules. These data suggest that MMP production in MP is dependent on cell type, differentiation, activation, and/or viral infection. Regulation of MMP expression by these factors may contribute to neuropil ECM degradation and leukocyte migration during HAD.

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