694 research outputs found
Aging cellular networks: chaperones as major participants
We increasingly rely on the network approach to understand the complexity of
cellular functions. Chaperones (heat shock proteins) are key "networkers",
which have among their functions to sequester and repair damaged protein. In
order to link the network approach and chaperones with the aging process, we
first summarize the properties of aging networks suggesting a "weak link theory
of aging". This theory suggests that age-related random damage primarily
affects the overwhelming majority of the low affinity, transient interactions
(weak links) in cellular networks leading to increased noise, destabilization
and diversity. These processes may be further amplified by age-specific network
remodelling and by the sequestration of weakly linked cellular proteins to
protein aggregates of aging cells. Chaperones are weakly linked hubs [i.e.,
network elements with a large number of connections] and inter-modular bridge
elements of protein-protein interaction, signalling and mitochondrial networks.
As aging proceeds, the increased overload of damaged proteins is an especially
important element contributing to cellular disintegration and destabilization.
Additionally, chaperone overload may contribute to the increase of "noise" in
aging cells, which leads to an increased stochastic resonance resulting in a
deficient discrimination between signals and noise. Chaperone- and other
multi-target therapies, which restore the missing weak links in aging cellular
networks, may emerge as important anti-aging interventions.Comment: 7 pages, 4 figure
Salivary Genomics, Transcriptomics and Proteomics: The Emerging Concept of the Oral Ecosystem and their Use in the Early Diagnosis of Cancer and other Diseases
There is an increasingly growing interest world-wide for the genomics, transcriptomics and proteomics of saliva and the oral cavity, since they provide a non-invasive source of unprecedently rich genetic information. The complexity of oral systems biology goes much beyond the human genome, transcriptome and proteome revealed by oral mucosal cells, gingival crevicular fluid, and saliva, and includes the complexity of the oral microbiota, the symbiotic assembly of bacterial, fungal and other microbial flora in the oral cavity. In our review we summarize the recent information on oral genomics, transcriptomics and proteomics, of both human and microbial origin. We also give an introduction and practical advice on sample collection, handling and storage for analysis. Finally, we show the usefulness of salivary and oral genomics in early diagnosis of cancer, as well as in uncovering other systemic diseases, infections and oral disorders. We close the review by highlighting a number of possible exploratory pathways in this emerging, hot research field
Personal and Network Dynamics in Performance of Knowledge Workers: A Study of Australian Breast Radiologists
published_or_final_versio
Multiple, weak hits confuse complex systems: A transcriptional regulatory network as an example
Robust systems, like the molecular networks of living cells are often
resistant to single hits such as those caused by high-specificity drugs. Here
we show that partial weakening of the Escherichia coli and Saccharomyces
cerevisiae transcriptional regulatory networks at a small number (3-5) selected
nodes can have a greater impact than the complete elimination of a single
selected node. In both cases, the targeted nodes have the greatest possible
impact; still the results suggest that in some cases broad specificity
compounds or multitarget drug therapies may be more effective than individual
high-affinity, high-specificity ones. Multiple but partial attacks mimic well a
number of in vivo scenarios and may be useful in the efficient modification of
other complex systems.Comment: 8 pages, 3 figures, 2 table
The Parameterized Complexity of Centrality Improvement in Networks
The centrality of a vertex v in a network intuitively captures how important
v is for communication in the network. The task of improving the centrality of
a vertex has many applications, as a higher centrality often implies a larger
impact on the network or less transportation or administration cost. In this
work we study the parameterized complexity of the NP-complete problems
Closeness Improvement and Betweenness Improvement in which we ask to improve a
given vertex' closeness or betweenness centrality by a given amount through
adding a given number of edges to the network. Herein, the closeness of a
vertex v sums the multiplicative inverses of distances of other vertices to v
and the betweenness sums for each pair of vertices the fraction of shortest
paths going through v. Unfortunately, for the natural parameter "number of
edges to add" we obtain hardness results, even in rather restricted cases. On
the positive side, we also give an island of tractability for the parameter
measuring the vertex deletion distance to cluster graphs
Stress-induced rearrangements of cellular networks: consequences for protection and drug design
The complexity of the cells can be described and understood by a number of
networks such as protein-protein interaction, cytoskeletal, organelle,
signalling, gene transcription and metabolic networks. All these networks are
highly dynamic producing continuous rearrangements in their links, hubs,
network-skeleton and modules. Here we describe the adaptation of cellular
networks after various forms of stress causing perturbations, congestions and
network damage. Chronic stress decreases link-density, decouples or even
quarantines modules, and induces an increased competition between network hubs
and bridges. Extremely long or strong stress may induce a topological phase
transition in the respective cellular networks, which switches the cell to a
completely different mode of cellular function. We summarize our initial
knowledge on network restoration after stress including the role of molecular
chaperones in this process. Finally, we discuss the implications of
stress-induced network rearrangements in diseases and ageing, and propose
therapeutic approaches both to increase the robustness and help the repair of
cellular networks.Comment: 9 pages, 1 table, 2 figures, invited paper of FEBS Letters Cellular
Stress special issu
Networking the way towards antimicrobial combination therapies
Publicado em "8th International Conference on Practical Applications of Computational Biology & Bioinformatics (PACBB 2014)"The exploration of new antimicrobial combinations is a pressing concern for Clinical Microbiology due to the growing number of resistant strains emerging in healthcare settings and in the general community. Researchers are screening agents with alternative modes of action and interest is rising for the potential of antimicrobial peptides (AMPs). This work presents the first ever network reconstruction of AMP combinations reported in the literature fighting Pseudomonas aeruginosa infections. The network, containing 193 combinations of AMPs with 39 AMPs and 154 traditional antibiotics, is expected to help in the design of new studies, notably by unveiling different mechanisms of action and helping in the prediction of new combinations and synergisms. The challenges faced in the attempted text-mining approaches and other considerations regarding the manual curation of the data are pointed out, reflecting about the future automation of this type of reconstruction as means to widen the scope of analysis
Communities as Well Separated Subgraphs With Cohesive Cores: Identification of Core-Periphery Structures in Link Communities
Communities in networks are commonly considered as highly cohesive subgraphs
which are well separated from the rest of the network. However, cohesion and
separation often cannot be maximized at the same time, which is why a
compromise is sought by some methods. When a compromise is not suitable for the
problem to be solved it might be advantageous to separate the two criteria. In
this paper, we explore such an approach by defining communities as well
separated subgraphs which can have one or more cohesive cores surrounded by
peripheries. We apply this idea to link communities and present an algorithm
for constructing hierarchical core-periphery structures in link communities and
first test results.Comment: 12 pages, 2 figures, submitted version of a paper accepted for the
7th International Conference on Complex Networks and Their Applications,
December 11-13, 2018, Cambridge, UK; revised version at
http://141.20.126.227/~qm/papers
Learning and innovative elements of strategy adoption rules expand cooperative network topologies
Cooperation plays a key role in the evolution of complex systems. However,
the level of cooperation extensively varies with the topology of agent networks
in the widely used models of repeated games. Here we show that cooperation
remains rather stable by applying the reinforcement learning strategy adoption
rule, Q-learning on a variety of random, regular, small-word, scale-free and
modular network models in repeated, multi-agent Prisoners Dilemma and Hawk-Dove
games. Furthermore, we found that using the above model systems other long-term
learning strategy adoption rules also promote cooperation, while introducing a
low level of noise (as a model of innovation) to the strategy adoption rules
makes the level of cooperation less dependent on the actual network topology.
Our results demonstrate that long-term learning and random elements in the
strategy adoption rules, when acting together, extend the range of network
topologies enabling the development of cooperation at a wider range of costs
and temptations. These results suggest that a balanced duo of learning and
innovation may help to preserve cooperation during the re-organization of
real-world networks, and may play a prominent role in the evolution of
self-organizing, complex systems.Comment: 14 pages, 3 Figures + a Supplementary Material with 25 pages, 3
Tables, 12 Figures and 116 reference
Heat shock partially dissociates the overlapping modules of the yeast protein-protein interaction network: a systems level model of adaptation
Network analysis became a powerful tool in recent years. Heat shock is a
well-characterized model of cellular dynamics. S. cerevisiae is an appropriate
model organism, since both its protein-protein interaction network
(interactome) and stress response at the gene expression level have been well
characterized. However, the analysis of the reorganization of the yeast
interactome during stress has not been investigated yet. We calculated the
changes of the interaction-weights of the yeast interactome from the changes of
mRNA expression levels upon heat shock. The major finding of our study is that
heat shock induced a significant decrease in both the overlaps and connections
of yeast interactome modules. In agreement with this the weighted diameter of
the yeast interactome had a 4.9-fold increase in heat shock. Several key
proteins of the heat shock response became centers of heat shock-induced local
communities, as well as bridges providing a residual connection of modules
after heat shock. The observed changes resemble to a "stratus-cumulus" type
transition of the interactome structure, since the unstressed yeast interactome
had a globally connected organization, similar to that of stratus clouds,
whereas the heat shocked interactome had a multifocal organization, similar to
that of cumulus clouds. Our results showed that heat shock induces a partial
disintegration of the global organization of the yeast interactome. This change
may be rather general occurring in many types of stresses. Moreover, other
complex systems, such as single proteins, social networks and ecosystems may
also decrease their inter-modular links, thus develop more compact modules, and
display a partial disintegration of their global structure in the initial phase
of crisis. Thus, our work may provide a model of a general, system-level
adaptation mechanism to environmental changes.Comment: 24 pages, 6 figures, 2 tables, 70 references + 22 pages 8 figures, 4
tables and 8 references in the enclosed Supplemen
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