ABSTRACT
Offshore platforms, subsea pipelines, wells and related fixed structures supporting the oil and gas (O&G) industry are prevalent in oceans across the globe, with many approaching the end of their operational life and requiring decommissioning. Although structures can possess high ecological diversity and productivity, information on how they interact with broader ecological processes remains unclear. Here, we review the current state of knowledge on the role of O&G infrastructure in maintaining, altering or enhancing ecological connectivity with natural marine habitats. There is a paucity of studies on the subject with only 33 papers specifically targeting connectivity and O&G structures, although other studies provide important related information. Evidence for O&G structures facilitating vertical and horizontal seascape connectivity exists for larvae and mobile adult invertebrates, fish and megafauna; including threatened and commercially important species. The degree to which these structures represent a beneficial or detrimental net impact remains unclear, is complex and ultimately needs more research to determine the extent to which natural connectivity networks are conserved, enhanced or disrupted. We discuss the potential impacts of different decommissioning approaches on seascape connectivity and identify, through expert elicitation, critical knowledge gaps that, if addressed, may further inform decision making for the life cycle of O&G infrastructure, with relevance for other industries (e.g. renewables). The most highly ranked critical knowledge gap was a need to understand how O&G structures modify and influence the movement patterns of mobile species and dispersal stages of sessile marine species. Understanding how different decommissioning options affect species survival and movement was also highly ranked, as was understanding the extent to which O&G structures contribute to extending species distributions by providing rest stops, foraging habitat, and stepping stones. These questions could be addressed with further dedicated studies of animal movement in relation to structures using telemetry, molecular techniques and movement models. Our review and these priority questions provide a roadmap for advancing research needed to support evidence-based decision making for decommissioning O&G infrastructure.
Subject(s)
Ecosystem , Fishes , Animals , Invertebrates , Larva , Oceans and SeasABSTRACT
Climate change and ENSO have triggered five mass coral bleaching events on Australia's Great Barrier Reef (GBR), three of which occurred in the last 5 years.1-5 Here, we explore the cumulative nature of recent impacts and how they fragment the reef's connectivity. The coverage and intensity of thermal stress have increased steadily over time. Cumulative bleaching in 2016, 2017, and 2020 is predicted to have reduced systemic larval supply by 26%, 50%, and 71%, respectively. Larval disruption is patchy and can guide interventions. The majority of severely bleached reefs (75%) are predicted to have experienced an 80%-100% loss of larval supply. Yet restoration would not be cost-effective in the 2% of such reefs (â¼30) that still experience high larval supply. Managing such climate change impacts will benefit from emerging theory on the facilitation of genetic adaptation,6,7 which requires the existence of regions with predictably high or low thermal stress. We find that a third of reefs constitute warm spots that have consistently experienced bleaching stress. Moreover, 13% of the GBR are potential refugia that avoid significant warming more than expected by chance, with a modest proportion (14%) within highly protected areas. Coral connectivity is likely to become increasingly disrupted given the predicted escalation of climate-driven disturbances,8 but the existence of thermal refugia, potentially capable of delivering larvae to 58% of the GBR, may provide pockets of systemic resilience in the near-term. Theories of conservation planning for climate change will need to consider a shifting portfolio of thermal environments over time.
Subject(s)
Anthozoa , Coral Reefs , Animals , Climate Change , LarvaABSTRACT
AbstractCrown-of-thorns sea stars (Acanthaster sp.) are among the most studied coral reef organisms, owing to their propensity to undergo major population irruptions, which contribute to significant coral loss and reef degradation throughout the Indo-Pacific. However, there are still important knowledge gaps pertaining to the biology, ecology, and management of Acanthaster sp. Renewed efforts to advance understanding and management of Pacific crown-of-thorns sea stars (Acanthaster sp.) on Australia's Great Barrier Reef require explicit consideration of relevant and tractable knowledge gaps. Drawing on established horizon scanning methodologies, this study identified contemporary knowledge gaps by asking active and/or established crown-of-thorns sea star researchers to pose critical research questions that they believe should be addressed to improve the understanding and management of crown-of-thorns sea stars on the Great Barrier Reef. A total of 38 participants proposed 246 independent research questions, organized into 7 themes: feeding ecology, demography, distribution and abundance, predation, settlement, management, and environmental change. Questions were further assigned to 48 specific topics nested within the 7 themes. During this process, redundant questions were removed, which reduced the total number of distinct research questions to 172. Research questions posed were mostly related to themes of demography (46 questions) and management (48 questions). The dominant topics, meanwhile, were the incidence of population irruptions (16 questions), feeding ecology of larval sea stars (15 questions), effects of elevated water temperature on crown-of-thorns sea stars (13 questions), and predation on juveniles (12 questions). While the breadth of questions suggests that there is considerable research needed to improve understanding and management of crown-of-thorns sea stars on the Great Barrier Reef, the predominance of certain themes and topics suggests a major focus for new research while also providing a roadmap to guide future research efforts.
Subject(s)
Anthozoa , Starfish , Animals , Australia , Biology , Coral Reefs , HumansABSTRACT
Many habitat-building corals undergo mass synchronous spawning events. Yet, despite the enormous amounts of larvae produced, larval dispersal from a single spawning event and the reliability of larval supply are highly dependent on vagaries of ocean currents. However, colonies from the same population will occasionally spawn over successive months. These split spawning events likely help to realign reproduction events to favourable environmental conditions. Here, we show that split spawning may benefit corals by increasing the reliability of larval supply. By modelling the dispersal of coral larvae across Australia's Great Barrier Reef, we find that split spawning increased the diversity of sources and reliability of larval supply the reefs could receive, especially in regions with low and intrinsically variable connectivity. Such increased larval supply might help counteract the expected declines in reproductive success associated with split spawning events.
Subject(s)
Anthozoa/physiology , Coral Reefs , Ecosystem , Larva/physiology , Animals , Australia , Biodiversity , Oceans and Seas , Reproduction , Time FactorsABSTRACT
The decline of coral cover on Australia's Great Barrier Reef (GBR) has largely been attributed to the cumulative pressures of tropical cyclones, temperature-induced coral bleaching, and predation by crown-of-thorns starfish (CoTS). In such a complex system, the effectiveness of any management intervention will become apparent only over decadal time scales. Systems modeling approaches are therefore essential to formulating and testing alternative management strategies. For a network of reefs, we developed a metacommunity model that incorporated the cumulative pressures of tropical cyclones, coral bleaching, predation, and competition between corals. We then tested the response of coral cover to management interventions including catchment restoration to reduce discharge onto the reef during cyclone-induced flood events and enhanced protection of trophic networks supporting predation of CoTS. Model results showed good agreement with long-term monitoring of the GBR, including cyclical outbreaks of CoTS driven by predator-prey dynamics on the network of reefs. Testing of intervention strategies showed that catchment restoration would likely improve coral cover. However, strategies that combined catchment restoration with enhanced CoTS predation were far more effective than catchment restoration alone.
Subject(s)
Anthozoa , Coral Reefs , Animals , Australia , Conservation of Natural Resources , StarfishABSTRACT
Australia's iconic Great Barrier Reef (GBR) continues to suffer from repeated impacts of cyclones, coral bleaching, and outbreaks of the coral-eating crown-of-thorns starfish (COTS), losing much of its coral cover in the process. This raises the question of the ecosystem's systemic resilience and its ability to rebound after large-scale population loss. Here, we reveal that around 100 reefs of the GBR, or around 3%, have the ideal properties to facilitate recovery of disturbed areas, thereby imparting a level of systemic resilience and aiding its continued recovery. These reefs (1) are highly connected by ocean currents to the wider reef network, (2) have a relatively low risk of exposure to disturbances so that they are likely to provide replenishment when other reefs are depleted, and (3) have an ability to promote recovery of desirable species but are unlikely to either experience or spread COTS outbreaks. The great replenishment potential of these 'robust source reefs', which may supply 47% of the ecosystem in a single dispersal event, emerges from the interaction between oceanographic conditions and geographic location, a process that is likely to be repeated in other reef systems. Such natural resilience of reef systems will become increasingly important as the frequency of disturbances accelerates under climate change.
Subject(s)
Anthozoa/growth & development , Coral Reefs , Ecosystem , Animals , Larva , Tidal WavesABSTRACT
Controlling the spread of invasive species, pests, and pathogens is often logistically limited to interventions that target specific locations at specific periods. However, in complex, highly connected systems, such as marine environments connected by ocean currents, populations spread dynamically in both space and time via transient connectivity links. This results in nondeterministic future distributions of species in which local populations emerge dynamically and concurrently over a large area. The challenge, therefore, is to choose intervention locations that will maximize the effectiveness of the control efforts. We propose a novel method to manage dynamic species invasions and outbreaks that identifies the intervention locations most likely to curtail population expansion by selectively targeting local populations most likely to expand their future range. Critically, at any point during the development of the invasion or outbreak, the method identifies the local intervention that maximizes the long-term benefit across the ecosystem by restricting species' potential to spread. In so doing, the method adaptively selects the intervention targets under dynamically changing circumstances. To illustrate the effectiveness of the method we applied it to controlling the spread of crown-of-thorns starfish (Acanthaster sp.) outbreaks across Australia's Great Barrier Reef. Application of our method resulted in an 18-fold relative improvement in management outcomes compared with a random targeting of reefs in putative starfish control scenarios. Although we focused on applying the method to reducing the spread of an unwanted species, it can also be used to facilitate the spread of desirable species through connectivity networks. For example, the method could be used to select those fragments of habitat most likely to rebuild a population if they were sufficiently well protected.
Subject(s)
Anthozoa , Conservation of Natural Resources , Starfish , Animals , Australia , Ecosystem , Population DynamicsABSTRACT
Many biological systems, from fragmented landscapes to host populations, can be represented as networks of connected habitat patches. Links between patches in these connectivity networks can represent equally diverse processes, from individuals moving through the landscape to pathogen transmissions or successive colonization events in metapopulations. Any of these processes can be characterized as stochastic, with functional links among patches that exist with various levels of certainty. This stochasticity then needs to be reflected in the algorithms that aim to predict the dispersal routes in these networks. Here we adapt the concept of reliability to characterize the likelihood that a specific path will be used for dispersal in a probabilistic connectivity network. The most reliable of the paths that connect two patches will then identify the most likely sequence of intermediate steps between these patches. Path reliability will be sensitive to targeted disruptions of individual links that form the path, and this can then be used to plan the interventions aimed at either preserving or disrupting the dispersal along that path. The proposed approach is general, and can be used to identify the most likely dispersal routes in various contexts, such as predicting patterns of migrations, colonizations, invasions and epidemics.
Subject(s)
Algorithms , Animal Distribution , Ecosystem , Models, Theoretical , Population Dynamics , Computer Simulation , Stochastic ProcessesABSTRACT
Under projections of global climate change and other stressors, significant changes in the ecology, structure and function of coral reefs are predicted. Current management strategies tend to look to the past to set goals, focusing on halting declines and restoring baseline conditions. Here, we explore a complementary approach to decision making that is based on the anticipation of future changes in ecosystem state, function and services. Reviewing the existing literature and utilizing a scenario planning approach, we explore how the structure of coral reef communities might change in the future in response to global climate change and overfishing. We incorporate uncertainties in our predictions by considering heterogeneity in reef types in relation to structural complexity and primary productivity. We examine 14 ecosystem services provided by reefs, and rate their sensitivity to a range of future scenarios and management options. Our predictions suggest that the efficacy of management is highly dependent on biophysical characteristics and reef state. Reserves are currently widely used and are predicted to remain effective for reefs with high structural complexity. However, when complexity is lost, maximizing service provision requires a broader portfolio of management approaches, including the provision of artificial complexity, coral restoration, fish aggregation devices and herbivore management. Increased use of such management tools will require capacity building and technique refinement and we therefore conclude that diversification of our management toolbox should be considered urgently to prepare for the challenges of managing reefs into the 21st century.
Subject(s)
Conservation of Natural Resources/economics , Coral Reefs , Ecology/methods , Ecology/economicsABSTRACT
RATIONALE: We describe a novel negative chemically activated fragmentation/positive chemically activated fragmentation (CAF-/CAF+) technique for protein identification. The technique was used to investigate Lactobacillus brevis adaptation to nutrient deprivation. METHODS: The CAF-/CAF+ method enables de novo sequencing of derivate peptides with negative and positive ion mode matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry (MS/MS). Peptide sequences obtained from MS/MS spectra were matched against the National Center for Biotechnology Information (NCBI) non-redundant (nr) database and confirmed by the mass spectrometry data of elucidated peptide mass sequences derived from the annotated genome. This improved protein identification method highlighted 36 differentially expressed proteins in the proteome of L. brevis after 75 days of starvation. RESULTS: The results revealed the key differences in the metabolic pathways that are responsible for the survival of L. brevis in a hostile environment. Proteomics analysis demonstrated that numerous proteins engaged in glucose and amino-acid catabolizing pathways, glycerolipid metabolizing pathways, and stress-response mechanisms are differentially expressed after long-term starvation. Amino acid and proteomics analysis indicated that starved L. brevis metabolized arginine, glycine, and histidine from dead cells as alternative nutrient sources. The production of lactic acid also varied between the parent cells and the starved cells. CONCLUSIONS: Differentially expressed proteins identified exclusively by peptide sequence reading provided promising results for CAF-/CAF+ implementation in a standard proteomics workflow (e.g., biomarker and mutation discovery and biotyping). The practical performance of a reliable de novo sequencing technique in routine proteomics analysis is emphasized in this article.
Subject(s)
Bacterial Proteins/metabolism , Levilactobacillus brevis/physiology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Bacterial Proteins/analysis , Proteomics/methods , Sequence Analysis, Protein/methods , Tandem Mass Spectrometry/methodsABSTRACT
Research into the molecular mechanism of Dupuytren's disease (DD) illustrates all the problems common to drug discovery in orphan diseases, but also in more commonly investigated ailments. Current findings characterize DD as a disease with complex molecular pathology, with changes in expression of multiple genes and proteins as well as many contributing risk factors. Some of the observed changes include genes and proteins that have been identified in a number of other pathological processes, such as TGF-ß, some which may be more specific to DD, such as ADAM12, and undoubtedly also some that have yet to be discovered in future studies. When all these results are taken into consideration, it can be deduced that DD is an end result of several pathological processes that can have many points of origin, and probably involves several subtypes that give rise to sufficiently similar clinical symptoms to be unified under a single medical term. Such breadth of view has become possible with the advent of functional genomics methods and system-wide overview of the molecular processes, which highlight molecular players and processes that might not be intuitively obvious from symptoms, as is the case with the observed parallels with wound-healing processes. As functional genomics methods allow researchers to compile a more complete image of the molecular mechanisms involved in DD pathogenesis, they also help to propose new drug targets that can be employed to develop an effective pharmacological treatment for DD. Identification of key molecular players in DD has already benefited from the integration of functional genomics and biocomputational methods, and such approach may reveal new ways how we can interfere with the emergence of the DD phenotype.
Subject(s)
Drug Discovery/methods , Dupuytren Contracture/drug therapy , Dupuytren Contracture/genetics , Genomics , Molecular Targeted Therapy , Dupuytren Contracture/metabolism , Humans , PhenotypeABSTRACT
Ecosystems today increasingly suffer invasions by multiple invasive species, some of which may share similar advantageous life history traits and ecological niche. In such cases, direct competition can influence invasion success of both species, and provide insights into competition without co-evolution in species equally novel to the environment. We used two widespread crayfish invaders of freshwater ecosystems of Europe, signal crayfish (Pacifastacus leniusculus) and spiny cheek crayfish (Orconectes limosus), to investigate how behavioural decisions in agonistic encounters contribute to competitive advantages in the absence of adaptation to either opponents or an environment. In direct competition against novel but comparable opponents, the key factor for establishing clear dominance of P. leniusculus in interspecific bouts was its greater tendency towards continued engagement in high-intensity fights. With O. limosus individuals consistently retreating from staged bouts as fights became more intense, P. leniusculus individuals did not need to adapt their strategy to be successful, suggesting that their agonistic behaviour intrinsically predisposed them to win. While both species are detrimental to invaded ecosystems, our results indicate that aggressive behaviour of P. leniusculus against unfamiliar opponents could allow it to more easily outcompete other comparable species and consequently present a potentially greater threat for native ecosystems.
Subject(s)
Agonistic Behavior , Astacoidea , Introduced Species , Animals , Male , Species SpecificityABSTRACT
Social networks rely on basic rules of conduct to yield functioning societies in both human and animal populations. As individuals follow established rules, their behavioral decisions shape the social network and give it structure. Using dynamic, self-organizing social network models we demonstrate that defying conventions in a social system can affect multiple levels of social and organizational success independently. Such actions primarily affect actors' own positions within the network, but individuals can also affect the overall structure of a network even without immediately affecting themselves or others. These results indicate that defying the established social norms can help individuals to change the properties of a social system via seemingly neutral behaviors, highlighting the power of rule-breaking behavior to transform convention-based societies, even before direct impacts on individuals can be measured.
Subject(s)
Choice Behavior , Social Behavior , Social Support , HumansABSTRACT
Social networks can be used to represent group structure as a network of interacting components, and also to quantify both the position of each individual and the global properties of a group. In a series of simulation experiments based on dynamic social networks, we test the prediction that social behaviors that help individuals reach prominence within their social group may conflict with their potential to benefit from their social environment. In addition to cases where individuals were able to benefit from improving both their personal relative importance and group organization, using only simple rules of social affiliation we were able to obtain results in which individuals would face a trade-off between these factors. While selection would favor (or work against) social behaviors that concordantly increase (or decrease, respectively) fitness at both individual and group level, when these factors conflict with each other the eventual selective pressure would depend on the relative returns individuals get from their social environment and their position within it. The presented results highlight the importance of a systems approach to studying animal sociality, in which the effects of social behaviors should be viewed not only through the benefits that those provide to individuals, but also in terms of how they affect broader social environment and how in turn this is reflected back on an individual's fitness.
Subject(s)
Social Behavior , Social Environment , Systems Biology/methods , Algorithms , Animals , Behavior, Animal , Computer Simulation , Models, Biological , Models, Statistical , Social Support , Time FactorsABSTRACT
Protein stabilization by solvent additives is frequently used concept in formulation development, although new technologies implemented over the past decade can improve protein biophysical as well as clinical properties by protein structural design (e.g. PEGylation, acylation, hesylation). The scope of this work was to evaluate the effect of chosen carbohydrate or polyol stabilizer in the formulation; firstly on linear peptide sequences on instable model of rHuG-CSF cleaved macromolecule by novel method named protein and peptide stabilizer pre-screening PPSP (formulated tryptic digest mixture stability evaluation in 54 h) and on overall stability of rHuG-CSF macromolecule by quantifying all relevant degradation parameters. Comprehensive protein stabilizing screening study included conformational analysis of formulated rHuG-CSF protein to obtain information on its secondary structure conformational stability. Protein aggregation induced by modulating conditions in solution (e.g. thermal stress and agitation) was monitored over discrete time periods. Oxidation and deamidation, as well as truncation or hydrolysis were accurately quantified. Together with pre-screening data, obtained by fast and resourceful amino acid sequence degradation analysis by LC-MS, statistical data evaluation of stabilizing contribution of substances selected from group of carbohydrates and polyols was performed. According to the statistical interpretation of obtained results the stabilizers were ranked in the following order: turanose, D-trehalose, lactitol, acetate buffer (non-stabilized sample), xylitol, cellobiitol, sorbitol, D-lyxose, leucrose, sorbitol without polysorbate, cellobiose.
Subject(s)
Carbohydrates/chemistry , Excipients/chemistry , Granulocyte Colony-Stimulating Factor/chemistry , Polymers/chemistry , Amino Acid Sequence , Chemistry, Pharmaceutical/methods , Chromatography, Liquid/methods , Drug Stability , Humans , Mass Spectrometry/methods , Protein Structure, Secondary , Recombinant Proteins , Solvents/chemistry , Technology, Pharmaceutical/methods , Time FactorsABSTRACT
Although functional genomics methods offer new viewpoint on molecular processes involved in particular pathological state, these methods, in particular proteomics, are still under-represented in Dupuytren's contracture research. However, several recent papers based on functional genomics technologies represent a breakthrough in studying Dupuytren's contracture as they revealed new molecular players that had been impossible to detect by traditional molecular biology methods. Using computational tools to provide biological context for such broad arrays of data accelerates the process of homing in on the potential molecular markers and drug targets. Interactomes, maps of protein-protein interactions characteristic for the disease and as such putative models of its molecular pathology, are especially useful for this purpose, facilitating the transition from global screening methods to specific experiments aimed at therapy development. The combination of these approaches in Dupuytren's contracture research might therefore facilitate the discovery of novel therapeutic targets and diagnostic markers indicative of disease progression.
Subject(s)
Drug Delivery Systems/methods , Dupuytren Contracture/genetics , Genomics/methods , Dupuytren Contracture/metabolism , Dupuytren Contracture/therapy , Gene Expression Profiling , Gene Regulatory Networks , Humans , Lipid Metabolism , Metabolomics/methods , Models, Biological , Proteomics/methodsABSTRACT
Non-steroidal anti-inflammatory drugs (NSAID) pharmacophores are interesting in designing potential anticancer drugs. Indeed, numerous experimental, epidemiologic and clinical studies suggest that NSAIDs are promising anticancer drugs. Herein, NSAID hydroxamic acids 3a-i were prepared by a new synthetic procedure and evaluated for their antiviral and cytostatic activity against malignant tumor cell lines and normal human fibroblasts (WI38). Antiviral activity evaluation results indicated that 3f had only a minor activity against the influenza virus A/H1N1 subtype with a selectivity index of 7-10. On the other hand, the results of the in vitro cytostatic activity evaluations revealed that the majority of NSAID hydroxamic acid derivatives 3a-i exhibited a strong non-specific antiproliferative effect at the highest concentration (100 microM) on the tested cell line panel. Only compounds 3b, 3e and 3i exerted a differential dose-dependent inhibitory activity against the growth of HeLa cells (p < 0.05) at concentration 10 microM. Among those three compounds, only compound 3b showed a selective cytostatic effect on HeLa in comparison with normal fibroblasts.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antiviral Agents/pharmacology , Cytostatic Agents/pharmacology , Hydroxamic Acids/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Cell Line, Tumor , Cytostatic Agents/chemical synthesis , Cytostatic Agents/chemistry , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Hydroxamic Acids/chemical synthesis , Hydroxamic Acids/chemistry , Influenza A virus/drug effectsABSTRACT
Dupuytren's disease (DD) is a fibroproliferative disorder, the cure for which is still limited to surgical excision of the affected fascia, often leading to high recurrence rates. Due to this fact, non-surgical treatments are being investigated, among them those targeting molecular processes of proliferation and differentiation in Dupuytren's cell cultures. Drugs with antiproliferative action may be valuable in DD treatment. Through characterization of changes on DD-specific cells, we, therefore, decided to test the therapeutic potential of new cytostatic drugs for DD treatment and/or for reduction of post-operative recurrence rates. The N-sulfonylpyrimidine derivative, amidino-substituted benzimidazo[1,2-a]quinoline, and amidino dihydrothienothienyl[2,3-c]quinolone hydrochloride, known to affect proliferation processes, were tested for their antiproliferative activity on primary fibroblasts/myofibroblasts cell cultures derived from the palmar fascia of patients with DD. Only amidino dihydrothienothienyl[2,3-c]quinolone hydrochloride acted in a highly specific manner on cells derived from diseased fascia of DD patients and exhibited a low cytotoxic effect. This result might be a consequence of its specific activity on cytoskeleton changes occurring in differentiating cells. A similar short-term differential antiproliferative effect was observed by the N-sulfonylpyrimidine derivative that was, however, completely lost after 6- and 14-day treatments. The amidino-substituted benzimidazo[1,2-a]quinoline exerted a strong non-specific, dose-related antiproliferative activity on cell types.
Subject(s)
Cell Proliferation/drug effects , Drug Evaluation, Preclinical , Dupuytren Contracture/drug therapy , Fascia/drug effects , Fibroblasts/drug effects , Prodrugs/pharmacology , Case-Control Studies , Cell Cycle/drug effects , Cell Transdifferentiation/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Drug Design , Dupuytren Contracture/pathology , Dupuytren Contracture/surgery , Fascia/pathology , Fasciotomy , Fibroblasts/pathology , Humans , Inhibitory Concentration 50 , Male , Middle Aged , Molecular Structure , Prodrugs/chemistry , Prodrugs/toxicity , Pyrimidines/pharmacology , Quinolines/pharmacology , Quinolones/pharmacology , Recurrence , Structure-Activity Relationship , Time FactorsABSTRACT
Dupuytren's disease (DD) is a fibromatosis characterized by non-malignant transformation of palmar fascia leading to permanent contraction of one or more fingers. Despite the extensive knowledge of its clinical pathogenesis, the aetiology of this disease remains obscure. In the present paper, we report for the first time on the proteomic profiling of diseased versus unaffected patient-matched palmar fasciae tissues from DD patients using two-dimensional gel electrophoresis coupled with mass spectrometry analysis. The herein identified proteins were then used to create the protein-protein interaction network (interactome). Such an integrated approach revealed the involvement of several different molecular processes related to DD progression, including extra- and intra-cellular signalling, oxidative stress, cytoskeletal changes, and alterations in cellular metabolism. In particular, autocrine regulation through ERBB-2 and IGF-1R receptors and the Akt signalling pathway have emerged as novel components of pro-survival signalling in Dupuytren's fibroblasts and thus might provide a basis for a new therapeutic strategy in Dupuytren's disease.