1,721,123 research outputs found
Saccharomyces cerevisiae as a model in ecotoxicological studies: a post-genomics perspective
No full textThe budding yeast Saccharomyces cerevisiae represents a well-consolidated and widely used eukaryotic model, with a number of features that make it an ideal organism to carry out functional toxicological studies. Several advantages are permitted by the use of yeast cells, as the possibility to identify molecular biomarkers, unknown mechanisms of action and novel potential targets. Thanks to the evolutionary conservation, yeast can provide also useful clues allowing the prioritization of more complex analyses and toxicity predictions in higher eukaryotes. The last two decades were incredibly fruitful for yeast "omics", but referring to the analysis of the effects of pesticides on yeast much still remains to be done. Furthermore, a deeper knowledge of the effects of environmental pollutants on biotechnological processes associated with the use of yeasts is to be hoped. © 2015 Elsevier B.V
Fixed points and attractors of additive reaction systems
Full text linkReaction systems are discrete dynamical systems that simulate biological processes within living cells through finite sets of
reactants, inhibitors, and products. In this paper, we study the computational complexity of deciding on the existence of
fixed points and attractors in the restricted class of additive reaction systems, in which each reaction involves at most one
reactant and no inhibitors. We prove that all the considered problems, that are known to be hard for other classes of
reaction systems, are polynomially solvable in additive systems. To arrive at these results, we provide several non-trivial
reductions to problems on a polynomially computable graph representation of reaction systems that might prove useful for
addressing other related problems in the future
Cycles and global attractors of reactantless and inhibitorless reaction systems
Full text linkWe explore the computational complexity of deciding the existence of fixed points and cycles that can be reached from any other states (called global attractors) in the dynamics of inhibitorless and reactantless reaction systems. The problems we consider are all known to be
-complete in the case of unconstrained reaction systems; in this paper, we show that some of them become polynomially solvable when limited to inhibitorless and reactantless reaction systems, while others remain PSPACE-complete. Specifically, we prove that the problems of deciding (i) if a given state belongs to a cycle, (ii) whether two reaction systems have at least one cycle in common, and (iii) whether they have the same set of cycles, remain PSPACE-complete even in the inhibitorless and reactantless classes, as well as the problem of deciding if a global cycle attractor exists in a reactantless reaction system. Interestingly, however, we demonstrate that no global cycle attractor of length at least 2 can exist in inhibitorless reaction systems; and no global cycle attractor of length greater than 2 can exist in reactantless reaction systems. Furthermore, we show that the problems of deciding whether a given state is a global attractor and whether a global fixed point attractor exists become polynomially solvable when restricted to inhibitorless and reactantless reaction systems
Fixed points and attractors of reactantless and inhibitorless reaction systems
Full text linkReaction systems are discrete dynamical systems that model biochemical processes in living
cells using finite sets of reactants, inhibitors, and products. We investigate the computational
complexity of a comprehensive set of problems related to the existence of fixed points and
attractors in two constrained classes of reaction systems, in which either reactants or inhibitors
are disallowed. These problems have biological relevance and have been extensively studied
in the unconstrained case; however, they remain unexplored in the context of reactantless
or inhibitorless systems. Interestingly, we demonstrate that although the absence of reactants
or inhibitors simplifies the system’s dynamics, it does not always lead to a reduction in the
complexity of the considered problems
Proteomics of osteosarcoma
No full textOsteosarcoma (OS) is the most common primary malignant tumor of bone and the third most common cancer in childhood and adolescence. Nowadays, early diagnosis, drug resistance and recurrence of the disease represent the major challenges in OS treatment. Post-genomics, and in particular proteomic technologies, offer an invaluable opportunity to address the level of biological complexity expressed by OS. Although the main goal of OS oncoproteomics is focused on diagnostic and prognostic biomarker discovery, in this review we describe and discuss global protein profiling approaches to other aspects of OS biology and pathophysiology, or to investigate the mechanism of action of chemotherapeutics. In addition, we present proteomic analyses carried out on OS cell lines as in vitro models for studying osteoblastic cell biology and the attractive opportunity offered by proteomics of OS cancer stem cells
Omics and rare diseases: challenges, applications, and future perspectives
No full textIntroduction: Rare diseases (RDs) are a heterogeneous group of diseases recognized as a relevant global health priority but posing aspects of complexity, such as geographical scattering of affected individuals, improper/late diagnosis, limited awareness, difficult surveillance and monitoring, limited understanding of natural history, and lack of treatment. Usually, RDs have a pediatric onset and are life-long, multisystemic, and associated with a poor prognosis. Areas covered: In this work, we review how high-throughput omics technologies such as genomics, transcriptomics, proteomics, metabolomics, epigenomics, and other well-established omics, which are increasingly more affordable and efficient, can be applied to the study of RDs promoting diagnosis, understanding of pathological mechanisms, biomarker discovery, and identification of treatments. Expert opinion: RDs, despite their challenges, offer a niche where collaborative efforts and personalized treatment strategies might be feasible using omics technologies. Specialized consortia fostering multidisciplinary collaboration, data sharing, and the development of biobanks and registries can be built; multi-omics approaches, including so far less exploited omics technologies, along with the implementation of AI tools can be undertaken to deepen our understanding of RDs, driving biomarker discovery and clinical interventions. Nevertheless, technical, ethical, legal, and societal issues must be clearly defined and addressed
Postgenomics of Neisseria meningitidis: An update
No full textNeisseria meningitidis infection represents a major life-threatening bacterial disease worldwide. Genomics has revolutionized every aspect of the field of microbiology. As a consequence of genome sequencing, the postgenomic era commenced 15 years ago. Comparative genomics, functional genomics and proteomics, as well as a combination of these techniques, will play important roles in providing vital information regarding bacterial biological complexity and pathogenic traits, and accelerate the development of therapeutic drugs and vaccines for combating infections. This review summarizes the current knowledge regarding different approaches aimed to shed light on meningococcal biology and pathogenesis, and to accelerate the development and characterization of vaccines against pathogenic meningococci. © 2009 Expert Reviews Ltd
Conformations and biological activities of Amyloid Beta Peptide 25-35
No full textAmyloid-β (Aβ) peptide is commonly found in human Alzheimer's disease (AD) brain and is the main component of Alzheimer amyloid plaques. The predominant forms of Aβ in the human brain are Aβ(1-40) and Aβ(1-42), but Aβ(25-35) fragment, physiologically present in elderly people, is the more toxic region and has been recently found to play a relevant role in AD, due to its peculiar aggregation properties. In this work, we review the current understanding on the conformations and biological activity of Aβ(25-35) exploring aggregation, cytotoxic and neurodegenerative properties of this fundamental Aβ fragment, in order to provide an effective starting point to better approach a pathology spread and problematic as AD
Oxidative stress and mechanisms of ochronosis in alkaptonuria
No full textAlkaptonuria (AKU) is a rare metabolic disease due to a deficient activity of the enzyme homogentisate 1,2-dioxygenase (HGD), involved in Phe and Tyr catabolism. Due to such a deficiency, AKU patients undergo accumulation of the metabolite homogentisic acid (HGA), which is prone to oxidation/polymerization reactions causing the production of a melanin-like pigment. Once the pigment is deposited onto connective tissues (mainly in joints, spine, and cardiac valves), a classical bluish-brown discoloration is imparted, leading to a phenomenon known as "ochronosis", the hallmark of AKU. A clarification of the molecular mechanisms for the production and deposition of the ochronotic pigment in AKU started only recently with a range of in vitro and ex vivo human models used for the study of HGA-induced effects. Thanks to redox-proteomic analyses, it was found that HGA could induce significant oxidation of a number of serum and chondrocyte proteins. Further investigations allowed highlighting how HGA-induced proteome alteration, lipid peroxidation, thiol depletion, and amyloid production could contribute to oxidative stress generation and protein oxidation in AKU. This review briefly summarizes the most recent findings on HGA-induced oxidative stress in AKU, helping in the clarification of the molecular mechanisms of ochronosis and potentially providing the basis for its pharmacological treatment. Future work should be undertaken in order to validate in vivo the results so far obtained in in vitro AKU models
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