The Open Biology Journal最新文献

{"title":"Special Issue: Fighting infections in developing countries by cost-affordable and sustainable means.","authors":"G. Borkow","doi":"10.2174/1874196701003030072","DOIUrl":"https://doi.org/10.2174/1874196701003030072","url":null,"abstract":"","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84700591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIF-1α Promotes A Hypoxia-Independent Cell Migration.","authors":"Liyuan Li, Chikezie O Madu, Andrew Lu, Yi Lu","doi":"10.2174/1874196701003010008","DOIUrl":"10.2174/1874196701003010008","url":null,"abstract":"<p><p>Hypoxia-inducible factor-1α (HIF-1α) is known as a transactivator for VEGF gene promoter. It can be induced by hypoxia. However, no study has been done so far to dissect HIF-1α-mediated effects from hypoxia or VEGF-mediated effects. By using a HIF-1α knockout (HIF-1α KO) cell system in mouse embryonic fibroblast (MEF) cells, this study analyzes cell migration and HIF-1α, hypoxia and VEGF activation. A hypoxia-mediated HIF-1α induction and VEGF transactivation were observed: both HIF-1α WT lines had significantly increased VEGF transactivation, as an indicator for HIF-1α induction, in hypoxia compared to normoxia; in contrast, HIF-1α KO line had no increased VEGF transactivation under hypoxia. HIF-1α promotes cell migration: HIF-1α-KO cells had a significantly reduced migration compared to that of the HIF-1α WT cells under both normoxia and hypoxia. The significantly reduced cell migration in HIF-1α KO cells can be partially rescued by the restoration of WT HIF-1α expression mediated by adenoviral-mediated gene transfer. Interestingly, hypoxia has no effect on cell migration: the cells had a similar cell migration rate under hypoxic and normoxic conditions for both HIF-1α WT and HIF-1α KO lines, respectively. Collectively, these data suggest that HIF-1α plays a role in MEF cell migration that is independent from hypoxia-mediated effects.</p>","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946250/pdf/nihms195928.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29312394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Misfolding Diseases","authors":"V. Bellotti, M. Stoppini","doi":"10.2174/1874196700902010228","DOIUrl":"https://doi.org/10.2174/1874196700902010228","url":null,"abstract":"Diseases caused by protein misfolding are an emerging pathologic category that are thought to share some basic common mechanisms and display impressive heterogeneity in terms of tissue involvement, age of onset and clinical features. The growing recognition of the impact that protein misfolding has on human diseases is certainly related to the phenomenon of population aging and the expansion of the population in which these diseases are more frequent, but it is also based on a scientific revolution that looks at protein dynamics and relates these data to their potential pathologic implications. The multidisciplinary exchange of knowledge between experts in apparently unrelated diseases, such as sickle cell anemia and Alzheimer's disease, has helped clarify the pathogenesis of these and many other diseases. The quick expansion of knowledge on the mechanisms of these diseases is priming pharmaceutical research that is now providing the first prototype drugs.","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84452308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Aggregation in the Cell Nucleus: Structure, Function and Topology","authors":"A. Mikecz","doi":"10.2174/1874196700902010193","DOIUrl":"https://doi.org/10.2174/1874196700902010193","url":null,"abstract":"The nucleus represents a cellular control unit that regulates all events concerning the storage and processing of DNA and RNA. It is organized by highly crowded, dynamic assemblies of proteins and nucleic acids in molecular machines, ribonucleoprotein complexes, clusters of ongoing nuclear processes, nuclear bodies, and chromatin. This review discusses the occurrence of nuclear protein aggregation with special emphasis on the functional architecture of the nucleus, and quality control by the ubiquitin-proteasome system.","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83100979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the Structure of Amyloid Fibrils","authors":"K. Marshall, L. Serpell","doi":"10.2174/1874196700902010185","DOIUrl":"https://doi.org/10.2174/1874196700902010185","url":null,"abstract":"Various proteins and peptides are able to self assemble into amyloid fibrils that are associated with disease. Structural characterisation of these fibres is limited by their insoluble and heterogeneous nature. However, advances in various techniques including X-ray diffraction, cryo-electron microscopy and solid state NMR have provided detailed information on various amyloid fibrils, from the long range order and macromolecular structure to the atomic interactions that promote assembly and stabilise the amyloid core. The cross- model has been widely accepted as a generic structure for most amyloid fibrils and is discussed in detail. It is clear, however, that polymorphisms are present, even in fibrils formed from the same precursor protein, and that these may represent differences in packing at a molecular level. To fully understand the roles of particular residues in amyloid formation and structure, short peptides can be used in conjunction with mutagenesis studies to assess their effects. The structural insights gained using a combination of techniques to study both full-length, disease related peptides and short fragments are essential if progress is to be made towards understanding why these fibres form and how to prevent their formation.","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85800534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Evolutionary Mechanisms Reduce Protein Aggregation","authors":"J. Reumers, F. Rousseau, J. Schymkowitz","doi":"10.2174/1874196700902010176","DOIUrl":"https://doi.org/10.2174/1874196700902010176","url":null,"abstract":"The folding of polypeptides into stable globular protein structures requires protein sequences with a relatively high hydrophobicity and secondary structure propensity. These biophysical properties, however, also favor protein aggregation via the formation of intermolecular beta-sheets and, as a result, globular structure and aggregation are inextricable properties of protein polypeptides. Aggregates that are enriched in beta-sheet structures have been found in diseased tissues in association with at least twenty different human disorders and the effect of aggregation on protein function include simple loss-of-function but also often a gain of toxicity. Given both the ubiquity and the potentially lethal consequences of protein aggregation, negative selective pressure strongly minimizes aggregation. Various evolutionary strategies keep aggregation in check, including (1) the optimisation of the thermodynamic stability of the protein, which precludes aggregation by burial of the aggregation prone regions in solvent inaccessible regions of the structure, (2) segregation between folding nuclei and aggregation nuclei within a protein sequence, (3) the placement of so-called gatekeeper residues at the flanks of aggregating segments, that reduce the aggregation rate of (partially) unfolded proteins, and (4) molecular chaperones that target aggregation nucleating sequences directly, thereby further suppressing aggregation in a cellular environment. In this review we describe the intrinsic features built into protein sequence and structure that protect against aggregation.","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79910279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amyloid Formation on Lipid Membrane Surfaces","authors":"P. Kinnunen","doi":"10.2174/1874196700902010163","DOIUrl":"https://doi.org/10.2174/1874196700902010163","url":null,"abstract":"Several lines of research have concluded lipid membranes to efficiently induce the formation of amyloid-type fibers by a number of proteins. In brief, membranes, particularly when containing acidic, negatively charged lipids, concentrate cationic peptides/proteins onto their surfaces, into a local low pH milieu. The latter together with the anisotropic low dielectricity environment of the lipid membrane further forces polypeptides to align and adjust their conformation so as to enable a proper arrangement of the side chains according to their physicochemical characteristics, creating a hydrophobic surface contacting the lipid hydrocarbon region. Concomitantly, the low dielectricity also forces the polypeptides to maximize intramolecular hydrogen bonding by folding into amphipathic  -helices, which further aggregate, the latter adding cooperativity to the kinetics of membrane association. After the above, fast first events, several slower, cooperative conformational transitions of the oligomeric polypeptide chains take place in the membrane surface. Relaxation to the free energy minimum involves a complex free energy landscape of the above system comprised of a soft membrane interacting with, and accommodating peptide polymers. The overall free energy landscape thus involves a region of polypeptide aggregation associated with folding: polypeptide physicochemical properties and available conformation/oligomerization state spaces as determined by the amino acid sequence. In this respect, of major interest are those natively disordered proteins interacting with lipids, which in the absence of a ligand have no inherent structure and may adapt different functional states. Key sequence features for lipid and membrane interactions from the point of view of amyloid formation are i) conformational ambiguity, ii) adoption of amphipathic structures, iii) ion binding, and iv) propensity for aggregation and amyloid fibrillation. The pathways and states of the polypeptide conformational transitions further depend on the lipid composition, which thus couples the inherent properties of lipid membranes to the inherent properties of proteins. In other words, different lipids and their mixtures generate a very complex and rich scale of environments, involving also a number of cooperative transitions, sensitive to exogenous factors (temperature, ions, pH, small molecules), with small scale molecular properties and interactions translating into large scale 2- and 3-D organization. These lipid surface properties and topologies determine and couple to the transitions of the added polypeptide, the latter now undergoing oligomerization, with a sequence of specific and cooperative conformational changes. The above aggregation/folding pathways and transient intermediates of the polypeptide oligomers appear to have distinct biological functions. The latter involve i) the control of enzyme catalytic activity, ii) cell defence (e.g. antimicrobial and cancer killing peptides/p","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81329317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Tightly Regulated and Compartmentalised Import, Sorting and Folding of Mitochondrial Proteins","authors":"L. Cassina, G. Casari","doi":"10.2174/1874196700902010200","DOIUrl":"https://doi.org/10.2174/1874196700902010200","url":null,"abstract":"Mitochondria are eukaryotic intracellular organelles that still bear the signatures of their prokaryotic ancestor and require nuclear assistance. They generously dispense energy to cells, but are also involved in several biosynthetic processes, as well as in cell signalling pathways and programmed cell death. Mitochondria are partitioned into four intra-organelle compartments: the outer membrane, the inner membrane, the intermembrane space and the matrix. Each compartment contains a unique set of proteins and a personalised system for guaranteeing protein homeostasis. What follows is a survey of the function and topology of the multiple systems that operate the concerted action of protein sorting and folding in the four mitochondrial compartments.","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76150721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amyloid Oligomer Structures and Toxicity","authors":"C. Glabe","doi":"10.2174/1874196700902010222","DOIUrl":"https://doi.org/10.2174/1874196700902010222","url":null,"abstract":"Amyloid accumulation is commonly associated with a number of important human degenerative diseases and recent findings indicate that soluble amyloid oligomers may represent the primary pathological species in degenerative diseases. Amyloid oligomers are structurally and morphologically diverse, raising the question on whether this diversity is pathologically significant and whether different types of oligomers may have different toxic activities. Many of the amyloids associated with neurodegenerative diseases form three immunologically distinct types of oligomers. Fibrillar oligomers are structurally related to fibrils and may represent small pieces of fibrils or fibril protofilaments. Prefibrillar oligomers are kinetic intermediates in fibril formation and annular protofibrils that resemble membrane pores. These three classes of oligomers share common structures and toxic activities. Focus on these common mechanisms of toxicity provides a means of simplifying the list of primary disease mechanisms and opens the possibility of developing broad spectrum therapeutics that target several amyloid related degenerative diseases.","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82868744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistance of Quiescent Human Diploid Fibroblasts to High Dose of External Oxidative Stress and Induction of Senescence","authors":"Danijela Domazet-Damjanov, M. Somayajulu-Niţu, S. Pandey","doi":"10.2174/1874196700902010149","DOIUrl":"https://doi.org/10.2174/1874196700902010149","url":null,"abstract":"In response to external oxidative stress/DNA damaging agents, mammalian cells may choose one of the following pathways to avoid propagation of the damaged cells: repair the DNA and proceed with the normal cell cycle; trigger apoptosis; or undergo senescence to block cell division. If these safeguard mechanisms fail, cells containing damaged/mutated DNA will continue to propagate leading to cancer. Working with Human Diploid Fibroblasts, we have observed that young quiescent fibroblasts, unlike dividing fibroblasts, do not undergo apoptosis when subjected to high dose of external oxidative stress. Interestingly, when those quiescent fibroblasts are sub-cultured following H2O2 treatment, they display all the features of the senescent cell phenotype. Our results have indicated that p21 and MnSOD over-expression in quiescent cells is highly correlated to resistance to oxidative stress and may induce senescence. Moreover, there was no observable DNA damage in quiescent fibroblasts after 500 μM H2O2 treatment even though oxidative damage to lipids and proteins was detected both before and after treatment. Most importantly, the mitochondrial membrane potential in quiescent cells remained unchanged even after exposure to a high dose of external oxidative stress. In dividing cells, Bcl-2 expression was down-regulated whereas Bax expression was up-regulated following oxidative stress. On the other hand, Bcl-2 levels remained high and Bax was down-regulated in quiescent cells under identical treatment. Our results reveal that the over-expression of p21 and Mn-SOD and the down-regulation of Bax in quiescent cells could be responsible for their resistance against external oxidative stress and onset of senescence.","PeriodicalId":22949,"journal":{"name":"The Open Biology Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75801108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}