Novel autoantigens immunogenic in COPD patients

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients.</p> <p>Methods</p> <p>An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC) for each clone and the separation COPD sera versus control sera.</p> <p>Results</p> <p>By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By <it>in silico </it>sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity.</p> <p>Conclusion</p> <p>The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.</p

Structure of NaFeSiO4, NaFeSi2O6, and NaFeSi3O8 glasses and glass-ceramics

The crystallization of iron-containing sodium silicate phases holds particular importance, both in the management high-level nuclear wastes and in geosciences. Here, we study three asquenched glasses and their heat-treated chemical analogues, NaFeSiO4, NaFeSi2O6, and NaFeSi3O8 (with nominal stoichiometries from feldspathoid, pyroxene, and feldspar mineral groups – i.e., Si/Fe = 1, 2, and 3 respectively) – using a variety of techniques. Phase analyses revealed that as-quenched NaFeSiO4 cannot accommodate all Fe in the glass phase (some Fe crystallizes as Fe3O4), whereas as-quenched NaFeSi2O6 and NaFeSi3O8 form amorphous glasses upon quenching. NaFeSi2O6 glass is the only composition that crystallizes into its respective isochemical crystalline polymorph, i.e. aegirine, upon isothermal heat-treatment. As revealed by Mössbauer spectroscopy, iron is predominantly present as 4-coordinated Fe3+ in all glasses, though it is present as 6-coordinated Fe3+ in the aegirine crystals (NaFeSi2O6), as expected from crystallography. Thus, Fe can form the crystalline phases in which it is octahedrally coordinated, even though it is mostly tetrahedrally coordinated in the parent glasses. Thermal behavior, magnetic properties, iron redox state (including Fe K-edge X-ray absorption), and vibrational properties (Raman spectra) of the above compositions are discussed

The modular systems biology approach to investigate the control of apoptosis in Alzheimer's disease neurodegeneration

Apoptosis is a programmed cell death that plays a critical role during the development of the nervous system and in many chronic neurodegenerative diseases, including Alzheimer's disease (AD). This pathology, characterized by a progressive degeneration of cholinergic function resulting in a remarkable cognitive decline, is the most common form of dementia with high social and economic impact. Current therapies of AD are only symptomatic, therefore the need to elucidate the mechanisms underlying the onset and progression of the disease is surely needed in order to develop effective pharmacological therapies. Because of its pivotal role in neuronal cell death, apoptosis has been considered one of the most appealing therapeutic targets, however, due to the complexity of the molecular mechanisms involving the various triggering events and the many signaling cascades leading to cell death, a comprehensive understanding of this process is still lacking. Modular systems biology is a very effective strategy in organizing information about complex biological processes and deriving modular and mathematical models that greatly simplify the identification of key steps of a given process. This review aims at describing the main steps underlying the strategy of modular systems biology and briefly summarizes how this approach has been successfully applied for cell cycle studies. Moreover, after giving an overview of the many molecular mechanisms underlying apoptosis in AD, we present both a modular and a molecular model of neuronal apoptosis that suggest new insights on neuroprotection for this disease

ACE2 is required for daughter cell-specific G(1) delay in Saccharomyces cerevisiae

Saccharomyces cerevisiae cells reproduce by budding to yield a mother cell and a smaller daughter cell. Although both mother and daughter begin G(1) simultaneously, the mother cell progresses through G(1) more rapidly. Daughter cell G(1) delay has long been thought to be due to a requirement for attaining a certain critical cell size before passing the commitment point in the cell cycle known as START. We present an alternative model in which the daughter cell-specific Ace2 transcription factor delays G(1) in daughter cells. Deletion of ACE2 produces daughter cells that proceed through G(1) at the same rate as mother cells, whereas a mutant Ace2 protein that is not restricted to daughter cells delays G(1) equally in both mothers and daughters. The differential in G(1) length between mothers and daughters requires the Cln3 G(1) cyclin, and CLN3-GFP reporter expression is reduced in daughters in an ACE2-dependent manner. Specific daughter delay elements in the CLN3 promoter are required for normal daughter G(1) delay, and these elements bind to an unidentified 127-kDa protein. This DNA-binding activity is enhanced by deletion of ACE2. These results support a model in which daughter cell G(1) delay is determined not by cell size but by an intrinsic property of the daughter cell generated by asymmetric cell division