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Alessandro Giuliani

Publications and source records attributed to Alessandro Giuliani.

29 records · Page 2Linked to original sources
PubMed2003

Protein aggregation/folding: the role of deterministic singularities of sequence hydrophobicity as determined by nonlinear signal analysis of acylphosphatase and Abeta(1-40).

The problem of protein folding vs. aggregation was investigated in acylphosphatase and the amyloid protein Abeta(1-40) by means of nonlinear signal analysis of their chain hydrophobicity. Numerical descriptors of recurrence patterns provided the basis for statistical evaluation of folding/aggregation distinctive features. Static and dynamic approaches were used to elucidate conditions coincident with folding vs. aggregation using comparisons with known protein secondary structure classifications, site-directed mutagenesis studies of acylphosphatase, and molecular dynamics simulations of amyloid protein, Abeta(1-40). The results suggest that a feature derived from principal component space characterized by the smoothness of singular, deterministic hydrophobicity patches plays a significant role in the conditions governing protein aggregation.

Acid Anhydride Hydrolases↗
PubMed2002

Thyroid hormone activates oligodendrocyte precursors and increases a myelin-forming protein and NGF content in the spinal cord during experimental allergic encephalomyelitis.

Remyelination in the adult central nervous system has been demonstrated in different experimental models of demyelinating diseases. However, there is no clear evidence that remyelination occurs in multiple sclerosis, the most diffuse demyelinating disease. In this article, we explore the possibility of promoting myelination in experimental allergic encephalomyelitis, a widely used experimental model of multiple sclerosis, by recruiting progenitors and channeling them into oligodendroglial lineage through administration of thyroid hormone (T4). A large number of proliferating cells (BrdUrd uptake and Ki67-IR) and the expression of markers for undifferentiated precursors (nestin) increased in the subventricular zone and spinal cord of experimental allergic encephalomyelitis animals. T4 administration reduces proliferation and nestin-immunoreactivity and up-regulates expression of markers for oligodendrocyte progenitors [polysialylated-neural cell adhesion molecule (PSA-NCAM), O4, A2B5] and mature oligodendrocytes (myelin basic protein) in the spinal cord, olfactory bulb, and subventricular zone.

Animals↗
PubMed2002

Recurrence quantification analysis reveals interaction partners in paramyxoviridae envelope glycoproteins.

The paramyxovirus envelope fuses with the host cell membrane by cooperative interaction of two transmembrane glycoproteins: the hemagglutinin neuraminidase (HN) and the fusion (F) glycoprotein. The interaction appears to be finely regulated, as both proteins must derive from the same viral species to obtain a functional interaction. Because HN and F do not form stable complexes, this interaction is poorly characterized. This article demonstrates that a modification of a classical bioinformatic method based on the co-evolution of interacting partners can detect the specificity of the HN and F interaction. The proposed approach relies on a relatively new nonlinear signal analysis technique, recurrence quantification analysis (RQA), applied to the hydrophobicity sequences of viral proteins. This technique is able to shed light on the interaction between HN and F proteins in the virus-cell fusion and, more generally, permits the quantitative comparison of nonhomologue protein systems. On the contrary, the same co-evolution approach, based on the classical sequence alignment procedure, was unable to discriminate interacting partners from the general strict correlation existing between the evolution of viral proteins as a whole. The cooperation between HN and F in the fusion process is thus demonstrated by a bioinformatic, purely sequence-dependent, perspective.

Computational Biology↗
PubMed2002

Thyroid hormone and retinoids affect motoneuron phenotype and reaction after axotomy in the spinal cord of adult rats.

Motoneuron phenotype in the spinal cord is regulated by an intrinsic genetic program, extrinsic environmental signals and target-derived molecules. Axonal lesions trigger a phenotype switch to foster repair phenomena and axonal re-growth. We have investigated the influence of the long-term treatment with thyroid hormone and all trans retinol palmitate (RA) on motoneuron phenotype and spinal cord reaction to axotomy in adult male rats. Neurochemical markers, investigated by in situ hybridization and immunocytochemistry, included choline acetyltransferase (ChAT), calcitonin gene-related peptide (CGRP) and neurotrophin low affinity receptor p75. Treatment was administered for 56 days and then mid-thigh sciatic axotomy was performed on a number of animals from each experimental groups; the rats were examined 9 days after surgery. The results indicate that: (1) Number and size of ChAT-immunoreactive neurons in the lumbar tract of the spinal cord was reduced in hypothyroid compared to control rats, whereas steady-state level of ChAT mRNA in labelled motoneurons failed to be modified by hypo and hyperthyroidism, but was increased by RA administration; (2) none of the administered treatments did alter CGRP mRNA level, whereas all of them influenced the axotomy-induced changes of motoneuron phenotype; (3) in hyperthyroid rats ChAT mRNA level of lumbar motoneurons not reduced homolateral to lesion while the number of ChAT-IR profiles was pronouncedly reduced; (4) up-regulation of p75 induced by peripheral nerve lesion was reduced in RA-treated rats. These data indicate that the motoneuron phenotype is regulated by transcription factors, which also play a role in phenotype switch regulation after axotomy.

Animals↗
PubMed2002

Cancer incidence and socioeconomic geography of Finland: a correlation study.

The influence that social determinants exert on cancer incidence and patterns is an expected aftermath of the predominantly environmental origin of cancer. This happens because social changes determine a wide range of individual behaviors, and hence of "proximate" causes of cancer. Whereas most of the previous social epidemiological studies focused on individual social classes and groups, in this paper we studied the influence of the social factors on cancer etiology at the larger scale of a whole country: Finland. The ecological analysis of cancer incidence and patterns in the Finnish regions pointed to both local and general correlations between tumors and socioeconomic descriptors. The most important correlations were: a) a general effect of economic and societal factors on cancer (namely, on the profiles of tumors in males and females, on the global cancer incidence in females, and on the difference in cancer incidence between the two sexes); b) a very specific pattern of correlations for the Ahvenanmaa islands; c) a clear geographic cline in tumor profile variability. The ecological epidemiology approach can provide important clues to public health policies.

Adolescent↗
PubMed2002

Comparison of transient otoacoustic emission responses from neonatal and adult ears.

Transient otoacoustic emission (TEOAE) responses from neonatal (age: 48 h) and adult subjects (age: 26.6 +/- 10.0 yr) were analyzed by the combined use of recurrence quantification analysis and singular value decomposition. The data from the two age groups showed significant differences and similarities. The neonatal responses presented less deterministic structures than those of the adults in terms of recurrent dynamic features. In both data sets, the same high level of individual specific dynamic features was observed. The results from the singular value decomposition analysis suggest that a large percentage of variability in all of the analyzed responses can be explained by four to five essential modes. This number is lower than that observed in simulated TEOAE responses generated by a five-component gammatone model. A possible explanation is presented, based on simple instrumental and morphoanatomic considerations.

Adult↗
PubMed2002

Review of nonlinear analysis of proteins through recurrence quantification.

This review considers the use of a nonlinear signal analysis tool, recurrence quantification analysis, as a method to study sequence/structure relationships of proteins. Four broad categories are discussed: (1) a point of view involving information contained in deterministic aspects of hydrophobicity; (2) the analysis of protein hydrophobicity "singularities"; (3) time-series analysis of protein dynamics simulations; and (4) prediction of protein secondary structure.

Algorithms↗
PubMedDate not supplied

Looking for an unambiguous geometrical definition of organic series from 3-d molecular similarity indices.

A mathematically consistent definition of series was derived by the application of Principal Component Analysis to 3-D similarity indices (ASP Software). For two data sets of aromatic molecules, a mono-dimensional numerical ordering was derived, corresponding to the consensus distance from the series lead. The series is unambiguously defined in terms of location along the mono-dimensional axis, along which shape and electrostatic features of the molecules vary in a coordinated way. Molecules along the axis are characterized by the same pattern of electrostatic potential and shape shared by the lead compound, of which they represent linearly "shifted" replicas. This approach can contribute to the exploration of the chemical spaces from a local "fine grain" perspective, thus complementing the "coarse grain" descriptions normally used in the analysis of large data sets.

Journal Article↗
PubMedDate not supplied

Structure-related statistical singularities along protein sequences: a correlation study.

A data set composed of 1141 proteins representative of all eukaryotic protein sequences in the Swiss-Prot Protein Knowledge base was coded by seven physicochemical properties of amino acid residues. The resulting numerical profiles were submitted to correlation analysis after the application of a linear (simple mean) and a nonlinear (Recurrence Quantification Analysis, RQA) filter. The main RQA variables, Recurrence and Determinism, were subsequently analyzed by Principal Component Analysis. The RQA descriptors showed that (i) within protein sequences is embedded specific information neither present in the codes nor in the amino acid composition and (ii) the most sensitive code for detecting ordered recurrent (deterministic) patterns of residues in protein sequences is the Miyazawa-Jernigan hydrophobicity scale. The most deterministic proteins in terms of autocorrelation properties of primary structures were found (i) to be involved in protein-protein and protein-DNA interactions and (ii) to display a significantly higher proportion of structural disorder with respect to the average data set. A study of the scaling behavior of the average determinism with the setting parameters of RQA (embedding dimension and radius) allows for the identification of patterns of minimal length (six residues) as possible markers of zones specifically prone to inter- and intramolecular interactions.

Amino Acid Sequence↗
PubMedDate not supplied

Charge and hydrophobicity patterning along the sequence predicts the folding mechanism and aggregation of proteins: a computational approach.

The presence of partially folded intermediates along the folding funnel of proteins has been suggested to be a signature of potentially aggregating systems. Many studies have concluded that metastable, highly flexible intermediates are the basic elements of the aggregation process. In a previous paper, we demonstrated how the choice between aggregation and folding behavior was influenced by hydrophobicity distribution patterning along the sequence, as quantified by recurrence quantification analysis (RQA) of the Myiazawa-Jernigan coded primary structures. In the present paper, we tried to unify the "partially folded intermediate" and "hydrophobicity/charge" models of protein aggregation verifying the ability of an empirical relation, developed for rationalizing the effect of different mutations on aggregation propensity of acyl-phosphatase and based on the combination of hydrophobicity RQA and charge descriptors, to discriminate in a statistically significant way two different protein populations: (a) proteins that fold by a process passing by partially folded intermediates and (b) proteins that do not present partially folded intermediates.

Acid Anhydride Hydrolases↗