Showing papers by "University of Florence published in 2002"

Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases.

Abstract: A range of human degenerative conditions, including Alzheimer's disease, light-chain amyloidosis and the spongiform encephalopathies, is associated with the deposition in tissue of proteinaceous aggregates known as amyloid fibrils or plaques. It has been shown previously that fibrillar aggregates that are closely similar to those associated with clinical amyloidoses can be formed in vitro from proteins not connected with these diseases, including the SH3 domain from bovine phosphatidyl-inositol-3'-kinase and the amino-terminal domain of the Escherichia coli HypF protein. Here we show that species formed early in the aggregation of these non-disease-associated proteins can be inherently highly cytotoxic. This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases.

Reactivation of Ocular Dominance Plasticity in the Adult Visual Cortex

Abstract: In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of the ECM is inhibitory for experience-dependent plasticity in the visual cortex. The organization of CSPGs into perineuronal nets coincided with the end of the critical period and was delayed by dark rearing. After CSPG degradation with chondroitinase-ABC in adult rats, monocular deprivation caused an ocular dominance shift toward the nondeprived eye. The mature ECM is thus inhibitory for experience-dependent plasticity, and degradation of CSPGs reactivates cortical plasticity.

Vascular Cognitive Impairment

Abstract: Cerebrovascular disease is the second most common cause of acquired cognitive impairment and dementia and contributes to cognitive decline in the neurodegenerative dementias. The current narrow definitions of vascular dementia should be broadened to recognise the important part cerebrovascular disease plays in several cognitive disorders, including the hereditary vascular dementias, multi-infarct dementia, post-stroke dementia, subcortical ischaemic vascular disease and dementia, mild cognitive impairment, and degenerative dementias (including Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies). Here we review the current state of scientific knowledge on the subject of vascular brain burden. Important non-cognitive features include depression, apathy, and psychosis. We propose use of the term vascular cognitive impairment, which is characterised by a specific cognitive profile involving preserved memory with impairments in attentional and executive functioning. Diagnostic criteria have been proposed for some subtypes of vascular cognitive impairment, and there is a pressing need to validate and further refine these. Clinical trials in vascular cognitive impairment are in their infancy but support the value of therapeutic interventions for symptomatic treatment.

Subcortical ischaemic vascular dementia

Abstract: Summary Vascular dementia is the second most common type of dementia. The subcortical ischaemic form (SIVD) frequently causes cognitive impairment and dementia in elderly people. SIVD results from small-vessel disease, which produces either arteriolar occlusion and lacunes or widespread incomplete infarction of white matter due to critical stenosis of medullary arterioles and hypoperfusion (Binswanger's disease). Symptoms include motor and cognitive dysexecutive slowing, forgetfulness, dysarthria, mood changes, urinary symptoms, and short-stepped gait. These manifestations probably result from ischaemic interruption of parallel circuits from the prefrontal cortex to the basal ganglia and corresponding thalamocortical connections. Brain imaging (computed tomography and magnetic resonance imaging) is essential for correct diagnosis. The main risk factors are advanced age, hypertension, diabetes, smoking, hyperhomocysteinaemia, hyperfibrinogenaemia, and other conditions that can cause brain hypoperfusion such as obstructive sleep apnoea, congestive heart failure, cardiac arrhythmias, and orthostatic hypotension. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) and some forms of cerebral amyloid angiopathy have a genetic basis. Treatment is symptomatic and prevention requires control of treatable risk factors.

[Responses of agricultural crops of free-air CO2 enrichment].

Abstract: Over the past decade, free-air CO2 enrichment (FACE) experiments have been conducted on several agricultural crops: wheat(Triticum aestivum L.), perennial ryegrass (Lolium perenne), and rice(Oryza sativa L.) which are C3 grasses; sorghum (Sorghum bicolor (L.) Moench), a C4 grass; white clover (Trifolium repens), a C3 legume; potato (Solanum tuberosum L.), a C3 forb with tuber storage; and cotton (Gossypium hirsutum L.) and grape (Vitis vinifera L.) which are C3 woody perennials. Using reports from these experiments, the relative responses of these crops was discussed with regard to photosynthesis, stomatal conductance, canopy temperature, water use, water potential, leaf area index, shoot and root biomass accumulation, agricultural yield, radiation use efficiency, specific leaf area, tissue nitrogen concentration, nitrogen yield, carbohydrate concentration, phenology, soil microbiology, soil respiration, trace gas emissions, and soil carbon sequestration. Generally, the magnitude of these responses varied with the functional type of plant and with the soil nitrogen and water status. As expected, the elevated CO2 increased photosynthesis and biomass production and yield substantially in C3 species, but little in C4, and it decreased stomatal conductance and transpiration in both C3 and C4 species and greatly improved water-use efficiency in all the crops. Growth stimulations were as large or larger under water-stress compared to well-watered conditions. Growth stimulations of non-legumes were reduced at low soil nitrogen, whereas elevated CO2 strongly stimulated the growth of the clover legume both at ample and under low N conditions. Roots were generally stimulated more than shoots. Woody perennials had larger growth responses to elevated CO2, while at the same time, their reductions in stomatal conductance were smaller. Tissue nitrogen concentrations went down while carbohydrate and some other carbon-based compounds went up due to elevated CO2, with leaves and foliage affected more than other organs. Phenology was accelerated slightly in most but not all species. Elevated CO2 affected some soil microbes greatly but not others, yet overall activity appears to be stimulated. Detection of statistically significant changes in soil organic carbon in any one study was impossible, yet combining results from several sites and years, it appears that elevated CO2 did increase sequestration of soil carbon. Whenever possible, comparisons were made between the FACE results and those from prior chamber-based experiments reviewed in the literature. Over all the data and parameters considered in this review, there are only two parameters for which the FACE- and chamber-based data appear to be inconsistent. One is that elevated CO2 from FACE appears to reduce stomatal conductance about one and a half times more than observed in prior chamber experiments. Similarly, elevated CO2 appears to have stimulated root growth relatively more than shoot growth under FACE conditions compared to chamber conditions. Nevertheless, for the most part, the FACE- and chamber-based results have been consistent, which gives confidence that conclusions drawn from both types of data are accurate. However, the more realistic FACE environment and the larger plot size have enabled more extensive robust multidisciplinary data sets to be obtained under conditions representative of open fields in the future high-CO2 world.

Putting order in risk measures

Abstract: This paper introduces a set of axioms that define convex risk measures. Duality theory provides the representation theorem for these measures and the link with pricing rules.

A Lyapunov approach to incremental stability properties

Abstract: Deals with several notions of incremental stability. In other words, the focus is on stability of trajectories with respect to one another, rather than with respect to some attractor. The aim is to present a framework for understanding such questions fully compatible with the well-known input-to-state stability approach. Applications of the newly introduced stability notions are also discussed.

Context-driven fusion of high spatial and spectral resolution images based on oversampled multiresolution analysis

Abstract: This paper compares two general and formal solutions to the problem of fusion of multispectral images with high-resolution panchromatic observations. The former exploits the undecimated discrete wavelet transform, which is an octave bandpass representation achieved from a conventional discrete wavelet transform by omitting all decimators and upsampling the wavelet filter bank. The latter relies on the generalized Laplacian pyramid, which is another oversampled structure obtained by recursively subtracting from an image an expanded decimated lowpass version. Both the methods selectively perform spatial-frequencies spectrum substitution from an image to another. In both schemes, context dependency is exploited by thresholding the local correlation coefficient between the images to be merged, to avoid injection of spatial details that are not likely to occur in the target image. Unlike other multiscale fusion schemes, both the present decompositions are not critically subsampled, thus avoiding possible impairments in the fused images, due to missing cancellation of aliasing terms. Results are presented and discussed on SPOT data.

A Comparison of U.S. and European University-Industry Relations in the Life Sciences

Abstract: We draw on diverse data sets to compare the institutional organization of upstream life science research across the United States and Europe. Understanding cross-national differences in the organization of innovative labor in the life sciences requires attention to the structure and evolution of biomedical networks involving public research organizations (universities, government laboratories, nonprofit research institutes, and research hospitals), science-based biotechnology firms, and multinational pharmaceutical corporations. We use network visualization methods and correspondence analyses to demonstrate that innovative research in biomedicine has its origins in regional clusters in the United States and in European nations. But the scientific and organizational composition of these regions varies in consequential ways. In the United States, public research organizations and small firms conduct R&D across multiple therapeutic areas and stages of the development process. Ties within and across these regions link small firms and diverse public institutions, contributing to the development of a robust national network. In contrast, the European story is one of regional specialization with a less diverse group of public research organizations working in a smaller number of therapeutic areas. European institutes develop local connections to small firms working on similar scientific problems, while cross-national linkages of European regional clusters typically involve large pharmaceutical corporations. We show that the roles of large and small firms differ in the United States and Europe, arguing that the greater heterogeneity of the U.S. system is based on much closer integration of basic science and clinical development.

Kinetic partitioning of protein folding and aggregation.

Abstract: We have systematically studied the effects of 40 single point mutations on the conversion of the denatured form of the α/β protein acylphosphatase (AcP) into insoluble aggregates. All the mutations that significantly perturb the rate of aggregation are located in two regions of the protein sequence, residues 16–31 and 87–98, each of which has a relatively high hydrophobicity and propensity to form β-sheet structure. The measured changes in aggregation rate upon mutation correlate with changes in the hydrophobicity and β-sheet propensity of the regions of the protein in which the mutations are located. The two regions of the protein sequence that determine the aggregation rate are distinct from those parts of the sequence that determine the rate of protein folding. Dissection of the protein into six peptides corresponding to different regions of the sequence indicates that the kinetic partitioning between aggregation and folding can be attributed to the intrinsic conformational preferences of the denatured polypeptide chain.

Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes.

Abstract: Phenotypic markers, localization, functional activities, and mechanisms of action in vitro of CD4+CD25+ T cells, purified from postnatal human thymuses, were investigated. These cells showed poor or no proliferation in mixed lymphocyte culture (MLC), and suppressed in a dose-dependent fashion the proliferative response to allogeneic stimulation of CD4+CD25− thymocytes. Virtually all CD4+CD25+ thymocytes constitutively expressed cytoplasmic T lymphocyte antigen (CTLA)-4, surface tumor necrosis factor type 2 receptor (TNFR2), and CCR8. They prevalently localized to perivascular areas of fibrous septa and responded to the chemoattractant activity of CCL1/I-309, which was found to be produced by either thymic medullary macrophages or fibrous septa epithelial cells. After polyclonal activation, CD4+CD25+ thymocytes did not produce the cytokines interleukin (IL)-2, IL-4, IL-5, IL-13, interferon γ, and only a very few produced IL-10, but all they expressed on their surface CTLA-4 and the majority of them also transforming growth factor (TGF)-β1. The suppressive activity of these cells was contact dependent and associated with the lack of IL-2 receptor (IL-2R) α-chain (CD25) expression in target cells. Such a suppressive activity was partially inhibited by either anti–CTLA-4 or anti–TGF-β1, and was completely blocked by a mixture of these monoclonal antibodies, which were also able to restore in target T cells the expression of IL-2R α-chain and, therefore, their responsiveness to IL-2. These data demonstrate that CD4+CD25+ human thymocytes represent a population of regulatory cells that migrate in response to the chemokine CCL1/I-309 and exert their suppressive function via the inhibition of IL-2R α-chain in target T cells, induced by the combined activity of CTLA-4 and membrane TGF-β1.

Speckle removal from SAR images in the undecimated wavelet domain

Abstract: Speckle reduction is approached as a minimum mean-square error (MMSE) filtering performed in the undecimated wavelet domain by means of an adaptive rescaling of the detail coefficients, whose amplitude is divided by the variance ratio of the noisy coefficient to the noise-free one. All the above quantities are analytically calculated from the speckled image, the variance and autocorrelation of the fading variable, and the wavelet filters only, without resorting to any model to describe the underlying backscatter. On the test image Lena corrupted by synthetic speckle, the proposed method outperforms Kuan's local linear MMSE filtering by almost 3-dB signal-to-noise ratio. When true synthetic aperture radar (SAR) images are concerned, empirical criteria based on distributions of multiscale local coefficient of variation, calculated in the undecimated wavelet domain, are introduced to mitigate the rescaling of coefficients in highly heterogeneous areas where the speckle does not obey a fully developed model, to avoid blurring strong textures and point targets. Experiments carried out on widespread test SAR images and on a speckled mosaic image, comprising synthetic shapes, textures, and details from optical images, demonstrate that the visual quality of the results is excellent in terms of both background smoothing and preservation of edge sharpness, textures, and point targets. The absence of decimation in the wavelet decomposition avoids typical impairments often introduced by critically subsampled wavelet-based denoising.

Antitumorigenic activity of the prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane-induced colon carcinogenesis in rats.

Abstract: Prebiotics such as fructans, and probiotics such as Lactobacilli or Bifidobacteria, or a combination of prebiotics and probiotics (synbiotics) are thought to be protective against colon cancer. Therefore, we studied whether the prebiotic inulin enriched with oligofructose (Raftilose-Synergy1, briefly, Synergy1, 10% of the diet), probiotics [Bifidobacterium lactis (Bb12) and Lactobacillus rhamnosus (LGG), each at 5x10(8) c.f.u./g diet] or synbiotics (a combination of the two) protect rats against azoxymethane (AOM)-induced colon cancer. Male F344 rats were divided into: Controls; PRE, which were fed a diet containing Synergy1; PRO, fed a diet containing LGG and Bb12; PREPRO, fed a diet containing Synergy1, LGG and BB12. Ten days after beginning the diets, rats were treated with AOM (15 mg/kg s.c. two times); dietary treatments were continued for the entire experiment. Thirty-one weeks after AOM, rats treated with Synergy1 (PRE and PREPRO groups) had a significantly lower (P < 0.001) number of tumours (adenomas and cancers) than rats without Synergy1 (colorectal tumours/rat were 1.9 +/- 1.7, 1.1 +/- 1.1, 2.2 +/- 1.4 and 0.9 +/- 1.2 in Controls, PRE, PRO and PREPRO groups, respectively, means +/- SD). A slight, not significant effect of probiotics in reducing malignant tumours was also observed (P = 0.079). Caecal short-chain fatty acids (SCFA) were higher (P < 0.001) in the groups treated with Synergy1. Apoptosis was increased in the normal mucosa of the PRO group, while no variation was observed in the tumours. Colonic proliferation was lower in the PRE group as compared with Controls. Glutathione S-transferase placental enzyme pi type expression, and to a lesser extent, inducible NO synthase were depressed in the tumours from rats in the PRE and PREPRO groups. Cycloxygenase-2 expression was increased in the tumours of control rats but not in those from PRE, PRO or PREPRO rats. In conclusion, prebiotic administration in the diet decreases AOM-induced carcinogenesis in rats.

Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis--a 2-year randomized placebo controlled trial.

Abstract: The aim of the strontium ranelate (SR) for treatment of osteoporosis (STRATOS) trial was to investigate the efficacy and safety of different doses of SR, a novel agent in the treatment of postmenopausal osteoporosis. A randomized, multicenter, double-blind, placebo-controlled trial was undertaken in 353 osteoporotic women with at least one previous vertebral fracture and a lumbar T-score <−2.4. Patients were randomized to receive placebo, 0.5 g, 1 g, or 2 g SR/d for 2 yr. The primary efficacy endpoint was lumbar bone mineral density (BMD), assessed by dual-energy x-ray absorptiometry. Secondary outcome measures included femoral BMD, incidence of new vertebral deformities, and biochemical markers of bone metabolism. Lumbar BMD, adjusted for bone strontium content, increased in a dose-dependent manner in the intention-to-treat population: mean annual slope increased from 1.4% with 0.5 g/d SR to 3.0% with 2 g/d SR, which was significantly higher than placebo (P < 0.01). There was a significant reduction in t...

Two atomic species superfluid.

Abstract: We produce a quantum degenerate mixture composed by two Bose-Einstein condensates of different atomic species, 41K and 87Rb We study the dynamics of the superfluid system in an elongated magnetic trap, where off-axis collisions between the two interacting condensates induce scissorlike oscillations

HLA-G expression in early embryos is a fundamental prerequisite for the obtainment of pregnancy

Abstract: Different mechanisms mediated by the expression of the HLA-class Ib HLA-G products are suggested to account for the induction of immune tolerance against the paternal antigens of the fetus during pregnancy. Soluble HLA-G antigens, mainly produced by cytotrophoblast cells at the materno-fetal interface and circulating in the body fluids, show a capacity analogous to that of membrane-boundstructures to inhibit NK cells. In the present report we have investigated, using specific ELISA, the presence of sHLA-G molecules in culture supernatants of early embryos obtained by in vitro fertilization (IVF) before transfer. The data obtained from the analysis of 285 supernatants corresponding to 101 IVF procedures (43 IVF, 58 intracytoplasmic sperm injection) identify two groups of patients on the basis of sHLA-G antigen presence. No differences in clinical parameters were observed between the groups, but positive embryo implantations occurred only in women showing sHLA-G molecules in culture supernatants (Fisher's exact p value 2.56×10–3). The results obtained indicate that expression of HLA-G products in embryo cells is a mandatory, but not sufficient, prerequisite for the development of pregnancy.

Chemokines in liver inflammation and fibrosis.

Abstract: Chemokines may be involved in the tissue response to injury regulating the influx of leukocytes, and modulating a number of other critical biologic actions, including angiogenesis, neoplastic growth, myo-fibroblast activation, and the response to viral infections. In the liver, up-regulated expression of different members of the chemokine system may be induced by almost all types of injury, and there is often a clear relation between the chemokine pattern activated by different types of injury and the predominant subclasses of leukocytes which infiltrate the liver. Neutralization of specific chemokines by passive immunization or the use of animals deficient in specific chemokines or chemokine receptors has indicated a causal relation between up-regulation of chemokines and leukocyte infiltration. Inflammation is part of the liver wound healing response, that in chronic conditions leads to the development of fibrosis and cirrhosis. Hepatic stellate cells, which play a leading role in the development of fibrosis following their transition to myofibroblasts, express different chemokines. Chemokine expression by stellate cells is regulated by soluble mediators, in particular pro-inflammatory cytokines, as well as growth factors, proteases, and products of oxidative stress. In addition, stellate cells also respond to chemokines with biologic actions relevant for tissue repair, such as cell migration or induction of other chemokines. These data indicate that chemokines in the liver may modulate the progression of liver fibrosis through actions on hepatic stellate cells.

Studies of the aggregation of mutant proteins in vitro provide insights into the genetics of amyloid diseases

Abstract: Protein aggregation and the formation of highly insoluble amyloid structures is associated with a range of debilitating human conditions, which include Alzheimer's disease, Parkinson's disease, and the Creutzfeldt-Jakob disease. Muscle acylphosphatase (AcP) has already provided significant insights into mutational changes that modulate amyloid formation. In the present paper, we have used this system to investigate the effects of mutations that modify the charge state of a protein without affecting significantly the hydrophobicity or secondary structural propensities of the polypeptide chain. A highly significant inverse correlation was found to exist between the rates of aggregation of the protein variants under denaturing conditions and their overall net charge. This result indicates that aggregation is generally favored by mutations that bring the net charge of the protein closer to neutrality. In light of this finding, we have analyzed natural mutations associated with familial forms of amyloid diseases that involve alteration of the net charge of the proteins or protein fragments associated with the diseases. Sixteen mutations have been identified for which the mechanism of action that causes the pathological condition is not yet known or fully understood. Remarkably, 14 of these 16 mutations cause the net charge of the corresponding peptide or protein that converts into amyloid deposits to be reduced. This result suggests that charge has been a key parameter in molecular evolution to ensure the avoidance of protein aggregation and identifies reduction of the net charge as an important determinant in at least some forms of protein deposition diseases.

New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions.

Abstract: Vitiligo is a skin disease that is caused by selective destruction of melanocytes and is characterized by white spots. Melanocytes and keratinocytes seem to exhibit a functional close relationship, mediated at least in part by keratinocyte-derived cytokines, which seem important for survival and activity of melanocytic cells. We wanted to investigate the hypothesis that in vitiligo the expression of epidermal cytokines may be modified compared with normal skin. In 15 patients with active, non-segmental vitiligo, biopsies were obtained from lesional, perilesional and non-lesional skin; normal skin from five healthy donors was also tested. Tissue sections were tested using immunohistochemistry for the expression of keratinocyte-derived cytokines with stimulating activity, such as granulocyte-monocyte colony stimulating factor (GM-CSF), basic fibroblastic growth factor (bFGF), and stem cell factor (SCF) or with inhibiting activity, such as interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) on melanocytes. Cytokine receptors and specific melanocytic markers were also investigated. No melanocyte was identified in lesional skin by means of specific markers or c-kit receptor, whereas in perilesional, non-lesional and healthy skin, melanocytes were found in similar number. In vitiligo skin a significantly lower expression of GM-CSF, bFGF and SCF was found, and a significantly higher expression of IL-6 and TNF-alpha was detected, compared with perilesional, non-lesional and healthy skin. In conclusion, we provided evidence that a significant change of epidermal cytokines exists in vitiligo skin compared with perilesional, non-lesional and healthy skin, suggesting that the cytokine production of epidermal microenvironment may be involved in vitiligo.

Fourier series method for measurement of multivariate volatilities

Abstract: We present a methodology based on Fourier series analysis to compute time series volatility when the data are observations of a semimartingale. The procedure is not based on the Wiener theorem for the quadratic variation, but on the computation of the Fourier coefficients of the process and therefore it relies on the integration of the time series rather than on its differentiation. The method is fully model free and nonparametric. These features make the method well suited for financial market applications, and in particular for the analysis of high frequency time series and for the computation of cross volatilities.

The K20 survey - I. Disentangling old and dusty star-forming galaxies in the ERO population

Abstract: We present the results of VLT optical spectroscopy of a complete sample of 78 EROs with over a field of 52 arcmin2 . About 70% of the 45 EROs with have been spectroscopically identified with old passively evolving and dusty star-forming galaxies at . The two classes are about equally populated and for each of them we present and discuss the average spectrum. From the old ERO average spectrum and for we derive a minimum age of ~3 Gyr, corresponding to a formation redshift of z f ≳ 2.4. PLE models with such formation redshifts well reproduce the density of old EROs (consistent with being passively evolving ellipticals), whereas the predictions of the current hierarchical merging models are lower than the observed densities by large factors (up to an order of magnitude). From the average spectrum of the star-forming EROs we estimate a substantial dust extinction with ≳ 0.5. The star formation rates, corrected for the average reddening, suggest a significant contribution from EROs to the cosmic star-formation density at .

CT and MRI rating of white matter lesions

Abstract: Rating scales play an important role in the evaluation of computed tomography (CT) or magnetic resonance-detected white matter lesions (WML). Unfortunately, this type of visual semiquantitative assessment is not yet an optimal tool because commonly agreed concepts regarding its use are lacking. To generate a discussion platform for further improvement of CT and MRI rating, we will provide some basic definitions, summarize the advantages and disadvantages of scoring schemes and review current efforts towards the improvement of this tool. Future research will have to concentrate on deepening our understanding of the histopathologic substrates of WML and on strategies to document their progression.