Showing papers by "University of Milan published in 2005"

The Transcriptional Landscape of the Mammalian Genome

Abstract: This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.

Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents.

Abstract: ContextTraditionally, stent thrombosis has been regarded as a complication of percutaneous coronary interventions during the first 30 postprocedural days. However, delayed endothelialization associated with the implantation of drug-eluting stents may extend the risk of thrombosis beyond 30 days. Data are limited regarding the risks and the impact of this phenomenon outside clinical trials.ObjectiveTo evaluate the incidence, predictors, and clinical outcome of stent thrombosis after implantation of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice.Design, Setting, and PatientsProspective observational cohort study conducted at 1 academic hospital and 2 community hospitals in Germany and Italy. A total of 2229 consecutive patients underwent successful implantation of sirolimus-eluting (1062 patients, 1996 lesions, 2272 stents) or paclitaxel-eluting (1167 patients, 1801 lesions, 2223 stents) stents between April 2002 and January 2004.InterventionsImplantation of a drug-eluting stent (sirolimus or paclitaxel). All patients were pretreated with ticlopidine or clopidogrel and aspirin. Aspirin was continued indefinitely and clopidogrel or ticlopidine for at least 3 months after sirolimus-eluting and for at least 6 months after paclitaxel-eluting stent implantation.Main Outcome MeasuresSubacute thrombosis (from procedure end through 30 days), late thrombosis (>30 days), and cumulative stent thrombosis.ResultsAt 9-month follow-up, 29 patients (1.3%) had stent thrombosis (9 [0.8%] with sirolimus and 20 [1.7%] with paclitaxel; P = .09). Fourteen patients had subacute thrombosis (0.6%) and 15 patients had late thrombosis (0.7%). Among these 29 patients, 13 died (case fatality rate, 45%). Independent predictors of stent thrombosis were premature antiplatelet therapy discontinuation (hazard ratio [HR], 89.78; 95% CI, 29.90-269.60; P<.001), renal failure (HR, 6.49; 95% CI, 2.60-16.15; P<.001), bifurcation lesions (HR, 6.42; 95% CI, 2.93-14.07; P<.001), diabetes (HR, 3.71; 95% CI, 1.74-7.89; P = .001), and a lower ejection fraction (HR, 1.09; 95% CI, 1.05-1.36; P<.001 for each 10% decrease).ConclusionsThe cumulative incidence of stent thrombosis 9 months after successful drug-eluting stent implantation in consecutive “real-world” patients was substantially higher than the rate reported in clinical trials. Premature antiplatelet therapy discontinuation, renal failure, bifurcation lesions, diabetes, and low ejection fraction were identified as predictors of thrombotic events.

Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation

Abstract: Background— The purpose of this study was to provide an updated worldwide report on the methods, efficacy, and safety of catheter ablation of atrial fibrillation (AF). Methods and Results— A questi...

Neuroglial activation and neuroinflammation in the brain of patients with autism

Abstract: Autism is a neurodevelopmental disorder characterized by impaired communication and social interaction and may be accompanied by mental retardation and epilepsy. Its cause remains unknown, despite evidence that genetic, environmental, and immunological factors may play a role in its pathogenesis. To investigate whether immune-mediated mechanisms are involved in the pathogenesis of autism, we used immunocytochemistry, cytokine protein arrays, and enzyme-linked immunosorbent assays to study brain tissues and cerebrospinal fluid (CSF) from autistic patients and determined the magnitude of neuroglial and inflammatory reactions and their cytokine expression profiles. Brain tissues from cerebellum, midfrontal, and cingulate gyrus obtained at autopsy from 11 patients with autism were used for morphological studies. Fresh-frozen tissues available from seven patients and CSF from six living autistic patients were used for cytokine protein profiling. We demonstrate an active neuroinflammatory process in the cerebral cortex, white matter, and notably in cerebellum of autistic patients. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)-1 and tumor growth factor-beta1, derived from neuroglia, were the most prevalent cytokines in brain tissues. CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP-1. Our findings indicate that innate neuroimmune reactions play a pathogenic role in an undefined proportion of autistic patients, suggesting that future therapies might involve modifying neuroglial responses in the brain.

Virtual computational chemistry laboratory - design and description

Abstract: Internet technology offers an excellent opportunity for the development of tools by the cooperative effort of various groups and institutions. We have developed a multi-platform software system, Virtual Computational Chemistry Laboratory, http://www.vcclab.org, allowing the computational chemist to perform a comprehensive series of molecular indices/properties calculations and data analysis. The implemented software is based on a three-tier architecture that is one of the standard technologies to provide client-server services on the Internet. The developed software includes several popular programs, including the indices generation program, DRAGON, a 3D structure generator, CORINA, a program to predict lipophilicity and aqueous solubility of chemicals, ALOGPS and others. All these programs are running at the host institutes located in five countries over Europe. In this article we review the main features and statistics of the developed system that can be used as a prototype for academic and industry models.

Breakdown of cortical effective connectivity during sleep.

Abstract: When we fall asleep, consciousness fades yet the brain remains active. Why is this so? To investigate whether changes in cortical information transmission play a role, we used transcranial magnetic stimulation together with high-density electroencephalography and asked how the activation of one cortical area (the premotor area) is transmitted to the rest of the brain. During quiet wakefulness, an initial response (approximately 15 milliseconds) at the stimulation site was followed by a sequence of waves that moved to connected cortical areas several centimeters away. During non-rapid eye movement sleep, the initial response was stronger but was rapidly extinguished and did not propagate beyond the stimulation site. Thus, the fading of consciousness during certain stages of sleep may be related to a breakdown in cortical effective connectivity.

Assessing computational tools for the discovery of transcription factor binding sites.

Abstract: The prediction of regulatory elements is a problem where computational methods offer great hope. Over the past few years, numerous tools have become available for this task. The purpose of the current assessment is twofold: to provide some guidance to users regarding the accuracy of currently available tools in various settings, and to provide a benchmark of data sets for assessing future tools.

Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS

Abstract: Calorie restriction extends life span in organisms ranging from yeast to mammals. Here, we report that calorie restriction for either 3 or 12 months induced endothelial nitric oxide synthase (eNOS) expression and 3',5'-cyclic guanosine monophosphate formation in various tissues of male mice. This was accompanied by mitochondrial biogenesis, with increased oxygen consumption and adenosine triphosphate production, and an enhanced expression of sirtuin 1. These effects were strongly attenuated in eNOS null-mutant mice. Thus, nitric oxide plays a fundamental role in the processes induced by calorie restriction and may be involved in the extension of life span in mammals.

Prognostic Value of Ambulatory and Home Blood Pressures Compared With Office Blood Pressure in the General Population Follow-Up Results From the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) Study

Abstract: Background— Studies in hypertensive patients suggest that ambulatory blood pressure (BP) is prognostically superior to office BP. Much less information is available in the general population, however. Obtaining this information was the purpose of the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. Methods and Results— Office, home, and 24-hour ambulatory BP values were obtained in 2051 subjects between 25 and 74 years of age who were representative of the general population of Monza (Milan, Italy). Subjects were followed up for an average of 131 months, during which time cardiovascular and noncardiovascular fatal events were recorded (n=186). Office, home, and ambulatory BP values showed a significant exponential direct relationship with risk of cardiovascular or all-cause death. The goodness of fit of the relationship was greater for systolic than for diastolic BP and for night than for day BP, but its overall value was not better for home or ambulatory than for office BP. The slope of...

Characterization of paramagnetic species in N-doped TiO2 powders by EPR spectroscopy and DFT calculations.

Abstract: Electron paramagnetic resonance (EPR), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculations are combined for the first time in an effort to characterize the paramagnetic species present in N-doped anatase TiO2 powders obtained by sol-gel synthesis. The experimental hyperfine coupling constants are well reproduced by two structurally different nitrogen impurities: substitutional and interstitial N atoms in the TiO2 anatase matrix. DFT calculations show that the nitrogen impurities induce the formation of localized states in the band gap. Substitutional nitrogen states lie just above the valence band, while interstitial nitrogen states lie higher in the gap. Excitations from these localized states to the conduction band may account for the absorption edge shift toward lower energies (visible region) observed in the case of N-doped TiO2 with respect to pure TiO2 (UV region). Calculations also show that nitrogen doping leads to a substantial reduction of the energy cost to form oxygen vacancies in bulk TiO2. This suggests that nitrogen doping is likely to be accompanied by oxygen vacancy formation. Finally, we propose that the relative abundance of the two observed nitrogen-doping species depends on the preparation conditions, such as the oxygen concentration in the atmosphere and the annealing temperature during synthesis.

Guidelines for the management of adult lower respiratory tract infections

Abstract: Guidelines for the management of adult lower respiratory tract infections (LRTIs) were first published by a Task Force of the European Respiratory Society (ERS) in 1998 [1]. In 2005, a completely revised version was produced, this time by a joint Task Force of the ERS and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) [2]. They used up-to-date methodology for guideline development, including a transparent and objective systematic literature search strategy, and evidence and recommendation grading [2]. Now, 6 yrs later, a joint Task Force of the two Societies, using the same methodology as in 2005, has produced a further update of these guidelines incorporating publications through to May 2010. The Task Force included an epidemiologist with expertise in guideline methodology and experts in the specialty areas relevant to LRTI management, including general practice, microbiology, infectious diseases, respiratory medicine, intensive care and public health. A short version of the guidelines containing only the recommendations has now been published in Clinical Microbiology and Infection [3], with more detailed versions available on each Society’s website. The guidelines cover the breadth of adult community-acquired respiratory infection, including prevention (both vaccine- and nonvaccine-related), infections in the community and infections in those admitted to hospital, including pneumonia, exacerbations of chronic obstructive pulmonary disease (COPD) and exacerbations of bronchiectasis. The …

Niche-independent symmetrical self-renewal of a mammalian tissue stem cell.

Abstract: Pluripotent mouse embryonic stem (ES) cells multiply in simple monoculture by symmetrical divisions In vivo, however, stem cells are generally thought to depend on specialised cellular microenvironments and to undergo predominantly asymmetric divisions Ex vivo expansion of pure populations of tissue stem cells has proven elusive Neural progenitor cells are propagated in combination with differentiating progeny in floating clusters called neurospheres The proportion of stem cells in neurospheres is low, however, and they cannot be directly observed or interrogated Here we demonstrate that the complex neurosphere environment is dispensable for stem cell maintenance, and that the combination of fibroblast growth factor 2 (FGF-2) and epidermal growth factor (EGF) is sufficient for derivation and continuous expansion by symmetrical division of pure cultures of neural stem (NS) cells NS cells were derived first from mouse ES cells Neural lineage induction was followed by growth factor addition in basal culture media In the presence of only EGF and FGF-2, resulting NS cells proliferate continuously, are diploid, and clonogenic After prolonged expansion, they remain able to differentiate efficiently into neurons and astrocytes in vitro and upon transplantation into the adult brain Colonies generated from single NS cells all produce neurons upon growth factor withdrawal NS cells uniformly express morphological, cell biological, and molecular features of radial glia, developmental precursors of neurons and glia Consistent with this profile, adherent NS cell lines can readily be established from foetal mouse brain Similar NS cells can be generated from human ES cells and human foetal brain The extrinsic factors EGF plus FGF-2 are sufficient to sustain pure symmetrical self-renewing divisions of NS cells The resultant cultures constitute the first known example of tissue-specific stem cells that can be propagated without accompanying differentiation These homogenous cultures will enable delineation of molecular mechanisms that define a tissue-specific stem cell and allow direct comparison with pluripotent ES cells

Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells.

Abstract: The control of damaging inflammation by the mucosal immune system in response to commensal and harmful ingested bacteria is unknown. Here we show epithelial cells conditioned mucosal dendritic cells through the constitutive release of thymic stromal lymphopoietin and other mediators, resulting in the induction of 'noninflammatory' dendritic cells. Epithelial cell-conditioned dendritic cells released interleukins 10 and 6 but not interleukin 12, and they promoted the polarization of T cells toward a 'classical' noninflammatory T helper type 2 response, even after exposure to a T helper type 1-inducing pathogen. This control of immune responses seemed to be lost in patients with Crohn disease. Thus, the intimate interplay between intestinal epithelial cells and dendritic cells may help to maintain gut immune homeostasis.

The Arecibo Legacy Fast ALFA survey. I. Science goals, survey design, and strategy

Abstract: The recently initiated Arecibo Legacy Fast ALFA (ALFALFA) survey aims to map ~7000 deg2 of the high Galactic latitude sky visible from Arecibo, providing a H I line spectral database covering the redshift range between -1600 and 18,000 km (s-1) with ~5 km s(-1) resolution. Exploiting Arecibo's large collecting area and small beam size, ALFALFA is specifically designed to probe the faint end of the H I mass function in the local universe and will provide a census of H I in the surveyed sky area to faint flux limits, making it especially useful in synergy with wide-area surveys conducted at other wavelengths. ALFALFA will also provide the basis for studies of the dynamics of galaxies within the Local Supercluster and nearby superclusters, allow measurement of the H I diameter function, and enable a first wide-area blind search for local H I tidal features, H I absorbers at z < 0.06, and OH megamasers in the redshift range 0.16 < z < 0.25. Although completion of the survey will require some 5 years, public access to the ALFALFA data and data products will be provided in a timely manner, thus allowing its application for studies beyond those targeted by the ALFALFA collaboration. ALFALFA adopts a two-pass, minimum intrusion, drift scan observing technique that samples the same region of sky at two separate epochs to aid in the discrimination of cosmic signals from noise and terrestrial interference. Survey simulations, which take into account large-scale structure in the mass distribution and incorporate experience with the ALFA system gained from tests conducted during its commissioning phase, suggest that ALFALFA will detect on the order of 20,000 extragalactic H I line sources out to z ~ 0.06, including several hundred with H I masses M(HI) < 10(7.5) M ?.

Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy

Abstract: Background— In patients with aggressive malignancies who are undergoing high-dose chemotherapy, even minimal elevation of troponin I (TnI) is associated with late left ventricular dysfunction. The time course of the subclinical myocardial damage and its impact on the clinical outcome have never been investigated previously. Methods and Results— In 703 cancer patients, we measured TnI soon after chemotherapy (early TnI) and 1 month later (late TnI). Troponin was considered positive for values ≥0.08 ng/mL. Clinical and left ventricular ejection fraction evaluation (echocardiography) were performed before chemotherapy, 1, 3, 6, and 12 months after the end of the treatment, and again every 6 months afterward. Three different TnI patterns were identified, and patients were grouped accordingly. In 495 patients, both early and late TnI values were <0.08 ng/mL (TnI−/− group); in 145, there was only an early increase (TnI+/− group); and in 63 patients, both values increased (TnI+/+ group). In the TnI−/− group, no ...

Theory of Carbon Doping of Titanium Dioxide

Abstract: Recent experimental studies have determined that carbon doping dramatically improves the photocatalytic activity of TiO2 in the visible-light region. Using density functional theory (DFT) calculations within the generalized gradient corrected approximation, we investigate various structural models of carbon impurities in both the anatase and rutile polymorphs of TiO2 and analyze the associated modifications of the electronic band structure. We compare the stability of all these diverse species on the basis of their energy of formation as a function of the oxygen chemical potential, which determines whether the system is in an oxidizing or reducing environment. At low carbon concentrations, we find that, under oxygen-poor conditions, substitutional (to oxygen) carbon and oxygen vacancies are favored, whereas, under oxygen-rich conditions, interstitial and substitutional (to Ti) C atoms are preferred. Higher carbon concentrations undergo an unexpected stabilization caused by multidoping effects, interpreted...

Normal huntingtin function: an alternative approach to Huntington's disease

Abstract: Several neurological diseases are characterized by the altered activity of one or a few ubiquitously expressed cell proteins, but it is not known how these normal proteins turn into harmful executors of selective neuronal cell death. We selected huntingtin in Huntington's disease to explore this question because the dominant inheritance pattern of the disease seems to exclude the possibility that the wild-type protein has a role in the natural history of this condition. However, even in this extreme case, there is considerable evidence that normal huntingtin is important for neuronal function and that the activity of some of its downstream effectors, such as brain-derived neurotrophic factor, is reduced in Huntington's disease.

Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study.

Abstract: Objective: Intraabdominal hypertension is associated with significant morbidity and mortality in surgical and trauma patients. The aim of this study was to assess, in a mixed population of critically ill patients, whether intraabdominal pressure at admission was an independent predictor for mortality and to evaluate the effects of intraabdominal hypertension on organ functions. Design: Multiple-center, prospective epidemiologic study. Setting: Fourteen intensive care units in six countries. Patients: A total of 265 consecutive patients admitted for >24 hrs during the 4-wk study period. Interventions: None. Measurements and Main Results: Intraabdominal pressure was measured twice daily via the bladder. Data recorded on admission were the patient demographics with Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation II score, and type of admission; during intensive care stay, Sepsis-Related Organ Failure Assessment score and intraabdominal pressure were measured daily together with fluid balance. Nonsurvivors had a significantly higher mean intraabdominal pressure on admission than survivors: 11.4 4.8 vs. 9.5 4.8 mm Hg. Independent predictors for mortality were age (odds ratio, 1.04; 95% confidence interval, 1.01‐1.06; p .003), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1; 95% confidence interval, 1.05‐1.15; p < .0001), type of intensive care unit admission (odds ratio, 2.5 medical vs. surgical; 95% confidence interval, 1.24‐5.16; p .01), and the presence of liver dysfunction (odds ratio, 2.5; 95% confidence interval, 1.06‐5.8; p .04). The occurrence of intraabdominal hypertension during the intensive care unit stay was also an independent predictor of mortality (relative risk, 1.85; 95% confidence interval, 1.12‐3.06; p .01). Patients with intraabdominal hypertension at admission had significantly higher Sepsis-Related Organ Failure Assessment scores during the intensive care unit stay than patients without intraabdominal hypertension. Conclusions: Intraabdominal hypertension on admission was associated with severe organ dysfunction during the intensive care unit stay. The mean intraabdominal pressure on admission was not an independent risk factor for mortality; however, the occurrence of intraabdominal hypertension during the intensive care unit stay was an independent outcome predictor. (Crit Care Med 2005; 33:315‐322)

γ-Alumina as a Support for Catalysts: A Review of Fundamental Aspects

Abstract: The present review discusses the most important aspects to take into consideration to improve the properties of γ-Al2O3 as a support for catalytic applications. We show that the synthetic route to γ-Al2O3 is the starting point that determines the micro- and macrostructure of the oxide and, consequently, allows control of the support characteristics. The relevance of the adequate structural characterization of the oxide as well as of its surface sorption behavior through the proton-affinity distributions, are considered. The usefulness of the latter during supported catalyst preparation, for catalytic active sites characterization, and for stability evaluation after calcination are discussed for the Co/γ-Al2O3 system in particular. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Effective field theories for heavy quarkonium

Abstract: We briefly review how nonrelativistic effective field theories give us a definition of the QCD potentials and a coherent field-theory-derived quantum-mechanical scheme to calculate the properties of bound states made by two or more heavy quarks. In this framework heavy quarkonium properties depend only on the QCD parameters (quark masses and αs) and nonpotential corrections are systematically accounted for. The relation between the form of the nonperturbative potentials and the low-energy QCD dynamics is also discussed.

A short γ-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225

Abstract: Gamma-ray bursts (GRBs) are either ‘long and soft’, or ‘short and hard’. The long-duration type leave a strong afterglow and have been extensively studied. So we have a good idea of what causes them: explosions of massive stars in distant star-forming galaxies. Short GRBs, with no strong afterglow, were harder to pin down. The Swift satellite, launched last November, is designed to study bursts as soon as they happen. Having shown its worth with long GRBs (reported in the 18 August issue of Nature), Swift has now bagged a short burst, GRB 050509B, precisely measured its location and detected the X-ray afterglow. Four papers this week report on this and another recent short burst. Now, over 20 years after they were first recognized, the likely origin of the short GRBs is revealed as a merger between neutron stars of a binary system and the instantaneous production of a black hole. Gamma-ray bursts (GRBs) come in two classes1: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z ≈ 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars2. In contrast, no short GRB had been accurately (< 10″) and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from—and the localization of—the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect3,4 if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.

Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.

Abstract: Background The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. Methods We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). Results An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, –20 percent; 95 percent confidence interval, –26 to –14 percent; P=0.001). The levofloxacin group had a lower rate of microbiological...

Comprehensive Interaction Map of the Arabidopsis MADS Box Transcription Factors

Abstract: Interactions between proteins are essential for their functioning and the biological processes they control. The elucidation of interaction maps based on yeast studies is a first step toward the understanding of molecular networks and provides a framework of proteins that possess the capacity and specificity to interact. Here, we present a comprehensive plant protein–protein interactome map of nearly all members of the Arabidopsis thaliana MADS box transcription factor family. A matrix-based yeast two-hybrid screen of >100 members of this family revealed a collection of specific heterodimers and a few homodimers. Clustering of proteins with similar interaction patterns pinpoints proteins involved in the same developmental program and provides valuable information about the participation of uncharacterized proteins in these programs. Furthermore, a model is proposed that integrates the floral induction and floral organ formation networks based on the interactions between the proteins involved. Heterodimers between flower induction and floral organ identity proteins were observed, which point to (auto)regulatory mechanisms that prevent the activity of flower induction proteins in the flower.