Showing papers by "Sapienza University of Rome published in 2000"

A flat Universe from high-resolution maps of the cosmic microwave background radiation

Abstract: The blackbody radiation left over from the Big Bang has been transformed by the expansion of the Universe into the nearly isotropic 2.73 K cosmic microwave background. Tiny inhomogeneities in the early Universe left their imprint on the microwave background in the form of small anisotropies in its temperature. These anisotropies contain information about basic cosmological parameters, particularly the total energy density and curvature of the Universe. Here we report the first images of resolved structure in the microwave background anisotropies over a significant part of the sky. Maps at four frequencies clearly distinguish the microwave background from foreground emission. We compute the angular power spectrum of the microwave background, and find a peak at Legendre multipole l_(peak) = (197 ± 6), with an amplitude ΔT_(200) = (69 ± 8) µK. This is consistent with that expected for cold dark matter models in a flat (euclidean) Universe, as favoured by standard inflationary models.

MAXIMA-1: A measurement of the cosmic microwave background anisotropy on angular scales of 10′-5°

Abstract: We present a map and an angular power spectrum of the anisotropy of the cosmic microwave background (CMB) from the first flight of MAXIMA. MAXIMA is a balloon-borne experiment with an array of 16 bolometric photometers operated at 100 mK. MAXIMA observed a 124 deg region of the sky with 10' resolution at frequencies of 150, 240 and 410 GHz. The data were calibrated using in-flight measurements of the CMB dipole anisotropy. A map of the CMB anisotropy was produced from three 150 and one 240 GHz photometer without need for foreground subtractions. Analysis of this CMB map yields a power spectrum for the CMB anisotropy over the range 36 {le} {ell} {le} 785. The spectrum shows a peak with an amplitude of 78 {+-} 6 {mu}K at {ell} {approx_equal} 220 and an amplitude varying between {approx} 40 {mu}K and {approx} 50 {mu}K for 400 {approx}< {ell} {approx}< 785.

Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells.

Abstract: Members of the Toll-like receptor (TLR) family probably play a fundamental role in pathogen recognition and activation of innate immunity. The present study used a systematic approach to analyze how different human leukocyte populations express specific transcripts for the first five characterized TLR family members. TLR1 was expressed in all leukocytes examined, including monocytes, polymorphonuclear leukocytes, T and B cells, and NK cells. In contrast TLR2, TLR4, and TLR5 were expressed in myelomonocytic elements. Exposure to bacterial products, such as LPS or lipoarabinomannan, or to proinflammatory cytokines increased TLR4 expression in monocytes and polymorphonuclear leukocytes, whereas IL-10 blocked this effect. TLR3 was only expressed in human dendritic cells (DC) wherein maturation induced by bacterial products or cytokines was associated with reduced expression. TLR3 mRNA expression was detected by in situ hybridization in DC and lymph nodes. These results demonstrate that TLR1 through TLR5 mRNAs are differentially expressed and regulated in human leukocytes. In particular, expression of TLR3 transcripts is restricted to DC that are the only elements which express the full TLR repertoire. These data suggest that TLR can be classified based on expression pattern as ubiquitous (TLR1), restricted (TLR2, TLR4, and TLR5 in myelomonocytic cells), and specific (TLR3 in DC) molecules.

Monitoring Natural and Synthetic Estrogens at Activated Sludge Sewage Treatment Plants and in a Receiving River Water

Abstract: Sewage treatment plant (STP) effluents with primarily domestic inputs are strongly suspected to be an important source of natural and synthetic estrogens contaminating the aquatic environment. Even a few ng/L of some of these substances can provoke reproductive disturbances in riverine fish. The main purpose of this investigation has been that of ascertaining whether activated sludge STPs (ASSTPs) are able to produce significant amounts of free estrogens. For this purpose, we have monitored monthly estriol (E3), estradiol (E2), estrone (E1) and ethinylestradiol (EE2) in influents and effluents of six Roman ASSTPs for five months. To do this, we have developed an original analytical method involving analyte extraction with a Carbograph 4 cartridge and LC coupled with negative turbo ion spray tandem mass spectrometry in the selected reaction monitoring mode. Analyte recovery ranged between 86 and 91%, and limits of quantification were below 1 ng/L. Over five months, inlet concentrations of E3, E2, E1 and EE...

Tracing European founder lineages in the Near Eastern mtDNA pool.

Abstract: Founder analysis is a method for analysis of nonrecombining DNA sequence data, with the aim of identification and dating of migrations into new territory. The method picks out founder sequence types in potential source populations and dates lineage clusters deriving from them in the settlement zone of interest. Here, using mtDNA, we apply the approach to the colonization of Europe, to estimate the proportion of modern lineages whose ancestors arrived during each major phase of settlement. To estimate the Palaeolithic and Neolithic contributions to European mtDNA diversity more accurately than was previously achievable, we have now extended the Near Eastern, European, and northern-Caucasus databases to 1,234, 2,804, and 208 samples, respectively. Both back-migration into the source population and recurrent mutation in the source and derived populations represent major obstacles to this approach. We have developed phylogenetic criteria to take account of both these factors, and we suggest a way to account for multiple dispersals of common sequence types. We conclude that (i) there has been substantial back-migration into the Near East, (ii) the majority of extant mtDNA lineages entered Europe in several waves during the Upper Palaeolithic, (iii) there was a founder effect or bottleneck associated with the Last Glacial Maximum, 20,000 years ago, from which derives the largest fraction of surviving lineages, and (iv) the immigrant Neolithic component is likely to comprise less than one-quarter of the mtDNA pool of modern Europeans.

Prosocial Foundations of Children's Academic Achievement

Abstract: The present longitudinal research demonstrates robust contributions of early prosocial behavior to children's developmental trajectories in academic and social domains. Both prosocial and ag- gressive behaviors in early childhood were tested as predictors of academic achievement and peer relations in adolescence 5 years later. Prosocialness included cooperating, helping, sharing, and con- soling, and the measure of antisocial aspects included proneness to verbal and physical aggression. Prosocialness had a strong positive impact on later academic achievement and social preferences, but early aggression had no significant effect on either outcome. The conceptual model accounted for 35% of variance in later academic achievement, and 37% of variance in social preferences. Additional analysis revealed that early academic achievement did not contribute to later academic achievement after controlling for effects of early prosocialness. Possible mediating processes by which prosocialness may affect academic achievement and other socially desirable devel- opmental outcomes are proposed. A major interest of parents, teachers, and societal agencies centers on discovering early predictors of children's developmental trajecto- ries, with the goal of guiding them in desirable directions (Hartup, 1985; Hays, 1994; Lewis, 1995). Such knowledge enables individuals who influence children's psychosocial development to promote so- Using a longitudinal design and structural equation modeling, we tested the relative impact of early prosocial and aggressive behaviors on children's academic achievement and social ties to their peers 5 years later. In our conceptual model, early prosocialness is negatively associated with aggressiveness, and promotes both positive peer re- lations and academic achievement. In contrast, early aggressiveness adversely affects both peer relations and academic accomplishments.

Atomic-scale structure and catalytic reactivity of the RuO(2)(110) surface

Abstract: The structure of RuO(2)(110) and the mechanism for catalytic carbon monoxide oxidation on this surface were studied by low-energy electron diffraction, scanning tunneling microscopy, and density-functional calculations. The RuO(2)(110) surface exposes bridging oxygen atoms and ruthenium atoms not capped by oxygen. The latter act as coordinatively unsaturated sites-a hypothesis introduced long ago to account for the catalytic activity of oxide surfaces-onto which carbon monoxide can chemisorb and from where it can react with neighboring lattice-oxygen to carbon dioxide. Under steady-state conditions, the consumed lattice-oxygen is continuously restored by oxygen uptake from the gas phase. The results provide atomic-scale verification of a general mechanism originally proposed by Mars and van Krevelen in 1954 and are likely to be of general relevance for the mechanism of catalytic reactions at oxide surfaces.

Use of two-block partial least-squares to study covariation in shape.

Abstract: The relatively new two-block partial least-squares method for analyzing the covariance between two sets of variables is described and contrasted with the well-known method of canonical correlation analysis. Their statistical properties, types of answers, and visualization techniques are discussed. Examples are given to show its usefulness in comparing two sets of variables—especially when one or both of the sets of variables are shape variables from a geometric morphometric study. (Canonical correlation; covariance; morphometrics; Mus musculus domesticus; partial least squares; Plethodon; visualization.)

Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones.

Abstract: The ability of marrow-derived osteoprogenitor cells to promote repair of critical-size tibial gaps upon autologous transplantation on a hydroxyapatite ceramic (HAC) carrier was tested in a sheep model. Conditions for in vitro expansion of sheep bone marrow stromal cells (BMSC) were established and the osteogenic potential of the expanded cells was validated. Ectopic implantation of sheep BMSC in immunocompromised mice led to extensive bone formation. When used to repair tibial gaps in sheep, cell-loaded implants (n = 2) conducted a far more extensive bone formation than did cell-free HAC cylinders (n = 2) over a 2-month period. In cell-loaded implants, bone formation was found to occur both within the internal macropore space and around the HAC cylinder while in control cell-free implants, bone formation was limited mostly to the outer surface and was not observed in most of the inner pores. As tested in an indentation assay, the stiffness of the complex HAC-bone material was found to be higher in cell-loaded implants compared to controls. Our pilot study on a limited number of large-sized animals suggests that the use of autologous BMSC in conjunction with HAC-based carriers results in faster bone repair compared to HAC alone. Potentially this combination could be used clinically in the treatment of extensive long bone defects.

The p53/p63/p73 family of transcription factors: overlapping and distinct functions

Abstract: The p53 gene is the most frequently mutated gene in human cancer. The identification of two homologues, p63 and p73, revealed that p53 is a member of a family of related transcription factors. Given that they share amino acid sequence identity reaching 63% in the DNA-binding domain, p53, p63 and p73 should have redundant functions in the regulation of gene expression. Indeed, p73 can activate p53-regulated genes and suppress growth or induce apoptosis. Moreover, p53 and p73 are both induced by DNA damage - albeit through distinct mechanisms. Other evidence, however, suggests that p63 and p73 are important for regulation of normal development. An extended C-terminal region, not found in p53, is alternatively spliced in p63 and p73. Within this C-terminal extension is a sterile a motif (SAM) previously found in other proteins that regulate development. The p63-deficient mice showed developmental abnormalities. Interestingly, the human p63 gene is mutated in children who have the disease Ectrodactyly, Ectodermal dysplasia and facial Clefts (EEC) syndrome, and the disease phenotype is similar to the one of p63-deficient mice. The p63 and p73 genes are rarely mutated in human cancer, although p73 loss is observed in neuroblastoma and a subtype of T-cell lymphoma. p53, p63 and p73 appear to have overlapping and distinct functions: p53 regulates the stress response to suppress tumors; p63 is essential for ectoderm development; and p73 might regulate both the stress response and development. Because p53 and p73 are linked to different upstream pathways, this family of transcription factors might regulate a common set of genes in response to different extracellular signals and developmental cues.

Hormonal responses to whole-body vibration in men.

Abstract: The aim of this study was to evaluate the acute responses of blood hormone concentrations and neuromuscular performance following whole-body vibration (WBV) treatment. Fourteen male subjects [mean (SD) age 25 (4.6) years] were exposed to vertical sinusoidal WBV, 10 times for 60 s, with 60 s rest between the vibration sets (a rest period lasting 6 min was allowed after 5 vibration sets). Neuromuscular performance tests consisting of counter-movement jumps and maximal dynamic leg presses on a slide machine, performed with an extra load of 160% of the subjects body mass, and with both legs were administered before and immediately after the WBV treatment. The average velocity, acceleration, average force, and power were calculated and the root mean square electromyogram (EMGrms) were recorded from the vastus lateralis and rectus femoris muscles simultaneously during the leg-press measurement. Blood samples were also collected, and plasma concentrations of testosterone (T), growth hormone (GH) and cortisol (C) were measured. The results showed a significant increase in the plasma concentration of T and GH, whereas C levels decreased. An increase in the mechanical power output of the leg extensor muscles was observed together with a reduction in EMGrms activity. Neuromuscular efficiency improved, as indicated by the decrease in the ratio between EMGrms and power. Jumping performance, which was measured using the counter-movement jump test, was also enhanced. Thus, it can be argued that the biological mechanism produced by vibration is similar to the effect produced by explosive power training (jumping and bouncing). The enhancement of explosive power could have been induced by an increase in the synchronisation activity of the motor units, and/or improved co-ordination of the synergistic muscles and increased inhibition of the antagonists. These results suggest that WBV treatment leads to acute responses of hormonal profile and neuromuscular performance. It is therefore likely that the effect of WBV treatment elicited a biological adaptation that is connected to a neural potentiation effect, similar to those reported to occur following resistance and explosive power training. In conclusion, it is suggested that WBV influences proprioceptive feedback mechanisms and specific neural components, leading to an improvement of neuromuscular performance. Moreover, since the hormonal responses, characterised by an increase in T and GH concentration and a decrease in C concentration, and the increase in neuromuscular effectiveness were simultaneous but independent, it is speculated that the two phenomena might have common underlying mechanisms.

The structural basis for the recognition of acetylated histone H4 by the bromodomain of histone acetyltransferase Gcn5p

Abstract: The bromodomain is an approximately 110 amino acid module found in histone acetyltransferases and the ATPase component of certain nucleosome remodelling complexes. We report the crystal structure at 1.9 A resolution of the Saccharomyces cerevisiae Gcn5p bromodomain complexed with a peptide corresponding to residues 15-29 of histone H4 acetylated at the zeta-N of lysine 16. We show that this bromodomain preferentially binds to peptides containing an N:-acetyl lysine residue. Only residues 16-19 of the acetylated peptide interact with the bromodomain. The primary interaction is the N:-acetyl lysine binding in a cleft with the specificity provided by the interaction of the amide nitrogen of a conserved asparagine with the oxygen of the acetyl carbonyl group. A network of water-mediated H-bonds with protein main chain carbonyl groups at the base of the cleft contributes to the binding. Additional side chain binding occurs on a shallow depression that is hydrophobic at one end and can accommodate charge interactions at the other. These findings suggest that the Gcn5p bromodomain may discriminate between different acetylated lysine residues depending on the context in which they are displayed.

Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo- controlled, randomized phase II trial

Abstract: In this ‘double-blind’, randomized, placebo-controlled phase II trial, we compared an altered peptide ligand of myelin basic protein with placebo, evaluating their safety and influence on magnetic resonance imaging in relapsing–remitting multiple sclerosis. A safety board suspended the trial because of hypersensitivity reactions in 9% of the patients. There were no increases in either clinical relapses or in new enhancing lesions in any patient, even those with hypersensitivity reactions. Secondary analysis of those patients completing the study showed that the volume and number of enhancing lesions were reduced at a dose of 5 mg. There was also a regulatory type 2 T helper-cell response to altered peptide ligand that cross-reacted with the native peptide.

Skeletal myogenic potential of human and mouse neural stem cells.

Abstract: Distinct cell lineages established early in development are usually maintained throughout adulthood. Thus, adult stem cells have been thought to generate differentiated cells specific to the tissue in which they reside. This view has been challenged; for example, neural stem cells can generate cells that normally originate from a different germ layer. Here we show that acutely isolated and clonally derived neural stem cells from mice and humans could produce skeletal myotubes in vitro and in vivo, the latter following transplantation into adult animals. Myogenic conversion in vitro required direct exposure to myoblasts, and was blocked if neural cells were clustered. Thus, a community effect between neural cells may override such myogenic induction. We conclude that neural stem cells, which generate neurons, glia and blood cells, can also produce skeletal muscle cells, and can undergo various patterns of differentiation depending on exposure to appropriate epigenetic signals in mature tissues.

Constraints on Cosmological Parameters from MAXIMA-1

Abstract: We set new constraints on a seven-dimensional space of cosmological parameters within the class of inflationary adiabatic models. We use the angular power spectrum of the cosmic microwave background measured over a wide range of l in the first flight of the MAXIMA balloon-borne experiment (MAXIMA-1) and the low-l results from the COBE Differential Microwave Radiometer experiment. We find constraints on the total energy density of the universe, Ω = 1.0img1.gif, the physical density of baryons, Ωbh2 = 0.03 ± 0.01, the physical density of cold dark matter, Ωcdmh2 = 0.2img2.gif, and the spectral index of primordial scalar fluctuations, ns = 1.08 ± 0.1, all at the 95% confidence level. By combining our results with measurements of high-redshift supernovae we constrain the value of the cosmological constant and the fractional amount of pressureless matter in the universe to 0.45 < ΩΛ < 0.75 and 0.25 < Ωm < 0.50, at the 95% confidence level. Our results are consistent with a flat universe and the shape parameter deduced from large-scale structure, and in marginal agreement with the baryon density from big bang nucleosynthesis.

Endoscopic cordectomy. A proposal for a classification by the Working Committee, European Laryngological Society.

Abstract: The European Laryngological Society is proposing a classification of different laryngeal endoscopic cordectomies in order to ensure better definitions of post-operative results. We chose to keep the word "cordectomy" even for partial resections because it is the term most often used in the surgical literature. The classification comprises eight types of cordectomies: a subepithelial cordectomy (type I), which is resection of the epithelium; a subligamental cordectomy (type II), which is a resection of the epithelium, Reinke's space and vocal ligament; transmuscular cordectomy (type III), which proceeds through the vocalis muscle; total cordectomy (type IV); extended cordectomy, which encompasses the contralateral vocal fold and the anterior commissure (type Va); extended cordectomy, which includes the arytenoid (type Vb); extended cordectomy, which encompasses the subglottis (type Vc); and extended cordectomy, which includes the ventricle (type Vd). Indications for performing those cordectomies may vary from surgeon to surgeon. The operations are classified according to the surgical approach used and the degree of resection in order to facilitate use of the classification in daily practice. Each surgical procedure ensures that a specimen is available for histopathological examination.

Constitutive activation of NF‐κB and T‐cell leukemia/lymphoma in Notch3 transgenic mice

Abstract: The multiplicity of Notch receptors raises the question of the contribution of specific isoforms to T-cell development. Notch3 is expressed in CD4–8– thymocytes and is down-regulated across the CD4–8– to CD4+8+ transition, controlled by pre-T-cell receptor signaling. To determine the effects of Notch3 on thymocyte development, transgenic mice were generated, expressing lck promoter-driven intracellular Notch3. Thymuses of young transgenics showed an increased number of thymocytes, particularly late CD4–8– cells, a failure to down-regulate CD25 in post-CD4–8– subsets and sustained activity of NF-κB. Subsequently, aggressive multicentric T-cell lymphomas developed with high penetrance. Tumors sustained characteristics of immature thymocytes, including expression of CD25, pTα and activated NF-κB via IKKα-dependent degradation of IκBα and enhancement of NF-κB-dependent anti-apoptotic and proliferative pathways. Together, these data identify activated Notch3 as a link between signals leading to NF-κB activation and T-cell tumorigenesis. The phenotypes of pre-malignant thymocytes and of lymphomas indicate a novel and particular role for Notch3 in co-ordinating growth and differentiation of thymocytes, across the pre-T/T cell transition, consistent with the normal expression pattern of Notch3.

Morphological and Functional Characteristics of Patent Foramen Ovale and Their Embolic Implications

Abstract: Background and Purpose—Transesophageal echocardiography (TEE) has detected a high prevalence of patent foramen ovale (PFO) in stroke patients, but the clinical implications of the distinctive characteristics of this patency are still a matter of debate. Methods—We studied 350 patients with acute ischemic stroke or transient ischemic attack (TIA) within 1 week of admission. Of these, 101 (29%) were identified by contrast TEE to have a PFO; 86 patients (25%) were cryptogenic stroke patients, and 163 were excluded because of the presence of a definite or possible arterial or clinical evidence of a source of emboli or small-vessel disease. Thirteen PFO subjects without a history of embolism were designated as the control group. All PFO and cryptogenic stroke patients were followed up by neurological visits. Results—Compared with controls, PFO patients with acute stroke or TIA more frequently presented with a right-to-left shunt at rest and a higher membrane mobility (P<0.05). Patients with these characteristi...

DNA Vaccination Against Rat Her-2/Neu p185 More Effectively Inhibits Carcinogenesis Than Transplantable Carcinomas in Transgenic BALB/c Mice

Abstract: The ability of vaccination with plasmids coding for the extracellular and the transmembrane domain of the product of transforming rat Her-2/neu oncogene (r-p185) to protect against r-p185(+) transplantable carcinoma (TUBO) cells and mammary carcinogenesis was evaluated. In normal BALB/c mice, DNA vaccination elicits anti-r-p185 Ab, but only a marginal CTL reactivity, and protects against a TUBO cell challenge. Massive reactive infiltration is associated with TUBO cell rejection. In BALB/c mice transgenic for the rat Her-2/neu gene (BALB-neuT), DNA vaccination elicits a lower anti-r-p185 Ab response, no CTL activity and only incompletely protects against TUBO cells, but markedly hampers the progression of carcinogenesis. At 33 wk of age, when control BALB-neuT mice display palpable tumors in all mammary glands, about 60% of immunized mice are tumor free, and tumor multiplicity is markedly reduced. Tumor-free mammary glands still display the atypical hyperplasia of the early stages of carcinogenesis, and a marked down-modulation of r-p185, along with a massive reactive infiltrate. However, BALB-neuT mice protected against mammary carcinogenesis fail to efficiently reject a TUBO cell challenge. This suggests that the mechanisms required for the rejection of transplantable tumors may not coincide with those that inhibit the slow progression of carcinogenesis.

Higher-order glass-transition singularities in colloidal systems with attractive interactions

Abstract: The transition from a liquid to a glass in colloidal suspensions of particles interacting through a hard core plus an attractive square-well potential is studied within the mode-coupling-theory framework. When the width of the attractive potential is much shorter than the hard-core diameter, a reentrant behavior of the liquid-glass line and a glass-glass-transition line are found in the temperature-density plane of the model. For small well-width values, the glass-glass-transition line terminates in a third-order bifurcation point, i.e., in a A3 (cusp) singularity. On increasing the square-well width, the glass-glass line disappears, giving rise to a fourth-order A4 (swallow-tail) singularity at a critical well width. Close to the A3 and A4 singularities the decay of the density correlators shows stretching of huge dynamical windows, in particular logarithmic time dependence.

Leptin induces direct vasodilation through distinct endothelial mechanisms.

Abstract: In this study, we reveal that leptin evokes an acute hypotensive effect in 6-hydroxydopamine sympathectomized rats (response to maximal leptin dose, mean blood pressure: from 92 +/- 4 to 78 +/- 2 mmHg, P < 0.01). This hemodynamic effect is related to a direct action of the hormone on vascular tone, since in aortic and mesenteric rings increasing doses of leptin evoke a dose-dependent vasorelaxation (aorta: from 3 +/- 1 to 36 +/- 3, n = 15; mesenteric: from 6 +/- 1 to 30 +/- 5, n = 10), which is impaired by endothelial denudation. In particular, leptin-evoked vasorelaxation is impaired by nitric oxide synthase inhibition in aorta (delta% of maximal response: from 36 +/- 3 to 3 +/- 1, P < 0.01) and by endothelium-derived hyperpolarizing factor (EDHF) inhibition in mesenteric arteries (delta% of maximal response: from 30 +/- 5 to 7 +/- 2, P < 0.01), suggesting that vasorelaxation evoked by leptin is heterogeneous and related to the vascular bed. Finally, the inhibition of nitric oxide synthase by NG-nitro-L-arginine-methyl ester does not modify blood pressure response to leptin, suggesting a predominant role of the EDHF mechanism in the hypotensive effect of leptin.