Sapienza University of Rome

About: Sapienza University of Rome is a education organization based out in Rome, Lazio, Italy. It is known for research contribution in the topics: Population & Medicine. The organization has 62002 authors who have published 155468 publications receiving 4397244 citations. The organization is also known as: La Sapienza & Università La Sapienza di Roma.

Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle

Abstract: Aging skeletal muscles suffer a steady decline in mass and functional performance, and compromised muscle integrity as fibrotic invasions replace contractile tissue, accompanied by a characteristic loss in the fastest, most powerful muscle fibers. The same programmed deficits in muscle structure and function are found in numerous neurodegenerative syndromes and disease-related cachexia. We have generated a model of persistent, functional myocyte hypertrophy using a tissue-restricted transgene encoding a locally acting isoform of insulin-like growth factor-1 that is expressed in skeletal muscle (mIgf-1). Transgenic embryos developed normally, and postnatal increases in muscle mass and strength were not accompanied by the additional pathological changes seen in other Igf-1 transgenic models. Expression of GATA-2, a transcription factor normally undetected in skeletal muscle, marked hypertrophic myocytes that escaped age-related muscle atrophy and retained the proliferative response to muscle injury characteristic of younger animals. The preservation of muscle architecture and age-independent regenerative capacity through localized mIgf-1 transgene expression suggests clinical strategies for the treatment of age or disease-related muscle frailty.

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.

Neutrophils Activate Plasmacytoid Dendritic Cells by Releasing Self-DNA–Peptide Complexes in Systemic Lupus Erythematosus

Abstract: Systemic lupus erythematosus (SLE) is a severe and incurable autoimmune disease characterized by chronic activation of plasmacytoid dendritic cells (pDCs) and production of autoantibodies against nuclear self-antigens by hyperreactive B cells. Neutrophils are also implicated in disease pathogenesis; however, the mechanisms involved are unknown. Here, we identified in the sera of SLE patients immunogenic complexes composed of neutrophil-derived antimicrobial peptides and self-DNA. These complexes were produced by activated neutrophils in the form of web-like structures known as neutrophil extracellular traps (NETs) and efficiently triggered innate pDC activation via Toll-like receptor 9 (TLR9). SLE patients were found to develop autoantibodies to both the self-DNA and antimicrobial peptides in NETs, indicating that these complexes could also serve as autoantigens to trigger B cell activation. Circulating neutrophils from SLE patients released more NETs than those from healthy donors; this was further stimulated by the antimicrobial autoantibodies, suggesting a mechanism for the chronic release of immunogenic complexes in SLE. Our data establish a link between neutrophils, pDC activation, and autoimmunity in SLE, providing new potential targets for the treatment of this devastating disease.

A Multidimensional unfolding method based on Bayes' theorem

Abstract: Bayes' theorem offers a natural way to unfold experimental distributions in order to get the best estimates of the true ones. The weak point of the Bayes approach, namely the need of the knowledge of the initial distribution, can be overcome by an iterative procedure. Since the method proposed here does not make use of continuous variables, but simply of cells in the spaces of the true and of the measured quantities, it can be applied in multidimensional problems.

First result from the Alpha Magnetic Spectrometer on the International Space Station: precision measurement of the positron fraction in primary cosmic rays of 0.5-350 GeV.

Abstract: A precision measurement by the Alpha Magnetic Spectrometer on the International Space Station of the positron fraction in primary cosmic rays in the energy range from 0.5 to 350 GeV based on 6.8 × 10(6) positron and electron events is presented. The very accurate data show that the positron fraction is steadily increasing from 10 to ∼ 250 GeV, but, from 20 to 250 GeV, the slope decreases by an order of magnitude. The positron fraction spectrum shows no fine structure, and the positron to electron ratio shows no observable anisotropy. Together, these features show the existence of new physical phenomena.