Gas1-induced Growth Suppression Requires a Transactivation-independent p53 Function.

In normal cells, induction of quiescence is accompanied by the increased expression of growth arrest-specific genes (gas). One of them, gas1, is regulated at the transcriptional level and codes for a membrane-associated protein (Gas1) which is down regulated during the G0-to-S phase transition in serum-stimulated cells. Gas1 is not expressed in growing or transformed cells, and when overexpressed in normal fibroblasts, it blocks the G0-to-S phase transition. Moreover, Gas1 blocks cell proliferation in several transformed cells with the exception of simian virus 40- or adenovirus-transformed cell lines. In this paper, we demonstrate that overexpression of Gas1 blocks cell proliferation in a p53-dependent manner and that the N-terminal domain-dependent transactivating function of p53 is dispensable for Gas1-induced growth arrest. These data therefore indicate that the other intrinsic transactivation-independent functions of p53, possibly related to regulation of apoptosis, should be involved in mediating Gas1-induced growth arrest

Faster N release, but not C loss, from leaf litter of invasives compared to native species in mediterranean ecosystems

Plant invasions can have relevant impacts on biogeochemical cycles, whose extent, in Mediterranean ecosystems, have not yet been systematically assessed comparing litter carbon (C) and nitrogen (N) dynamics between invasive plants and native communities. We carried out a 1-year litterbag experiment in 4 different plant communities (grassland, sand dune, riparian and mixed forests) on 8 invasives and 24 autochthonous plant species, used as control. Plant litter was characterized for mass loss, N release, proximate lignin and litter chemistry by 13C CPMAS NMR. Native and invasive species showed significant differences in litter chemical traits, with invaders generally showing higher N concentration and lower lignin/N ratio. Mass loss data revealed no consistent differences between native and invasive species, although some woody and vine invaders showed exceptionally high decomposition rate. In contrast, N release rate from litter was faster for invasive plants compared to native species. N concentration, lignin content and relative abundance of methoxyl and N-alkyl C region from 13C CPMAS NMR spectra were the parameters that better explained mass loss and N mineralization rates. Our findings demonstrate that during litter decomposition invasive species litter has no different decomposition rates but greater N release rate compared to natives. Accordingly, invasives are expected to affect N cycle in Mediterranean plant communities, possibly promoting a shift of plant assemblages

Thermally stable external cavity laser based on silicon nitride periodic nanostructures

In this paper we demonstrate a thermally stable silicon nitride external cavity (SiN EC) laser based on a 250 μm sized Reflective Semiconductor Optical Amplifier (RSOA) butt-coupled to a series of Si 3 N 4 Bragg gratings acting as wavelength selective reflectors. The laser shows power outputs over 3 mW, a very low lasing threshold of 12 mA and with a typical Side-Mode Suppression Ratio of 45 dB. In this configuration a mode-hop free lasing regime over a range of 47 mA has been achieved (from 15 mA to 62 mA). Thermal stability of the lasing wavelength at temperatures up to 80°C is demonstrated. Further on, experimental results on a passive chip based on new 1D photonic crystal cavities are shown to have higher Q-Factors. This paves the way to avoiding thermal wavelength drifts and unlocks the possibility for these devices to be integrated in Dense WDM and optical-interconnect technologies, where transceivers must operate over a wide temperature range without active cooling

Energy, forest, and indoor air pollution models for Sagarmatha National Park and Buffer Zone, Nepal

This paper presents the results of management-oriented research on energy, forest, and human health issues in a remote mountain area, the Sagarmatha National Park and Buffer Zone (SNPBZ), Nepal. The research was based on a broader, integrated participatory framework ultimately intended for use in adaptive management. The present study focused on the application of a participatory modeling framework to address problems related to energy demand and consumption, forest condition, and indoor air pollution, which were defined by the stakeholders as important issues to be addressed. The models were developed using a generalizing design that allows for user-friendly adaptation to other contexts (free download at http://hkkhpartnership.org). Moreover, we simulated management scenarios in collaboration with all modeling actors with the aim of building consensus on the understanding of the system as well as supporting decision-makers' capacity not only to respond to changes, but also to anticipate them. Importantly, the system dynamics assessment found that the SNPBZ forests are affected by an increasing demand for fuelwood (occurring due to tourism growth), as one of the main sources of energy. Selected forests show an average reduction of 38 in forest biomass from 1992 to 2008. This shows that the business-as-usual scenario is unlikely to result in the preservation of the current forest status; in fact, such preservation would require 75 of fuelwood to be replaced with alternative energy sources. At the same time, a 75 reduction of fuelwood use (and an 80 reduction of dung use) would reduce indoor carbon monoxide (CO) concentrations to the standard limits for CO exposure set by the World Health Organization

A comparison of Power Doppler with conventional sonographic imaging for the evaluation of renal artery stenosis

BACKGROUND: Power Doppler (PD) has improved diagnostic capabilities of vascular sonography, mainly because it is independent from the angle of insonation. We evaluated this technique in a prospective comparison with conventional imaging, consisting in Duplex and Color Doppler, for the evaluation of Renal Artery (RA) stenosis. METHODS: Sensitivity, specificity and predictive values of PD and conventional imaging were assessed in a blinded fashion on eighteen patients, 9 with angiographic evidence of unilateral RA stenosis (hypertensive patients) and 9 with angiographically normal arteries (control group). PD images were interpreted with an angiography-like criteria. RESULTS: In the control group both techniques allowed correct visualization of 16 out of the 18 normal arteries (93% specificity). Only in five hypertensive patients RA stenosis was correctly identified with conventional technique (56% sensitivity and 86% negative predictive value); PD was successful in all hypertensive patients (100% sensitivity and negative predictive value), since the operators could obtain in each case of RA stenosis a sharp color signal of the whole vessel with a clear "minus" at the point of narrowing of the lumen. All results were statistically significant (p < 0.01). CONCLUSIONS: This study demonstrates that PD is superior to conventional imaging, in terms of sensitivity and specificity, for the diagnosis of RA stenosis, because it allows a clear visualization of the whole stenotic vascular lumen. Especially if it is used in concert with the other sonographic techniques, PD can enable a more accurate imaging of renovascular disease with results that seem comparable to selective angiography

Transcriptional Downregulation of Rice rpL32 Gene under Abiotic Stress Is Associated with Removal of Transcription Factors within the Promoter Region

Background: The regulation of ribosomal proteins in plants under stress conditions has not been well studied. Although a few reports have shown stress-specific post-transcriptional and translational mechanisms involved in downregulation of ribosomal proteins yet stress-responsive transcriptional regulation of ribosomal proteins is largely unknown in plants. Methodology/Principal Findings: In the present work, transcriptional regulation of genes encoding rice 60S ribosomal protein L32 (rpL32) in response to salt stress has been studied. Northern and RT-PCR analyses showed a significant downregulation of rpL32 transcripts under abiotic stress conditions in rice. Of the four rpL32 genes in rice genome, the gene on chromosome 8 (rpL32_8.1) showed a higher degree of stress-responsive downregulation in salt sensitive rice variety than in tolerant one and its expression reverted to its original level upon withdrawal of stress. The nuclear run-on and promoter:reporter assays revealed that the downregulation of this gene is transcriptional and originates within the promoter region. Using in vivo footprinting and electrophoretic mobility shift assay (EMSA), cis-elements in the promoter of rpL32_8.1 showing reduced binding to proteins in shoots of salt stressed rice seedlings were identified. Conclusions: The present work is one of the few reports on study of stress downregulated genes. The data revealed that rpL32 gene is transcriptionally downregulated under abiotic stress in rice and that this transcriptional downregulation i

Mutant p53 as a guardian of the cancer cell

Forty years of research have established that the p53 tumor suppressor provides a major barrier to neoplastic transformation and tumor progression by its unique ability to act as an extremely sensitive collector of stress inputs, and to coordinate a complex framework of diverse effector pathways and processes that protect cellular homeostasis and genome stability. Missense mutations in the TP53 gene are extremely widespread in human cancers and give rise to mutant p53 proteins that lose tumor suppressive activities, and some of which exert trans-dominant repression over the wild-type counterpart. Cancer cells acquire selective advantages by retaining mutant forms of the protein, which radically subvert the nature of the p53 pathway by promoting invasion, metastasis and chemoresistance. In this review, we consider available evidence suggesting that mutant p53 proteins can favor cancer cell survival and tumor progression by acting as homeostatic factors that sense and protect cancer cells from transformation-related stress stimuli, including DNA lesions, oxidative and proteotoxic stress, metabolic inbalance, interaction with the tumor microenvironment, and the immune system. These activities of mutant p53 may explain cancer cell addiction to this particular oncogene, and their study may disclose tumor vulnerabilities and synthetic lethalities that could be exploited for hitting tumors bearing missense TP53 mutations

L’anziano attivo. Proposte e riflessioni per la terza e la quarta età

Il problema della senilità si pone ormai in Italia, come in tutte le società avanzate, in termini assai diversi dal passato. I saggi compresi nel presente volume intervengono su tutti gli aspetti della senilità - da quelli psicologici, sanitari e affettivi a quelli assistenziali, economici e giuridici - per suggerire indicazioni operative e possibili soluzioni.- Indice #4- Prefazione, Marcello Pacini #10- Introduzione, Giuliano Urbani #12- Prima parte Per una nuova concezione della condizione anziana #20- L’età del tempo libero, Norberto Bobbio #22- L’anziano protagonista in una società che cambia, Gian Maria Capuani e Giannino Piana #26- La piccola immortalità, Nando dalla Chiesa #36- L’anziano come risorsa sociale: il volontariato dopo la pensione, Fausto Melloni #44- Seconda Parte Aspetti sociali della condizione anziana #62- Psicogerontologia: attualità e nuove prospettive, Maria Antonietta Aveni Casucci #64- L’invecchiamento della popolazione italiana in un contesto internazionale, Antonio Golini e Agostino Lori #82- L’anziano e l’innovazione tecnologica, Francesco Jovane e Roberto Groppetti #114- La tutela giuridica dell’anziano, Luigi Mengoni #128- La salute dell’anziano: valutazione dei meccanismi di plasticità, Renzo Rozzini, Angelo Bianchetti e Marco Trabucchi #140- Lavoratori anziani: ambivalenza e interventi, Harris T. Schrank e Joan M. Waring #156- Il medico e l’anziano, Carlo Vergani #176- La normalità incerta, Virginio Oddone e Fabrizio Fabris #188- Il quadro organizzativo per una corretta assistenza socio-sanitaria alla popolazione anziana, Gaetano Maria Fara #200- Terza Parte Le tendenze della riflessione #216- La condizione degli anziani in Italia, Claudio Calvaruso #218- Anziani attivi: un possibile esempio di nuova centralità del sociale, Vincenzo Cesareo #228- Appendice Un contributo di ricerca #246- Figli adulti e genitori anziani: una nuova relazione tra le generazioni, Giovanna Rossi #24

Cells of the adult human heart

Abstract: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies