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Burla R.,SapienzaUniversity Rome | Carcuro M.,SapienzaUniversity Rome | Raffa G.D.,SapienzaUniversity Rome | Galati A.,SapienzaUniversity Rome | And 15 more authors.
PLoS Genetics | Year: 2015

Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes from incomplete replication, degradation and detection as DNA breaks. Mammalian telomeres are protected by shelterin, a multiprotein complex that binds the TTAGGG telomeric repeats and recruits a series of additional factors that are essential for telomere function. Although many shelterin-associated proteins have been so far identified, the inventory of shelterin-interacting factors required for telomere maintenance is still largely incomplete. Here, we characterize AKTIP/Ft1 (human AKTIP and mouse Ft1 are orthologous), a novel mammalian shelterin-bound factor identified on the basis of its homology with the Drosophila telomere protein Pendolino. AKTIP/Ft1 shares homology with the E2 variant ubiquitin-conjugating (UEV) enzymes and has been previously implicated in the control of apoptosis and in vesicle trafficking. RNAi-mediated depletion of AKTIP results in formation of telomere dysfunction foci (TIFs). Consistent with these results, AKTIP interacts with telomeric DNA and binds the shelterin components TRF1 and TRF2 both in vivo and in vitro. Analysis of AKTIP- depleted human primary fibroblasts showed that they are defective in PCNA recruiting and arrest in the S phase due to the activation of the intra S checkpoint. Accordingly, AKTIP physically interacts with PCNA and the RPA70 DNA replication factor. Ft1-depleted p53-/- MEFs did not arrest in the S phase but displayed significant increases in multiple telomeric signals (MTS) and sister telomere associations (STAs), two hallmarks of defective telomere replication. In addition, we found an epistatic relation for MST formation between Ft1 and TRF1, which has been previously shown to be required for replication fork progression through telomeric DNA. Ch-IP experiments further suggested that in AKTIP-depleted cells undergoing the S phase, TRF1 is less tightly bound to telomeric DNA than in controls. Thus, our results collectively suggest that AKTIP/Ft1 works in concert with TRF1 to facilitate telomeric DNA replication. © 2015 Burla et al.


Brezin E.,Ecole Normale Superieure de Paris | Brezin E.,French National Center for Scientific Research | Franz S.,University Paris - Sud | Parisi G.,SapienzaUniversity Rome | Parisi G.,University of Rome La Sapienza
Physical Review B - Condensed Matter and Materials Physics | Year: 2010

We consider two identical copies of a finite dimensional spin glass coupled at their boundaries. This allows to identify the analog for a spin glass of twisted boundary conditions in ferromagnetic system and it leads to a definition of an interface free energy that should scale with a positive power of the system size in the spin-glass phase. In this paper we study within mean-field theory the behavior of this interface at the spin-glass critical temperature Tc. We show that the leading scaling of the interface free energy may be obtained by simple scaling arguments using a cubic field theory of critical spin glasses and neglecting the replica symmetry-breaking dependence. © 2010 The American Physical Society.


Di Marco M.,SapienzaUniversity Rome | Di Marco M.,University of Queensland | Brooks T.,International Union for Conservation of Nature | Brooks T.,University of the Philippines at Los Baños | And 23 more authors.
Conservation Biology | Year: 2016

World governments have committed to increase the global protected areas coverage by 2020, but the effectiveness of this commitment for protecting biodiversity depends on where new protected areas are located. Threshold- and complementarity-based approaches have been independently used to identify important sites for biodiversity. We brought together these approaches by performing a complementarity-based analysis of irreplaceability in important bird and biodiversity areas (IBAs), which are sites identified using a threshold-based approach. We determined whether irreplaceability values are higher inside than outside IBAs and whether any observed difference depends on known characteristics of the IBAs. We focused on 3 regions with comprehensive IBA inventories and bird distribution atlases: Australia, southern Africa, and Europe. Irreplaceability values were significantly higher inside than outside IBAs, although differences were much smaller in Europe than elsewhere. Higher irreplaceability values in IBAs were associated with the presence and number of restricted-range species; number of criteria under which the site was identified; and mean geographic range size of the species for which the site was identified (trigger species). In addition, IBAs were characterized by higher irreplaceability values when using proportional species representation targets, rather than fixed targets. There were broadly comparable results when measuring irreplaceability for trigger species and when considering all bird species, which indicates a good surrogacy effect of the former. Recently, the International Union for Conservation of Nature has convened a consultation to consolidate global standards for the identification of key biodiversity areas (KBAs), building from existing approaches such as IBAs. Our results informed this consultation, and in particular a proposed irreplaceability criterion that will allow the new KBA standard to draw on the strengths of both threshold- and complementarity-based approaches. © 2016, Society for Conservation Biology.


Gabriele S.,Third University of Rome | Teresi L.,Third University of Rome | Varano V.,Third University of Rome | Evangelista A.,SapienzaUniversity Rome | And 3 more authors.
Computational Vision and Medical Image Processing IV - Proceedings of Eccomas Thematic Conference on Computational Vision and Medical Image Processing, VIPIMAGE 2013 | Year: 2014

We present and discuss a method to infer non invasively information on the fiber architecture in real LV walls. The method post–processes the echocardiographic data acquired by three–dimensional Speckle Tracking Echocardiography (3DSTE) through a MatLab–based protocol, already presented, discussed and validated in [5]. Our results reveals the difference between the role of endocardial and epicardial principal strain lines, at the systolic peak, and set the bases for possible future investigations aimed to analyze the onset of specific cardiac diseases through noninvasive analysis of LV fiber architecture. © 2014 Taylor & Francis Group, London.


Cenci G.,SapienzaUniversity Rome | Ciapponi L.,SapienzaUniversity Rome | Marzullo M.,SapienzaUniversity Rome | Raffa G.D.,SapienzaUniversity Rome | And 7 more authors.
PLoS Genetics | Year: 2015

Drosophila telomeres are sequence-independent structures that are maintained by transposition to chromosome ends of three specialized retroelements (HeT-A, TART and TAHRE; collectively designated as HTT) rather than telomerase activity. Fly telomeres are protected by the terminin complex (HOAP-HipHop-Moi-Ver) that localizes and functions exclusively at telomeres and by non-terminin proteins that do not serve telomere-specific functions. Although all Drosophila telomeres terminate with HTT arrays and are capped by terminin, they differ in the type of subtelomeric chromatin; the Y, XR, and 4L HTT are juxtaposed to constitutive heterochromatin, while the XL, 2L, 2R, 3L and 3R HTT are linked to the TAS repetitive sequences; the 4R HTT is associated with a chromatin that has features common to both euchromatin and heterochromatin. Here we show that mutations in pendolino (peo) cause telomeric fusions (TFs). The analysis of several peo mutant combinations showed that these TFs preferentially involve the Y, XR and 4th chromosome telomeres, a TF pattern never observed in the other 10 telomere-capping mutants so far characterized. peo encodes a non-terminin protein homologous to the E2 variant ubiquitin-conjugating enzymes. The Peo protein directly interacts with the terminin components, but peo mutations do not affect telomeric localization of HOAP, Moi, Ver and HP1a, suggesting that the peo-dependent telomere fusion phenotype is not due to loss of terminin from chromosome ends. peo mutants are also defective in DNA replication and PCNA recruitment. However, our results suggest that general defects in DNA replication are unable to induce TFs in Drosophila cells. We thus hypothesize that DNA replication in Peo-depleted cells results in specific fusigenic lesions concentrated in heterochromatin-associated telomeres. Alternatively, it is possible that Peo plays a dual function being independently required for DNA replication and telomere capping. © 2015 Cenci et al.


Evangelista A.,Ospedale San Giovanni Calibita Fatebenefratelli Isola Tiberina | Gabriele S.,Third University of Rome | Nardinocchi P.,SapienzaUniversity Rome | Piras P.,SapienzaUniversity Rome | And 5 more authors.
Lecture Notes in Computational Vision and Biomechanics | Year: 2015

We present recent investigations on the state of strain in human left ventricle based on the synergy between continuum mechanics and echocardiographic imaging. When data from three-dimensional Speckle Tracking Echocardiography are available, special strain directions can be detected on the epicardial and endocardial surfaces, which are well-known in continuum mechanics as principal strain lines (PSLs), further classified into primary and secondary strain lines. An appropriate investigation on PSLs can help to identify lines where strains are largest as primary and smallest as secondary. As PSLs change when cardiac diseases appear, the challenge is that the analysis may allow for the identification of new indicators of cardiac function. © Springer International Publishing Switzerland 2015


Lionetti V.,SapienzaUniversity Rome | Cervone F.,SapienzaUniversity Rome | Bellincampi D.,SapienzaUniversity Rome
Journal of Plant Physiology | Year: 2012

The cell wall is a complex structure mainly composed by a cellulose-hemicellulose network embedded in a cohesive pectin matrix. Pectin is synthesized in a highly methyl esterified form and is de-esterified in muro by pectin methyl esterases (PMEs). The degree and pattern of methyl esterification affect the cell wall structure and properties with consequences on both the physiological processes of the plants and their resistance to pathogens. PME activity displays a crucial role in the outcome of the plant-pathogen interactions by making pectin more susceptible to the action of the enzymes produced by the pathogens. This review focuses on the impact of pectin methyl esterification in plant-pathogen interactions and on the dynamic role of its alteration during pathogenesis. © 2012 Elsevier GmbH.


PubMed | SapienzaUniversity Rome
Type: Journal Article | Journal: Best practice & research. Clinical rheumatology | Year: 2016

The term inflammatory myopathies (IMs) comprise a group of muscle diseases formed by four main categories known as polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). Due to the increasing evidence of IMs over the course of different autoimmune diseases, the overlap myositis (OM) has been recently recognized as a possible stand-alone entity. IMs are characterized by a wide spectrum of autoantibodies, and the panel of myositis-associated autoantibodies (MAA) has dramatically increased over the last years giving the clinicians a further crucial support to differentiate the different types of myositis. This study aims to collect the most relevant evidence published up to date on the most commonly described OM with a particular emphasis on their histological aspects and also serological features.

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