CNR Institute of Biomedical Technologies

Padova, Italy

CNR Institute of Biomedical Technologies

Padova, Italy
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Mannini L.,CNR Institute of Biomedical Technologies | Menga S.,CNR Institute of Biomedical Technologies | Musio A.,CNR Institute of Biomedical Technologies | Musio A.,Instituto Toscano Tumori
Human Mutation | Year: 2010

Cohesin is responsible for sister chromatid cohesion, ensuring the correct chromosome segregation. Beyond this role, cohesin and regulatory cohesin genes seem to play a role in preserving genome stability and gene transcription regulation. DNA damage is thought to be a major culprit for many human diseases, including cancer. Our present knowledge of the molecular basis underlying genome instability is extremely limited. Mutations in cohesin genes cause human diseases such as Cornelia de Lange syndrome and Roberts syndrome/SC phocomelia, and all the cell lines derived from affected patients show genome instability. Cohesin mutations have also been identified in colorectal cancer. Here, we will discuss the human disorders caused by alterations of cohesin function, with emphasis on the emerging role of cohesin as a genome stability caretaker. © 2010 Wiley-Liss, Inc.


Bachis A.,Georgetown University | Avdoshina V.,Georgetown University | Zecca L.,CNR Institute of Biomedical Technologies | Parsadanian M.,Georgetown University | Mocchetti I.,Georgetown University
Journal of Neuroscience | Year: 2012

The molecular mechanisms leading to synaptic simplification and neuronal apoptosis in human immunodeficiency virus type 1 (HIV-1)-positive subjects are unknown. The HIV protein gp120 reduced the length of neuronal processes similarly to the proneurotrophin pro- brain-derived neurotrophic factor (proBDNF). Intriguingly, the effects of both proBDNF and gp120 were blocked by inhibitors of the p75 neurotrophin receptor, suggesting that proBDNF and gp120 share a similar mechanism of neurotoxicity. Therefore, we tested the hypothesis that gp120 affects the release of proBDNF. Using rat primary neurons, we observed that gp120 promotes a time-dependent intracellular and extracellular accumulation of proBDNF concomitantly with a decrease in mature BDNF. A similar imbalance in the ratio proBDNF/mature BDNF was confirmed in postmortem brains of HIV-positive subjects cognitively impaired and motor impaired. Therefore, it is conceivable to formulate the hypothesis that HIV neurotoxicity includes a gp120-mediated alteration of BDNF processing. To determine the cellular mechanism whereby gp120 produces an accumulation of proBDNF, we examined the levels of intracellular and extracellular enzymes that proteolytically cleave proBDNF furin and tissue plasminogen, respectively. In rat neurons exposed to gp120, intracellular furin levels decreased before cell death, whereas tissue plasminogen changed only during apoptosis. Our data suggest that HIV, through gp120, reduces proBDNF processing by affecting furin levels, and therefore causes an altered balance between antiapoptotic and proapoptotic neurotrophins. Our studies identify a new mechanism that may explain how HIV promotes neuronal injury. © 2012 the authors.


Capotosto P.,University of Chieti Pescara | Capotosto P.,CNR Institute of Biomedical Technologies | Babiloni C.,University of Foggia | Romani G.L.,University of Chieti Pescara | And 4 more authors.
Cerebral Cortex | Year: 2012

We have recently shown that interference with repetitive transcranial magnetic stimulation (rTMS) of right posterior intraparietal sulcus (IPS) cortex during the allocation of spatial attention leads to abnormal desynchronization of anticipatory (pretarget) electroencephalographic alpha rhythms (8-12 Hz) in occipital-parietal cortex and the detection of subsequently presented visual targets (Capotosto et al. 2009). Since lesion data suggest that lesions of the right frontoparietal cortices produce more severe and long-lasting deficits of visual spatial attention than lesions of the left hemisphere, here, we used the mentioned rTMS-electroencephalographic procedure to test if the control of anticipatory alpha rhythms by IPS is asymmetrically organized in the 2 hemispheres. Results showed that interference with either left or right IPS during covert spatial attention equally disrupted the normally lateralized anticipatory modulation of occipital visual cortex, with stronger alpha desynchronization contralaterally to the attended visual field. In contrast, only interference with right IPS induced a paradoxical pretarget synchronization of alpha rhythms and bilateral deficits of target identification. These results suggest that the control of spatial topography of anticipatory alpha rhythms in occipital- parietal cortex is shared between left and right IPS cortex, but that right IPS uniquely contributes to a bilateral prestimulus activation of occipital visual cortex. © The Author 2011.


Capotosto P.,CNR Institute of Biomedical Technologies | Corbetta M.,CNR Institute of Biomedical Technologies | Corbetta M.,University of Washington | Romani G.L.,CNR Institute of Biomedical Technologies | Babiloni C.,University of Foggia
Journal of Cognitive Neuroscience | Year: 2012

TMS interference over right intraparietal sulcus (IPS) causally disrupts behaviorally and EEG rhythmic correlates of endogenous spatial orienting before visual target presentation [Capotosto, P., Babiloni, C., Romani, G. L., & Corbetta, M. Differential contribution of right and left parietal cortex to the control of spatial attention: A simultaneous EEG-rTMS study. Cerebral Cortex, 22, 446-454, 2012; Capotosto, P., Babiloni, C., Romani, G. L., & Corbetta, M. Fronto-parietal cortex controls spatial attention through modulation of anticipatory alpha rhythms. Journal of Neuroscience, 29, 5863-5872, 2009]. Here we combine data from our previous studies to examine whether right parietal TMS during spatial orienting also impairs stimulus-driven reorienting or the ability to efficiently process unattended stimuli, that is, stimuli outside the current focus of attention. Healthy volunteers (n = 24) performed a Posner spatial cueing task while their EEG activity was being monitored. Repetitive TMS (rTMS) was applied for 150 msec simultaneously to the presentation of a central arrow directing spatial attention to the location of an upcoming visual target. Right IPS-rTMS impaired target detection, especially for stimuli presented at unattended locations; it also caused a modulation of the amplitude of parieto-occipital positive ERPs peaking at about 480 msec (P3) post-target. The P3 significantly decreased for unattended targets and significantly increased for attended targets after right IPS-rTMS as compared with sham stimulation. Similar effects were obtained for left IPS stimulation albeit in a smaller group of volunteers. We conclude that disruption of anticipatory processes in right IPS has prolonged effects that persist during target processing. The P3 decrement may reflect interference with postdecision processes that are part of stimulus-driven reorienting. Right IPS is a node of functional interaction between endogenous spatial orienting and stimulusdriven reorienting processes in human vision. © 2012 Massachusetts Institute of Technology.


Ricchelli F.,CNR Institute of Biomedical Technologies | Sileikyte J.,University of Padua | Bernardi P.,University of Padua
Biochimica et Biophysica Acta - Bioenergetics | Year: 2011

The mitochondrial permeability transition is an increase of permeability of the inner mitochondrial membrane to ions and solutes with an exclusion size of about 1500 Da. It is generally accepted that the permeability transition is due to opening of a high-conductance channel, the permeability transition pore. Although the molecular nature of the permeability transition pore remains undefined, a great deal is known about its regulation and role in pathophysiology. This review specifically covers the characterization of the permeability transition pore by chemical modification of specific residues through photoirradiation of mitochondria after treatment with porphyrins. The review also illustrates the basic principles of the photodynamic effect and the mechanisms of phototoxicity and discusses the unique properties of singlet oxygen generated by specific porphyrins in discrete mitochondrial domains. These experiments provided remarkable information on the role, interactions and topology of His and Cys residues in permeability transition pore modulation and defined an important role for the outer membrane 18 kDa translocator protein (formerly known as the peripheral benzodiazepine receptor) in regulation of the permeability transition. © 2011 Elsevier B.V.


Granzotto A.,CNR Institute of Biomedical Technologies | Zatta P.,CNR Institute of Biomedical Technologies
PLoS ONE | Year: 2011

It has been recently suggested that resveratrol can be effective in slowing down Alzheimer's disease (AD) development. As reported in many biochemical studies, resveratrol seems to exert its neuro-protective role through inhibition of β-amyloid aggregation (Aβ), by scavenging oxidants and exerting anti-inflammatory activities. In this paper, we demonstrate that resveratrol is cytoprotective in human neuroblastoma cells exposed to Aβ and or to Aβ-metal complex. Our findings suggest that resveratrol acts not through anti-aggregative pathways but mainly via its scavenging properties. © 2011 Granzotto, Zatta.


Castellana S.,University of Bari | Vicario S.,CNR Institute of Biomedical Technologies | Saccone C.,CNR Institute of Biomedical Technologies | Saccone C.,University of Bari
Genome Biology and Evolution | Year: 2011

The mitochondrial genome is a fundamental component of the eukaryotic domain of life, encoding for several important subunits of the respiratory chain, the main energy production system in cells. The processes by means of which mitochondrial DNA (mtDNA) replicates, expresses itself and evolves have been explored over the years, although various aspects are still debated. In this review, we present several key points in modern research on the role of evolutionary forces in affecting mitochondrial genomes in Metazoa. In particular, we assemble the main data on their evolution, describing the contributions of mutational pressure, purifying, and adaptive selection, and how they are related. We also provide data on the evolutionary fate of the mitochondrial synonymous variation, related to the nonsynonymous variation, in comparison with the pattern detected in the nucleus. Elevated mutational pressure characterizes the evolution of the mitochondrial synonymous variation, whereas purging selection, physiologically due to phenomena such as cell atresia and intracellular mtDNA selection, guarantees coding sequence functionality. This enables mitochondrial adaptive mutations to emerge and fix in the population, promoting mitonuclear coevolution. © The Author(s) 2010.


Navarro B.,CNR Institute of Plant virology | Gisel A.,CNR Institute of Biomedical Technologies | Rodio M.E.,CNR Institute of Plant virology | Delgado S.,Polytechnic University of Valencia | And 2 more authors.
Plant Journal | Year: 2012

How viroids, tiny non-protein-coding RNAs (∼250-400 nt), incite disease is unclear. One hypothesis is that viroid-derived small RNAs (vd-sRNAs; 21-24 nt) resulting from the host defensive response, via RNA silencing, may target for cleavage cell mRNAs and trigger a signal cascade, eventually leading to symptoms. Peach latent mosaic viroid (PLMVd), a chloroplast-replicating viroid, is particularly appropriate to tackle this question because it induces an albinism (peach calico, PC) strictly associated with variants containing a specific 12-14-nt hairpin insertion. By dissecting albino and green leaf sectors of Prunus persica (peach) seedlings inoculated with PLMVd natural and artificial variants, and cloning their progeny, we have established that the hairpin insertion sequence is involved in PC. Furthermore, using deep sequencing, semi-quantitative RT-PCR and RNA ligase-mediated rapid amplification of cDNA ends (RACE), we have determined that two PLMVd-sRNAs containing the PC-associated insertion (PC-sRNA8a and PC-sRNA8b) target for cleavage the mRNA encoding the chloroplastic heat-shock protein 90 (cHSP90), thus implicating RNA silencing in the modulation of host gene expression by a viroid. Chloroplast malformations previously reported in PC-expressing tissues are consistent with the downregulation of cHSP90, which participates in chloroplast biogenesis and plastid-to-nucleus signal transduction in Arabidopsis. Besides PC-sRNA8a and PC-sRNA8b, both deriving from the less-abundant PLMVd (-) strand, we have identified other PLMVd-sRNAs potentially targeting peach mRNAs. These results also suggest that sRNAs derived from other PLMVd regions may downregulate additional peach genes, ultimately resulting in other symptoms or in a more favorable host environment for viroid infection. © 2012 Blackwell Publishing Ltd.


Chiappori F.,CNR Institute of Biomedical Technologies | Merelli I.,CNR Institute of Biomedical Technologies | Colombo G.,CNR Institute of Chemistry of Molecular Recognition | Milanesi L.,CNR Institute of Biomedical Technologies | Morra G.,CNR Institute of Chemistry of Molecular Recognition
PLoS Computational Biology | Year: 2012

Investigating ligand-regulated allosteric coupling between protein domains is fundamental to understand cell-life regulation. The Hsp70 family of chaperones represents an example of proteins in which ATP binding and hydrolysis at the Nucleotide Binding Domain (NBD) modulate substrate recognition at the Substrate Binding Domain (SBD). Herein, a comparative analysis of an allosteric (Hsp70-DnaK) and a non-allosteric structural homolog (Hsp110-Sse1) of the Hsp70 family is carried out through molecular dynamics simulations, starting from different conformations and ligand-states. Analysis of ligand-dependent modulation of internal fluctuations and local deformation patterns highlights the structural and dynamical changes occurring at residue level upon ATP-ADP exchange, which are connected to the conformational transition between closed and open structures. By identifying the dynamically responsive protein regions and specific cross-domain hydrogen-bonding patterns that differentiate Hsp70 from Hsp110 as a function of the nucleotide, we propose a molecular mechanism for the allosteric signal propagation of the ATP-encoded conformational signal. © 2012 Chiappori et al.


Correa Leite M.L.,CNR Institute of Biomedical Technologies
Clinical and Applied Thrombosis/Hemostasis | Year: 2011

Aim: To examine the relationship between some blood parameters and mild kidney dysfunction. Participants and Methods: A total of 719 Italian men aged 42 to 74 years from a population-based survey carried out in the town of Bollate (Milan). General linear models were used to examine the variations in plasma fibrinogen, hematocrit, platelet counts, mean platelet volume, and uric acid across levels of kidney function (estimated on the basis of glomerular filtration rate [GFR]), adjusting for age, education, smoking, alcohol consumption, physical activity (evaluated as TV watching, engaging in sport practice, and walking/cycling), waist circumference, arm muscle area, high-density lipoprotein (HDL)-cholesterol, triglycerides, hypertension, diabetes, cardiovascular disease history, and nonsteroid anti-inflammatory, diuretic, and antihypertensive drug use. Results: Plasma fibrinogen and hematocrit levels increased, and platelet counts and mean platelet volume significantly decreased as GFR fell to <80 or <70 mL/min per 1.73 m 2; stratified analysis revealed an association with serum uric acid levels. Alterations compatible with an increased cardiovascular risk were particularly evident among the participants with higher uric acid levels, whereas those indicative of platelet dysfunction were found among participants with lower levels. Conclusions: Parameters affecting hemostasis and blood viscosity are altered when kidney function is only slightly reduced, and the patterns of these relationships seem to be influenced by the levels of serum uric acid, whose easy and inexpensive measurement could have prognostic value. © The Author(s) 2011.

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