1,354,335 research outputs found
Un giorno alla volta, un'ora alla volta
No full textIl volume, nato un’idea di Daniele Di Benedetto e Marianna Bruno, e realizzato a cura dell’Associazione Sanfilippo Fighters Odv, racconta le storie meravigliose dei bambini e dei ragazzi affetti dalla Mucopolisaccaridosi di tipo III, meglio nota come Sinfrome di Sanfilippo, una malattia rara ereditaria con insorgenza pediatrica che causa una progressiva e inesorabile degenerazione neurologica con perdita delle capacità motorie e rapido deterioramento cognitivo (capacità di apprendimento e di comunicazione). Come si legge in quarta di copertina del volume, il libro racconta «Storie di parole acquisite e poi dimenticate. Storie di corse al parco che diventano passi lenti e incerti. Storie di bambini e adolescenti capaci di sorridere, anche solo con gli occhi. Storie di un futuro preso con forza e portato via. Storie di una vita vissuta un giorno alla volta, un’ora alla volta.»
Prefazione di Alessandro Fraldi. Con un testo di Gabriele Cirilli. L'immagine di copertina è di Federica Di Stefano. L’acquisto del libro sostiene le attività dell’Associazione Sanfilippo Fighters Odv
The Mechanical Beauty of Hierarchically Organized Living Structures
No full textBy traveling through the inner structure of biological tissues, for instance by means of a scanning or a transmission electron microscope, unexpectedly exact geometries and symmetries in the form of perfect
lattices, honeycomb networks, helical macromolecules
and polyhedral shapes resulting from minimal surfaces can
be observed. Furthermore, by exploring cells and tissues at
meso‐, micro and nano‐scale levels, one discovers that self-similarity and hierarchy replicate that geometrical order and
surprisingly characterize all the biological architectures, in this way de facto governing the key biomechanical functions and biochemical signaling at the basis of the life
A lesson from earthquake engineering for selectively damaging cancer cell structures
No full textThe progressive falling of barriers among disciplines is opening unforeseen scenarios in diagnosis and treatment of cancer diseases. By sharing models and mature knowledge in physics, engineering, computer sciences and molecular biology, synergistic efforts have in fact contributed in the last years to re-think still unsolved problems, shedding light on key roles of mechanobiology in tumors and envisaging new effective strategies for a precise medicine. The use of ultrasounds for altering cancer cells’ program is one of the most attracting grounds to be explored in oncophysics, although how to administer mechanical energy to impair selected cell structures and functions simultaneously overcoming the critical trade-off between the impact of the cure and the patient risk still remains an open issue. Within this framework, by starting from the theoretical possibility of selectively attacking malignant cells by exploiting the stiffness discrepancies between tumor and healthy single cells, first proposed by Fraldi et al. (2015), we here investigate the in-frequency response of an overall spherical close-packing of geometrically equal polyhedral cells to gain insights into how mechanical resonance and vibration-induced failure phenomena can be oriented to destroy specific target units when both the cell populations coexist, as it happens for in vivo cases. Inspired by the dynamic action of earthquakes – which fracture only selected elements among adjacent ones in the same structure or damage individual constructions in contiguous buildings – we study the harmonic response of hierarchically architectured cell agglomerates, inhabited by both tumor and healthy cells that interact mutually throughout the extra-cellular matrix and whose cytoskeleton is modeled as a nonlinear soft-tensegrity structure. Numerical Finite Element results show that, at frequencies compatible with low intensity therapeutic ultrasounds, mechanical resonance and possible fatigue cycles of the pre-stressed actin filaments and microtubules can be selectively induced in cancer cells as a function of the global volume fraction of the cell species, paving the way for future engineered treatment protocols
Visco-elastic and thermal-induced damaging in time-dependent reshaping of human cornea after conductive keratoplasty
No full textWith the aim of investigating the role played by both the radiofrequency-induced thermal damaging and the viscoelasticity of the tissue in human cornea surface reshaping—time dependent key factors for the success of the surgical outcome in the short-term post-intervention period—the Conductive Keratoplasty (CK, a surgical technique used for the correction of farsightedness) has been simulated with reference to the protocol adopted for moderate hyperopia. By means of a transient thermal analysis, the amount of the local thermal-induced tissue damaging has been computed in order to remap the constitutive properties of the corneal tissue. Successively, a mechanical non-linear analysis has been performed for predicting the corneal curvature around the optical zone during the post-surgery period. The study aims to contribute some firm thermo-mechanical roots to better understand the corneal tissue response to thermal insults and its reshaping predictability in a long period
The Amyloid Inhibitor CLR01 Relieves Autophagy and Ameliorates Neuropathology in a Severe Lysosomal Storage Disease
No full textFraldi and colleagues demonstrated that multiple amyloid proteins progressively aggregate in neurons of a severe lysosomal storage disease, impairing autophagy degradation and triggering neurodegeneration. They also showed that inhibiting amyloid deposition protects against neurodegeneration, thus providing evidence that amyloid aggregation is a new attractive target for the treatment of LSDs
Influence of actual plastic hinge placement on the behavior of ductile frames
No full textThe ultimate load and collapsing modes of steel frames under combined vertical and horizontal forces are investigated through finite element (FE) modelling and limit analysis. Consideration is given to a frequently overlooked problem which is the kinematics arising from the actual rotation of the plastic hinges under axial force and bending moment. This fact draws attention to the necessity of a careful assessment of the limit analysis approaches, a fact that might be seen as somewhat in line with the outcome from famous paradoxes, such as the one by Stüssi and Kollbrunner (1935), which can only be solved by making reference to both elastic and plastic deformations. As a result, it can be shown that in such a manner, it is possible to obtain a handy tool capable of competing with much more computationally expensive methodologies. The approach may be relevant to practising engineers dealing with code prescriptions and standardization committees
Functional correction of CNS lesions in an MPS-IIIA mouse model by intracerebral AAV-mediated delivery of sulfamidase and SUMF1 genes
No full textMucopolysaccharidosis type IIIA (MPS-IIIA or Sanfilippo syndrome) is a lysosomal storage disorder caused by the congenital deficiency of sulfamidase (SGSH) enzyme and consequent accumulation of partially degraded heparan sulfate (HS) in lysosomes. The central nervous system (CNS) is the predominant site of tissue damage in MPS-IIIA. Here we describe a gene therapy approach for MPS-IIIA in a mouse model using recombinant adeno-associated virus serotype 5 (AAV2/5) as a vehicle to deliver therapeutic genes to the CNS. SUMF1 (SUlfatase Modifying Factor 1) exhibits an enhancing effect on sulfatase activity when co-expressed with sulfatases. Consistent with these findings, we demonstrated that co-delivery of SUMF1 and SGSH (via an AAV2/5-CMV-SGSH-IRES-SUMF1 vector) resulted in a synergistic increase in SGSH activity, both in primary neural cells and in murine brain. A study aimed at testing the therapeutic efficacy of simultaneous brain administration of SUMF1 and SGSH was then performed by injecting the lateral ventricles of newborn MPS-IIIA/normal mice with either AAV2/5-CMV-SGSH-IRES-SUMF1 or AAV2/5-CMV-GFP vectors. Widespread GFP expression was observed within the GFP-injected brain, and a stable and significant increase of SGSH activity was detected in several brain regions following SGSH-IRES-SUMF1 administration. Treatment with AAV2/5-CMV-SGSH-IRES-SUMF1 vectors resulted in a visible reduction in lysosomal storage and inflammatory markers in transduced brain regions. Finally, the MPS-IIIA mice treated with therapeutic genes displayed an improvement in both motor and cognitive functions. Our results suggest that early treatment of CNS lesions by AAV-mediated intraventricular injection of both SGSH and SUMF1 genes may represent a feasible therapy for MPS-IIIA.Alessandro Fraldi, Kim Hemsley, Allison Crawley, Alessia Lombardi, Adeline Lau, Leanne Sutherland, Alberto Auricchio, Andrea Ballabio and John J. Hopwoo
In vivo Gene Therapy to the Liver and Nervous System: Promises and Challenges
No full textIn vivo genetic engineering has recently shown remarkable potential as a novel effective treatment for an ever-growing number of diseases, as also witnessed by the recent marketing authorization of several in vivo gene therapy products. In vivo genetic engineering comprises both viral vector-mediated gene transfer and the more recently developed genome/epigenome editing strategies, as long as they are directly administered to patients. Here we first review the most advanced in vivo gene therapies that are commercially available or in clinical development. We then highlight the major challenges to be overcome to fully and broadly exploit in vivo gene therapies as novel medicines, discussing some of the approaches that are being taken to address them, with a focus on the nervous system and liver taken as paradigmatic examples
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