186,402 research outputs found
All-atom simulations to studying metallodrugs/target interactions
No full textMetallodrugs are extensively used to treat and diagnose distinct disease types. The unique physical–chemical properties of metal ions offer tantalizing opportunities to tailor effective scaffolds for selectively targeting specific biomolecules. Modern experimental techniques have collected a large body of structural data concerning the interactions of metallodrugs with their biomolecular targets, although being unable to exhaustively assess the molecular basis of their mechanism of action. In this scenario, the complementary use of accurate computational methods allows uncovering the minutiae of metallodrugs/targets interactions and their underlying mechanism of action at an atomic-level of detail. This knowledge is increasingly perceived as an invaluable requirement to rationally devise novel and selective metallodrugs. Building on literature studies, selected largely from the last 2 years, this compendium encompasses a cross-section of the current role, advances, and challenges met by computer simulations to decipher the mechanistic intricacies of prototypical metallodrugs
Art loving bugs: the resurrection of Spinello Aretino from Pisa’s Cemetery
No full textDuring 1391–1392, Spinello Aretino painted a cycle of frescoes in Pisa’s cemetery on the theme
“Storie dei Santi Martiri Efisio e Potito”, highly prized by contemporaries and by Vasari. Twenty
years ago, one of these frescoes, “Conversione di S. Efisio e Battaglia” (Conversion of S. Efisio and
Battle), because of discolouring and bad damage caused by humidity and atmospheric pollution,
was removed from the walls using the “tear-off” technique, consisting in covering the surface
with a strong cloth bound to the surface with generous layers of formaldehyde-treated glue. As
luck would have it, this large fresco (3.50 6 7.80 m) was abandoned in a storehouse for more
than 20 years. When the curators attempted to remove the cloth, much to their dismay they
found that the glue resisted any attempt at digestion, even when treated with concoctions of the
most aggressive proteolytic enzymes available on the market. It is likely that during the long
storage the glue became slowly cross-linked by the formaldehyde to the point of forming an
intricate mass of untreatable proteinaceous material. Thus, although poor Spinello died presumably
as a bona fide Christian, his painting was condemned to wear the burka, Muslim-fashion,
for the rest of its life. When we recently treated the fresco with a suspension of viable Pseudomonas
stutzeri cells, these bacteria, although agnostic, were able to fully digest the hardened
glue and restore to life Spinello’s glorious painting. We show here how proteomics helped us
solve the riddle of how these bacteria acted on the burka-obscured fresco
All-atom simulations to studying metallodrugs/target interactions
No full textMetallodrugs are extensively used to treat and diagnose distinct disease types. The unique physical–chemical properties of metal ions offer tantalizing opportunities to tailor effective scaffolds for selectively targeting specific biomolecules. Modern experimental techniques have collected a large body of structural data concerning the interactions of metallodrugs with their biomolecular targets, although being unable to exhaustively assess the molecular basis of their mechanism of action. In this scenario, the complementary use of accurate computational methods allows uncovering the minutiae of metallodrugs/targets interactions and their underlying mechanism of action at an atomic-level of detail. This knowledge is increasingly perceived as an invaluable requirement to rationally devise novel and selective metallodrugs. Building on literature studies, selected largely from the last 2 years, this compendium encompasses a cross-section of the current role, advances, and challenges met by computer simulations to decipher the mechanistic intricacies of prototypical metallodrugs
Post-traumatic proximal radioulnar synostosis: results of surgical treatment and review of the literature
No full textBackground: Post-traumatic proximal radioulnar synostosis is a very rare and disabling condition whose surgical treatment has traditionally been viewed with pessimism. The results of the few case series in the literature are conflicting. Our aims were (1) to describe the clinical results of a case series treated surgically by a single elbow surgeon and (2) to review the literature. Methods: Twelve patients were evaluated. Preoperative radiographs and computed tomography scans were performed. According to the Viola and Hastings classification, there was 1 case of type IC synostosis; 3, type IIA; 2, type IIIA; and 8, type IIIB. Two patients had a double synostosis. The synostosis was excised in 10 cases; in addition, radial head excision, radial head arthroplasty, and proximal radial diaphyseal resection were performed in 1, 3, and 2 cases, respectively. The Mayo Elbow Performance Score, modified American Shoulder and Elbow Surgeons score, and QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score were used for the preoperative and postoperative evaluation. The nonparametric Wilcoxon signed rank test was used for the statistical analysis. Results: The mean follow-up period was 20.5 months. The final mean extension-flexion and pronation-supination arcs were 116° and 123°, respectively. Significant improvements were found in the Mayo Elbow Performance Score (P =.005), modified American Shoulder and Elbow Surgeons score (P =.012), and QuickDASH score (P =.002), with mean values of 24, 28, and 17, respectively. One synostosis recurrence and one late disassembly of the radial head arthroplasty were observed. Conclusions: Post-traumatic proximal radioulnar synostosis surgery is effective, but careful preoperative planning based on the pathoanatomic characteristics of each type of synostosis and associated lesions is mandatory. Synostosis excision is performed in most cases, whereas additional surgical procedures should be considered in selected cases
Il cambiamento nel modo di produzione della conoscenza. Un’esplorazione degli effetti delle infrastrutture di ricerca nel lavoro degli scienziati sociali
No full textPratiche di ricerca fondate su condivisione della ricchezza informativa, intensità del dato e maggiore capacità di “fare rete” per la risoluzione delle questioni scientifiche stanno configurando un "nuovo percorso per la scienza". Lo sfruttamento condiviso di dati osservazionali e sperimentali alimentato grazie alla disponibilità di risorse fisiche o virtuali, quali le infrastrutture di ricerca, sta caratterizzando lo sforzo collettivo delle comunità scientifiche in misura sempre maggiore. Nel dominio delle scienze sociali, esse sono rappresentate primariamente dai database di ricerca strutturati, come le collezioni di dati derivate da progetti specifici e quelle di interesse europeo o di caratura internazionale caratterizzate da aggiornamento costante e ampia apertura. Il lavoro intende esplorare gli effetti dell’utilizzo di tali risorse nell'ambito della comunità dei sociologi operando uno studio di caso applicato al maggior polo universitario e al maggior ente pubblico di ricerca italiani: Sapienza Università di Roma e Consiglio Nazionale delle Ricerche. La domanda di ricerca si focalizza sul cambiamento indotto dall'utilizzo delle infrastrutture di ricerca nei processi che presiedono alla produzione di nuova conoscenza, in particolare per quanto riguarda lo sviluppo del disegno della ricerca, l’attivazione di dinamiche collaborative e l’orientamento all'interdisciplinarità, e indaga inoltre su quale sia il giudizio degli scienziati sociali in riferimento alle ricadute di tale sfruttamento sui prodotti della ricerca
Art-loving bugs: the resurrection of Spinello Aretino from Pisa's cemetery.
No full textDuring 1391-1392, Spinello Aretino painted a cycle of frescoes in Pisa's cemetery on the theme "Storie dei Santi Martiri Efisio e Potito", highly prized by contemporaries and by Vasari. Twenty years ago, one of these frescoes, "Conversione di S. Efisio e Battaglia" (Conversion of S. Efisio and Battle), because of discolouring and bad damage caused by humidity and atmospheric pollution, was removed from the walls using the "tear-off" technique, consisting in covering the surface with a strong cloth bound to the surface with generous layers of formaldehyde-treated glue. As luck would have it, this large fresco (3.50 x 7.80 m) was abandoned in a storehouse for more than 20 years. When the curators attempted to remove the cloth, much to their dismay they found that the glue resisted any attempt at digestion, even when treated with concoctions of the most aggressive proteolytic enzymes available on the market. It is likely that during the long storage the glue became slowly cross-linked by the formaldehyde to the point of forming an intricate mass of untreatable proteinaceous material. Thus, although poor Spinello died presumably as a bona fide Christian, his painting was condemned to wear the burka, Muslim-fashion, for the rest of its life. When we recently treated the fresco with,a suspension of viable Pseudomonas stutzeri cells, these bacteria, although agnostic, were able to fully digest the hardened glue and restore to life Spinello's glorious painting. We show here how proteomics helped us solve the riddle of how these bacteria acted on the burka-obscured fresco
Midterm results of radiocapitellar arthroplasty of the elbow: a multicentre prospective study on two different implants
No full textAims The aim of this study was to analyze the results of two radiocapitellar prostheses in a large case series followed prospectively, with medium-term follow-up. Patients and Methods A total of 31 patients with a mean age of 54 years (27 to 73) were analyzed; nine had primary osteoarthritis (OA) and 17 had post-traumatic OA, three had capitellar osteonecrosis, and two had a fracture. Overall, 17 Lateral Resurfacing Elbow (LRE) and 14 Uni-Elbow Radio-Capitellum Implant (UNI-E) arthroplasties were performed. Pre- and postoperative assessment involved the Mayo Elbow Performance Score (MEPS), the Quick Disabilities of the Arm, Shoulder and Hand (Q-DASH) score, and the modified American Shoulder Elbow Surgeons (m-ASES) score. Results The mean follow-up was 6.8 years (3.8 to 11.5). The mean MEPS, m-ASES, and Q-DASH scores improved significantly by 50 (p < 0.001), 55 (p < 0.001), and 54 points (p < 0.001), respectively, with no differences being detected between the implants. Preoperative pronation and supination were worse in patients in whom the UNI-E was used. Two patients with the UNI-E implant had asymptomatic evidence of gross loosening. Conclusion Radiocapitellar arthroplasty yielded a significant improvement in elbow function at a mean follow-up of 6.8 years, with a high implant survival rate when the LRE was used in patients with primary or post-traumatic OA, without radial head deformity, and when the UNI-E was used in patients in whom radial head excision was indicated
Distal humerus hemiarthroplasty: surgical technique
No full textDistal humerus hemiarthroplasty (DHH) is a recent therapeutic option for the treatment of some acute unreconstructable humeral fractures, for the salvage of sequelae related to non-operative management or failed internal humeral fixation as well as in other rare pathological conditions. Standard anterior-posterior and lateral view X-rays and a CT scans are mandatory for an adequate preoperative planning. The main osseous and soft tissue stabilizers of the elbow should be intact or at least reparable because elbow stability is mandatory to be able to perform a DHH; in addition, both the medial and lateral columns should be either intact or reconstructable to guarantee an adequate soft tissue reinsertion and healing. This chapter aims to describe in detail the surgical technique of DHH. In particular the choice of the articular spool size, the orientation of the flexion-extension axis, and the reconstruction of soft tissue stabilizers represent the main key points for an optimal implantation
Computing Metal-Binding Proteins for Therapeutic Benefit
No full textOver one third of biomolecules rely on metal ions to exert their cellular functions. Metal ions can play a structural role by stabilizing the structure of biomolecules, a functional role by promoting a wide variety of biochemical reactions, and a regulatory role by acting as messengers upon binding to proteins regulating cellular metal-homeostasis. These diverse roles in biology ascribe critical implications to metal-binding proteins in the onset of many diseases. Hence, it is of utmost importance to exhaustively unlock the different mechanistic facets of metal-binding proteins and to harness this knowledge to rationally devise novel therapeutic strategies to prevent or cure pathological states associated with metal-dependent cellular dysfunctions. In this compendium, we illustrate how the use of a computational arsenal based on docking, classical, and quantum-classical molecular dynamics simulations can contribute to extricate the minutiae of the catalytic, transport, and inhibition mechanisms of metal-binding proteins at the atomic level. This knowledge represents a fertile ground and an essential prerequisite for selectively targeting metal-binding proteins with small-molecule inhibitors aiming to (i) abrogate deregulated metal-dependent (mis)functions or (ii) leverage metal-dyshomeostasis to selectively trigger harmful cells death
Computing Metal‐Binding Proteins for Therapeutic Benefit
No full textOver one third of biomolecules rely on metal ions to exert their cellular functions. Metal ions can play a structural role by stabilizing the structure of biomolecules, a functional role by promoting a wide variety of biochemical reactions, and a regulatory role by acting as messengers upon binding to proteins regulating cellular metal-homeostasis. These diverse roles in biology ascribe critical implications to metal-binding proteins in the onset of many diseases. Hence, it is of utmost importance to exhaustively unlock the different mechanistic facets of metal-binding proteins and to harness this knowledge to rationally devise novel therapeutic strategies to prevent or cure pathological states associated with metal-dependent cellular dysfunctions. In this compendium, we illustrate how the use of a computational arsenal based on docking, classical, and quantum-classical molecular dynamics simulations can contribute to extricate the minutiae of the catalytic, transport, and inhibition mechanisms of metal-binding proteins at the atomic level. This knowledge represents a fertile ground and an essential prerequisite for selectively targeting metal-binding proteins with small-molecule inhibitors aiming to (i) abrogate deregulated metal-dependent (mis)functions or (ii) leverage metal-dyshomeostasis to selectively trigger harmful cells death
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