114 research outputs found
Quaestiones iuris. Contributi del Seminario permanente dei ricercatori del Dipartimento di Scienze giuridiche
No full textIl volume “Quaestiones iuris” costituisce la prima raccolta degli interventi proposti nell’ambito del “Seminario permanente dei ricercatori”, organizzato dal Dipartimento di Scienze giuridiche dell’Università Cattolica di Milano.
La varietà delle questioni affrontate nei vari seminari, legata alla libera proposta dei temi da parte di ciascun ricercatore, ha consentito, pur muovendo da specifiche prospettive d’indagine, di restituire la complessità che connota l’esperienza giuridica come fenomeno ormai frammentario e frammentato. Schegge sparpagliate a comporre, faticosamente, uno specchio sempre meno riconoscibile: quaestiones iuris, nell’accezione medievale di quaestio.
Propiziando il confronto interdisciplinare, i contributi proposti affrontano tematiche come la giustizia riparativa nel sistema penale e penitenziario (Biancamaria Spricigo), l’autodichìa delle Camere nello Stato costituzionale (Leonardo Brunetti), i riflessi in ambito giuridico-penalistico della trasformazione della società in senso multiculturale (Lara Ferla), il giusto processo e la dinamica delle norme nel tempo (Michele Massa) e l’esperibilità dell’actio aquae pluviae arcendae nel diritto romano (Francesca Scotti).
Una specifica attenzione è stata dedicata, ogni anno, alla ricorrenza del Giorno della Memoria, evento costantemente al centro dell’attenzione del Dipartimento di Scienze giuridiche e dell’Università Cattolica. Ciò ha costituito un momento di rinnovata riflessione intorno a accadimenti di gravità estrema, nonché in relazione agli esiti ai quali può condurre il ricorso al diritto ove la forma giuridica divenga strumento di oltraggio irreversibile a beni primari come la vita e la dignità umana. Proprio da siffatti propositi muovono l’intervento di natura storico-giuridica di Saverio Gentile e, in prospettiva penalistica con un’impronta giusletteraria, il contributo di Arianna Visconti. Sulla delicata questione del negazionismo si sono soffermati Matteo Caputo e Gabriele Della Morte, dialogando nella duplice prospettiva penalistica e internazionalistica
Combination treatment of dupilumab with bortezomib in a patient with IgG kappa gammopathy of renal significance, uremic pruritus and chronic lichenoid dermatitis
No full text: Chronic pruritus (CP) is one of the most frequent symptoms among dermatological conditions, capable of reducing the quality of life (QoL). CP may be induced by atopic dermatitis or other dermatological and/or non-dermatological conditions. In this article, we report the case of a patient affected by generalized CP, characterised by multiple papulo-nodular and escoriatic lesions, developed after the onset of an immunoglobulin G (IgG) kappa monoclonal gammopathy of renal significance (MGRS), associated with renal insufficiency. Therefore, a combined treatment with dupilumab for CP and bortezomib for the hematologic malignancy was administered to the patient. The present case report highlights the efficacy of dupilumab for the treatment of CP. Moreover, no relevant side effects were recorded during the treatment in combination with other systemic biological drugs for other systemic pathologies
Tellurium-Doped Silanised Bioactive Glass–Chitosan Hydrogels: A Dual Action for Antimicrobial and Osteoconductive Platforms
No full textUV-cured methacrylated chitosan (MCHIT) hydrogels were achieved in the presence of silanised tellurium-doped silica bioactive glass (BG-Te-Sil) to produce an antimicrobial and osteoconductive scaffold for tissue engineering applications. Methacrylation of chitosan enabled efficient crosslinking, and the curing process was evaluated by means of Fourier-transform infrared spectroscopy (FTIR) and photorheology analyses. Compressive testing on crosslinked hydrogels showed that the silanised, bioactive, doped glass increased the hydrogel’s elastic modulus by up to 200% compared to unreinforced controls. Antibacterial assays against Staphylococcus aureus ATCC 43300 revealed a significant (p < 0.05) reduction in bacterial metabolic activity for hydrogels containing 50 wt% of the Te-doped bioactive glass. In vitro cytocompatibility with human bone-marrow mesenchymal stem cells demonstrated sustained viability and uniform distribution at 72 h (live/dead staining, AlamarBlue). Under H2O2-induced oxidative stress, reinforced hydrogels downregulated pro-inflammatory genes (TNF-α, IFN-γ, IL-1β, and PGES-2). These results suggest that the presence of the silanised bioactive glass can significantly enhance mechanical stability, antibacterial properties, and anti-inflammatory responses without affecting cytocompatibility, making these hydrogels promising for tissue engineering applications
LZTR1 model
No full textInteractive HTML page showing LZTR1 protein model and where mutants and phosphorylation sites localise. For a live version see Here.
Utilises NGL JS library.
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Mutanalyst, an online tool for assessing the mutational spectrum of epPCR libraries with poor sampling
No full textBackground: Assessing library diversity is an important control step in a directed evolution experiment. To do this, a limited amount of colonies from a test library are sequenced and tested. In the case of an error-prone PCR library, the spectrum of the identified mutations - the proportions of mutations of a specific nucleobase to another-is calculated enabling the user to make more informed predictions on library diversity and coverage. However, the calculations of the mutational spectrum are severely affected by the limited sample sizes.Results: Here an online program, called Mutanalyst, is presented, which not only automates the calculations, but also estimates errors involved. Specifically, the errors are calculated thanks to the complementarity of DNA, which means that a mutation has a complementary mutation on the other sequence. Additionally, in the case of determining the mean number of mutations per sequence it does so by fitting to a Poisson distribution, which is more robust than calculating the average in light of the small sampling size.Conclusion: As a result of the added measures to keep into account of small sample size the user can better assess whether the library is satisfactory or whether error-prone PCR conditions should be adjusted. The program is available at www.mutanalyst.com
matteoferla/ITPA_analysis: Final code
No full textAnalysis of variants of ITPA (no mutant data is stored here
Liver perfusion in multiorgan harvesting for transplantation
No full textIn 1984 Starzl described a technique of multiple organ in situ flushing and procurement from heart beating donors that was widely adopted by various transplantation institutions throughout the world. The same author has recently described a simpler, fast technique that seems to provide similar or better results. We report our experience of liver procurement with different procurement procedures
ROBOTIC LIVING-DONOR KIDNEY HARVESTING. DOES LONGER WARM ISCHEMIC TIME AFFECT THE TRANSPLANT OUTCOME?
No full textBackground: Warm Ischemia Time (WIT) has been proven to be detrimental
for graft recovery after transplantation. We herein report the outcome of
kidney transplants from living donor according to different WIT in our robotic
harvesting setting.
Methods: In our institution, since November 26th 2009, all kidneys harvesting
from living donors have been performed using the Da Vinci robot. Different
surgical techniques, different surgical teams and different instruments
like, for example, the vascular stapler devices have been used. This is the
reason why we experienced wide range of WIT. We finally relate the kidney
transplant function to the Graft WIT in order to find out if our longest WIT
has somehow affected the transplants outcome.
Results: From November 26th 2009 to December 27th 2020 we performed
168 kidney transplants from living donors. WIT varied from 120 to 943 seconds
(median 235). WIT has been divided in three different time intervals:
A) Tertile: 1) up to 210 seconds (31.8%), 2) from 210 to 260 seconds
(35.7%), 3) more than 260 seconds (32.5%); B) Median: less than 235 seconds
(49%) and more than 235 seconds (51%); C) Deciles: first 9 deciles
<360 seconds (89.2%), last deciles > 360 seconds (10.8%). At statistical
analysis we did not find any statistically significant correlation between the
WIT of our series and the kidney transplants outcome as far as creatinine
at discharge, delayed graft function, acute rejections, thrombosis, urinary
fistula, lymphorrea and overall complications are concerned.
Conclusions: Although WIT should be kept as short as possible in organ
transplantation, WIT up to 943 seconds in living donor kidney transplant
doesn’t seem to have any detrimental effect on the kidney recovery after
transplantation. This finding can be useful to the surgeon who will not have
to rush while staplering perhaps in difficult conditions or in presence of multiple
vessels
Catalytic Multitasking in MetC: one enzyme, multiple reactions
No full textUnlike most modern enzymes, which perform a single reaction, primordial enzymes are believed to have each performed a broad range of reactions. Consequently, most modern enzymes are poor comparative models for inferring the properties of primordial enzymes. The aim of this thesis was to identify and characterise modern enzymes that have evolved to catalyse multiple reactions on multiple substrates, in order to better understand the properties of primordial enzymes.
Using bioinformatics and phylogenetics, I have discovered that, in three distinct clades, one enzyme (MetC) has taken over the role of the absent alanine racemase (Alr). Two of the three MetC enzymes have also taken over the role of the absent glutamate racemase (MurI). Even though MetC, MurI and Alr are not homologous. In other organisms, such as Escherichia coli, MetC catalyses the β-elimination of cystathionine in methionine biosynthesis. The E. coli MetC has a small promiscuous alanine racemisation activity, but no detectable glutamate racemisation activity.
Two of the clades —the genus Pelagibacter and the family Anaplasmataceae, which includes Wolbachia— were in the same class, the Alphaproteobacteria, but the precise location was under debate in the literature. Therefore, I used phylogenetic methods to determine that they did belong to sister orders and that the AT-richness of their genomes is ancestral, rather than a source of bias.
The three enzymes investigated are located in different groups along the MetC tree. Using in vitro activity assays, I found that the enzyme most similar to E. coli MetC, Pelagibacter ubique MetC, could racemise alanine, but could not racemise glutamate. Further away on the tree, Wolbachia MetC has glutamate and alanine racemisation activities that are both stronger than its cystathionine β-elimination activity in terms of turnover numbers (kcat). While, in a basal group, Thermotoga maritima MetC possess the strongest glutamate racemising activity of the enzymes studied. These three enzymes were also able to promiscuously cleave cysteine.
The three enzymes had Michaelis constants (KM) for the various substrates that are comparable to those of each dedicated enzyme (MetC, Alr and MurI) in other organisms, while having turnover numbers (kcat) that are much lower than those of each dedicated enzyme. It was conjectured that this balance of kinetic parameters in these enzymes is due to the physiological necessity of operating with low concentrations of each substrate, yet producing a limited amount of product due to the low cellular demand for each metabolite.
The crystal structure of T. maritima MetC was solved, showing that it may possess glutamate racemisation activity because an active site tryptophan forms a hydrogen bond with the terminal carboxyl group of the bound glutamate. The structure also revealed a latch-like loop close to the active site entrance.
I used directed evolution in an attempt to improve the cystathionine elimination activity of T. maritima MetC. A mutant (S86T/S305C) was identified that possessed a more permissive active site with decreased Michaelis constants for all activities, including those that had not been under selection. This may indicate that wild-type T. maritima MetC has a tight balance of kinetic parameters that needs to be relaxed before it can be evolved into an enzyme with a single activity.
Overall, the properties of these enzymes reveal how multiple activities are balanced in a single active site and offer new insights into the likely nature of primordial enzymes
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