122,176 research outputs found
Synaptic GluN2A-Containing NMDA Receptors: From Physiology to Pathological Synaptic Plasticity
No full textN-Methyl-d-Aspartate Receptors (NMDARs) are ionotropic glutamate-gated receptors. NMDARs are tetramers composed by several homologous subunits of GluN1-, GluN2-, or GluN3-type, leading to the existence in the central nervous system of a high variety of receptor subtypes with different pharmacological and signaling properties. NMDAR subunit composition is strictly regulated during development and by activity-dependent synaptic plasticity. Given the differences between GluN2 regulatory subunits of NMDAR in several functions, here we will focus on the synaptic pool of NMDARs containing the GluN2A subunit, addressing its role in both physiology and pathological synaptic plasticity as well as the contribution in these events of different types of GluN2A-interacting proteins
Polimirfismo del gene dell'ACE ed eritrocitosi nel trapianto di rene
No full textIntroduzione. L’eritrocitosi post-trapianto (PTE) può essere responsabile d’importanti complicanze.
Gli ACE inibitori (ACE-i) sono stati proposti nella terapia della PTE perché in grado di ridurre l’ischemia renale (dipendente
dall’angiotensina II), ritenuta un fattore patogenetico importante. Tuttavia l’efficacia degli ACEi nel trattamento della
PTE è variabile. In questo studio è stato valutato se il polimorfismo del gene dell’ACE può influenzare la prevalenza di PTE
e la risposta terapeutica agli ACEi.
Metodi. Pazienti sottoposti a trapianto renale erano retrospettivamente valutati. La PTE era diagnosticata sulla base dello
stabile aumento di ematocrito (Ht; >50%). Cause secondarie d’aumento di Ht erano escluse mediante esame clinico, ecografia
renale, esami ematologici. Erano rilevati: comparsa di PTE, dose di ACEi somministrata, pressione arteriosa, e clearance
della creatinina. I pazienti erano divisi in due gruppi; gruppo A, pazienti trattati con ACEi; gruppo B, pazienti trattati
con salassi periodici. Sulla base del valore di Ht dopo terapia con ACEi, i pazienti del gruppo A erano ulteriormente suddivisi
in “responder” (Ht <50%) e “non-responder”. Il polimorfismo del gene dell’ACE era determinato mediante PCR in
tutti i pazienti con PTE ed era confrontato con quello di un gruppo controllo; un ulteriore confronto era effettuato tra quello
dei “responder” e quello dei “non-responder”.
Conclusioni. La PTE era riscontrata in 55 (53 M, 2 F) pazienti dei 470 esaminati. Tra i pazienti trattati con ACEi (n. 38;
69%), Ht era completamente normalizzato in 29 (76%, “responder”) mentre rimane elevato in 9 (24%, “non-responder”). I
restanti 17 pazienti erano trattati con flebotomie intermittenti. Il polimorfismo del gene dell’ACE riscontrato nei pazienti
con PTE non era differente da quello del gruppo controllo né era differente tra i pazienti “responder” e “non-responder”.
Risultati. I risultati del presente studio indicano che il polimorfismo del gene dell’ACE non influenza l’incidenza della
PTE né l’efficacia della terapia con ACEi
Blockchain in surgery: are we ready for the digital revolution?
No full textThroughout time, surgery evolved from an old fashioned
and rough discipline to one of the most exciting felds in
medicine, tightly linked to historical technological advancements. To cite only a few, minimal access surgery including
laparoscopic and robotic surgery, real-time intraoperative
angiography with fuorescent dyes and coherent laser imaging systems, 4K ultra-high-defnition optics, 3D printing,
virtual and augmented reality. Our daily practice has also
changed with the introduction of electronic medical records,
with the consequent possibility of running big data analytics
and artifcial intelligence algorithm
LINKING NMDA RECEPTOR-DEPENDENT PLASTICITY AND NEURONAL ARCHITECTURE: THE ROLE OF RING FINGER PROTEIN 10
No full textAn active synapse-to-nucleus communication is essential for long-term changes in neurons, like the regulation of neuronal plasticity and shaping neuronal morphology. Next to the fast electrochemical signaling, neurons employ a slower mechanism that involves a recently discovered class of proteins, the synaptonuclear messengers. Different studies showed the pivotal role of synaptonuclear messengers in the modulation of synaptic transmission at excitatory synapses. On the other hand, alterations of synaptonuclear messengers’ activity have been correlated to synaptic failure as observed in different synaptopathies, including both neurodevelopmental disorders and neurodegenerative diseases. Ring Finger Protein 10 (RNF10) has been recently identified as a novel synapse-to-nucleus signaling protein that specifically links the activation of synaptic GluN2A-containing NMDA receptors (NMDARs) to gene expression. RNF10 synaptonuclear trafficking is responsible for the remodeling of dendritic spines that substance the postsynaptic modifications required for long-term potentiation (LTP). However, the molecular mechanisms leading to NMDAR/RNF10 complex disruption and for initiating the importin-mediated trafficking of RNF10 to the nucleus remain unclear. In this PhD project we investigated the molecular mechanisms that underlie RNF10 activation and in this matter we discovered a protein kinase C (PKC)-dependent phosphorylation event on RNF10-Ser31, which drives RNF10 synaptonuclear trafficking. Moreover, we show that pSer31-RNF10 plays a role both in synaptonuclear signaling and in neuronal morphology. In particular, the prevention of Ser31 RNF10 phosphorylation induces a decrease in spine density, neuronal branching, and CREB signaling, while opposite effects are obtained by mimicking a stable RNF10 phosphorylation at Ser31.Based on these results, we investigated the role of RNF10 in vivo, in the RNF10-/- mouse model. In particular we studied the putative involvement of the synaptonuclear protein in neurodevelopment, focusing our attention on the first three weeks of postnatal life, which represents the critical period for neuronal differentiation and synaptogenesis in rodents. We found that RNF10-/- mice have an alteration in brain morphology, in particular in the hippocampal area, and impaired cognition. At a microscopic level, RNF10-/- deficiency alters the molecular composition and the morphology of the glutamatergic synapse. In the CA1 region of the Hippocampus, dendritic arborization of RNF10-/- neurons is severely reduced and LTP induction is compromised. Overall, these results add novel information about the functional and structural role of synaptonuclear protein messengers in shaping dendritic architecture and regulating synaptic plasticity in hippocampal neurons
A Multi-Language Comparison of Influences on Author Verification using Character N-Grams
No full textWe create a new multi-language corpus for author verification based on Wikipedia talkpages, and evaluate the influence that differences in topic and time have on character n-gram author profiles. Topic alignment between two texts is found to increase author verification precision, and an authors writing style is found to change over time, but not more significantly after 3 years than after 1 year.Information ArchitectureWISElectrical Engineering, Mathematics and Computer Scienc
A surgical instrument cover for the prevention of thermal injuries during laparoscopic operations
No full textAccidental thermal injuries are infrequent, nonetheless, dangerous complications in laparoscopic surgery. Burns are produced because of direct contact, lack of instrument insulation and capacitive coupling. Biological fluids on the surface of laparoscopic instruments behave as electric conductors on the sheath and may be responsible for accidental thermal injuries. Our hypothesis is that using an insulator device may prevent those injuries. Materials and Methods: After evaluating different materials for dielectric properties, costs, and temperature increase tolerance, we selected polytetrafluoroethylene (PTFE) to develop a sleeve that works as an electrical insulator when applied on the sheath of laparoscopic instruments. Efficacy of this PTFE cover in reducing conduction of electricity was tested on both reusable and disposable laparoscopic instruments. Results: Electric conduction of the laparoscopic instrument sheaths was tested using an ex vivo model that reproduces the abdominal environment in basal conditions and in presence of blood. Electric conduction of laparoscopic instruments was measured before and after the placement of the PTFE cover. We measured a significant difference in electric resistance on the sheath's surface without and with blood, revealing a weak electrical conduction: infinity versus a median value of 251.11 Mohm, respectively. Conclusions: This ex vivo study demonstrated that a PTFE sleeve may reduce electricity conduction of laparoscopic instruments. A pilot in vivo study is planned to test its safety and efficacy
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The vanishing author in computer-generated works: a critical analysis of recent Australian case law
No full textAbstract
The use of software is ubiquitous in the creation of many copyright works, yet the requirement in copyright law that every work have a human author who engages in independent intellectual effort means that its use may prevent copyright subsistence. Several recent Australian cases have refocused attention on authorship as an essential criterion of copyright subsistence, and these cases suggest that much computer-produced output may be authorless and thus lack copyright protection. This article, the first in a two-part series, analyses how each case deals with the question of authorship of computer-produced works and why the use of software diminishes copyright protection for a significant number of computer-generated works. The article critiques the application of conventional notions of human authorship developed in the pre-computer age to modern productions and suggests alternative approaches to authorship that satisfy both the major objectives of copyright policy and the need to adapt to the computer age. The article argues that, without a broader judicial approach to authorship of computer-generated works, Parliament must remedy the lacuna in protection for these ‘authorless’ works. Possible solutions for reform are suggested. In a forthcoming article, the author comprehensively examines those reform proposals
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