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Progettazione, sintesi ed attività di inibitori del Proteasoma a base peptidica
No full textThe ubiquitin-proteasome pathway represents an attractive target in the
development of new drug therapies.
In particular, the proteasome 26S, a multicatalytic threonine protease
complex, is involved in intracellular ubiquitinated-protein degradation and
many biological processes, such as cell cycle control and differentiation,
apoptosis and generation of antigenic peptides presented by major
histocompatibility complex class I (MHC I) molecules.
The activity of 26S proteasome is located in a central 20S core, the proteoliytic
chamber is composed of four stacked rings capped by two 19S regulatory
complexes. Each ring is composed for seven b subunits with three different
active sites: in particular, the b1 subunit contains a peptidyl-glutamyl peptide
hydrolizing active site (PGPH), the b2 subunit expresses tryptic-like (T-L)
activity, and b5 contains a chimotryptic-like (ChT-L) activity.
Modulation of the proteasome activity by specific inhibitors may represent an
useful tool for the treatment of tumors, metabolic and autoimmune disorders.
The aim of this PhD work is the design, sythesis and evaluation of the
biological activity of several classes peptide-based proteasome inhibitors,
containing different pharmacophoric moieties at the C-terminal position as a
potential substrate for Michael addiction by the catalytic threonine through a
mechanism similar to that of the well-known inhibitors.
Herein we reported studies of the molecules bearing as pharmacophoric Cterminal
function: N-allyl vinil ester, a,b-unsaturated N-acylpyrrole, vinyl
ketone, butadienyl vinyl ester, divinyl ketone and isoxazolin vinyl ester groups.
In accordance with the results obtained in previous series, the
pharmacophoric units are linked to oligopeptidic sequences functionalized at
the N-terminal by appropriated groups.
Biological evaluation of the all new compounds was carried out to assess their
inhibition of the trypsin-like, chymotrypsin-like and post-acidic activities of
proteasome using the isolated enzyme purified from lymphoblastoid cell lines.
Some compounds as a,b-unsaturated N-acylpyrrole and vinyl ketone analogs
showed selective inhibition of the proteasome subunits in a mM range, while
other derivatives bearing different pharmacophoric units don’t provide a
favorable biological response
A practical guide to the pharmacological and behavioral therapy of Narcolepsy
No full textNarcolepsy is a rare, chronic, and disabling central nervous system hypersomnia; two forms can be recognized: narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). Its etiology is still largely unknown, but studies have reported a strong association between NT1 and HLA, as well as a pathogenic association with the deficiency of cerebrospinal hypocretin-1. Thus, the most reliable pathogenic hypothesis is an autoimmune process destroying hypothalamic hypocretin-producing cells. A definitive cure for narcolepsy is not available to date, and although the research in the field is highly promising, up to now, current treatments have aimed to reduce the symptoms by means of different pharmacological approaches. Moreover, overall narcolepsy symptoms management can also benefit from non-pharmacological approaches such as cognitive behavioral therapies (CBTs) and psychosocial interventions to improve the patients' quality of life in both adult and pediatric-affected individuals as well as the well-being of their families. In this review, we summarize the available therapeutic options for narcolepsy, including the pharmacological, behavioral, and psychosocial interventions
Periodic leg movements during sleep in narcoleptic patients with or without restless legs syndrome
No full textLight-Triggered Thiol-Exchange on Gold Nanoparticles at Low Micromolar Concentrations in Water
No full textThe place-exchange reaction of thiol-containing
peptides in a cationic monolayer on gold nanoparticles occurs
very rapidly at low micromolar concentrations in water with
excellent control over the degree of substitution. The driving
force for this process is the binding of anionic peptides to a
cationic monolayer surface which causes a strong increase in
the local concentration of thiols. The place-exchange reaction
can be triggered by light using a photolabile protecting group
on the thiol moiety
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Loneliness and problematic social networking sites use in young adults with poor vs. good sleep quality: The moderating role of gender
Full text link: Despite the evidence of a relationship between loneliness, problematic social networking sites use (PSNSU), and sleep quality, associations between specific PSNSU symptoms and loneliness in individuals with poor vs. good sleep quality and possible gender differences have yet to be understood. We examined the relationships between loneliness and PSNSU symptoms (i.e., preference for online social interaction - POSI, mood regulation, deficient self-regulation, and negative outcomes), and possible moderating effects of gender for individuals with poor vs. good sleep quality. Seven hundred and sixty-three young adults completed an online survey including self-report measures of sleep quality, loneliness, and PSNSU symptoms. Individuals with poor sleep quality reported higher levels of loneliness and greater scores on all PSNSU domains than those with good sleep quality. Slope analyses revealed that in men vs. women with poor sleep quality, greater deficient self-regulation of social networking sites use was associated with lower levels of loneliness. Conversely, in men vs. women with good sleep quality, greater POSI was associated with higher levels of loneliness. Our findings showed that individuals with poor sleep quality are characterized by higher levels of loneliness and more severe PSNSU symptoms that may be the result of sleep disturbance-related metabolic, neural, and hormonal processes. Moreover, our results highlight gender differences for individuals with poor vs. good sleep quality which may help clarify the nature of the association between loneliness and PSNSU
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
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