354 research outputs found
In the Name of the Working Class: Narratives of Labour Activism in Contemporary China
Since their appearance in the mid-1990s, Chinese labour NGOs have mostly
focused on disseminating labour law and guiding labour disputes through
official channels. In so doing, they have assisted the Chinese Communist
Party in achieving its paramount goal of maintaining social stability. In
line with this approach, activists in these organizations have traditionally
framed their work in terms of “public interest” or “legality,” both of which
resonate with the hegemonic discourses of the Party-state. However, earlier
this decade a minority of Chinese labour activists began to employ some
new counterhegemonic narratives centred on the experience of the labour
movement and the practice of collective bargaining that attempted to recode
the proletarian experience outside of its official representation. In this paper
we analyze this discursive shift through the voices of the activists involved,
and argue that the rise of these new counterhegemonic voices was one
of the reasons that led to the Party-state cracking down on labour NGOs
Progettazione, sintesi ed attivitĂ di inibitori del Proteasoma a base peptidica
The 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
Depression and mania symptoms mediate the relationship between insomnia and psychotic-like experiences in the general population
Psychotic-like experiences (PLEs) are subclinical forms of psychosis commonly experienced in the general population. The nature of PLEs has yet to be clearly defined, yet mood and sleep disturbances may be two predictors. Sleep disturbance increases paranoia and hallucinations in experimental studies, and insomnia is considered a longitudinal precursor of psychosis. Mood disturbances including depression and mania, which can be induced by insomnia, can also result in psychotic symptoms. However, whether insomnia may predict PLEs via the mediation of mood disturbance has yet to be fully clarified. To advance this field, the aim of this study was to investigate the mediation role of depression and mania symptoms on the relationship between insomnia and PLEs.
1.086 community members (28.32±9.04 years, 58.1% females) cross-sectionally completed self-reported measures of insomnia severity, depression/mania symptoms, and PLEs. Bivariate correlations, hierarchical multiple regressions and mediation analyses with bootstrap approach were performed. Insomnia and mood disturbances (depression/mania) were significantly associated with PLEs (β = 0.06, p < .05; β = 0.225, p < .001, respectively). Mediation analysis revealed a significant indirect effect between insomnia and PLEs mediated by mood disturbance through bootstrap approach (β=0.13, se= 0.02, 95% CI: 0.10 - 0.17). Our results support the view of insomnia and mood disturbances as predictors of PLEs in the general population and foster the replication of these findings using longitudinal designs
STITCH 3: zooming in on protein-chemical interactions
To facilitate the study of interactions between proteins and chemicals, we have created STITCH, an aggregated database of interactions connecting over 300 000 chemicals and 2.6 million proteins from 1133 organisms. Compared to the previous version, the number of chemicals with interactions and the number of high-confidence interactions both increase 4-fold. The database can be accessed interactively through a web interface, displaying interactions in an integrated network view. It is also available for computational studies through downloadable files and an API. As an extension in the current version, we offer the option to switch between two levels of detail, namely whether stereoisomers of a given compound are shown as a merged entity or as separate entities. Separate display of stereoisomers is necessary, for example, for carbohydrates and chiral drugs. Combining the isomers increases the coverage, as interaction databases and publications found through text mining will often refer to compounds without specifying the stereoisomer. The database is accessible at http://stitch.embl.d
Meditation-Relaxation (MR Therapy) for Sleep Paralysis: A Pilot Study in Patients With Narcolepsy
Sleep paralysis (SP) is a condition where a person is paralyzed upon waking or falling asleep. SP afflicts ~20% of people, and is also one of the typical symptoms in narcolepsy. During SP the sleeper may experience hallucinations. Unsurprisingly, SP is associated with great fear globally. To date, there are no published clinical trials or outcome data for treating this condition. However, few non-pharmacological interventions have been proposed, including cognitive behavioral approaches, and case studies showing clinical amelioration with auto-hypnosis and Meditation-Relaxation (MR) therapy. The latter for instance showed positive preliminary results; when applied for 8 weeks it reduced SP frequency and anxiety/worry symptoms. With this paper we aimed to evaluate, with a small-scale pilot study, the efficacy of MR therapy for SP in patients with narcolepsy. Ten patients with narcolepsy and SP were enrolled in the study. Notably, MR therapy (n = 6), applied for 8 weeks, resulted in a dramatic decrease in the number of days SP occurred (50% reduction); and the total number of SP episodes (54% reduction) in the last month of the study (demonstrated by large within-group effect sizes); unlike the control intervention (deep breathing) (n = 4). These findings are preliminary and exploratory given the small sample. Nonetheless, they represent the first proof of concept at providing empirically-guided insights into the possible efficacy of a novel treatment for frequently occurring SP. Although the study was conducted in patients with narcolepsy we cautiously suggest that the findings may generalize to individuals with isolated SP
Exploring Addictive Online Behaviors in Patients with Narcolepsy Type 1
Background: Narcolepsy type 1 (NT1) is a rare neurological sleep disorder caused by the loss of neurons that produce hypocretin—a peptide that plays a crucial role in addictive behaviors. We aimed to compare, for the first time, levels of problematic online gaming, problematic social media use, and compulsive Internet use between NT1 patients and healthy controls (HC), and to evaluate the association between anxiety, depression, and emotion dysregulation with addictive online behaviors in NT1 patients. Methods: A total of 43 patients with NT1 and 86 sex- and age-matched HC participated in an online cross-sectional survey. Results: NT1 patients did not differ from HC in terms of problematic social media use and compulsive Internet use but displayed higher levels of problematic online gaming compared to HC. Higher levels of emotion dysregulation were significantly associated with higher levels of problematic social media use and compulsive Internet use, while none of the tested factors were associated with problematic online gaming. Conclusion: NT1 patients and HC had similar levels of problematic social media use and compulsive Internet use, but NT1 patients showed higher levels of problematic online gaming. Emotion dysregulation might be an intervention target for reducing compulsive Internet use and problematic social media use
Insecure adult attachment and reflective functioning as mechanisms of the relationship between traumatic life events and suicidal ideation: A path analysis
The relationship between traumatic life events and increased suicide risk has been well reported in literature. However, the complex nature of suicidality phenomena still hinders our ability to comprehend the mediation mechanism underlying this association. In this study, we examined the mediating role of adult attachment and reflective functioning in the relationship between traumatic life events and suicidal ideation. Nine hundred and fifty Italian adults completed an online survey evaluating traumatic life events, adult attachment, reflective functioning and suicidal ideation. The path analysis showed that the positive relationship between traumatic life events and suicidal ideation was partially mediated by attachment anxiety and reflective functioning. From a clinical point of view, these results support the relevance of evaluating and improving patients' ability to mentalize as a part of psychotherapeutic intervention aimed at reducing suicidality in people with a history of traumatic experiences and attachment anxiety
The Brain Correlates of Laugh and Cataplexy in Childhood Narcolepsy
The brain suprapontine mechanisms associated with human cataplexy have not been clarified. Animal data suggest that the amygdala and the ventromedial prefrontal cortex are key regions in promoting emotion-induced cataplectic attacks. Twenty-one drug-naive children/adolescent (13 males, mean age 11 years) with recent onset of narcolepsy type 1 (NT1) were studied with fMRI while viewing funny videos using a "naturalistic" paradigm. fMRI data were acquired synchronously with EEG, mylohyoid muscle activity, and the video of the patient's face. Whole-brain hemodynamic correlates of (1) a sign of fun and amusement (laughter) and of (2) cataplexy were analyzed and compared. Correlations analyses between these contrasts and disease-related variables and behavioral findings were performed
STRING v9.1: protein-protein interaction networks, with increased coverage and integration
Complete knowledge of all direct and indirect interactions between proteins in a given cell would represent an important milestone towards a comprehensive description of cellular mechanisms and functions. Although this goal is still elusive, considerable progress has been made—particularly for certain model organisms and functional systems. Currently, protein interactions and associations are annotated at various levels of detail in online resources, ranging from raw data repositories to highly formalized pathway databases. For many applications, a global view of all the available interaction data is desirable, including lower-quality data and/or computational predictions. The STRING database (http://string-db.org/) aims to provide such a global perspective for as many organisms as feasible. Known and predicted associations are scored and integrated, resulting in comprehensive protein networks covering >1100 organisms. Here, we describe the update to version 9.1 of STRING, introducing several improvements: (i) we extend the automated mining of scientific texts for interaction information, to now also include full-text articles; (ii) we entirely re-designed the algorithm for transferring interactions from one model organism to the other; and (iii) we provide users with statistical information on any functional enrichment observed in their network
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