The Ubiquitin-like Proteins of .

In this review, we present a comprehensive list of the ubiquitin-like modifiers (Ubls) of , a common model organism used to study fundamental cellular processes that are conserved in complex multicellular organisms, such as humans. Ubls are a family of proteins that share structural relationships with ubiquitin, and which modify target proteins and lipids. These modifiers are processed, activated and conjugated to substrates by cognate enzymatic cascades.

Strategies for Monitoring "Ubiquitin C-Terminal Hydrolase 1" (Yuh1) Activity.

The family of ubiquitin C-terminal hydrolases (UCHs(releases ε-linked amide bonds positioned at the C-terminus of ubiquitin. UCHL3 is a highly conserved and dual functional member of this family, recognizing C-terminal extensions of two paralogous modifiers: ubiquitin and NEDD8. The Saccharomyces cerevisiae orthologue of UCHL3, namely, Yuh1, is the only UCH family member in this organism.

Self-Oriented Empathy and Personality Organisation Level: Insights from a Psychiatric Sample.

Objective: Empathy functioning is among the criteria to delineate psychiatric diagnosis. However, the self-oriented empathy dimension is almost neglected in the existing literature. On the basis of previous fragmented contributions, we hypothesised that an individual's level of personality organisation is explained by this facet of empathy more than the other components of empathy, both transversally and independently from the specific psychiatric diagnosis.

Clinical, Radiological, and Pathological Diagnosis of Fibro-Osseous Lesions of the Oral and Maxillofacial Region: A Retrospective Study.

Background: Fibro-osseous lesions (FOL) of the jaw represent a rare, benign group of lesions that share similar clinical, radiological, and histopathological features and are characterized by progressive, variable replacement of healthy bone tissue by fibrous connective tissue.

Methods: This retrospective study aimed to evaluate the incidence of fibro-osseous lesions and to reassess the efficacy of case-specific treatment management from a clinical, radiological, and histopathological perspective based on 14 years of data.

Results: Forty-four patients with a radiological and/or histopathological diagnosis of benign FOLs were identified and re-evaluated.

Evaluation of Preventive Treatment Protocols for Patients under Antiresorptive Therapy Undergoing Tooth Extraction at a Swiss University Clinic.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a dreaded complication in patients with compromised bone metabolism. The purpose of the present study was to examine the occurrence of ARONJ and its related factors among patients with a history of antiresorptive therapy undergoing tooth extraction using preventive protocols at a Swiss university clinic. Data were retrospectively pooled from health records of patients having received a surgical tooth extraction between January 2015 and April 2020 in the Clinic of Cranio-Maxillofacial and Oral surgery, University of Zurich.

The molecular basis of Rac-GTP action-promoting binding of p67 to Nox2 by disengaging the β hairpin from downstream residues.

p67 fulfils a key role in the assembly/activation of the NADPH oxidase by direct interaction with Nox2. We proposed that Rac-GTP serves both as a carrier of p67 to the membrane and an inducer of a conformational change enhancing its affinity for Nox2. This study provides evidence for the latter function: (i) oxidase activation was inhibited by p67 peptides (106-120) and (181-195), corresponding to the β hairpin and to a downstream region engaged in intramolecular bonds with the β hairpin, respectively; (ii) deletion of residues 181-193 and point mutations Q115R or K181E resulted in selective binding of p67 to Nox2 peptide (369-383); (iii) both deletion and point mutations led to a change in p67 , expressed in increased apparent molecular weights; (iv) p67 was bound to p67 peptide (181-195) and to a cluster of peptides (residues 97-117), supporting the participation of selected residues within these sequences in intramolecular bonds; (v) p67 failed to bind to Nox2 peptide (369-383), following interaction with Rac1-GTP, but a (p67 -Rac1-GTP) chimera exhibited marked binding to the peptide, similar to that of p67 deletion and point mutants; and (vi) size exclusion chromatography of the chimera revealed its partition in monomeric and polymeric forms, with binding to Nox2 peptide (369-383) restricted to polymers.

as a Toolkit for COP9 Signalosome Research.

The COP9 signalosome (CSN) is a highly conserved eukaryotic multi-subunit enzyme, regulating cullin RING ligase activities and accordingly, substrate ubiquitination and degradation. We showed that the CSN complex of that is deviated in subunit composition and in sequence homology harbors a highly conserved cullin deneddylase enzymatic core complex. We took advantage of the non-essentiality of the CSN-NEDD8/Rub1 axis, together with the enzyme-substrate cross-species activity, to develop a sensitive fluorescence readout assay, suitable for biochemical assessment of cullin deneddylation by CSNs from various origins.

Enhanced Neural Empathic Responses in Patients with Spino-Bulbar Muscular Atrophy: An Electrophysiological Study.

Background: Spino-bulbar muscular atrophy is a rare genetic X-linked disease caused by testosterone insensitivity. An inverse correlation has been described between testosterone levels and empathic responses. The present study explored the profile of neural empathic responding in spino-bulbar muscular atrophy patients.

The necessity of NEDD8/Rub1 for vitality and its association with mitochondria-derived oxidative stress.

Access of molecular oxygen to the respiratory electron transport chain at the mitochondria costs in the generation of reactive oxygen-derived species (ROS). ROS induces progressive damage to macromolecules in all living cells, hence, rapid defense mechanisms to maintain cellular redox homeostasis are vital. NEDD8/Rub1 is a highly conserved ubiquitin-like modifier that has recently been identified as a key regulator of cellular redox homeostasis.

Fluorescence Detection of Increased Reactive Oxygen Species Levels in Saccharomyces cerevisiae at the Diauxic Shift.

The budding yeast Saccharomyces cerevisiae is a facultative organism that is able to utilize both anaerobic and aerobic metabolism, depending on the composition of carbon source in the growth medium. When glucose is abundant, yeast catabolizes it to ethanol and other by-products by anaerobic fermentation through the glycolysis pathway. Following glucose exhaustion, cells switch to oxygenic respiration (a.

p67 -derived self-assembled peptides prevent Nox2 NADPH oxidase activation by an auto-inhibitory mechanism.

Activation of the Nox2-dependent NADPH oxidase is the result of a conformational change in Nox2 induced by interaction with the cytosolic component p67 . In preliminary work we identified a cluster of overlapping 15-mer synthetic peptides, corresponding to p67 residues 259-279, which inhibited oxidase activity in an in vitro, cell-free assay, but the results did not point to a competitive mechanism. We recently identified an auto-inhibitory intramolecular bond in p67 , one extremity of which was located within the 259-279 sequence, and we hypothesized that inhibition by exogenous peptides might mimic intrinsic auto-inhibition.

The COP9 signalosome mediates the Spt23 regulated fatty acid desaturation and ergosterol biosynthesis.

The COP9 signalosome (CSN) is a conserved eukaryotic complex, essential for vitality in all multicellular organisms and critical for the turnover of key cellular proteins through catalytic and non-catalytic activities. Saccharomyces cerevisiae is a powerful model organism for studying fundamental aspects of the CSN complex, since it includes a conserved enzymatic core but lacks non-catalytic activities, probably explaining its non-essentiality for life. A previous transcriptomic analysis of an S.

p67 binds to a newly identified site in Nox2 following the disengagement of an intramolecular bond-Canaan sighted?

Activation of the phagocyte NADPH oxidase involves a conformational change in Nox2. The effector in this process is p67 and there is evidence for a change in the configuration of p67 being required for binding to Nox2. To study this, we measured binding of p67 to a library of Nox2 peptides and binding of NusA-Nox2 fusion proteins to p67 .

Empathy In Neurodegenerative Diseases: A Systematic Review.

Introduction: Empathy, in its affective and cognitive components, is a crucial interpersonal ability. It is broadly studied in the field of psychopathology, whereas its study in the neurodegenerative diseases is relatively recent. Existing literature, though, focused on a reduced subset of considered diseases, which often found a compromise in empathy abilities.

Cell-Free NADPH Oxidase Activation Assays: A Triumph of Reductionism.

The superoxide (O)-generating NADPH oxidase complex of phagocytes comprises a membrane-associated heterodimeric flavocytochrome, known as cytochrome b (consisting of NOX2 and p22) and four cytosolic regulatory proteins, p47, p67, p40, and the small GTPase Rac. Under physiological conditions, in the resting phagocyte, O generation is initiated by engagement of membrane receptors by a variety of stimuli, followed by signal transduction sequences leading to the translocation of the cytosolic components to the membrane and their association with the cytochrome, a process known as NADPH oxidase assembly. A consequent conformational change in NOX2 initiates the electron flow along a redox gradient, from NADPH to molecular oxygen (O), leading to the one-electron reduction of O to O.

Statins interfere with the attachment of mtDNA to the inner mitochondrial membrane.

The 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme of the mevalonate pathway for the synthesis of cholesterol in mammals (ergosterol in fungi), is inhibited by statins, a class of cholesterol lowering drugs. Indeed, statins are in a wide medical use, yet statins treatment could induce side effects as hepatotoxicity and myopathy in patients. We used as a model to investigate the effects of statins on mitochondria.

The Proteasome Lid Triggers COP9 Signalosome Activity during the Transition of Cells into Quiescence.

The class of Cullin-RING E3 ligases (CRLs) selectively ubiquitinate a large portion of proteins targeted for proteolysis by the 26S proteasome. Before degradation, ubiquitin molecules are removed from their conjugated proteins by deubiquitinating enzymes, a handful of which are associated with the proteasome. The CRL activity is triggered by modification of the Cullin subunit with the ubiquitin-like protein, NEDD8 (also known as Rub1 in ).

Using Synthetic Peptides for Exploring Protein-Protein Interactions in the Assembly of the NADPH Oxidase Complex.

The NADPH oxidase complex, responsible for reactive oxygen species (ROS) generation by phagocytes, consists of a membrane-associated flavocytochrome b (a heterodimer of NOX2 and p22) and the cytosolic components p47, p67, Rac(1 or 2), and p40. NOX2 carries all redox stations through which electrons flow from NADPH to molecular oxygen, to generate the primary ROS, superoxide. For the electron flow to start, a conformational change in NOX2 is required.

Proteasome lid bridges mitochondrial stress with Cdc53/Cullin1 NEDDylation status.

Cycles of Cdc53/Cullin1 rubylation (a.k.a NEDDylation) protect ubiquitin-E3 SCF (Skp1-Cullin1-F-box protein) complexes from self-destruction and play an important role in mediating the ubiquitination of key protein substrates involved in cell cycle progression, development, and survival.

Unimpaired Neuropsychological Performance and Enhanced Memory Recall in Patients with Sbma: A Large Sample Comparative Study.

Peculiar cognitive profile of patients with SBMA has been described by fragmented literature. Our retrospective study reports the neuropsychological evaluations of a large cohort of patients in order to contribute towards the understanding of this field. We consider 64 neuropsychological evaluations assessing mnesic, linguistic and executive functions collected from 2013 to 2015 in patients attending at Motor Neuron Disease Centre of University of Padova.

Binding of p67 to Nox2 is stabilized by disulfide bonds between cysteines in the Cys-Gly-Cys triad in Nox2 and in p67.

A central event in the activation of the phagocyte NADPH oxidase involves binding of p67 to the dehydrogenase region of Nox2. The identity of the binding site in Nox2 is unknown. By measuring binding of p67 to synthetic Nox2 peptides, we previously identified a sequence corresponding to Nox2 residues 357-383, as a potential binding site.

Turning off NADPH oxidase-2 by impeding p67 activation in infected mouse macrophages reduced viral entry and inflammation.

Background: Targeting cells of the host immune system is a promising approach to fight against Influenza A virus (IAV) infection. Macrophage cells use the NADPH oxidase-2 (NOX2) enzymatic complex as a first line of defense against pathogens by generating superoxide ions O and releasing HO. Herein, we investigated whether targeting membrane -embedded NOX2 decreased IAV entry via raft domains and reduced inflammation in infected macrophages.