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ABSTRACT Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a progressive degeneration of the striatonigral, olivo-ponto-cerebellar, and autonomic systems. Glial cytoplasmic inclusions (GCIs) containing alpha-synuclein represent the hallmark of MSA and are recapitulated in mice expressing alpha-synuclein in oligodendrocytes. To assess if oligodendroglial expression of human wild-type alpha-synuclein in mice (proteolipid promoter, PLP-SYN) could be associated with age-related deficits, PLP-SYN and wild-type mice were assessed for motor function, brain morphometry, striatal levels of dopamine and metabolites, dopaminergic loss, and distribution of GCIs. PLP-SYN displayed age-related impairments on a beam-traversing task. MRI revealed a significantly smaller brain volume in PLP-SYN mice at 12 months, which further decreased at 18 months together with increased volume of ventricles and cortical atrophy. The distribution of GCIs was reminiscent of MSA with a high burden in the basal ganglia. Mild dopaminergic cell loss was associated with decreased dopamine turnover at 18 months. These data indicate that PLP-SYN mice may recapitulate some of the progressive features of MSA and deliver endpoints for the evaluation of therapeutic strategies. Synapse 68:98-106, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Leber's hereditary optic neuropathy, the most frequent mitochondrial disease due to mitochondrial DNA point mutations in complex I, is characterized by the selective degeneration of retinal ganglion cells, leading to optic atrophy and loss of central vision prevalently in young males. The current study investigated the reasons for the higher prevalence of Leber's hereditary optic neuropathy in males, exploring the potential compensatory effects of oestrogens on mutant cell metabolism. Control and Leber's hereditary optic neuropathy osteosarcoma-derived cybrids (11778/ND4, 3460/ND1 and 14484/ND6) were grown in glucose or glucose-free, galactose-supplemented medium. After having shown the nuclear and mitochondrial localization of oestrogen receptors in cybrids, experiments were carried out by adding 100 nM of 17β-oestradiol. In a set of experiments, cells were pre-incubated with the oestrogen receptor antagonist ICI 182780. Leber's hereditary optic neuropathy cybrids in galactose medium presented overproduction of reactive oxygen species, which led to decrease in mitochondrial membrane potential, increased apoptotic rate, loss of cell viability and hyper-fragmented mitochondrial morphology compared with control cybrids. Treatment with 17β-oestradiol significantly rescued these pathological features and led to the activation of the antioxidant enzyme superoxide dismutase 2. In addition, 17β-oestradiol induced a general activation of mitochondrial biogenesis and a small although significant improvement in energetic competence. All these effects were oestrogen receptor mediated. Finally, we showed that the oestrogen receptor β localizes to the mitochondrial network of human retinal ganglion cells. Our results strongly support a metabolic basis for the unexplained male prevalence in Leber's hereditary optic neuropathy and hold promises for a therapeutic use for oestrogen-like molecules. [ABSTRACT FROM AUTHOR]

Background and purpose:Nocistatin (NST) is a neuropeptide generated from cleavage of the nociceptin/orphanin FQ (N/OFQ) precursor. Evidence has been presented that NST acts as a functional antagonist of N/OFQ, although NST receptor and transduction pathways have not yet been identified. We previously showed that N/OFQ inhibited [3H]5-hydroxytryptamine ([3H]5-HT) release from mouse cortical synaptosomes via activation of NOP receptors. We now investigate whether NST regulates [3H]5-HT release in the same preparation.Experimental approach:Mouse and rat cerebrocortical synaptosomes in superfusion, preloaded with [3H]5-HT and stimulated with 1 min pulses of 10 mM KCl, were used.Key results:Bovine NST (b-NST) inhibited the K+-induced [3H]5-HT release, displaying similar efficacy but lower potency than N/OFQ. b-NST action underwent concentration-dependent and time-dependent desensitization, and was not prevented either by the NOP receptor antagonist [Nphe1 Arg14,Lys15]N/OFQ(1-13)-NH2 (UFP-101) or by the non-selective opioid receptor antagonist, naloxone. Contrary to N/OFQ, b-NST reduced [3H]5-HT release from synaptosomes obtained from NOP receptor knockout mice. However, both N/OFQ and NST were ineffective in synaptosomes pre-treated with the Gi/o protein inhibitor, Pertussis toxin. NST-N/OFQ interactions were also investigated. Co-application of maximal concentrations of both peptides did not result in additive effects, whereas pre-application of maximal b-NST concentrations partially attenuated N/OFQ inhibition.Conclusions and implications:We conclude that b-NST inhibits [3H]5-HT release via activation of Gi/o protein linked pathways, not involving classical opioid receptors and the NOP receptor. The present data strengthen the view that b-NST is, per se, a biologically active peptide endowed with agonist activity.British Journal of Pharmacology (2007) 152, 549–555; doi:10.1038/sj.bjp.0707377; published online 9 July 2007 [ABSTRACT FROM AUTHOR]

Copper nanowires (CuNWs), featuring anisotropic highly conductive crystalline facets, represent an ideal nanostructure to fabricate on-demand materials as transparent electrodes and efficient electrocatalysts. The development of reliable and robust CuNWs requires achieving a full control over their synthesis and morphology growth, a challenge that continues to puzzle materials scientists. In this study, we systematically investigated the correlation between the critical synthetic parameters and the structural properties of nanowires using a design of experiments (DOE) approach. Multiparametric variation of experimental reaction conditions combined with orthogonal technical analysis allowed us to develop a sound predictive model that provides guidelines for designing CuNWs with controlled morphology and reaction yield. Beyond these synthetic achievements, voltammetric and electrocatalytic experiments were used to correlate the CuNWs morphology and structure to their catalytic activity and selectivity toward CO 2 electroreduction, thus opening new avenues for further intersectoral actions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: To investigate the distribution of sperm DNA fragmentation (SDF) values and their association with clinical and seminal parameters in idiopathic infertile men., Design, Patients, Measurements: Data from 3224 primary infertile men (belonging to couples having failed to conceive a pregnancy within 12 months) who underwent a thorough diagnostic work-up were analysed. A SDF value ≥ 30% (according to Sperm Chromatin Structure Assay) was considered pathologic. We excluded: (1) men with genetic abnormalities; (2) men with history of cryptorchidism; (3) men with biochemical hypogonadism; (4) men with clinical varicocele; and (5) men with other possible known aetiological factors. Descriptive statistics and logistic regression analyses were used to describe the whole cohort., Results: Of all, 792 (23%) men with at least one abnormal WHO semen parameter but without any identified aetiologic factor for infertility, were considered as idiopathic infertile men. Of 792, 418 (52.7%) men had SDF ≥30%. Men with pathologic SDF were older (p = .02), had higher Follicle-stimulating hormone (FSH) (p = .04) but lower total testosterone (p = .03) values than those with SDF <30%. The homoeostatic model assessment index for insulin resistance (HOMA-IR) was higher in men with SDF ≥30% (p = .01). Idiopathic infertile men with SDF ≥30% presented with lower sperm concentration (p < .001) and lower progressive sperm motility (p < .01) than those with SDF < 30%. Logistic regression analysis revealed that older age (OR: 1.1, p = .02) and higher HOMA-IR score (OR: 1.8, p = .03) were associated with SDF ≥ 30%, after accounting for FSH and sperm concentration values., Conclusions: Approximately half of infertile men categorized as idiopathic had pathologic SDF values. Idiopathic infertile men with pathologic SDF showed worse clinical, hormonal and semen parameters than those with normal SDF values. These results suggest that including SDF testing could be clinically relevant over the real-life management work-up of infertile men., (© 2024 John Wiley & Sons Ltd.)

Purpose: To examine temporal-spatial distribution of heat generated upon laser activation in a bench model of renal calyx. To establish reference values for a safety distance between the laser fiber and healthy tissue during laser lithotripsy., Methods: We developed an in-vitro experimental setup employing a glass pipette and laser activation under various intra-operative parameters, such as power and presence of irrigation. A thermal camera was used to monitor both temporal and spatial temperature changes during uninterrupted 60-second laser activation. We computed the thermal dose according to Sapareto and Dewey's formula at different distances from the laser fiber tip, in order to determine a safety distance., Results: A positive correlation was observed between average power and the highest recorded temperature (Spearman's coefficient 0.94, p < 0.001). Irrigation was found to reduce the highest recorded temperature, with a maximum average reduction of 9.4 °C at 40 W (p = 0.002). A positive correlation existed between average power and safety distance values (Spearman's coefficient 0.86, p = 0.001). A thermal dose indicative of tissue damage was observed at 20 W without irrigation (safety distance 0.93±0.11 mm). While at 40 W, irrigation led to slight reduction in mean safety distance (4.47±0.85 vs. 5.22±0.09 mm, p = 0.08)., Conclusions: Laser settings with an average power greater than 10 W deliver a thermal dose indicative of tissue damage, which increases with higher average power values. According to safety distance values from this study, a maximum of 10 W should be used in the ureter, and a maximum of 20 W should be used in kidney in presence of irrigation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Alternating current (AC) and pulsed electrolysis are gaining traction in electro(organic) synthesis due to their advantageous characteristics. We employed AC electrolysis in electrochemically mediated Atom Transfer Radical Polymerization (eATRP) to facilitate the regeneration of the activator Cu I complex on Cu 0 electrodes. Additionally, Cu 0 served as a slow supplemental activator and reducing agent (SARA ATRP), enabling the activation of alkyl halides and the regeneration of the Cu I activator through a comproportionation reaction. We harnessed the distinct properties of Cu 0 dual regeneration, both chemical and electrochemical, by employing sinusoidal, triangular, and square-wave AC electrolysis alongside some of the most active ATRP catalysts available. Compared to linear waveform (DC electrolysis) or SARA ATRP (without electrolysis), pulsed and AC electrolysis facilitated slightly faster and more controlled polymerizations of acrylates. The same AC electrolysis conditions could successfully polymerize eleven different monomers across different mediums, from water to bulk. Moreover, it proved effective across a spectrum of catalyst activity, from low-activity Cu/2,2-bipyridine to highly active Cu complexes with substituted tripodal amine ligands. Chain extension experiments confirmed the high chain-end fidelity of the produced polymers, yielding functional and high molecular-weight block copolymers. SEM analysis indicated the robustness of the Cu 0 electrodes, sustaining at least 15 consecutive polymerizations., (© 2024 Wiley-VCH GmbH.)

Nucleic acid-binding dyes ( NuABDs ) are fluorogenic probes that light up after binding to nucleic acids. Taking advantage of their fluorogenicity, NuABDs have been widely utilized in the fields of nanotechnology and biotechnology for diagnostic and analytical applications. We demonstrate the potential of NuABDs together with an appropriate nucleic acid scaffold as an intriguing photocatalyst for precisely controlled atom-transfer radical polymerization (ATRP). Additionally, we systematically investigated the thermodynamic and electrochemical properties of the dyes, providing insights into the mechanism that drives the photopolymerization. The versatility of the NuABD -based platform was also demonstrated through successful polymerizations using several NuABDs in conjunction with diverse nucleic acid scaffolds, such as G-quadruplex DNA or DNA nanoflowers. This study not only extends the horizons of controlled photopolymerization but also broadens opportunities for nucleic acid-based materials and technologies, including nucleic acid-polymer biohybrids and stimuli-responsive ATRP platforms.

An electrochemically controlled atom transfer radical polymerization ( e ATRP) was successfully carried out with a minimal amount (ppm-level) of FeBr 3 catalyst in a nonpolar solvent, specifically anisole. Traditionally, nonpolar media have been advantageous for Fe-based ATRP, but their low conductivity has hindered any electrochemical application. This study introduces the application of electrocatalytic methods in a highly nonpolar polymerization medium. Precise control over the polymerization was obtained by employing anhydrous anisole with only 400 ppm of FeBr 3 and applying a negative overpotential of 0.3 V. Additionally, employing an undivided cell setup with two simple iron wire electrodes resulted in a significant 15-fold reduction in electrical resistance compared to traditional divided cell setups. This enabled the production of polymers with a dispersity of ≤1.2. Lastly, an examination of kinetic and thermodynamic aspects indicated that the ppm-level catalysis was facilitated by the high ATRP equilibrium constant of Fe catalysts in nonpolar environments.

In catalysis, linear free energy relationships (LFERs) are commonly used to identify reaction descriptors that enable the prediction of outcomes and the design of more effective catalysts. Herein, LFERs are established for the reductive cleavage of the C(sp 3 )-X bond in alkyl halides (RX) by Cu complexes. This reaction represents the activation step in atom transfer radical polymerization and atom transfer radical addition/cyclization. The values of the activation rate constant, k act , for 107 Cu complex/RX couples in 5 different solvents spanning over 13 orders of magnitude were effectively interpolated by the equation: log  k act = s C ( I + C + S ), where I , C , and S are, respectively, the initiator, catalyst, and solvent parameters, and s C is the catalyst-specific sensitivity parameter. Furthermore, each of these parameters was correlated to relevant descriptors, which included the bond dissociation free energy of RX and its Tolman cone angle θ, the electron affinity of X, the radical stabilization energy, the standard reduction potential of the Cu complex, the polarizability parameter π* of the solvent, and the distortion energy of the complex in its transition state. This set of descriptors establishes the fundamental properties of Cu complexes and RX that determine their reactivity and that need to be considered when designing novel systems for atom transfer radical reactions. Finally, a multivariate linear regression (MLR) approach was adopted to develop an objective model that surpassed the predictive capability of the LFER equation. Thus, the MLR model was employed to predict k act values for >2000 Cu complex/RX pairs.

Introduction and Objectives: The use of ureteral access sheaths (UAS) limits the irrigation-induced increase in intrarenal pressure during ureteroscopy (URS). We investigated the relationship between UAS and rates of postoperative infectious complications in stone patients treated with URS., Materials and Methods: Data from 369 stone patients treated with URS from September 2016 to December 2021 at a single institution were analyzed. UAS (10/12 Fr) placement was attempted in case of intrarenal surgery. The chi-square test was used to assess the relationship between the use of UAS and fever, sepsis, and septic shock. Univariable and multivariable logistic regression analyses tested the association of patients' characteristics and operative data and the rate of postoperative infectious complications., Results: Full data collection of 451 URS procedures was available. Overall, UAS was used in 220 (48.8%) procedures. As for postoperative infectious sequalae, we recorded fever ( n = 52; 11.5%), sepsis ( n = 10; 2.2%), and septic shock ( n = 6; 1.3%). Of those, UAS was not used in 29 (55.8%), 7 (70%), and 5 (83.3%) cases, respectively (all p > 0.05). At multivariable logistic regression analysis, performing URS without UAS was not associated with the risk of having fever and sepsis, but it increased the risk of septic shock (OR = 14.6; 95% CI = 1.08-197.1). Moreover, age-adjusted CCI score (for fever-OR = 1.23; 95% CI = 1.07-1.42, sepsis-OR = 1.47; 95% CI = 1.09-1.99, and septic shock-OR = 1.61; 95% CI = 1.08-2.42, respectively), history of fever secondary to stones (for fever-OR = 2.23; 95% CI = 1.02-4.90) and preoperative positive urine culture (for sepsis-OR = 4.87; 95% CI = 1.12-21.25) did emerge as further associated risk factors., Conclusions: The use of UAS emerged to prevent the onset of septic shock in patients treated with URS, with no clear benefit in terms of fever and sepsis. Further studies may help clarify whether the reduction in fluid reabsorption load mediated by UAS is protective against life-threatening conditions in case of infectious complications. The patients' baseline characteristics remain the main predictors of infectious sequelae in a clinical setting.