Pd Samples Research Articles

Blepharoclonus as a Potential Novel Clinical Marker in Parkinson’s Disease (P3-11.009)

Blepharoclonus as a Potential Novel Clinical Marker in Parkinson’s Disease (P3-11.009)

Partial Discharge Data Augmentation and Pattern Recognition for Unbalanced and Small Sample Scenarios

To improve the accuracy of partial discharge pattern recognition under unbalanced and small sample conditions, a method of partial discharge data augmentation and pattern recognition using the generative adversarial network embedded deep auto-encoder (DAE-GAN) is proposed. First, deep Auto-encoder (DAE) is embedded into a Generative Adversarial Network (GAN), and DAE is used to guide the generation process to improve the authenticity of generated samples. Second, complement samples of PD samples are added to the training process of the Generative Adversarial Network to solve the problem of small PD samples. Finally, extended equalization training samples are used to fine-tune the discriminator of the model to realize PD pattern recognition. DAE-GAN is used for data augmentation and pattern recognition of partial discharge experimental signals. The results show that, compared with other algorithms, the authenticity and probability distribution fitting accuracy of partial discharge samples generated by DAE-GAN are higher and the accuracy of partial discharge recognition is improved by 8.24% after data augmentation.

Rapid Fabrication of Fe and Pd Thin Films as SERS-Active Substrates via Dynamic Hydrogen Bubble Template Method

Fe and Pd thin film samples have been fabricated in a rapid fashion utilizing the versatile technique of dynamic hydrogen bubble template (DHBT) method via potentiostatic electrodeposition over a copper substrate. The morphology of the samples is dendritic, with the composition being directly proportional to the deposition time. All the samples have been tested as SERS substrates for the detection of Rhodamine 6G (R6G) dye. The samples perform very well, with the best performance shown by the Pd samples. The lowest detectable R6G concentration was found to be 10-6 M (479 μgL-1) by one of the Pd samples with the deposition time of 180 s. The highest enhancement of signals noticed in this sample can be attributed to its morphology, which is more nanostructured compared to other samples, which is extremely conducive to the phenomenon of localized surface plasmon resonance (LSPR). Overall, these samples are cheaper, easy to prepare with a rapid fabrication method, and show appreciable SERS performance.

Aging of Pd under tritium: Influence of 3He generation and associated mechanisms

An experimental and theoretical study has been conducted to improve the understanding of the Pd tritide aging process. Tritide aging due to tritium radioactive decay produces 3He which create nanobubbles in the metal matrix. Pd samples are aged up to 20 years to cover the three steps of aging: bubble nucleation (∼ few days), bubble growth (∼ few years) and 3He massive release (over 10 years, depending on the initial tritium loading). All the experimental measurements are used as input/output data for the theoretical aging mechanism modeling. The bubble nucleation/growth modeling is improved thanks to these additional data. A sample aged over 20 years has been fully characterized which allows proposing a mechanism and the corresponding modeling for the last step of the aging process: the 3He release. The models provide a material behavior that agrees with microscopic and macroscopic observations.

Performance of copper and palladium metal-semiconductor Schottky diode for optoelectronics

The growth of ZnO nanorods (NRs) have been performed by chemical bath deposition (CBD) method on ITO glass substrate. The optical properties along with the structural of ZnO NRs were studies by Field Emission Scanning Electron Microscope (FESEM), energy-dispersive X-ray (EDX), X-Ray Diffraction (XRD), and UV-Visible (UV-Vis) analysis. A 100 nm of Cu metal and Pd metal were deposited on top of synthesized ZnO NRs via sputtering. The electrical properties including I-V characteristics, rectifying ratio, Schottky Barrier Height (SBH) and ideality factor were investigated. Difference in work function for both metals resulting in different I-V characteristics, hence different value of rectifying ratio, SBH and ideality factor. The Cu sample possessed rectifying ratio, SBH and ideality factor of 1.07, 0.66 eV and 6.1 respectively, while Pd sample exhibits 87.84, 0.43 eV and 5 respectively. These intriguing values made possible for these metals to potentially serve as contact for ZnO-based optoelectronics devices, e.g LED, and random laser.

Decomposition of formic acid via carboxyl mechanism on the graphene nanosheet decorated by Cr, Mn, Fe, Co, Ni, Pd, Ag, and Cd metals: A DFT study

The carboxyl mechanism of formic acid decomposition was investigated on the graphene nanosheet decorated with 8 single metal atoms from the thermodynamics and kinetics point of view using DFT computations. The thermodynamic results showed that for all metal-doped graphene surfaces, the adsorption of studied entities in the gas phase was more favorable compared to the solution phase. The Mn-doped graphene surface was more suitable for the adsorption of studied entities than the other surfaces. Adsorption of CO as a poisoning entity was also more favored on Mn-doped graphene with the highest adsorption energy of −47.56 kJ/mol while the Pd and Co samples were less poisoned with CO intermediate. Our kinetic studies demonstrated that the C–H bond activation was the rate-determining step of formic acid decomposition for all of the examined systems in the gas and solution phases. Additionally, formic acid decomposition was kinetically more suitable on the Mn-doped graphene nanosheet with the lowest activation energy of 73.19 kJ/mol.

Impact of ammonia treatment and platinum group or nickel metal decoration on the activated carbon storage of carbon dioxide and methane

Greenhouse gases, chiefly carbon dioxide (CO2) and methane (CH4), emission is responsible for the global warming and heat waves which strike the world causing floods and droughts everywhere with more CO2 attributions. The adsorption and desorption capacities of CO2 and CH4 at room temperature and up to 5.0 and 100 bar, respectively, were investigated for the untreated and ammonia-treated activated carbons (ACs), metal-anchored (metal: Ru, Rh, Pd, Ir or Ni) samples. We merged ammonia treatment and metal decoration to discover their influences on the CO2 and CH4 storage capability of ACs and the potential use of such modified ACs for capturing greenhouse gases and purifying natural gas from CO2. The CO2 storage capacities ranged between 25.2 and 27.7 wt% at 5.0 bar with complete regeneration upon desorption, while the uptakes for CH4 were in the range of 9.6 − 12.6 wt% at 35 bar with hysteresis behavior of the adsorbed gas. The highest adsorption capacities were achieved for the pristine samples, showing that metal decoration reduced slightly the adsorption. Ammonia-treated samples showed minor enhancing effect on the CH4 adsorption in comparison to the CO2 adsorption. The higher adsorption capacities of CO2 than those of CH4 could be employed for upgrading the natural gas, while the 9.6 wt% (2.2 mmol g−1) CO2 storage capacity would allow for its removal from the flue gases at ambient temperature and pressure. The higher adsorption capacity and preferentiality of CO2 over CH4 could be attributed mainly to its higher quadrupole moment and its higher clustering above the AC surfaces, while a minor effect, if any, would be attributed to the modifications of the ACs, implying that physisorption mechanism acted significantly in the adsorption process in comparison to chemisorption mechanism at the studied conditions.

Microwave-assisted synthesis of iridium oxide and palladium nanoparticles supported on a nitrogen-rich covalent triazine framework as superior electrocatalysts for the hydrogen evolution and oxygen reduction reaction.

Iridium oxide (IrOx-NP) and palladium nanoparticles (Pd-NP) were supported on a 2,6-dicyanopyridine-based covalent-triazine framework (DCP-CTF) by energy-saving and sustainable microwave-assisted thermal decomposition reactions in propylene carbonate and in the ionic liquid [BMIm][NTf2]. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) confirm well-distributed NPs with sizes from 2 to 13 nm stabilized on the CTF particles. Metal contents between 10 and 41 wt% were determined by flame atomic absorption spectroscopy (AAS). Nitrogen sorption measurements of the metal-loaded CTFs revealed Brunauer–Emmett–Teller (BET) surface areas between 904 and 1353 m2 g−1. The composites show superior performance toward the hydrogen evolution reaction (HER) with low overpotentials from 47 to 325 mV and toward the oxygen reduction reaction (ORR) with high half-wave potentials between 810 and 872 mV. IrOx samples in particular show high performances toward HER while the Pd samples show better performance toward ORR. In both reactions, electrocatalysts can compete with the high performance of Pt/C. Exemplary cyclic voltammetry durability tests with 1000 cycles and subsequent TEM analyses show good long-term stability of the materials. The results demonstrate the promising synergistic effects of NP-decorated CTF materials, resulting in a high electrocatalytic activity and stability.

Tuning Catalytic Activity in Ultrathin Bimetallic Nanowires Via Surface Segregation: Application in Electrochemical Methanol Oxidation

The reaction kinetics and efficiency in any catalytic process is controlled by the adsorption and desorption of reactant and intermediates on the surface of catalyst. As a consequence, the surface properties, composition and geometry of the catalyst dictates the mechanism of reactions. The surface electronic structure is modulated by variations in surface and subsurface atomic configurations, e.g., ordering and surface segregation, which in turn can vividly affects catalytic properties.1,2 A great deal of efforts are being devoted to develop efficient heterogenous catalyst by critically controlling the surface structure and chemistry. Here, I would like to present results on two different strategies for controlling the surface composition in ultrathin bimetallic AuPd nanowires. Au nanowire template-based method was used to grow AuPd wires by gradually increasing the amount of Pd.3 Percentage of composition of Au and Pd in AuPd nanowires gave either alloy nanowires with Au-rich compositions or core-shell structure at higher Pd compositions with Au-rich core and Pd-rich shell. Surface morphology of alloyed nanowires were induced through segregation of Pd to the surface by annealing under controlled CO atmosphere. High resolution microscopic imaging was possible due to the fact of substantial difference in the atomic number between Au and Pd. Electrocatalytic methanol oxidation reaction (MOR) in alkaline medium is important for energy conversion and was selected to study the catalytic activity of AuPd nanowires. A nearly monotonic increase of MOR potential was observed with increase in Pd content. Interestingly, a typical volcano type behavior of the specific activity was observed with different composition and with 40 and 50% Pd samples showed the optimum values in terms of current, potential and If/Ib values. Owing to a higher Pd content of CO-annealed nanowires, a lowering of potential was observed though the specific activity was maintained. These findings provide clear strategies to independently control the reaction potential and the activities of nanocatalysts with smaller amounts of the expensive active metal. The compositional effects on the electronic structure of the AuPd nanowires (catalyst surface) as well as binding energy of intermediates involved in the MOR was investigated using DFT calculations. d-band center analysis was employed to check interaction of CO* which a major intermediate of MOR with the catalyst surface. The theoretical investigation align well with the experimental results where it was found that the MOR potential increases with increasing amount of Pd and for the Au rich case the reaction does not reach up to CO2 but yields HCHO as a product at lower potentials. From our experimental finding it was evident that it is possible to lower the MOR potential to attain comparable or better activity through enrichment with the precious metal on the surface while essentially dropping the real quantity used.

Chemically prepared Pd-Cd alloy nanocatalysts as the highly active material for formic acid electrochemical oxidation

In this research, different Pd-Cd alloy electrocatalysts (Pd6.3Cd, Pd2.6Cd, Pd1.1Cd, PdCd1.7, and PdCd5.6) were synthesized by a simple chemical method. The field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), EDX mapping, and X-Ray diffraction (XRD) techniques were employed for the characterization of the prepared samples. These electrocatalysts were deposited on the surface of the glassy carbon electrode and the obtained electrodes were employed for formic acid oxidation in sulphuric acid solution using electrochemical methods. Our results demonstrated that in comparison with the Pd sample, the prepared Pd-Cd alloys possessed higher electrocatalytic activity for formic acid oxidation. It was also found that the Pd6.3Cd sample was the best electrocatalyst with a mass activity of 597.06 mA mg−1Pd among all studied samples. This mass activity was significantly higher compared to the commercial Pd sample. Additionally, the Pd6.3Cd sample was the best sample against poisoning with adsorbed CO intermediate.

Antagonistic network signature of motor function in Parkinson\u2019s disease revealed by connectome-based predictive modeling

Motor impairment is a core clinical feature of Parkinson’s disease (PD). Although the decoupled brain connectivity has been widely reported in previous neuroimaging studies, how the functional connectome is involved in motor dysfunction has not been well elucidated in PD patients. Here we developed a distributed brain signature by predicting clinical motor scores of PD patients across multicenter datasets (total n = 236). We decomposed the Pearson’s correlation into accordance and discordance via a temporal discrete procedure, which can capture coupling and anti-coupling respectively. Using different profiles of functional connectivity, we trained candidate predictive models and tested them on independent and heterogeneous PD samples. We showed that the antagonistic model measured by discordance had the best sensitivity and generalizability in all validations and it was dubbed as Parkinson’s antagonistic motor signature (PAMS). The PAMS was dominated by the subcortical, somatomotor, visual, cerebellum, default-mode, and frontoparietal networks, and the motor-visual stream accounted for the most part of predictive weights among network pairs. Additional stage-specific analysis showed that the predicted scores generated from the antagonistic model tended to be higher than the observed scores in the early course of PD, indicating that the functional signature may vary more sensitively with the neurodegenerative process than clinical behaviors. Together, these findings suggest that motor dysfunction of PD is represented as antagonistic interactions within multi-level brain systems. The signature shows great potential in the early motor evaluation and developing new therapeutic approaches for PD in the clinical realm.

Enhancement of voltage controlled magnetic anisotropy (VCMA) through electron depletion

Recent advancement in the switching of perpendicular magnetic tunnel junctions with an electric field has been a milestone for realizing ultra-low energy memory and computing devices. To integrate with current spin-transfer torque-magnetic tunnel junction and spin–orbit torque-magnetic tunnel junction devices, the typical linear fJ/V m range voltage controlled magnetic anisotropy (VCMA) needs to be significantly enhanced with approaches that include new materials or stack engineering. A possible bidirectional and 1.1 pJ/V m VCMA effect has been predicted by using heavily electron-depleted Fe/MgO interfaces. To improve upon existing VCMA technology, we have proposed inserting high work function materials underneath the magnetic layer. This will deplete electrons from the magnetic layer biasing the gating window into the electron-depleted regime, where the pJ/V m and bidirectional VCMA effect was predicted. We have demonstrated tunable control of the Ta/Pd(x)/Ta underlayer's work function. By varying the Pd thickness (x) from 0 to 10 nm, we have observed a tunable change in the Ta layer's work function from 4.32 to 4.90 eV. To investigate the extent of the electron depletion as a function of the Pd thickness in the underlayer, we have performed DFT calculations on supercells of Ta/Pd(x)/Ta/CoFe/MgO, which demonstrate that electron depletion will not be fully screened at the CoFe/MgO interface. Gated pillar devices with Hall cross geometries were fabricated and tested to extract the anisotropy change as a function of applied gate voltage for samples with various Pd thicknesses. The electron-depleted Pd samples show three to six times VCMA improvement compared to the electron accumulated Ta control sample.

Psychometric Properties of a Cultural Adapted Version of the Assessment of Identity Development in Adolescence in Panama.

The Assessment of Identity Development in Adolescence (AIDA) is a self-report instrument to detect pathological development of Identity. In Panamá, psychometric instruments for assessment of psychopathology in adolescence are lacking. Our aim was to develop a valid and reliable version of the AIDA Inventory for Panamanian Population. AIDA was adapted to Spanish considering cultural aspects of Panamanian population. Two pilot tests were performed prior to main test to assess item-total correlation at subscale, primary scale and total scale levels and internal consistency at subscale level. A mixed sample of students and PD patients (N = 315) completed the AIDA inventory, the “Strength and Difficulties Questionnaire” and “Defense Style Questionnaire−40.” AIDA was retested in a sub sample from school population (n = 98). The Structured Clinical Interview for Axis II Disorders was used for diagnosis of personality disorders in the patient sample (n = 25). Psychometric properties were tested to assess internal consistency, reliability, factorial validity, convergent validity, and criterion validity. AIDA Panama showed excellent internal consistency for the total scale Identity Diffusion with Cronbach's α:0.94 and a retest reliability of 0.84. A Bifactorial CFA was modeled to assess the dimensionality of the inventory. The proportion between OmegaH and Omega at total scales 96% of the variance is explained by a general factor. Furthermore, the Explained Common Variance for the General Factor is 73% supporting unidimensionality. In line with theory, AIDA total scale showed a high positive correlation (r = 0.67) with Total Difficulties scale and high positive correlation (r = 0.71) with Immature Defense scale. The AIDA total score differed highly significant (p = 0.000) between the patient sample and the students with a large effect size (d = 1.02).ConclusionThe adaptation and validation of AIDA for Panamanian adolescent population was successful with good psychometric properties and significant correlations with related psychopathological constructs. AIDA showed high clinical validity by providing a valid discrimination between the school sample and a diagnosed PD sample, in line with the assumption that impaired identity functioning is at the core of personality disorders, especially in adolescence.

Impact of the Experimental Parameters on Catalytic Activity When Preparing Polymer Protected Bimetallic Nanoparticle Catalysts on Activated Carbon.

Sol immobilization is used to produce bimetallic catalysts with higher activity to monometallic counterparts for a wide range of environmental and commercial catalytic transformations. Analysis of complementary surface characterization (XPS, Boehm’s titration, and zeta potential measurements) was used to elucidate alterations in the surface functionality of two activated carbon supports during acid exposure. When considered in parallel to the experimentally determined electrostatic and conformational changes of the polymer surrounding the nanoparticles, an electrostatic model is proposed describing polymer protected nanoparticle deposition with several polymer–carbon support examples described. Consideration of the electrostatic interactions ensures full deposition of the polymer protected nanoparticles and at the same time influences the structure of the bimetallic nanoparticle immobilized on the support. The normalized activity of AuPd catalysts prepared with 133 ppm H2SO4 has a much higher activity for the direct synthesis of hydrogen peroxide compared to catalysts prepared in the absence of acid. Detailed characterization by XPS indicates that the surface becomes enriched in Au in the Au–Pd samples prepared with acid, suggesting an improved dispersion of smaller bimetallic nanoparticles, rich in Au, that are known to be highly active for the direct synthesis reaction. Subsequent microscopy measurements confirmed this hypothesis, with the acid addition catalysts having a mean particle size ∼2 nm smaller than the zero acid counterparts. The addition of acid did not result in a morphology change, and random alloyed bimetallic AuPd nanoparticles were observed in catalysts prepared by sol immobilization in the presence and absence of acid. This work shows that the deposition of polymer protected AuPd nanoparticles onto activated carbon is heavily influenced by the acid addition step in the sol immobilization process. The physicochemical properties of both the polymer and the activated carbon support should be considered when designing a bimetallic nanoparticle catalyst by sol immobilization to ensure the optimum performance of the final catalyst.

Identifying the hub gene and immune infiltration of Parkinson’s disease using bioinformatical methods

BackgroundParkinson’s disease (PD) is a common neurodegenerative disorder that affects 1%–2% of the population over 60 years old. Immune response dysfunction in the brain contributes to the occurrence and development of PD. This study aimed to uncover the potential diagnostic genes for PD and characterize the immune cell infiltrates. MethodsWe downloaded the microarray data of patients with PD samples from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify the modules linked to PD in the GSE20163 dataset. Meanwhile, differentially expressed genes (DEGs) between the healthy control samples and PD samples were also identified. Then the PD-related genes were integrated based on the genes in the key module and DEGs. Functional enrichment analysis was used to explore the molecular mechanisms of these PD-related genes. Protein-protein interaction (PPI) network and least absolute shrinkage and selection operator (LASSO) analysis were used to further screen candidate genes for PD. Gene set enrichment analysis (GSEA) was applied to explore the biological functions of these candidate genes. The infiltration of immune cells was detected by single-sample gene set enrichment analysis (ssGSEA) algorithm in the GSE20163 dataset, and Pearson analysis was used to investigate the correlation of candidate genes with immune cells and immune checkpoint proteins. The expression of candidate genes in clinical samples was verified by qPCR. ResultsAltogether, we found a unique gene module related to PD, where 109 DEGs were identified in the GSE20163 dataset. Following these results, we screened 68 genes associated with PD. Gene Expression Omnibus (GEO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that these genes were markedly enriched in the pathway of synthesis and transport of neurons. Three candidate genes (SLC18A2, CALB1, and SYNGR3) were further identified in PD patients through PPI network and LASSO analysis. The receiver operating characteristic (ROC) curve indicated that the three candidate genes had a good performance in distinguishing the PD samples from healthy control samples. The proportions of the aDC, DC, NK CD56dim cells, and follicular helper T cells (TFH) were obviously different between the healthy control and PD samples. Moreover, CTLA4, LAG3, CEACAM1, and CD27 were highly expressed in the PD group. GSEA analysis for candidate genes revealed that they were all closely related to the neurogenic disease. Additionally, the three candidate genes were all strongly correlated with the above immune cells and immune checkpoint proteins. The qPCR results validated the expression differences of SLC18A2 and SYNGR3 in the clinical PD and control samples. ConclusionThe three candidate genes may be a useful tool for diagnosing PD patients. These findings provide a reference for exploring new therapeutic targets and strategies for PD treatment.

Association between Parkinson\u2019s disease and the faecal eukaryotic microbiota

Parkinson’s disease (PD) is one of the most common neurodegenerative disease, and is so far not considered curable. PD patients suffer from several motor and non-motor symptoms, including gastrointestinal dysfunctions and alterations of the enteric nervous system. Constipation and additional intestinal affections can precede the classical motor symptoms by several years. Recently, we reported effects of PD and related medications on the faecal bacterial community of 34 German PD patients and 25 age-matched controls. Here, we used the same collective and analysed the V6 and V7 hypervariable region of PCR-amplified, eukaryotic 18S rRNA genes using an Illumina MiSeq platform. In all, 53% (18) of the PD samples and 72% (18) of the control samples yielded sufficient amplicons for downstream community analyses. The PD samples showed a significantly lower alpha and a different beta eukaryotic diversity than the controls. Most strikingly, we observed a significantly higher relative abundance of sequence affiliated with the Geotrichum genus in the PD samples (39.7%), when compared to the control samples (0.05%). In addition, we observed lower relative abundances of sequences affiliated with Aspergillus/Penicillium, Charophyta/Linum, unidentified Opisthokonta and three genera of minor abundant zooflagellates in the PD samples. Our data add knowledge to the small body of data about the eukaryotic microbiota of PD patients and suggest a potential association of certain gut eukaryotes and PD.

Long‐term Pseudogymnoascus destructans surveillance data reveal factors contributing to pathogen presence

AbstractThe disease white‐nose syndrome (WNS) was first recognized in upstate New York in 2006 and has since spread across much of the United States (U.S.), causing severe mortality in several North American bat species. To aid in the identification and monitoring of at‐risk bat populations, we evaluate factors associated with the presence of the causative fungal agent of WNS, Pseudogymnoascus destructans (Pd), in the continental United States. We obtained Pd samples through hibernaculum surveys conducted from 2013 to 2020, with all samples analyzed at the U.S. Geological Survey National Wildlife Health Center. Using generalized additive models, we estimated the likelihood of Pd presence under three different hypotheses: human‐mediated, species‐mediated, and hibernaculum type. In addition to hypothesis‐related predictor variables, a subset of models included a smoothed nonseparable effect of longitude and latitude and a smoothed effect of time since study onset to account for spatial and temporal autocorrelation. Under all hypotheses, models indicated probability of Pd detection is best described by the smoothed nonseparable effect of longitude and latitude and a smoothed effect of time since onset of this study. After accounting for spatial and temporal autocorrelations, only hibernaculum type significantly affected Pd presence, with mines and culverts/tunnels less likely to contain Pd compared with caves. Reduced likelihood of Pd presence in mines and culverts/tunnels bodes well for bats of the western and southern United States, where use of these hibernaculum types is more common. While our findings can help guide monitoring and management efforts, the potential for long‐distance dispersal combined with variation in community composition and hibernation ecology between the western and eastern United States necessitates the continued monitoring of Pd presence.

Inverted Hysteresis Loops in the Fe73.5Cu1Nb3Si13.5B9 Alloy With Small Coercivity

The phenomenon of inverted hysteresis loop has been observed in many materials for the past decades. However, the physical origin of the inverted hysteresis loop has long been debated. Here, we report the completely inverted hysteresis loop with a clockwise cycle in the soft-magnetic nanocrystalline Fe73.5Cu1Nb3Si13.5B9 alloy and amorphous Fe73.5Cu1Nb3Si13.5B9 alloy at room temperature. The negative remanence and positive coercivity were observed in the descending branch of magnetization curve when the scan field range was above 1 KOe. By comparing the results with that of the standard Pd sample, we found that the net coercivities of the nanocrystalline Fe73.5Cu1Nb3Si13.5B9 alloy and standard Pd sample are almost equal for the different scanning field ranges. Therefore, it is confirmed that the phenomenon of completely inverted hysteresis loop is caused by the remanence of superconducting magnet rather than the structural inhomogeneity effects. Our results suggest that special care should be taken during the measurement of hysteresis loops using MPMS 3, especially for the materials with small coercivity.

A glutaminyl cyclase-catalyzed \u03b1-synuclein modification identified in human synucleinopathies

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is neuropathologically characterized by degeneration of dopaminergic neurons of the substantia nigra (SN) and formation of Lewy bodies and Lewy neurites composed of aggregated α-synuclein. Proteolysis of α-synuclein by matrix metalloproteinases was shown to facilitate its aggregation and to affect cell viability. One of the proteolysed fragments, Gln79-α-synuclein, possesses a glutamine residue at its N-terminus. We argue that glutaminyl cyclase (QC) may catalyze the pyroglutamate (pGlu)79-α-synuclein formation and, thereby, contribute to enhanced aggregation and compromised degradation of α-synuclein in human synucleinopathies. Here, the kinetic characteristics of Gln79-α-synuclein conversion into the pGlu-form by QC are shown using enzymatic assays and mass spectrometry. Thioflavin T assays and electron microscopy demonstrated a decreased potential of pGlu79-α-synuclein to form fibrils. However, size exclusion chromatography and cell viability assays revealed an increased propensity of pGlu79-α-synuclein to form oligomeric aggregates with high neurotoxicity. In brains of wild-type mice, QC and α-synuclein were co-expressed by dopaminergic SN neurons. Using a specific antibody against the pGlu-modified neo-epitope of α-synuclein, pGlu79-α-synuclein aggregates were detected in association with QC in brains of two transgenic mouse lines with human α-synuclein overexpression. In human brain samples of PD and dementia with Lewy body subjects, pGlu79-α-synuclein was shown to be present in SN neurons, in a number of Lewy bodies and in dystrophic neurites. Importantly, there was a spatial co-occurrence of pGlu79-α-synuclein with the enzyme QC in the human SN complex and a defined association of QC with neuropathological structures. We conclude that QC catalyzes the formation of oligomer-prone pGlu79-α-synuclein in human synucleinopathies, which may—in analogy to pGlu-Aβ peptides in Alzheimer’s disease—act as a seed for pathogenic protein aggregation.

MO900ENHANCED EXPRESSION OF THIOREDOXIN-INTERACTING PROTEIN (TXNIP) RESULTS IN REDUCED TRX ACTIVITY AND INCREASED OXIDATIVE DNA-DAMAGE IN PERITONEAL DIALYSIS PATIENTS*

Abstract Background and Aims Peritoneal dialysis (PD) is an effective method of renal replacement therapy (RRT). The long-term use of PD as a RRT is limited due to adverse effects of high glucose-based PD solutions to the structure and function of the peritoneal membrane. PD patients show excessive oxidative stress compared to healthy controls. However, there are only scare information on pathophysiological mechanisms leading to oxidative DNA-damage in PD patients. Therefore, the aim of this study was to elucidate the mechanism leading to excessive oxidative stress in human samples of the peritoneal membrane. Method Human peritoneal biopsies of healthy controls, PD patients and patients with EPS were collected. Protein expression of TXNIP was analysed by ELISA using plasma samples and by immunohistochemistry of peritoneal biopsies using a Histo-Score. Protein expression of TRX was examined by immunohistochemistry. To measure TRX activity a kit based on the reduction of insulin by reduced TRX was used. The resulting oxidative DNA-damage was investigated by immunohistochemistry using a Histo-Score or by ELISA using plasma samples of patients. Results Biopsies from the peritoneum of 8 healthy controls, 11 uremic patients, 22 patients on PD < 12 months or 29 patients on PD > 12 months and of 13 patients with EPS were collected. The age of the uremic patients was higher (median 65.0 years, IQR: 49.0-75.0) than in the other subgroups (PD < 12 months: median 62.0 years, IQR: 52.25-68.25, PD > 12 months: median 60.0 years, IQR: 39.5-70.5 and EPS: median 51.00 years, IQR: 40.0-57.5). In general, there were more female participants in the control-group (75 %) compared to all other groups (uremic group: 27%, PD < 12 months: 18 %, PD >12 months: 41% and EPS group 33 %). Time on PD was longer in EPS patients (median 72.0 months) than in PD patients (PD <12 months: median 10.0 months and PD > 12 months: 39.0 months). The ELISA study of plasma samples showed that TXNIP is upregulated in all groups compared to healthy controls. Immunohistochemically studies of peritoneal biopsies showed also an upregulation of TXNIP upon exposure to high glucose-based dialysis fluids (PD and EPS group). Interestingly, a glucose-related change in protein expression of its interacting partner and cellular anti-oxidant TRX was only observed in EPS samples. TRX activity in uremic patients was almost unchanged compared to healthy controls except for one patient. However, enhanced TXNIP expression correlated with a reduced activity of TRX in samples of PD as well as EPS patients. Reduced TRX activity resulted in an increase of produced ROS. Therefore, the effect on the generation of oxidative damage was analysed by ELISA of plasma samples and by immunohistochemistry on peritoneal sections. Both analysis showed an increase in the oxidative DNA-damage marker 8-Hydroxydesoxyguanosin (8-OHdG) in all PD samples and samples of EPS patients compared to the control group. Conclusion Here, we show that high glucose-based peritoneal dialysis solutions lead to an upregulation of TXNIP expression in human peritoneal samples. This increase in TXNIP expression reduces the activity of its interacting partner an antioxidant TRX leading to an increase in ROS production and enhanced levels of DNA-damage. In this study, we elucidate for the first time a novel mechanism showing that glucose-dependent upregulation of TXNIP induces a perturbation of the intracellular redox equilibrium leading to alterations of the peritoneal membrane. Therefore, manipulation of TXNIP expression may be a promising therapeutic target to improve peritoneal membrane function.