Dont die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra?

A hallmark of Parkinsons disease is the specific degeneration of dopaminergic neurons in the substantia nigra pars compacta. Interestingly, not all of these neurons are affected to the same extent. Studies revealed that neurons located more ventrally within the substantia nigra pars compacta have a higher prevalence to degenerate than those located in the dorsal tier. The underlying reasons for this selective neuronal vulnerability are still unknown. The aim of the present study was to gain a better understanding of molecular differences between these two neuronal subpopulations that may explain the selective neuronal vulnerability within the human substantia nigra. For this purpose, the neurons from the ventral as well as dorsal tier of the substantia nigra were specifically isolated out of neuropathologically unremarkable human substantia nigra sections with laser microdissection. Following, their proteome was analyzed by data independent acquisition mass spectrometry. The samples were analysed donor-specifically and not pooled for this purpose. A total of 5,391 proteins were identified in the substantia nigra. Of these, 2,453 proteins could be quantified in 100% of the dorsal tier samples. 1,629 could be quantified in 100% of the ventral tier samples. Nine proteins were differentially regulated with a log2 value ≥0.5 and a Qvalue ≤0.05. Of these 7 were higher abundant in the dorsal tier and 2 higher in the ventral tier. These proteins are associated with the cytoskeleton, neuronal plasticity, or calcium homeostasis. With these findings a deeper understanding can be gained of the selective neuronal vulnerability within the substantia nigra and of protective mechanisms against neurodegeneration in specific neuronal subpopulations

Impact of diastolic pulmonary gradient and pulmonary artery pulse index on outcomes in heart transplant patients—Results from the Eurotransplant database

BackgroundPredicting complications associated with pulmonary hypertension (PH) after cardiac transplantation is an important factor when considering cardiac transplantation. The transpulmonary gradient (TPG) is recommended to quantify PH in transplant candidates. Nonetheless, PH remains a common driver of mortality. The diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) can differentiate post- from combined pre- and post-capillary PH and may improve estimation of PH-associated risks. We used a large European cohort of transplant candidates to assess whether the pulmonary pulsatility index (PAPi), improves prediction of graft failure and mortality compared to DPG and PVR.MethodsOut of all patients undergoing heart transplantation between 2009 and 2019 in Eurotransplant member states (n = 10,465), we analyzed the impact of PH (mPAP > 25 mmHg) and right heart catheter hemodynamic data on graft failure and mortality within 1–5 years.ResultsIn 1,407 heart transplant patients with PH (79% male, median age 54 years, IQR 39–69 years), the median PVR was 2.5 WU (IQR 1.6 WU) with a median mPAP (pulmonary arterial pressure) of 32 mmHg (IQR 9 mmHg). Patients with low (< 3 mmHg) DPG had a better 5 year survival than those with higher DPG (log rank p = 0.023). TPG, mPAP, PAPi, and PVR did not improve prediction of survival. Low PAPi (OR = 2.24, p < 0.001) and high PVR (OR = 2.12, p = 0.005) were associated with graft failure.ConclusionPAPI and PVR are associated with graft failure in patients with PH undergoing cardiac transplantation. DPG is associated with survival in this cohort

Dataset containing physiological amounts of spike-in proteins into murine C2C12 background as a ground truth quantitative LC-MS/MS reference

In this article, we present a data dependent acquisition (DDA) dataset which was generated as a reference and ground truth quantitative dataset. While initially used to compare samples measured with DDA and data independent acquisition (DIA) (Barkovits et al., 2020), the presented dataset holds potential value as a benchmark reference for any workflows working on DDA data. The entire dataset consists of 15 LC-MS/MS measurements composed of five distinct spike-in-states, each with three replicates. To generate the data set, a C2C12 (immortalized mouse myoblast) cell lysate was used as a complex background for five different states which were simulated by spiking 13 defined proteins at different concentrations. For this purpose, the cell lysate was used in a constant amount of 20 µg for all samples and different amounts of the 13 selected proteins ranging from 0.1 to 10 pmol were added, reflecting physiological amounts of proteins. Afterwards, all samples were tryptically digested using the same method. From each sample 200 ng tryptic peptides were measured in triplicates on a Q Exactive HF (Thermo Fisher Scientific). The mass range for MS1 was set to 350–1400 m/z with a resolution of 60,000 at 200 m/z. HCD fragmentation of the Top10 abundant precursor ions was performed at 27% NCE. The fragment analysis (MS2) was performed with a resolution of 30,000 at 200 m/z

Proteomic characterization of neuromelanin granules isolated from human substantia nigra by laser-microdissection

Neuromelanin is a complex polymer pigment found primarily in the dopaminergic neurons of human substantia nigra. Neuromelanin pigment is stored in granules including a protein matrix and lipid droplets. Neuromelanin granules are yet only partially characterised regarding their structure and function. To clarify the exact function of neuromelanin granules in humans, their enrichment and in-depth characterization from human substantia nigra is necessary. Previously published global proteome studies of neuromelanin granules in human substantia nigra required high tissue amounts. Due to the limited availability of human brain tissue we established a new method based on laser microdissection combined with mass spectrometry for the isolation and analysis of neuromelanin granules. With this method it is possible for the first time to isolate a sufficient amount of neuromelanin granules for global proteomics analysis from ten 10 μm tissue sections. In total 1,000 proteins were identified associated with neuromelanin granules. More than 68% of those proteins were also identified in previously performed studies. Our results confirm and further extend previously described findings, supporting the connection of neuromelanin granules to iron homeostasis and lysosomes or endosomes. Hence, this method is suitable for the donor specific enrichment and proteomic analysis of neuromelanin granules

Concentration-dependent atomic mobilities in FCC CoCrFeMnNi high-entropy alloys

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Human tear fluid proteome dataset for usage as a spectral library and for protein modeling

This article provides a detailed dataset of human tear fluid proteins. Samples were fractionated by sodium dodecyl sulfate (SDS) gel electrophoresis resulting in 48 fractions that were spiked with an indexed retention time (iRT) peptide standard. These data are based on a data-dependent acquisition (DDA) mass spectrometric approach and can be used for example as a spectral library for tear fluid proteome analysis by data-independent acquisition (DIA). Moreover, the provided data set can be used with optimized HPLC and mass spectrometric settings for proteins/peptides of interest. Besides these aspects, this dataset can serve as a protein overview for gene ontology enrichment analysis and for modeling and benchmarking of multiple signaling pathways associated with the ocular surface in healthy or disease stages. The mass spectrometry proteomics data from the described workflow have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD011075

Portal alumni

Begonnen hat es um 1900 mit Qualitätskontrolle, später folgte Qualitätsprüfung und seit Mitte der 90er Jahre hat das Thema Qualitätsmanagement Einzug gehalten in alle Bereiche von Politik und Gesellschaft. Im Gesundheitswesen, der Justiz und auch an vielen Hochschulen wurden spezielle Stellen eingerichtet, die sich gezielt mit der Umsetzung von Qualitätsentwicklung oder Qualitätsmanagement befassen. Das übergeordnete Ziel bei Einführung eines Qualitätsmanagements ist es, die Wettbewerbsfähigkeit der Organisation sowie auch die Zufriedenheit der Mitglieder der Institutionen und weiterer Stakeholder zu steigern, indem die Qualität der Tätigkeiten und der jeweiligen Rahmenbedingungen erhalten und optimiert wird. Mit der bewussten Entscheidung zur Qualitätssicherung und -entwicklung beginnt ein fortlaufender Prozess, der stetig intensiv begleitet werden muss. Qualitätsmanagement wirkt nachhaltig, in dem durch die Schaffung regelmäßiger und systematischer Strukturen und Prozesse auch zukünftig den beteiligten Personen ein optimales Handeln entsprechend der dann geltenden Bedingungen ermöglicht wird. Portal alumni widmet sich in seinem zehnten Heft diesem Thema und hat Absolventen der Universität Potsdam nach ihrem Tätigkeitsfeld im Qualitätsmanagement und den entsprechenden Erfolgen befragt. Dabei zeigt sich, dass Ehemalige Einsatzbereiche in Wirtschaft und Unternehmen aber auch in Sport, Bildung oder Hochschulen gefunden haben. Daneben berichten wir in diesem Heft von einem Projekt des Career Service, dem Schnupperjobben, und auch die Berichte über die Geschehnisse an Ihrer Alma mater kommen nicht zu kurz