The Protective Effect of Docosahexaenoic Acid on Mitochondria in SH-SY5Y Model of Rotenone-Induced Toxicity.

Polyunsaturated fatty acids in particular omega-3 fatty acids, such as docosahexaenoic acid (DHA), are essential nutrients and components of the plasma membrane. They are involved in various processes, including synaptic development, functionality, integrity, and plasticity, and are therefore thought to have general neuroprotective properties. Considerable research evidence further supports the beneficial effects of omega-3 fatty acids, specifically on mitochondria, through their antioxidant and anti-apoptotic properties, making them an attractive addition in treatment options for neurodegenerative disorders in which mitochondrial alterations are commonly observed.

Unsaturated Fatty Acids Are Decreased in Aβ Plaques in Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (Aβ) plaques in the brain, contributing to neurodegeneration. This study investigates lipid alterations within these plaques using a novel, label-free, multimodal approach. Combining infrared (IR) imaging, machine learning, laser microdissection (LMD), and flow injection analysis mass spectrometry (FIA-MS), we provide the first comprehensive lipidomic analysis of chemically unaltered Aβ plaques in post-mortem human AD brain tissue.

Middle-throughput LC-MS-based platelet proteomics with minute sample amounts using semi-automated positive pressure FASP in 384-well format (PF384).

Comprehensive characterization of platelets requires various functional assays and analysis techniques, including omics-disciplines, each requiring an individual aliquot of a given sample. Consequently, the sample material per assay is often highly limited rendering downscaling a prerequisite for effective sample exploitation. Here we present a transfer of our recently introduced 96-well-based proteomics workflow (PF96) into the 384-well format (PF384) allowing for a significant increase in sensitivity when processing minute platelet protein amounts.

ProtGraph: a tool for the quick and comprehensive exploration and exploitation of the peptide search space derived from protein sequence databases using graphs.

Due to computational resource limitations, in mass spectrometry based proteomics only a limited set of peptide sequences is used for the matching against measured spectra. We present an approach to represent proteins by graphs and allow not only the canonical sequences but also known isoforms and annotated amino acid variations, e.g.

Metabolic Adaptation in Epilepsy: From Acute Response to Chronic Impairment.

Epilepsy is characterized by hypersynchronous neuronal discharges, which are associated with an increased cerebral metabolic rate of oxygen and ATP demand. Uncontrolled seizure activity (status epilepticus) results in mitochondrial exhaustion and ATP depletion, which potentially generate energy mismatch and neuronal loss. Many cells can adapt to increased energy demand by increasing metabolic capacities.

Mitochondrial DNA abundance in blood is associated with Alzheimer's disease- and dementia-risk.

The mitochondrial cascade hypothesis of Alzheimer's disease (AD) has been portrayed through molecular, cellular, and animal studies; however large epidemiological studies are lacking. This study aimed to explore the association of mitochondrial DNA copy number (mtDNAcn), a marker representative of mtDNA abundance per cell, with risk of incident all-cause dementia, AD, and vascular dementia diagnosis within 17 years and dementia-related blood biomarkers (P-tau181, GFAP, and NfL). Additionally, sex-stratified analyses were completed.

Activation of the MAPK network provides a survival advantage during the course of COVID-19-induced sepsis: a real-world evidence analysis of a multicenter COVID-19 Sepsis Cohort.

Purpose: There is evidence that lower activity of the RAF/MEK/ERK network is associated with positive outcomes in mild and moderate courses of COVID-19. The effect of this cascade in COVID-19 sepsis is still undetermined. Therefore, we tested the hypothesis that activity of the RAF/MEK/ERK network in COVID-19-induced sepsis is associated with an impact on 30-day survival.

Comparison of peripheral blood automated hematopoietic progenitor cell count and flow cytometric CD34+ cell count.

Background: Stem cell apheresis in the context of autologous stem cell transplantation requires an accurate cluster of differentiantion 34 (CD34) count determined by flow cytometry as the current gold standard. Since flow cytometry is a personnel and time-intensive diagnostic tool, automated stem cell enumeration may provide a promising alternative. Hence, this study aimed to compare automated hematopoietic progenitor enumeration carried out on a Sysmex XN-20 module compared with conventional flow cytometric measurements.

Observations from the Proteomics Bench.

Many challenges in proteomics result from the high-throughput nature of the experiments. This paper first presents pre-analytical problems, which still occur, although the call for standardization in omics has been ongoing for many years. This article also discusses aspects that affect bioinformatic analysis based on three sets of reference data measured with different orbitrap instruments.

Use of Multiple Machine Learning Approaches for Selecting Urothelial Cancer-Specific DNA Methylation Biomarkers in Urine.

Diagnosing urothelial cancer (UCa) via invasive cystoscopy is painful, specifically in men, and can cause infection and bleeding. Because the UCa risk is higher for male patients, urinary non-invasive UCa biomarkers are highly desired to stratify men for invasive cystoscopy. We previously identified multiple DNA methylation sites in urine samples that detect UCa with a high sensitivity and specificity in men.

WOMBAT-P: Benchmarking Label-Free Proteomics Data Analysis Workflows.

The inherent diversity of approaches in proteomics research has led to a wide range of software solutions for data analysis. These software solutions encompass multiple tools, each employing different algorithms for various tasks such as peptide-spectrum matching, protein inference, quantification, statistical analysis, and visualization. To enable an unbiased comparison of commonly used bottom-up label-free proteomics workflows, we introduce WOMBAT-P, a versatile platform designed for automated benchmarking and comparison.

Subjective cognitive complaints and blood biomarkers of neurodegenerative diseases: a longitudinal cohort study.

Background: Subjective cognitive complaints (SCC) have been mostly studied in the context of Alzheimer's disease in memory clinic settings. The potential of combining SCC with genetic information and blood biomarkers of neurodegenerative diseases for risk assessment of dementia and depression in the absence of dementia among community-dwelling older adults has so far not been explored.

Methods: Data were based on a population-based cohort of 6357 participants with a 17-year follow-up (ESTHER study) and a clinic-based cohort of 422 patients.

Assessment of MYC and TERT copy number variations in lung cancer using digital PCR.

Objective: Lung cancer is the second most frequent cancer type and the most common cause of cancer-related deaths worldwide. Alteration of gene copy numbers are associated with lung cancer and the determination of copy number variations (CNV) is appropriate for the discrimination between tumor and non-tumor tissue in lung cancer. As telomerase reverse transcriptase (TERT) and v-myc avian myelocytomatosis viral oncogene homolog (MYC) play a role in lung cancer the aims of this study were the verification of our recent results analyzing MYC CNV in tumor and non-tumor tissue of lung cancer patients using an independent study group and the assessment of TERT CNV as an additional marker.

Investigation of Inter- and Intra-Day Variability of Tear Fluid Regarding Flow Rate, Protein Concentration as well as Protein Composition.

Purpose: The purpose of this study was to present the determination of inter- and intra-day variations in tear flow rate, and tear fluid protein concentration, as well as protein composition regarding their impact for future biomarker studies.

Methods: Tear fluid was collected noninvasively from 18 healthy subjects by performing Schirmer tests at 4 different time points repetitive in a period of 2 days. The tear flow rate on the Schirmer test strips was measured.

The good or the bad: an overview of autoantibodies in traumatic spinal cord injury.

Infections remain the most common cause of death after traumatic spinal cord injury, likely due to a developing immune deficiency syndrome. This, together with a somewhat contradictory development of autoimmunity in many patients, are two major components of the maladaptive systemic immune response. Although the local non-resolving inflammation in the lesioned spinal cord may lead to an antibody formation against autoantigens of the injured spinal cord tissue, there are also natural (pre-existing) autoantibodies independent of the injury.

Changes in the Proteome of Platelets from Patients with Critical Progression of COVID-19.

Platelets, the smallest cells in human blood, known for their role in primary hemostasis, are also able to interact with pathogens and play a crucial role in the immune response. In severe coronavirus disease 2019 (COVID-19) cases, platelets become overactivated, resulting in the release of granules, exacerbating inflammation and contributing to the cytokine storm. This study aims to further elucidate the role of platelets in COVID-19 progression and to identify predictive biomarkers for disease outcomes.

Serum neurofilament light chain does not detect self-reported treatment-related fluctuations in chronic inflammatory demyelinating polyneuropathy.

Introduction: Serum neurofilament light chain (sNfL) is a marker for axonal degeneration. Patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) often report a fluctuation of symptoms throughout one treatment cycle with intravenous immunoglobulins (IVIG). The aim of this study was to determine whether sNfL is suitable to quantify patient-reported symptom fluctuations.

Alzheimer's polygenic risk scores, APOE, Alzheimer's disease risk, and dementia-related blood biomarker levels in a population-based cohort study followed over 17 years.

Background: In order to utilize polygenic risk scores (PRSs) for Alzheimer's disease (AD) in a meaningful way, influential factors (i.e. training set) and prediction across groups such as APOE e4 (APOE4) genotype as well as associations to dementia-related biomarkers should be explored.

ATP binding and ATP hydrolysis in full-length MsbA monitored via time-resolved Fourier transform infrared spectroscopy.

The essential ATPase MsbA is a lipid flippase that serves as a prototype for multi drug resistant ABC transporters. Its physiological function is the transport of lipopolisaccharides to build up the outer membranes of Gram-negative bacteria. Although several structural and biochemical studies of MsbA have been conducted previously, a detailed picture of the dynamic processes that link ATP hydrolysis to allocrit transport remains elusive.

A Clickable Photosystem I, Ferredoxin, and Ferredoxin NADP Reductase Fusion System for Light-Driven NADPH Regeneration.

Photosynthetic organisms like plants, algae, and cyanobacteria use light for the regeneration of dihydronicotinamide dinucleotide phosphate (NADPH). The process starts with the light-driven oxidation of water by photosystem II (PSII) and the released electrons are transferred via the cytochrome b f complex towards photosystem I (PSI). This membrane protein complex is responsible for the light-driven reduction of the soluble electron mediator ferredoxin (Fd), which passes the electrons to ferredoxin NADP reductase (FNR).

Lewy bodies, iron, inflammation and neuromelanin: pathological aspects underlying Parkinson's disease.

Since the description of some peculiar symptoms by James Parkinson in 1817, attempts have been made to define its cause or at least to enlighten the pathology of "Parkinson's disease (PD)." The vast majority of PD subtypes and most cases of sporadic PD share Lewy bodies (LBs) as a characteristic pathological hallmark. However, the processes underlying LBs generation and its causal triggers are still unknown.

Lesional Antibody Synthesis and Complement Deposition Associate With De Novo Antineuronal Antibody Synthesis After Spinal Cord Injury.

Background And Objectives: Spinal cord injury (SCI) disrupts the fine-balanced interaction between the CNS and immune system and can cause maladaptive aberrant immune responses. The study examines emerging autoantibody synthesis after SCI with binding to conformational spinal cord epitopes and surface peptides located on the intact neuronal membrane.

Methods: This is a prospective longitudinal cohort study conducted in acute care and inpatient rehabilitation centers in conjunction with a neuropathologic case-control study in archival tissue samples ranging from acute injury (baseline) to several months thereafter (follow-up).

Data-driven subtyping of Parkinson's disease: comparison of current methodologies and application to the Bochum PNS cohort.

Considerable efforts have been made to better describe and identify Parkinson's disease (PD) subtypes. Cluster analyses have been proposed as an unbiased development approach for PD subtypes that could facilitate their identification, tracking of progression, and evaluation of therapeutic responses. A data-driven clustering analysis was applied to a PD cohort of 114 subjects enrolled at St.