Autoantibodies Targeting Nephrin in Podocytopathies.

Background: Minimal change disease and primary focal segmental glomerulosclerosis in adults, along with idiopathic nephrotic syndrome in children, are immune-mediated podocytopathies that lead to nephrotic syndrome. Autoantibodies targeting nephrin have been found in patients with minimal change disease, but their clinical and pathophysiological roles are unclear.

Methods: We conducted a multicenter study to analyze antinephrin autoantibodies in adults with glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, antineutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis, as well as in children with idiopathic nephrotic syndrome and in controls.

Metabolic Communication by SGLT2 Inhibition.

Background: SGLT2 (sodium-glucose cotransporter 2) inhibitors (SGLT2i) can protect the kidneys and heart, but the underlying mechanism remains poorly understood.

Methods: To gain insights on primary effects of SGLT2i that are not confounded by pathophysiologic processes or are secondary to improvement by SGLT2i, we performed an in-depth proteomics, phosphoproteomics, and metabolomics analysis by integrating signatures from multiple metabolic organs and body fluids after 1 week of SGLT2i treatment of nondiabetic as well as diabetic mice with early and uncomplicated hyperglycemia.

Results: Kidneys of nondiabetic mice reacted most strongly to SGLT2i in terms of proteomic reconfiguration, including evidence for less early proximal tubule glucotoxicity and a broad downregulation of the apical uptake transport machinery (including sodium, glucose, urate, purine bases, and amino acids), supported by mouse and human SGLT2 interactome studies.

An integrated organoid omics map extends modeling potential of kidney disease.

Kidney organoids are a promising model to study kidney disease, but their use is constrained by limited knowledge of their functional protein expression profile. Here, we define the organoid proteome and transcriptome trajectories over culture duration and upon exposure to TNFα, a cytokine stressor. Older organoids increase deposition of extracellular matrix but decrease expression of glomerular proteins.

Comparison of SPEED, S-Trap, and In-Solution-Based Sample Preparation Methods for Mass Spectrometry in Kidney Tissue and Plasma.

Mass spectrometry is a powerful technique for investigating renal pathologies and identifying biomarkers, and efficient protein extraction from kidney tissue is essential for bottom-up proteomic analyses. Detergent-based strategies aid cell lysis and protein solubilization but are poorly compatible with downstream protein digestion and liquid chromatography-coupled mass spectrometry, requiring additional purification and buffer-exchange steps. This study compares two well-established detergent-based methods for protein extraction (in-solution sodium deoxycholate (SDC); suspension trapping (S-Trap)) with the recently developed sample preparation by easy extraction and digestion (SPEED) method, which uses strong acid for denaturation.

Pathogenicity of Human Anti-PLA 2 R1 Antibodies in Minipigs: A Pilot Study.

Significance Statement: Membranous nephropathy (MN) is an autoimmune kidney disease characterized by immune deposits in the glomerular basement membrane. Circulating anti-phospholipase A 2 receptor 1 (PLA 2 R1) antibodies are detectable in 70%-80% of patients with MN, but experimental evidence of pathogenicity has been lacking. This study demonstrates the pathogenicity of human anti-PLA 2 R1 antibodies in minipigs, a model for MN that intrinsically expresses PLA 2 R1 on podocytes.

Male guanine-rich RNA sequence binding factor 1 knockout mice (Grsf1) gain less body weight during adolescence and adulthood.

The guanine-rich RNA sequence binding factor 1 (GRSF1) is an RNA-binding protein of the heterogenous nuclear ribonucleoprotein H/F (hnRNP H/F) family that binds to guanine-rich RNA sequences forming G-quadruplex structures. In mice and humans there are single copy GRSF1 genes, but multiple transcripts have been reported. GRSF1 has been implicated in a number of physiological processes (e.

Netrin G1 Is a Novel Target Antigen in Primary Membranous Nephropathy.

Background: Primary membranous nephropathy (MN) is caused by circulating autoantibodies binding to antigens on the podocyte surface. PLAR1 is the main target antigen in 70%-80% of cases, but the pathogenesis is unresolved in 10%-15% of patients.

Methods: We used native western blotting to identify IgG4 autoantibodies, which bind an antigen endogenously expressed on podocyte membranes, in the serum of the index patient with MN.

Circulating cardiac biomarkers improve risk stratification for incident cardiovascular disease in community dwelling populations.

Background: Plasma cardiac markers may assist in prediction of incident cardiovascular disease.

Methods: The incremental value of cardiac Troponins (T and I) and NT-proBNP added to risk factors in the PREDICT score for incident cardiovascular disease (CVD) in primary care, was assessed in 4102 asymptomatic participants in a randomised controlled trial of Vitamin D (ViDA). Findings were corroborated in 2528 participants in a separate community-based observational registry of CVD-free volunteers (HVOLS).

Consensus draft of the native mouse podocyte-ome.

The podocyte is a key cell in maintaining renal filtration barrier integrity. Several recent studies have analyzed the genome and transcriptome in the podocyte at deep resolution. This avenue of "podocyte-ome" research was enabled by a variety of techniques, including ) single-cell transcriptomics, ) FACS with and without genetically encoded markers, and ) deep proteomics.

The calcium-sensing receptor stabilizes podocyte function in proteinuric humans and mice.

Calcimimetic agents allosterically increase the calcium ion sensitivity of the calcium-sensing receptor (CaSR), which is expressed in the tubular system and to a lesser extent in podocytes. Activation of this receptor can reduce glomerular proteinuria and structural damage in proteinuric animal models. However, the precise role of the podocyte CaSR remains unclear.

Potentials and barriers of using digital tools for collecting daily measurements in multiple sclerosis research.

Objective: Digital tools offer new ways of collecting outcome data in intervention research. Little is known about the potentials and barriers of using such tools for outcome measurement in multiple sclerosis trials. This study aimed to examine reporting adherence and barriers experienced by people with multiple sclerosis in an intervention study using three different digital tools for outcome measurement.

[Plasmatic and urinary pyroglutamic acid measurement by capillary zone electrophoresis in chronic poisoning with acetaminophen in children].

An increase of pyroglutamic acid, or 5-oxoproline plasmatic concentration was reported in metabolic acidosis observed after chronic intake of some drugs, as acetaminophen. We developed a simple, fast and reproducible method by capillary zone electrophoresis using a commercial Anion Analysis Kit to quantify pyroglutamic acid, in plasma after acetonitrile precipitation, and after simple dilution in urines. Fumaric acid was used as internal standard in both.

Reaction dynamics and residue identification of haemoglobin modification by acrolein, a lipid-peroxidation by-product.

Background: Lipid hydroperoxides decompose to reactive aldehydes, such as acrolein. Measurement of oxidative stress markers in the clinic could improve risk stratification for patients.

Methods: To aid the development of diagnostic oxidative stress markers, we defined the acrolein modifications of haemoglobin using mass spectrometry.

Notch3-Dependent Effects on Adult Neurogenesis and Hippocampus-Dependent Learning in a Modified Transgenic Model of CADASIL.

We and others have reported that Notch3 is a regulator of adult hippocampal neurogenesis. (CADASIL), the most common genetic form of vascular dementia, is caused by mutations in . The present study intended to investigate whether there is a correlation between altered adult hippocampal neurogenesis and spatial memory performance in CADASIL transgenic mice.

Proteolysis and inflammation of the kidney glomerulus.

Proteases play a central role in regulating renal pathophysiology and are increasingly evaluated as actionable drug targets. Here, we review the role of proteolytic systems in inflammatory kidney disease. Inflammatory kidney diseases are associated with broad dysregulations of extracellular and intracellular proteolysis.

Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals.

To identify circulating proteins predictive of acute cardiovascular disease events in the general population, we performed a proteomic screen in plasma from asymptomatic individuals. A "Discovery cohort" of 25 individuals who subsequently incurred a cardiovascular event within 3 years (median age = 70 years, 80% male) was matched to 25 controls remaining event-free for > 5 years (median age = 72 years, 80% male). Plasma proteins were assessed by data independent acquisition mass spectrometry (DIA-MS).

Prolyl Oligopeptidase From : Biochemical Characterization and Involvement in Macrophage Infection.

is a flagellated protozoan and one of the main causative agents of visceral leishmaniasis. This disease usually affects the human reticuloendothelial system, can cause death and available therapies may lead to serious side effects. Since it is a neglected tropical disease, the incentives for the development of new drugs are insufficient.

Virus study for continuous low pH viral inactivation inside a coiled flow inverter.

Continuous processing for the production of monoclonal antibodies (mAb) gains more and more importance. Several solutions exist for all the necessary production steps, leading to the possibility to build fully continuous processes. Low pH viral inactivation is a part of the standard platform process for mAb production.

Superresolution Microscopy of Single Rare-Earth Emitters in YAG and H3 Centers in Diamond.

We demonstrate superresolution imaging of single rare-earth emitting centers, namely, trivalent cerium, in yttrium aluminum garnet crystals by means of stimulated emission depletion (STED) microscopy. The achieved all-optical resolution is ≈50  nm. Similar results were obtained on H3 color centers in diamond.

Biomarkers of Traumatic Brain Injury: Temporal Changes in Body Fluids.

Traumatic brain injuries (TBIs) are caused by a hit to the head or a sudden acceleration/deceleration movement of the head. Mild TBIs (mTBIs) and concussions are difficult to diagnose. Imaging techniques often fail to find alterations in the brain, and computed tomography exposes the patient to radiation.