Complement C5a Induces Renal Injury in Diabetic Kidney Disease by Disrupting Mitochondrial Metabolic Agility.

The sequelae of diabetes include microvascular complications such as diabetic kidney disease (DKD), which involves glucose-mediated renal injury associated with a disruption in mitochondrial metabolic agility, inflammation, and fibrosis. We explored the role of the innate immune complement component C5a, a potent mediator of inflammation, in the pathogenesis of DKD in clinical and experimental diabetes. Marked systemic elevation in C5a activity was demonstrated in patients with diabetes; conventional renoprotective agents did not therapeutically target this elevation.

PAM forms an atypical SCF ubiquitin ligase complex that ubiquitinates and degrades NMNAT2.

PHR (AM/ighwire/PM-1) proteins are conserved RING E3 ubiquitin ligases that function in developmental processes, such as axon termination and synapse formation, as well as axon degeneration. At present, our understanding of how PHR proteins form ubiquitin ligase complexes remains incomplete. Although genetic studies indicate NMNAT2 is an important mediator of PHR protein function in axon degeneration, it remains unknown how PHR proteins inhibit NMNAT2.

Relationship between urinary sodium-to-potassium ratio and ambulatory blood pressure in patients with diabetes mellitus.

Previous studies investigating the relationship between sodium intake and blood pressure have mostly relied on dietary recall and clinic blood pressure measurement. In this cross-sectional study, we aimed to investigate the relationship between 24 hour urinary sodium and potassium excretion, and their ratio, with 24 hour ambulatory blood pressure parameters including nocturnal blood pressure dipping in patients with type 1 and 2 diabetes. We report that in 116 patients with diabetes, systolic blood pressure was significantly predicted by the time of day, age, the interaction between dipping status with time, and 24 hour urinary sodium-to-potassium ratio (R  = 0.

Correction: Using Automated HbA1c Testing to Detect Diabetes Mellitus in Orthopedic Inpatients and Its Effect on Outcomes.

[This corrects the article DOI: 10.1371/journal.pone.

Using Automated HbA1c Testing to Detect Diabetes Mellitus in Orthopedic Inpatients and Its Effect on Outcomes.

Aims: The prevalence of diabetes is rising, and people with diabetes have higher rates of musculoskeletal-related comorbidities. HbA1c testing is a superior option for diabetes diagnosis in the inpatient setting. This study aimed to (i) demonstrate the feasibility of routine HbA1c testing to detect the presence of diabetes mellitus, (ii) to determine the prevalence of diabetes in orthopedic inpatients and (iii) to assess the association between diabetes and hospital outcomes and post-operative complications in orthopedic inpatients.

Defining Minimal Binding Regions in Regulator of Presynaptic Morphology 1 (RPM-1) Using Neurons Reveals Differential Signaling Complexes.

The intracellular signaling protein regulator of presynaptic morphology 1 (RPM-1) is a conserved regulator of synapse formation and axon termination in RPM-1 functions in a ubiquitin ligase complex with the F-box protein FSN-1 and functions through the microtubule binding protein RAE-1. Using a structure-function approach and positive selection for transgenic , we explored the biochemical relationship between RPM-1, FSN-1, and RAE-1. This led to the identification of two new domains in RPM-1 that are sufficient for binding to FSN-1, called FSN-1 binding domain 2 (FBD2) and FBD3.

Denosumab-associated hypocalcaemia: incidence, severity and patient characteristics in a tertiary hospital setting.

Purpose: Denosumab-associated hypocalcaemia (DAH) has been reported in patients with osteoporosis or metastatic bone disease and is associated with stages 4 and 5 chronic kidney disease (CKD, estimated glomerular filtration rate <30 mL/min/1.73m ). Other risk factors for hypocalcaemia have not been fully elucidated.

Inpatient HbA1c testing: a prospective observational study.

Objective: To use admission inpatient glycated hemoglobin (HbA1c) testing to help investigate the prevalence of unrecognized diabetes, the cumulative prevalence of unrecognized and known diabetes, and the prevalence of poor glycemic control in both. Moreover, we aimed to determine the 6-month outcomes for these patients. Finally, we aimed to assess the independent association of diabetes with these outcomes.

Neuronal development in Caenorhabditis elegans is regulated by inhibition of an MLK MAP kinase pathway.

We show that loss-of-function mutations in kinases of the MLK-1 pathway (mlk-1, mek-1, and kgb-1/jnk) function cell-autonomously in neurons to suppress defects in synapse formation and axon termination caused by rpm-1 loss of function. Our genetic analysis also suggests that the phosphatase PPM-1, like RPM-1, is a potential inhibitor of kinases in the MLK-1 pathway.

Identification of a peptide inhibitor of the RPM-1 · FSN-1 ubiquitin ligase complex.

The Pam/Highwire/RPM-1 (PHR) proteins include: Caenorhabditis elegans RPM-1 (Regulator of Presynaptic Morphology 1), Drosophila Highwire, and murine Phr1. These important regulators of neuronal development function in synapse formation, axon guidance, and axon termination. In mature neurons the PHR proteins also regulate axon degeneration and regeneration.

RPM-1 uses both ubiquitin ligase and phosphatase-based mechanisms to regulate DLK-1 during neuronal development.

The Pam/Highwire/RPM-1 (PHR) proteins are key regulators of neuronal development that function in axon extension and guidance, termination of axon outgrowth, and synapse formation. Outside of development, the PHR proteins also regulate axon regeneration and Wallerian degeneration. The PHR proteins function in part by acting as ubiquitin ligases that degrade the Dual Leucine zipper-bearing Kinase (DLK).

Renal structure in normoalbuminuric and albuminuric patients with type 2 diabetes and impaired renal function.

Objective: The structural basis of normoalbuminuric renal insufficiency in patients with type 2 diabetes remains to be elucidated. We compared renal biopsy findings in patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) and measured GFR of <60 mL/min/1.73 m2, associated with either normo-, micro-, or macroalbuminuria.

RAE-1, a novel PHR binding protein, is required for axon termination and synapse formation in Caenorhabditis elegans.

Previous studies in Caenorhabditis elegans showed that RPM-1 (Regulator of Presynaptic Morphology-1) regulates axon termination and synapse formation. To understand the mechanism of how rpm-1 functions, we have used mass spectrometry to identify RPM-1 binding proteins, and have identified RAE-1 (RNA Export protein-1) as an evolutionarily conserved binding partner. We define a RAE-1 binding region in RPM-1, and show that this binding interaction is conserved and also occurs between Rae1 and the human ortholog of RPM-1 called Pam (protein associated with Myc).

Less fat reduction per unit weight loss in type 2 diabetic compared with nondiabetic obese individuals completing a very-low-calorie diet program.

The objective was to compare weight loss and change in body composition in obese subjects with and without type 2 diabetes mellitus during a very-low-calorie diet (VLCD) program. Seventy weight-matched subjects with diabetes or normal fasting glucose (controls) participated in a 24-week VLCD study. Primary end points were changes in anthropometry, body composition, and fasting plasma insulin and β-hydroxybutyrate concentrations.

PPM-1, a PP2Cα/β phosphatase, regulates axon termination and synapse formation in Caenorhabditis elegans.

The PHR (Pam/Highwire/RPM-1) proteins are evolutionarily conserved ubiquitin ligases that regulate axon guidance and synapse formation in Caenorhabditis elegans, Drosophila, zebrafish, and mice. In C. elegans, RPM-1 (Regulator of Presynaptic Morphology-1) functions in synapse formation, axon guidance, axon termination, and postsynaptic GLR-1 trafficking.

Modulation of the cellular expression of circulating advanced glycation end-product receptors in type 2 diabetic nephropathy.

Background: Advanced glycation end-products (AGEs) and their receptors are prominent contributors to diabetic kidney disease.

Methods: Flow cytometry was used to measure the predictive capacity for kidney impairment of the AGE receptors RAGE, AGE-R1, and AGE-R3 on peripheral blood mononuclear cells (PBMCs) in experimental models of type 2 diabetes (T2DM) fed varied AGE containing diets and in obese type 2 diabetic and control human subjects.

Results: Diets high in AGE content fed to diabetic mice decreased cell surface RAGE on PBMCs and in type 2 diabetic patients with renal impairment (RI).

Outcomes for general medical inpatients with diabetes mellitus and new hyperglycaemia.

Objectives: To investigate the relationship between admission glycaemic status and inpatient mortality in patients with and without pre-existing diabetes.

Design: Prospective observational cohort study.

Setting: A general medical ward in an Australian tertiary referral hospital.