See the power in kidney cells with ATP biosensor.

Yamamoto et al. developed an exciting technical advance to examine intracellular adenosine triphosphate levels with single-cell resolution in intact living kidney tissue, including in tubular and vascular segments that lie deep under the kidney surface. The work is a significant advance on prior in vivo biosensor studies, and it allows for mechanistic investigation of alterations in cell metabolism, kidney disease pathobiology, and the effects of drug treatments on energy sources in different kidney cell types.

Angiotensin II Directly Increases Endothelial Calcium and Nitric Oxide in Kidney and Brain Microvessels In Vivo With Reduced Efficacy in Hypertension.

Background: The vasoconstrictor effects of angiotensin II via type 1 angiotensin II receptors in vascular smooth muscle cells are well established, but the direct effects of angiotensin II on vascular endothelial cells (VECs) in vivo and the mechanisms how VECs may mitigate angiotensin II-mediated vasoconstriction are not fully understood. The present study aimed to explore the molecular mechanisms and pathophysiological relevance of the direct actions of angiotensin II on VECs in kidney and brain microvessels in vivo.

Methods And Results: Changes in VEC intracellular calcium ([Ca]) and nitric oxide (NO) production were visualized by intravital multiphoton microscopy of cadherin 5-Salsa6f mice or the endothelial uptake of NO-sensitive dye 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate, respectively.

Neuronally differentiated macula densa cells regulate tissue remodeling and regeneration in the kidney.

Tissue regeneration is limited in several organs, including the kidney, contributing to the high prevalence of kidney disease globally. However, evolutionary and physiological adaptive responses and the presence of renal progenitor cells suggest an existing remodeling capacity. This study uncovered endogenous tissue remodeling mechanisms in the kidney that were activated by the loss of body fluid and salt and regulated by a unique niche of a minority renal cell type called the macula densa (MD).

Physiological Mechanisms of Dietary Salt Sensing in the Brain, Kidney, and Gastrointestinal Tract.

Excess dietary salt (NaCl) intake is strongly correlated with cardiovascular disease and is a major contributing factor to the pathogenesis of hypertension. NaCl-sensitive hypertension is a multisystem disorder that involves renal dysfunction, vascular abnormalities, and neurogenically-mediated increases in peripheral resistance. Despite a major research focus on organ systems and these effector mechanisms causing NaCl-induced increases in arterial blood pressure, relatively less research has been directed at elucidating how NaCl is sensed by various tissues to elicit these downstream effects.

Grain Refiner Settling and Its Effect on the Melt Quality of Aluminum Casting Alloys.

Grain refiner particles, which are intended to induce the formation of fine equiaxed grain structure during the solidification of aluminum alloys, are prone to settling during the holding of the liquid metal, which phenomenon can affect not only the grain size but the spatial distribution of the double oxide films in the melt. In this study, the settling of AlTi inoculant particles, as well as its effects on melt quality and grain refinement, were studied. During the experiments, the Ti-concentration of a liquid Al-Si-Mg-Cu alloy was increased to 0.

The role of TRPC6 calcium channels and P2 purinergic receptors in podocyte mechanical and metabolic sensing.

Podocyte calcium (Ca2+) signaling plays important roles in the (patho)physiology of the glomerular filtration barrier. Overactivation of podocyte transient receptor potential canonical (TRPC) channels including TRPC6 and purinergic signaling via P2 receptors that are known mechanosensors can increase podocyte intracellular Ca2+ levels ([Ca2+]i) and cause cell injury, proteinuria and glomerular disease including in diabetes. However, important mechanistic details of the trigger and activation of these pathways in vivo in the intact glomerular environment are lacking.

Intravital imaging reveals glomerular capillary distension and endothelial and immune cell activation early in Alport syndrome.

Alport syndrome (AS) is a genetic disorder caused by mutations in type IV collagen that lead to defective glomerular basement membrane, glomerular filtration barrier (GFB) damage, and progressive chronic kidney disease. While the genetic basis of AS is well known, the molecular and cellular mechanistic details of disease pathogenesis have been elusive, hindering the development of mechanism-based therapies. Here, we performed intravital multiphoton imaging of the local kidney tissue microenvironment in a X-linked AS mouse model to directly visualize the major drivers of AS pathology.

New Endothelial Mechanisms in Glomerular (Patho)biology and Proteinuria Development Captured by Intravital Multiphoton Imaging.

In the past two decades, intravital imaging using multiphoton microscopy has provided numerous new visual and mechanistic insights into glomerular biology and disease processes including the function of glomerular endothelial cells (GEnC), podocytes, and the development of proteinuria. Although glomerular endothelial injury is known to precede podocyte damage in several renal diseases, the primary role of GEnCs in proteinuria development received much less attention compared to the vast field of podocyte pathobiology. Consequently, our knowledge of GEnC mechanisms in glomerular diseases is still emerging.

A new view of macula densa cell protein synthesis.

Macula densa (MD) cells, a chief sensory cell type in the nephron, are endowed with unique microanatomic features including a high density of protein synthetic organelles and secretory vesicles in basal cell processes ("maculapodia") that suggest a so far unknown high rate of MD protein synthesis. This study aimed to explore the rate and regulation of MD protein synthesis and their effects on glomerular function using novel transgenic mouse models, newly established fluorescence cell biology techniques, and intravital microscopy. Sox2-tdTomato kidney tissue sections and an -propargyl puromycin incorporation-based fluorescence imaging assay showed that MD cells have the highest level of protein synthesis within the kidney cortex followed by intercalated cells and podocytes.

The effect of sand quality on the bending strength and thermal distortion of chemically bonded sand cores.

The quality of chemically bonded sand cores used during the manufacturing process of cast components is highly dependent on the properties of the sand, which constitutes the refractory base media of the core. One of the main advantages of the application of different types of sands as molding aggregates that after casting, they can be reclaimed and can be used again during core shooting. The properties of the sand, however, could be remarkably changed during the casting and reclamation processes.

Serial intravital imaging captures dynamic and functional endothelial remodeling with single-cell resolution.

Endothelial cells are important in the maintenance of healthy blood vessels and in the development of vascular diseases. However, the origin and dynamics of endothelial precursors and remodeling at the single-cell level have been difficult to study in vivo owing to technical limitations. Therefore, we aimed to develop a direct visual approach to track the fate and function of single endothelial cells over several days and weeks in the same vascular bed in vivo using multiphoton microscopy (MPM) of transgenic Cdh5-Confetti mice and the kidney glomerulus as a model.

A new view of macula densa cell microanatomy.

Although macula densa (MD) cells are chief regulatory cells in the nephron with unique microanatomical features, they have been difficult to study in full detail due to their inaccessibility and limitations in earlier microscopy techniques. The present study used a new mouse model with a comprehensive imaging approach to visualize so far unexplored microanatomical features of MD cells, their regulation, and functional relevance. MD-GFP mice with conditional and partial induction of green fluorescent protein (GFP) expression, which specifically and intensely illuminated only single MD cells, were used with fluorescence microscopy of fixed tissue and live MD cells in vitro and in vivo with complementary electron microscopy of the rat, rabbit, and human kidney.

Essential role and therapeutic targeting of the glomerular endothelial glycocalyx in lupus nephritis.

Lupus nephritis (LN) is a major organ complication and cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). There is an unmet medical need for developing more efficient and specific, mechanism-based therapies, which depends on improved understanding of the underlying LN pathogenesis. Here we present direct visual evidence from high-power intravital imaging of the local kidney tissue microenvironment in mouse models showing that activated memory T cells originated in immune organs and the LN-specific robust accumulation of the glomerular endothelial glycocalyx played central roles in LN development.

Renomedullary Interstitial Cell Endothelin A Receptors Regulate BP and Renal Function.

Background: The physiologic role of renomedullary interstitial cells, which are uniquely and abundantly found in the renal inner medulla, is largely unknown. Endothelin A receptors regulate multiple aspects of renomedullary interstitial cell function .

Methods: To assess the effect of targeting renomedullary interstitial cell endothelin A receptors , we generated a mouse knockout model with inducible disruption of renomedullary interstitial cell endothelin A receptors at 3 months of age.

Novel fluorescence techniques to quantitate renal cell biology.

Fluorescence microscopy techniques are powerful tools to study tissue dynamics, cellular function and biology both in vivo and in vitro. These tools allow for functional assessment and quantification along with qualitative analysis, thus providing a comprehensive understanding of various cellular processes under normal physiological and disease conditions. The main focus of this chapter is the recently developed method of serial intravital multiphoton microscopy that has helped shed light on the dynamic alterations of the spatial distribution and fate of single renal cells or cell populations and their migration patterns in the same tissue region over several days in response to various stimuli within the living kidney.

The macula densa prorenin receptor is essential in renin release and blood pressure control.

The prorenin receptor (PRR) was originally proposed to be a member of the renin-angiotensin system (RAS); however, recent work questioned their association. The present paper describes a functional link between the PRR and RAS in the renal juxtaglomerular apparatus (JGA), a classic anatomical site of the RAS. PRR expression was found in the sensory cells of the JGA, the macula densa (MD), and immunohistochemistry-localized PRR to the MD basolateral cell membrane in mouse, rat, and human kidneys.

Combined use of electron microscopy and intravital imaging captures morphological and functional features of podocyte detachment.

The development of podocyte injury and albuminuria in various glomerular pathologies is still incompletely understood due to technical limitations in studying the glomerular filtration barrier (GFB) in real-time. We aimed to directly visualize the early morphological and functional changes of the GFB during the development of focal segmental glomerulosclerosis (FSGS) using a combination of transmission electron microscopy (TEM) and in vivo multiphoton microscopy (MPM) in the rat puromycin aminonucleoside (PAN) model. We hypothesized that this combined TEM + MPM experimental approach would provide a major technical improvement that would benefit our mechanistic understanding of podocyte detachment.

ORAI1 Activates Proliferation of Lymphatic Endothelial Cells in Response to Laminar Flow Through Krüppel-Like Factors 2 and 4.

Rationale: Lymphatic vessels function to drain interstitial fluid from a variety of tissues. Although shear stress generated by fluid flow is known to trigger lymphatic expansion and remodeling, the molecular basis underlying flow-induced lymphatic growth is unknown.

Objective: We aimed to gain a better understanding of the mechanism by which laminar shear stress activates lymphatic proliferation.

Night shift work and stomach cancer risk in the MCC-Spain study.

Objectives: Night shift work has been classified as a probable human carcinogen by the International Agency for Research on Cancer, based on experimental studies and limited evidence on human breast cancer risk. Evidence at other cancer sites is scarce. We evaluated the association between night shift work and stomach cancer risk in a population-based case-control study.

[Utility of B-type natriuretic peptide in children].

Unlabelled: Serum brain natriuretic peptide (BNP) has been reported to indicate ventricular dysfunction, however, in children it has not been studied yet in our country.

Purpose: 157 BNP tests were performed in 107 children, on the one hand, to evaluate its clinical value, to assess LV or systemic RV function in patients with transposition of great arteries after Senning operation, on the other hand, to prove the relation between BNP, MRI and echocardiographic ventricular function parameters. PATIENTS' AGE: 4 months-20 years, mean 12.

[Quantification of right and left ventricular function with magnetic resonance imaging after Senning operation for complete transposition of the great arteries].

Introduction: The different non-invasive examinations do not result in unambigous results about the long-term determination of right ventricular function providing systemic circulation in children with transposition of the great arteries operated with Senning procedure.

Aim: The goal of study was to determine the application of MRI for the observation of right and left ventricular morphology and function, for the recognition of the progression of the disease, and for the necessity of reoperation.

Methods: The authors have observed the morphology and function of the right and left ventricule by ECG triggered short axis MR pictures.