Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.

While significant advances have been made in understanding renal pathophysiology, less is known about the role of glycosphingolipid (GSL) metabolism in driving organ dysfunction. Here, we used a small molecule inhibitor of glucosylceramide synthase to modulate GSL levels in three mouse models of distinct renal pathologies: Alport syndrome (Col4a3 KO), polycystic kidney disease (Nek8), and steroid-resistant nephrotic syndrome (Nphs2 cKO). At the tissue level, we identified a core immune-enriched transcriptional signature that was shared across models and enriched in human polycystic kidney disease.

Phase Transition and Point Defects in the Ferroelectric Molecular Perovskite (MDABCO)(NH)I.

We measured the anelastic, dielectric and structural properties of the metal-free molecular perovskite (ABX3) (MDABCO)(NH4)I3, which has already been demonstrated to become ferroelectric below TC= 448 K. Both the dielectric permittivity measured in air on discs pressed from powder and the complex Young's modulus measured on resonating bars in a vacuum show that the material starts to deteriorate with a loss of mass just above TC, introducing defects and markedly lowering TC. The elastic modulus softens by 50% when heating through the initial TC, contrary to usual ferroelectrics, which are stiffer in the paraelectric phase.

Lead-Free Perovskite Thin Films with Tailored Pockels-Kerr Effects for Photonics.

Pockels and Kerr effects are linear and nonlinear electro-optical effects, respectively, used in many applications. The modulation of the refractive index is employed in different photonic circuits. However, the greatest challenge is in photonic elements for quantum computing at room temperature.

Anti-microRNA-21 Therapy on Top of ACE Inhibition Delays Renal Failure in Alport Syndrome Mouse Models.

Alport mice serve as an animal model for renal fibrosis. MicroRNA-21 (miR-21) expression has been shown to be increased in the kidneys of Alport syndrome patients. Here, we investigated the nephroprotective effects of Lademirsen anti-miR-21 therapy.

Structural Transitions and Stability of FAPbI and MAPbI: The Role of Interstitial Water.

We studied the influence of water on the structural stability and transformations of MAPI and FAPI by anelastic and dielectric spectroscopies under various temperature and H2O partial pressure protocols. Before discussing the new results in terms of interstitial water in MAPI and FAPI, the literature is briefly reviewed, in search of other studies and evidences on interstitial water in hybrid halide perovskites. In hydrated MAPI, the elastic anomaly between the cubic α and tetragonal β phases may be depressed by more than 50%, demonstrating that there are H2O molecules dispersed in the perovskite lattice in interstitial form, that hinder the long range tilting of the PbI6 octahedra.

Stability of Cubic FAPbI from X-ray Diffraction, Anelastic, and Dielectric Measurements.

Among the hybrid metal-organic perovskites for photovoltaic applications, FAPbI (FAPI) has the best performance regarding efficiency and the worst regarding stability, even though the reports on its stability are highly contradictory. In particular, since at room temperature the cubic α phase, black and with high photovoltaic efficiency, is metastable against the yellow hexagonal δ phase, it is believed that α-FAPI spontaneously transforms into δ-FAPI within a relatively short time. We performed X-ray diffraction and thermogravimetric measurements on loose powder of FAPI, and present the first complete dielectric and anelastic spectra of compacted FAPI samples under various conditions.

Probing the dielectric, piezoelectric and magnetic behavior of CoFeO/BNT-BT composite thin film fabricated by sol-gel and spin-coating methods.

We investigated in this paper a novel bilayer composite obtained by sol-gel and spin coating of the ferroelectric 0.92NaBiTiO-0.08BaTiO (abbreviated as BNT-BT) and ferromagnetic CoFeO phases, for miniature low-frequency magnetic sensors and piezoelectric sensors.

Competition between Polar and Antiferrodistortive Modes and Correlated Dynamics of the Methylammonium Molecules in MAPbI from Anelastic and Dielectric Measurements.

The mechanisms behind the exceptional photovoltaic properties of the metallorganic perovskites are still debated and include a ferroelectric (FE) state from the ordering of the electric dipoles of the organic molecules. We present the first anelastic (complex Young's modulus) and new dielectric measurements on CHNHPbI, which provide new insight into the reorientation dynamics of the organic molecules and the reason why they do not form a FE state. The permittivity is fitted within the tetragonal phase with an expression that includes the coupling between FE and octahedral tilt modes, indicating that the coupling is competitive and prevents FE ordering.

Combined use of Mössbauer spectroscopy, XPS, HRTEM, dielectric and anelastic spectroscopy for estimating incipient phase separation in lead titanate-based multiferroics.

The formation of separate phases in crystalline materials is promoted by doping with elements with different valences and ionic radii. Control of the formation of separate phases in multiferroics is extremely important for their magnetic, ferroelectric and elastic properties, which are relevant for multifunctional applications. The ordering of dopants and incipient phase separation were studied in lead titanate-based multiferroics with the formula (Pb0.

Impact of thickness variation on structural, dielectric and piezoelectric properties of (Ba,Ca)(Ti,Zr)O epitaxial thin films.

It is shown that the dielectric and piezoelectric properties of Ba(TiZr)O-x(BaCa)TiO (x = 0.45) (BCTZ 45) epitaxial thin films have a nontrivial dependence on film thickness. BCTZ 45 epitaxial films with different thicknesses (up to 400 nm) have been deposited on SrTiO by pulsed laser deposition and investigated by different combined techniques: conventional and off-axis X-ray diffraction, high resolution transmission electron microscopy and dielectric and piezoforce microscopy.

Lead-Free Piezoelectric (Ba,Ca)(Zr,Ti)O Thin Films for Biocompatible and Flexible Devices.

In this work, we report the synthesis of functional biocompatible piezoelectric (1 - x)Ba(TiZr)TiO-x(BaCa)TiO, x = 0.45 (BCZT45), thin films with high piezoelectric properties. Pulsed-laser-based techniques, classical pulsed-laser deposition and matrix-assisted pulsed-laser evaporation, were used to synthesize the BCZT45 thin films.

Joining Chemical Pressure and Epitaxial Strain to Yield Y-doped BiFeO3 Thin Films with High Dielectric Response.

BiFeO3 is one of the most promising multiferroic materials but undergoes two major drawbacks: low dielectric susceptibility and high dielectric loss. Here we report high in-plane dielectric permittivity (ε' ∼2500) and low dielectric loss (tan δ < 0.01) obtained on Bi0.

RNA-binding Protein Musashi Homologue 1 Regulates Kidney Fibrosis by Translational Inhibition of p21 and Numb mRNA.

RNA-binding proteins (RBPs) are recognized as key posttranscriptional regulators that not only modulate the spatiotemporal expression of genes during organism development but also regulate disease pathogenesis. Very limited information exists on the potential role of RBPs in modulating kidney fibrosis, which is a major hallmark of chronic kidney disease. Here, we report a novel mechanism in kidney fibrosis involving a RBP, Musashi homologue 1 (Msi1), which is expressed in tubular epithelial cells.

Application of small RNA sequencing to identify microRNAs in acute kidney injury and fibrosis.

Establishing a microRNA (miRNA) expression profile in affected tissues provides an important foundation for the discovery of miRNAs involved in the development or progression of pathologic conditions. We conducted small RNA sequencing to generate a temporal profile of miRNA expression in the kidneys using a mouse model of folic acid-induced (250mg/kgi.p.

High Permittivity (1 - x)Ba(Zr(0.2)Ti(0.8))O3 - x(Ba(0.7)Ca(0.3))TiO3 (x = 0.45) Epitaxial Thin Films with Nanoscale Phase Fluctuations.

Epitaxial (1 - x)Ba(Ti0.8Zr0.2)TiO3 - x(Ba0.

RNA Sequencing Identifies Novel Translational Biomarkers of Kidney Fibrosis.

CKD is the gradual, asymptomatic loss of kidney function, but current tests only identify CKD when significant loss has already happened. Several potential biomarkers of CKD have been reported, but none have been approved for preclinical or clinical use. Using RNA sequencing in a mouse model of folic acid-induced nephropathy, we identified ten genes that track kidney fibrosis development, the common pathologic finding in patients with CKD.

MicroRNA-155 deficient mice experience heightened kidney toxicity when dosed with cisplatin.

The development of nephrotoxicity limits the maximum achievable dosage and treatment intervals for cisplatin chemotherapy. Therefore, identifying mechanisms that regulate this toxicity could offer novel methods to optimize cisplatin delivery. MicroRNAs are capable of regulating many different genes, and can influence diverse cellular processes, including cell death and apoptosis.

Pharmacological and genetic depletion of fibrinogen protects from kidney fibrosis.

Fibrinogen (Fg) has been implicated in the pathogenesis of several fibrotic disorders by acting as a profibrotic ligand for a variety of cellular surface receptors and by modulating the provisional fibrin matrix formed after injury. We demonstrated increased renal Fg expression after unilateral ureteral obstruction and folic acid (FA) nephropathy in mice, respectively. Urinary Fg excretion was also increased in FA nephropathy.

Early murine polymicrobial sepsis predominantly causes renal injury.

Multiple organ failure in sepsis substantially increases mortality. This study examined if there was greater hepatic, pancreatic, splenic, or renal injury in mice that would die during sepsis induced by cecal ligation and puncture (CLP) compared with that of those that would survive. Mice were stratified into groups predicted to die (Die-P) or predicted to live (Live-P) in the first 5 days after CLP based on plasma interleukin 6 levels.

Cecal ligation and puncture-induced murine sepsis does not cause lung injury.

Objective: The cause of death in murine models of sepsis remains unclear. The primary purpose of this study was to determine if significant lung injury develops in mice predicted to die after cecal ligation and puncture-induced sepsis compared with those predicted to live.

Design: Prospective, laboratory controlled experiments.

Sepsis chronically in MARS: systemic cytokine responses are always mixed regardless of the outcome, magnitude, or phase of sepsis.

The paradigm of systemic inflammatory response syndrome-to-compensatory anti-inflammatory response syndrome transition implies that hyperinflammation triggers acute sepsis mortality, whereas hypoinflammation (release of anti-inflammatory cytokines) in late sepsis induces chronic deaths. However, the exact humoral inflammatory mechanisms attributable to sepsis outcomes remain elusive. In the first part of this study, we characterized the systemic dynamics of the chronic inflammation in dying (DIE) and surviving (SUR) mice suffering from cecal ligation and puncture sepsis (days 6-28).

Acute oral ethanol exposure triggers asthma in cockroach allergen-sensitized mice.

Asthma may be triggered by multiple mediators, including allergen-IgE cross-linking and non-IgE mechanisms. Several clinical studies have shown acute ethanol consumption exacerbates asthma, yet no animal model exists to study this process. We developed a model of ethanol-triggered asthma in allergen-sensitized mice to evaluate the mechanisms of ethanol inducing asthma-like responses.

Octahedral tilting, monoclinic phase and the phase diagram of PZT.

Anelastic and dielectric spectroscopy measurements on PbZr(1-x)Ti(x)O(3) (PZT) close to the morphotropic (MPB) and antiferroelectric boundaries provide new insight into some controversial aspects of its phase diagram. No evidence is found of a border separating monoclinic (M) from rhombohedral (R) phases, in agreement with recent structural studies supporting a coexistence of the two phases over a broad composition range x<0.5, with the fraction of M increasing toward the MPB.

Enhancing Nrf2 pathway by disruption of Keap1 in myeloid leukocytes protects against sepsis.

Rationale: Sepsis syndrome is characterized by inappropriate amplified systemic inflammatory response and bacteremia that promote multiorgan failure and mortality. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) regulates a pleiotropic cytoprotective defense program including antioxidants and protects against several inflammatory disorders by inhibiting oxidative tissue injuries. However, the role of enhanced Nrf2 activity in modulating innate immune responses to microbial infection and pathogenesis of sepsis is unclear.