Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury

OBJECTIVES: Transient receptor potential vanilloid 1 (TRPV1) -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of renal function under pathophysiological conditions. Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). However, it is unknown whether inhibition of these channels is detrimental in AKI or not. We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist), capsazepine (TRPV1 antagonist) and using Trpv1-/- mice. METHODS AND RESULTS: Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion. Mice were pretreated with capsaicin (0.3 mg/kg body weight) or capsazepine (50 mg/kg body weight). Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL) abundance and Ly-6B.2 positive polymorphonuclear inflammatory cells in injured kidneys. Neither capsazepine nor deficiency of TRPV1 did deteriorate renal function or histology after AKI. Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE) or epoxyeicosatrienoic acids (EETs) are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI. CONCLUSIONS: Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli

Renal fibrosis, immune cell infiltration and changes of TRPC channel expression after unilateral ureteral obstruction in Trpc6-/- mice

Background/Aims: The transient receptor potential cation channel subfamily C member 6 (TRPC6) is a Ca-permeable nonselective cation channel and has received recent attention because of its capability to promote chronic kidney disease (CKD). The aims of this study were (i) to examine whether deletion of TRPC6 impacts on renal fibrosis and inflammatory cell infiltration in an early CKD model of unilateral ureter obstruction (UUO) in mice; and (ii) whether TRPC6-deficiency as well as UUO affect the regulation of TRPC expression in murine kidneys. Methods: Wild-type (WT), Trpc6-knockout (Trpc6) and New Zealand obese (NZO) mice underwent sham operation or unilateral ureteral obstruction (UUO). The kidneys were harvested 7 days after surgery. We examined renal fibrosis and inflammatory cell infiltration by histological and immunohistochemical staining. The mRNA expression of TRPC members and markers of fibrosis and inflammation in kidney were assessed by using real-time quantitative reverse transcription PCR. Results: Histological and immunohistochemical analyses revealed less inflammatory cell infiltration (F4/80 and CD3) in UUO kidneys of Trpc6 mice compared to UUO kidneys of WT mice as well as less fibrosis. Genomic deletion of TRPC6 also affected the expression of pro-fibrotic genes in UUO Trpc6 kidneys compared to UUO WT kidneys while the expression of pro-inflammatory genes did not differ. UUO caused marked up-regulation of Trpc6 and down-regulation of Trpc1 mRNA in kidneys of WT and NZO mice. Trpc3 mRNA expression was significantly elevated in kidneys of Trpc6 mice underwent UUO while the levels did not change in kidneys of neither WT nor in NZO mice underwent UUO. Conclusion: TRPC6 contributes to renal fibrosis and immune cell infiltration in the UUO mouse model. Therefore, inhibition of TRPC6 emerges as a promising novel therapeutic strategy for treatment of chronic kidney failure in chronic obstructive nephropathy. However, confounding genomic and non-genomic effects of other TRPC channels should be taken into consideration to fully comprehend the renoprotective potential of targeting TRPC6 therapeutically under chronic kidney damaging conditions

Isolation of Radial Glia-Like Neural Stem Cells from Fetal and Adult Mouse Forebrain via Selective Adhesion to a Novel Adhesive Peptide-Conjugate

Preferential adhesion of neural stem cells to surfaces covered with a novel synthetic adhesive polypeptide (AK-cyclo[RGDfC]) provided a unique, rapid procedure for isolating radial glia-like cells from both fetal and adult rodent brain. Radial glia-like (RGl) neural stem/progenitor cells grew readily on the peptide-covered surfaces under serum-free culture conditions in the presence of EGF as the only growth factor supplement. Proliferating cells derived either from fetal (E 14.5) forebrain or from different regions of the adult brain maintained several radial glia-specific features including nestin, RC2 immunoreactivity and Pax6, Sox2, Blbp, Glast gene expression. Proliferating RGl cells were obtained also from non-neurogenic zones including the parenchyma of the adult cerebral cortex and dorsal midbrain. Continuous proliferation allowed isolating one-cell derived clones of radial glia-like cells. All clones generated neurons, astrocytes and oligodendrocytes under appropriate inducing conditions. Electrophysiological characterization indicated that passive conductance with large delayed rectifying potassium current might be a uniform feature of non-induced radial glia-like cells. Upon induction, all clones gave rise to GABAergic neurons. Significant differences were found, however, among the clones in the generation of glutamatergic an

Temporal characteristics of speech: The effect of age and speech style

Aging affects temporal characteristics of speech. It is still a question how these changes occur in different speech styles which require various cognitive skills. In this paper speech rate, articulation rate, and pauses of 20 young and 20 old speakers are analyzed in four speech tyles: spontaneous narrative, narrative recalls, a three-participant conversation, and reading aloud. Results show that age has a significant effect only on speech rate, articulation rate, and frequency of pauses. Speech style has a higher effect on temporal parameters than speakers’ age

Spinel ferrite nanocrystals embedded inside ZnO: magnetic, electronic and magneto-transport properties

In this paper we show that spinel ferrite nanocrystals (NiFe2O4, and CoFe2O4) can be texturally embedded inside a ZnO matrix by ion implantation and post-annealing. The two kinds of ferrites show different magnetic properties, e.g. coercivity and magnetization. Anomalous Hall effect and positive magnetoresistance have been observed. Our study suggests a ferrimagnet/semiconductor hybrid system for potential applications in magneto-electronics. This hybrid system can be tuned by selecting different transition metal ions (from Mn to Zn) to obtain various magnetic and electronic properties.Comment: 12 pages, 14 figs. accepted for publication at PR

Thermal QCD in a non-uniform magnetic background

Off-central heavy-ion collisions are known to feature magnetic fields with magnitudes and characteristic gradients corresponding to the scale of the strong interactions. In this work, we employ equilibrium lattice simulations of the underlying theory, QCD, involving similar inhomogeneous magnetic field profiles to achieve a better understanding of this system. We simulate three flavors of dynamical staggered quarks with physical masses at a range of magnetic fields and temperatures, and extrapolate the results to the continuum limit. Analyzing the impact of the field on the quark condensate and the Polyakov loop, we find non-trivial spatial features that render the QCD medium qualitatively different as in the homogeneous setup, especially at temperatures around the transition. In addition, we construct leading-order chiral perturbation theory for the inhomogeneous background and compare its prediction to our lattice results at low temperature. Our findings will be useful to benchmark effective theories and low-energy models of QCD for a better description of peripheral heavy-ion collisions.Comment: 24 pages, 15 figure

Effects of climate variation on bird escape distances modulate community responses to global change

Warm thanks to Jacqui Sykoff for substantially improving the readability of former versions of the manuscript. GM was supported by the Hungarian Ministry for Innovation and Technology within the framework of the Thematic Excellence Programme 2020 (TKP2020-IKA-12, TKP2020-NKA-16).. KT was supported by institutional research funding IUT (34-8) of the Estonian Ministry of Education and Research. This paper is a contribution to the project URBILAND (PID2019-107423GA-I00/SRA 1013039/501100011033), funded by the Spanish Research Agency.Climate and land use are rapidly changing environmental conditions. Behavioral responses to such global perturbations can be used to incorporate interspecific interactions into predictive models of population responses to global change. Flight initiation distance (FID) reflects antipredator behaviour defined as the distance at which an individual takes flight when approached by a human, under standardized conditions. This behavioural trait results from a balance between disturbance, predation risk, food availability and physiological needs, and it is related to geographical range and population trends in European birds. Using 32,145 records of flight initiation distances for 229 bird species during 2006-2019 in 24 European localities, we show that FIDs decreased with increasing temperature and precipitation, as expected if foraging success decreased under warm and humid conditions. Trends were further altered by latitude, urbanisation and body mass, as expected if climate effects on FIDs were mediated by food abundance and need, differing according to position in food webs, supporting foraging models. This provides evidence for a role of behavioural responses within food webs on how bird populations and communities are affected by global change.Hungarian Ministry for Innovation and Technology TKP2020-IKA-12 TKP2020-NKA-16Ministry of Education and Research, Estonia 34-8Spanish Research Agency PID2019-107423GA-I00/SRA 1013039/50110001103