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

Methodological Investigations on a Neuropteroidea Community

The same Neuropteroidea community was collected and studied in Hungary in the years 1991 and 1992 by using different trapping techniques: a) Malaise trap, b) suction trap, c) yellow pan trap and d) light trap. The studies aimed to compare the different sampling methods for individual species, families and for the whole Neuropteroidea community. In case the whole Neuropteroidea community the trapped individual numbers collected by the suction trap surpassed all other trap types. Relatively high numbers of Neuropteroidea could be collected both by light trap and Malaise traps. The yellow pan traps did not succeed in catching large enough samples neither from point of view of sample size nor from species richness. According to the number of species collected there were not discovered any big difference between the catches of suction trap, Malaise traps and light trap. By evaluating according to families it was stated that in case of the family Raphidiidae the Malaise trap yielded larger and more diverse samples than any other methods; however by increasing the number of yellow pan traps it is possible to augment the number of caught individuals. The suction traps were found very satisfactory in collecting members of the family Coniopterygidae. For the members of the families Hemerobiidae and Chrysopidae both the suction traps and light traps were found effective, although suction traps were more successful in collecting Chrysopidae species. Similarly, by evaluating the data according to individual species it was found that the Malaise traps tended to “under-represent” species belonging to Hemerobius humulinus, Hemerobius Lutescens, Chrysopa pallens and the ones belonging to Chrysoperla carnea complex compared to the suction trap. The opposing situation was perceived with Micromus lanosus and Chrysopa perla. Similarly – compared to suction trap – the light trap significantly “under-represented” the species Hemerobius humulinus, Hemerobius lutescens, Chrysopa pallens, Chrysoperla carnea and Dichochrysa prasina and “over-represented” Micromus angulatus, Sympherobius pygmaeus and Chrysopa phyllochroma. The diversity of Neuropteroidea collected by Malaise trap and light trap surpassed significantly the one of suction trap and yellow pan traps. The assemblages collected by different sampling methods showed some overlapping, but differed in their characters

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

Study of Neuropteroidea (Raphidioptera, Neuroptera) Communities by Using Malaise Traps in an Untreated Orchard and its Environment

Neuropteroidea communities were studied near Budapest (Nagykovácsi) in an abandoned, mixed orchard and its neighbouring environment: a shrub community without a closed canopy; a shrub level of the canopied oak forest by using Malaise traps. In the open shrub verge of the orchard larger, and in the oak forest more diverse Neuropteroidea community developed than in the other investigated habitats. The Neuropteroidea communities studied did not show stable compositions in the investigated habitats and years. By studying the linkage conditions of different species to different habitats, it was established that Hypochrysa elegans was strongly bound to the shrub level of the closed oak forest. Besides that, both in the shrub level and in the open forest edge, the species Micromus lanosus, Micromus angulatus, Hemerobius micans, Hemerobius lutescens and Hemerobius humulinus were found with higher density. The species Dichrostigma flavipes, Chrysopa formosa, Chrysopa perla, Xanthostigma xanthostigma, Chrysoperla carnea and Dichochrysa prasina occurred in all three habitats, thus they have to be regarded as habitat generalists. By passing beyond these tendencies Dichrostigma flavipes, Chrysopa formosa and Chrysopa perla seemed to be more attached to the shrubby edge

Methyl (Z)-2-chloro-3-(2-methoxy­carbonyl­phen­yl)prop-2-enoate

In the title compound, C12H11ClO4, the propenoate C=C bond is in the Z configuration. The propenoate C=O and C=C groups are essentially coplanar [C=C—C=O torsion angle = 172.4 (3)°] with the O atom synperiplanar to the Cl atom. However, the π systems of the aromatic ring and chloro­propenoate substituent are not coplanar; the corresponding dihedral angle is 51.5 (1)°. The noncoplanarity is likely due to steric inter­actions between the propenoate H atom and the ortho-methoxy­carbonyl group on the aromatic ring. Even in the observed noncoplanar conformation, the ortho C=O to H distance (2.40 Å) is less than the sum of the van der Waals radii of O and H (2.65 Å)

Transient receptor potential vanilloid 4 channel deficiency aggravates tubular damage after acute renal ischaemia reperfusion

Transient receptor potential vanilloid 4 (TRPV4) cation channels are functional in all renal vascular segments and mediate endothelium-dependent vasorelaxation. Moreover, they are expressed in distinct parts of the tubular system and activated by cell swelling. Ischaemia/reperfusion injury (IRI) is characterized by tubular injury and endothelial dysfunction. Therefore, we hypothesised a putative organ protective role of TRPV4 in acute renal IRI. IRI was induced in TRPV4 deficient (Trpv4 KO) and wild-type (WT) control mice by clipping the left renal pedicle after right-sided nephrectomy. Serum creatinine level was higher in Trpv4 KO mice 6 and 24 hours after ischaemia compared to WT mice. Detailed histological analysis revealed that IRI caused aggravated renal tubular damage in Trpv4 KO mice, especially in the renal cortex. Immunohistological and functional assessment confirmed TRPV4 expression in proximal tubular cells. Furthermore, the tubular damage could be attributed to enhanced necrosis rather than apoptosis. Surprisingly, the percentage of infiltrating granulocytes and macrophages were comparable in IRI-damaged kidneys of Trpv4 KO and WT mice. The present results suggest a renoprotective role of TRPV4 during acute renal IRI. Further studies using cell-specific TRPV4 deficient mice are needed to clarify cellular mechanisms of TRPV4 in IRI

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

Demonstration of Gd-GEM detector design for neutron macromolecular crystallography applications

The European Spallation Source (ESS) in Lund, Sweden will become the world's most powerful thermal neutron source. The Macromolecular Diffractometer (NMX) at the ESS requires three 51.2 x 51.2~cm$^{2}$ detectors with reasonable detection efficiency, sub-mm spatial resolution, a narrow point spread function (PSF) and good time resolution. This work presents measurements with the improved version of the NMX detector prototype consisting of a Triple-GEM detector with natural Gd converter and a low material budget readout. The detector was successfully tested at the neutron reactor of the Budapest Neutron Centre (BNC) and at the D16 instrument at the Institut Laue-Langevin (ILL) in Grenoble. The measurements with Cadmium and Gadolinium masks in Budapest demonstrate that the point spread function of the detector lacks long tails that could impede the measurement of diffraction spot intensities. On the D16 instrument at ILL, diffraction spots from Triose phosphate isomerase w/ 2-phosphoglycolate (PGA) inhibitor were measured both in the D16 Helium-3 detector and the Gd-GEM. The comparison between the two detectors show a similar point spread function in both detectors, and the expected efficiency ratio compared to the Helium-3 detector. Both measurements together thus give good indications that the Gd-GEM detector fits the requirements for the NMX instrument at ESS