Diabetes-induced increase of renal medullary hydrogen peroxide and urinary angiotensinogen is similar in normotensive and hypertensive rats

Aims

Activation of renal renin–angiotensin system (RAS) and reactive oxygen species (ROS) are the main pathophysiological mechanisms associated with kidney injury both in diabetes and hypertension. However, the contribution to medullary damage when the two pathologies coexist has seldom been explored.

Main methods

Diabetes was induced with streptozotocin in twelve week-old male Wistar and spontaneously hypertensive rats (SHR) rats; controls received vehicle. Three weeks later, systolic blood pressure (SBP), plasma and urinary angiotensinogen (AGT), renal oxidative stress and metabolic status were evaluated.

Key findings

SBP was higher in SHR-controls than in Wistar-controls (200 ± 6 and 127 ± 3 mmHg, respectively) and decreased in SHR-diabetics but not in Wistar-diabetics (143 ± 8 and 122 ± 6 mmHg, respectively). Renal medullary hydrogen peroxide (H₂O₂) production was similarly increased in diabetics (Wistar: 0.32 ± 0.04 and 1.11 ± 0.10 nmol/mg protein, respectively; SHR: 0.40 ± 0.05 and 0.90 ± 0.14 nmol/mg protein, respectively) and positively correlated with glycemia (Wistar: r = 0.7166, SHR: r = 0.7899, p < 0.05) and urinary AGT excretion (Wistar: r = 0.8333; SHR: r = 0.8326, p < 0.05). Cortical H₂O₂ production was higher in SHR-controls than in Wistar-controls (1.10 ± 0.09 and 0.26 ± 0.04 nmol/mg protein, respectively) and diabetes induction decreased it in SHR (0.70 ± 0.09 nmol/mg protein). Diabetes increased urinary AGT excretion by more than 7-fold and decreased plasma AGT concentration by more than 1.5-fold in both strains.

Significance

Our results show that STZ-induced diabetes increases medullary H₂O₂ production and urinary AGT excretion with similar magnitude in normotensive and hypertensive animals. Reducing blood pressure attenuates hypertension-associated cortical damage but does not prevent medullary dysfunction.     

Water stress and recovery in the performance of two Eucalyptus globulus clones: physiological and biochemical profiles

Eucalyptus plantations are among the most productive forest stands in Portugal and Spain, being mostly used for pulp production and, more recently, as an energy crop. However, the region's Mediterranean climate, with characteristic severe summer drought, negatively affects eucalypt growth and increases mortality. Although the physiological response to water shortage is well characterized for this species, evidence about the plants' recovery ability remains scarce. In order to assess the physiological and biochemical response of Eucalyptus globulus during the recovery phase, two genotypes (AL‐18 and AL‐10) were submitted to a 3‐week water stress period at two different intensities (18 and 25% of field capacity), followed by 1 week of rewatering. Recovery was assessed 1 day and 1 week after rehydration. Drought reduced height, biomass, water potential, NPQ and gas exchange in both genotypes. Contrarily, the levels of pigments, chlorophyll fluorescence parameters (F_v/F_m and φ_PSII), MDA and ABA increased. During recovery, the physiological and biochemical profile of stressed plants showed a similar trend: they experienced reversion of altered traits (MDA, ABA, E, g_s, pigments), while other parameters did not recover (φ_PSII, NPQ). Furthermore, an overcompensation of CO₂ assimilation was achieved 1 week after rehydration, which was accompanied by greater growth and re‐establishment of oxidative balance. Both genotypes were tolerant to the tested conditions, although clonal differences were found. AL‐10 was more productive and showed a more rapid and dynamic response to rehydration (namely in carotenoid content, φ_PSII and NPQ) compared to clone AL‐18.     

Mitochondrial Dysfunction and Decrease in Body Weight of a Transgenic Knock-in Mouse Model for TDP-43

The majority of amyotrophic lateral sclerosis (ALS) cases as well as many patients suffering from frontotemporal lobar dementia (FTLD) with ubiquitinated inclusion bodies show TDP-43 pathology, the protein encoded by the TAR DNA-binding protein (Tardbp) gene. We used recombinase-mediated cassette exchange to introduce an ALS patient cDNA into the mouse Tdp-43 locus. Expression levels of human A315T TDP-43 protein were 300% elevated in heterozygotes, whereas the endogenous mouse Tdp-43 was decreased to 20% of wild type levels as a result of disturbed feedback regulation. Heterozygous TDP-43^A315TKi mutants lost 10% of their body weight and developed insoluble TDP-43 protein starting as early as 3 months after birth, a pathology that was exacerbated with age. We analyzed the splicing patterns of known Tdp-43 target genes as well as genome-wide gene expression levels in different tissues that indicated mitochondrial dysfunction. In heterozygous mutant animals, we observed a relative decrease in expression of Parkin (Park2) and the fatty acid transporter CD36 along with an increase in fatty acids, HDL cholesterol, and glucose in the blood. As seen in transmission electron microscopy, neuronal cells in motor cortices of TDP-43^A315TKi animals had abnormal neuronal mitochondrial cristae formation. Motor neurons were reduced to 90%, but only slight motoric impairment was detected. The observed phenotype was interpreted as a predisease model, which might be valuable for the identification of further environmental or genetic triggers of neurodegeneration.     

In vivo glenohumeral translation under anterior loading in an open-MRI set-up

The evaluation of the glenohumeral joint laxity requires the estimate of displacements of the humeral head centre (HHC) with respect to the glenoid. To the authors? knowledge, several studies have been conducted to estimate HHC translations in vivo but data under anterior loading conditions has not been collected yet. Aim of this study was to develop a non-invasive experimental methodology based on magnetic resonance (MR) imaging for the in vivo evaluation of the HHC translations due to an anteriorly directed force. Fourteen asymptomatic shoulders were acquired using a horizontal open MR scanner with the subjects in the supine position both at 15° and 90° of arm abduction with and without an anterior force of 20 N applied at the HHC level. When no load was applied, from 15° to 90° of arm abduction, the HHC moved, anteriorly (1.5±1.3 mm) and superiorly (1.8±1.3 mm) while smaller displacements were observed medio-laterally (0.4±0.7 mm). Under the application of the anterior force the 3D displacement of the HHC with respect to the glenoid was 1.6±1.2 mm and 1.3 ±0.7 mm, respectively at 15° and 90° of arm abduction. The level of precision associated to the GHJ translation was less than 0.33 mm along all directions i.e. one order of magnitude smaller than the relevant translations. In conclusion, the MRI-based methodology allowed for the analysis of HHC displacements under conditions of anterior loads within an acceptable level of reliability.     

Anopheles species composition explains differences in Plasmodium transmission in La Guajira,northern Colombia

Malaria in La Guajira, the most northern state of Colombia, shows two different epidemiological patterns. Malaria is endemic in the municipality of Dibulla whereas in Riohacha it is characterised by sporadic outbreaks. This study aimed to establish whether differences in transmission patterns could be attributed to different vector species. The most abundant adult female species were Anopheles aquasalis, exclusive to Riohacha, and Anopheles darlingi, restricted to Dibulla. Anopheles mosquitoes were identified using morphology and the molecular markers internal transcribed spacer 2 and cytochrome c oxidase I. All specimens (n = 1,393) were tested by ELISA to determine natural infection rates with Plasmodium falciparum and Plasmodium vivax. An. darlingi was positive for P. vivax 210, with an infection rate of 0.355% and an entomological inoculation rate of 15.87 infective bites/person/year. Anopheles albimanus larvae were the most common species in Riohacha, found in temporary swamps; in contrast, in Dibulla An. darlingi were detected mainly in permanent streams. Distinctive species composition and larval habitats in each municipality may explain the differences in Plasmodium transmission and suggest different local strategies should be used for vector control.     

Effects of Egg and Circulating Testosterone on Ring‐Necked Pheasant (Phasianus colchicus) Male Traits and Combat Outcome

Studies of avian species have shown that maternal effects mediated by the transfer of egg hormones can profoundly affect offspring phenotype and fitness. We previously demonstrated that the injection of a physiological amount of testosterone (T) in the eggs of ring‐necked pheasants (Phasianus colchicus) disrupted the covariation among male morphological traits at sexual maturity and positively affected male mating success. Here, we investigate whether egg T exposure affected adult male circulating T levels at the onset of the breeding season (reflecting gonadal maturation), and the relationship between circulating T and male traits. Egg T exposure did not affect pre‐mating plasma T. T levels were not associated with the expression of secondary sexual and non‐sexual traits or socio‐sexual behaviour (social rank, overall fighting ability and mating success). However, wattle brightness decreased with increasing circulating T in males hatched from T‐eggs (T‐males) but not among control males. In dyadic encounters during the peak mating period, control males with higher pre‐mating T levels had higher chances of being dominant over other control males. However, higher pre‐mating T levels did not predict success in male‐male competition in encounters involving T‐males. We suggest that the long‐term effects of egg T on male phenotype do not originate from differential gonadal maturation according to egg T treatment. Rather, prenatal androgens may have priming effects on functioning of target tissues, translating into differential phenotypic effects according to androgen exposure during embryonic development.     

Wood density proxies of adaptive traits linked with resistance to drought in Douglas fir (Pseudotsuga menziesii (Mirb.) Franco)

Key message

Proxies of adaptive traits for resistance to drought were discovered among original annual ring density variables in Douglas fir.

Abstract

A comparison of dead and surviving Douglas fir trees following the 2003 drought was made to define proxies of adaptive traits for resistance to drought. Increment cores were sampled from trees from three French regions: Centre, Midi-Pyrénées and Burgundy. Original tree-ring variables were calculated, based on a sliding density criterion dividing the microdensity profile into high- and low-density segments. Tree rings were analysed at each site in a number of consecutive annual rings before the 2003 drought event. Comparison between pairs of surviving and dead trees and between pairs of randomly selected trees (whether dead or alive) supports the evidence of systematic dissimilarities between surviving and dead trees in a number of original density variables. Correlation analysis between original and conventional ring density variables indicates a weak association. We found that the surviving trees were denser than the dead trees in all three sites, but that the denser part of the ring varied from region to region. We identified several original density variables intended to be used as proxies of adaptive traits in future studies of genetic determinism of Douglas fir resistance to drought.