24 research outputs found
Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria
Locomotion of Niphargus amphipods from cave lakes and streams
Locomotion is a complex trait directly linked to different fitness components such as foraging, mate-finding, and escaping from predators. In a food-limited subterranean environment a strong selection for an energetically optimal strategy of locomotion is expected and should lead to different strategies among closely related species adapted to different microhabitats. Due to its taxonomic and ecological diversity, the amphipod genus Niphargus is an ideal model system for studying locomotion strategies of species affiliated with different subterranean aquatic microhabitats. Such species differ from each other morphologically, and we predicted that they also evolved alternative strategies of locomotion. In this study, we examined three species from cave lakes and five species from cave streams or springs. After collection all species were first acclimated in a cave laboratory. Then, we video-recorded behaviour in a rectangular open-field arena of approximately 10 individuals per species. A single individual at a time was recorded under red light for 20 minutes. Videos were used to construct ethograms of distinct locomotor behaviours such as swimming, crawling, and walking. A video-tracking analysis was performed to extract variables like total path covered, time spent moving, average and maximal speed. Individuals were euthanized and measured for several morphological traits likely related to locomotion. Additionally, we measured activities of enzymes acetylcholinesterase and glutathione S-transferase, which are likely related to animals’ locomotor and metabolic activity, respectively. Preliminary analyses suggest that species from lakes and streams differ in locomotor behaviour. Interestingly, variation in locomotor behaviour was larger among lake species, possibly implying that selection for the optimal locomotion strategy is stronger and more uniform in streams than in lakes
Loss of Ability To Self-Heal Malaria upon Taurine Transporter Deletion▿ †
Deletion of the taurine transporter gene (taut) results in lowered levels of taurine, the most abundant amino acid in mammals. Here, we show that taut−/− mice have lost their ability to self-heal blood-stage infections with Plasmodium chabaudi malaria. All taut−/− mice succumb to infections during crisis, while about 90% of the control taut+/+ mice survive. The latter retain unchanged taurine levels even at peak parasitemia. Deletion of taut, however, results in the lowering of circulating taurine levels from 540 to 264 μmol/liter, and infections cause additional lowering to 192 μmol/liter. Peak parasitemia levels in taut−/− mice are approximately 60% higher than those in taut+/+ mice, an elevation that is associated with increased systemic tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) levels, as well as with liver injuries. The latter manifest as increased systemic ammonia levels, a perturbed capacity to entrap injected particles, and increased expression of genes encoding TNF-α, IL-1β, IL-6, inducible nitric oxide synthase (iNOS), NF-κB, and vitamin D receptor (VDR). Autopsy reveals multiorgan failure as the cause of death for malaria-infected taut−/− mice. Our data indicate that taut-controlled taurine homeostasis is essential for resistance to P. chabaudi malaria. Taurine deficiency due to taut deletion, however, impairs the eryptosis of P. chabaudi-parasitized erythrocytes and expedites increases in systemic TNF-α, IL-1β, and ammonia levels, presumably contributing to multiorgan failure in P. chabaudi-infected taut−/− mice
Urinary Exosomal miRNA Signature in Type II Diabetic Nephropathy Patients.
MicroRNAs (miRNAs) are short non-coding RNA species which are important post-transcriptional regulators of gene expression and play an important role in the pathogenesis of diabetic nephropathy. miRNAs are present in urine in a remarkably stable form packaged in extracellular vesicles, predominantly exosomes. In the present study, urinary exosomal miRNA profiling was conducted in urinary exosomes obtained from 8 healthy controls (C), 8 patients with type II diabetes (T2D) and 8 patients with type II diabetic nephropathy (DN) using Agilent´s miRNA microarrays. In total, the expression of 16 miRNA species was deregulated (>2-fold) in DN patients compared to healthy donors and T2D patients: the expression of 14 miRNAs (miR-320c, miR-6068, miR-1234-5p, miR-6133, miR-4270, miR-4739, miR-371b-5p, miR-638, miR-572, miR-1227-5p, miR-6126, miR-1915-5p, miR-4778-5p and miR-2861) was up-regulated whereas the expression of 2 miRNAs (miR-30d-5p and miR-30e-5p) was down-regulated. Most of the deregulated miRNAs are involved in progression of renal diseases. Deregulation of urinary exosomal miRNAs occurred in micro-albuminuric DN patients but not in normo-albuminuric DN patients. We used qRT-PCR based analysis of the most strongly up-regulated miRNAs in urinary exosomes from DN patients, miRNAs miR-320c and miR-6068. The correlation of miRNA expression and micro-albuminuria levels could be replicated in a confirmation cohort. In conclusion, urinary exosomal miRNA content is altered in type II diabetic patients with DN. Deregulated miR-320c, which might have an impact on the TGF-β-signaling pathway via targeting thrombospondin 1 (TSP-1) shows promise as a novel candidate marker for disease progression in type II DN that should be evaluated in future studies
The interplay between habitat use, morphology and locomotion in subterranean crustaceans of the genus Niphargus
Linagliptin treatment is associated with altered cobalamin (VitB12) homeostasis in mice and humans
Abstract Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used for the treatment of type 2 diabetes, with additional beneficial effects for the kidney. Treatment of mice with linagliptin revealed increased storage of cobalamin (Cbl, Vitamin B12) in organs if a standard Cbl diet (30 µg Cbl/kg chow) is given. In order to translate these findings to humans, we determined methylmalonic acid (MMA), a surrogate marker of functional Cbl homeostasis, in human plasma and urine samples (n = 1092) from baseline and end of trial (6 months after baseline) of the previously completed MARLINA-T2D clinical trial. We found that individuals with medium Cbl levels (MMA between 50 and 270 nmol/L for plasma, 0.4 and 3.5 µmol/mmol creatinine for urine, at baseline and end of trial) exhibited higher MMA values at the end of study in placebo compared with linagliptin. Linagliptin might inhibit the N-terminal degradation of the transcobalamin receptor CD320, which is necessary for uptake of Cbl into endothelial cells. Because we demonstrate that linagliptin led to increased organ levels of Cbl in mice, sustained constant medium MMA levels in humans, and inhibited CD320 processing by DPP-4 in-vitro, we speculate that linagliptin promotes intra-cellular uptake of Cbl by prolonging half-life of CD320