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A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
This work is focused on the influence of an ionic liquid (IL), i.e. ethyl-methylimidazolium hexylsulfate, on the spontaneous formation of microemulsions with ionic surfactants. The influence of the ionic liquid on Structure formation in the optically clear phase region in water/toluene/pentanol mixtures in presence of the cationic surfactant CTAB was studied in more detail. The results show a significant increase of the transparent phase region by adding the ionic liquid. Conductometric investigations demonstrate that adding the ionic liquid can drastically reduce the droplet- droplet interactions in the L-2 phase. H-1 nuclear magnetic resonance (H-1 NMR) diffusion coefficient measurements in combination with dynamic light scattering measurements clearly show that inverse microemulsion droplets still exist, but the droplet size is decreased to 2 nm. A more detailed characterisation of the isotropic phase channel by means of conductivity measurements, dynamic light scattering (DLS), H-1 NMR and cryo-scanning electron microscopy (SEM), allows the identification of a bicontinuous sponge phase between the L-1 and L-2 phase. When the poly(ethyleneimine) is added, the isotropic phase range is reduced drastically, but the inverse microemulsion range still exists.
Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.
Background:
It has previously been shown that conditioning activities consisting of repetitive hops have the
potential to induce better drop jump (DJ) performance in recreationally active individuals. In the present pilot study,
we investigated whether repetitive conditioning hops can also increase reactive jump and sprint performance in
sprint-trained elite athletes competing at an international level.
Methods:
Jump and sprint performances of 5 athletes were randomly assessed under 2 conditions. The control
condition (CON) comprised 8 DJs and 4 trials of 30-m sprints. The intervention condition (HOP) consisted of 10
maximal repetitive two-legged hops that were conducted 10 s prior to each single DJ and sprint trial. DJ
performance was analyzed using a one-dimensional ground reaction force plate. Step length (SL), contact time (CT),
and sprint time (ST) during the 30-m sprints were recorded using an opto-electronic measurement system.
Results:
Following the conditioning activity, DJ height and external DJ peak power were both significantly
increased by 11 % compared to the control condition. All other variables did not show any significant differences
between HOP and CON.
Conclusions:
In the present pilot study, we were able to demonstrate large improvements in DJ performance even
in sprint-trained elite athletes following a conditioning activity consisting of maximal two-legged repetitive hops.
This strengthens the hypothesis that plyometric conditioning exercises can induce performance enhancements in
elite athletes that are even greater than those observed in recreationally active athletes.. In addition, it appears that
the transfer of these effects to other stretch-shortening cycle activities is limited, as we did not observe any
changes in sprint performance following the plyometric conditioning activity.
Background: It has previously been shown that conditioning activities consisting of repetitive hops have the potential to induce better drop jump (DJ) performance in recreationally active individuals. In the present pilot study, we investigated whether repetitive conditioning hops can also increase reactive jump and sprint performance in sprint-trained elite athletes competing at an international level. Methods: Jump and sprint performances of 5 athletes were randomly assessed under 2 conditions. The control condition (CON) comprised 8 DJs and 4 trials of 30-m sprints. The intervention condition (HOP) consisted of 10 maximal repetitive two-legged hops that were conducted 10 s prior to each single DJ and sprint trial. DJ performance was analyzed using a one-dimensional ground reaction force plate. Step length (SL), contact time (CT), and sprint time (ST) during the 30-m sprints were recorded using an opto-electronic measurement system. Results: Following the conditioning activity, DJ height and external DJ peak power were both significantly increased by 11 % compared to the control condition. All other variables did not show any significant differences between HOP and CON. Conclusions: In the present pilot study, we were able to demonstrate large improvements in DJ performance even in sprint-trained elite athletes following a conditioning activity consisting of maximal two-legged repetitive hops. This strengthens the hypothesis that plyometric conditioning exercises can induce performance enhancements in elite athletes that are even greater than those observed in recreationally active athletes.. In addition, it appears that the transfer of these effects to other stretch-shortening cycle activities is limited, as we did not observe any changes in sprint performance following the plyometric conditioning activity.
A conformational study of N-acetyl glucosamine derivatives utilizing residual dipolar couplings
(2013)
A new approach to analyze multi-component Saturation Transfer Difference (STD) NMR spectra by combining the STD and the DOSY experiment is proposed. The resulting pulse sequence was successfully used to simplify an exemplary multi- component protein/substrate system by means of standard DOSY processing methods. Furthermore, the same experiment could be applied to calculate the ratio of saturated substrate molecules and its saturation rate in the case of competitive interactions. This ratio depends on the strength of this interaction between the substrates and the protein, so that this kind of information could be extracted from the results of our experiment.
A conformational study of N-acetyl glucosamine derivatives utilizing residual dipolar couplings
(2011)
The conformational analyses of six non-rigid N-acetyl glucosamine (NAG) derivatives employing residual dipolar couplings (RDCs) and NOEs together with molecular dynamics (MD) simulations are presented. Due to internal dynamics we had to consider different conformer ratios existing in solution. The good quality of the correlation between theoretically and experimentally obtained RDCs show the correctness of the calculated conformers even if the ratios derived from the MD simulations do not exactly meet the experimental data. If possible, the results were compared to former published data and commented.