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Purpose of reviewIncretin-based therapy with glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors is considered a promising therapeutic option for type 2 diabetes mellitus. Cumulative evidence, mainly from preclinical animal studies, reveals that incretin-based therapies also may elicit beneficial effects on kidney function. This review gives an overview of the physiology, pathophysiology, and pharmacology of the renal incretin system.Recent findingsActivation of GLP-1R in the kidney leads to diuretic and natriuretic effects, possibly through direct actions on renal tubular cells and sodium transporters. Moreover, there is evidence that incretin-based therapy reduces albuminuria, glomerulosclerosis, oxidative stress, and fibrosis in the kidney, partially through GLP-1R-independent pathways. Molecular mechanisms by which incretins exert their renal effects are understood incompletely, thus further studies are needed.SummaryThe GLP-1R and DPP-4 are expressed in the kidney in various species. The kidney plays an important role in the excretion of incretin metabolites and most GLP-1R agonists and DPP-4 inhibitors, thus special attention is required when applying incretin-based therapy in renal impairment. Preclinical observations suggest direct renoprotective effects of incretin-based therapies in the setting of hypertension and other disorders of sodium retention, as well as in diabetic and nondiabetic nephropathy. Clinical studies are needed in order to confirm translational relevance from preclinical findings for treatment options of renal diseases.
A Co(II)-imidazolate-4-amide-5-imidate based MOF, IFP-5, is synthesized by using an imidazolate anion-based novel ionic liquid as a linker precursor under solvothermal conditions. IFP-5 shows significant amounts of gas (N-2, CO2, CH4 and H-2) uptake capacities. IFP-5 exhibits an independent high spin Co(II) centre and antiferromagnetic coupling.
We investigate nonlinear problems which appear as Euler-Lagrange equations for a variational problem. They include in particular variational boundary value problems for nonlinear elliptic equations studied by F. Browder in the 1960s. We establish a solvability criterion of such problems and elaborate an efficient orthogonal projection method for constructing approximate solutions.
The complementary advantages of GPS and seismic measurements are well recognized in seismotectonic monitoring studies. Therefore, integrated processing of the two data streams has been proposed recently in an attempt to obtain accurate and reliable information of surface displacements associated with earthquakes. A hitherto still critical issue in the integrated processing is real-time detection and precise estimation of the transient baseline error in the seismic records. Here, we report on a new approach by introducing the seismic acceleration corrected by baseline errors into the state equation system. The correction is performed and regularly updated in short epochs (with increments which may be as short as seconds), so that station position, velocity, and acceleration can be constrained very tightly and baseline error can be estimated as a random-walk process. With the adapted state equation system, our study highlights the use of a new approach developed for integrated processing of GPS and seismic data by means of sequential least-squares adjustment. The efficiency of our approach is demonstrated and validated using simulated, experimental, and real datasets. The latter were collected at collocated GPS and seismic stations around the 4 April 2010, E1 Mayor-Cucapah earthquake (Mw, 7.2). The results have shown that baseline errors of the strong-motion sensors are corrected precisely and high-precision seismic displacements are real-timely obtained by the new approach.
ResultsUnder conditions of elevated prenatal maternal stress, children carrying one or two DRD4 7r alleles were at increased risk of a diagnosis of CD/ODD. Moreover, homozygous carriers of the DRD4 7r allele displayed more externalizing behavior following exposure to higher levels of prenatal maternal stress, while homozygous carriers of the DRD4 4r allele turned out to be insensitive to the effects of prenatal stress.
ConclusionsThis study is the first to report a gene-environment interaction related to DRD4 and prenatal maternal stress using data from a prospective study, which extends earlier findings on the impact of prenatal maternal stress with respect to childhood antisocial behavior.
QuestionDoes eutrophication drive vegetation change in pine forests on nutrient deficient sites and thus lead to the homogenization of understorey species composition?
LocationForest area (1600ha) in the Lower Spreewald, Brandenburg, Germany.
MethodsResurvey of 77 semi-permanent plots after 45yr, including vascular plants, bryophytes and ground lichens. We applied multidimensional ordination of species composition, dissimilarity indices, mean Ellenberg indicator values and the concept of winner/loser species to identify vegetation change between years. Differential responses along a gradient of nutrient availability were analysed on the basis of initial vegetation type, reflecting topsoil N availability of plots.
ResultsSpecies composition changed strongly and overall shifted towards higher N and slightly lower light availability. Differences in vegetation change were related to initial vegetation type, with strongest compositional changes in the oligotrophic forest type, but strongest increase of nitrophilous species in the mesotrophic forest type. Despite an overall increase in species number, species composition was homogenized between study years due to the loss of species (mainly ground lichens) on the most oligotrophic sites.
ConclusionsThe response to N enrichment is confounded by canopy closure on the N-richest sites and probably by water limitation on N-poorest sites. The relative importance of atmospheric N deposition in the eutrophication effect is difficult to disentangle from natural humus accumulation after historical litter raking. However, the profound differences in species composition between study years across all forest types suggest that atmospheric N deposition contributes to the eutrophication, which drives understorey vegetation change and biotic homogenization in Central European Scots pine forests on nutrient deficient sites.
Not only the apples
(2014)
Focus sensitive particles highlight the relevance of contextual alternatives for the interpretation of a sentence. Two experiments tested whether this leads to better encoding and therefore, ultimately, better recall of focus alternatives. Participants were presented with auditory stimuli that introduced a set of elements ("context sentence") and continued in three different versions: the critical sentences either contained the exclusive particle nur ("only"), the inclusive particle sogar ("even"), or no particle (control condition). After being exposed to blocks of ten trials, participants were asked to recall the elements in the context sentence. The results show that both particles enhanced memory performance for the alternatives to the focused element, relative to the control condition. The results support the assumption that information-structural alternatives are better encoded in memory in the presence of a focus sensitive particle.
To assess the ecological and economic implications of the redistributive land reform in semi-arid Namibia, we investigated to what extent land reform beneficiaries adjust herd size and herd composition according to environmental (rainfall, vegetation) and economic variables (herd size, financial assets, running costs). We performed model-based role-plays with Namibian land reform beneficiaries, simulating 10 years of rangeland management.
Our study revealed that the farmers surveyed mainly manage their herds according to their economic situation (herd size and account balance) but do not take environmental variability (rainfall and vegetation) into account. Further, our results indicate that, due to financial pressure, farmers are not able to apply their desired management strategies, and that owners of small farms face a higher risk of economic failure. However, farmers apply rather conservative and constant stocking rates and will thus, given the current economic limitations, likely not contribute to semi-arid savanna degradation.
We conclude that land reform beneficiaries need support to be able to apply straightforward and efficient management strategies. This could be achieved by facilitating cooperation between small farming businesses and by supporting initial investment in productive cattle herds at the time of redistribution of the land.
In addition to sensory decline, age-related losses in auditory perception also reflect impairments in attentional modulation of perceptual saliency. Using an attention and intensity-modulated dichotic listening paradigm, we investigated electrophysiological correlates of processing conflicts between attentional focus and perceptual saliency in 25 younger and 26 older adults. Participants were instructed to attend to the right or left ear, and perceptual saliency was manipulated by varying the intensities of both ears. Attentional control demand was higher in conditions when attentional focus and perceptual saliency favored opposing ears than in conditions without such conflicts. Relative to younger adults, older adults modulated their attention less flexibly and were more influenced by perceptual saliency. Our results show, for the first time, that in younger adults a late negativity in the event-related potential (ERP) at fronto-central and parietal electrodes was sensitive to perceptual-attentional conflicts during auditory processing (N450 modulation effect). Crucially, the magnitude of the N450 modulation effect correlated positively with task performance. In line with lower attentional flexibility, the ERP waveforms of older adults showed absence of the late negativity and the modulation effect. This suggests that aging compromises the activation of the frontoparietal attentional network when processing the competing and conflicting auditory information.