A laboratory approach for characterizing chronic fatigue: what does metabolomics tell us?

Metabolomics - Pre-eclampsia is a hypertensive gestational disorder that affects approximately 5% of all pregnancies. As the pathophysiological processes of pre-eclampsia are still uncertain, the...     

Point-of-care measurements reveal release of purines into venous blood of stroke patients

Purinergic Signalling - Stroke is a leading cause of death and disability. Here, we examine whether point-of-care measurement of the purines, adenosine, inosine and hypoxanthine, which are...     

Enhanced generation of intraluminal vesicles in neuronal late endosomes in the brain of a Down syndrome mouse model with endosomal dysfunction

Down syndrome (DS) is a human genetic disease caused by trisomy of chromosome 21 and characterized by early developmental brain abnormalities. Dysfunctional endosomal pathway in neurons is an early event of DS and Alzheimer's disease. Recently, we have demonstrated that exosome secretion is upregulated in human DS postmortem brains, in the brain of the trisomic mouse model Ts[Rb(12.17¹⁶)]2Cje (Ts2) and by DS fibroblasts as compared with disomic controls. High levels of the tetraspanin CD63, a regulator of exosome biogenesis, were observed in DS brains. Partially blocking exosome secretion by DS fibroblasts exacerbated a pre‐existing early endosomal pathology. We thus hypothesized that enhanced CD63 expression induces generation of intraluminal vesicles (ILVs) in late endosomes/multivesicular bodies (MVBs), increasing exosome release as an endogenous mechanism to mitigate endosomal abnormalities in DS. Herein, we show a high‐resolution electron microscopy analysis of MVBs in neurons of the frontal cortex of 12‐month‐old Ts2 mice and littermate diploid controls. Our quantitative analysis revealed that Ts2 MVBs are larger, more abundant, and contain a higher number of ILVs per neuron compared to controls. These findings were further corroborated biochemically by Western blot analysis of purified endosomal fractions showing higher levels of ILVs proteins in the same fractions containing endosomal markers in the brain of Ts2 mice compared to controls. These data suggest that upregulation of ILVs production may be a key homeostatic mechanism to alleviate endosomal dysregulation via the endosomal–exosomal pathway.     

Individual variation in early‐life telomere length and survival in a wild mammal

Individual variation in survival probability due to differential responses to early‐life environmental conditions is important in the evolution of life histories and senescence. A biomarker allowing quantification of such individual variation, and which links early‐life environmental conditions with survival by providing a measure of conditions experienced, is telomere length. Here, we examined telomere dynamics among 24 cohorts of European badgers (Meles meles). We found a complex cross‐sectional relationship between telomere length and age, with no apparent loss over the first 29 months, but with both decreases and increases in telomere length at older ages. Overall, we found low within‐individual consistency in telomere length across individual lifetimes. Importantly, we also observed increases in telomere length within individuals, which could not be explained by measurement error alone. We found no significant sex differences in telomere length, and provide evidence that early‐life telomere length predicts lifespan. However, while early‐life telomere length predicted survival to adulthood (≥1 year old), early‐life telomere length did not predict adult survival probability. Furthermore, adult telomere length did not predict survival to the subsequent year. These results show that the relationship between early‐life telomere length and lifespan was driven by conditions in early‐life, where early‐life telomere length varied strongly among cohorts. Our data provide evidence for associations between early‐life telomere length and individual life history, and highlight the dynamics of telomere length across individual lifetimes due to individuals experiencing different early‐life environments.     

Evaluation of α-hydroxycinnamic acids as pyruvate carboxylase inhibitors

Through a structure-based drug design project (SBDD), potent small molecule inhibitors of pyruvate carboxylase (PC) have been discovered. A series of α-keto acids (7) and α-hydroxycinnamic acids (8) were prepared and evaluated for inhibition of PC in two assays. The two most potent inhibitors were 3,3′-(1,4-phenylene)bis[2-hydroxy-2-propenoic acid] (8u) and 2-hydroxy-3-(quinoline-2-yl)propenoic acid (8v) with IC₅₀ values of 3.0 ± 1.0 μM and 4.3 ± 1.5 μM respectively. Compound 8v is a competitive inhibitor with respect to pyruvate (K_i = 0.74 μM) and a mixed-type inhibitor with respect to ATP, indicating that it targets the unique carboxyltransferase (CT) domain of PC. Furthermore, compound 8v does not significantly inhibit human carbonic anhydrase II, matrix metalloproteinase-2, malate dehydrogenase or lactate dehydrogenase.     

Balancing competing life‐stage requirements in salmon habitat rehabilitation: between a rock and a hard place

Gravel augmentation is often applied to rivers and streams to rehabilitate salmonid spawning and incubation habitat. However, the effect of gravel size on salmon spawning utilization and embryo survival during incubation is not well understood. We conducted an experiment on a regulated and previously mined Northern California salmonid‐bearing stream in which different sized gravel (small, medium, and large) patches were placed into the stream's degraded spawning reach. We documented Oncorhynchus tshawytscha (Chinook salmon) spawning activity within the three gravel sizes for two seasons. In addition, we deployed Chinook salmon embryos into each gravel size patch and allowed them to incubate until estimated emergence time. Although all experimental gravel sizes were predicted to be within the spawning population's mobilization capabilities, model results indicated the probability of salmon building redds decreased as substrate size increased. Conversely, embryo survival increased as gravel size increased. A possible mechanism of disparate Chinook salmon embryo survival is provided by an observed decrease in embryo survival correlating with greater presence of embryo predators (leeches), which are associated with smaller gravel. Our results indicate a parent‐offspring conflict in optimal spawning gravel size for Chinook salmon, and suggest that an intermediate gravel size would maximize overall reproductive success across both spawning and incubation life stages.     

Interactive Visualization and Industrial Ecology: Applications,Challenges, and Opportunities

The emergence of increasingly complex data in industrial ecology (IE) has caused scholarly interest in interactive visualization (IV). IV allows users to interact with data, aiding in processing and interpreting complex datasets, processes, and simulations. Consequently, IV can help IE practitioners communicate the complexities of their methods and results, shed light on the underlying research assumptions, and enable more transparent monitoring of data quality and error. This can significantly increase the reach and impact of research, promote transparency, reproducibility, and open science, as well as improve the clarity and presentation of IE research. A review of current IV applications reveals that, while data exploration has received some attention among IE practitioners, IV applications in scientific communication are clearly lacking. With the help of a working example, we explore the value of IV, discuss its operationalization, and highlight challenges that the IE community must face during IV uptake. Such challenges include technical and knowledge limitations, limits on user interaction, and implementation strategies. With these challenges in mind, we outline key aspects needed to lift the IE field to the forefront of scientific communication in the coming years. Among these, we draft the basic principles of a “Hub for Interactive Visualization in Industrial Ecology” (HIVE), a point of encounter where IE practitioners could find an array of data visualization tools that are geared toward IE datasets. IV is here to stay, and its inceptive stage presents many opportunities to IE practitioners to shape its operationalization and benefit from early adoption.     

Asymmetric introgression between fishes in the Red River basin of Texas is associated with variation in water quality

When ecologically divergent taxa encounter one another, hybrid zones can form when reproductive isolation is incomplete. The location of such hybrid zones can be influenced by environmental variables, and an ecological context can provide unique insights into the mechanisms by which species diverge and are maintained. Two ecologically differentiated species of small benthic fishes, the endemic and imperiled prairie chub, Macrhybopsis australis, and the shoal chub, Macrhybopsis hyostoma, are locally sympatric within the upper Red River Basin of Texas. We integrated population genomic data and environmental data to investigate species divergence and the maintenance of species boundaries in these two species. We found evidence of advanced‐generation asymmetric hybridization and introgression, with shoal chub alleles introgressing more frequently into prairie chubs than the reciprocal. Using a Bayesian Genomic Cline framework, patterns of genomic introgression were revealed to be quite heterogeneous, yet shoal chub alleles were found to have likely selectively introgressed across species boundaries significantly more often than prairie chub alleles, potentially explaining some of the observed asymmetry in hybridization. These patterns were remarkably consistent across two sampled geographic regions of hybridization. Several environmental variables were found to significantly predict individual admixture, suggesting ecological isolation might maintain species boundaries.     

Accounting for heterogeneity when estimating stopover duration,timing and population size of red knots along the Luannan Coast of Bohai Bay,China

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