Collapse of the native ruffe (<Emphasis Type="Italic">Gymnocephalus cernua</Emphasis>) population in the Biesbosch lakes (the Netherlands) owing to round goby (<Emphasis Type="Italic">Neogobius melanostomus</Emphasis>) invasion

We investigated the change in benthic fish communities in three artificial lakes of the Biesbosch area in the Netherlands between two time periods: before and after the invasion of round goby (Neogobius melanostomus). Native ruffe (Gymnocephalus cernua), the dominant species in benthic gillnet and littoral beach seining catches before the invasion, almost completely disappeared in all lakes only 2 years after the invasion. We found a significant increase in 0 + perch (Perca fluviatilis) and, in some lakes, pikeperch (Sander lucioperca) abundance in gillnet catches after invasion. In the post-invasion period, the 0 + fish community was dominated by perch, and the older fish community was dominated by round goby. The species richness of 0 + fish increased in the post-invasion period owing to the invasion of gobiids. However, it did not change for older fish between periods. Our results clearly show that, owing to a similar benthic lifestyle and high niche overlap, ruffe was the only species negatively influenced by the round goby invasion. The competitive superiority of round goby over ruffe is so strong that the once-dominant species of the overall benthic fish community collapsed after only a few years of coexistence.     

ATXN1-CIC Complex Is the Primary Driver of Cerebellar Pathology in Spinocerebellar Ataxia Type 1 through a Gain-of-Function Mechanism

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Hybrid asexuality as a primary postzygotic barrier between nascent species: On the interconnection between asexuality,hybridization and speciation

Although sexual reproduction is ubiquitous throughout nature, the molecular machinery behind it has been repeatedly disrupted during evolution, leading to the emergence of asexual lineages in all eukaryotic phyla. Despite intensive research, little is known about what causes the switch from sexual reproduction to asexuality. Interspecific hybridization is one of the candidate explanations, but the reasons for the apparent association between hybridization and asexuality remain unclear. In this study, we combined cross‐breeding experiments with population genetic and phylogenomic approaches to reveal the history of speciation and asexuality evolution in European spined loaches (Cobitis). Contemporary species readily hybridize in hybrid zones, but produce infertile males and fertile but clonally reproducing females that cannot mediate introgressions. However, our analysis of exome data indicates that intensive gene flow between species has occurred in the past. Crossings among species with various genetic distances showed that, while distantly related species produced asexual females and sterile males, closely related species produce sexually reproducing hybrids of both sexes. Our results suggest that hybridization leads to sexual hybrids at the initial stages of speciation, but as the species diverge further, the gradual accumulation of reproductive incompatibilities between species could distort their gametogenesis towards asexuality. Interestingly, comparative analysis of published data revealed that hybrid asexuality generally evolves at lower genetic divergences than hybrid sterility or inviability. Given that hybrid asexuality effectively restricts gene flow, it may establish a primary reproductive barrier earlier during diversification than other “classical” forms of postzygotic incompatibilities. Hybrid asexuality may thus indirectly contribute to the speciation process.     

Synthesis and affinity studies of himbacine derived muscarinic receptor antagonists

A series of himbacine (1)-related analogues has been prepared featuring three different isomeric configurations with respect to the B-ring (a, b and natural c) and three different interconnecting two-carbon unsaturated units [natural (E)-ene, (Z)-ene, and yne]. The study of the binding affinities of the nine resulting compounds, including synthetic (+)-himbacine (3c), towards the M(1)-M(4) muscarine receptor subtypes revealed that analogues 3a and 5c display a promising 10-fold selectivity for the M(2) receptor as compared to the M(1) receptor.     

Rearrangement of mitochondrial pyruvate dehydrogenase subunit dihydrolipoamide dehydrogenase protein–protein interactions by the MDM2 ligand nutlin‐3

Drugs targeting MDM2's hydrophobic pocket activate p53. However, these agents act allosterically and have agonist effects on MDM2's protein interaction landscape. Dominant p53‐independent MDM2‐drug responsive‐binding proteins have not been stratified. We used as a variable the differential expression of MDM2 protein as a function of cell density to identify Nutlin‐3 responsive MDM2‐binding proteins that are perturbed independent of cell density using SWATH‐MS. Dihydrolipoamide dehydrogenase, the E3 subunit of the mitochondrial pyruvate dehydrogenase complex, was one of two Nutlin‐3 perturbed proteins identified fours hour posttreatment at two cell densities. Immunoblotting confirmed that dihydrolipoamide dehydrogenase was induced by Nutlin‐3. Depletion of MDM2 using siRNA also elevated dihydrolipoamide dehydrogenase in Nutlin‐3 treated cells. Mitotracker confirmed that Nutlin‐3 inhibits mitochondrial activity. Enrichment of mitochondria using TOM22+ immunobeads and TMT labeling defined key changes in the mitochondrial proteome after Nutlin‐3 treatment. Proximity ligation identified rearrangements of cellular protein–protein complexes in situ. In response to Nutlin‐3, a reduction of dihydrolipoamide dehydrogenase/dihydrolipoamide acetyltransferase protein complexes highlighted a disruption of the pyruvate dehydrogenase complex. This coincides with an increase in MDM2/dihydrolipoamide dehydrogenase complexes in the nucleus that was further enhanced by the nuclear export inhibitor Leptomycin B. The data suggest one therapeutic impact of MDM2 drugs might be on the early perturbation of specific protein–protein interactions within the mitochondria. This methodology forms a blueprint for biomarker discovery that can identify rearrangements of MDM2 protein–protein complexes in drug‐treated cells.     

Metabolically Healthy Obesity and the Risk of Cardiovascular Disease in the Elderly Population

BackgroundWhether being metabolically healthy obese (MHO)—defined by the presence of obesity in the absence of metabolic syndrome—is associated with subsequent cardiovascular disease (CVD) remains unclear and may depend on the participants’ age. We examined the association of being MHO with CVD risk in the elderly.ConclusionsIn our elderly population, we found that the presence of obesity without metabolic syndrome did not confer a higher CVD risk. However, metabolic syndrome was strongly associated with CVD risk, and was associated with an increased risk in all BMI categories. Therefore, preventive interventions targeting cardiometabolic risk factors could be considered in elderly, regardless of weight status.     

Forecasting model of <Emphasis Type="Italic">Corylus</Emphasis>, <Emphasis Type="Italic">Alnus</Emphasis>, and <Emphasis Type="Italic">Betula</Emphasis> pollen concentration levels using spatiotemporal correlation properties of pollen count

The aim of the study was to create and evaluate models for predicting high levels of daily pollen concentration of Corylus, Alnus, and Betula using a spatiotemporal correlation of pollen count. For each taxon, a high pollen count level was established according to the first allergy symptoms during exposure. The dataset was divided into a training set and a test set, using a stratified random split. For each taxon and city, the model was built using a random forest method. Corylus models performed poorly. However, the study revealed the possibility of predicting with substantial accuracy the occurrence of days with high pollen concentrations of Alnus and Betula using past pollen count data from monitoring sites. These results can be used for building (1) simpler models, which require data only from aerobiological monitoring sites, and (2) combined meteorological and aerobiological models for predicting high levels of pollen concentration.     

Spatiotemporal models for predicting high pollen concentration level of Corylus,Alnus, and Betula

Corylus, Alnus, and Betula trees are among the most important sources of allergic pollen in the temperate zone of the Northern Hemisphere and have a large impact on the quality of life and productivity of allergy sufferers. Therefore, it is important to predict high pollen concentrations, both in time and space. The aim of this study was to create and evaluate spatiotemporal models for predicting high Corylus, Alnus, and Betula pollen concentration levels, based on gridded meteorological data. Aerobiological monitoring was carried out in 11 cities in Poland and gathered, depending on the site, between 2 and 16 years of measurements. According to the first allergy symptoms during exposure, a high pollen count level was established for each taxon. An optimizing probability threshold technique was used for mitigation of the problem of imbalance in the pollen concentration levels. For each taxon, the model was built using a random forest method. The study revealed the possibility of moderately reliable prediction of Corylus and highly reliable prediction of Alnus and Betula high pollen concentration levels, using preprocessed gridded meteorological data. Cumulative growing degree days and potential evaporation proved to be two of the most important predictor variables in the models. The final models predicted not only for single locations but also for continuous areas. Furthermore, the proposed modeling framework could be used to predict high pollen concentrations of Corylus, Alnus, Betula, and other taxa, and in other countries.