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Spotlight on the underdogs
(2017)
Alternaria (A.) is a genus of widespread fungi capable of producing numerous, possibly health-endangering Alternaria toxins (ATs), which are usually not the focus of attention. The formation of ATs depends on the species and complex interactions of various environmental factors and is not fully understood. In this study the influence of temperature (7 °C, 25 °C), substrate (rice, wheat kernels) and incubation time (4, 7, and 14 days) on the production of thirteen ATs and three sulfoconjugated ATs by three different Alternaria isolates from the species groups A. tenuissima and A. infectoria was determined. High-performance liquid chromatography coupled with tandem mass spectrometry was used for quantification. Under nearly all conditions, tenuazonic acid was the most extensively produced toxin. At 25 °C and with increasing incubation time all toxins were formed in high amounts by the two A. tenuissima strains on both substrates with comparable mycotoxin profiles. However, for some of the toxins, stagnation or a decrease in production was observed from day 7 to 14. As opposed to the A. tenuissima strains, the A. infectoria strain only produced low amounts of ATs, but high concentrations of stemphyltoxin III. The results provide an essential insight into the quantitative in vitro AT formation under different environmental conditions, potentially transferable to different field and storage conditions
We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1 beta and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects.
Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs) via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H) screen with prototype FV (PFV) Gag protein as bait we identified human polo-like kinase 2 (hPLK2), a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P) motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt) particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells.
Models are useful tools for understanding and predicting ecological patterns and processes. Under ongoing climate and biodiversity change, they can greatly facilitate decision-making in conservation and restoration and help designing adequate management strategies for an uncertain future. Here, we review the use of spatially explicit models for decision support and to identify key gaps in current modelling in conservation and restoration. Of 650 reviewed publications, 217 publications had a clear management application and were included in our quantitative analyses. Overall, modelling studies were biased towards static models (79%), towards the species and population level (80%) and towards conservation (rather than restoration) applications (71%). Correlative niche models were the most widely used model type. Dynamic models as well as the gene-to-individual level and the community-to-ecosystem level were underrepresented, and explicit cost optimisation approaches were only used in 10% of the studies. We present a new model typology for selecting models for animal conservation and restoration, characterising model types according to organisational levels, biological processes of interest and desired management applications. This typology will help to more closely link models to management goals. Additionally, future efforts need to overcome important challenges related to data integration, model integration and decision-making. We conclude with five key recommendations, suggesting that wider usage of spatially explicit models for decision support can be achieved by 1) developing a toolbox with multiple, easier-to-use methods, 2) improving calibration and validation of dynamic modelling approaches and 3) developing best-practise guidelines for applying these models. Further, more robust decision-making can be achieved by 4) combining multiple modelling approaches to assess uncertainty, and 5) placing models at the core of adaptive management. These efforts must be accompanied by long-term funding for modelling and monitoring, and improved communication between research and practise to ensure optimal conservation and restoration outcomes.
The Arabidopsis Kinome
(2014)
Background
Protein kinases constitute a particularly large protein family in Arabidopsis with important functions in cellular signal transduction networks. At the same time Arabidopsis is a model plant with high frequencies of gene duplications. Here, we have conducted a systematic analysis of the Arabidopsis kinase complement, the kinome, with particular focus on gene duplication events. We matched Arabidopsis proteins to a Hidden-Markov Model of eukaryotic kinases and computed a phylogeny of 942 Arabidopsis protein kinase domains and mapped their origin by gene duplication.
Results
The phylogeny showed two major clades of receptor kinases and soluble kinases, each of which was divided into functional subclades. Based on this phylogeny, association of yet uncharacterized kinases to families was possible which extended functional annotation of unknowns. Classification of gene duplications within these protein kinases revealed that representatives of cytosolic subfamilies showed a tendency to maintain segmentally duplicated genes, while some subfamilies of the receptor kinases were enriched for tandem duplicates. Although functional diversification is observed throughout most subfamilies, some instances of functional conservation among genes transposed from the same ancestor were observed. In general, a significant enrichment of essential genes was found among genes encoding for protein kinases.
Conclusions
The inferred phylogeny allowed classification and annotation of yet uncharacterized kinases. The prediction and analysis of syntenic blocks and duplication events within gene families of interest can be used to link functional biology to insights from an evolutionary viewpoint. The approach undertaken here can be applied to any gene family in any organism with an annotated genome.
Objective: We investigated the effects of combined balance and strength training on measures of balance and muscle strength in older women with a history of falls.
Methods: Twenty-seven older women aged 70.4 ± 4.1 years (age range: 65 to 75 years) were randomly allocated to either an intervention (IG, n = 12) or an active control (CG, n = 15) group. The IG completed 8 weeks combined balance and strength training program with three sessions per week including visual biofeedback using force plates. The CG received physical therapy and gait training at a rehabilitation center. Training volumes were similar between the groups. Pre and post training, tests were applied for the assessment of muscle strength (weight-bearing squat [WBS] by measuring the percentage of body mass borne by each leg at different knee flexions [0°, 30°, 60°, and 90°], sit-to-stand test [STS]), and balance. Balance tests used the modified clinical test of sensory interaction (mCTSIB) with eyes closed (EC) and opened (EO), on stable (firm) and unstable (foam) surfaces as well as spatial parameters of gait such as step width and length (cm) and walking speed (cm/s).
Results: Significant group × time interactions were found for different degrees of knee flexion during WBS (0.0001 < p < 0.013, 0.441 < d < 0.762). Post hoc tests revealed significant pre-to-post improvements for both legs and for all degrees of flexion (0.0001 < p < 0.002, 0.697 < d < 1.875) for IG compared to CG. Significant group × time interactions were found for firm EO, foam EO, firm EC, and foam EC (0.006 < p < 0.029; 0.302 < d < 0.518). Post hoc tests showed significant pre-to-post improvements for both legs and for all degrees of oscillations (0.0001 < p < 0.004, 0.753 < d < 2.097) for IG compared to CG. This study indicates that combined balance and strength training improved percentage distribution of body weight between legs at different conditions of knee flexion (0°, 30°, 60°, and 90°) and also decreased the sway oscillation on a firm surface with eyes closed, and on foam surface (with eyes opened or closed) in the IG.
Conclusion: The higher positive effects of training seen in standing balance tests, compared with dynamic tests, suggests that balance training exercises including lateral, forward, and backward exercises improved static balance to a greater extent in older women.
Background: Agility in general and change-of-direction speed (CoD) in particular represent important performance determinants in elite soccer.
Objectives: The objectives of this study were to determine the effects of a 6-week neuromuscular training program on agility performance, and to determine differences in movement times between the slower and faster turning directions in elite soccer players. Materials and Methods: Twenty male elite soccer players from the Stade Rennais Football Club (Ligue 1, France) participated in this study. The players were randomly assigned to a neuromuscular training group (NTG, n = 10) or an active control (CG, n = 10) according to their playing position. NTG participated in a 6-week, twice per week neuromuscular training program that included CoD, plyometric and dynamic stability exercises. Neuromuscular training replaced the regular warm-up program. Each training session lasted 30 min. CG continued their regular training program. Training volume was similar between groups. Before and after the intervention, the two groups performed a reactive agility test that included 180° left and right body rotations followed by a 5-m linear sprint. The weak side was defined as the left/right turning direction that produced slower overall movement times (MT). Reaction time (RT) was assessed and defined as the time from the first appearance of a visual stimulus until the athlete’s first movement. MT corresponded to the time from the first movement until the athlete reached the arrival gate (5 m distance).
Results: No significant between-group baseline differences were observed for RT or MT. Significant group x time interactions were found for MT (p = 0.012, effect size = 0.332, small) for the slower and faster directions (p = 0.011, effect size = 0.627, moderate). Significant pre-to post improvements in MT were observed for NTG but not CG (p = 0.011, effect size = 0.877, moderate). For NTG, post hoc analyses revealed significant MT improvements for the slower (p = 0.012, effect size = 0.897, moderate) and faster directions (p = 0.017, effect size = 0.968, moderate).
Conclusion: Our results illustrate that 6 weeks of neuromuscular training with two sessions per week included in the warm-up program, significantly enhanced agility performance in elite soccer players. Moreover, improvements were found on both sides during body rotations. Thus, practitioners are advised to focus their training programs on both turning directions.
The innovative dual-purpose chicken approach aims at contributing to the transition towards sustainable poultry production by avoiding the culling of male chickens. To successfully integrate sustainability aspects into innovation, goal congruency among actors and clearly communicating the added value within the actor network and to consumers is needed. The challenge of identifying common sustainability goals calls for decision support tools. The objectives of our research were to investigate whether the tool could assist in improving communication and marketing with respect to sustainability and optimizing the value chain organization. Three actor groups participated in the tool application, in which quantitative and qualitative data were collected. The results showed that there were manifold sustainability goals within the innovation network, but only some goals overlapped, and the perception of their implementation also diverged. While easily marketable goals such as ‘animal welfare’ were perceived as being largely implemented, economic goals were prioritized less often, and the implementation was perceived as being rather low. By visualizing congruencies and differences in the goals, the tool helped identify fields of action, such as improved information flows and prompted thinking processes. We conclude that the tool is useful for managing complex decision processes with several actors involved.
Human and murine studies identified the lysosomal enzyme acid sphingomyelinase (ASM) as a target for antidepressant therapy and revealed its role in the pathophysiology of major depression. In this study, we generated a mouse model with overexpression of Asm (Asm-tg(fb)) that is restricted to the forebrain to rule out any systemic effects of Asm overexpression on depressive-like symptoms. The increase in Asm activity was higher in male Asm-tg(fb) mice than in female Asm-tg(fb) mice due to the breeding strategy, which allows for the generation of wild-type littermates as appropriate controls. Asm overexpression in the forebrain of male mice resulted in a depressive-like phenotype, whereas in female mice, Asm overexpression resulted in a social anxiogenic-like phenotype. Ceramides in male Asm-tg(fb) mice were elevated specifically in the dorsal hippocampus. mRNA expression analyses indicated that the increase in Asm activity affected other ceramide-generating pathways, which might help to balance ceramide levels in cortical brain regions. This forebrain-specific mouse model offers a novel tool for dissecting the molecular mechanisms that play a role in the pathophysiology of major depression.
In einer prospektiven Längsschnittstudie wurden Auswirkungen früher psychosozialer Risiken bis ins junge Erwachsenenalter untersucht und dabei die Rolle von affektiver und behavioraler Dysregulation im Kindesalter als vermittelndem Faktor überprüft. Drei Monate nach der Geburt wurde das Vorliegen von 11 psychosozialen Belastungsfaktoren erfasst. Im Alter von 8 – 15 Jahren wurde dreimal das Child Behavior Checklist-Dysregulationsprofil (CBCL-DP) erhoben. Mit 25 Jahren wurde ein Strukturiertes Klinisches Interview durchgeführt und 309 der Teilnehmer füllten den Young Adult Self-Report aus. Frühe psychosoziale Risiken gingen mit einem erhöhten Risiko für das Vorliegen eines Substanzmissbrauchs im jungen Erwachsenenalter sowie mit erhöhtem externalisierendem und internalisierendem Problemverhalten einher. Der Zusammenhang zwischen frühen psychosozialen Risiken und späterem externalisierendem bzw. internalisierendem Problemverhalten wurde durch das CBCL-DP vermittelt.