Characterization of DCL4 missense alleles provides insights into its ability to process distinct classes of dsRNA substrates

In the model plant Arabidopsis thaliana, four Dicer‐like proteins (DCL1–4) mediate the production of various classes of small RNAs (sRNAs). Among these four proteins, DCL4 is by far the most versatile RNaseIII‐like enzyme, and previously identified dcl4 missense alleles were shown to uncouple the production of the various classes of DCL4‐dependent sRNAs. Yet little is known about the molecular mechanism behind this uncoupling. Here, by studying the subcellular localization, interactome and binding to the sRNA precursors of three distinct dcl4 missense alleles, we simultaneously highlight the absolute requirement of a specific residue in the helicase domain for the efficient production of all DCL4‐dependent sRNAs, and identify, within the PAZ domain, an important determinant of DCL4 versatility that is mandatory for the efficient processing of intramolecular fold‐back double‐stranded RNA (dsRNA) precursors, but that is dispensable for the production of small interfering RNAs (siRNAs) from RDR‐dependent dsRNA susbtrates. This study not only provides insights into the DCL4 mode of action, but also delineates interesting tools to further study the complexity of RNA silencing pathways in plants, and possibly other organisms.     

Synthesis and biological evaluation of longanlactone analogues as neurotrophic agents

Longanlactone analogues were synthesized using a route featuring Friedel-Crafts acylation, Sonogashira coupling and 1,3-dipolar cycloaddition reactions. Structure–activity relationships were investigated for neurotrophic activity. Compound 6 was found to have the most potent neurotrophic activity among all the synthesized analogues in Neuro2a cells as evidenced by a battery of in vitro/cell based assays for assessment of neurogenic and potential neurotrophic activity including neurite outgrowth assay and real time PCR for popular markers of augmented neurotrophic activity. Compound 6 might serve as a template for further development of highly effective neurotrophic molecules.     

Responses of biotic interactions of dominant and subordinate species to decadal warming and simulated rotational grazing in Tibetan alpine meadow

Warming increases competition among plant species in alpine communities by ameliorating harsh environmental conditions, such as low temperatures. Grazing, as the main human activity, may mitigate the effect of warming, as previously reported. However, it is critical to refine the effects of warming on biotic interactions among species, for example, by taking the competitive ability of species into consideration. Based on a 10-year warming and grazing experiment in a Tibetan alpine meadow, we evaluated interspecific biotic interactions of dominant and subordinate species, using the approach of interspecific spatial associations. Warming significantly increased competition between subordinate and dominant species as well as among subordinate species, but not among dominant species. Moreover, facilitation of dominant-subordinate species also increased under warming. Simulated rotational grazing had similar effects to warming, with increasing interspecific competition. Our results show that, when studying the effects of warming on biotic interactions among species, it is necessary to characterize different species pairs relative to their competitive ability, and that simulated rotational grazing does not mitigate the effects of warming in the long term. Our results also provide evidence that the spatial pattern of species is a critical mechanism in species coexistence.     

Deregulation of neuronal miRNAs induced by amyloid-β or TAU pathology

Background

Despite diverging levels of amyloid-β (Aβ) and TAU pathology, different mouse models, as well as sporadic AD patients show predictable patterns of episodic memory loss. MicroRNA (miRNA) deregulation is well established in AD brain but it is unclear whether Aβ or TAU pathology drives those alterations and whether miRNA changes contribute to cognitive decline.

Methods

miRNAseq was performed on cognitively intact (4 months) and impaired (10 months) male APPtg (APP^swe/PS1^L166P) and TAUtg (THY-Tau22) mice and their wild-type littermates (APPwt and TAUwt). We analyzed the hippocampi of 12 mice per experimental group (n =?96 in total), and employed a 2-way linear model to extract differentially expressed miRNAs. Results were confirmed by qPCR in a separate cohort of 4 M and 10 M APPtg and APPwt mice (n =?7–9 per group) and in human sporadic AD and non-demented control brain. Fluorescent in situ hybridization identified their cellular expression. Functional annotation of predicted targets was performed using GO enrichment. Behavior of wild-type mice was assessed after intracerebroventricular infusion of miRNA mimics.

Results

Six miRNAs (miR-10a-5p, miR-142a-5p, miR-146a-5p, miR-155-5p, miR-211-5p, miR-455-5p) are commonly upregulated between APPtg and TAUtg mice, and four of these (miR-142a-5p, miR-146a-5p, miR-155-5p and miR-455-5p) are altered in AD patients. All 6 miRNAs are strongly enriched in neurons. Upregulating these miRNAs in wild-type mice is however not causing AD-related cognitive disturbances.

Conclusion

Diverging AD-related neuropathologies induce common disturbances in the expression of neuronal miRNAs. 4 of these miRNAs are also upregulated in AD patients. Therefore these 4 miRNAs (miR-142a-5p, miR-146a-5p, miR-155-5p and miR-455-5p) appear part of a core pathological process in AD patients and APPtg and TAUtg mice. They are however not causing cognitive disturbances in wild-type mice. As some of these miRNA target AD relevant proteins, they may be, in contrast, part of a protective response in AD.

     

Functional impairment of MSC induced by transient warming events: Correlation with loss of adhesion and altered cell size

Background

We recently showed that transient warming effects decreased the functional and adhesion properties of mesenchymal stromal cells (MSC) while post-thaw viability remained high. In an attempt to better predict functional impairment of cryopreserved MSC, we further analysed the correlation between viability, immunosuppressive activity and adhesion of cells exposed or not to warming events.

Morphological variability of Tragopogon pterodes Pančić ex Petrović achenes: taxonomic evaluation of heterocarpy

This study presents the carpological heterogeneity of Tragopogon pterodes, an endemic plant species from Balkan Peninsula. The goal of this paper was to determine the variability of morphological characters of achenes and assess the degree of their morphological differentiation relative to the position they occupy in the receptacle. Analysis included four different populations of T. pterodes and examination of 18 (8 qualitative and 10 quantitative) characters of achenes in total. Data analysis employed basic statistic, univariate (ANOVA, Tukey HSD) and multivariate (CDA, CA) analyses to check the level of heterocarpy in this species. The results indicate possible morphological differentiation of three groups of achenes (outer, median and inner achenes), depending of their position on the receptacle. The members of all three types were described, illustrated and compared. The variability of investigated carpological characters in this species is providing important information prior to their further taxonomic treatment.     

Diet-induced obesity and associated disorders are prevented by natural bioactive type 1 fish collagen peptides (Naticol®) treatment

To fight against metabolic disorders such as insulin resistance, new alimentary behaviors are developed. For instance, hyperproteined, gluten-free, or collagen-enriched diets could be preconized in order to reduce the consequences of obesity. In this aim, this study evaluates the potential effects of warm sea fish collagen peptides (Naticol®) on representative metabolic and inflammatory parameters. For that, male C57Bl6/J mice fed with either a chow- (CD) or high-fat diet (HFD) were submitted or not to specific collagen peptides in drinking water (4 g/kg bw/d) for 20 weeks. Weight, body composition, glucose tolerance, and insulin sensitivity were followed up. Effects of fish collagen peptides on various blood parameters reflecting the metabolism status were also measured (free fatty acids, triglycerides, cholesterol, hormones) together with adipocyte inflammation. Results showed that HFD-fed mice supplemented by fish collagen peptides exhibited a significant lower increase in body weight as soon as the twelfth week of treatment whereas no effect of the peptide was observed in CD fed mice. In line with this result, a weaker increase in fat mass in HFD-fed mice supplemented with Naticol® at both 9 and 18 weeks of treatment was also observed. In spite of this resistance to obesity promoted by fish collagen peptides treatment, no difference in glucose tolerance was found between groups whereas mice treated with Naticol® exhibited a lower basal glycemia. Also, even if no effect of the treatment on adipocyte lipolysis was found, a decrease of inflammatory cytokines was retrieved in collagen-supplemented group arguing for a potential better insulin sensitivity. Altogether, these results need to be completed but are the first describing a benefic role of warm sea fish collagen peptides in a context of metabolic disease paving the route for a potential utilization in human obesity-associated disorders.