PrimPol-deficient cells exhibit a pronounced G2 checkpoint response following UV damage

PrimPol is a recently identified member of the archaeo-eukaryote primase (AEP) family of primase-polymerases. It has been shown that this mitochondrial and nuclear localized enzyme plays roles in the maintenance of both unperturbed replication fork progression and in the bypass of lesions after DNA damage. Here, we utilized an avian (DT40) knockout cell line to further study the consequences of loss of PrimPol (PrimPol^?/?) on the downstream maintenance of cells after UV damage. We report that PrimPol^?/? cells are more sensitive to UV-C irradiation in colony survival assays than Pol η-deficient cells. Although this increased UV sensitivity is not evident in cell viability assays, we show that this discrepancy is due to an enhanced checkpoint arrest after UV-C damage in the absence of PrimPol. PrimPol^?/? arrested cells become stalled in G2, where they are protected from UV-induced cell death. Despite lacking an enzyme required for the bypass and maintenance of replication fork progression in the presence of UV damage, we show that PrimPol^?/? cells actually have an advantage in the presence of a Chk1 inhibitor due to their slow progression through S-phase.     

Effects of IGF‐1 isoforms on muscle growth and sarcopenia

The decline in skeletal muscle mass and strength occurring in aging, referred as sarcopenia, is the result of many factors including an imbalance between protein synthesis and degradation, changes in metabolic/hormonal status, and in circulating levels of inflammatory mediators. Thus, factors that increase muscle mass and promote anabolic pathways might be of therapeutic benefit to counteract sarcopenia. Among these, the insulin‐like growth factor‐1 (IGF‐1) has been implicated in many anabolic pathways in skeletal muscle. IGF‐1 exists in different isoforms that might exert different role in skeletal muscle. Here we study the effects of two full propeptides IGF‐1Ea and IGF‐1Eb in skeletal muscle, with the aim to define whether and through which mechanisms their overexpression impacts muscle aging. We report that only IGF‐1Ea expression promotes a pronounced hypertrophic phenotype in young mice, which is maintained in aged mice. Nevertheless, examination of aged transgenic mice revealed that the local expression of either IGF‐1Ea or IGF‐1Eb transgenes was protective against age‐related loss of muscle mass and force. At molecular level, both isoforms activate the autophagy/lysosome system, normally altered during aging, and increase PGC1‐α expression, modulating mitochondrial function, ROS detoxification, and the basal inflammatory state occurring at old age. Moreover, morphological integrity of neuromuscular junctions was maintained and preserved in both MLC/IGF‐1Ea and MLC/IGF‐1Eb mice during aging. These data suggest that IGF‐1 is a promising therapeutic agent in staving off advancing muscle weakness.     

Anthropogenic nitrogen enrichment enhances soil carbon accumulation by impacting saprotrophs rather than ectomycorrhizal fungal activity

There is evidence that anthropogenic nitrogen (N) deposition enhances carbon (C) sequestration in boreal forest soils. However, it is unclear how free‐living saprotrophs (bacteria and fungi, SAP) and ectomycorrhizal (EM) fungi responses to N addition impact soil C dynamics. Our aim was to investigate how SAP and EM communities are impacted by N enrichment and to estimate whether these changes influence decay of litter and humus. We conducted a long‐term experiment in northern Sweden, maintained since 2004, consisting of ambient, low N additions (0, 3, 6, and 12 kg N ha^?1 year^?1) simulating current N deposition rates in the boreal region, as well as a high N addition (50 kg N ha^?1 year^?1). Our data showed that long‐term N enrichment impeded mass loss of litter, but not of humus, and only in response to the highest N addition treatment. Furthermore, our data showed that EM fungi reduced the mass of N and P in both substrates during the incubation period compared to when only SAP organisms were present. Low N additions had no effect on microbial community structure, while the high N addition decreased fungal and bacterial biomasses and altered EM fungi and SAP community composition. Actinomycetes were the only bacterial SAP to show increased biomass in response to the highest N addition. These results provide a mechanistic understanding of how anthropogenic N enrichment can influence soil C accumulation rates and suggest that current N deposition rates in the boreal region (≤12 kg N ha^?1 year^?1) are likely to have a minor impact on the soil microbial community and the decomposition of humus and litter.     

Neuronal ribonucleoprotein granules: Dynamic sensors of localized signals

Membrane‐less organelles, because of their capacity to dynamically, selectively and reversibly concentrate molecules, are very well adapted for local information processing and rapid response to environmental fluctuations. These features are particularly important in the context of neuronal cells, where synapse‐specific activation, or localized extracellular cues, induce signaling events restricted to specialized axonal or dendritic subcompartments. Neuronal ribonucleoprotein (RNP) particles, or granules, are nonmembrane bound macromolecular condensates that concentrate specific sets of mRNAs and regulatory proteins, promoting their long‐distance transport to axons or dendrites. Neuronal RNP granules also have a dual function in regulating the translation of associated mRNAs: while preventing mRNA translation at rest, they fuel local protein synthesis upon activation. As revealed by recent work, rapid and reversible switches between these two functional modes are triggered by modifications of the networks of interactions underlying RNP granule assembly. Such flexible properties also come with a cost, as neuronal RNP granules are prone to transition into pathological aggregates in response to mutations, aging, or cellular stresses, further emphasizing the need to better understand the mechanistic principles governing their dynamic assembly and regulation in living systems.     

Natural and Regenerated Saltmarshes Exhibit Similar Soil and Belowground Organic Carbon Stocks,Root Production and Soil Respiration

Ecosystems - Saltmarshes provide many valuable ecosystem services including storage of a large amount of ‘blue carbon’ within their soils. To date, up to 50% of the world’s...     

Developmentally Arrested Precursors of Pontine Neurons Establish an Embryonic Blueprint of the Drosophila Central Complex

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Enantioselective total synthesis of altersolanol A and N

The development of the first enantioselective total synthesis of altersolanol N is reported. The decisive step of the synthesis is the enantioselective formation of the tetrahydroanthraquinone nucleus by a [4 + 2]-cycloaddition in high yield and with excellent diastereo- and enantioselectivity (>95:5 dr and 95:5 er). In addition, a demanding selective monoacetylation of the OH group at the C-2 position was achieved: an epoxide ring opening with the participation of a neighbouring acetyl group could be established. The route proved to be an efficient alternative to also access enantiomerically pure altersolanol A.