Dnmt1 activity is dispensable in δ-cells but is essential for α-cell homeostasis

In addition to β-cells, pancreatic islets contain α- and δ-cells, which respectively produce glucagon and somatostatin. The reprogramming of these two endocrine cell types into insulin producers, as observed after a massive β-cell ablation in mice, may help restoring a functional β-cell mass in type 1 diabetes. Yet, the spontaneous α-to-β and δ-to-β conversion processes are relatively inefficient in adult animals and the underlying epigenetic mechanisms remain unclear. Several studies indicate that the conserved chromatin modifiers DNA methyltransferase 1 (Dnmt1) and Enhancer of zeste homolog 2 (Ezh2) are important for pancreas development and restrict islet cell plasticity. Here, to investigate the role of these two enzymes in α- and δ-cell development and fate maintenance, we genetically inactivated them in each of these two cell types. We found that loss of Dnmt1 does not enhance the conversion of α- or δ-cells toward a β-like fate. In addition, while Dnmt1 was dispensable for the development of these two cell types, we noticed a gradual loss of α-, but not δ-cells in adult mice. Finally, we found that Ezh2 inactivation does not enhance α-cell plasticity, and, contrary to what is observed in β-cells, does not impair α-cell proliferation. Our results indicate that both Dnmt1 and Ezh2 play distinct roles in the different islet cell types.     

Feeding ecology of the highly threatened common bottlenose dolphin of the Gulf of Ambracia,Greece, through stable isotope analysis

The Gulf of Ambracia, in northwestern Greece, hosts a highly threatened community of about 150 common bottlenose dolphins (Tursiops truncatus). Until now, information on their feeding habits was derived exclusively from fish scale samples collected during surface-feeding events targeting small schooling epipelagic fish. The aim of this study was to determine the diet of bottlenose dolphins living in the Gulf of Ambracia through the application of Bayesian isotopic mixing models. Skin biopsy samples of 16 dolphins were analyzed and no difference related to sex or age-class was found in δ¹³C and δ¹⁵N values. Results suggested that the dolphin diet was mainly based on Trachurus trachurus, species belonging to the family Sparidae: Diplodus annularis, Lithognathus mormyrus, and Sepia officinalis, which represented together about 42% ± 15% of the biomass ingested, followed by species belonging to the order Clupeiformes (Engraulis encrasicolus, Sardinella aurita, and Sardina pilchardus) and the genus Gobius (37% ± 17%). A better understanding of the feeding habits of these dolphins sheds light on the feeding ecology of this highly threatened population by, for instance, evidencing interactions with artisanal fisheries sharing the same target species, and is key for identifying adequate management measures consistent with an ecosystem-based approach.     

Isotopic evidence for increased carbon and nitrogen exchanges between peatland plants and their symbiotic microbes with rising atmospheric CO2 concentrations since 15,000 cal. year BP

Whether nitrogen (N) availability will limit plant growth and removal of atmospheric CO₂ by the terrestrial biosphere this century is controversial. Studies have suggested that N could progressively limit plant growth, as trees and soils accumulate N in slowly cycling biomass pools in response to increases in carbon sequestration. However, a question remains over whether longer-term (decadal to century) feedbacks between climate, CO₂ and plant N uptake could emerge to reduce ecosystem-level N limitations. The symbioses between plants and microbes can help plants to acquire N from the soil or from the atmosphere via biological N₂ fixation—the pathway through which N can be rapidly brought into ecosystems and thereby partially or completely alleviate N limitation on plant productivity. Here we present measurements of plant N isotope composition (δ¹⁵N) in a peat core that dates to 15,000 cal. year BP to ascertain ecosystem-level N cycling responses to rising atmospheric CO₂ concentrations. We find that pre-industrial increases in global atmospheric CO₂ concentrations corresponded with a decrease in the δ¹⁵N of both Sphagnum moss and Ericaceae when constrained for climatic factors. A modern experiment demonstrates that the δ¹⁵N of Sphagnum decreases with increasing N₂-fixation rates. These findings suggest that plant-microbe symbioses that facilitate N acquisition are, over the long term, enhanced under rising atmospheric CO₂ concentrations, highlighting an ecosystem-level feedback mechanism whereby N constraints on terrestrial carbon storage can be overcome.     

Involvement of protein kinase Cδ in induction of apoptosis by cationic liposomes in macrophage-like RAW264.7 cells

We have recently demonstrated that reactive oxygen species (ROS) play an important role in RAW264.7 cell apoptosis induced by cationic liposomes composed of stearylamine (SA-liposomes). In this study, we investigated whether protein kinase Cδ PKCδ) is involved in apoptosis induced by cationic liposomes. Tyrosine phosphorylation, nuclear localization, and cleavage of PKCδ were observed following the treatment of cells with SA-liposomes, suggesting that SA-liposomes activate PKCδ. Rottlerin, a specific inhibitor of PKCδ, inhibited ROS generation and also suppressed apoptosis. Cell surface proteoglycans may contribute to PKCδ activation by SA-liposomes. These findings suggest that PKCδ is strongly associated with apoptosis induced by SA-liposomes.     

Effect of heme on the activity of chick embryo liver mitochondrial δ-aminolevulinate synthase

We have examined the effect of heme on the activity of native δ-aminolevulinate synthase isolated from drug-induced chick embryo liver mitochondria. The enzyme was not inhibited by concentrations of heme up to 1nM and this finding makes it improbable that heme acts physiologically to control mitochondrial δ-aminolevulinate synthase activity.     

The biosynthesis,metabolism and translocation of β-amyrin in Sorghum bicolor

The biosynthesis of [¹⁴C] β-amyrin and three other labelled 3β-hydroxypentacyclic triterpenes from [2-^14C] acetate in leaves of Sorghum bicolor was demonstrated. Evidence for the metabolism of [¹⁴C] β-amyrin to the corresponding C-3 ketone (β-amyrone) and for the transport of [¹⁴C] β-amyrin in leaves was also obtained.     

Deubiquitinase OTUD3 regulates metabolism homeostasis in response to nutritional stresses

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Two forms of human DNA polymerase δ: Who does what and why?

DNA polymerase δ (Pol δ) plays a central role in lagging strand DNA synthesis in eukaryotic cells, as well as an important role in DNA repair processes. Human Pol δ4 is a heterotetramer of four subunits, the smallest of which is p12. Pol δ3 is a trimeric form that is generated in vivo by the degradation of the p12 subunit in response to DNA damage, and during entry into S-phase. The biochemical properties of the two forms of Pol δ, as well as the changes in their distribution during the cell cycle, are reviewed from the perspective of understanding their respective cellular functions. Biochemical and cellular studies support a role for Pol δ3 in gap filling during DNA repair, and in Okazaki fragment synthesis during DNA replication. Recent studies of cells in which p12 expression is ablated, and are therefore null for Pol δ4, show that Pol δ4 is not required for cell viability. These cells have a defect in homologous recombination, revealing a specific role for Pol δ4 that cannot be performed by Pol δ3. Pol δ4 activity is required for D-loop displacement synthesis in HR. The reasons why Pol δ4 but not Pol δ3 can perform this function are discussed, as well as the question of whether helicase action is needed for efficient D-loop displacement synthesis. Pol δ4 is largely present in the G1 and G2/M phases of the cell cycle and is low in S phase. This is discussed in relation to the availability of Pol δ4 as an additional layer of regulation for HR activity during cell cycle progression.     

Enhanced foliar 15N enrichment with increasing nitrogen addition rates: Role of plant species and nitrogen compounds

Determining the abundance of N isotope (δ¹⁵N) in natural environments is a simple but powerful method for providing integrated information on the N cycling dynamics and status in an ecosystem under exogenous N inputs. However, whether the input of different N compounds could differently impact plant growth and their ¹⁵N signatures remains unclear. Here, the response of ¹⁵N signatures and growth of three dominant plants (Leymus chinensis, Carex duriuscula, and Thermopsis lanceolata) to the addition of three N compounds (NH₄HCO₃, urea, and NH₄NO₃) at multiple N addition rates were assessed in a meadow steppe in Inner Mongolia. The three plants showed different initial foliar δ¹⁵N values because of differences in their N acquisition strategies. Particularly, T. lanceolata (N₂-fixing species) showed significantly lower ¹⁵N signatures than L. chinensis (associated with arbuscular mycorrhizal fungi [AMF]) and C. duriuscula (associated with AMF). Moreover, the foliar δ¹⁵N of all three species increased with increasing N addition rates, with a sharp increase above an N addition rate of ~10 g N m⁻² year⁻¹. Foliar δ¹⁵N values were significantly higher when NH₄HCO₃ and urea were added than when NH₄NO₃ was added, suggesting that adding weakly acidifying N compounds could result in a more open N cycle. Overall, our results imply that assessing the N transformation processes in the context of increasing global N deposition necessitates the consideration of N deposition rates, forms of the deposited N compounds, and N utilization strategies of the co-existing plant species in the ecosystem.     

Palmitoylation and PDE6δ regulate membrane-compartment-specific substrate ubiquitylation and degradation

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