The Late Eocene ‘Whiskey Creek’ methane-seep deposit (western Washington State)

The Late Eocene ‘Whiskey Creek’ deposit (Pysht Formation, Olympic Penisula, Washington State) formed at a methane-seep. Early diagenetic micrites and aragonite cement have δ¹³C values as low as −36‰ indicating that the seepage fluids contained methane. With respect to micrite samples, low δ¹³C values correlate with relatively high δ¹³O values andvice versa. Ongoing micrite formation after the cessation of the seepage during increased burial might have altered the isotopic composition of the microcrystalline carbonates toward lower δ¹³O values and higher δ¹³C values. Alternatively, the trend in isotope values may reflect a change in the composition of seepage fluids. The principal difference between these scenarios is the duration of seepage with respect to micrite formation. Two petrographically similar varieties of blocky calcite spar are related to different carbonate sources. The δ¹³C values range from −32 to −29‰ for one type of blocky spar and are either the result of methane oxidation or indicate thermal decarboxylation of organic matter. Low δ¹⁸O values are in favour of the latter. For the other type of spar, δ¹³C values as high as +6‰ indicate carbonate formation within the zone of methanogensis. The ‘Whiskey Creek’ limestone exhibits a chaotic fabric produced by a variety of processes, including bioturbation, concretionary carbonate formation, earlyin situ brecciation, carbonate corrosion, and late fracturing of the rock. Two varieties of micrite aggregates are responsible for the nodular fabric of the limestone. Smoothly-shaped pyritiferous micrite nodules are of diagenetic origin and formed in a manner similar to that which produces carbonate concretions. Apart from being induced by anaerobic oxidation of methane, their formation is proposed to be linked to iron reduction and sulphide formation. The second, dominant variety is represented by irregularly-shaped, nodular to angular micrite aggregates surrounded by massive rims of pyrite, resulting from carbonate corrosion. A pure, fluorescent seam-micrite, constructive in origin, lines cavities or surrounds micritic aggregates.     

Anti-glycation effect and the α-amylase,lipase, and α-glycosidase inhibition properties of a polyphenolic fraction derived from citrus wastes

Abstract

The advanced glycation end products (AGEs) constitute a wide variety of substances synthesized from interactions between amino groups of proteins and reducing sugars, which excess induces pathogenesis of chronic diseases. Brazil is the major producer of citrus, a low-cost source of hesperidin, which is a polyphenol recognized for its capacity to inhibit AGEs formation. This is the first work to evaluate the effects of a polyphenolic fraction derived from citrus wastes on the antiglycation and on the inhibition properties of digestive enzymes on the possibility to process these wastes in high value-added products. At concentrations of 10, 15 and 20?mg/mL inhibition of AGEs was higher than 60%. The extracts were able to inhibit by 76% the activity of pancreatic lipase and by 98% the activity of α-glucosidase. For the α-amylase the inhibition capacity was lower than 50%. Strong correlation was obtained among anti-glycation with polyphenolic content and antioxidant capacity.     

MiR‐29 coordinates age‐dependent plasticity brakes in the adult visual cortex

The authors regret having omitted grant attributions in the original publication. The funding section is herewith updated to reflect the change. “Funding attributed to Tommaso Pizzorusso was provided by EPIGEN Flagship project and PRIN2017HM8FA, funding attributed to Alessandro Cellerino was provided by Fondazione Pisa ETHERNA project, funding attributed to Pierre Baldi was provided by NIH (grant NIH {"type":"entrez-nucleotide","attrs":{"text":"GM123558","term_id":"221306858","term_text":"GM123558"}}GM123558), funding attributed to Jessica Kwok was provided by the Leverhulme Trust project grant (RPG‐2018‐100).”     

Functional Differences in Ionic Regulation between Alternatively Spliced Isoforms of the Na+-Ca2+ Exchanger from Drosophila melanogaster

Ion transport and regulation were studied in two, alternatively spliced isoforms of the Na⁺-Ca²⁺ exchanger from Drosophila melanogaster. These exchangers, designated CALX1.1 and CALX1.2, differ by five amino acids in a region where alternative splicing also occurs in the mammalian Na⁺-Ca²⁺ exchanger, NCX1. The CALX isoforms were expressed in Xenopus laevis oocytes and characterized electrophysiologically using the giant, excised patch clamp technique. Outward Na⁺-Ca²⁺ exchange currents, where pipette Ca²⁺ _o exchanges for bath Na⁺ _i, were examined in all cases. Although the isoforms exhibited similar transport properties with respect to their Na⁺ _i affinities and current–voltage relationships, significant differences were observed in their Na⁺ _i- and Ca²⁺ _i-dependent regulatory properties. Both isoforms underwent Na⁺ _i-dependent inactivation, apparent as a time-dependent decrease in outward exchange current upon Na⁺ _i application. We observed a two- to threefold difference in recovery rates from this inactive state and the extent of Na⁺ _i-dependent inactivation was approximately twofold greater for CALX1.2 as compared with CALX1.1. Both isoforms showed regulation of Na⁺-Ca²⁺ exchange activity by Ca²⁺ _i, but their responses to regulatory Ca²⁺ _i differed markedly. For both isoforms, the application of cytoplasmic Ca²⁺ _i led to a decrease in outward exchange currents. This negative regulation by Ca²⁺ _i is unique to Na⁺-Ca²⁺ exchangers from Drosophila, and contrasts to the positive regulation produced by cytoplasmic Ca²⁺ for all other characterized Na⁺-Ca²⁺ exchangers. For CALX1.1, Ca²⁺ _i inhibited peak and steady state currents almost equally, with the extent of inhibition being ≈80%. In comparison, the effects of regulatory Ca²⁺ _i occurred with much higher affinity for CALX1.2, but the extent of these effects was greatly reduced (≈20–40% inhibition). For both exchangers, the effects of regulatory Ca²⁺ _i occurred by a direct mechanism and indirectly through effects on Na⁺ _i-induced inactivation. Our results show that regulatory Ca²⁺ _i decreases Na⁺ _i-induced inactivation of CALX1.2, whereas it stabilizes the Na⁺ _i-induced inactive state of CALX1.1. These effects of Ca²⁺ _i produce striking differences in regulation between CALX isoforms. Our findings indicate that alternative splicing may play a significant role in tailoring the regulatory profile of CALX isoforms and, possibly, other Na⁺-Ca²⁺ exchange proteins.     

The Alzheimer-like phosphorylation of tau protein reduces microtubule binding and involves Ser-Pro and Thr-Pro motifs.

Tau protein can be transformed into an Alzheimer-like state by phosphorylation with a kinase activity from brain [Biernat et al. (1992) EMBO J. 11, 1593-1597]. Here we show that the phosphorylation at Ser-Pro motifs strongly decreases tau's affinity for microtubules. The major reduction occurs during the first of the three main stages of phosphorylation. The data explain the lower stability of microtubules resulting from the pathological tau phosphorylation.     

3’UTR Shortening Potentiates MicroRNA-Based Repression of Pro-differentiation Genes in Proliferating Human Cells

Most mammalian genes often feature alternative polyadenylation (APA) sites and hence diverse 3’UTR lengths. Proliferating cells were reported to favor APA sites that result in shorter 3’UTRs. One consequence of such shortening is escape of mRNAs from targeting by microRNAs (miRNAs) whose binding sites are eliminated. Such a mechanism might provide proliferation-related genes with an expression gain during normal or cancerous proliferation. Notably, miRNA sites tend to be more active when located near both ends of the 3’UTR compared to those located more centrally. Accordingly, miRNA sites located near the center of the full 3’UTR might become more active upon 3''UTR shortening. To address this conjecture we performed 3'' sequencing to determine the 3'' ends of all human UTRs in several cell lines. Remarkably, we found that conserved miRNA binding sites are preferentially enriched immediately upstream to APA sites, and this enrichment is more prominent in pro-differentiation/anti-proliferative genes. Binding sites of the miR17-92 cluster, upregulated in rapidly proliferating cells, are particularly enriched just upstream to APA sites, presumably conferring stronger inhibitory activity upon shortening. Thus 3’UTR shortening appears not only to enable escape from inhibition of growth promoting genes but also to potentiate repression of anti-proliferative genes.