Investigating the carbon isotope composition and leaf wax n-alkane concentration of C3 and C4 plants in Stiffkey saltmarsh, Norfolk, UK

The carbon isotope composition of terrestrial plants records valuable ecophysiological and palaeoecological information. However, interspecies variability in 13C/12C, at both the bulk and compound-specific (CS) level, requires further exploration across a range of ecosystem types. Here, we present bulk and n-alkane δ13C values, and n-alkane concentrations, from seven plants (C3 and C4) growing in a temperate UK saltmarsh. Inter- and intra-species variation in n-alkane δ13C values among C3 plants ranged from 8‰ (n-C31) to 10‰ (n-C27) across the 2011 and 2012 growing seasons, exceeding variability in bulk tissue (7‰). In contrast, the C4 monocot showed < 2‰ seasonal shifts in bulk and CS values. As a result of the variability in our CS data, we calculate that n-alkane based C3/C4 reconstructions in temperate saltmarshes have a maximum uncertainty of ∼11%. For dicots and succulents, seasonal bulk and CS δ13C trends diverged, while for C3 and C4 monocots, bulk and CS values followed similar temporal patterns. Fractionation between bulk and n-alkane carbon isotope values varied from −4 to −10‰ for C3 plants, and reached −13‰ for the C4 monocot. We explain discrepancies between bulk and n-alkane δ13C values by referring to possible interspecies variation in salinity adaptation, which may influence the partitioning of pyruvate, shifting the isotopic composition of lipid biomarkers. These findings open new avenues for empirical studies to further understand the metabolic processes fractionating carbon during the synthesis of n-alkanes, enhancing interpretation of the biomarker signal from the geological record

Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens

Objectives Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy. Methods Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male). DNA was extracted from whole blood and genotyping for CYP2B6 (516G → T, rs3745274), CAR (540C → T, rs2307424) and PXR (44477T → C, rs1523130; 63396C → T, rs2472677; and 69789A → G, rs763645) was conducted. Binary logistic regression using the backwards method was employed to assess the influence of SNPs and demographics on early discontinuation. Results Of the 373 patients, 131 withdrew from therapy within the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6 516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking status (OR = 0.45; P = 0.002) were associated with discontinuation within 3 months. Conclusions These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these association