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•Knowledge of leaf waxes of South American Temperate Forest plant species is lacking.•Three leaf wax classes on twelve dominant plant species were analyzed.•The n-alkanoic acids, ...n-alkanes and n-alkanols differ within and among species.•It is possible to differentiate among species using leaf wax classes.•A potential use of leaf wax classes as a chemotaxonomic biomarker is proposed.
Plant leaf waxes are used as vegetation biomarkers in several archives (i.e. soils, lake and marine sediments), study of these compounds in modern plants is needed to makes their application and interpretation more robust. However, in the South American Temperate Forest (STF), few species have been studied. The main goal of this research was to characterize twelve dominant modern species of the STF using three classes of leaf wax compounds, n-alkanoic acids, n-alkanes and n-alkanols. In addition, we evaluate the potential of leaf waxes as a vegetation and chemotaxonomic biomarker in the region, considering species that were found in different sampling sites and therefore environmental conditions. Clear differences among leaf wax abundance (μg/g) and ACL (average chain length) within and among the twelve species were found. Only the ACL of n-alkanoic acids and n-alkanols allows differentiation between leaf habit species (i.e. evergreen vs. deciduous), with high values associated with evergreen and low values with deciduous plants. This study differentiates the five species found in more than one site (i.e. different environmental condition) using different combinations of leaf waxes and in addition using only n-alkanes. It was not possible to differentiate among all sites with any combination of leaf waxes. The differences in the distribution of leaf waxes among species is an expected pattern in the study area, and it seems reliable to use the ACL as a vegetation biomarker differentiating between evergreen and deciduous species. The clear chemotaxonomic differences among the five species exposed to different and natural environmental conditions and the high preservation potential of the study area allow us to suggest that leaf waxes are likely a reliable tool to be incorporated in quantitative models to track vegetation and may be useful as a chemotaxonomic biomarker at the species level.
Background and aims
Soil properties and climate influence leaf chemical traits producing intraspecific variation in plants. Studies evaluating their importance in the South American Temperate Forest ...(STF) species are scarce. This study aimed to evaluate the intraspecific differences in five evergreen species of the rainforest considering two contrasting areas (i.e. temperature and precipitation), linking soil and climate with plants traits.
Methods
Soil properties (C
org
%, N%, C/N, δ
13
C, δ
15
N, pH and temperature), climate variables (mean annual precipitation and temperature MAP; MAT) and leaf chemical traits (C%, N% and P%, C/N, N/P, δ
13
C and δ
15
N) were measured and compared between two areas in the Northern Patagonia (42°- 44°S). In addition, the relationship of leaf chemical traits with soil and climate was assessed.
Results
Significant differences were found in soil (C
org
%, C/N and pH;
p
< 0.05) and climate (
p
< 0.05), with MAP identified as the most common factor controlling soil properties (C
org
%, C/N and δ
15
N). Intraspecific differences in leaf chemical traits were found between areas, but not in all traits. The most common leaf chemical trait with significant differences was C%. Higher mean C% values were found in the island in plants and soils. High number of correlations (
n
= 13 correlations;
p
< 0.05) were found between leaf chemical traits. On the other hand, only MAP was a significant predictor of δ
13
C in the leaves.
Conclusion
The leaf chemical traits variability suggests a species-specific response to the soil and climate conditions, with important influence of precipitation as the most common predictor of soil properties and δ
13
C in the leaves.
Eriosyce is one of most species-rich genera within Notocacteae (Cactaceae) harboring a variety of stem and flower morphologies, and fruits with basal abscission. The lack of a well-sampled molecular ...phylogeny contributes to the current taxonomic instability of the genus, where its circumscription and infrageneric classification has been questioned. Specimens of Eriosyce (63 taxa) plus 19 outgroups were analyzed through sequencing three plastid noncoding introns (rpl32-trnL, trnL-trnF, trnH-psbA), one plastid gene (ycf1), and one nuclear gene (PHYC). Individual markers and concatenated matrices were analyzed using maximum likelihood and Bayesian approaches. Phylogenetic analyses strongly support the monophyly of Eriosyce s.l. Furthermore, seven clades within Eriosyce s.l. were defined based on supported branches, although one of them was weakly supported. Our results suggest that some past taxonomic proposals have low phylogenetic support and should no longer be used, e.g., based on their scattered positions in the phylogenetic reconstruction, several infraspecific taxa appear unrelated to the typical form of the species in which they had been placed. We present a phylogeny-informed infrageneric classification of the genus Eriosyce, and new combinations are proposed to update the nomenclature of species and sections.
•In general, no linear relationship between leaf waxes and elevation is observed.•Chusquea sp. n-alkanoic acid abundance is correlated with precipitation and aridity.•A. araucana n-alkane ACL and ...abundance are correlated with temperature.•High relative abundance of n-alkanoic acids (>60%) in the three plant species.•Different abundance and ACL among species in both n-alkanes and n-alkanols.
The n-alkyl leaf waxes of the temperate forest of South America are poorly studied, despite being a biogeographically isolated forest spanning wide environmental conditions. To evaluate whether local species adaptation and environmental changes influence the n-alkyl leaf wax composition, we measured the molecular abundance and distribution of n-alkyl leaf waxes (n-alkanoic acids, n-alkanes and n-alkanols) of three dominant native species from southern temperate forest in South America. We surveyed Araucaria araucana (n = 9), Nothofagus dombeyi (n = 17) and Chusquea sp. (n = 21) at different elevations. The relationship of n-alkyl leaf wax abundance and distribution with elevation is not significant in any species, except for n-alkane ACL (average chain length) in Chusquea sp. Significant correlations are found for n-alkanoic acid abundance with precipitation and aridity in Chusquea sp. and n-alkane abundance and ACL with temperature in A. araucana. These data suggest a species-specific response to environmental variables. The main similarity in the three species is a higher abundance of n-alkanoic acids (>60%) relative to other n-alkyl leaf waxes. Only n-alkanols are not correlated to any environmental variable, and neither ACL nor Cmax overlap among species. These results suggest n-alkanols as a potential chemotaxonomic indicator at a lower taxonomic level in the region.
Plasma proteins vascular endothelial growth factor (VEGF), soluble VEGF receptor 2 (sVEGFR-2), carbonic anhydrase IX (CAIX), tissue inhibitor of metalloproteinase 1 (TIMP-1), and Ras p21 and one ...tumor gene (VHL) were analyzed to identify prognostic biomarkers or indicators of response to sorafenib in a subset of patients enrolled in the Treatment Approaches in Renal Cancer Global Evaluation Trial.
Nine hundred three patients with advanced renal cell carcinoma (RCC) were randomized to 400 mg sorafenib twice a day or placebo. Samples collected at baseline and after 3 and 12 weeks were subjected to enzyme-linked immunosorbent assays. VHL exons were sequenced from tumor biopsies.
Baseline biomarker data were available for VEGF (n = 712), sVEGFR-2 (n = 713), CAIX (n = 128), TIMP-1 (n = 123), Ras p21 (n = 125), and VHL mutational status (n = 134). Higher Eastern Cooperative Oncology Group performance status (ECOG PS) score correlated with elevated baseline VEGF (P < 0.0001) and a higher incidence of VHL mutations (P = 0.008), whereas higher Memorial Sloan-Kettering Cancer Center (MSKCC) score correlated with elevated VEGF (P < 0.0001), CAIX (P = 0.027), and TIMP-1 (P = 0.0001). Univariable analyses of baseline levels in the placebo cohort identified VEGF (P = 0.0024), CAIX (P = 0.034), TIMP-1 (P = 0.001), and Ras p21 (P = 0.016) as prognostic biomarkers for survival. TIMP-1 remained prognostic for survival in a multivariable analysis model (P = 0.002) that also included ECOG PS, MSKCC score, and the other biomarkers assayed. In the placebo cohort, TIMP-1 (P < 0.001) and Ras p21 (P = 0.048) levels increased at 12 weeks. In the sorafenib cohort, VEGF levels increased at 3 and 12 weeks of treatment (both weeks P < 0.0001), whereas sVEGFR-2 (both weeks P < 0.0001) and TIMP-1 levels (P = 0.002, week 3; P = 0.006, week 12) decreased.
VEGF, CAIX, TIMP-1, and Ras p21 levels were prognostic for survival in RCC patients. Of these, TIMP-1 has emerged as being independently prognostic.
Mature survival data and evaluation of vascular endothelial growth factor (VEGF) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study in ...patients with renal cell carcinoma (RCC) are reported.
Nine hundred three previously treated patients were randomly assigned to receive sorafenib versus placebo. On demonstration of progression-free survival (PFS) benefit with sorafenib, patients assigned to placebo were offered sorafenib. Overall survival (OS) was determined at two planned interim analyses and one final analysis, with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib. The relationships between baseline VEGF level and prognosis and efficacy were evaluated.
The final OS of patients receiving sorafenib was comparable with that of patients receiving placebo (17.8 v 15.2 months, respectively; hazard ratio HR = 0.88; P = .146); however, when post-cross-over placebo survival data were censored, the difference became significant (17.8 v 14.3 months, respectively; HR = 0.78; P = .029). Adverse events at 16 months after cross over were similar to those previously reported. Baseline VEGF levels correlated with Eastern Cooperative Oncology Group performance status (P < .0001), Memorial Sloan-Kettering Cancer Center score (P < .0001), and PFS and OS in univariate (PFS, P = .0013; OS, P = .0009) and multivariate (PFS, P = .0231; OS, P = .0416) analyses of placebo patients and with short OS by multivariate analysis of patients receiving sorafenib (P = .0145). Both high-VEGF (P < .01) and low-VEGF (P < .01) groups benefited from sorafenib.
Although an OS benefit was not seen on a primary intent-to-treat analysis, results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib, suggesting an important cross-over effect. VEGF levels are prognostic for PFS and OS in RCC. The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC.
Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have adverse outcomes. We evaluated the efficacy and safety of the phosphatidylinositol 3-kinase inhibitor copanlisib in ...patients with relapsed/refractory DLBCL and assessed the relationship between efficacy and DLBCL cell of origin (COO; activated B-cell like ABC and germinal center B-cell like GCB) and other biomarkers. The primary endpoint was objective response rate (ORR) in DLBCL COO subgroups (ABC, GCB, and unclassifiable) and by CD79B mutational status (NCT02391116). Sixty-seven patients received copanlisib (ABC DLBCL, n = 19; GCB DLBCL, n = 30; unclassifiable, n = 3; missing, n = 15). The ORR was 19.4%; 31.6% and 13.3% in ABC and GCB DLBCL patients, respectively. ORR was 22.2%/20.0% for patients with/without CD79B mutations (wild type, n = 45; mutant, n = 9; missing, n = 13). Overall median progression-free survival and duration of response were 1.8 and 4.3 months, respectively. Adverse events included hypertension (40.3%), diarrhea (37.3%), and hyperglycemia (32.8%). Aberrations were detected in 338 genes, including BCL2 (53.7%) and MLL2 (53.7%). A 16-gene signature separating responders from nonresponders was identified. Copanlisib treatment demonstrated a manageable safety profile in patients with relapsed/refractory DLBCL and a numerically higher response rate in ABC vs. GCB DLBCL patients.
Validated biomarkers of prognosis and response to drug have not been identified for patients with hepatocellular carcinoma (HCC). One of the objectives of the phase III, randomized, controlled ...Sorafenib HCC Assessment Randomized Protocol (SHARP) trial was to explore the ability of plasma biomarkers to predict prognosis and therapeutic efficacy.
In SHARP, 602 patients with advanced HCC were randomized to receive either oral sorafenib 400 mg twice a day per os or matching placebo daily on a continuous basis. Ten plasma biomarkers implicated in the pathogenesis of HCC were measured in 491 patients at baseline and in 305 after 12 weeks of treatment. The candidate biomarkers were analyzed to identify correlates of prognosis or predictors of response to sorafenib.
In both the entire patient population and the placebo cohort, baseline angiopoietin 2 (Ang2) and VEGF concentrations independently predicted survival. Clinical variables such as macroscopic vascular invasion, Eastern Cooperative Oncology Group (ECOG) performance status, and baseline α-fetoprotein and alkaline phosphatase concentrations also independently predicted survival in these groups. In the sorafenib cohort, trends toward enhanced survival benefit from sorafenib were observed in patients with high s-c-KIT or low hepatocyte growth factor concentration at baseline (P of interaction = 0.081 and 0.073, respectively).
The angiogenesis biomarkers Ang2 and VEGF were independent predictors of survival in patients with advanced HCC. In contrast, none of the biomarkers tested significantly predicted response to sorafenib.
PREMISE OF THE STUDY: Species of the endemic Chilean cactus genus Copiapoa have cylindrical or (sub)globose stems that are solitary or form (large)clusters and typically yellow flowers. Many species ...are threatened with extinction. Despite being icons of the Atacama Desert and well loved by cactus enthusiasts, the evolution and diversity of Copiapoa has not yet been studied using a molecular approach. METHODS: Sequence data of three plastid DNA markers (rpl32-trnL, trnH-psbA, ycf1) of 39 Copiapoa taxa were analyzed using maximum likelihood and Bayesian inference approaches. Species distributions were modeled based on geo-referenced localities and climatic data. Evolution of character states of four characters (root morphology, stem branching, stem shape, and stem diameter) as well as ancestral areas were reconstructed using a Bayesian and maximum likelihood framework, respectively. KEY RESULTS: Clades of species are revealed. Though 32 morphologically defined species can be recognized, genetic diversity between some species and infraspecific taxa is too low to delimit their boundaries using plastid DNA markers. Recovered relationships are often supported by morphological and biogeographical patterns. The origin of Copiapoa likely lies between southern Peru and the extreme north of Chile. The Copiapó Valley limited colonization between two biogeographical areas. CONCLUSIONS: Copiapoa is here defined to include 32 species and five heterotypic subspecies. Thirty species are classified into four sections and two subsections, while two species remain unplaced. A better understanding of evolution and diversity of Copiapoa will allow allocating conservation resources to the most threatened lineages and focusing conservation action on real biodiversity.
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