Subtype-specific KRAS mutations in advanced lung adenocarcinoma: A retrospective study of patients treated with platinum-based chemotherapy

Background: Platinum-based chemotherapy is the most common treatment in advanced-stage lung adenocarcinoma. Because the clinical significance of KRAS mutational status in this setting has not yet been clearly determined, a mutation subtype-specific analysis was performed in the so far largest cohort of Caucasian patients with KRAS mutant advanced-stage lung adenocarcinoma treated with platinum-based chemotherapy. Methods: 505 Caucasian stage III-IV lung adenocarcinoma patients with known amino acid substitution-specific KRAS mutational status and treated with platinum-based chemotherapy were included. The correlations of subtype-specific KRAS mutations with smoking status, progression-free and overall survival (PFS and OS, respectively) and therapeutic response were analysed. Results: Among 338 KRAS wild-type, 147 codon 12 mutant and 20 codon 13 mutant patients, there were no mutation-related significant differences in PFS or OS (P values were 0.534 and 0.917, respectively). Eastern Cooperative Oncology Group (ECOG) status and clinical stage were significant independent prognostic factors. KRAS mutation showed a significant correlation with smoking status (P = 0.018). Importantly, however, G12V KRAS mutant patients were significantly more frequent among never-smokers than all other codon 12 KRAS mutant (G12x) subtypes (P = 0.016). Furthermore, this subgroup tended to have a higher response rate (66% versus 47%; P = 0.077). A modestly longer median PFS was also found in the G12V mutant cohort (233 days; versus 175 days in the G12x group; P = 0.145). Conclusions: While KRAS mutation status per se is neither prognostic nor predictive in stage III-IV lung adenocarcinoma, subtype-specific analysis may indeed identify clinically relevant subgroups of patients that may ultimately influence treatment decisions. © 2014 The Authors

Reactive oxygen species metabolism and plant-fungal interactions

Fungal interactions with plants can involve specific morphogenetic developments to access host cells, the suppression of plant defenses, and the establishment of a feeding lifestyle that nourishes the colonizer often—but not always—at the expense of the host. Reactive oxygen species (ROS) metabolism is central to the infection process, and the stage-specific production and/or neutralization of ROS is critical to the success of the colonization process. ROS metabolism during infection is dynamic—sometimes seemingly contradictory—and involves endogenous and exogenous sources. Yet, intriguingly, molecular decision-making involved in the spatio-temporal control of ROS metabolism is largely unknown. When also considering that ROS demands are similar between pathogenic and beneficial fungal-plant interactions despite the different outcomes, the intention of our review is to synthesize what is known about ROS metabolism and highlight knowledge gaps that could be hindering the discovery of novel means to mediate beneficial plant-microbe interactions at the expense of harmful plant-microbe interactions

Cicer super-pangenome provides insights into species evolution and agronomic trait loci for crop improvement in chickpea

Chickpea (Cicer arietinum L.)—an important legume crop cultivated in arid and semiarid regions—has limited genetic diversity. Efforts are being undertaken to broaden its diversity by utilizing its wild relatives, which remain largely unexplored. Here, we present the Cicer super-pangenome based on the de novo genome assemblies of eight annual Cicer wild species. We identified 24,827 gene families, including 14,748 core, 2,958 softcore, 6,212 dispensable and 909 species-specific gene families. The dispensable genome was enriched for genes related to key agronomic traits. Structural variations between cultivated and wild genomes were used to construct a graph-based genome, revealing variations in genes affecting traits such as flowering time, vernalization and disease resistance. These variations will facilitate the transfer of valuable traits from wild Cicer species into elite chickpea varieties through marker-assisted selection or gene-editing. This study offers valuable insights into the genetic diversity and potential avenues for crop improvement in chickpea

Recent Ψ′ results from Mark III

Results on ψ′ decays from Mark III are presented. With a data sample of 240,000 ψ′ events, we measure ψ′→ π + π − ψ, ψ′→ ηψ, ψ′→ γχ c, ψ′→ γ4 π ±, ψ′→ γ6 π ±, and perform a search for ψ′→ ϱπ. Implications of our measurements are discussed