A plant sesquiterpene lactone and its derivative reduce cutaneous side effect of vemurafenib,a BRAF inhibitor drug to treat late stage melanoma

OBJECTIVE To investigate the pharmacological effect of a plant sesquiterpene lactone(designated D)and its semi-organically synthesized novel derivative(designated S)and the role of lipid mediators,viz.,oxylipins in attenuating vemurafenib-induced cutaneous side effects.METHODS A DMBA/TPAinduced skin carcinogenesis mouse model mimicking cutaneous side effect caused by vemurafenib was established to evaluate the efficacy of compound D and S in reversal of vemurafenib side effect.Comparative oxylipin metabolomics platform using UPLC-TQD mass spectrometry coupled with partial least squares-discriminant analysis(PLS-DA)analysis,cell-based assays,and immunochemistry analysis were performed to elucidate the mechanism insights of DET and S compounds and the role of specific oxylipins in skin cancer carcinogenesis.RESULTS Vemurafenib treatment expedited the skin papillomas formation in DMBA-TPA treated mouse from week 6 to week 3.Both D and S compounds could suppress the vemurafenib side effect and also decrease total papillomas numbers(55% to 72%)and average sizes(66% to 89%).Oxylipins metabolome analysis shows that specific arachidonic acid metabolites may play a role in vemurafenib-induced squamous cell carcinoma or keratoacanthomas formation in mouse skin that can be deregulated by D or S compound treatment.Notably,S compound can inhibit vemurafenib-induced paradoxical activation of MAP kinases in mouse skin or in NRAS mutant melanoma cells.CONCLUSION Our results indicate that plant sesquiterpene lactone D and its novel analog can reduce cutaneous side effect of vemurafenib through novel modes of action by inhibiting paradoxical activation of MAP kinases and de-regulating pro-inflammation mediators COX-2 and specific ecosanoid-type of oxylipins.This study may suggest a novel adjuvant therapy approach in treatment of BRAFV600 Emutant melanoma.

Changes in rainfall partitioning caused by the replacement of native dry forests of Lithraea molleoides by exotic plantations of Pinus elliottii in the dry Chaco mountain forests, central Argentina

The replacement of native dry forests by commercial(exotic)tree plantations could generate changes in rainfall partitioning,which further affects the water cycle.In this study,we determined(i)the rainfall partitioning into interception,throughfall and stemflow,(ii)the role of rainfall event size on rainfall partitioning,(iii)the pH of water channelized as throughfall and stemflow,and(iv)the runoff in Lithraea molleoides(a native species)and Pinus elliottii(an exotic species)stands in the dry Chaco mountain forests,central Argentina.On average,interception,throughfall and stemflow accounted for 19.3%,79.5%and 1.2%of the gross rainfall in L.molleoides stand,and 32.6%,66.7%and 0.7%of the gross rainfall in P.elliottii stand,respectively.Amounts of interception,throughfall and stemflow presented positive linear relationships with the increment of rainfall event size for both tree species(P<0.01 in all cases).Percentages of interception,throughfall and stemflow were all related to the increment of rainfall event size,showing different patterns.With increasing rainfall event size,interception exponentially decreased,throughfall asymptotically increased and stemflow linearly increased.Both P.elliottii and L.molleoides stands presented significant differences in the pH values of water channelized as throughfall(6.3 vs.6.7,respectively;P<0.01)and stemflow(4.5 vs.5.8,respectively;P<0.01).Runoff occupied only 0.3%of the gross rainfall in P.elliottii stand and was zero in L.molleoides stand.Our results showed that the native species L.molleoides presented 13.6%more water reaching the topsoil(i.e.,net rainfall;net rainfall=gross rainfall-interception-runoff)than the exotic species P.elliottii.This study improves our understanding of the effects of native vegetation replacement on the local water balance in the dry forest ecosystems.

The soft glumes of common wheat are sterile-lemmas as determined by the domestication gene Q

The Q gene in common wheat encodes an APETALA2(AP2) transcription factor that causes the free threshing attribute. Wheat spikelets bearing several florets are subtended by a pair of soft glumes that allow free liberation of seeds. In wild species, the glumes are tough and rigid,making threshing difficult. However, the nature of these "soft glumes", caused by the domestication allele Q is not clear. Here, we found that over expression of Q in common wheat leads to homeotic florets at glume positions. We provide phenotypic, microscopy, and marker genes evidence to demonstrate that the soft glumes of common wheat are in fact lemma-like organs, or so-called sterile-lemmas. By comparing the structures subtending spikelets in wheat and other crops such as rice and maize, we found that AP2 genes may play conserved functions in grasses by manipulating vestigial structures, such as floret-derived soft glumes in wheat and empty glumes in rice. Conversion of these seemingly vegetative organs to reproductive organs may be useful in yield improvement of crop species.

Genetic control of compound leaf development in the mungbean(Vigna radiata L.)

Many studies suggest that there are distinct regulatory processes controlling compound leaf development in different clades of legumes.Loss of function of the LEAFY(LFY)orthologs results in a reduction of leaf complexity to different degrees in inverted repeat-lacking clade(IRLC)and non-IRLC species.To further understand the role of LFY orthologs and the molecular mechanism in compound leaf development in non-IRLC plants,we studied leaf development in unifoliate leaf(un)mutant,a classical mutant of mungbean(Vigna radiata L.),which showed a complete conversion of compound leaves into simple leaves.Our analysis revealed that UN encoded the mungbean LFY ortholog(VrLFY)and played a significant role in leaf development.In situ RNA hybridization results showed that STM-like KNOXI genes were expressed in compound leaf primordia in mungbean.Furthermore,increased leaflet number in heptafoliate leaflets1(hel1)mutants was demonstrated to depend on the function of VrLFY and KNOXI genes in mungbean.Our results suggested that HEL1 is a key factor coordinating distinct processes in the control of compound leaf development in mungbean and its related non-IRLC legumes.

Optimization of Agrobacterium-mediated Rice Transformation

[ Objective] This study aimed to optimize Agrobacterium-mediated transformation in rice. [ Method] Transgenic rice seedlings were obtained by opti- mizing and modifying the classical transformation methods. [ Result] Mature embryos were adopted and sterilized by HgC12. Transformation efficiency achieved the maximum when OD600 was 0.10, which increased by 23% over the previous method. [ Conchuslon] The study provided technical reference for related researches of Agrobacterium-mediated transformation in rice.

Approaches to the Elaboration of Regeneration and Transformation Systems for Elite Kazakh Cotton Varieties

The development and wide application of genetic transformation for cotton improvement are restrained by the unresolved problem of genotype dependence in regeneration in vitro.High embryogenic and regenerative potential have been obtained for limited number of Coker type genotypes。

Transcriptional regulation of bark freezing tolerance in apple(Malus domestica Borkh.)

Freezing tolerance is a significant trait in plants that grow in cold environments and survive through the winter.Apple(Malus domestica Borkh.)is a cold-tolerant fruit tree,and the cold tolerance of its bark is important for its survival at low temperatures.However,little is known about the gene activity related to its freezing tolerance.To better understand the gene expression and regulation properties of freezing tolerance in dormant apple trees,we analyzed the transcriptomic divergences in the bark from 1-year-old branches of two apple cultivars,“Golden Delicious”(G)and“Jinhong”(H),which have different levels of cold resistance,under chilling and freezing treatments.“H”can safely overwinter below−30℃in extremely low-temperature regions,whereas“G”experiences severe freezing damage and death in similar environments.Based on 28 bark transcriptomes(from the epidermis,phloem,and cambium)from 1-year-old branches under seven temperature treatments(from 4 to−29°C),we identified 4173 and 7734 differentially expressed genes(DEGs)in“G”and“H”,respectively,between the chilling and freezing treatments.A gene coexpression network was constructed according to this expression information using weighted gene correlation network analysis(WGCNA),and seven biologically meaningful coexpression modules were identified from the network.The expression profiles of the genes from these modules suggested the gene regulatory pathways that are responsible for the chilling and freezing stress responses of“G”and/or“H.”Module 7 was probably related to freezing acclimation and freezing damage in“H”at the lower temperatures.This module contained more interconnected hub transcription factors(TFs)and cold-responsive genes(CORs).Modules 6 and 7 contained C-repeat binding factor(CBF)TFs,and many CBF-dependent homologs were identified as hub genes.We also found that some hub TFs had higher intramodular connectivity(KME)and gene significance(GS)than CBFs.Specifically,most hub TFs in modules 6 and 7 were activated at the beginning of the early freezing stress phase and maintained upregulated expression during the whole freezing stress period in“G”and“H”.The upregulation of DEGs related to methionine and carbohydrate biosynthetic processes in“H”under more severe freezing stress supported the maintenance of homeostasis in the cellular membrane.This study improves our understanding of the transcriptional regulation patterns underlying freezing tolerance in the bark of apple branches.

Nuclear phylogeny and insights into wholegenome duplications and reproductive development of Solanaceae plants

Solanaceae,the nightshade family,have2700 species,including the important crops potato and tomato,ornamentals,and medicinal plants.Several sequenced Solanaceae genomes show evidence for wholegenome duplication(WGD),providing an excellent opportunity to investigate WGD and its impacts.Here,we generated 93 transcriptomes/genomes and combined them with 87 public datasets,for a total of 180 Solanaceae species representing all four subfamilies and 14 of 15 tribes.Nearly 1700 nuclear genes from these transcriptomic/genomic datasets were used to reconstruct a highly resolved Solanaceae phylogenetic tree with six major clades.The Solanaceae tree supports four previously recognized subfamilies(Goetzeioideae,Cestroideae,Nicotianoideae,and Solanoideae)and the designation of three other subfamilies(Schizanthoideae,Schwenckioideae,and Petunioideae),with the placement of several previously unassigned genera.We placed a Solanaceae-specific whole-genome triplication(WGT1)at81 million years ago(mya),before the divergence of Schizanthoideae from other Solanaceae subfamilies at73 mya.In addition,we detected two gene duplication bursts(GDBs)supporting proposed WGD events and four other GDBs.An investigation of the evolutionary histories of homologs of carpel and fruit developmental genes in 14 gene(sub)families revealed that 21 gene clades have retained gene duplicates.These were likely generated by the Solanaceae WGT1 and may have promoted fleshy fruit development.This study presents a well-resolved Solanaceae phylogeny and a new perspective on retained gene duplicates and carpel/fruit development,providing an improved understanding of Solanaceae evolution.

Angiosperm-wide analysis of fruit and ovary evolution aided by a new nuclear phylogeny supports association of the same ovary type with both dry and fleshy fruits

Fruit functions in seed protection and dispersal and belongs to many dry and fleshy types,yet their evolutionary pattern remains unclear in part due to uncertainties in the phylogenetic relationships among several orders and families.Thus we used nuclear genes of 502 angiosperm species representing 231 families to reconstruct a well supported phylogeny,with resolved relationships for orders and families with previously uncertain placements.Using this phylogeny as a framework,molecular dating supports a Triassic origin of the crown angiosperms,followed by the emergence of most orders in the Jurassic and Cretaceous and their rise to ecological dominance during the Cretaceous Terrestrial Revolution.The robust phylogeny allowed an examination of the evolutionary pattern of fruit and ovary types,revealing a trend of parallel carpel fusions during early diversifications in eudicots,monocots,and magnoliids.Moreover,taxa in the same order or family with the same ovary type can develop either dry or fleshy fruits with strong correlations between specific types of dry and fleshy fruits;such associations of ovary,dry and fleshy fruits define several ovaryfruit"modules"each found in multiple families.One of the frequent modules has an ovary containing multiple ovules,capsules and berries,and another with an ovary having one or two ovules,achenes(or other single-seeded dry fruits)and drupes.This new perspective of relationships among fruit types highlights the closeness of specific dry and fleshy fruit types,such as capsule and berry,that develop from the same ovary type and belong to the same module relative to dry and fleshy fruits of other modules(such as achenes and drupes).Further analyses of gene families containing known genes for ovary and fruit development identified phylogenetic nodes with multiple gene duplications,supporting a possible role of whole-genome duplications,in combination with climate changes and animal behaviors,in angiosperm fruit and ovary diversification.

Revealing the role of CCoAOMT1: fine-tuning bHLH transcription factors for optimal anther development

The tapetum,a crucial innermost layer encompassing male reproductive cells within the anther wall,plays a pivotal role in normal pollen development.The transcription factors (TFs) bHLH010/089/091 redundantly facilitate the rapid nuclear accumulation of DYSFUNCTIONAL TAPETUM 1,a gatekeeper TF in the tapetum.Nevertheless,the regulatory mechanisms governing the activity of bHLH010/089/091 remain unknown.In this study,we reveal that caffeoyl coenzyme A O-methyltransferase 1 (CCoAOMT1) is a negative regulator affecting the nuclear localization and function of bHLH010 and bHLH089,probably through their K259 site.Our findings underscore that CCoAOMT1 promotes the nuclear export and degradation of bHLH010 and bHLH089.Intriguingly,elevated CCoAOMT1 expression resulted in defective pollen development,mirroring the phenotype observed in bhlh010 bhlh089 mutants.Moreover,our investigation revealed that the K259A mutation in the bHLH089 protein disrupted its translocation from the nucleus to the cytosol and impeded its degradation induced by CCoAOMT1.Importantly,transgenic plants with the probHLH089::bHLH089^(K259A)construct failed to rescue proper pollen development or gene expression in bhlh010 bhlh089 mutants.Collectively,these findings emphasize the need to maintain balanced TF homeostasis for male fertility.They firmly establish CCoAOMT1 as a pivotal regulator that is instrumental in achieving equilibrium between the induction of the tapetum transcriptional network and ensuring appropriate anther development.

The Mechanisms of Brassinosteroids＇ Action： From Signal Transduction to Plant Development

Brassinosteroids play diverse roles in plant growth and development. Plants deficient in brassinosteroid （BR） biosynthesis or defective in signal transduction show many abnormal developmental phenotypes, indicating the importance of both BR biosynthesis and the signaling pathway in regulating these biological processes. Recently, using genetics, proteomics, genomics, cell biology, and many other approaches, more components involved in the BR signaling pathway were identified. Furthermore, the physiological, cellular, and molecular mechanisms by which BRs regulate various aspects of plant development, are being discovered. These include root development, anther and pollen development and formation, stem elongation, vasculature differentiation, and cellulose biosynthesis, suggesting that the biological functions of BRs are far beyond promoting cell elongation, This review will focus on the up-to-date progresses about regulatory mechanisms of the BR signaling pathway and the physiological and molecular mechanisms whereby BRs regulate plant growth and development.

Genetic and Epigenetic Effects of Plant-Pathogen Interactions： An Evolutionary Perspective

Recent reports suggest that exposure to stress is capable of influencing the frequency and pattern of inherited changes in various parts of the genome. In this review, we will discuss the influence of viral pathogens on somatic and meiotic genome stability of Nicotiana tabacum and Arabidopsis thaliana. Plants infected with a compatible pathogen generate a systemic recombination signal that precedes the spread of pathogens and results in changes in the somatic and meiotic recombination frequency. The progeny of infected plants exhibit changes in global and locusspecific DNA methylation patterns, genomic rearrangements at transgenic reporter loci and resistance gene-like-loci, and even tolerance to pathogen infection and abiotic stress. Here, we will discuss the contribution of environmental stresses to genome evolution and will focus on the role of heritable epigenetic changes in response to pathogen infection.

Involvement of Histone Modifcations in Plant Abiotic Stress Responses

As sessile organisms, plants encounter various environmental stimuli including abiotic stresses during their lifecycle. To survive under adverse conditions, plants have evolved intricate mechanisms to perceive external signals and respond accordingly. Responses to various stresses largely depend on the plant capacity to modulate the transcriptome rapidly and specifically. A number of studies have shown that the molecular mechanisms driving the responses of plants to environmental stresses often depend on nucleosome histone post-translational modifications including histone acetylation, methylation, ubiquitination, and phosphorylation. The combined effects of these modifications play an essential role in the regulation of stress responsive gene expression. In this review, we highlight our current understanding of the epigenetic mechanisms of histone modifications and their roles in plant ahiotic stress response.

Ligand Perception,Activation,and Early Signaling of Plant Steroid Receptor Brassinosteroid Insensitive 1

Leucine-rich repeat receptor-like kinases （LRR-RLKs） belong to a large group of cell surface proteins involved in many aspects of plant development and environmental responses in both monocots and dicots. Brassinosteroid insensitive 1 （BRI1）, a member of the LRR X subfamily, was first identified through several forward genetic screenings for mutants insensitive to brassinosteroids （BRs）, which are a class of plant-specific steroid hormones. Since its identification, BRI1 and its homologs had been proved as receptors perceiving BRs and initiating BR signaling. The co-receptor BRIl-associated kinase 1 and its homologs, and other BRI1 interacting proteins such as its inhibitor BRI1 kinase inhibitor I （BKI1） were identified by genetic andbiochemical approaches. The detailed mechanisms of BR perception by BRI1 and the activation of BRI1 receptor complex have also been elucidated. Moreover, several mechanisms for termination of the activated BRI1 signaling were also discovered. In this review, we will focus on the recent advances on the mechanism of BRI1 phosphorylation and activation, the regulation of its receptor complex, the structure basis of BRI1 ectodomain and BR recognition, its direct substrates, and the termination of the activated BRI1 receptor complex.