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1.
Ocular allergy: update on clinical trials.
Bielory, L, Schoenberg, D
Current opinion in allergy and clinical immunology. 2019;(5):495-502
Abstract
PURPOSE OF REVIEW The purpose of this article is to provide an update on the advances made through recent clinical trials regarding the treatment of the signs and symptoms of allergic conjunctivitis and its associated conditions. RECENT FINDINGS Recent studies have demonstrated significant advancement in the various forms of immunotherapy treatments. Nutritional interventions such as probiotics have surfaced as a viable complementary treatment option. Novel delivery methods such as contact lenses have been further studied along with a new tacrolimus formulation to improve ocular levels of the drug. SUMMARY Currently, the primary advances in treatment for allergic conjunctivitis has shifted from new ophthalmic agents to immunotherapy and improvement of drug delivery. This includes the classic subcutaneous and sublingual and the novel epicutaneous and intralymphatic immunotherapy delivery systems as well as an edible rice vaccine. New targets for treatment have spurred research into new antagonist drugs such as (OC000459), a prostaglandin D2 antagonist. The Marinosolv formulation using tacrolimus shows promise and may be considered for other ophthalmic agents in the future. Other nonpharmacological treatments such as stenting and mechanical barrier gel have demonstrated their usefulness in treating ocular symptoms.
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Auxin EvoDevo: Conservation and Diversification of Genes Regulating Auxin Biosynthesis, Transport, and Signaling.
Matthes, MS, Best, NB, Robil, JM, Malcomber, S, Gallavotti, A, McSteen, P
Molecular plant. 2019;(3):298-320
Abstract
The phytohormone auxin has been shown to be of pivotal importance in growth and development of land plants. The underlying molecular players involved in auxin biosynthesis, transport, and signaling are quite well understood in Arabidopsis. However, functional characterizations of auxin-related genes in economically important crops, specifically maize and rice, are still limited. In this article, we comprehensively review recent functional studies on auxin-related genes in both maize and rice, compared with what is known in Arabidopsis, and highlight conservation and diversification of their functions. Our analysis is illustrated by phylogenetic analysis and publicly available gene expression data for each gene family, which will aid in the identification of auxin-related genes for future research. Current challenges and future directions for auxin research in maize and rice are discussed. Developments in gene editing techniques provide powerful tools for overcoming the issue of redundancy in these gene families and will undoubtedly advance auxin research in crops.
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3.
Solanum lycopersicum GOLDEN 2-LIKE 2 transcription factor affects fruit quality in a light- and auxin-dependent manner.
Lupi, ACD, Lira, BS, Gramegna, G, Trench, B, Alves, FRR, Demarco, D, Peres, LEP, Purgatto, E, Freschi, L, Rossi, M
PloS one. 2019;(2):e0212224
Abstract
Plastids are organelles responsible for essential aspects of plant development, including carbon fixation and synthesis of several secondary metabolites. Chloroplast differentiation and activity are highly regulated by light, and several proteins involved in these processes have been characterised. Such is the case of the GOLDEN 2-LIKE (GLK) transcription factors, which induces the expression of genes related to chloroplast differentiation and photosynthesis. The tomato (Solanum lycopersicum) genome harbours two copies of this gene, SlGLK1 and SlGLK2, each with distinct expression patterns. While the former predominates in leaves, the latter is mainly expressed in fruits, precisely at the pedicel region. During tomato domestication, the selection of fruits with uniform ripening fixed the mutation Slglk2, nowadays present in most cultivated varieties, what penalised fruit metabolic composition. In this study, we investigated how SlGLK2 is regulated by light, auxin and cytokinin and determined the effect of SlGLK2 on tocopherol (vitamin E) and sugar metabolism, which are components of the fruit nutritional and industrial quality. To achieve this, transcriptional profiling and biochemical analysis were performed throughout fruit development and ripening from SlGLK2, Slglk2, SlGLK2-overexpressing genotypes, as well as from phytochrome and hormonal deficient mutants. The results revealed that SlGLK2 expression is regulated by phytochrome-mediated light perception, yet this gene can induce chloroplast differentiation even in a phytochrome-independent manner. Moreover, auxin was found to be a negative regulator of SlGLK2 expression, while SlGLK2 enhances cytokinin responsiveness. Additionally, SlGLK2 enhanced chlorophyll content in immature green fruits, leading to an increment in tocopherol level in ripe fruits. Finally, SlGLK2 overexpression resulted in higher total soluble solid content, possibly by the regulation of sugar metabolism enzyme-encoding genes. The results obtained here shed light on the regulatory network that interconnects SlGLK2, phytohormones and light signal, promoting the plastidial activity and consequently, influencing the quality of tomato fruit.
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4.
Computationally Guided Discovery and Experimental Validation of Indole-3-acetic Acid Synthesis Pathways.
Garcia, DC, Cheng, X, Land, ML, Standaert, RF, Morrell-Falvey, JL, Doktycz, MJ
ACS chemical biology. 2019;(12):2867-2875
Abstract
Elucidating the interaction networks associated with secondary metabolite production in microorganisms is an ongoing challenge made all the more daunting by the rate at which DNA sequencing technology reveals new genes and potential pathways. Developing the culturing methods, expression conditions, and genetic systems needed for validating pathways in newly discovered microorganisms is often not possible. Therefore, new tools and techniques are needed for defining complex metabolic pathways. Here, we describe an in vitro computationally assisted pathway description approach that employs bioinformatic searches of genome databases, protein structural modeling, and protein-ligand-docking simulations to predict the gene products most likely to be involved in a particular secondary metabolite production pathway. This information is then used to direct in vitro reconstructions of the pathway and subsequent confirmation of pathway activity using crude enzyme preparations. As a test system, we elucidated the pathway for biosynthesis of indole-3-acetic acid (IAA) in the plant-associated microbe Pantoea sp. YR343. This organism is capable of metabolizing tryptophan into the plant phytohormone IAA. BLAST analyses identified a likely three-step pathway involving an amino transferase, an indole pyruvate decarboxylase, and a dehydrogenase. However, multiple candidate enzymes were identified at each step, resulting in a large number of potential pathway reconstructions (32 different enzyme combinations). Our approach shows the effectiveness of crude extracts to rapidly elucidate enzymes leading to functional pathways. Results are compared to affinity purified enzymes for select combinations and found to yield similar relative activities. Further, in vitro testing of the pathway reconstructions revealed the "underground" nature of IAA metabolism in Pantoea sp. YR343 and the various mechanisms used to produce IAA. Importantly, our experiments illustrate the scalable integration of computational tools and cell-free enzymatic reactions to identify and validate metabolic pathways in a broadly applicable manner.
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5.
Mitochondrial Pyruvate Dehydrogenase Contributes to Auxin-Regulated Organ Development.
Ohbayashi, I, Huang, S, Fukaki, H, Song, X, Sun, S, Morita, MT, Tasaka, M, Millar, AH, Furutani, M
Plant physiology. 2019;(2):896-909
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Abstract
Pyruvate dehydrogenase is the first enzyme (E1) of the PDH complex (PDC). This multienzyme complex contains E1, E2, and E3 components and controls the entry of carbon into the mitochondrial tricarboxylic acid cycle to enable cellular energy production. The E1 component of the PDC is composed of an E1α catalytic subunit and an E1β regulatory subunit. In Arabidopsis (Arabidopsis thaliana), there are two mitochondrial E1α homologs encoded by IAA-CONJUGATE-RESISTANT 4 (IAR4) and IAR4-LIKE (IAR4L), and one mitochondrial E1β homolog. Although IAR4 was reported to be involved in auxin conjugate sensitivity and auxin homeostasis in root development, its precise role remains unknown. Here, we provide experimental evidence that mitochondrial PDC E1 contributes to polar auxin transport during organ development. We performed genetic screens for factors involved in cotyledon development and identified an uncharacterized mutant, macchi-bou 1 (mab1). MAB1 encodes a mitochondrial PDC E1β subunit that can form both a homodimer and a heterodimer with IAR4. The mab1 mutation impaired MAB1 homodimerization, reduced the abundance of IAR4 and IAR4L, weakened PDC enzymatic activity, and diminished mitochondrial respiration. A metabolomics analysis showed significant changes in metabolites including amino acids in mab1 and, in particular, identified an accumulation of Ala. These results suggest that MAB1 is a component of the Arabidopsis mitochondrial PDC E1. Furthermore, in mab1 mutants and seedlings where the TCA cycle was pharmacologically blocked, we found reduced abundance of the PIN-FORMED (PIN) auxin efflux carriers, possibly due to impaired PIN recycling and enhanced PIN degradation in vacuoles. Therefore, we suggest that mab1 induces defective polar auxin transport via metabolic abnormalities.
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6.
Systems Biology Approach Pinpoints Minimum Requirements for Auxin Distribution during Fruit Opening.
Li, XR, Vroomans, RMA, Fox, S, Grieneisen, VA, Østergaard, L, Marée, AFM
Molecular plant. 2019;(6):863-878
Abstract
The phytohormone auxin is implied in steering various developmental decisions during plant morphogenesis in a concentration-dependent manner. Auxin maxima have been shown to maintain meristematic activity, for example, of the root apical meristem, and position new sites of outgrowth, such as during lateral root initiation and phyllotaxis. More recently, it has been demonstrated that sites of auxin minima also provide positional information. In the developing Arabidopsis fruit, auxin minima are required for correct differentiation of the valve margin. It remains unclear, however, how this auxin minimum is generated and maintained. Here, we employ a systems biology approach to model auxin transport based on experimental observations. This allows us to determine the minimal requirements for its establishment. Our simulations reveal that two alternative processes-which we coin "flux-barrier" and "flux-passage"-are both able to generate an auxin minimum, but under different parameter settings. Both models are in principle able to yield similar auxin profiles but present qualitatively distinct patterns of auxin flux. The models were tested by tissue-specific inducible ablation, revealing that the auxin minimum in the fruit is most likely generated by a flux-passage process. Model predictions were further supported through 3D PIN localization imaging and implementing experimentally observed transporter localization. Through such an experimental-modeling cycle, we predict how the auxin minimum gradually matures during fruit development to ensure timely fruit opening and seed dispersal.
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7.
Molecular Responses during Plant Grafting and Its Regulation by Auxins, Cytokinins, and Gibberellins.
Sharma, A, Zheng, B
Biomolecules. 2019;(9)
Abstract
Plant grafting is an important horticulture technique used to produce a new plant after joining rootstock and scion. This is one of the most used techniques by horticulturists to enhance the quality and production of various crops. Grafting helps in improving the health of plants, their yield, and the quality of plant products, along with the enhancement of their postharvest life. The main process responsible for successful production of grafted plants is the connection of vascular tissues. This step determines the success rate of grafts and hence needs to be studied in detail. There are many factors that regulate the connection of scion and stock, and plant hormones are of special interest for researchers in the recent times. These phytohormones act as signaling molecules and have the capability of translocation across the graft union. Plant hormones, mainly auxins, cytokinins, and gibberellins, play a major role in the regulation of various key physiological processes occurring at the grafting site. In the current review, we discuss the molecular mechanisms of graft development and the phytohormone-mediated regulation of the growth and development of graft union.
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8.
Strain- or Stress-Sensing in Mechanochemical Patterning by the Phytohormone Auxin.
Julien, JD, Pumir, A, Boudaoud, A
Bulletin of mathematical biology. 2019;(8):3342-3361
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Abstract
Both chemical and mechanical fields are known to play a major role in morphogenesis. In plants, the phytohormone auxin and its directional transport are essential for the formation of robust patterns of organs, such as flowers or leaves, known as phyllotactic patterns. The transport of auxin was recently shown to be affected by mechanical signals, and conversely, auxin accumulation in incipient organs affects the mechanical properties of the cells. The precise interaction between mechanical fields and auxin transport, however, is poorly understood. In particular, it is unknown whether transport is sensitive to the strain or to the stress exerted on a given cell. Here, we investigate the nature of this coupling with the help of theoretical models. Namely, we introduce the effects of either mechanical stress or mechanical strain in a model of auxin transport and compare the patterns predicted with available experimental results, in which the tissue is perturbed by ablations, chemical treatments, or genetic manipulations. We also study the robustness of the patterning mechanism to noise and investigate the effect of a shock that changes abruptly its parameters. Although the model predictions with the two different feedbacks are often indistinguishable, the strain feedback seems to better agree with some of the experiments. The computational modeling approach used here, which enables us to distinguish between several possible mechanical feedbacks, offers promising perspectives to elucidate the role of mechanics in tissue development, and may help providing insight into the underlying molecular mechanisms.
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9.
Translating auxin responses into ovules, seeds and yield: Insight from Arabidopsis and the cereals.
Shirley, NJ, Aubert, MK, Wilkinson, LG, Bird, DC, Lora, J, Yang, X, Tucker, MR
Journal of integrative plant biology. 2019;(3):310-336
Abstract
Grain production in cereal crops depends on the stable formation of male and female gametes in the flower. In most angiosperms, the female gamete is produced from a germline located deep within the ovary, protected by several layers of maternal tissue, including the ovary wall, ovule integuments and nucellus. In the field, germline formation and floret fertility are major determinants of yield potential, contributing to traits such as seed number, weight and size. As such, stimuli affecting the timing and duration of reproductive phases, as well as the viability, size and number of cells within reproductive organs can significantly impact yield. One key stimulant is the phytohormone auxin, which influences growth and morphogenesis of female tissues during gynoecium development, gametophyte formation, and endosperm cellularization. In this review we consider the role of the auxin signaling pathway during ovule and seed development, first in the context of Arabidopsis and then in the cereals. We summarize the gene families involved and highlight distinct expression patterns that suggest a range of roles in reproductive cell specification and fate. This is discussed in terms of seed production and how targeted modification of different tissues might facilitate improvements.
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A DAO1-Mediated Circuit Controls Auxin and Jasmonate Crosstalk Robustness during Adventitious Root Initiation in Arabidopsis.
Lakehal, A, Dob, A, Novák, O, Bellini, C
International journal of molecular sciences. 2019;(18)
Abstract
Adventitious rooting is a post-embryonic developmental program governed by a multitude of endogenous and environmental cues. Auxin, along with other phytohormones, integrates and translates these cues into precise molecular signatures to provide a coherent developmental output. Auxin signaling guides every step of adventitious root (AR) development from the early event of cell reprogramming and identity transitions until emergence. We have previously shown that auxin signaling controls the early events of AR initiation (ARI) by modulating the homeostasis of the negative regulator jasmonate (JA). Although considerable knowledge has been acquired about the role of auxin and JA in ARI, the genetic components acting downstream of JA signaling and the mechanistic basis controlling the interaction between these two hormones are not well understood. Here we provide evidence that COI1-dependent JA signaling controls the expression of DAO1 and its closely related paralog DAO2. In addition, we show that the dao1-1 loss of function mutant produces more ARs than the wild type, probably due to its deficiency in accumulating JA and its bioactive metabolite JA-Ile. Together, our data indicate that DAO1 controls a sensitive feedback circuit that stabilizes the auxin and JA crosstalk during ARI.