ICT1 is an Arabidopsis thaliana line that overexpresses the gene encoding the S30 ribosomal subunit, leading to tolerance to exogenous indole-3-carbinol. Indole-3-carbinol (I3C) is a protective chemical formed as a breakdown of I3M in cruciferous vegetables. The overexpression of S30 in ICT1 results in transcriptional changes that prime the plant for the I3C, or biotic insult. Emerging evidence suggests that ribosomal proteins play important extra-ribosomal roles in various biochemical and developmental processes, such as transcription and stress resistance. In an attempt to elucidate the mechanism leading to I3C and stress resistance in ICT1, and using a multi-pronged approach employing transcriptomics, metabolomics, phenomics, and physiological studies, we show that overexpression of S30 leads to specific transcriptional alterations, which lead to both changes in metabolites connected to biotic and oxidative stress tolerance and, surprisingly, to photomorphogenesis.

Indole-3-carbinol (I3C), a hydrolysis product of indole-3-methylglucosinolate, is toxic to herbivorous insects and pathogens. In mammals, I3C is extensively studied for its properties in cancer prevention and treatment. Produced in Brassicaceae, I3C reversibly inhibits root elongation in a concentration-dependent manner. This inhibition is partially explained by the antagonistic action of I3C on auxin signaling through TIR1. To further elucidate the mode of action of I3C in plants, we have employed a forward-genetic amiRNA screen that circumvents functional redundancy. We identified and characterized two amiRNA lines with impaired I3C response. The first line, ICT2, targets the phosphatidylinositol 4-phosphate 5-kinase family (PIP5K), exhibiting tolerance to I3C, while the second line, ICS1, targets the Wall-Associated Kinases (WAK1–3) family, showing susceptibility to I3C. Both lines maintain I3C-induced antagonism of auxin signaling, indicating that their phenotypes are due to auxin-independent mechanisms. Transcript profiling experiments reveal that both lines are transcriptionally primed to respond to I3C treatment. Physiological, metabolomic, and transcriptomic analysis reveal that these kinases mediate numerous developmental processes and are involved in abiotic and biotic stress responses.

Probiotic fermented foods are perceived as contributing to human health, however solid evidence for their presumptive therapeutic systemic benefits is generally lacking. Here we report that tryptophol acetate and tyrosol acetate, small molecule metabolites secreted by the probiotic milk-fermented yeast Kluyveromyces marxianus inhibit hyperinflammation (e.g., “cytokine storm”). Comprehensive in vivo and in vitro analyses, employing LPS-induced hyperinflammation models, reveal dramatic effects of the molecules, added in tandem, on mice morbidity, laboratory parameters, and mortality. Specifically, we observed attenuated levels of the pro-inflammatory cytokines IL-6, IL-1α, IL-1β and TNF-α, and reduced reactive oxygen species. Importantly, tryptophol acetate and tyrosol acetate did not completely suppress pro-inflammatory cytokine generation, rather brought their concentrations back to baseline levels thus maintaining core immune functions, including phagocytosis. The anti-inflammatory effects of tryptophol acetate and tyrosol acetate were mediated through downregulation of TLR4, IL-1R, and TNFR signaling pathways and increased A20 expression, leading to NF-kB inhibition. Overall, this work illuminates phenomenological and molecular details underscoring anti-inflammatory properties of small molecules identified in a probiotic mixture, pointing to potential therapeutic avenues against severe inflammation.

AbstractThis chapter focusses on the role of science, technology and innovation (STI) in transforming the food systems of Asia and the Pacific to achieve long-term environmentally sustainable food and nutritional security (FNS). A “whole of systems” approach is required to address the issues, and that work is urgently needed to define ‘healthy’ diets for different regions, societies and cultures. Emphasis should shift from the provision of calories to the supply of balanced patterns of all essential nutrients, and the ‘holistic’ properties of foods should be recognised. The chapter identifies countries and regions, within Asia, considered to be at particularly high risk for future food insecurity. Systems analysis should be applied across the agricultural and food sectors of these countries to identify the actual technical and other impediments to FNS. It is envisaged that the results from such an analysis would be used to formulate a ‘blueprint’ for agricultural and food STI in Asia. Overarching recommendations are the establishment of a trans-national funding mechanism for the entire region, focussing on targeted interdisciplinary STI, and the establishment of regional centres of excellence for research, education and extension, focussing on the identified key areas of opportunity. It was concluded that there is an urgent need for investment and action.

Probiotic fermented foods are perceived as contributing to human health and capable of protecting against inflammation processes, however solid mechanistic evidence for the putative therapeutic benefits are generally lacking. Here we report that tryptophol acetate and tyrosol acetate, small molecule metabolites secreted by the probiotic milk-fermented yeast Kluyveromyces marxianus exhibit remarkable anti-inflammatory properties. Comprehensive in vivo and in vitro experimental analyses, employing LPS-induced “cytokine storm” models, reveal dramatic effects of the two molecules, added in tandem, on mice morbidity, laboratory parameters and mortality. In parallel, significant attenuation of pro-inflammatory cytokines including IL-6, IL- 1α, IL - 1β and TNF- α , and reduction of reactive oxygen species were recorded. Importantly, tryptophol acetate and tyrosol acetate did not completely suppress cytokine generation, but rather brought their concentrations back to baseline levels, enabling maintenance of core immune functions, including phagocytosis. The anti-inflammatory effects of tryptophol acetate and tyrosol acetate were mediated through downregulation of TLR4, IL-1R, and TNFR signaling pathways and increased A20 expression, leading to NF-kB attenuation. Moreover, the two molecules had a significant impact on mice microbiome, increasing the abundance of the genus Bactericides, known to exhibit anti-inflammatory properties. Overall, this work illuminates pronounced and broad-based immune modulation properties of probiotic yeast-secreted metabolites, underscoring potential new therapeutic avenues for severe inflammation pathologies.

Seaweed-derived extracts hold the promise of providing novel biostimulants to sustainably increase crop yields. The objective of this work was to determine whether ulvan crude extract could be used as a biostimulant for terrestrial plants. Herein we show that the crude extract of ulvan, extracted from cultivated Ulva sp., promotes growth of Arabidopsis thaliana. Ulvan's stimulative effect is both dose- and light intensity-dependent. We tested the effects of supplementation of 6 crude ulvan extract concentrations in the 0.01mg/ml - 1.43mg/ml range on A. thaliana growth for 3 weeks after sowing on agar plates under 90μmol m-2 sec-1 and 320μmol m-2 sec-1 light intensities. The addition of 0.07mg/ml ulvan extract to plant growth media for 3 weeks under 320μmol m-2 sec-1 light intensity led to an increase of 174% in root length, 83% in root dry weight, 54% in shoot dry weight, and 62% of total plant dry weight compared to untreated controls. The addition of 0.07mg/ml ulvan extract to plant growth media for 3 weeks in 90μmol m-2 sec-1 led to an increase of 120% in root length; no effect was observed on the total plant, shoot, or root weights compared to untreated controls. These results have applicative importance, as the use of biostimulants, such as ulvan, could potentially reduce the use of harmful agrochemicals, thus mitigating their negative environmental impacts, while increasing crop yield and contributing to global food security.

In nature, plants are exposed to several environmental stresses that can be continuous or recurring. Continuous stress can be lethal, but stress after priming can increase the tolerance of a plant to better prepare for future stresses. Reports have suggested that transcription factors are involved in stress memory after recurrent stress; however, less is known about the factors that regulate the resetting of stress memory. Here, we uncovered a role for Constitutive Photomorphogenesis 5A (CSN5A) in the regulation of stress memory for resetting transcriptional memory genes (APX2 and HSP22) and H3K4me3 following recurrent heat stress. Furthermore, CSN5A is also required for the deposition of H3K4me3 following recurrent heat stress. Thus, CSN5A plays an important role in the regulation of histone methylation and transcriptional stress memory after recurrent heat stress.

Indole-3-carbinol (I3C), a hydrolysis product of indole-3-methylglucosinolate, is toxic to herbivorous insects and pathogens. In mammals, I3C is extensively studied for its properties in cancer prevention and treatment. Produced in Brassicaceae, I3C reversibly inhibits root elongation in a concentration-dependent manner. This inhibition is partially explained by the antagonistic action of I3C on auxin signaling through TIR1. To further elucidate the mode of action of I3C in plants, we have identified and characterized a novel Arabidopsis mutant tolerant to I3C, ICT1. This mutant was identified following screening of the Full-length cDNA Over-eXpression library (FOX) seed collection for root growth in the presence of exogenous I3C. ICT1 carries the AT2G19750 gene, which encodes an S30 ribosomal protein. Overexpression, but not knockout, of the S30 gene causes tolerance to I3C. The tolerance is specific to I3C, since ICT1 did not exhibit pronounced tolerance to other indole or benzoxazinoid molecules tested. ICT1 maintains I3C-induced antagonism of auxin signaling, indicating that the tolerance is due to an auxin-independent mechanism. Transcript profiling experiments revealed that ICT1 is transcriptionally primed to respond to I3C treatment.

The vertebrate intestine has a continuous dorsal mesentery between pharynx and anus that facilitates intestinal mobility. Based on width and fate the dorsal mesentery can be subdivided into that of the caudal foregut, midgut, and hindgut. The dorsal mesentery of stomach and duodenum is wide and topographically complex due to strong and asymmetric growth of the stomach. The associated formation of the lesser sac partitions the dorsal mesentery into the right-sided "caval fold" that serves as conduit for the inferior caval vein and the left-sided mesogastrium. The thin dorsal mesentery of the midgut originates between the base of the superior and inferior mesenteric arteries, and follows the transient increase in intestinal growth that results in small-intestinal looping, intestinal herniation and, subsequently, return. The following fixation of a large portion of the abdominal dorsal mesentery to the dorsal peritoneal wall by adhesion and fusion is only seen in primates and is often incomplete. Adhesion and fusion of mesothelial surfaces in the lesser pelvis results in the formation of the "mesorectum". Whether Toldt's and Denonvilliers' "fasciae of fusion" identify the location of the original mesothelial surfaces or, alternatively, represent the effects of postnatal wear and tear due to intestinal motility and intra-abdominal pressure changes, remains to be shown. "Malrotations" are characterized by growth defects of the intestinal loops with an ischemic origin and a narrow mesenteric root due to insufficient adhesion and fusion.

Can plants hear? That is, can they sense airborne sounds and respond to them? Here we show that Oenothera drummondii flowers, exposed to the playback sound of a flying bee or to synthetic sound-signals at similar frequencies, produced sweeter nectar within 3 minutes, potentially increasing the chances of cross pollination. We found that the flowers vibrated mechanically in response to these sounds, suggesting a plausible mechanism where the flower serves as the plant’s auditory sensory organ. Both the vibration and the nectar response were frequency-specific: the flowers responded to pollinator sounds, but not to higher frequency sound. Our results document for the first time that plants can rapidly respond to pollinator sounds in an ecologically relevant way. Sensitivity of plants to pollinator sound can affect plant-pollinator interactions in a wide range of ways: Plants could allocate their resources more adequately, focusing on the time of pollinator activity; pollinators would then be better rewarded per time unit; flower shape may be selected for its effect on hearing ability, and not only on signaling; and pollinators may evolve to make sounds that the flowers can hear. Finally, our results suggest that plants may be affected by other sounds as well, including antropogenic ones.

The COP9 (constitutive photomorphogenesis 9) signalosome (CSN) is an evolutionarily conserved protein complex which regulates various growth and developmental processes. However, the role of CSN during environmental stress is largely unknown. Using Arabidopsis as model organism, we used CSN hypomorphic mutants to study the role of the CSN in plant responses to environmental stress and found that heat stress specifically enhanced the growth of csn5a-1 but not the growth of other hypomorphic photomorphogenesis mutants tested. Following heat stress, csn5a-1 exhibits an increase in cell size, ploidy, photosynthetic activity, and number of lateral roots and an upregulation of genes connected to the auxin response. Immunoblot analysis revealed an increase in deneddylation of CUL1 but not CUL3 following heat stress in csn5a-1, implicating improved CUL1 activity as a basis for the improved growth of csn5a-1 following heat stress. Studies using DR5::N7-VENUS and DII-VENUS reporter constructs confirm that the heat-induced growth is due to an increase in auxin signaling. Our results indicate that CSN5A has a specific role in deneddylation of CUL1 and that CSN5A is required for the recovery of AUX/IAA repressor levels following recurrent heat stress to regulate auxin homeostasis in Arabidopsis.

The COP9 (Constitutive photomorphogenesis 9) signalosome (CSN) is a highly conserved protein complex that influences several signaling and developmental processes. The COP9 signalosome consists of eight subunits, among which two subunits, CSN5 and CSN6, contain an Mpr1/Pad1 N-terminal (MPN) domain and the remaining six subunits contain a proteasome, COP9 signalosome, and initiation factor 3 (PCI) domain. In plants, each MPN subunit is encoded by two genes, which is not the case in other organisms. This review aims to provide in-depth knowledge of each COP9 signalosome subunit, concentrating on genetic analysis of both partial and complete loss-of-function mutants. At the beginning of this review, the role of COP9 signalosome in the hormonal signaling and defense is discussed, whereas later sections deal in detail with the available partial loss-of-function, hypomorphic mutants of each subunit. All available hypomorphic mutants are compared based on their growth response and deneddylation activity.

Carotenoid cleavage dioxygenases (CCDs) form hormones and signaling molecules.Here we show that a member of an overlooked plant CCD subfamily from rice, that we name Zaxinone Synthase (ZAS), can produce zaxinone, a novel apocarotenoid metabolite in vitro.Loss-of-function mutants (zas) contain less zaxinone, exhibit retarded growth and showed elevated levels of strigolactones (SLs), a hormone that determines plant architecture, mediates mycorrhization and facilitates infestation by root parasitic weeds, such as Striga spp.Application of zaxinone can rescue zas phenotypes, decrease SL content and release and promote root growth in wild-type seedlings.In conclusion, we show that zaxinone is a key regulator of rice development and biotic interactions and has potential for increasing crop growth and combating Striga, a severe threat to global food security.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.semcdb.2019.02.004. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Like all living organisms, without exception, plants integrate many external signals to adapt to their environment and increase their fitness. Is this a proof of intelligence? It depends on the meaning of the word; and it really does not matter.

A diet rich in cruciferous vegetables such as cauliflower, broccoli, and cabbage has long been considered healthy, and various epidemiological studies suggest that the consumption of cruciferous vegetables contributes to a cancer-protecting diet. While these vegetables contain a vast array of phytochemicals, the mechanism by which these vegetables counteract cancer is still largely unresolved. Numerous in situ studies have implicated indole-3-carbinol, a breakdown product of the glucosinolate indole-3-ylmethylglucosinolate, as one of the phytochemicals with anti-cancer properties. Indole-3-carbinol influences a range of cellular processes, but the mechanisms by which it acts on cancer cells are slowly being revealed. Recent studies on the role of indole-3-carbinol in Arabidopsis opens the door for cross-kingdom comparisons that can help in understanding the roles of this important phytohormone in both plant biology and combatting cancer.

MotivationThe COP9 signalosome is a highly conserved multi-protein complex consisting of eight subunits, which influences key developmental pathways through its regulation of protein stability and transcription. In Arabidopsis thaliana, mutations in the COP9 Signalosome exhibit a number of diverse pleiotropic phenotypes. Total or partial loss of COP9 Signalosome function in Arabidopsis leads to misregulation of a number of genes involved in DNA methylation, suggesting that part of the pleiotropic phenotype is due to global effects on DNA methylation.ResultsWe determined and analyzed the methylomes and transcriptomes of both partial- and total-loss-of-function Arabidopsis mutants of the COP9 Signalosome. Our results support the hypothesis that the COP9 Signalosome has a global genome-wide effect on methylation and that this effect is at least partially encoded in the DNA. Our analyses suggest that COP9 Signalosome-dependent methylation is related to gene expression regulation in various ways. Differentially methylated regions tend to be closer in the 3D conformation of the genome to differentially expressed genes. These results suggest that the COP9 Signalosome has a more comprehensive effect on gene expression than thought before, and this is partially related to regulation of methylation. The high level of COP9 Signalosome conservation among eukaryotes may also suggest that COP9 Signalosome regulates methylation not only in plants but also in other eukaryotes, including humans.Supplementary informationSupplementary data are available at Bioinformatics online.

A diet rich in cruciferous vegetables such as cauliflower, broccoli, and cabbage has long been considered healthy, and various epidemiological studies suggest that the consumption of cruciferous vegetables contributes to a cancer-protecting diet. While these vegetables contain a vast array of phytochemicals, the mechanism by which these vegetables counteract cancer is still largely unresolved. Numerous in situ studies have implicated indole-3-carbinol, a breakdown product of the glucosinolate indole-3-ylmethylglucosinolate, as one of the phytochemicals with anti-cancer properties. Indole-3-carbinol influences a range of cellular processes, but the mechanisms by which it acts on cancer cells are slowly being revealed. Recent studies on the role of indole-3-carbinol in Arabidopsis opens the door for cross-kingdom comparisons that can help in understanding the roles of this important phytohormone in both plant biology and combatting cancer.