Circular RNAs modulate the floral fate acquisition in soybean shoot apical meristem.

BACKGROUND: Soybean (Glycine max), a major oilseed and protein source, requires a short-day photoperiod for floral induction. Though key transcription factors controlling flowering have been identified, the role of the non-coding genome is limited. Circular RNAs (circRNAs) recently emerged as a novel class of RNAs with critical regulatory functions. However, a study on circRNAs during the floral transition of a crop plant is lacking. We investigated the expression and potential function of circRNAs in floral fate acquisition by soybean shoot apical meristem in response to short-day treatment. RESULTS: Using deep sequencing and in-silico analysis, we denoted 384 circRNAs, with 129 exhibiting short-day treatment-specific expression patterns. We also identified 38 circRNAs with predicted binding sites for miRNAs that could affect the expression of diverse downstream genes through the circRNA-miRNA-mRNA network. Notably, four different circRNAs with potential binding sites for an important microRNA module regulating developmental phase transition in plants, miR156 and miR172, were identified. We also identified circRNAs arising from hormonal signaling pathway genes, especially abscisic acid, and auxin, suggesting an intricate network leading to floral transition. CONCLUSIONS: This study highlights the gene regulatory complexity during the vegetative to reproductive transition and paves the way to unlock floral transition in a crop plant.

Genome-wide analysis reveals the crucial role of lncRNAs in regulating the expression of genes controlling pollen development.

KEY MESSAGE: The genomic location and stage-specific expression pattern of many long non-coding RNAs reveal their critical role in regulating protein-coding genes crucial in pollen developmental progression and male germ line specification. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 bp with no apparent protein-coding potential. Multiple investigations have revealed high expression of lncRNAs in plant reproductive organs in a cell and tissue-specific manner. However, their potential role as essential regulators of molecular processes involved in sexual reproduction remains largely unexplored. We have used developing field mustard (Brassica rapa) pollen as a model system for investigating the potential role of lncRNAs in reproductive development. Reference-based transcriptome assembly performed to update the existing genome annotation identified novel expressed protein-coding genes and long non-coding RNAs (lncRNAs), including 4347 long intergenic non-coding RNAs (lincRNAs, 1058 expressed) and 2,045 lncRNAs overlapping protein-coding genes on the opposite strand (lncNATs, 780 expressed). The analysis of expression profiles reveals that lncRNAs are significant and stage-specific contributors to the gene expression profile of developing pollen. Gene co-expression networks accompanied by genome location analysis identified 38 cis-acting lincRNA, 31 cis-acting lncNAT, 7 trans-acting lincRNA and 14 trans-acting lncNAT to be substantially co-expressed with target protein-coding genes involved in biological processes regulating pollen development and male lineage specification. These findings provide a foundation for future research aiming at developing strategies to employ lncRNAs as regulatory tools for gene expression control during reproductive development.

Melatonin and Abiotic Stress Tolerance in Crop Plants.

Increasing food demand by the growing human population and declining crop productivity due to climate change affect global food security. To meet the challenges, developing improved crops that can tolerate abiotic stresses is a priority. Melatonin in plants, also known as phytomelatonin, is an active component of the various cellular mechanisms that alleviates oxidative damage in plants, hence supporting the plant to survive abiotic stress conditions. Exogenous melatonin strengthens this defence mechanism by enhancing the detoxification of reactive by-products, promoting physiological activities, and upregulating stress-responsive genes to alleviate damage during abiotic stress. In addition to its well-known antioxidant activity, melatonin protects against abiotic stress by regulating plant hormones, activating ER stress-responsive genes, and increasing protein homoeostasis, heat shock transcription factors and heat shock proteins. Under abiotic stress, melatonin enhances the unfolded protein response, endoplasmic reticulum-associated protein degradation, and autophagy, which ultimately protect cells from programmed cell death and promotes cell repair resulting in increased plant survival.

Pokkali: A Naturally Evolved Salt-Tolerant Rice Shows a Distinguished Set of lncRNAs Possibly Contributing to the Tolerant Phenotype.

Pokkali is a strong representation of how stress-tolerant genotypes have evolved due to natural selection pressure. Numerous omics-based investigations have indicated different categories of stress-related genes and proteins, possibly contributing to salinity tolerance in this wild rice. However, a comprehensive study towards understanding the role of long-noncoding RNAs (lncRNAs) in the salinity response of Pokkali has not been done to date. We have identified salt-responsive lncRNAs from contrasting rice genotypes IR64 and Pokkali. A total of 63 and 81 salinity-responsive lncRNAs were differentially expressed in IR64 and Pokkali, respectively. Molecular characterization of lncRNAs and lncRNA-miRNA-mRNA interaction networks helps to explore the role of lncRNAs in the stress response. Functional annotation revealed that identified lncRNAs modulate various cellular processes, including transcriptional regulation, ion homeostasis, and secondary metabolite production. Additionally, lncRNAs were predicted to bind stress-responsive transcription factors, namely ERF, DOF, and WRKY. In addition to salinity, expression profiling was also performed under other abiotic stresses and phytohormone treatments. A positive modulation in TCONS_00035411, TCONS_00059828, and TCONS_00096512 under both abiotic stress and phytohormone treatments could be considered as being of potential interest for the further functional characterization of IncRNA. Thus, extensive analysis of lncRNAs under various treatments helps to delineate stress tolerance mechanisms and possible cross-talk.

Biomolecules of mushroom: a recipe of human wellness.

The Indian system of medicine - Ayurveda says "When diet is wrong, medicine is of no use. When diet is correct, medicine is of no use". In this context, mushroom constitutes one of the major resources for nutraceuticals. Biomolecules of mushrooms have attracted the attention of researchers around the globe due to their proven healthy attributes. They have a plenitude of health-giving properties and these range from immunomodulatory, antiviral, antibacterial, antifungal, antioxidant, anti-inflammatory, antitumor, anticancer, anti-HIV, antidiabetic, anticholesterolic to antiarthritic activities.Mushrooms contain both primary and secondary metabolites. The primary metabolites provide energy while the secondary metabolite exhibits medicinal properties. Hence, the mushroom can be a recipe for human wellness and will play a significant role in fighting COVID-19 pandemics and other infectious diseases.The key findings suggested in this paper refer to the exploration of health and the healing traits of biomolecules of mushrooms. This article reviews the current status of the medicinal attributes of mushrooms and their biomolecules in different diseases such as cardiovascular, diabetes, reproductive diseases, cancer, and neurodegenerative diseases. The global malnutrition-related morbidity and mortality among children under five and lactating women presents a frightening picture and also a black spot on the human face. Malnutrition is responsible for more ill-health than any other cause. Mushrooms as a rich source of bioactive compounds can be claimed as "Best from the Waste" since they grow on the most abundant organic wastes of the Earth, the lignocellulosic substrate, and 'Best of the Rest' because they are excellent nutraceutical resources.

Recent Overview of Resveratrol's Beneficial Effects and Its Nano-Delivery Systems.

Natural polyphenols have a wide variety of biological activities and are taken into account as healthcare materials. Resveratrol is one such natural polyphenol, belonging to a group known as stilbenoids (STBs). Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is mainly found in grapes, wine, nuts, and berries. A wide range of biological activities has been demonstrated by resveratrol, including antimicrobial, antioxidant, antiviral, antifungal, and antiaging effects, and many more are still under research. However, as with many other plant-based polyphenol products, resveratrol suffers from low bioavailability once administered in vivo due to its susceptibility to rapid enzyme degradation by the body's innate immune system before it can exercise its therapeutic influence. Therefore, it is of the utmost importance to ensure the best use of resveratrol by creating a proper resveratrol delivery system. Nanomedicine and nanodelivery systems utilize nanoscale materials as diagnostic tools or to deliver therapeutic agents in a controlled manner to specifically targeted locations. After a brief introduction about polyphenols, this review overviews the physicochemical characteristics of resveratrol, its beneficial effects, and recent advances on novel nanotechnological approaches for its delivery according to the type of nanocarrier utilized. Furthermore, the article summarizes the different potential applications of resveratrol as, for example, a therapeutic and disease-preventing anticancer and antiviral agent.

Endoscopic vacuum therapy (EVT) in the management of oesophageal perforations and post-operative leaks.

INTRODUCTION: Oesophageal perforations and post-oesophagectomy anastomotic leaks are associated with high morbidity and mortality. Endoscopic vacuum therapy (EVT) is a novel treatment strategy with the potential to promote healing and ameliorate sepsis. Only two cases of its use have been reported in the UK in the management of oesophageal wall defects, representing a limited aetiological and demographic spectrum. MATERIAL AND METHODS: From May to December 2019, 7 patients aged 27-85 years underwent EVT for disparate oesophageal wall defects. Data regarding technical success and feasibility were analysed. RESULTS: Complete defect resolution was achieved in six cases (86%), requiring median of 13 days of treatment (range 6-23), and necessitating three replacement procedures (range 1-4). Significant improvement in C-reactive protein was achieved in all patients undergoing treatment (p = .015). No severe complications occurred that resulted directly from sponge placement, however two individuals (33%) developed oesophageal stricture necessitating endoscopic balloon dilatation, and one died whilst undergoing treatment. CONCLUSION: In selected patients EVT is a safe, valuable tool for the management of a spectrum of oesophageal wall defects, with the potential to reduce associated morbidity and mortality. While this work significantly expands upon the UK reported experience of EVT, we outline the requirement for a national, prospective registry of EVT use in oesophageal leaks and perforations. ABBREVIATIONS: AL: anastomotic leak; CRP: C-reactive protein; CT: computed tomography; EVT: endoscopic vacuum therapy; HES: hospital episode statistics; OGD: oesophago-gastro-duodenoscopy; SEMS: oesophageal stenting with self-expanding stents; UK: United Kingdom.

Circular RNAs Repertoire and Expression Profile during Brassica rapa Pollen Development.

Circular RNAs (circRNAs) are covalently closed RNA molecules generated by the back-splicing of exons from linear precursor mRNAs. Though various linear RNAs have been shown to play important regulatory roles in many biological and developmental processes, little is known about the role of their circular counterparts. In this study, we performed high-throughput RNA sequencing to delineate the expression profile and potential function of circRNAs during the five stages of pollen development in Brassica rapa. A total of 1180 circRNAs were detected in pollen development, of which 367 showed stage-specific expression patterns. Functional enrichment and metabolic pathway analysis showed that the parent genes of circRNAs were mainly involved in pollen-related molecular and biological processes such as mitotic and meiotic cell division, DNA processes, protein synthesis, protein modification, and polysaccharide biosynthesis. Moreover, by predicting the circRNA-miRNA network from our differentially expressed circRNAs, we found 88 circRNAs with potential miRNA binding sites, suggesting their role in post-transcriptional regulation of the genes. Finally, we confirmed the back-splicing sites of nine selected circRNAs using divergent primers and Sanger sequencing. Our study presents the systematic analysis of circular RNAs during pollen development and forms the basis of future studies for unlocking complex gene regulatory networks underpinning reproduction in flowering plants.

Analysis of the quinoa genome reveals conservation and divergence of the flowering pathways.

Quinoa (Chenopodium quinoa Willd.) is a grain crop grown in the Andes renowned as a highly nutritious plant exhibiting tolerance to abiotic stress such as drought, cold and high salinity. Quinoa grows across a range of latitudes corresponding to differing day lengths, suggesting regional adaptations of flowering regulation. Improved understanding and subsequent modification of the flowering process, including flowering time, ensuring high yields, is one of the key factors behind expansion of cultivation zones and goals of the crop improvement programs worldwide. However, our understanding of the molecular basis of flower initiation and development in quinoa is limited. Here, we use a computational approach to perform genome-wide identification and analysis of 611 orthologues of the Arabidopsis thaliana flowering genes. Conservation of the genes belonging to the photoperiod, gibberellin and autonomous pathways was observed, while orthologues of the key genes found in the vernalisation pathway (FRI, FLC) were absent from the quinoa genome. Our analysis indicated that on average each Arabidopsis flowering gene has two orthologous copies in quinoa. Several genes including orthologues of MIF1, FT and TSF were identified as homologue-rich genes in quinoa. We also identified 459 quinoa-specific genes uniquely expressed in the flower and/or meristem, with no known orthologues in other species. The genes identified provide a resource and framework for further studies of flowering in quinoa and related species. It will serve as valuable resource for plant biologists, crop physiologists and breeders to facilitate further research and establishment of modern breeding programs for quinoa.

Correction to: Analysis of the quinoa genome reveals conservation and divergence of the flowering pathways.

The above article was published online with incorrect Fig. 5 legend. The legend for Fig. 4 was repeated in Fig. 5.

High temperature susceptibility of sexual reproduction in crop plants.

Climate change-induced increases in the frequency of extreme weather events, particularly heatwaves, are a serious threat to crop productivity. The productivity of grain crops is dependent on the success of sexual reproduction, which is very sensitive to heat stress. Male gametophyte development has been identified as the most heat-vulnerable stage. This review outlines the susceptibility of the various stages of sexual reproduction in flowering plants from the time of floral transition to double fertilization. We summarize current knowledge concerning the molecular mechanisms underpinning the heat stress-induced aberrations and abnormalities at flowering, male reproductive development, female reproductive development, and fertilization. We highlight the stage-specific bottlenecks in sexual reproduction, which regulate seed set and final yields under high-temperature conditions, together with the outstanding research questions concerning genotypic and species-specific differences in thermotolerance observed in crops. This knowledge is essential for trait selection and genetic modification strategies for the development of heat-tolerant genotypes and high-temperature-resilient crops.

MCRiceRepGP: a framework for the identification of genes associated with sexual reproduction in rice.

Rice is an important cereal crop, being a staple food for over half of the world's population, and sexual reproduction resulting in grain formation underpins global food security. However, despite considerable research efforts, many of the genes, especially long intergenic non-coding RNA (lincRNA) genes, involved in sexual reproduction in rice remain uncharacterized. With an increasing number of public resources becoming available, information from different sources can be combined to perform gene functional annotation. We report the development of MCRiceRepGP, a machine learning framework which integrates heterogeneous evidence and employs multicriteria decision analysis and machine learning to predict coding and lincRNA genes involved in sexual reproduction in rice. The rice genome was reannotated using deep-sequencing transcriptomic data from reproduction-associated tissue/cell types identifying previously unannotated putative protein-coding genes and lincRNAs. MCRiceRepGP was used for genome-wide discovery of sexual reproduction associated coding and lincRNA genes. The protein-coding and lincRNA genes identified have distinct expression profiles, with a large proportion of lincRNAs reaching maximum expression levels in the sperm cells. Some of the genes are potentially linked to male- and female-specific fertility and heat stress tolerance during the reproductive stage. MCRiceRepGP can be used in combination with other genome-wide studies, such as genome-wide association studies, giving greater confidence that the genes identified are associated with the biological process of interest. As more data, especially about mutant plant phenotypes, become available, the power of MCRiceRepGP will grow, providing researchers with a tool to identify candidate genes for future experiments. MCRiceRepGP is available as a web application (http://mcgplannotator.com/MCRiceRepGP/).

Genome-wide analysis of the Hsf gene family in Brassica oleracea and a comparative analysis of the Hsf gene family in B. oleracea, B. rapa and B. napus.

The global climate change-induced abiotic and biotic stresses are predicted to affect crop-growing seasons and crop yield. Heat stress transcription factors (Hsfs) have been suggested to play a significant role in various stress responses. They are an integral part of the signal transduction pathways that operate in response to environmental stresses. Brassica oleracea is one of the agronomical important crop species which consists of cabbage, cauliflower, broccoli, Brussels sprout, kohlrabi and kale. The identification and roles of Hsfs in this important Brassica species are unknown. The availability of whole genome sequence of B. oleracea provides us an opportunity for performing in silico analysis of Hsf genes in B. oleracea. Thirty-five putative genes encoding Hsf proteins were identified and classified into A, B and C classes. Their evolution, physical location, gene structure, domain structure and tissue-specific expression patterns were investigated. Further, a comparative analysis of the Hsf gene family in B. oleracea, B. rapa and B. napus highlighted the role of hybridisation and allopolyploidy in the evolution of the largest known Hsf gene family in B. napus. The presence of orthologous gene clusters, found in Brassica species, but not in A. thaliana, suggested that polyploidisation has resulted in the formation of new Brassica-specific orthologous gene clusters. Gene duplication analysis indicated that the evolution of the Hsf gene family was under strong purifying selection in these Brassica species. High-level synteny was observed within the B. napus genome. Conservation of physical location, the similarity of structure and similar expression profiles between the B. napus Hsf genes and the corresponding genes from B. oleracea and B. rapa suggest a high functional similarity between these genes. This study paves the way for further investigation of Hsf genes in improving stress tolerance in B. oleracea. The genes thus identified may be useful for developing crop varieties resilient to the global climate change.

The Long Intergenic Noncoding RNA (LincRNA) Landscape of the Soybean Genome.

Long intergenic noncoding RNAs (lincRNAs) are emerging as important regulators of diverse biological processes. However, our understanding of lincRNA abundance and function remains very limited especially for agriculturally important plants. Soybean (Glycine max) is a major legume crop plant providing over a half of global oilseed production. Moreover, soybean can form symbiotic relationships with Rhizobium bacteria to fix atmospheric nitrogen. Soybean has a complex paleopolyploid genome and exhibits many vegetative and floral development complexities. Soybean cultivars have photoperiod requirements restricting its use and productivity. Molecular regulators of these legume-specific developmental processes remain enigmatic. Long noncoding RNAs may play important regulatory roles in soybean growth and development. In this study, over one billion RNA-seq read pairs from 37 samples representing nine tissues were used to discover 6,018 lincRNA loci. The lincRNAs were shorter than protein-coding transcripts and had lower expression levels and more sample specific expression. Few of the loci were found to be conserved in two other legume species (chickpea [Cicer arietinum] and Medicago truncatula), but almost 200 homeologous lincRNAs in the soybean genome were detected. Protein-coding gene-lincRNA coexpression analysis suggested an involvement of lincRNAs in stress response, signal transduction, and developmental processes. Positional analysis of lincRNA loci implicated involvement in transcriptional regulation. lincRNA expression from centromeric regions was observed especially in actively dividing tissues, suggesting possible roles in cell division. Integration of publicly available genome-wide association data with the lincRNA map of the soybean genome uncovered 23 lincRNAs potentially associated with agronomic traits.

GLI3 repressor determines Hedgehog pathway activation and is required for response to SMO antagonist glasdegib in AML.

The Hedgehog (Hh) signaling pathway is activated in many cancers and is a promising target for therapeutic development. Deletions in the receptor Patched (PTCH) or activating mutations in Smoothened (SMO) have been reported in basal cell carcinoma and medulloblastoma, but are largely absent in most tumor types. Therefore, the mechanism of pathway activation in most cancers, including hematological malignancies, remains unknown. In normal tissues, Hh pathway activation via PTCH/SMO causes an increase in the downstream transcriptional activator GLI1 and a decrease in the GLI3 transcriptional repressor (GLI3R). In this article, we confirm that the Hh pathway is active in acute myeloid leukemia (AML), however, this activity is largely independent of SMO. Epigenetic and gene expression analysis of The Cancer Genome Atlas AML data set reveals that GLI3 expression is silenced in most AML patient samples, and the GLI3 locus is abnormally methylated. We show that GLI3R is required for the therapeutic effect of SMO antagonists in AML samples and restoration of GLI3R suppresses the growth of AML. We additionally demonstrate that GLI3R represses AML growth by downregulating AKT expression. In summary, this study provides the first evidence that GLI3R plays an essential role in SMO-independent Hh signaling in AML, and suggests that GLI3R could serve as a potential biomarker for patient selection in SMO antagonist clinical trials. Furthermore, these data support rational combinations of hypomethylating agents with SMO antagonists in clinical trials.

Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria from three highly malarious states in India.

BACKGROUND: Anti-malarial drug resistance continues to be a leading threat to malaria control efforts and calls for continued monitoring of waning efficacy of artemisinin-based combination therapy (ACT). Artesunate + sulfadoxine/pyrimethamine (AS + SP) is used for the treatment of uncomplicated Plasmodium falciparum malaria in India. However, resistance against AS + SP is emerged in northeastern states. Therefore, artemether-lumefantrine (AL) is the recommended first line treatment for falciparum malaria in north eastern states. This study investigates the therapeutic efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in three malaria-endemic states in India. The data generated through this study will benefit the immediate implementation of second-line ACT as and when required. METHODS: This was a one-arm prospective evaluation of clinical and parasitological responses for uncomplicated falciparum malaria using WHO protocol. Patients diagnosed with uncomplicated mono P. falciparum infection were administered six-dose regimen of AL over 3 days and subsequent follow-up was carried out up to 28 days. Molecular markers msp-1 and msp-2 were used to differentiate recrudescence and re-infection and K13 propeller gene was amplified and sequenced covering the codon 450-680. RESULTS: A total of 402 eligible patients were enrolled in the study from all four sites. Overall, adequate clinical and parasitological response (ACPR) was 98 % without PCR correction and 99 % with PCR correction. At three study sites, ACPR rates were 100 %, while at Bastar, cure rate was 92.5 % on day 28. No early treatment failure was found. The PCR-corrected endpoint finding confirmed that one late clinical failure (LCF) and two late parasitological failures (LPF) were recrudescences. The PCR corrected cure rate was 96.5 %. The mean fever clearance time was 27.2 h ± 8.2 (24-48 h) and the mean parasite clearance time was 30.1 h ± 11.0 (24-72 h). Additionally, no adverse event was recorded. Analysis of total 186 samples revealed a mutation in the k13 gene along with non-synonymous mutation at codon M579T in three (1.6 %) samples. CONCLUSION: AL is an efficacious drug for the treatment of uncomplicated falciparum malaria. However, regular monitoring of AL is required in view of malaria elimination initiatives, which will be largely dependent on therapeutic interventions, regular surveillance and targeted vector control.

Application of gold nanoparticles for gastrointestinal cancer theranostics: A systematic review.

Gold nanoparticles (GNPs) are readily synthesised structures that absorb light strongly to generate thermal energy which induces photothermal destruction of malignant tissue. This review examines the efficacy, potential challenges and toxicity from in vitro and in vivo applications of GNPs in oesophageal, gastric and colon cancers. A systematic literature search of Medline, Embase, Web of Science and Cochrane databases was performed using PRISMA guidelines. Two hundred and eighty-four papers were reviewed with sixteen studies meeting the inclusion criteria. The application of GNPs in eleven in vivo rodent studies with GI adenocarcinoma demonstrated excellent therapeutic outcomes but poor corroboration in terms of the cancer cells used, photothermal irradiation regimes, fluorophores and types of nanoparticles. There is compelling evidence of the translational potential of GNPs to be complimentary to surgery and feasible in the photothermal therapy of GI cancer but reproducibility and standardisation require development prior to GI cancer clinical trials. FROM THE CLINICAL EDITOR: Gold nanoparticles are one of the most potentially useful nanoparticles. This is especially true in cancer therapeutics because of their photothermal properties. In this comprehensive article, the authors reviewed the application and efficacy of gold nanoparticles in both the diagnosis and treatment of GI cancers. This review should provide a stimulus for researchers to further develop and translate these nanoparticles into future clinical trials.

miRNAs in the crosstalk between phytohormone signalling pathways.

Phytohormones are signal molecules produced within the plant that control its growth and development through the regulation of gene expression. Interaction between different phytohormone pathways is essential in coordinating tissue outgrowth in response to environmental changes, such as the adaptation of root development to water deficit or the initiation of seed germination during imbibition. Recently, microRNAs (miRNAs) have emerged as key regulators of phytohormone response pathways in planta by affecting their metabolism, distribution, and perception. Here we review current knowledge on the miRNA-mediated regulations involved in phytohormone crosstalk. We focus on the miRNAs exhibiting regulatory links with more than one phytohormone pathway and discuss their possible implication in coordinating multiple phytohormone responses during specific developmental processes.