Enhancing Micropropagation of Adenophora liliifolia: Insights from PGRs, Natural Extracts, and pH Optimization.

The endangered plant species Adenophora liliifolia faces threats to its survival in the wild, necessitating the development of effective micropropagation techniques for potential reintroduction efforts. This study demonstrates that Adenophora liliifolia effectively reproduces on MS synthetic medium with diverse plant growth regulators (PGR) and natural extracts, facilitating swift micropropagation for potential future reintroduction endeavors. It highlights the substantial impact of PGR composition and natural extracts on the growth and development of A. liliifolia. The ideal growth medium for A. liliifolia was determined to be ½ MS with specific treatments. Additionally, incorporating silver nitrate (AgNO3) at 5 mg L-1 into the medium led to enhanced root formation and shoot length, albeit excessive concentrations adversely affected root development. Varying concentrations of NAA significantly affected different plant growth parameters, with the 0.1 mg L-1 treatment yielding comparable plant height to the control. Moreover, 50 mL L-1 of coconut water bolstered root formation, while 200 mL L-1 increased shoot formation during in vitro propagation. However, elevated doses of coconut water (CW) impeded root development but stimulated shoot growth. Experiments measuring chlorophyll a + b and carotenoid content indicated higher concentrations in the control group than differing levels of applied coconut water. Optimizing pH levels from 6.8-7 to 7.8-8.0 notably enhanced plant height and root formation, with significant carotenoid accumulation observed at pH 6.8-7. Soil samples from A. liliifolia's natural habitat exhibited a pH of 6.65. Ultimately, the refined in vitro propagation protocol effectively propagated A. liliifolia, representing a pioneering effort and setting the stage for future restoration initiatives and conservation endeavors.

Critical role of cyclic electron transport around photosystem I in the maintenance of photosystem I activity.

In angiosperms, cyclic electron transport around photosystem I (PSI) is mediated by two pathways that depend on the PROTON GRADIENT REGULATION 5 (PGR5) protein and the chloroplast NADH dehydrogenase-like (NDH) complex, respectively. In the Arabidopsis double mutants defective in both pathways, plant growth and photosynthesis are impaired. The pgr5-1 mutant used in the original study is a missense allele and accumulates low levels of PGR5 protein. In this study, we generated two knockout (KO) alleles, designated as pgr5-5 and pgr5-6, using the CRISPR-Cas9 technology. Although both KO alleles showed a severe reduction in P700 similar to the pgr5-1 allele, NPQ induction was less severely impaired in the KO alleles than in the pgr5-1 allele. In the pgr5-1 allele, the second mutation affecting NPQ size was mapped to ~21 cM south of the pgr5-1 locus. Overexpression of the pgr5-1 allele, encoding the glycine130-to-serine change, complemented the pgr5-5 phenotype, suggesting that the pgr5-1 mutation destabilizes PGR5 but that the mutant protein retains partial functionality. Using two KO alleles, we created the double mutants with two chlororespiratory reduction (crr) mutants defective in the NDH complex. The growth of the double mutants was notably impaired. In the double mutant seedlings that survived on the medium containing sucrose, PSI activity evaluated by the P700 oxidation was severely impaired, whereas PSII activity was only mildly impaired. Cyclic electron transport around PSI is required to maintain PSI activity.

Autonomous differentiation of transgenic cells requiring no external hormone application: the endogenous gene expression and phytohormone behaviors.

The ectopic overexpression of developmental regulator (DR) genes has been reported to improve the transformation in recalcitrant plant species because of the promotion of cellular differentiation during cell culture processes. In other words, the external plant growth regulator (PGR) application during the tissue and cell culture process is still required in cases utilizing DR genes for plant regeneration. Here, the effect of Arabidopsis BABY BOOM (BBM) and WUSCHEL (WUS) on the differentiation of tobacco transgenic cells was examined. We found that the SRDX fusion to WUS, when co-expressed with the BBM-VP16 fusion gene, significantly influenced the induction of autonomous differentiation under PGR-free culture conditions, with similar effects in some other plant species. Furthermore, to understand the endogenous background underlying cell differentiation toward regeneration, phytohormone and RNA-seq analyses were performed using tobacco leaf explants in which transgenic cells were autonomously differentiating. The levels of active auxins, cytokinins, abscisic acid, and inactive gibberellins increased as cell differentiation proceeded toward organogenesis. Gene Ontology terms related to phytohormones and organogenesis were identified as differentially expressed genes, in addition to those related to polysaccharide and nitrate metabolism. The qRT-PCR four selected genes as DEGs supported the RNA-seq data. This differentiation induction system and the reported phytohormone and transcript profiles provide a foundation for the development of PGR-free tissue cultures of various plant species, facilitating future biotechnological breeding.

Expanding the Spectrum of NR4A3 Fusion-Positive Gynecologic Leiomyosarcomas.

Recurrent gene fusions have been observed in epithelioid and myxoid variants of uterine leiomyosarcoma. PGR::NR4A3 fusions were recently described in a subset of epithelioid leiomyosarcomas exhibiting rhabdoid morphology. In this study, we sought to expand the clinical, morphologic, immunohistochemical, and genetic features of gynecologic leiomyosarcomas harboring NR4A3 rearrangements with PGR and novel fusion partners. We identified 9 gynecologic leiomyosarcomas harboring PGR::NR4A3, CARMN::NR4A3, ACTB::NR4A3, and possible SLCO5A1::NR4A3 fusions by targeted RNA sequencing. Tumors frequently affected premenopausal women, involving the uterine corpus, uterine cervix, or pelvis. All were similarly characterized by lobules of monomorphic epithelioid and/or spindled cells arranged in sheets, cords, trabeculae, and micro- and macrocysts associated with abundant myxoid matrix and hemorrhage, creating labyrinth-like or pulmonary edema-like architecture. Myogenic differentiation with frequent estrogen receptor and progesterone receptor staining and no CD10 expression characterized all tumors. All cases showed high NR4A3 RNA expression levels and NOR1 (NR4A3) nuclear staining similar to salivary gland acinic cell carcinomas and a subset of extraskeletal myxoid chondrosarcomas harboring NR4A3 rearrangements. NOR1 (NR4A3) immunohistochemistry may serve as a useful diagnostic marker of NR4A3 fusion-positive gynecologic leiomyosarcomas.

Enhanced Reduction of Ferredoxin in PGR5-Deficient Mutant of Arabidopsis thaliana Stimulated Ferredoxin-Dependent Cyclic Electron Flow around Photosystem I.

The molecular entity responsible for catalyzing ferredoxin (Fd)-dependent cyclic electron flow around photosystem I (Fd-CEF) remains unidentified. To reveal the in vivo molecular mechanism of Fd-CEF, evaluating ferredoxin reduction-oxidation kinetics proves to be a reliable indicator of Fd-CEF activity. Recent research has demonstrated that the expression of Fd-CEF activity is contingent upon the oxidation of plastoquinone. Moreover, chloroplast NAD(P)H dehydrogenase does not catalyze Fd-CEF in Arabidopsis thaliana. In this study, we analyzed the impact of reduced Fd on Fd-CEF activity by comparing wild-type and pgr5-deficient mutants (pgr5hope1). PGR5 has been proposed as the mediator of Fd-CEF, and pgr5hope1 exhibited a comparable CO2 assimilation rate and the same reduction-oxidation level of PQ as the wild type. However, P700 oxidation was suppressed with highly reduced Fd in pgr5hope1, unlike in the wild type. As anticipated, the Fd-CEF activity was enhanced in pgr5hope1 compared to the wild type, and its activity further increased with the oxidation of PQ due to the elevated CO2 assimilation rate. This in vivo research clearly demonstrates that the expression of Fd-CEF activity requires not only reduced Fd but also oxidized PQ. Importantly, PGR5 was found to not catalyze Fd-CEF, challenging previous assumptions about its role in this process.

PGR-KITLG signaling drives a tumor-mast cell regulatory feedback to modulate apoptosis of breast cancer cells.

The immune microenvironment constructed by tumor-infiltrating immune cells and the molecular phenotype defined by hormone receptors (HRs) have been implicated as decisive factors in the regulation of breast cancer (BC) progression. Here, we found that the infiltration of mast cells (MCs) informed impaired prognoses in HR(+) BC but predicted improved prognoses in HR(-) BC. However, molecular features of MCs in different BC remain unclear. We next discovered that HR(-) BC cells were prone to apoptosis under the stimulation of MCs, whereas HR(+) BC cells exerted anti-apoptotic effects. Mechanistically, in HR(+) BC, the KIT ligand (KITLG), a major mast cell growth factor in recruiting and activating MCs, could be transcriptionally upregulated by the progesterone receptor (PGR), and elevate the production of MC-derived granulin (GRN). GRN attenuates TNFα-induced apoptosis in BC cells by competitively binding to TNFR1. Furthermore, disruption of PGR-KITLG signaling by knocking down PGR or using the specific KITLG-cKIT inhibitor iSCK03 potently enhanced the sensitivity of HR(+) BC cells to MC-induced apoptosis and exerted anti-tumor activity. Collectively, these results demonstrate that PGR-KITLG signaling in BC cells preferentially induces GRN expression in MCs to exert anti-apoptotic effects, with potential value in developing precision medicine approaches for diagnosis and treatment.

Comprehensive and Accurate Molecular Profiling of Breast Cancer through mRNA Expression of ESR1, PGR, ERBB2, MKI67, and a Novel Proliferation Signature.

BACKGROUND: An accurate status determination of breast cancer biomarkers (ER, PR, HER2, Ki67) is crucial for guiding patient management. The "gold standard" for assessing these biomarkers in FFPE tissue is IHC, which faces challenges in standardization and exhibits substantial variability. In this study, we compare the concordance of a new commercial RT-qPCR kit with IHC in determining BC biomarker status. METHODS: The performance was evaluated using 634 FFPE specimens, which underwent histological analysis in accordance with standard of care methods. HER2 2+ tumors were referred to ISH testing. An immunoreactive score of ≥2/12 was considered positive for ER/PR and 20% staining was used as a cut-off for Ki67 high/low score. RT-qPCR and results calling were performed according to the manufacturer's instructions. RESULTS: High concordance with IHC was seen for all markers (93.2% for ER, 87.1% for PR, 93.9% for HER2, 77.9% for Ki67 and 80.1% for proliferative signature (assessed against Ki67 IHC)). CONCLUSIONS: By assessing the concordance with the results obtained through IHC, we sought to demonstrate the reliability and utility of the kit for precise BC subtyping. Our findings suggest that the kit provides a highly precise and accurate quantitative assessment of BC biomarkers.

Unraveling the dataset transcriptomic response of Hydrangea macrophylla stem to mechanical stimulation: De novo assembly and functional annotation.

A crucial attribute of potted ornamental plants is compactness characterized by well branched plants with rather short stems bearing numerous flowers. To gain plant compactness, producers use plant growth regulators (PGRs), in particular growth retardants during culture. However, due to their negative environmental impacts, growth retardants are progressively withdrawn from the market. As a response, eco-friendly alternative methods to chemicals need to be developed. One method consists in mimicking mechanical stimulation (MS) imposed by wind on plants which causes reduction in stem elongation, an increase in stem diameter and an increase in branching, all contributing to plant compactness. So far, few plant species were studied under MS and little is known on molecular response mechanisms to MS. This first transcriptomic data after MS in Hydrangea macrophylla will contribute unravelling how plants respond to mechanical stimuli. RNAseq data were obtained from total mRNA of stems collected 15 min before MS and 1, 3, 24 and 72 h after MS treatment. RNA from non-MS treated plants were used as control. MS treatment consisted in 12 consecutive bendings (i.e. 6 forth and 6 back) applied at 9 a.m. during 1 h and for a single day. From RNAseq data a de novo assembly of the transcriptome was produced and 78,398 transcripts functionally annotated. These transcriptomic data also contribute to a better knowledge of how outdoor crop respond to the increasing frequency of strong harmful winds under climate change.

Co-expression of GR79 EPSPS and GAT generates high glyphosate-resistant alfalfa with low glyphosate residues.

Weed competition seriously threatens the yield of alfalfa, the most important forage legume worldwide, thus generating herbicide-resistant alfalfa varieties is becoming a necessary cost-effective strategy to assist farmers for weed control. Here, we report the co-expression of plant codon-optimized forms of GR79 EPSPS (pGR79 EPSPS) and N-acetyltransferase (pGAT) genes, in alfalfa, via Agrobacterium-mediated transformation. We established that the pGR79 EPSPS-pGAT co-expression alfalfa lines were able to tolerate up to tenfold higher commercial usage of glyphosate and produced approximately ten times lower glyphosate residues than the conventional cultivar. Our findings generate an elite herbicide-resistant germplasm for alfalfa breeding and provide a promising strategy for developing high-glyphosate-resistant and low-glyphosate-residue forages. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00119-3.

A molecular toolbox to study progesterone receptor signaling.

Progesterone receptor (PR) signaling is required for mammary gland development and homeostasis. A major bottleneck in studying PR signaling is the lack of sensitive assays to measure and visualize PR pathway activity both quantitatively and spatially. Here, we develop new tools to study PR signaling in human breast epithelial cells. First, we generate optimized Progesterone Responsive Element (PRE)-luciferase constructs and demonstrate that these new reporters are a powerful tool to quantify PR signaling activity across a wide range of progesterone concentrations in two luminal breast cancer cell lines, MCF7 and T47D. We also describe a fluorescent lentiviral PRE-GFP reporter as a novel tool to visualize PR signaling at the single-cell level. Our reporter constructs are sensitive to physiological levels of progesterone. Second, we show that low background signaling, and high levels of PR expression are a prerequisite for robustly measuring PR signaling. Increasing PR expression by transient transfection, stable overexpression in MCF7 or clonal selection in T47D, drastically improves both the dynamic range of luciferase reporter assays, and the induction of endogenous PR target genes as measured by qRT-PCR. We find that the PR signaling response differs per cell line, target gene and hormone concentration used. Taken together, our tools allow a more rationally designed approach for measuring PR signaling in breast epithelial cells.

Blood Plasma Small Non-Coding RNAs as Diagnostic Molecules for the Progesterone-Receptor-Negative Phenotype of Serous Ovarian Tumors.

The expression level of the progesterone receptor (PGR) plays a crucial role in determining the biological characteristics of serous ovarian carcinoma. Low PGR expression is associated with chemoresistance and a poorer outcome. In this study, our objective was to explore the relationship between tumor progesterone receptor levels and RNA profiles (miRNAs, piwiRNAs, and mRNAs) to understand their biological characteristics and behavior. To achieve this, we employed next-generation sequencing of small non-coding RNAs, quantitative RT-PCR, and immunohistochemistry to analyze both FFPE and frozen tumor samples, as well as blood plasma from patients with benign cystadenoma (BSC), serous borderline tumor (SBT), low-grade serous ovarian carcinoma (LGSOC), and high-grade serous ovarian carcinoma (HGSOC). Our findings revealed significant upregulation of MMP7 and MUC16, along with downregulation of PGR, in LGSOC and HGSOC compared to BSC. We observed significant correlations of PGR expression levels in tumor tissue with the contents of miR-199a-5p, miR-214-3p, miR-424-3p, miR-424-5p, and miR-125b-5p, which potentially target MUC16, MMP7, and MMP9, as well as with the tissue content of miR-16-5p, miR-17-5p, miR-20a-5p, and miR-93-5p, which are associated with the epithelial-mesenchymal transition (EMT) of cells. The levels of EMT-associated miRNAs were significantly correlated with the content of hsa_piR_022437, hsa_piR_009295, hsa_piR_020813, hsa_piR_004307, and hsa_piR_019914 in tumor tissues. We developed two optimal logistic regression models using the quantitation of hsa_piR_020813, miR-16-5p, and hsa_piR_022437 or hsa_piR_004307, hsa_piR_019914, and miR-93-5p in the tumor tissue, which exhibited a significant ability to diagnose the PGR-negative tumor phenotype with 93% sensitivity. Of particular interest, the blood plasma levels of miR-16-5p and hsa_piR_022437 could be used to diagnose the PGR-negative tumor phenotype with 86% sensitivity even before surgery and chemotherapy. This knowledge can help in choosing the most effective treatment strategy for this aggressive type of ovarian cancer, such as neoadjuvant chemotherapy followed by cytoreduction in combination with hyperthermic intraperitoneal chemotherapy and targeted therapy, thus enhancing the treatment's effectiveness and the patient's longevity.

Evaluating the Oxidation Rate of Reduced Ferredoxin in Arabidopsis thaliana Independent of Photosynthetic Linear Electron Flow: Plausible Activity of Ferredoxin-Dependent Cyclic Electron Flow around Photosystem I.

The activity of ferredoxin (Fd)-dependent cyclic electron flow (Fd-CEF) around photosystem I (PSI) was determined in intact leaves of Arabidopsis thaliana. The oxidation rate of Fd reduced by PSI (vFd) and photosynthetic linear electron flow activity are simultaneously measured under actinic light illumination. The vFd showed a curved response to the photosynthetic linear electron flow activity. In the lower range of photosynthetic linear flow activity with plastoquinone (PQ) in a highly reduced state, vFd clearly showed a linear relationship with photosynthetic linear electron flow activity. On the other hand, vFd increased sharply when photosynthetic linear electron flow activity became saturated with oxidized PQ as the net CO2 assimilation rate increased. That is, under higher photosynthesis conditions, we observed excess vFd resulting in electron flow over photosynthetic linear electron flow. The situation in which excess vFd was observed was consistent with the previous Fd-CEF model. Thus, excess vFd could be attributed to the in vivo activity of Fd-CEF. Furthermore, the excess vFd was also observed in NAD(P)H dehydrogenase-deficient mutants localized in the thylakoid membrane. The physiological significance of the excessive vFd was discussed.

[Updated CAP guidelines for determining molecular biological subtypes of breast cancer]. / Obnovlennye rekomendatsii CAP po opredeleniyu molekulyarno-biologicheskikh podtipov raka molochnoi zhelezy.

Updated 2023 guidelines from the College of American Pathologists (CAP) on immunohistochemical detection of human epidermal growth factor receptor type 2 (HER2), receptors of estrogen (ER) and progesterone (PgR), and the cell proliferation marker Ki-67 in breast cancer are presented. Attention is drawn to the emergence of two new terms «ER Low Positive¼ and «HER2 Low¼ to characterize tumors with low expression of estrogen receptors and HER2.

Arabidopsis mutants lacking DLDG1 and non-photochemical quenching-related proteins reveal the regulatory role of DLDG1 in chloroplast pH homeostasis.

The control of pH in chloroplasts is important to regulate photosynthesis, although details of the precise regulatory mechanisms of H+ homeostasis in chloroplasts are not fully understood. We recently found that the cyanobacterial PxcA homolog DLDG1 is involved in plastidial pH control. PxcA and DLDG1 have been thought to control light-dependent H+ extrusion across the cyanobacterial cytoplasmic and chloroplast envelope membranes, respectively. To investigate DLDG1-dependent pH control in chloroplasts, we crossed the dldg1 mutant with various mutants lacking known non-photochemical quenching (NPQ)-related proteins, such as fluctuating-light acclimation protein 1 (FLAP1), PsbS/NPQ4, and proton gradient regulation 5 (PGR5). Phenotypes of these double mutants revealed that PsbS works upstream of DLDG1, PGR5 affects NPQ independently from DLDG1, and the ΔpH regulation by FLAP1 and DLDG1 are independent of each other.

Persistence of Abscisic Acid Analogs in Plants: Chemical Control of Plant Growth and Physiology.

Abscisic acid (ABA) is a plant hormone that regulates numerous plant processes, including plant growth, development, and stress physiology. ABA plays an important role in enhancing plant stress tolerance. This involves the ABA-mediated control of gene expression to increase antioxidant activities for scavenging reactive oxygen species (ROS). ABA is a fragile molecule that is rapidly isomerized by ultraviolet (UV) light and catabolized in plants. This makes it challenging to apply as a plant growth substance. ABA analogs are synthetic derivatives of ABA that alter ABA's functions to modulate plant growth and stress physiology. Modifying functional group(s) in ABA analogs alters the potency, selectivity to receptors, and mode of action (i.e., either agonists or antagonists). Despite current advances in developing ABA analogs with high affinity to ABA receptors, it remains under investigation for its persistence in plants. The persistence of ABA analogs depends on their tolerance to catabolic and xenobiotic enzymes and light. Accumulated studies have demonstrated that the persistence of ABA analogs impacts the potency of its effect in plants. Thus, evaluating the persistence of these chemicals is a possible scheme for a better prediction of their functionality and potency in plants. Moreover, optimizing chemical administration protocols and biochemical characterization is also critical in validating the function of chemicals. Lastly, the development of chemical and genetic controls is required to acquire the stress tolerance of plants for multiple different uses.

Inactivation of photosynthetic cyclic electron transports upregulates photorespiration for compensation of efficient photosynthesis in Arabidopsis.

Plants have multiple mechanisms to maintain efficient photosynthesis. Photosynthetic cyclic electron transports around photosystem I (CET), which includes the PGR5/PGRL1 and NDH pathways, and photorespiration play a crucial role in photosynthetic efficiency. However, how these two mechanisms are functionally linked is not clear. In this study, we revealed that photorespiration could compensate for the function of CET in efficient photosynthesis by comparison of the growth phenotypes, photosynthetic properties monitored with chlorophyll fluorescence parameters and photosynthetic oxygen evolution in leaves and photorespiratory activity monitored with the difference of photosynthetic oxygen evolution rate under high and low concentration of oxygen conditions between the deleted mutant PGR5 or PGRL1 under NDH defective background (pgr5 crr2 or pgrl1a1b crr2). Both CET mutants pgr5 crr2 and pgrl1a1b crr2 displayed similar suppression effects on photosynthetic capacities of light reaction and growth phenotypes under low light conditions. However, the total CET activity and photosynthetic oxygen evolution of pgr5 crr2 were evidently lower than those of pgrl1a1b crr2, accompanied by the upregulation of photorespiratory activity under low light conditions, resulting in severe suppression of photosynthetic capacities of light reaction and finally photodamaged phenotype under high light or fluctuating light conditions. Based on these findings, we suggest that photorespiration compensates for the loss of CET functions in the regulation of photosynthesis and that coordination of both mechanisms is essential for maintaining the efficient operation of photosynthesis, especially under stressed conditions.

Targeting YAP1 ameliorates progesterone resistance in endometriosis.

STUDY QUESTION: Does YAP1 inhibition alleviate progesterone resistance in endometriosis? SUMMARY ANSWER: YAP1 inhibition reduces progesterone resistance in vitro and in vivo. WHAT IS KNOWN ALREADY: Progesterone resistance not only causes treatment failure for endometriosis but also inhibits eutopic endometrial cell proliferation, dysregulates decidualization, and reduces the success rates of pregnancy. Hippo/yes-associated protein 1 (YAP1) signaling pathway plays an important role in the pathogenesis of endometriosis. STUDY DESIGN, SIZE, DURATION: Paraffin-embedded tissues containing paired endometriotic and endometrial specimens (n = 42) and serum samples isolated from normal controls (n = 15) or endometriotic patients with (n = 25) or without (n = 21) prior dienogest treatment were analyzed. A mouse model of endometriosis was also used to evaluate the effects of YAP1 inhibition on progesterone resistance. PARTICIPANTS/MATERIALS, SETTING, METHODS: Primary endometriotic and endometrial stromal cells treated with YAP1 inhibitor or miR-21 mimic/inhibitor were used for the in vitro studies including decidualization induction, chromatin immunoprecipitation (ChIP), and RNA immunoprecipitation. Tissue specimens and serum from human and mouse were used for immunohistochemistry staining, exosome isolation, and microRNA (miRNA) quantification, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Herein, we report, by using ChIP-PCR and RNA-IP, that YAP1 inhibits progesterone receptor (PGR) expression through upregulation of miR-21-5p. Upregulation of miR-21-5p not only reduces PGR expression but also inhibits endometrial stromal cell decidualization. Indeed, levels of YAP1 and miR-21-5p are inversely correlated with the level of PGR in human endometrial samples. In contrast, knockdown of YAP1 or treatment with verteporfin (VP), a YAP1 inhibitor, reduces miR-21-5p expression, thus leading to an increase in PGR expression in ectopic endometriotic stromal cells. In the mouse model of endometriosis, treatment with VP increases PGR expression and enhances decidualization. More importantly, VP synergistically increases the treatment effect of progestin in causing the regression of endometriotic lesions and improves the decidualization capability of the endometrium. Interestingly, treatment with dienogest, a synthetic progestin, reduces YAP1 and miR-21-5p expression in human cells and in the mouse model of endometriosis. Patients who received dienogest treatment for 6 months show a significant decrease in serum extracellular vesicle-associated miR-21-5p level. LARGE SCALE DATA: A public dataset (GSE51981) containing a large cohort of endometriotic tissues is available from the Gene Expression Omnibus (GEO). LIMITATIONS, REASONS FOR CAUTION: A large cohort of clinical samples is needed to verify the current diagnostic value of miR-21-5p in future studies. WIDER IMPLICATIONS OF THE FINDINGS: The reciprocal regulation of YAP1 and PGR suggests that combined YAP1 inhibitor and progestin may be a better therapeutic approach for treating endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Ministry of Science and Technology, Taiwan (MOST-111-2636-B-006-012, MOST-111-2314-B-006-075-MY3, and MOST-106-2320-B-006-072-MY3). The authors have no conflict of interest to disclose.

International agreements and the plant genetics research community: A guide to practice.

Plant genetic resources (PGR), including collections held in national and international gene banks, provide access to a wide array of genetic diversity and are critical to genomics research, conservation efforts, and applied breeding. Yet, there is a general lack of awareness in the research community about the rules and treaties that govern the use of PGR, about access and benefit sharing obligations contained in international treaties and/or national laws, and about how best to comply with potentially applicable requirements. This article provides a brief history and overview of three key international agreements, namely the Convention on Biological Diversity, the Nagoya Protocol, and the International Treaty on Plant Genetic Resources for Food and Agriculture, which collectively address responsibilities and obligations related to the use of much of the world's PGR. By highlighting the coverage and key considerations of each agreement, the article provides a guide for those who use PGR in plant genetics research to better understand when and how international agreements apply, and-where the rules are unclear-to suggest best practices for compliance with existing agreements.