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Plants synchronize their growth and development with environmental changes, which is critical for their survival. Among their life cycle transitions, seed germination is key for ensuring the survival and optimal growth of the next generation. However, even under favorable conditions, often germination can be blocked by seed dormancy, a regulatory multilayered checkpoint integrating internal and external signals. Intricate genetic and epigenetic mechanisms underlie seed dormancy establishment, maintenance, and release. In this review, we focus on recent advances that shed light on the complex mechanisms associated with physiological dormancy, prevalent in seed plants, with Arabidopsis thaliana serving as a model. Here, we summarize the role of multiple epigenetic regulators, but with a focus on histone modifications such as acetylation and methylation, that finely tune dormancy responses and influence dormancy-associated gene expression. Understanding these mechanisms can lead to a better understanding of seed biology in general, as well as resulting in the identification of possible targets for breeding climate-resilient plants. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs) are the mesenchymal tumors of the gastrointestinal tract. Extra Gastrointestinal stromal tumors (EGISTs) are rare neoplasms that occur outside the gastrointestinal tract [1]. Miettinen et al. [2] described the first EGIST in 1999. EGIST accounts for 10% of all GISTs [3]. The main distinction between GIST and EGIST is the site of origin of the primary tumor, as GIST occurs throughout the GI tract, from the esophagus to the anus, whereas EGIST is a tumor without any connection with the intestinal wall and are reported in the retroperitoneum, mesentery, and omentum [4]. Hu et al. [5] reported a first case report of EGIST of larynx.We present a second case report of Extra-gastrointestinal stromal tumor of larynx a 47-year-old male reported to ENT Department Command Hospital Central Command Lucknow with complaints of Hoarseness. On examination found to have right vocal cord growth for which he underwent excision of right vocal cord growth. Histopathological examination showed typical of a spindle-cell GIST, showing strong immunoreactivity for CD 117, DOG1, Vimentin and CD 99. 6 months follow up post surgery with no recurrence. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST. [ABSTRACT FROM AUTHOR]

Summary: Seed dormancy governs germination timing, with both evolutionary and applied consequences. Despite extensive studies on the hormonal and genetic control of these processes, molecular mechanisms directly linking dormancy and germination remain poorly understood.By screening a collection of lines overexpressing Arabidopsis transcription factors, we identified ERF50 as a key gene to control dormancy and germination. To study its regulation, we measured seed‐related physiological parameters in loss‐of‐function mutants and carried out transactivation, protein interaction and ChIP‐PCR analyses.We found direct ERF50‐mediated repression of DOG1 and activation of EXPA2 transcription, which results in enhanced seed germination. Although ERF50 expression is increased by DOG1 in dormant seeds, ERF50 germination‐promoting activity is blocked by RGL2.The physiological, genetic and molecular evidence gathered here supports that ERF50 controls germination timing by regulating DOG1 levels to leverage its role as enhancer of seed germination, via RGL2 antagonism on EXPA2 expression. Our results highlight the central role of ERF50 as a feedback regulator to couple and fine‐tune seed dormancy and germination. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the expression of CD117 and DOG1 in triple-negative breast cancer (TNBC) and to explore their relationship with clinicopathologic features and prognosis.MethodsThe patients with TNBC in Peking Union Medical College Hospital from 2000 to 2011 were retrospectively collected and tissue microarrays were made. The expression of CD117 and DOG1 in tumor cells was detected by immunohistochemistry to analyze their relationship with the clinicopathological characteristics of the patients, such as age, tumor diameter, American Joint Committee on Cancer (AJCC) cancer stage, histological grade, P53, and Ki-67 proliferation index, and explore the effect of both on the survival of patients.ResultsA total of 185 TNBC patients meeting the inclusion and exclusion criteria were selected, of which 24 (12.97%) were CD117 positive and 22 (11.89%) were DOG1 positive, with a co-expression rate of 1.62%. Compared with CD117-negative patients, CD117-positive patients had higher Ki-67 proliferation index (87.50% vs. 67.70%, P=0.048), basal-like TNBC (95.83% vs. 74.53%, P=0.020), and P53 diffuse positive (33.33% vs. 13.66%, P=0.032).Compared with DOG1-negative patients, DOG1-positive patients had lower proportions of tumor diameter ≤2 cm (22.73% vs. 45.40%, P=0.026) and basal-like TNBC (54.55% vs. 80.37%, P=0.015). The median follow-up was 71 months (range: 2-170 months), 4 cases (2.16%) were lost to follow-up, 66 cases (35.68%) relapsed or had distant metastasis, and 34 cases (18.38%) died. Survival analysis showed that AJCC stage (HR=7.624, 95% CI: 2.187-26.576, P=0.001) and CD117 positive with P53 diffuse strong positive (HR=3.942, 95% CI: 1.366-11.379, P=0.011) were negatively correlated with the overall survival of TNBC patients.ConclusionsThe expression of CD117 and DOG1 were significantly related to basal-like TNBC, CD117 positive with P53 diffuse strong positive may be correlated with a shorter overall survival and a higher mortality risk.

Malignant gastrointestinal neuroectodermal tumor (GNET), also referred to as clear cell sarcoma-like tumor of the GI tract is a rare mesenchymal tumor of the gastrointestinal tract. It has to be distinguished from various mimickers including gastrointestinal stromal tumor (GIST) due to its aggressive course and different natural history and therapeutic approach. Here we report a case of GNET arising in the small intestine with aberrant DOG1 expression posing a diagnostic challenge. In this context, the combination of clinical, histomorphological, immunohistochemical, and molecular features helped to establish a proper diagnosis. [ABSTRACT FROM AUTHOR]

Aquaporins (AQPs) regulate the transport of water and other substrates, aiding plants in adapting to stressful environments. However, the knowledge of AQPs in salt‐secreting and viviparous Avicennia marina is limited. In this study, 46 AmAQPs were identified in A. marina genome, and their subcellular localisation and function in transporting H2O2 and boron were assessed through bioinformatics analysis and yeast transformation. Through analysing their expression patterns via RNAseq and real‐time quantitative polymerase chain reaction, we found that most AmAQPs were downregulated in response to salt and tidal flooding. AmPIP (1;1, 1;7, 2;8, 2;9) and AmTIP (1;5, 1;6) as salt‐tolerant candidate genes may contribute to salt secretion together with Na+/H+ antiporters. AmPIP2;1 and AmTIP1;5 were upregulated during tidal flooding and may be regulated by anaerobic‐responsive element and ethylene‐responsive element cis‐elements, aiding in adaptation to tidal inundation. Additionally, we found that the loss of the seed desiccation and dormancy‐related TIP3 gene, and the loss of the seed dormancy regulator DOG1 gene, or DOG1 protein lack heme‐binding capacity, may be genetic factors contributing to vivipary. Our findings shed light on the role of AQPs in A. marina adaptation to intertidal environments and their relevance to salt secretion and vivipary. Summary statement: AmAQPs respond to salinity and tidal inundation in Avicennia marina, some of which play a role in salt gland secretion and function as water effluxes. The absence of TIP3, an aquaporin isoform, and the loss of DOG1, or its ability to bind to heme, may be one of the causes of vivipary in mangrove plants. [ABSTRACT FROM AUTHOR]

SUMMARY: DELAY OF GERMINATION 1 is a key regulator of dormancy in flowering plants before seed germination. Bryophytes develop haploid spores with an analogous function to seeds. Here, we investigate whether DOG1 function during germination is conserved between bryophytes and flowering plants and analyse the underlying mechanism of DOG1 action in the moss Physcomitrium patens. Phylogenetic and in silico expression analyses were performed to identify and characterise DOG1 domain‐containing genes in P. patens. Germination assays were performed to characterise a Ppdog1‐like1 mutant, and replacement with AtDOG1 was carried out. Yeast two‐hybrid assays were used to test the interaction of the PpDOG1‐like protein with DELLA proteins from P. patens and A. thaliana. P. patens possesses nine DOG1 domain‐containing genes. The DOG1‐like protein PpDOG1‐L1 (Pp3c3_9650) interacts with PpDELLAa and PpDELLAb and the A. thaliana DELLA protein AtRGA in yeast. Protein truncations revealed the DOG1 domain as necessary and sufficient for interaction with PpDELLA proteins. Spores of Ppdog1‐l1 mutant germinate faster than wild type, but replacement with AtDOG1 reverses this effect. Our data demonstrate a role for the PpDOG1‐LIKE1 protein in moss spore germination, possibly alongside PpDELLAs. This suggests a conserved DOG1 domain function in germination, albeit with differential adaptation of regulatory networks in seed and spore germination. Significance Statement: Seed and spore germination are considered analogous because they occur in the sporophyte (seed plants) and gametophyte (bryophytes). Here we show that an ortholog of Arabidopsis DELAY OF GERMINATION 1 (DOG1) controls spore germination in the moss P. patens, suggesting deep evolutionary conservation of germination control of reproductive diaspores. [ABSTRACT FROM AUTHOR]

Dormancy enables plant seeds to time germination until environmental conditions become favorable for seedling survival and growth. The dormancy characteristics of seeds are of important ecological adaptive significance and notable agricultural value. Phytohormone abscisic acid (ABA) and gibberellin (GA) are the key factors for seed dormancy and germination. Mature seeds in dormancy state contain high levels of ABA and low levels of GA. ABA induces and maintains seed dormancy, while GA antagonizes ABA and promotes seed germination. DELAY OF GERMINATION-1 (DOG1) is a major regulator of seed dormancy and had a synergistic effect with ABA to delay germination. DOG1 enhances ABA signal transduction by combining with PP2C ABA hypersensitive germination (AHG1/AHG3), and inhibits the action of AHG1 to increase ABA sensitivity and impose seed dormancy. Imprinted genes are regulated by epigenetic mechanisms before and after fertilization, and are closely related to the establishment and release of seed dormancy. In recent years, remarkable progress has been made in the regulation of seed dormancy. In the present paper, we reviewed the effects of phytohormones ABA and GA on seed dormancy and germination, the action mechanism regulating seed dormancy by DOG1, and the epigenetic regulation of seed dormancy and germination. In addition, we also propose some scientific issues that need to be further investigated in this field to provide some information for understanding the molecular mechanism of seed dormancy and germination, breeding in anti-preharvest sprouting in crop plants, and promoting the germination of dormant seeds. [ABSTRACT FROM AUTHOR]

Seed dormancy, an important adaptive trait that governs germination timing, is endogenously controlled by phytohormones and genetic factors. DELAY OF GERMINATION 1 (DOG1) is the vital genetic regulator of dormancy, significantly affecting the expression of numerous ABA and GA metabolic genes. However, whether DOG1 could influence the expression of other phytohormone-related genes is still unknown. Here, we comprehensively investigated all well-documented hormone-related genes which might be affected in dog1–2 dry or imbibed seeds by using whole-transcriptome sequencing (RNA-seq). We found that DOG1 could systematically control the expression of phytohormone-related genes. An evident decrease was observed in the endogenous signal intensity of abscisic acid (ABA) and indole-3-acetic acid (IAA), while a dramatic increase appeared in that of gibberellins (GA), brassinosteroids (BR), and cytokinin (CK) in the dog1–2 background, which may contribute considerably to its dormancy-deficient phenotype. Collectively, our data highlight the role of DOG1 in balancing the expression of phytohormone-related genes and provide inspirational evidence that DOG1 may integrate the phytohormones network to control seed dormancy.

Summary: The phytohormones abscisic acid (ABA) and gibberellic acid (GA) antagonistically control the shift between seed dormancy and its alleviation. DELAY OF GERMINATION1 (DOG1) is a critical regulator that determines the intensity of primary seed dormancy, but its underlying regulatory mechanism is unclear.In this study, we combined physiological, biochemical, and genetic approaches to reveal that a bHLH transcriptional factor WRKY36 progressively silenced DOG1 expression to break seed dormancy through ABI5‐BINDING PROTEIN 2 (AFP2) as the negative regulator of ABA signal.AFP2 interacted with WRKY36, which recognizes the W‐BOX in the DOG1 promoter to suppress its expression; Overexpressing WRKY36 broke primary seed dormancy, whereas wrky36 mutants showed strong primary seed dormancy. In addition, AFP2 recruited the transcriptional corepressor TOPLESS‐RELATED PROTEIN2 (TPR2) to reduce histone acetylation at the DOG1 locus, ultimately mediating WRKY36‐dependent inhibition of DOG1 expression to break primary seed dormancy.Our result proposes that the WRKY36‐AFP2‐TPR2 module progressively silences DOG1 expression epigenetically, thereby fine‐tuning primary seed dormancy. [ABSTRACT FROM AUTHOR]

Discovered On Gastrointestinal stromal tumors protein 1 (DOG1), a major calcium-activated chloride channel, has been used as a common diagnostic marker for gastrointestinal stromal tumors. However, the therapeutic application of DOG1 was not well defined. Here, we aim to investigate its potential as a therapeutic target for an antibody-drug conjugate (ADC) in various cancers of the alimentary tract and metastasis. The DOG1 expression profile was determined among TCGA samples and tissue microarrays. High levels of DOG1 expression were ubiquitously observed in multiple cancer samples from the alimentary tract determined by TCGA samples and tissue microarrays. Circulating tumor cells isolated from metastatic colon cancer patients were also positive for DOG1 expression. The mechanisms of anti-DOG1 antibody were investigated by dual-luciferase reporter assay. The anti-DOG1 antibody could inhibit proliferation and metastasis via p53 signaling in limited cancer cell lines. The anti-DOG1 antibody was conjugated with a microtubule inhibitor DM4, to construct a new anti-DOG1-DM4-ADC to strengthen its activity. The anti-DOG1-DM4-ADC showed cytotoxicity at the nanomolar level in vitro. In the murine xenograft tumor models, treatment of anti-DOG1-DM4-ADC achieved a significant tumor growth inhibition rate. Our study indicates that anti-DOG1-DM4-ADC may be promising therapeutic molecules for DOG1-positive alimentary tract tumors and may be effective in inhibiting recurrence after curative resection of liver metastases of colorectal origin. [ABSTRACT FROM AUTHOR]

• Artificial maturation has been achieved in immature cucumber seeds through after-ripening treatments. • After ripening treatments increased the viability and vigour of the immature seeds. • After-ripening treatments increased endo-β-mannanase activity and levels of IAA and SA hormone, whereas ABA levels have decreased. Also, negative correlation was noted between endo-β-mannanase and ABA. • Maturation treatments in cucumber seeds have reduced the expressions of ABI3 and DOG1 genes and increased the expressions of AMY, MAN2, and Sm1 genes. • Companies engaged in autumn production in the seed industry can benefit from After-ripening and improve their immature seed lots. Seed maturation, which involves a number of physiological and molecular events, is a crucial and intricate process in plant production. Since immature seeds can pose significant problems for both growers and producers, it is necessary to harvest them at the right maturity stage when seed viability and vigour are at their highest. Nevertheless, in the contemporary era, seed producers are compelled to engage in off-season productions in order to meet the rising demands of the market. This has led to the seeds being harvested before they reached full maturity. Considering the problems faced by the seed producers, the present study was designed to stimulate a model for seed maturation by leveraging combinations of moisture, temperature, and treatment time in two hybrid cucumber varieties harvested 40 days after anthesis in the autumn season through after-ripening treatments. Following treatments, a series of physiological, biochemical and molecular analyses were conducted in order to ascertain the efficacy of the treatments under consideration. In this context, the efficacy of the applications was evaluated not only by assessing seed viability and vigour, but also by examining the role of certain hydrolytic enzymes and endogenous hormone levels at the physiological and molecular levels in seed maturation. Accordingly, after-ripening treatments have contributed to the maturation of cucumber seeds, resulting in an increase of up to 110 % and 156 % in both total and normal germination rates, respectively. Furthermore, these treatments have been shown to provide up to 56 % faster germination. In addition, there was a notable enhancement in the endo-β-mannanase enzyme activity, which was found to be correlated with the expression of the CsMAN2 gene during the maturation process. Concerning the responses of the endogenous hormones, it was observed that abscisic acid (ABA) levels decreased with treatments, whereas indole-3-acetic acid (IAA) and salicylic acid (SA) levels showed an increase. Concerning the correlation analysis, endo-β-mannanase enzyme positively correlated with viability parameters (r = 0.859 and r = 0864, P < 0.001) and negatively correlated with ABA hormone (r = 0.666, P < 0.05). Furthermore, the expression levels of the seed maturation genes CsSm1 and CsMAN2 were found to increase with the application of the treatments, while the expression levels of the CsABI3 and CsDOG1 genes were observed to decrease. Although temperature-related variations have been observed during the growing period of plants, the responses of seeds to after-ripening treatments have yielded intriguing results under different conditions. [ABSTRACT FROM AUTHOR]

SUMMARY: Seed dormancy is an adaptive trait that enables plants to survive adverse conditions and restart growth in a season and location suitable for vegetative and reproductive growth. Control of seed dormancy is also important for crop production and food quality because it can help induce uniform germination and prevent preharvest sprouting. Rice preharvest sprouting quantitative trait locus analysis has identified Seed dormancy 4 (Sdr4) as a positive regulator of dormancy development. Here, we analyzed the loss‐of‐function mutant of the Arabidopsis ortholog, Sdr4 Like1 (SFL1), and found that the sfl1‐1 seeds showed precocious germination at the mid‐ to late‐maturation stage similar to rice sdr4 mutant, but converted to become more dormant than the wild type during maturation drying. Coordinated with the dormancy levels, expression levels of the seed maturation and dormancy master regulator genes, ABI3, FUS3, and DOG1 in sfl1‐1 seeds were lower than in wild type at early‐ and mid‐maturation stages, but higher at the late‐maturation stage. In addition to the seed dormancy phenotype, sfl1‐1 seedlings showed a growth arrest phenotype and heterochronic expression of LAFL (LEC1, ABI3, FUS3, LEC2) and DOG1 in the seedlings. These data suggest that SFL1 is a positive regulator of initiation and termination of the seed dormancy program. We also found genetic interaction between SFL1 and the SFL2, SFL3, and SFL4 paralogs of SFL1, which impacts on the timing of the phase transition from embryo maturation to seedling growth. Significance Statement: Seed dormancy is an adaptive trait for wild species and an agronomically important trait for cultivated species. We found that the Arabidopsis ortholog of rice Sdr4, SFL1, positively regulates the initiation and termination of the seed dormancy program. Our data suggest functional conversion of SFL1 from a positive to a negative feedback regulator for expression of the seed maturation master regulator genes, LAFL, which accomplish phase transition from embryo to vegetative development. [ABSTRACT FROM AUTHOR]

DOG1 is a transmembrane protein originally discovered on gastrointestinal stromal tumors and works as a calcium-activated chloride channel protein. There are a limited number of articles on the potential utility of this antibody in the diagnosis of salivary gland tumors in routine practice. In this study, we aimed to investigate the role of DOG1 as an immunohistochemical marker in patients with salivary acinic cell carcinoma (ACC) through meta-analysis. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2010 to September 2021. The literature search revealed 148 articles, of which 20 were included in the study. The overall rate of DOG1 expression in salivary acinic cell carcinoma was 55% (95% CI = 0.43–0.58). Although ACC is a challenging diagnosis, paying careful attention to the cytomorphological features in conjunction with DOG1 immunostaining can help to reach an accurate diagnosis. [ABSTRACT FROM AUTHOR]

Genetic and biochemical studies have greatly advanced our understanding of the biology of seeds in recent years. Another area of study, which could accelerate contemporary seed biology research, is phylogenomics that integrates the wealth of genome sequence data with evolutionary biology. The recent phylogenomic study of the DELAY OF GERMINATION1 family genes exemplifies how the molecular evolution of seed genes can be traced back through early diverging plants and what implications can be obtained from the analysis of seed gene diversification at ancient times. The identification of possible ancestors of seed genes in non-seed plants could illuminate the ancient roots of the molecular mechanisms driving seed maturation programmes. It is possible that the origins of molecular mechanisms associated with the induction of seed storage proteins and desiccation tolerance proteins date back to the time of, or even prior to, early diverging land plants. Abscisic acid-dependent growth arrest or dormancy mechanisms might date back to red algae, one of the oldest algal groups. Thus, understanding algal cell biology will also be an integral part of future seed biology research. Unravelling key events associated with the evolution of seed- and non-seed plants will not only advance basic research but could also contribute to applied aspects of seed science, potentially leading to technology development for agriculture. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs) have been rarely reported in guinea pigs. We aimed to characterize the clinical and pathological features of GISTs in 4 guinea pigs and investigate the presence of mutations in exon 11 of the KIT proto-oncogene receptor tyrosine kinase (Kit) gene. Two subjects were male and 2 were female; 2 were 6 years old, 1 was 7 years old, and 1 was of an unknown age. Three cases had primary gastric tumors, whereas 1 had a primary small intestinal tumor. All cases had tumors that extended from the submucosa to the serosa with extraluminal growth. A gastric tumor had gastric, pancreatic, and cecal metastases. Histologically, the tumors were sharply demarcated and composed of spindle cells arranged in bundles, intermixed with small amounts of collagenous stroma. The tumor cells had mild atypia with few mitotic figures (0–5/50 high power fields, 7.95 mm2) and were immunolabeled for KIT and Discovered-on-GIST 1 (DOG1). All cases had mutations in exon 11 of the Kit gene. These findings indicate that GISTs in guinea pigs are similar to those in humans and dogs. GISTs in guinea pigs are potentially malignant submucosal tumors with KIT- and DOG1-immunolabeling, exon 11 KIT mutations, and the possibility of metastasis. [ABSTRACT FROM AUTHOR]

Plants synchronize their growth and development with environmental changes, which is critical for their survival. Among their life cycle transitions, seed germination is key for ensuring the survival and optimal growth of the next generation. However, even under favorable conditions, often germination can be blocked by seed dormancy, a regulatory multilayered checkpoint integrating internal and external signals. Intricate genetic and epigenetic mechanisms underlie seed dormancy establishment, maintenance, and release. In this review, we focus on recent advances that shed light on the complex mechanisms associated with physiological dormancy, prevalent in seed plants, with Arabidopsis thaliana serving as a model. Here, we summarize the role of multiple epigenetic regulators, but with a focus on histone modifications such as acetylation and methylation, that finely tune dormancy responses and influence dormancy-associated gene expression. Understanding these mechanisms can lead to a better understanding of seed biology in general, as well as resulting in the identification of possible targets for breeding climate-resilient plants., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Simple Summary: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal (GI) tract. All GISTs are potentially malignant and, in general, the risk is proportional to the tumor size. Due to their location within the muscularis propria, GISTs require an endoscopic ultrasound for intramural sampling, although jumbo forceps sampling can be diagnostic in ulcerated lesions. GISTs usually affect people aged between 60 and 70 years, with no gender predominance. Symptomatic tumors mostly present with GI bleeding, anemia, early satiety, and abdominal fullness. The main treatment of GISTs is complete surgical resection, ideally with the preservation of tumor integrity to prevent intra-abdominal dissemination due to rupture and spillage. Advanced-stage tumors require targeted therapy with tyrosine kinase inhibitors and multidisciplinary oncologic care. Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) system. Most GISTs originate from the interstitial cells of Cajal (ICC), the pacemaker cell situated between the circular and longitudinal layers of the muscularis propria along the GI tract. In this population-based study using the SEER database, we sought to identify demographic, clinical, and pathologic factors that affect the prognosis and survival of patients with this neoplasm. Molecular genetic advances, current management guidelines, and advances in targeted therapy are discussed. Methods: Demographic and clinical data from GIST patients were retrieved from the SEER research plus database for the period 2000–2018. Statistical analysis was performed with IBM SPSS® v20.2 software using the Chi-square test, paired t-test, multivariate analysis, and Kaplan–Meier functions. Results: A total of 10,833 patients with GIST were identified. Most patients were between 60–74 years of age: 40%, Caucasian: 68%, and the male to female ratio was 1.1:1. The most common primary tumor sites were stomach: 63%, small intestine: 30%, rectum: 3%, and esophagus: 0.7%. When reported, the grade of differentiation was well: 38%, moderately: 32%, undifferentiated: 19%, poorly: 12%. The size of most tumors ranged between 6–10 cm: 36% and they were treated by surgical intervention: 82% and/or chemotherapy/targeted therapy: 39%. The stage was localized: 66%, advanced: 19%, and regional: 15%. The 5-year survival was 74% (95% confidence interval (95% CI) = 72.6–74.7), and the 5-year cause-specific survival 82% (95% CI = 80.7–82.6). The 5-year cause-specific survival by treatment included surgery at 86% (95% CI = 85.4–87.3), chemotherapy/targeted therapy with or without surgery at 77% (95% CI = 75.7–78.9), and radiation at 75% (95% CI = 74.5–80). On multivariable analysis tumor size > 5 cm, poorly and undifferentiated grade, age > 60, and distant metastases at presentation were associated with worse overall survival. Conclusion: GISTs comprise 1–2% of malignancies of the GI tract, usually affect male Caucasians between the ages of 60 and 74 years, most tumors occur in the stomach and small intestine, and are usually >5 cm, but still localized, at the time of diagnosis. Most tumors receive multimodality surgical and chemotherapy/targeted therapy treatment, with a 5-year overall survival of 74% and cause-specific survival of 82%. GIST patients would benefit from enrollment in large clinical trials to establish better therapy guidelines for unresectable, treatment-refractory, and recurrent tumors. [ABSTRACT FROM AUTHOR]

Seed dormancy ensures plant survival but many mechanisms remain unclear. A high-throughput RNA-seq analysis investigated the mechanisms involved in the establishment of dormancy in dimorphic seeds of Xanthium strumarium (L.) developing in one single burr. Results showed that DOG1, the main dormancy gene in Arabidopsis thaliana L., was over-represented in the dormant seed leading to the formation of two seeds with different cell wall properties. Less expression of DME/EMB1649, UBP26, EMF2, MOM, SNL2, and AGO4 in the non-dormant seed was observed, which function in the chromatin remodelling of dormancy-associated genes through DNA methylation. However, higher levels of ATXR7/SDG25, ELF6, and JMJ16/PKDM7D in the nondormant seed that act at the level of histone demethylation and activate germination were found. Dramatically lower expression in the splicing factors SUA, PWI, and FY in non-dormant seed may indicate that variation in RNA splicing for ABA sensitivity and transcriptional elongation control of DOG1 is of importance for inducing seed dormancy. Seed size and germination may be influenced by respiratory factors, and alterations in ABA content and auxin distribution and responses. TOR (a serine/threonine-protein kinase) is likely at the centre of a regulatory hub controlling seed metabolism, maturation, and germination. Over-representation of the respirationassociated genes (ACO3, PEPC3, and D2HGDH) was detected in non-dormant seed, suggesting differential energy supplies in the two seeds. Degradation of ABA biosynthesis and/or proper auxin signalling in the large seed may control germinability, and suppression of endoreduplication in the small seed may be a mechanism for cell differentiation and cell size determination. [ABSTRACT FROM AUTHOR]

Seed germination and flowering, two critical developmental transitions in plant life cycles, are coordinately regulated by genetic and environmental factors to match plant establishment and reproduction to seasonal cues. The DELAY OF GERMINATION1 (DOG1) gene is involved in regulating seed dormancy in response to temperature and has also been associated genetically with pleiotropic flowering phenotypes across diverse Arabidopsis thaliana accessions and locations. Here we show that DOG1 can regulate seed dormancy and flowering times in lettuce (Lactuca sativa, Ls) and Arabidopsis through an influence on levels of microRNAs (miRNAs) miR156 and miR172. In lettuce, suppression of LsDOG1 expression enabled seed germination at high temperature and promoted early flowering in association with reduced miR156 and increased miR172 levels. In Arabidopsis, higher miR156 levels resulting from overexpression of the MIR156 gene enhanced seed dormancy and delayed flowering. These phenotypic effects, as well as conversion of MIR156 transcripts to miR156, were compromised in DOG1 loss-of-function mutant plants, especially in seeds. Overexpression of MIR172 reduced seed dormancy and promoted early flowering in Arabidopsis, and the effect on flowering required functional DOG1 Transcript levels of several genes associated with miRNA processing were consistently lower in dry seeds of Arabidopsis and lettuce when DOG1 was mutated or its expression was reduced; in contrast, transcript levels of these genes were elevated in a DOG1 gain-of-function mutant. Our results reveal a previously unknown linkage between two critical developmental phase transitions in the plant life cycle through a DOG1-miR156-miR172 interaction.

Seed dormancy—the absence of seed germination under favorable germination conditions—is a plant trait that evolved to enhance seedling survival by avoiding germination under unsuitable environmental conditions. In Arabidopsis, dormancy levels are influenced by the seed coat composition, while the endosperm is essential to repress seed germination of dormant seeds upon their imbibition. Recent research has shown that the mother plant modulates its progeny seed dormancy in response to seasonal temperature changes by changing specific aspects of seed coat and endosperm development. This process involves genomic imprinting by means of epigenetic marks deposited in the seed progeny and regulators previously known to regulate flowering time. This review discusses and summarizes these discoveries and provides an update on our present understanding of the role of DOG1 and abscisic acid, two key contributors to dormancy. [ABSTRACT FROM AUTHOR]

Objective: The diverse site of origin and classification complexity of salivary glands tumors increase difficulties in their diagnosis. This study aimed to evaluate the specificity and diagnostic ability of immunohistochemical expressions of IMP3 versus DOG1 and p63 in cases of such tumors. Material and Method: Thirty paraffin-embedded salivary gland tumors were obtained from the Pathology Department Archive. Their diagnosis was confirmed. The specimens were then re-classified and evaluated using the IMP3, DOG1 and p63 immunohistochemical markers. Results: There were 8 pleomorphic adenoma (PA), 12 mucoepidermoid carcinoma (MEC) and 10 adenoid cystic carcinoma (ADC) cases. All 12 MECs (100%) were IMP3 positive, while 30% of ADCs and only 25% of PAs were positive for IMP3. There was a statistically significant relationship between salivary gland tumors and IMP3 immunostaining (P =0.03). As regards to DOG1 results, 12.5% of PAs showed variable luminal positive immunostaining and 40% of ADCs showed weak luminal and abluminal immunostaining while 16.7% of MEC showed cytoplasmic staining. On the other hand, all ADCs (100%) showed moderate p63 reactivity in the nuclei of abluminal cells. All MEC cases (100%) were also p63-positive, showing a strong diffuse nuclear reactivity. A statistically significant relationship was noticed between salivary gland tumors and p63 immunostaining (P < 0.05). Conclusion: IMP3 is more sensitive for diagnosis of MEC than ADC. p63 is statistically significant in diagnosing salivary gland tumors (MEC and ADC). On the other hand, DOG1 staining is not sensitive in diagnosis of studied malignant salivary gland tumors, limiting its diagnostic utility.

Summary: Temperature variation during seed set is an important modulator of seed dormancy and impacts the performance of crop seeds through effects on establishment rate. It remains unclear how changing temperature during maturation leads to dormancy and growth vigour differences in nondormant seedlings.Here we take advantage of the large seed size in Brassica oleracea to analyse effects of temperature on individual seed tissues.We show that warm temperature during seed maturation promotes seed germination, while removal of the endosperm from imbibed seeds abolishes temperature‐driven effects on germination. We demonstrate that cool temperatures during early seed maturation lead to abscisic acid (ABA) retention specifically in the endosperm at desiccation. During this time temperature affects ABA dynamics in individual seed tissues and regulates ABA catabolism. We also show that warm‐matured seeds preinduce a subset of germination‐related programmes in the endosperm, whereas cold‐matured seeds continue to store maturation‐associated transcripts including DOG1 because of effects on mRNA degradation before quiescence, rather than because of the effect of temperature on transcription.We propose that effects of temperature on seed vigour are explained by endospermic ABA breakdown and the divergent relationships between temperature and mRNA breakdown and between temperature, seed moisture and the glass transition. [ABSTRACT FROM AUTHOR]

Seed germination and flowering are two critical developmental transitions in the life cycles of plants. These transitions are coordinately regulated by exogenous environmental cues and endogenous hormonal signals to match plant establishment and reproduction to the appropriate seasons. The phytohormones, abscisic acid (ABA) and gibberellins (GAs), are the key players that antagonistically regulate seed dormancy and germination; ABA positively modulates dormancy induction and maintenance, while GA stimulates germination. For the control of flowering time, GA has been shown to have a positive role in the modulation of floral transition, whereas both positive and negative roles have been recorded for ABA in this process. DELAY OF GERMINATION 1 (DOG1) delays floral transition and functions in dormancy induction and maintenance, acting in parallel with ABA and/or GA. However, DOG1 is also involved in ABA and GA antagonism through affecting hormone biosynthesis and/or signal transduction pathways. Moreover, the expression of DOG1 is directly regulated by ABA. In this review, we summarize recent developments in seed dormancy and flowering research on the model plant Arabidopsis thaliana, focusing on the crosstalk between ABA, GA, and DOG1. Finally, the open questions and remaining challenges in this field are presented. [ABSTRACT FROM AUTHOR]

Background DOG1 (ANO1; TMEM16A) is a voltage-gated calcium-activated chloride and bicarbonate channel. DOG1 is physiologically expressed in Cajal cells, where it plays an important role in regulating intestinal motility and its expression is a diagnostic hallmark of gastrointestinal stromal tumors (GIST). Data on a possible role of DOG1 in pancreatic cancer are rare and controversial. The aim of our study was to clarify the prevalence of DOG1 expression in pancreatic cancer and to study its association with parameters of cancer aggressiveness. Methods DOG1 expression was analyzed by immunohistochemistry in 599 pancreatic cancers in a tissue microarray format and in 12 cases of pancreatitis on large tissue sections. Results DOG1 expression was always absent in normal pancreas but a focal weak expression was seen in four of 12 cases of pancreatitis. DOG1 expression was, however, common in pancreatic cancer. Membranous and cytoplasmic DOG1 expression in tumor cells was highest in pancreatic ductal adenocarcinomas (61% of 444 interpretable cases), followed by cancers of the ampulla Vateri (43% of 51 interpretable cases), and absent in 6 acinus cell carcinomas. DOG1 expression in tumor associated stroma cells was seen in 76 of 444 (17%) pancreatic ductal adenocarcinomas and in seven of 51 (14%) cancers of the ampulla Vateri. Both tumoral and stromal DOG1 expression were unrelated to tumor stage, grade, lymph node and distant metastasis, mismatch repair protein deficiency and the density of CD8 positive cytotoxic T-lymphocytes in the subgroups of ductal adenocarcinomas and cancers of ampulla Vateri. Overall, the results of our study indicate that DOG1 may represent a potential biomarker for pancreatic cancer diagnosis and a putative therapeutic target in pancreatic cancer. However, DOG1 expression is unrelated to pancreatic cancer aggressiveness.

Background. DOG1 (ANO1; TMEM16A) is a voltage-gated calcium-activated chloride and bicarbonate channel. DOG1 is physiologically expressed in Cajal cells, where it plays an important role in regulating intestinal motility and its expression is a diagnostic hallmark of gastrointestinal stromal tumors (GIST). Data on a possible role of DOG1 in pancreatic cancer are rare and controversial. The aim of our study was to clarify the prevalence of DOG1 expression in pancreatic cancer and to study its association with parameters of cancer aggressiveness. Methods. DOG1 expression was analyzed by immunohistochemistry in 599 pancreatic cancers in a tissue microarray format and in 12 cases of pancreatitis on large tissue sections. Results. DOG1 expression was always absent in normal pancreas but a focal weak expression was seen in four of 12 cases of pancreatitis. DOG1 expression was, however, common in pancreatic cancer. Membranous and cytoplasmic DOG1 expression in tumor cells was highest in pancreatic ductal adenocarcinomas (61% of 444 interpretable cases), followed by cancers of the ampulla Vateri (43% of 51 interpretable cases), and absent in 6 acinus cell carcinomas. DOG1 expression in tumor associated stroma cells was seen in 76 of 444 (17%) pancreatic ductal adenocarcinomas and in seven of 51 (14%) cancers of the ampulla Vateri. Both tumoral and stromal DOG1 expression were unrelated to tumor stage, grade, lymph node and distant metastasis, mismatch repair protein deficiency and the density of CD8 positive cytotoxic T-lymphocytes in the subgroups of ductal adenocarcinomas and cancers of ampulla Vateri. Overall, the results of our study indicate that DOG1 may represent a potential biomarker for pancreatic cancer diagnosis and a putative therapeutic target in pancreatic cancer. However, DOG1 expression is unrelated to pancreatic cancer aggressiveness. [ABSTRACT FROM AUTHOR]

The diagnosis and surveillance of gastrointestinal stromal tumor (GIST) rely on pathology and immunochemistry (IHC), making it complicated and invasive. Noninvasive and convenient biomarkers of this disease need to be explored. The high specificity and sensitivity of IHC in detecting GIST 1 (DOG1) in biopsy indicate that it is also expressed in circulating tumor cells of the blood and may be an ideal biomarker for GIST. This aimed to detect the expression of DOG1 in peripheral blood cells (PBCs) and determine the relationship between DOG1 expression and clinical factors. A total of 45 patients with GIST and 46 healthy controls (HCs) were recruited from the Second Affiliated Hospital of Nanchang University between December 2015 and June 2018. PBCs were isolated from peripheral venous blood by density gradient centrifugation. RNA was extracted from PBCs, and DOG1 mRNA was detected by quantitative reverse transcription polymerase chain reaction. DOG1 mRNA expression between GIST and HC was compared, and the relationship between clinical factors and DOG1 was also analyzed. DOG1 mRNA expression in PBCs was significantly higher in patients with GIST than that in HCs (3.326 [1.942–5.328] versus 0.744 [0.269–1.087], p < 0.01). The specificity and sensitivity were 88.9% and 89.1%, respectively (AUC = 0.912). Tumor diameter and risk of aggressive behavior were correlated with DOG1 expression, and other clinical factors (sex, age, location, number of phase-splitting cells, Ki-67 index, metastatic status) did not show any relationship with DOG1 expression. However, clinical factors, including tumor diameter and risk grade, were not independent factors in DOG1 expression when multivariate analysis was conducted. DOG1 expressions were significantly higher in patients with GIST than that in HCs. Tumor diameter and risk classification correlated with DOG1 expression but were not independent factors. DOG1 in PBCs is a promising noninvasive biomarker for GIST. [ABSTRACT FROM AUTHOR]

DOG1 is a transmembrane protein originally discovered on gastrointestinal stromal tumors and works as a calcium-activated chloride channel protein. There are a limited number of articles on the potential utility of this antibody in the diagnosis of salivary gland tumors in routine practice. In this study, we aimed to investigate the role of DOG1 as an immunohistochemical marker in patients with salivary acinic cell carcinoma (ACC) through meta-analysis. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2010 to September 2021. The literature search revealed 148 articles, of which 20 were included in the study. The overall rate of DOG1 expression in salivary acinic cell carcinoma was 55% (95% CI = 0.43–0.58). Although ACC is a challenging diagnosis, paying careful attention to the cytomorphological features in conjunction with DOG1 immunostaining can help to reach an accurate diagnosis.

Summary: The DELAY OF GERMINATION1 (DOG1) family genes (DFGs) in Arabidopsis thaliana are involved in seed dormancy, reserve accumulation, and desiccation tolerance. Decoding the molecular evolution of DFGs is key to understanding how these seed programs evolved. This article demonstrates that DFGs have diverged in the four lineages DOG1, DOG1‐LIKE4 (DOGL4), DOGL5 and DOGL6, whereas DOGL1, DOGL2 and DOGL3 arose separately within the DOG1 lineage. The systematic DFG nomenclature proposed in this article addresses the current issues of inconsistent DFG annotation and highlights DFG genomic synteny in angiosperms. DFG pseudogenes, or collapsed coding sequences, hidden in the genomes of early‐diverging angiosperms are documented here. They suggest ancient birth and loss of DFGs over the course of angiosperm evolution. The proposed models suggest that the origin of DFG diversification dates back to the most recent common ancestor of living angiosperms. The presence of a single form of DFG in nonflowering plants is discussed. Phylogenetic analysis of gymnosperm, lycophyte, and liverwort DFGs and similar genes found in mosses and algae suggests that DFGs diverged from the TGACG motif‐binding transcription factor genes before the divergence of the bryophyte lineage. [ABSTRACT FROM AUTHOR]

Background: Acinic cell carcinoma (AcCC) is diagnostically challenging on fine‐needle aspiration because it can mimic several other neoplasms or even normal acinar tissue. Immunopositivity for DOG1, especially circumferential membranous staining, can support the diagnosis of AcCC but is not entirely specific, and it is prone to technical and interpretive challenges on small specimens. NR4A3 (nuclear receptor subfamily 4 group A member 3) translocation and nuclear NR4A3 overexpression were recently described in the majority of AcCCs. Here, the authors evaluate the performance of NR4A3 immunohistochemistry (IHC) and NR4A3 break‐apart fluorescence in situ hybridization (FISH) on cell block preparations and compare them with DOG1 IHC in distinguishing AcCC from other entities in the differential diagnosis. Methods: The authors identified 34 cytology cell blocks with lesional cells, including 11 specimens of AcCC (2 of which derived from 1 patient and showed high‐grade transformation) as well as 2 secretory carcinomas, 7 salivary duct carcinomas, 4 mucoepidermoid carcinomas, 3 oncocytomas, 3 renal cell carcinomas, and 6 specimens containing nonneoplastic salivary gland tissue. NR4A3 IHC, DOG1 IHC, and NR4A3 FISH were attempted for all cases. Results: NR4A3 IHC had 81.8% sensitivity and 100% specificity for AcCC, whereas NR4A3 FISH had 36.4% sensitivity and 100% specificity, although 4 cases (3 mucoepidermoid carcinomas and 1 salivary gland tissue sample) could not be analyzed because of low cellularity. Notably, no normal acinar tissue specimens showed NR4A3 positivity by IHC or FISH. In addition, DOG1 IHC had 72.7% sensitivity and 92% specificity. Conclusions: NR4A3 IHC is highly specific for the diagnosis of AcCC and is more sensitive than DOG1 IHC and NR4A3 FISH. In addition, NR4A3 IHC performance is not improved by the inclusion of DOG1 IHC. Finally, NR4A3 positivity resolves the perennial problem of distinguishing AcCC from normal acinar tissue. Nuclear receptor subfamily 4 group A member 3 (NR4A3) immunohistochemistry (IHC) is sensitive and specific for the diagnosis of acinic cell carcinoma in cytology cell block preparations, with better performance than DOG1 IHC. NR4A3 fluorescence in situ hybridization is also specific for acinic cell carcinoma but is less useful with limited tissue and is less sensitive than NR4A3 IHC. [ABSTRACT FROM AUTHOR]

Drought and heat stresses are two major environmental stress factors that severely threaten crop growth and productivity. Plant delay of germination 1-like (DOG1L) family genes play important roles in various developmental processes and stress responses. In our previous study, a tobacco DOG1L gene (NtDOG1L-T) was found to regulate seedling growth and drought response. Unfortunately, the role of DOG1L genes in heat stress response is yet to be studied. Here, we present data supporting the role of DOG1L genes in heat stress and possible underlying molecular mechanisms. Transcript levels of NtDOG1L-T were rapidly induced by heat or abscisic acid (ABA) treatment. Furthermore, NtDOG1L-T promoter activity was markedly activated by ABA or heat stress, as revealed by histochemical staining in transgenic tobacco seedlings. Overexpression of NtDOG1L-T in transgenic lines improved heat stress tolerance. The NtDOG1L-T-transgenic plants exhibited lower levels of reactive oxygen species (ROS) and lipid peroxidation but higher antioxidant enzyme activities in response to heat stress. Furthermore, transcript abundance of some defense-, heat-, and ABA-responsive marker genes was significantly upregulated, as shown by reverse transcription quantitative PCR (qPCR) in these transgenic plants. In conclusion, NtDOG1L-T positively regulates heat stress tolerance possibly by modulation of antioxidant capability and defense-, heat-, and ABA-related gene expression in tobacco. This study may provide valuable resource for the potential exploitation of DOG1Ls in genetic improvement of heat stress tolerance in crops.

Primary seed dormancy is acquired during seed development and maturation, which is important for plant fitness and survival. DELAY OF GERMINATION1 (DOG1) plays a critical role in inducing seed dormancy. DOG1 expression increases rapidly during seed development, but the precise mechanism underlying this process remains elusive. In this study, we showed that mutants with a loss or reduced function of the chromatin-remodeling factor PICKLE (PKL) exhibit increased seed dormancy. PKL associates with DOG1 chromatin and inhibits its transcription. We found that PKL physically interacts with LUX ARRHYTHMO (LUX), a member of the evening complex (EC) of the circadian clock. Furthermore, LUX directly binds to a specific coding sequence of DOG1, and DOG1 acts genetically downstream of PKL and LUX. Mutations in either LUX or EARLY FLOWERING3 (ELF3) encoding another member of the EC led to increased DOG1 expression and enhanced seed dormancy. Surprisingly, these phenotypes were abolished when the parent plants were grown under continuous light. In addition, we observed that loss of function of either PKL or LUX decreased H3K27me3 levels at the DOG1 locus. Taken together, our study reveals a regulatory mechanism in which EC proteins coordinate with PKL to transmit circadian signals for directly regulating DOG1 expression and seed dormancy during seed development.

Abstract Background Since the advent of immunohistochemistry for the diagnosis of stromal tumours, the incidence of leiomyosarcomas has significantly decreased. Nowadays, gastric leiomyosarcoma is an exceptionally rare tumour. We report the second case in the English literature of gastric leiomyosarcoma revealed with massive bleeding and hemodynamic instability and diagnostic pitfalls that we encountered. Case presentation A 63-year-old woman, with 2 years’ history of dizziness and weakness probably related to an anaemic syndrome, presented to the emergency room with hematemesis, melena and hemodynamic instability. On examination, she had conjunctival pallor with reduced general condition, blood pressure of 90/45 mmHg and a pulse between 110 and 120 beats per minute. On digital rectal examination, she had melena. Laboratory blood tests revealed a haemoglobin level at 38 g/L. The patient was admitted to the intensive care department. After initial resuscitation, transfusion and intravenous Omeprazole continuous infusion, her condition was stabilized. She underwent upper gastrointestinal endoscopy showing a tumour of the cardia, protruding in the lumen with mucosal ulceration and clots in the stomach. Biopsies were taken. Histological examination showed interlacing bundles of spindle cells, ill-defined cell borders, elongated hyperchromatic nuclei with marked pleomorphism and paranuclear vacuolization. Immunohistochemistry showed positivity for Vimentine, a strong and diffuse immunoreactivity for smooth muscle actin (SMA). Immunoreactivities for KIT and DOG1 were doubtful. Computed tomography scan revealed a seven-cm tumour of the cardia, without adenopathy or liver metastasis. The patient underwent laparotomy. A total gastrectomy was performed without lymphadenectomy. Post-operative course was uneventful. Histological examination of the tumour specimen found the same features as preoperative biopsies with negative margins. We solicited a second opinion of an expert in a reference centre for sarcomas in France, who confirmed the diagnosis of a high grade gastric leiomyosarcoma. Conclusion Gastric leiomyosarcoma is a rare tumour. Diagnosis is based on histological examination with immunohistochemistry, which could be sometimes confusing like in our case. The validation of a pathological expert is recommended.

Drought and heat stresses are two major environmental stress factors that severely threaten crop growth and productivity. Plant delay of germination 1-like (DOG1L) family genes play important roles in various developmental processes and stress responses. In our previous study, a tobacco DOG1L gene (NtDOG1L-T) was found to regulate seedling growth and drought response. Unfortunately, the role of DOG1L genes in heat stress response is yet to be studied. Here, we present data supporting the role of DOG1L genes in heat stress and possible underlying molecular mechanisms. Transcript levels of NtDOG1L-T were rapidly induced by heat or abscisic acid (ABA) treatment. Furthermore, NtDOG1L-T promoter activity was markedly activated by ABA or heat stress, as revealed by histochemical staining in transgenic tobacco seedlings. Overexpression of NtDOG1L-T in transgenic lines improved heat stress tolerance. The NtDOG1L-T -transgenic plants exhibited lower levels of reactive oxygen species (ROS) and lipid peroxidation but higher antioxidant enzyme activities in response to heat stress. Furthermore, transcript abundance of some defense-, heat-, and ABA-responsive marker genes was significantly upregulated, as shown by reverse transcription quantitative PCR (qPCR) in these transgenic plants. In conclusion, NtDOG1L-T positively regulates heat stress tolerance possibly by modulation of antioxidant capability and defense-, heat-, and ABA-related gene expression in tobacco. This study may provide valuable resource for the potential exploitation of DOG1Ls in genetic improvement of heat stress tolerance in crops. [ABSTRACT FROM AUTHOR]

Objective: The diverse site of origin and classification complexity of salivary glands tumors increase difficulties in their diagnosis. This study aimed to evaluate the specificity and diagnostic ability of immunohistochemical expressions of IMP3 versus DOG1 and p63 in cases of such tumors. Material and Method: Thirty paraffin-embedded salivary gland tumors were obtained from the Pathology Department Archive. Their diagnosis was confirmed. The specimens were then re-classified and evaluated using the IMP3, DOG1 and p63 immunohistochemical markers. Results: There were 8 pleomorphic adenoma (PA), 12 mucoepidermoid carcinoma (MEC) and 10 adenoid cystic carcinoma (ADC) cases. All 12 MECs (100%) were IMP3 positive, while 30% of ADCs and only 25% of PAs were positive for IMP3. There was a statistically significant relationship between salivary gland tumors and IMP3 immunostaining (P =0.03). As regards to DOG1 results, 12.5% of PAs showed variable luminal positive immunostaining and 40% of ADCs showed weak luminal and abluminal immunostaining while 16.7% of MEC showed cytoplasmic staining. On the other hand, all ADCs (100%) showed moderate p63 reactivity in the nuclei of abluminal cells. All MEC cases (100%) were also p63-positive, showing a strong diffuse nuclear reactivity. A statistically significant relationship was noticed between salivary gland tumors and p63 immunostaining (P <0.05). Conclusion: IMP3 is more sensitive for diagnosis of MEC than ADC. p63 is statistically significant in diagnosing salivary gland tumors (MEC and ADC). On the other hand, DOG1 staining is not sensitive in diagnosis of studied malignant salivary gland tumors, limiting its diagnostic utility. [ABSTRACT FROM AUTHOR]

Key message: A wheat protein phosphatase PP2C-a10, which interacted with TaDOG1L1 and TaDOG1L4, promoted seed germination and decreased drought tolerance of transgenic Arabidopsis. Seed dormancy and germination are critical to plant fitness. DELAY OF GERMINATION 1 (DOG1) is a quantitative trait locus for dormancy in Arabidopsis thaliana. Some interactions between DOG1 and the type 2C protein phosphatases (PP2Cs) have been reported in Arabidopsis. However, the research on molecular functions and regulations of DOG1Ls and group A PP2Cs in wheat (Triticum aestivum. L), an important crop plant, is rare. In this study, the whole TaDOG1L family was identified. Expression analysis revealed that TaDOG1L2, TaDOG1L4 and TaDOG1L-N2 specially expressed in wheat grains, while others displayed distinct expression patterns. Yeast two-hybrid analysis of TaDOG1Ls and group A TaPP2Cs revealed interaction patterns differed from those in Arabidopsis, and TaDOG1L1 and TaDOG1L4 interacted with TaPP2C-a10. The qRT-PCR analysis showed that TaPP2C-a10 exhibited the highest transcript level in wheat grains. Further investigation showed that ectopic expression of TaPP2C-a10 in Arabidopsis promoted seed germination and decreased sensitivity to ABA during germination stage. Additionally, TaPP2C-a10 transgenic Arabidopsis exhibited decreased tolerance to drought stress. Finally, the phylogenetic analysis indicated that TaPP2C-a10 gene was conserved in angiosperm during evolutionary process. Overall, our results reveal the role of TaPP2C-a10 in seed germination and abiotic stress response, as well as the functional diversity of TaDOG1L family. [ABSTRACT FROM AUTHOR]

Summary: Seedling emergence timing is crucial in competitive plant communities and so contributes to species fitness. To understand the mechanistic basis of variation in seedling emergence timing, we exploited the contrasting behaviour of two Arabidopsis thaliana ecotypes: Cape Verde Islands (Cvi) and Burren (Bur‐0).We used RNA‐Seq analysis of RNA from exhumed seeds and quantitative trait loci (QTL) analyses on a mapping population from crossing the Cvi and Bur‐0 ecotypes.We determined genome‐wide expression patterns over an annual dormancy cycle in both ecotypes, identifying nine major clusters based on the seasonal timing of gene expression, and variation in behaviour between them. QTL were identified for depth of seed dormancy and seedling emergence timing (SET).Both analyses showed a key role for DOG1 in determining depth of dormancy, but did not support a direct role for DOG1 in generating altered seasonal patterns of seedling emergence. The principle QTL determining SET (SET1: dormancy cycling) is physically close on chromosome 5, but is distinct from DOG1. We show that SET1 and two other SET QTLs each contain a candidate gene (AHG1, ANAC060, PDF1 respectively) closely associated with DOG1 and abscisic acid signalling and suggest a model for the control of SET in the field. See also the Commentary on this article by Smith & Weller, 225: 1821–1823. [ABSTRACT FROM AUTHOR]

Seed dormancy and germination are two closely linked physiological traits that have great impacts on adaptation and survival of seed plants. Seed dormancy strengthen and germination potential are comprehensively influenced by a variety of internal factors and external environment cues. Environmental factors, such as water content, light condition, ambient temperature, and nitrogen availability, act as signal input to determine whether seeds keep in a dormant state or start to germinate. Light, temperature, and nitrogen availability are the most critical environmental factors that have profound impacts on seed dormancy and germination. However, the mechanisms underlying the regulation of seed dormancy and germination by environmental signals are still poorly understood. In this review, we summarize the current knowledge of signal transduction networks linking environmental stimulus to seed dormancy establishment, dormancy break and germination, underscoring the dominating roles of temperature, light, and nitric oxide. We review temperature, light, and nitric oxide signaling pathway separately as well as the integration of these signaling pathways with phytohormone abscisic acid (ABA) and gibberellins (GA) signaling pathway in the context of seed dormancy and germination. [ABSTRACT FROM AUTHOR]

The molecular mechanisms underlying seed dormancy and germination are not fully understood. Here, we show that Arabidopsis thaliana SEED DORMANCY 4-LIKE (AtSdr4L) is a novel specific regulator of dormancy and germination. AtSdr4L encodes a protein with an unknown biochemical function that is localized in the nucleus and is expressed specifically in seeds. Loss of function of AtSdr4L results in increased seed dormancy. The germination of freshly harvested seeds of the Atsdr4l mutant is insensitive to gibberellin (GA). After-ripened mutant seeds are hypersensitive to the GA biosynthesis-inhibitor paclobutrazol but show unaltered sensitivity to abscisic acid. Several GA biosynthesis genes and GA-regulated cell wall remodeling genes are down-regulated in the mutant in both dormant and after-ripened seeds. These results suggest that the Atsdr4l mutation causes both decreased GA biosynthesis and reduced responses. In addition, a genetic analysis indicated that AtSdr4L is epistatic to DELAY OF GERMINATION1 (DOG1) for dormancy and acts upstream of RGA-LIKE 2 (RGL2) in the GA pathway. We propose that AtSdr4L regulates seed dormancy and germination by mediating both the DOG1 and GA pathways. [ABSTRACT FROM AUTHOR]

High temperatures can significantly impact wheat growth and grain yields during the grain-filling stage. In this study, we identified genes that respond to high-temperature stress during the grain-filling stage. We also identified and characterized 24 novel genes of the DOG1 gene family in hexaploid wheat. Motif analysis and conserved domain search revealed substantial similarities among TaDOG1 family members. Phylogenetic analysis demonstrated the evolutionary conservation of the TaDOG1 family across various plant species. Tissue-specific expression profiling indicated consistent patterns, with TaDOG1 genes predominantly expressed in stem tissues. Only TaDOG1 - 1 exhibited enhanced expression, particularly during hard dough and ripening stages. TaDOG1-1 and TaDOG1-7 exhibited increased expression under heat stress during the grain-filling stage, indicating their heat-responsive nature. Cis -element analysis revealed potential regulatory motifs, suggesting the involvement of TaDOG1-1 and TaDOG1-7 in stress tolerance mechanisms. Yeast two-hybrid screening revealed interacting proteins, including stress-responsive and grain development-associated proteins. To understand the biological function, we overexpressed TaDOG1-1 in Arabidopsis plants and observed enhanced thermotolerance under basal heat stress. Under heat stress, the transgenic plants exhibited increased biomass and elevated expression levels of heat-responsive genes. Furthermore, TaDOG1-1 –overexpressing plants showed improved survival rates under soil heat stress, along with a greater accumulation of antioxidant enzymes in leaves. In this study, the identification and functions of the DOG1 gene family provide valuable insights for developing genetic engineering strategies aimed at improving wheat yield under high-temperature stress. • 24 novel genes of the DOG1 gene family were identified and characterized in hexaploid wheat. • TaDOG1 genes exhibited distinct expression patterns in different tissues and response to high-temperature stress. • TaDOG1-1 -overexpressing Arabidopsis plants exhibited significant thermotolerance. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. The most common site is stomach, followed by small intestine, colon, and esophagus. However, GIST from the anal canal is an extremely rare tumor. Here, we report an extremely rare case of GIST of the anal canal in a 40-year-old female with a history of irregular bowel habits mixed with blood and constipation for 4 months. Diagnosis was made on the basis of histopathological and immunohistochemical examination.

Objective: We aimed to review our archives in order to evaluate both the diagnostic and prognostic significance of DOG1 on gastrointestinal stromal tumors (GISTs), and add further insight about those issues to the current literature including some conflicting results. Material and Method: DOG1 was evaluated in 100 cases of GISTs, immunohistochemically. Immunostaining index was counted for each antibody by using both the intensity and extent of staining. The association between immunostaining index of DOG1 and CD117, CD34, SMA desmin, S-100, and Ki-67 index and clinicopathological features were analyzed. Results: Ninety cases were positive for DOG1, and 89 were positive for CD117. All CD117-negative tumors were positive for DOG1. High-risk group was directly correlated with tumor diameter, cellularity, necrosis, nuclear pleomorphism, mitotic count and Ki-67 index, by univariate analysis. The association between high-risk group and tumor diameter, mitotic count, and Ki-67 index was proved by multivariate analysis. Immunostaining index of DOG1, Ki-67 index, mitotic count, ulceration and hemorrhage were inversely correlated with overall survival by univariate analysis. The adverse impact of DOG1 ISI and mitotic count on overall survival were supported by multivariate analysis. Conclusion: DOG1 positivity was detected in most of GISTs and all in CD117-negative cases as a result underlining its diagnostic utility. Additionally, DOG1 overexpression was related with adverse prognosis. Thus, we suggest that immunostaining index of DOG1 should routinely be used while diagnosing GIST, and DOG1 might be considered as a potential prognostic tool and a target for novel therapies.

Production of morphologically and physiologically variable seeds is an important strategy that helps plants to survive in unpredictable natural conditions. However, the model plant Arabidopsis thaliana and most agronomically essential crops produce visually homogenous seeds. Using automated phenotype analysis, we observed that small seeds in Arabidopsis tend to have higher primary and secondary dormancy levels than large seeds. Transcriptomic analysis revealed distinct gene expression profiles between large and small seeds. Large seeds have higher expression of translation-related genes implicated in germination competence. By contrast, small seeds have elevated expression of many positive regulators of dormancy, including a key regulator of this process, the DOG1 gene. Differences in DOG1 expression are associated with differential production of its alternative cleavage and polyadenylation isoforms; in small seeds, the proximal poly(A) site is selected, resulting in a short mRNA isoform. Furthermore, single-seed RNA sequencing analysis demonstrated that large seeds resemble DOG1 knockout mutant seeds. Finally, on the single-seed level, expression of genes affected by seed size is correlated with expression of genes that position seeds on the path toward germination. Our results demonstrate an unexpected link between seed size and dormancy phenotypes in a species that produces highly homogenous seed pools, suggesting that the correlation between seed morphology and physiology is more widespread than initially assumed., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)