Dormancy Mechanisms Research Articles

Embryonic dormancy in Aedes aegypti and Aedes albopictus (Diptera: Culicidae): a survival and dispersal mechanism

Aedes aegypti and Aedes albopictus are the main vectors of arboviruses such as dengue, Zika virus, and chikungunya. Ae. aegypti is a widely spread mosquito in tropical and subtropical regions, whereas Ae. albopictus is a culicid of Asian origin that shows exophilic behavior and can be found in subtropical and temperate areas. Climatic factors could influence the distribution of both species, making them use genetic and environmental resources to adapt to the environment, activating survival mechanisms (embryonic dormancy) that increase the developmental period and keep their offspring in the environment. From this perspective, this review aimed to compare the different physiological mechanisms of embryonic dormancy between Ae. aegypti and Ae. albopictus and their impact on the development and environmental adaptability of these two species. A total of 62 articles were identified in the PubMed, Scopus, and Web of Science databases corresponding to the period from 1981 to 2021. In diapause, the results mentioned above are indirectly linked to temperature and directly linked to photoperiod variations. With regard to quiescence, temperature and humidity are directly related to the activation of this mechanism. In conclusion, it is essential to highlight the expansion of arboviruses such as dengue, chikungunya, yellow fever, and Zika virus and their relationship with embryonic dormancy, diapause and quiescence, extremely important strategies for Ae. aegypti and Ae. albopictus to keep their offspring in the environment under adverse conditions.

Unveiling the Complex Ecosystem of Breast Cancer: Crucial Insights for Patients and Doctors.

Breast cancer, a multifaceted disease, presents a dynamic ecosystem where the primary tumor interacts intricately with its microenvironment, circulatory system, and distant organs. Circulating tumor cells (CTCs) disseminate from the primary tumor to organs, such as the brain, lungs, liver, and bones, encountering various fates: cell death, cellular dormancy, or senescence. Dormant cells, characterized by reversible growth arrest at the G0/G1 phase of the cell cycle, pose a significant challenge as they evade conventional treatments and can later reawaken, leading to cancer relapse. The phenomenon of tumor dormancy is influenced by the tumor microenvironment, immune modulation, and cellular adaptations. Emerging evidence suggests that breast-conserving surgery coupled with radiation therapy offers superior survival benefits compared to mastectomy, potentially due to the 'breast homing phenomenon.' This hypothesis posits that residual breast tissue provides a niche for reactivated dormant cells, reducing distant metastasis. Immunotherapy and lifestyle modifications, including diet and exercise, show promise in managing dormant cells. Understanding the mechanisms of dormancy and developing targeted therapies are crucial for achieving long-term remission and potentially curing breast cancer.

Comparative Analysis of Transcriptomes to Identify Genes during Bud Dormancy of Pyrus pyrifolia ‘Huanghua’

The study of pear dormancy mechanisms is currently a major research area in pear production and has high economic significance for agricultural production. We selected the southern sand pear cultivar Pyrus pyrifolia ‘Huanghua’ as the test material to study the pear dormancy process through microscopic observation of pear flower buds. The endodormancy period is abbreviated as D_bud. Similarly, the endodormancy release initiation period and the ecodormancy period are referred to as DB_bud and G_bud, respectively. Meanwhile, RNA sequencing was used to obtain the gene expression profile of Pyrus pyrifolia ‘Huanghua’ flower buds. The RNA sequencing results indicated that there were 224 differentially expressed genes (DEGs) in endodormancy (D) vs. endodormancy release initiation period (DB), while 975 were identified between endodormancy and ecodormancy (G). Finally, a total of 868 DEGs were found in the DB vs. G comparison. The expression levels of the genes Pbr009498.1 (LAX1-1), Pbr012348.1 (LAX1-2), Pbr021158.1 (GH35), and Pbr031621.1 (LAX2) encoding IAA were significantly higher during the DB_bud than during the D_bud. The expression level of Pbr025864.2 (IAA13) during the D_bud was significantly higher than the DB_bud and G_bud. The Pbr041942.1 (GID1B) gene also showed a significant increase during ecodormancy. Taken together, these results suggest that these genes, annotated as LAX1, GH35, LAX2, IAA13, and GID1C, are involved in endodormancy maintenance and in the transition from endodormancy to ecodormancy in Pyrus pyrifolia ‘Huanghua’.

Methodological and Physiological Study during Seed Dormancy Release of Symplocos paniculata.

Symplocos paniculata are reported to exhibit seed dormancy, which impedes its cultivation and widespread adoption. In this study, a comprehensive method was established to overcome seed dormancy by subjecting seeds to scarification in 98% H2SO4 for 10 min, followed by 1000 mg·L-1 GA3 soaking for 48 h and stratification at 4 °C for 100 days. The seed germination percentage has increased significantly, to a peak of 42.67%, though the seeds could not germinate timely by NaOH scarification. Additionally, the dynamic changes of key stored substances (proteins, soluble sugars, starches, and fats), associated enzyme activities (amylases, peroxidase, and catalase), and endogenous hormones (abscisic acid, gibberellic acid, and indole-3-acetic acid) in seeds were investigated. The results demonstrated a continuous degradation of starch and fat in S. paniculata seeds, while the levels of protein and soluble sugar exhibited fluctuations, which probably facilitated seed dormancy breaking through energy supply and transformation. The enzymatic activities underwent rapid changes, accompanied by a gradual decrease in ABA content within the seeds with increasing stratification time. Notably, GA3, GA3/ABA, and (GA3 + IAA)/ABA showed significant increases, indicating their positive regulatory roles in seed germination. This study clarified the dormancy mechanism and established an effective method for the release dormancy of S. paniculata seeds.

Stem cell quiescence and dormancy in plant meristems.

Plants exhibit opportunistic developmental patterns, alternating between growth and dormancy in response to external cues. Moreover, quiescence plays a critical role in proper plant growth and development, particularly within the root apical meristem and the shoot apical meristem. In these meristematic tissues, cells with relatively slower mitotic activity are present in the quiescent center and the central zone, respectively. These centers form long-term reservoirs of stem cells maintaining the meristematic stem cell niche, and thus sustaining continuous plant development and adaptation to changing environments. This review explores early observations, structural characteristics, functions, and gene regulatory networks of the root and shoot apical meristems. It also highlights the intricate mechanism of dormancy within the shoot apical meristem. The aim is to contribute to a holistic understanding of quiescence in plants, which is fundamental for the proper growth and environmental response of plants.

Unraveling the role of PlARF2 in regulating deed formancy in Paeonia lactiflora.

PlARF2 can positively regulate the seed dormancy in Paeonia lactiflora Pall. and bind the RY cis-element. Auxin, a significant phytohormone influencing seed dormancy, has been demonstrated to be regulated by auxin response factors (ARFs), key transcriptional modulators in the auxin signaling pathway. However, the role of this class of transcription factors (TFs) in perennials with complex seed dormancy mechanisms remains largely unexplored. Here, we cloned and characterized an ARF gene from Paeonia lactiflora, named PlARF2, which exhibited differential expression levels in the seeds during the process of seed dormancy release. The deduced amino acid sequence of PlARF2 had high homology with those of other plants and contained typical conserved Auxin_resp domain of the ARF family. Phylogenetic analysis revealed that PlARF2 was closely related to VvARF3 in Vitis vinifera. The subcellular localization and transcriptional activation assay showed that PlARF2 is a nuclear protein possessing transcriptional activation activity. The expression levels of dormancy-related genes in transgenic callus indicated that PlARF2 was positively correlated with the contents of PlABI3 and PlDOG1. The germination assay showed that PlARF2 promoted seed dormancy. Moreover, TF Centered Yeast one-hybrid assay (TF-Centered Y1H), electrophoretic mobility shift assay (EMSA) and dual-luciferase reporter assay analysis (Dual-Luciferase) provided evidence that PlARF2 can bind to the 'CATGCATG' motif. Collectively, our findings suggest that PlARF2, as TF, could be involved in the regulation of seed dormancy and may act as a repressor of germination.

Abstract CT223: Dormancy reprograming therapy of 5-azacitidine (AZA) and all-trans retinoic acid (ATRA) in biochemically recurrent prostate cancer

Abstract Microenvironmental signals and epigenetic changes can instruct proliferative disseminated tumor cells to enter dormancy. The combination of Azacitidine (AZA) and All-trans retinoid acid (ATRA) can reprogram active prostate cancer (PCa) cells into a dormant state. Herein, we evaluated the safety and clinical activity of AZA + ATRA in patients (pts) with biochemically recurrent PCa. Eligible pts were those with diagnosis of PCa post-local therapy with rising PSA (PSADT < 10 mo). Pts were excluded if they had radiographic evidence of disease or if they were a candidate for salvage radiation therapy (RT). Eligible pts were randomized 1:1 to arm A vs. B. All pts received Lupron 7.5 mg IM at the start of study. Four weeks later, pts entered a 24-week treatment (tx) phase. Pts in arm A received AZA 40 mg/m2 SQ x 5 days and ATRA 45 mg/m2 PO x 5 days Q4W for 12 weeks (w), followed by 12w of observation. Pts in arm B underwent 12w of observation, followed by 12w of AZA and ATRA at same dosing as arm A. All pts underwent follow up until initiation of next tx. The primary endpoint was safety and tolerability as assessed by CTCAE v5.0. Key secondary endpoints included % of pts with prolongation of PSADT pre- and post-tx and time to next treatment (TTNT). Levels of dormancy biomarkers, BMP4 and BMP7, were quantified using ELISA. Circulating tumor cells (CTCs) were analyzed for positive expression of NR2F1 using immunofluorescence. Wilcoxon signed rank test was used for comparing the PSADT. All statistical analysis was performed in R. Fourteen pts were enrolled (A: N=6, B: N=8) with a median age of 66 (range 54-77). At baseline, mean PSA was 4.75 ng/ml (A: 7.11, B: 2.99) and mean PSADT was 2.89 months (A: 3.51, B: 2.43). Eight (57.1%) pts had a Gleason score > 8 at initial diagnosis (A: 83.3%, B: 37.5%). There were no reported Grade > 3 treatment-related adverse events (TRAEs) and no treatment discontinuations. The most common TRAEs included hot flashes, white blood cell decreased and lymphocyte count decreased (all 8.3% each), and anemia (5.6%). There was prolongation of PSADT pre- and post-tx in 6 (46%) pts, however, overall difference in PSADT was non-significant [p>0.1]. 13 out of 14 (93%) pts had TTNT of > 6 months. One pt developed radiographic progression prior to completion of tx phase and a total of 6 pts (42.8%) within 3 months of tx phase. Out of 8 pts, 37.5% and 75% of pts showed increased levels of BMP4 and BMP7 respectively. Upon tx, CTC count decreased in 3 out of 5 pts analyzed, while CTCs were undetectable in two pts. Upon tx, NR2F1 expression could not be detected due to non-detection of CTCs, except for one pt who showed 100% NR2F1 positive CTCs in follow up. AZA + ATRA appears safe and well tolerated, and there was clinical activity in a small subset of pts potentially correlated with dormancy. Additional prospective clinical studies are needed to elucidate dormancy mechanisms further and optimize dosing strategy. Citation Format: Vaibhav G. Patel, Deepak Singh, Himanshu Joshi, Bobby Liaw, Che-Kai Tsao, Matthew Galsky, Lindsay Diamond, Julio Agguire-Ghiso, William Oh. Dormancy reprograming therapy of 5-azacitidine (AZA) and all-trans retinoic acid (ATRA) in biochemically recurrent prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT223.

Determination of cyclic adenosine phosphate and protein content in dormant chlamydospore and nondormant chlamydospore of Arthrobotrys flagrans.

Arthrobotrys flagrans, a nematode-eating fungus, is an effective component of animal parasitic nematode biocontrol agents. In the dried formulation, the majority of spores are in an endogenous dormant state. This study focuses on dormant chlamydospore and nondormant chlamydospore of A. flagrans to investigate the differences in cyclic adenosine monophosphate (cAMP) and protein content between the two types of spores. cAMP and soluble proteins were extracted from the nondormant chlamydospore and dormant chlamydospore of two isolates of A. flagrans. The cAMP Direct Immunoassay Kit and Bradford protein concentration assay kit (Coomassie brilliant blue method) were used to detect the cAMP and protein content in two types of spores. Results showed that the content of cAMP in dormant spores of both isolates was significantly higher than that in nondormant spores (p < 0.05). The protein content of dormant spores in DH055 bacteria was significantly higher than that of nondormant spores (p < 0.05). In addition, the protein content of dormant spores of the SDH035 strain was slightly higher than that of nondormant spores, but the difference was not significant (p > 0.05). The results obtained in this study provide evidence for the biochemical mechanism of chlamydospore dormancy or the germination of the nematophagous fungus A. flagrans.

Abstract A077: The utility of surgical minimal residual disease after frontline treatment for prognostic and investigational opportunities in advanced ovarian cancer

Abstract Cure rates for patients with advanced stage ovarian cancer have not changed significantly over the last four decades likely due to inability to eradicate residual cancer cells after frontline therapy. Identifying clinically undetectable minimal residual disease (MRD) after frontline therapy by second look laparoscopy (SLL) has potential to a) uncover mechanisms of chemoresistance and tumor dormancy, b) identify MRD-specific therapeutic targets, and c) allow for earlier intervention with investigational therapies. The objective of this study is to describe the initial safety and feasibility of SLL and illustrate clinical and pathological correlates. Methods: This IRB-approved observational, single-center study includes patients with epithelial high-grade ovarian cancer with complete CA-125 and radiologic response after frontline treatment (combination of surgery and platinum-taxane chemotherapy) who underwent SLL from 4/2017-6/2023. Patients were subsequently offered standard of care or investigational maintenance therapy options based on homologous recombination deficiency (HRD) and MRD status. Summary statistics described the study population, chi-square tests compared categorical variables, and progression free survival (PFS) based on MRD status was estimated using Kaplan-Meier method and compared using log rank test. Results: 70 patients underwent SLL with a median of 8.5 biopsies (range 3-16). The majority of patients had stage III-IV disease (90%), and high-grade serous histology (90%). Approximately half (51.4%) of patients underwent neoadjuvant chemotherapy (NACT) with interval tumor reductive surgery (TRS). MRD was present in 32 patients (45.7%), and the presence of MRD was associated with a worse PFS (HR 3.0, 95% CI 1.5-5.8; 12.5 vs. 24.8 months; p=0.001). MRD was more frequent among NACT recipients compared to those who underwent primary TRS (63% vs 26%, P=0.002), those with HRD negative tumors (58% vs 24%, P=0.025), and those with R1 versus R0 resections (71% vs 39%, P=0.024). Of patients with MRD, 22 patients (71%) received bevacizumab until progression as part of a clinical trial (NCT02884648), 3 (10%) received bevacizumab off trial, 5 (16%) received a PARP inhibitor (all HRD positive), and 1 received other therapy. There were two (2.9%) intraoperative complications (both enterotomies) requiring conversion to laparotomy. Conclusions: SLL is feasible, overall safe, and detected MRD in 46% of ovarian cancer patients who were in radiologic and CA-125 remission after frontline therapy. PFS was significantly shorter for patients with residual disease, despite those patients all receiving additional therapy. Knowledge of MRD status in this patient population enables interventional, observational, and translational opportunities, as well as personalized prognostic counseling. MRD rate may also have utility as an early surrogate for efficacy in trials evaluating novel frontline investigational therapies. Future studies will compare the performance of circulating tumor DNA (ctDNA) versus surgical MRD. Citation Format: Anne Knisely, Roni Nitecki, J. Alejandro Rauh-Hain, R. Tyler Hillman, Jolyn S. Taylor, Lois M. Ramondetta, Michaela O. Grinsfelder, Lauren P. Cobb, David M. Boruta, Gwyn Richardson, Pamela T. Soliman, Aaron Shafer, Shannon N. Westin, Nicole D. Fleming, Travis T. Sims, Anil K. Sood, Pedro T. Ramirez, Karen H. Lu, Amir A. Jazaeri. The utility of surgical minimal residual disease after frontline treatment for prognostic and investigational opportunities in advanced ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A077.

Low‐cost tools for large‐scale seed scarification: efficiency in two species from South American arid lands

The use of native plants for arid land restoration requires the application of pre‐germination treatments to alleviate seed dormancy mechanisms. As it is known, scarification allows several valuable species to overcome the primary forms of dormancy. However, supplying large quantities of scarified seeds at a low cost represents a significant challenge. In this context, our objective was to evaluate locally constructed machines accessible to people of degraded lands in a state of poverty. The effectiveness was evaluated by comparing two native shrubs from South American arid lands, Larrea divaricata and L. cuneifolia. Four treatments were applied: control (T0), mechanical scarification with a hand drill equipped with sandpaper on its head (T1), and mechanical scarification for 15 seconds (T2) and 30 seconds (T3) with a self‐constructed machine, capable of regulating pressure and speed. For both species, the germination probability was higher with T2 (0.82 ± 0.02) compared to T0 (0.28 ± 0.03) and T1 (0.65 ± 0.03). T3 presented intermediate values (0.75 ± 0.03) but did not differ significantly from T1 and T2. Our results show the effectiveness of a locally constructed seed scarification tool to upscale seed‐based restoration in arid lands.

Abscisic acid-induced transcription factor PsMYB306 negatively regulates tree peony bud dormancy release.

Bud dormancy is a crucial strategy for perennial plants to withstand adverse winter conditions. However, the regulatory mechanism of bud dormancy in tree peony (Paeonia suffruticosa) remains largely unknown. Here, we observed dramatically reduced and increased accumulation of abscisic acid (ABA) and bioactive gibberellins (GAs) GA1 and GA3, respectively, during bud endodormancy release of tree peony under prolonged chilling treatment. An Illumina RNA sequencing study was performed to identify potential genes involved in the bud endodormancy regulation in tree peony. Correlation matrix, principal component, and interaction network analyses identified a downregulated MYB transcription factor gene, PsMYB306, the expression of which positively correlated with 9-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (PsNCED3) expression. Protein modeling analysis revealed 4 residues within the R2R3 domain of PsMYB306 to possess DNA binding capability. Transcription of PsMYB306 was increased by ABA treatment. Overexpression of PsMYB306 in petunia (Petunia hybrida) inhibited seed germination and plant growth, concomitant with elevated ABA and decreased GA contents. Silencing of PsMYB306 accelerated cold-triggered tree peony bud burst and influenced the production of ABA and GAs and the expression of their biosynthetic genes. ABA application reduced bud dormancy release and transcription of ENT-KAURENOIC ACID OXIDASE 1 (PsKAO1), GA20-OXIDASE 1 (PsGA20ox1), and GA3-OXIDASE 1 (PsGA3ox1) associated with GA biosynthesis in PsMYB306-silenced buds. In vivo and in vitro binding assays confirmed that PsMYB306 specifically transactivated the promoter of PsNCED3. Silencing of PsNCED3 also promoted bud break and growth. Altogether, our findings suggest that PsMYB306 negatively modulates cold-induced bud endodormancy release by regulating ABA production.

Evaluation of Dormancy Mechanism in Teak (Tectona grandis Linn.f) True Seeds Collected from Multiple Provenances and Forest Types of India

Teak drupes were collected from seven geographical locations spread over four forest types (dry deciduous, moist deciduous, very moist deciduous, and semi-deciduous) from India. In order to study the dormancy mechanism associated with teak true seeds. The true seeds present inside the drupes from each provenance were extracted without causing any damage to the true seeds. The extracted true seeds were used to study the morphological and physiological characteristics. The true seeds were carefully inoculated in MS medium to observe germination. Twenty-eight days after sowing, the result revealed that Andhra Pradesh provenance recorded the highest true seed germination of 58 percent compared to all other provenances. These results clearly indicate that not only physical and mechanical dormancy is involved in teak for decreased germination but also morphological/physiological dormancy plays a major role in teak true seed germination.

Intracardiac Injection Mouse Model to Study Cancer Cell Dormancy in Brain Metastasis.

Brain metastasis is a highly complex process, and some cancer cells enter a dormant state after extravasation into the brain. The molecular mechanism of dormancy remains largely unknown and is still under intense investigation. Here, we outline a basic approach to generating and analyzing experimental mouse models to study dormant cancer cells in the brain. Cancer cells stably expressing EGFP and firefly luciferase are injected into the left ventricle of athymic nude mice. After confirmation of brain metastasis by bioluminescence imaging, brain slices are prepared and subjected to Ki67 staining. In addition, a methodology for recovering brain metastatic cancer cells from the mouse brain is described, providing technical tips for unraveling the mysteries of cancer cell dormancy in brain metastasis.

Genetic, Epigenetic, and Environmental Control of Seed Dormancy and Germination.

Seed germination is controlled by a combination of the seed dormancy level and environmental conditions such as light, temperature, moisture, and nitrate levels. Seed dormancy is programed genetically, but it is also sensitive to maternal environmental conditions before and after anthesis. Recent developments in molecular genetics and bioinformatics have greatly enhanced our understanding of the molecular mechanisms of seed dormancy and germination in model plants and economically important crop species. This chapter focuses on temperature as an environmental factor and discusses the genetic and epigenetic mechanisms of dormancy and germination.

Light and Ethephon Overcoming Seed Dormancy in Friar's Crown (Melocactus zehntneri, Cactaceae), a Brazilian Cactus.

Seed germination in Melocactus and other cactus species is hampered by dormancy. However, most studies failed to achieve high seed-germination rates, suggesting a complex mechanism of dormancy in Cactaceae. Thus, the objective of this study was to evaluate whether factors such as light and phytoregulators overcome the dormancy in the seeds of the friar's crown cactus (Melocactus zehntneri). Two consecutive experimental sets were designed: one with seed germination under filter paper conditions and different wavelengths and Photosynthetically Photon Flux Densities (PPFDs); and one in vitro experiment using a culture medium to evaluate the influence of different phytoregulators, such as gibberellic acid (GA3), benzylaminopurine (BAP) and ethephon (ET), both in the germination of seeds of M. zehntneri. Seeds of M. zehntneri are positive photoblastic. Red light and gradual increases in PPFD resulted in the highest germination rates (60.8-61.7%) and germination speed index (4.4-4.5). In vitro seeding in culture media increased the germination percentage to 76% in control without phytoregulators. Ethephon showed a major effect in releasing the germination of dormant seeds of M. zehntneri, totaling 98% of seeds germinated under in vitro conditions, while GA3 and BAP showed minor or no effect on germination. The present study resulted in an efficient in vitro technique for germination and a better understanding of cacti seed dormancy.

HP-ECD: Heuristic Prophet protocol based on energy balance,cache optimization, and asynchronous dormancy

In opportunistic networks, opportunistic routing protocols are used for nodes to forward messages, which are the core technology to realize various opportunistic network applications. However, the existing opportunistic routing protocols generally have three problems: Key nodes forwarded too many messages, resulting in unbalanced energy consumption; Delivered message still occupies the cache space of nodes, resulting in the loss of undelivered message; Nodes constantly sense their surroundings and forward messages, resulting in rapid energy depletion. To better solve these problems, this paper proposes HP-ECD: heuristic Prophet routing protocol based on energy balance, cache optimization, and asynchronous dormancy. Based on Prophet, First, the HP-ECD defines the message forwarding benefits based on multiple node attributes and message importance, to realize the energy balance mechanism of nodes. Then, the HP-ECD designs the message delivery list based on the node history information, to realize the cache optimization mechanism of nodes. Finally, the HP-ECD determines whether a node is in dormancy based on the node running status, to realize the asynchronous dormancy mechanism of nodes. Simulation results show that, compared with Epidemic, Prophet, and EC-CW, HP-ECD greatly improves the message delivery rate and average remaining energy, and reduces the routing overhead rate and average storage time.

Seed dormancy mechanism and dormancy-breaking methods in wild raspberry (Rubus fraxinifolius Poir.)

Raspberries are subtropical plants that contain high levels of vitamin C, antibacterial and anti-inflammatory. They can potentially be developed as horticultural and medicinal plants. Dormancy is a challenge in the cultivation of raspberries (Rubus fraxinifolius Poir.). This study was conducted as two separate experiments. The first experiment aimed to identify the dormancy mechanism of R. fraxinifolius seed. In a two-factor factorial design, the first factor was seed storage, as unstored and three-month-stored, and the second factor was chemical-immersed treatment consisting of control, H2SO4, acetone, GA3, KNO3, H2SO4-GA3, acetone-GA3, H2SO4-KNO3, acetone-KNO3. The second experiment was aimed at determining dormancy-breaking methods for R. fraxinifolius seeds. In main plots were filter paper and cocopeat germination substrates. The subplots included control, immersed with distilled water, H2SO4, ultrafine bubble water, and temperature treatment at −80 °C, 50 °C, and 70 °C. The germination of unstored and three-month-stored seeds increased after H2SO4 treatment (36 to 82% and 82 to 94%, respectively). Seed germination increased after three months of storage. There was an increase in cytokinin hormone levels along with germination enhancement. The seeds went into physical dormancy because their seed coat was hard, and they went into physiological dormancy because of low cytokinin concentration. Stratification at 50 °C increased germination (78.5 to 93.0%), reduced dormancy intensity (15 to 6.5%), and increased the percentage of the speed of germination (1.99 to 3.12 ) on filter paper substrate.

Tumor removal limits prostate cancer cell dissemination in bone and osteoblasts induce cancer cell dormancy through focal adhesion kinase

BackgroundDisseminated tumor cells (DTCs) can enter a dormant state and cause no symptoms in cancer patients. On the other hand, the dormant DTCs can reactivate and cause metastases progression and lethal relapses. In prostate cancer (PCa), relapse can happen after curative treatments such as primary tumor removal. The impact of surgical removal on PCa dissemination and dormancy remains elusive. Furthermore, as dormant DTCs are asymptomatic, dormancy-induction can be an operational cure for preventing metastases and relapse of PCa patients.MethodsWe used a PCa subcutaneous xenograft model and species-specific PCR to survey the DTCs in various organs at different time points of tumor growth and in response to tumor removal. We developed in vitro 2D and 3D co-culture models to recapitulate the dormant DTCs in the bone microenvironment. Proliferation assays, fluorescent cell cycle reporter, qRT-PCR, and Western Blot were used to characterize the dormancy phenotype. We performed RNA sequencing to determine the dormancy signature of PCa. A drug repurposing algorithm was applied to predict dormancy-inducing drugs and a top candidate was validated for the efficacy and the mechanism of dormancy induction.ResultsWe found DTCs in almost all mouse organs examined, including bones, at week 2 post-tumor cell injections. Surgical removal of the primary tumor reduced the overall DTC abundance, but the DTCs were enriched only in the bones. We found that osteoblasts, but not other cells of the bones, induced PCa cell dormancy. RNA-Seq revealed the suppression of mitochondrial-related biological processes in osteoblast-induced dormant PCa cells. Importantly, the mitochondrial-related biological processes were found up-regulated in both circulating tumor cells and bone metastases from PCa patients’ data. We predicted and validated the dormancy-mimicking effect of PF-562,271 (PF-271), an inhibitor of focal adhesion kinase (FAK) in vitro. Decreased FAK phosphorylation and increased nuclear translocation were found in both co-cultured and PF-271-treated C4-2B cells, suggesting that FAK plays a key role in osteoblast-induced PCa dormancy.ConclusionsOur study provides the first insights into how primary tumor removal enriches PCa cell dissemination in the bones, defines a unique osteoblast-induced PCa dormancy signature, and identifies FAK as a PCa cell dormancy gatekeeper.

Low-Temperature-Induced Winter Dormancy in a Predatory Stink Bug Eocanthecona furcellata (Wolff) in the Subtropics

Insects have developed dormancy mechanisms to survive coldness in winters. The specific forms of winter dormancy, however, vary among different geographical and climatic zones and species. While there is extensive research on winter dormancy in insect pests and parasitoids in temperate zones, our understanding of how predatory insects, such as predatory stink bugs in subtropical regions, cope with cold winters and the specific forms of dormancy they undergo remains limited. The effects of winter temperatures on the population dynamics, development, and reproduction of the predatory stink bug Eocanthecona furcellata in the subtropics were investigated through greenhouse and laboratory experiments. E. furcellata exhibits two distinct peaks in population distribution throughout the year: one in April–May and another in October–November. Interestingly, the proportions of adults show an opposite pattern to the population dynamics, with the highest proportions of adults observed during the winter and summer seasons, when temperatures are the lowest and the highest, respectively. Laboratory studies showed that E. furcellata reared at lower temperatures (16 °C, 18 °C, and 20 °C) experienced prolonged development and higher mortality rates for eggs and nymphs compared to higher temperatures (22 °C and 26 °C). Further experiments observed that E. furcellata adults reared at 16 °C, 18 °C, and 20 °C entered into winter dormancy, where ovarian development was either completely halted or slowed down. The observed high proportion of E. furcellata adults and low proportion of nymphs during the cold winter months align well with the dormancy period. This study sheds light on the underlying mechanisms driving the population dynamics of E. furcellata during the subtropical winter. These findings have significant implications in accurately predicting the population dynamics of E. furcellata, implementing effective field release strategies, and optimizing cold storage techniques in the context of biological control programs.

THU485 The Impact Of Cured, Fried Bacon On The Reemergence From Breast Cancer Dormancy

Abstract Disclosure: C.P. Schane: None. A. Nelczyk: None. C. Chen: None. H. Vidana Gamage: None. M. Kadiri: None. M.T. McHenry: None. S. Bendre: None. N. Krawczynska: None. M.A. Henn: None. D.C. Castro: None. J. Chen: None. R.I. Tejeda: None. S. Hsiao: None. N.J. Engeseth: None. J.V. Sweedler: None. M.K. Wendt: None. T. Fan: None. W.G. Helferich: None. E.R. Nelson: None. One in eight women will develop breast cancer in her lifetime, with metastasis being the leading cause of mortality. Once the cells colonize the metastatic site, they do not always immediately begin to proliferate, but remain dormant. These dormant cells reside in the tissue, until mechanisms, which remain unknown, awaken the dormant cells and they resume malignant proliferation. Due to the large and growing population of breast cancer survivors at risk of metastatic recurrence, there is an urgent need to elucidate the mechanisms of dormancy and develop therapeutics to prevent reemergence. Elevated levels of circulating cholesterol are a risk factor for breast cancer recurrence. Preclinical work has demonstrated that oxysterol cholesterol metabolites such as 27-hydroxycholesterol (27HC) can promote tumor metastasis. Here, we show that exogenous 27HC lead to a more rapid reemergence from dormancy, using the syngeneic mouse D2.0R model of mammary cancer dormancy. Since it would be expected that cooking high cholesterol foods, such as bacon, under oxidative conditions, such as pan-frying, would produce fat containing cancer-promoting cholesterol metabolites, we hypothesized that consumption of such cooked foods would also promote reemergence from dormancy. Interestingly, consumption of cured, fried bacon fat (cfBF), but not uncured fried bacon fat (ufBF) resulted in reemergence. When metastatic tissues were assessed, it was found that consumption of cfBF dramatically reduced mast cell numbers. Since mast cells (MC) are major contributors to local histamine production, we next tested whether various anti-histamines could alter dormancy. This led to the striking finding that H2 antagonists promoted the breaking of dormancy. Our ongoing work is aimed at further elucidating this novel metastatic axis: Diet - MC - H2 - Dormancy, with the ultimate goal of leveraging it to develop novel therapeutic targets or lifestyle interventions. Therefore, our results are expected to provide the foundation for dietary and medical approaches to reduce the risk of recurrence among breast cancer survivors. This work was supported by the American Institute for Cancer Research grant (713063), the National Cancer Institute (R01CA234025) and Department of Defense Breast Cancer Research Program Era of Hope Scholar Award (BC200206). Further support awarded to ATN from a National Institutes of Environment Health Sciences and Research Training in Toxicology and Environmental Health (T32) Fellowship (ES007326). Presentation: Thursday, June 15, 2023