The apparent seasonal biphenism in Drosophila suzukii stems in reality from continuous reaction norms.

The spotted wing drosophila (SWD) is supposed to show only two distinct seasonal phenotypes: the dark, diapausing winter morph (WM) and the light, reproductively active summer morph (SM). It is unclear if these phenotypes result from a true developmental switch or from the expression of extreme phenotypes of continuous thermal reaction norms. This study aims to investigate this question by examining traits across a range of temperatures. Using 12 developmental temperatures (8 to 30 °C), we assessed traits including viability, growth, morphology, cold tolerance, metabolic rate, and ovarian maturation. Gradual increases in temperature induced gradual changes in all these traits, indicating classical nonlinear thermal reaction norms. Low temperatures (14 °C and below) produced flies with extended development, dark color, larger size, increased cold tolerance, reduced metabolism, and delayed oogenesis, characteristic of the WM. Given the months required for emergence and egg maturation at cold, distinct generations of SWD may develop in discrete environments resulting in an apparent biphenism. What appears to be distinct phenotypes (WM and SM) may actually result from continuous thermal reaction norms. This implies the need for precise terminology in SWD. We recommend using terms like 'winter-acclimated' or 'winter phenotype' rather than 'winter morph'. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Colorectal cancer cell dormancy: An insight into pathways.

Cancer cell dormancy (CCD) in colorectal cancer (CRC) poses a significant challenge to effective treatment. In CRC, CCD contributes to tumour recurrence, drug resistance, and amplifying the disease's burden. The molecular mechanisms governing CCD and strategies for eliminating dormant cancer cells remain largely unexplored. Therefore, understanding the molecular mechanisms governing dormancy is crucial for improving patient outcomes and developing targeted therapies. This editorial highlights the complex interplay of signalling pathways and factors involved in colorectal CCD, emphasizing the roles of Hippo/YAP, pluripotent transcription factors such as NANOG, HIF-1α signalling, and Notch signalling pathways. Additionally, ERK/p38α/ß/MAPK pathways, AKT signalling pathway, and Extracellular Matrix Metalloproteinase Inducer, along with some potential less explored pathways such as STAT/p53 switch and canonical and non-canonical Wnt and SMAD signalling, are also involved in promoting colorectal CCD. Highlighting their clinical significance, these findings may offer the potential for identifying key dormancy regulator pathways, improving treatment strategies, surmounting drug resistance, and advancing personalized medicine approaches. Moreover, insights into dormancy mechanisms could lead to the development of predictive biomarkers for identifying patients at risk of recurrence and the tailoring of targeted therapies based on individual dormancy profiles. It is essential to conduct further research into these pathways and their modulation to fully comprehend CRC dormancy mechanisms and enhance patient outcomes.

Stable Isotope Labelling Reveals Water and Carbon Fluxes in Temperate Tree Saplings Before Budbreak.

Despite considerable experimental effort, the physiological mechanisms governing temperate tree species' water and carbon dynamics before the onset of the growing period remain poorly understood. We applied 2H-enriched water during winter dormancy to the soil of four potted European tree species. After 8 weeks of chilling, hydrogen isotopes in stem, twig and bud water were measured six times during 2 consecutive weeks of forcing conditions (Experiment 1). Additionally, we pulse-labelled above-ground plant tissues using 2H-enriched water vapour and 13C-enriched CO2 7 days after exposure to forcing conditions to trace atmospheric water and carbon uptake (Experiment 2). Experiment 1 revealed soil water incorporation into the above-ground organs of all species during the chilling phase and significant species-specific differences in water allocation during the forcing conditions, which we attributed to differences in structural traits. Experiment 2 illustrated water vapour incorporation into all above-ground tissue of all species. However, the incorporation of carbon was found for evergreen saplings only. Our results suggest that temperate trees take up and reallocate soil water and absorb atmospheric water to maintain sufficient above-ground tissue hydration during winter. Therefore, our findings provide new insights into the water allocation dynamics of temperate trees during early spring.

The molecular mechanisms of chemotherapeutic resistance in tumors (Review).

Chemotherapy remains a prevalent treatment for a wide range of tumors; however, the majority of patients undergoing conventional chemotherapy experience varying levels of chemoresistance, ultimately leading to suboptimal outcomes. The present article provided an in­depth review of chemotherapy resistance in tumors, emphasizing the underlying factors contributing to this resistance in tumor cells. It also explored recent advancements in the identification of key molecules and molecular mechanisms within the primary chemoresistant pathways.

Lung-resident alveolar macrophages regulate the timing of breast cancer metastasis.

Breast disseminated cancer cells (DCCs) can remain dormant in the lungs for extended periods, but the mechanisms limiting their expansion are not well understood. Research indicates that tissue-resident alveolar macrophages suppress breast cancer metastasis in lung alveoli by inducing dormancy. Through ligand-receptor mapping and intravital imaging, it was found that alveolar macrophages express transforming growth factor (TGF)-ß2. This expression, along with persistent macrophage-cancer cell interactions via the TGF-ßRIII receptor, maintains cancer cells in a dormant state. Depleting alveolar macrophages or losing the TGF-ß2 receptor in cancer cells triggers metastatic awakening. Aggressive breast cancer cells are either suppressed by alveolar macrophages or evade this suppression by avoiding interaction and downregulating the TGF-ß2 receptor. Restoring TGF-ßRIII in aggressive cells reinstates TGF-ß2-mediated macrophage growth suppression. Thus, alveolar macrophages act as a metastasis immune barrier, and downregulation of TGF-ß2 signaling allows cancer cells to overcome macrophage-mediated growth suppression.

Protein aggregation is a consequence of the dormancy-inducing membrane toxin TisB in Escherichia coli.

Bacterial dormancy is a valuable strategy to survive stressful conditions. Toxins from chromosomal toxin-antitoxin systems have the potential to halt cell growth, induce dormancy, and eventually promote a stress-tolerant persister state. Due to their potential toxicity when overexpressed, sophisticated expression systems are needed when studying toxin genes. Here, we present a moderate expression system for toxin genes based on an artificial 5' untranslated region. We applied the system to induce expression of the toxin gene tisB from the chromosomal type I toxin-antitoxin system tisB/istR-1 in Escherichia coli. TisB is a small hydrophobic protein that targets the inner membrane, resulting in depolarization and ATP depletion. We analyzed TisB-producing cells by RNA-sequencing and revealed several genes with a role in recovery from TisB-induced dormancy, including the chaperone genes ibpAB and spy. The importance of chaperone genes suggested that TisB-producing cells are prone to protein aggregation, which was validated by an in vivo fluorescent reporter system. We moved on to show that TisB is an essential factor for protein aggregation upon DNA damage mediated by the fluoroquinolone antibiotic ciprofloxacin in E. coli wild-type cells. The occurrence of protein aggregates correlates with an extended dormancy duration, which underscores their importance for the life cycle of TisB-dependent persister cells. IMPORTANCE: Protein aggregates occur in all living cells due to misfolding of proteins. In bacteria, protein aggregation is associated with cellular inactivity, which is related to dormancy and tolerance to stressful conditions, including exposure to antibiotics. In Escherichia coli, the membrane toxin TisB is an important factor for dormancy and antibiotic tolerance upon DNA damage mediated by the fluoroquinolone antibiotic ciprofloxacin. Here, we show that TisB provokes protein aggregation, which, in turn, promotes an extended state of cellular dormancy. Our study suggests that protein aggregation is a consequence of membrane toxins with the potential to affect the duration of dormancy and the outcome of antibiotic therapy.

KAR1-dormancy release in Avena fatua caryopses includes increased AfMAN gene expression and ENDO-ß-MANNANASE activity in the coleorhiza and radicle.

KAR1, at very low concentration (3x10-9 M) released dormancy in Avena fatua caryopses, which was expressed in almost complete emergence of coleorhiza (CE) and radicle (RE) just after three days of germination. The dormancy-releasing effect of KAR1 was associated with an increased activity of ENDO-ß-MANNANASE (MAN; EC 3.2.1.78) (hydrolase and transglycosylase) in coleorhiza and radicle before RE. The MAN genes, MAN1, MAN2, MAN3, MAN4, and MAN5 were for the first time identified in the genome of A. fatua. KAR1 induced expression of AfMAN1-3 and AfMAN5 in the coleorhiza and AfMAN2 and AfMAN3 in the radicle during caryopses germination. The increase in transcripts in the coleorhiza of AfMAN1,5 after 8 h and AfMAN3,5 after 12 h germination in the presence of KAR1 is probably responsible for the increase in MAN activity determined after 18 h before RE. KAR1 also increased AfMAN3 expression in radicle after 12 h which probably caused the increased MAN activity after 18 h. Therefore, release of caryopses dormancy by KAR1 involves increasing expression of MAN genes and MAN activity both in the coleorhiza and radicle, which might facilitate the passage of the radicle through the coleorhiza. The work provides the first data on the contribution of MAN, present in coleorhiza and radicle, in the dormancy release of caryopses by KAR1.

Progressive heterogeneity of enlarged and irregularly shaped apicoplasts in Plasmodium falciparum persister blood stages after drug treatment.

Morphological modifications and shifts in organelle relationships are hallmarks of dormancy in eukaryotic cells. Communications between altered mitochondria and nuclei are associated with metabolic quiescence of cancer cells that can survive chemotherapy. In plants, changes in the pathways between nuclei, mitochondria, and chloroplasts are associated with cold stress and bud dormancy. Plasmodium falciparum parasites, the deadliest agent of malaria in humans, contain a chloroplast-like organelle (apicoplast) derived from an ancient photosynthetic symbiont. Antimalarial treatments can fail because a fraction of the blood-stage parasites enter dormancy and recrudesce after drug exposure. Altered mitochondrial-nuclear interactions in these persisters have been described for P. falciparum, but interactions of the apicoplast remained to be characterized. In the present study, we examined the apicoplasts of persisters obtained after exposure to dihydroartemisinin (a first-line antimalarial drug) followed by sorbitol treatment, or after exposure to sorbitol treatment alone. As previously observed, the mitochondrion of persisters was consistently enlarged and in close association with the nucleus. In contrast, the apicoplast varied from compact and oblate, like those of active ring-stage parasites, to enlarged and irregularly shaped. Enlarged apicoplasts became more prevalent later in dormancy, but regular size apicoplasts subsequently predominated in actively replicating recrudescent parasites. All three organelles, nucleus, mitochondrion, and apicoplast, became closer during dormancy. Understanding their relationships in erythrocytic-stage persisters may lead to new strategies to prevent recrudescences and protect the future of malaria chemotherapy.

Initiation of tumor dormancy by the lymphovascular embolus.

Cancer dormancy followed by recurrence remains an enigma in cancer biology. Since both local and systemic recurrences are thought to emanate from dormant micrometastasis which take origin from lymphovascular tumor emboli we wondered whether the process of dormancy might initiate within lymphovascular emboli. This study combines experimental studies with a patient-derived xenograft (PDX) of inflammatory breast cancer (Mary-X) that spontaneously forms spheroids in vitro and budding lymphovascular tumor emboli in vivo with observational studies utilizing tissue microarrays (TMAs) of human breast cancers. In the experimental studies, Mary-X during both lymphovascular emboli formation in vivo and spheroidgenesis in vitro exhibited decreased proliferation, a G0/G1 cell cycle arrest and decreased mTOR signaling. This induction of dormancy required calpain-mediated E-cadherin proteolysis and was mediated by decreased P13K signaling, resulting in decreased mTOR activity. In observational human breast cancer studies, increased E-cadherin immunoreactivity due to increased E-cad/NTF-1 but both decreased Ki-67 and mTOR activity was observed selectively and differentially within the lymphovascular tumor emboli. Both our experimental as well as observational studies indicate that in vivo lymphovascular tumor emboli and their in vitro spheroid equivalent initiate dormancy through these pathways.

AINTEGUMENTA-LIKE genes regulate reproductive growth and bud dormancy in Platanus acerifolia.

KEY MESSAGE: Platanus acerifolia AIL genes PaAIL5a/b and PaAIL6b participate in FT-AP1/FUL-AIL pathways to regulate bud dormancy. In addition, PaAIL6a/b can promote flowering, and PaAIL5b and PaAIL6b affect floral development. Bud dormancy and floral induction are essential processes for perennial plants, they are both regulated by photoperiod, temperature, and hormones, indicating the existence of common regulators for both processes. AINTEGUMENTA-LIKE (AIL) genes regulate reproductive growth of annual plants, including floral induction and flower development, and their homologs in poplar and grape act downstream of the florigen gene FT and the floral meristem identity genes AP1/FUL and function to maintain growth and thus inhibit dormancy induction. However, it is not known whether AIL homologs participate in the reproduction processes in perennials and whether the Platanus acerifolia AIL genes are involved in dormancy. P. acerifolia is a perennial woody plant whose reproductive growth is strongly associated with dormancy. Here, we isolated four AIL homologs from P. acerifolia, PaAIL5a, PaAIL5b, PaAIL6a, and PaAIL6b, and systematically investigated their functions by ectopic-overexpression in tobacco. The findings demonstrate that PaAIL5a/b and PaAIL6b respond to short day, low temperature, and hormone signals and act as the components of the FT-AP1/FUL-AIL pathway to regulate the bud dormancy in P. acerifolia. Notably, PaAIL5a/b and PaAIL6b function downstream of PaFTL-PaFUL1/2/3 to inhibit the dormancy induction and downstream of PaFT-PaFUL2/3 to promote the dormancy release. In addition, PaAIL6a/b were found to accelerate flowering in transgenic tobacco, whereas PaAIL5b and PaAIL6b affected the flower development. Together, our results suggest that PaAIL genes may act downstream of different PaFT/PaFTL and PaFUL proteins to fulfill conservative and diverse roles in floral initiation, floral development, and dormancy regulation in P. acerifolia.

Spring resting egg production of the calanoid copepod, Eurytemora affinis, in a freshet-dominated estuary.

Seasonal peaks in river discharge, such as snowmelt-dominated freshets, are predictable events that can have a large effect on flushing rates and salinity in estuaries. Resting eggs, which many coastal and estuarine copepods produce for overwintering or aestivation, could also serve to bridge predictable peaks in river discharge. We assessed the timing of resting egg production of the egg-carrying estuarine copepod, Eurytemora affinis (Poppe), in relation to river discharge in the Fraser River Estuary, Canada. Approximately 30 field-collected females were individually incubated on 12 occasions over the period February 2015-May 2016. Eurytemora affinis abundance and population structure were investigated from vertical net tow samples collected twice monthly to monthly. Resting eggs occurred primarily in May 2015 and May 2016 (6.5 and 9.2 eggs day-1, respectively), a month prior to peak flows, and the proportion of offspring that were resting eggs increased with river discharge. Eurytemora affinis reached a minimum abundance in July 2015, when the population was dominated by adults (86%). Resting egg production in E. affinis is typically considered an overwintering mechanism but we suggest that the ultimate driver of resting egg production in this population is avoidance of flushing and/or low salinities.

A regulatory module mediating temperature control of cell-cell communication facilitates tree bud dormancy release.

The control of cell-cell communication via plasmodesmata (PD) plays a key role in plant development. In tree buds, low-temperature conditions (LT) induce a switch in plasmodesmata from a closed to an open state, which restores cell-to-cell communication in the shoot apex and releases dormancy. Using genetic and cell-biological approaches, we have identified a previously uncharacterized transcription factor, Low-temperature-Induced MADS-box 1 (LIM1), as an LT-induced, direct upstream activator of the gibberellic acid (GA) pathway. The LIM1-GA module mediates low temperature-induced plasmodesmata opening, by negatively regulating callose accumulation to promote dormancy release. LIM1 also activates expression of FT1 (FLOWERING LOCUS T), another LT-induced factor, with LIM1-FT1 forming a coherent feedforward loop converging on low-temperature regulation of gibberellin signaling in dormancy release. Mathematical modeling and experimental validation suggest that negative feedback regulation of LIM1 by gibberellin could play a crucial role in maintaining the robust temporal regulation of bud responses to low temperature. These results reveal genetic factors linking temperature control of cell-cell communication with regulation of seasonally-aligned growth crucial for adaptation of trees.

Evolutionary origin and functional investigation of the widely conserved plant PEBP gene STEPMOTHER OF FT AND TFL1 (SMFT).

Genes of the family PHOSPHATIDYLETHANOLAMINE-BINDING PROTEINS (PEBP) have been intensely studied in plants for their role in cell (re)programming and meristem differentiation. Recently, sporadic reports of the presence of a new type of PEBP in plants became available, highly similar to the YY-PEBPs of prokaryotes. A comprehensive investigation of their spread, origin, and function revealed conservation across the plant kingdom. The YY-PEBP clade in plants seems to have resulted from a single Horizontal Gene Transfer (HGT) episode from a prokaryotic organism to an ancestral streptophyte. YY-PEBPs are also present in other eukaryotes, such as certain fungi, diatoms, and rotifers, and these cases derive from independent HGT events. Reciprocally, the occurrence of the eukaryotic CETS/RKIP type PEBPs (CR-PEBPs) was noticed in bacteria of the genus Nocardia, showing that HGT has occurred as well from eukaryotes to prokaryotes. Based on these observations, we propose that the current model of the PEBP family in plants needs to be updated with the clade STEPMOTHER OF FT AND TFL1 (SMFT). SMFT genes not only share high sequence conservation but also show specific expression in homologous plant structures that serve as propagules. Functional analysis of Arabidopsis smft mutant lines pointed to a function for this gene in regulating seed germination, both concerning primary dormancy release and in response to adverse high-temperature conditions. Overall, our study reveals an increasing complexity in the evolutionary history of the PEBP gene family, unlocking new potential in understanding the evolution and functional spectrum of these important key regulatory genes.

Dormancy and awakening of cancer cells: the extracellular vesicle-mediated cross-talk between Dr. Jekill and Mr. Hyde.

Cancer cell dormancy is a reversible process whereby cancer cells enter a quiescent state characterized by cell cycle arrest, inhibition of cell migration and invasion, and increased chemoresistance. Because of its reversibility and resistance to treatment, dormancy is a key process to study, monitor, and interfere with, in order to prevent tumor recurrence and metastasis and improve the prognosis of cancer patients. However, to achieve this goal, further studies are needed to elucidate the mechanisms underlying this complex and dynamic dual process. Here, we review the contribution of extracellular vesicles (EVs) to the regulation of cancer cell dormancy/awakening, focusing on the cross-talk between tumor and non-tumor cells in both the primary tumor and the (pre-)metastatic niche. Although EVs are recognized as key players in tumor progression and metastasis, as well as in tumor diagnostics and therapeutics, their role specifically in dormancy induction/escape is still largely elusive. We report on the most recent and promising results on this topic, focusing on the EV-associated nucleic acids involved. We highlight how EV studies could greatly contribute to the identification of dormancy signaling pathways and a dormancy/early awakening signature for the development of successful diagnostic/prognostic and therapeutic approaches.

The MKK3 module integrates nitrate and light signals to modulate secondary dormancy in Arabidopsis thaliana.

Seed dormancy corresponds to a reversible blockage of germination. Primary dormancy is established during seed maturation, while secondary dormancy is set up on the dispersed seed, following an exposure to unfavorable factors. Both dormancies are relieved in response to environmental factors, such as light, nitrate, and coldness. Quantitive Trait Locus (QTL) analyses for preharvest sprouting identified MKK3 kinase in cereals as a player in dormancy control. Here, we showed that MKK3 also plays a role in secondary dormancy in Arabidopsis within a signaling module composed of MAP3K13/14/19/20, MKK3, and clade-C MAPKs. Seeds impaired in this module acquired heat-induced secondary dormancy more rapidly than wild-type (WT) seeds, and this dormancy is less sensitive to nitrate, a signal able to release dormancy. We also demonstrated that MPK7 was strongly activated in the seed during dormancy release, especially in response to light and nitrate. This activation was greatly reduced in map3k13/14/19/20 and mkk3 mutants. Finally, we showed that the module was not regulated and apparently did not regulate the genes controlling abscisic acid/gibberellin acid hormone balance, one of the crucial mechanisms of seed dormancy control. Overall, our work identified a MAPK module controlling seed germination and enlarged the panel of functions of the MKK3-related modules in plants.

Dormancy regulator Prunus mume DAM6 promotes ethylene-mediated leaf senescence and abscission.

Leaf senescence and abscission in autumn are critical phenological events in deciduous woody perennials. After leaf fall, dormant buds remain on deciduous woody perennials, which then enter a winter dormancy phase. Thus, leaf fall is widely believed to be linked to the onset of dormancy. In Rosaceae fruit trees, DORMANCY-ASSOCIATED MADS-box (DAM) transcription factors control bud dormancy. However, apart from their regulatory effects on bud dormancy, the biological functions of DAMs have not been thoroughly characterized. In this study, we revealed a novel DAM function influencing leaf senescence and abscission in autumn. In Prunus mume, PmDAM6 expression was gradually up-regulated in leaves during autumn toward leaf fall. Our comparative transcriptome analysis using two RNA-seq datasets for the leaves of transgenic plants overexpressing PmDAM6 and peach (Prunus persica) DAM6 (PpeDAM6) indicated Prunus DAM6 may up-regulate the expression of genes involved in ethylene biosynthesis and signaling as well as leaf abscission. Significant increases in 1-aminocyclopropane-1-carboxylate accumulation and ethylene emission in DEX-treated 35S:PmDAM6-GR leaves reflect the inductive effect of PmDAM6 on ethylene biosynthesis. Additionally, ethephon treatments promoted autumn leaf senescence and abscission in apple and P. mume, mirroring the changes due to PmDAM6 overexpression. Collectively, these findings suggest that PmDAM6 may induce ethylene emission from leaves, thereby promoting leaf senescence and abscission. This study clarified the effects of Prunus DAM6 on autumn leaf fall, which is associated with bud dormancy onset. Accordingly, in Rosaceae, DAMs may play multiple important roles affecting whole plant growth during the tree dormancy induction phase.

Persistence and Culturability of Escherichia coli under Induced Toxin Expression.

BACKGROUND/OBJECTIVES: Bacteria are well known to enter dormancy under stress conditions. However, the mechanisms of different dormancy-related phenotypes are still under debate and many questions remain unanswered. This study aims to better understand the effects of toxin gene expression on the dormancy of Escherichia coli. METHODS: The effects of toxin gene expression on growth, persistence, and culturability were characterized. Specifically, we detailed dose- and time-dependent dormancy of E. coli and its susceptibility to ofloxacin via arabinose-induced hipA toxin gene expression under the PBAD promoter. A new plot was developed to better describe the dynamic changes in culturability and persistence. The expression level of hipA was determined using qPCR and cellular activities were monitored using fluorescence imaging and flow cytometry. RESULTS: High-level persister formation and strong tolerance to ofloxacin were observed after high-level hipA induction. The new plot reveals more information than the changes in persistence alone, e.g., reduced culturability of E. coli and thus deeper dormancy under high-level hipA induction. Consistently, controlled hipA induction led to decreased cellular activities at promoter PrrnBP1 and an increase in the non-culturable subpopulation. CONCLUSIONS: Overall, this study provides new insights into dormancy induced by toxin gene expression and a more comprehensive view of persistence and culturability. The findings may help develop better control agents against dormant bacterial cells.

Dormancy characteristics of lammas-growth seedlings of subtropical trees and their phenological responses to experimental warming.

Lammas growth of trees means the additional growth of the shoot after the growth cessation and bud set in late summer. In temperate tree species, lammas growth occurs irregularly and is often regarded as abnormal, disturbed growth. In subtropical tree species, however, lammas growth is a prevalent phenomenon, possibly due to the prolonged occurrence of high temperatures in the autumn. The occurrence of lammas growth extends the growing season of trees, but its influence on subsequent dormancy phenomena and bud burst phenology remains largely unexplored. By comparing seedlings showing lammas growth with others not showing it, we carried out an experimental study of how lammas growth affects the bud burst phenology and the underlying dormancy phenomena under both ambient and controlled chilling, forcing, and warming conditions in four subtropical tree species: Carya illinoinensis, Cinnamomum japonicum, Phoebe chekiangensis, and Torreya grandis. With the exception of C. illinoinensis, lammas growth delayed bud burst in all the species under ambient conditions. In a chilling experiment, the delay appeared to be due to higher minimum forcing requirement, higher dormancy depth, and in T. grandis, also to lower chilling sensitivity in the lammas-growth seedlings than in the non-lammas-growth ones. However, a spring warming experiment showed that the sensitivity of bud burst to spring temperatures was higher in the lammas-growth seedlings than in the non-lammas-growth ones. Because of this, the difference between the two phenotypes in the timing of bud burst vanished with increasing warming. Our findings elucidate the significant impact of lammas growth on the dormancy dynamics of subtropical tree species, highlighting the necessity to better understand how the physiological phenomena causing lammas growth change the trees' subsequent environmental responses under changing climatic conditions.

mTOR activity paces human blastocyst stage developmental progression.

Many mammals can temporally uncouple conception from parturition by pacing down their development around the blastocyst stage. In mice, this dormant state is achieved by decreasing the activity of the growth-regulating mTOR signaling pathway. It is unknown whether this ability is conserved in mammals in general and in humans in particular. Here, we show that decreasing the activity of the mTOR signaling pathway induces human pluripotent stem cells (hPSCs) and blastoids to enter a dormant state with limited proliferation, developmental progression, and capacity to attach to endometrial cells. These in vitro assays show that, similar to other species, the ability to enter dormancy is active in human cells around the blastocyst stage and is reversible at both functional and molecular levels. The pacing of human blastocyst development has potential implications for reproductive therapies.

Characterization of Escherichia coli Persisters from Biofilm Culture: Multiple Dormancy Levels and Multigenerational Memory in Formation.

Persister cells (PCs), a subpopulation occurring within normal cells, exhibit a transient tolerance to antibiotics because of their dormant state. PCs are categorized into two types: type I PCs, which emerge during the stationary phase, and type II PCs, which emerge during the logarithmic phase. Using the conventional colony-forming method, we previously demonstrated that type I PCs of Escherichia coli form more frequently in air-solid biofilm culture than in liquid culture. In the current study, we modified a cell filamentation method as a more efficient and rapid alternative for quantifying PCs. This modified method yielded results consistent with those of the conventional method with 103-104 times higher sensitivity and less detection time, within several hours, and further revealed the existence of multiple levels of type I PCs, including a substantial number of deeply dormant cells. This study also discovered a potential epigenetic memory mechanism, spanning several generations (four or six cell divisions), which influences type II PC formation based on prior biofilm experience in E. coli.