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The capacity to regenerate lost organs is widespread among animals, and yet the number of species in which regeneration has been experimentally probed using molecular and functional assays is very small. This is also the case for insects, for which we still lack a complete picture of their regeneration mechanisms and the extent of their conservation. Here, we contribute to filling this gap by investigating regeneration in the mayfly Cloeon dipterum . We focus on the abdominal gills of Cloeon nymphs, which are critical for osmoregulation and gas exchange. After amputation, gills re-grow faster than they do during normal development. Direct cell count and EdU assays indicate that growth acceleration involves an uniform increase in cell proliferation throughout the gill, rather than a localized growth zone. Accordingly, transcriptomic analysis reveals an early enrichment in cell cycle-related genes. Other gene classes are also enriched in regenerating gills, including protein neddylation and other proteostatic processes. We then showed the conservation of these mechanisms by functionally testing protein neddylation, the activin signalling pathway or the mRNA-binding protein Lin28, among other genes, in Drosophila larval/pupal wing regeneration. Globally, our results contribute to elucidating regeneration mechanisms in mayflies and the conservation of mechanisms involved in regeneration across insects.

Submerged macrophytes can overgrow and negatively affect freshwater ecosystems. This study aimed to investigate the use of chlormequat (CQ) to regulate submerged Vallisneria natans growth as well as its impact on the microbial community of epiphytic biofilms. V. natans height under CQ dosages of 20, 100, and 200 mg/L decreased within 21 days by 12.57%, 30.07%, and 44.62%, respectively, while chlorophyll content increased by 1.94%, 20.39%, and 38.83%. At 100 mg/L, CQ reduced the diversity of bacteria in the biofilm attached to V. natans leaves but increased the diversity of the eukaryotic microbial community. CQ strongly inhibited Cyanobacteria; compared with the control group, the treatment group experienced a significant reduction from 36.54% to 2.61%. Treatment significantly inhibited Gastrotricha and Rotifera, two dominant phyla of eukaryotes in the leaf biofilm, reducing their relative abundances by 17.41% and 6.48%, respectively. CQ significantly changed the leaf biofilm microbial community correlation network. The treatment group exhibited lower modularity (2.012) compared with the control group (2.249); however, the central network of the treated group contained a higher number of microbial genera (13) than the control group (4), highlighting the significance of eukaryotic genera in the network. The results obtained from this study provide invaluable scientific context and technical understanding pertinent to the restoration of submerged macrophytes within aquatic ecosystems. PRACTITIONER POINTS: Chlormequat reduced the plant height but increased leaf chlorophyll content. Chlormequat reduced biofilm bacterial diversity but increased eukaryotic diversity. Chlormequat affected the bacterial-fungal association networks in biofilms., (© 2024 Water Environment Federation.)

The atypical cadherins Fat and Dachsous (Ds) signal through the Hippo pathway to regulate growth of numerous organs, including the Drosophila wing. Here, we find that Ds-Fat signaling tunes a unique feature of cell proliferation found to control the rate of wing growth during the third instar larval phase. The duration of the cell cycle increases in direct proportion to the size of the wing, leading to linear-like growth during the third instar. Ds-Fat signaling enhances the rate at which the cell cycle lengthens with wing size, thus diminishing the rate of wing growth. We show that this results in a complex but stereotyped relative scaling of wing growth with body growth in Drosophila . Finally, we examine the dynamics of Fat and Ds protein distribution in the wing, observing graded distributions that change during growth. However, the significance of these dynamics is unclear since perturbations in expression have negligible impact on wing growth., Competing Interests: AL, JO, FW, RC No competing interests declared, (© 2023, Liu et al.)

Suppressor of cytokine signaling 1 (SOCS1) is a potent regulator immune cell responses and a proven tumor suppressor. Inhibition of SOCS1 in T cells can boost antitumor immunity, whereas its loss in tumor cells increases tumor aggressivity. Investigations into the tumor suppression mechanisms so far focused on tumor cell-intrinsic functions of SOCS1. However, it is possible that SOCS1 expression in tumor cells also regulate antitumor immune responses in a cell-extrinsic manner via direct and indirect mechanisms. Here, we discuss the evidence supporting the latter, and its implications for antitumor immunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ilangumaran, Gui, Shukla and Ramanathan.)

Organ size is controlled by numerous factors including mechanical forces, which are mediated in part by the Hippo pathway. In growing Drosophila epithelial tissues, cytoskeletal tension influences Hippo signaling by modulating the localization of key pathway proteins to different apical domains. Here, we discovered a Hippo signaling hub at basal spot junctions, which form at the basal-most point of the lateral membranes and resemble adherens junctions in protein composition. Basal spot junctions recruit the central kinase Warts via Ajuba and E-cadherin, which prevent Warts activation by segregating it from upstream Hippo pathway proteins. Basal spot junctions are prominent when tissues undergo morphogenesis and are highly sensitive to fluctuations in cytoskeletal tension. They are distinct from focal adhesions, but the latter profoundly influences basal spot junction abundance by modulating the basal-medial actomyosin network and tension experienced by spot junctions. Thus, basal spot junctions couple morphogenetic forces to Hippo pathway activity and organ growth., Competing Interests: Declaration of interests K.F.H. is a member of the Developmental Cell advisory board., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The steroid hormone 20-hydroxy-ecdysone (20E) promotes proliferation in Drosophila wing precursors at low titer but triggers proliferation arrest at high doses. Remarkably, wing precursors proliferate normally in the complete absence of the 20E receptor, suggesting that low-level 20E promotes proliferation by overriding the default anti-proliferative activity of the receptor. By contrast, 20E needs its receptor to arrest proliferation. Dose-response RNA sequencing (RNA-seq) analysis of ex vivo cultured wing precursors identifies genes that are quantitatively activated by 20E across the physiological range, likely comprising positive modulators of proliferation and other genes that are only activated at high doses. We suggest that some of these "high-threshold" genes dominantly suppress the activity of the pro-proliferation genes. We then show mathematically and with synthetic reporters that combinations of basic regulatory elements can recapitulate the behavior of both types of target genes. Thus, a relatively simple genetic circuit can account for the bimodal activity of this hormone., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

White blister rust, caused by the oomycete Albugo candida, is a widespread disease of Brassica crops. The Brassica relative Arabidopsis thaliana uses the paired immune receptor complex CSA1-CHS3/DAR4 to resist Albugo infection. The CHS3/DAR4 sensor NLR, which functions together with its partner, the helper NLR CSA1, carries an integrated domain (ID) with homology to DA1 peptidases. Using domain swaps with several DA1 homologs, we show that the LIM-peptidase domain of the family member CHS3/DAR4 functions as an integrated decoy for the family member DAR3, which interacts with and inhibits the peptidase activities of the three closely related peptidases DA1, DAR1, and DAR2. Albugo infection rapidly lowers DAR3 levels and activates DA1 peptidase activity, thereby promoting endoreduplication of host tissues to support pathogen growth. We propose that the paired immune receptor CSA1-CHS3/DAR4 detects the actions of a putative Albugo effector that reduces DAR3 levels, resulting in defense activation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Extracellular signal-regulated kinase 7 (ERK7), also known as ERK8 and MAPK15, is an atypical member of the MAP kinase family. Compared with other MAP kinases, the biological roles of ERK7 remain poorly understood. Recent work, however, has revealed several novel functions for ERK7. These include a highly conserved essential role in ciliogenesis, the ability to control cell growth, metabolism and autophagy, as well as the maintenance of genomic integrity. ERK7 functions through phosphorylation-dependent and -independent mechanisms and it is activated by cellular stressors, including DNA-damaging agents, and nutrient deprivation. Here, we summarize recent developments in understanding ERK7 function, emphasizing its conserved roles in cellular and physiological regulation., (© 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Metabolic engineering of microorganisms aims to design strains capable of producing valuable compounds under relevant industrial conditions and in an economically competitive manner. From this perspective, and beyond the need for a catalyst, biomass is essentially a cost-intensive, abundant by-product of a microbial conversion. Yet, few broadly applicable strategies focus on the optimal balance between product and biomass formation. Here, we present a genetic control module that can be used to precisely modulate growth of the industrial bacterial chassis Pseudomonas putida KT2440. The strategy is based on the controllable expression of the key metabolic enzyme complex pyruvate dehydrogenase (PDH) which functions as a metabolic valve. By tuning the PDH activity, we accurately controlled biomass formation, resulting in six distinct growth rates with parallel overproduction of excess pyruvate. We deployed this strategy to identify optimal growth patterns that improved the production yield of 2-ketoisovalerate and lycopene by 2.5- and 1.38-fold, respectively. This ability to dynamically steer fluxes to balance growth and production substantially enhances the potential of this remarkable microbial chassis for a wide range of industrial applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Plant glutamate receptor homologs (GLRs), which function as key calcium channels, play pivotal roles in various developmental processes as well as stress responses. The moss Physcomitrium patens , a representative of the earliest land plant lineage, possess multiple pathways of hormone signaling for coordinating growth and adaptation responses. However, it is not clear whether GLRs are connected to hormone-mediated growth control in the moss. In this study, we report that one of the two GLRs in P. patens , PpGLR1, involves in abscisic acid (ABA)-mediated growth regulation. ABA represses the growth of wild-type moss, and intriguingly, the PpGLR1 transcript levels are significantly increased in response to ABA treatment, based on both gene expression and the PpGLR1pro::GUS reporter results. Furthermore, the growth of Ppglr1 knockout moss mutants is hypersensitive to ABA treatment. These results suggest that PpGLR1 plays a critical role in ABA-mediated growth regulation, which provide useful information for our further investigation of the regulatory mechanism between Ca 2+ signal and ABA in moss growth control.

Rapid growth and survival are two key traits that enable bacterial cells to thrive in their natural habitat. The guanosine tetraphosphate and pentaphosphate [(p)ppGpp], also known as "magic spot", is a key second messenger inside bacterial cells as well as chloroplasts of plants and green algae. (p)ppGpp not only controls various stages of central dogma processes (replication, transcription, ribosome maturation and translation) and central metabolism but also regulates various physiological processes such as pathogenesis, persistence, motility and competence. Under extreme conditions such as nutrient starvation, (p)ppGpp-mediated stringent response is crucial for the survival of bacterial cells. This mini-review highlights some of the very recent progress on the key role of (p)ppGpp in bacterial growth control in light of cellular resource allocation and cell size regulation. We also briefly discuss some recent functional insights into the role of (p)ppGpp in plants and green algae from the angle of growth and development and further discuss several important open directions for future studies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The evolutionarily conserved Hippo pathway coordinates cell proliferation, differentiation and apoptosis to regulate organ growth and tumorigenesis. Hippo signaling activity is tightly controlled by various upstream signals including growth factors and cell polarity, but the full extent to which the pathway is regulated during development remains to be resolved. Here, we report the identification of Shaggy, the homolog of mammalian Gsk3β, as a novel regulator of the Hippo pathway in Drosophila. Our results show that Shaggy promotes the expression of Hippo target genes in a manner that is dependent on its kinase activity. Loss of Shaggy leads to Yorkie inhibition and downregulation of Hippo pathway target genes. Mechanistically, Shaggy acts upstream of the Hippo pathway and negatively regulates the abundance of the FERM domain containing adaptor protein Expanded. Our results reveal that Shaggy is functionally required for Crumbs/Slmb-mediated downregulation of Expanded in vivo, providing a potential molecular link between cellular architecture and the Hippo signaling pathway., (© 2022. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Organ growth driven by cell proliferation is an exponential process. As a result, even small variations in proliferation rates, when integrated over a relatively long developmental time, will lead to large differences in size. How organs robustly control their final size despite perturbations in cell proliferation rates throughout development is a long-standing question in biology. Using a mathematical model, we show that in the developing wing of the fruit fly, Drosophila melanogaster , variations in proliferation rates of wing-committed cells are inversely proportional to the duration of cell recruitment, a differentiation process in which a population of undifferentiated cells adopt the wing fate by expressing the selector gene, vestigial . A time-course experiment shows that vestigial-expressing cells increase exponentially while recruitment takes place, but slows down when recruitable cells start to vanish, suggesting that undifferentiated cells may be driving proliferation of wing-committed cells. When this observation is incorporated in our model, we show that the duration of cell recruitment robustly determines a final wing size even when cell proliferation rates of wing-committed cells are perturbed. Finally, we show that this control mechanism fails when perturbations in proliferation rates affect both wing-committed and recruitable cells, providing an experimentally testable hypothesis of our model.

The neurotoxin β-N-methylamino-L-alanine (BMAA) is an environmental factor connected to neurodegenerative diseases. BMAA can be produced by various microorganisms (e.g. bacteria, cyanobacteria, dinoflagellates and diatoms) present in diverse ecosystems. No previous study has revealed the function of BMAA in diatoms. In the present study, we combined physiological data with metabolomic and transcriptional data in order to investigate the effect and function of BMAA in the diatom Phaeodactylum tricornutum. P. tricornutum, exposed to different concentrations of exogenous BMAA, showed concentration dependent responses. When the concentration of supplemented BMAA was sufficient to arrest the growth of P. tricornutum, oxidative stress and obstructed carbon fixation were obtained from the specific metabolite and transcriptional data. Results also indicated increased concentration of intracellular chlorophyll a and alterations in the GS-GOGAT cycle, whereas the urea cycle was suppressed. We therefore conclude that BMAA represents a toxic metabolite able to control the growth of P. tricornutum by triggering oxidative stress, and further influencing photosynthesis and nitrogen metabolisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The phytohormone abscisic acid (ABA) promotes plant tolerance to major stresses such as drought, partly by modulating growth through poorly understood mechanisms. Here, we show that ABA-triggered repression of cell proliferation in the Arabidopsis thaliana root meristem relies on the swift subcellular relocalization of SNF1-RELATED KINASE 1 (SnRK1). Under favorable conditions, the SnRK1 catalytic subunit, SnRK1α1, is enriched in the nuclei of root cells, and this is accompanied by normal cell proliferation and meristem size. Depletion of two key drivers of ABA signaling, SnRK2.2 and SnRK2.3, causes constitutive cytoplasmic localization of SnRK1α1 and reduced meristem size, suggesting that, under nonstress conditions, SnRK2s promote growth by retaining SnRK1α1 in the nucleus. In response to ABA, SnRK1α1 translocates to the cytoplasm, and this is accompanied by inhibition of target of rapamycin (TOR), decreased cell proliferation, and reduced meristem size. Blocking nuclear export with leptomycin B abrogates ABA-driven SnRK1α1 relocalization to the cytoplasm and ABA-elicited inhibition of TOR. Furthermore, fusing SnRK1α1 to an SV40 nuclear localization signal leads to defective ABA-dependent TOR repression. Altogether, we demonstrate that SnRK2-dependent changes in SnRK1α1 subcellular localization are crucial for inhibiting TOR and root growth in response to ABA. Rapid relocalization of central regulators such as SnRK1 may represent a general strategy of eukaryotic organisms to respond to environmental changes.

Growth control establishes organism size, requiring mechanisms to sense and adjust growth during development. Studies of single cells revealed that size homeostasis uses distinct control methods. In multicellular organisms, mechanisms that regulate single cell growth must integrate control across organs and tissues during development to generate adult size and shape. We leveraged the roundworm Caenorhabditis elegans as a scalable and tractable model to collect precise growth measurements of thousands of individuals, measure feeding behavior, and quantify changes in animal size and shape during a densely sampled developmental time course. As animals transitioned from one developmental stage to the next, we observed changes in body aspect ratio while body volume remained constant. Then, we modeled a physical mechanism by which constraints on cuticle stretch could cause changes in C. elegans body shape. The model-predicted shape changes are consistent with those observed in the data. Theoretically, cuticle stretch could be sensed by the animal to initiate larval-stage transitions, providing a means for physical constraints to influence developmental timing and growth rate in C. elegans., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Protein tyrosine phosphatase, mitochondrial 1 (PTPMT1) is a mitochondrial phosphatase that is highly conserved in animals. Functional analyses using knockout animals have revealed a variety of physiological roles of PTPMT1 in vertebrates and insects. However, because of the high lethality of knockout in these animals, the roles of PTPMT1 in the later postembryonic development remain relatively obscure. In the present study, using the RNA interference technique, we analyzed PTPMT1 functions in later larval stages of the red flour beetle, Tribolium castaneum . PTPMT1 was expressed in both anterior and posterior parts of the body constitutively without obvious fluctuations from the middle larval instar through pupation. The PTPMT1 -knockdown larvae injected with PTPMT1 double-stranded RNA at the middle instar showed a prolonged larval period, which was mainly caused by an extra larval molt. On the other hand, the increase in adult body length was subtle in the PTPMT1 -knockdown T. castaneum , and the head capsule width was smaller than that of the control animals at the same larval instar. The expression levels of genes encoded by the mitochondrial genome were reduced in PTPMT1 -knockdown larvae, indicating that PTPMT1 plays an important role in mitochondrial function in T. castaneum , like in other species. By contrast, the expression levels of a juvenile hormone (JH)-biosynthetic gene and a JH-signaling gene were rather increased in the PTPMT1 -knockdown larvae, which may have been caused indirectly by the reduction of larval growth rate. Altogether, these findings indicate that PTPMT1 is required for the proper growth rate via some mitochondrial physiological role in T. castaneum larvae.

Many cellular activities in bacteria are organized according to their growth rate. The notion that ppGpp measures the cell’s growth rate is well accepted in the field of bacterial physiology. However, despite decades of interrogation and the identification of multiple molecular interactions that connects ppGpp to some aspects of cell growth, we lack a system-level, quantitative picture of how this alleged “measurement” is performed. Through quantitative experiments, we show that the ppGpp pool responds inversely to the rate of translational elongation in Escherichia coli. Together with its roles in inhibiting ribosome biogenesis and activity, ppGpp closes a key regulatory circuit that enables the cell to perceive and control the rate of its growth across conditions. The celebrated linear growth law relating the ribosome content and growth rate emerges as a consequence of keeping a supply of ribosome reserves while maintaining elongation rate in slow growth conditions. Further analysis suggests the elongation rate itself is detected by sensing the ratio of dwelling and translocating ribosomes, a strategy employed to collapse the complex, high-dimensional dynamics of the molecular processes underlying cell growth to perceive the physiological state of the whole.

The Ras-Raf-MEK-ERK signaling pathway, the first well-established MAPK pathway, plays essential roles in cell proliferation, survival, differentiation and development. It is activated in over 40% of human cancers owing to mutations of Ras, membrane receptor tyrosine kinases and other oncogenes. The Raf family consists of three isoforms, A-Raf, B-Raf and C-Raf. Since the first discovery of a truncated mutant of C-Raf as a transforming oncogene carried by a murine retrovirus, forty years of extensive studies have provided a wealth of information on the mechanisms underlying the activation, regulation and biological functions of the Raf family. However, the mechanisms by which activation of A-Raf and C-Raf is accomplished are still not completely understood. In contrast, B-Raf can be easily activated by binding of Ras-GTP, followed by cis -autophosphorylation of the activation loop, which accounts for the fact that this isoform is frequently mutated in many cancers, especially melanoma. The identification of oncogenic B-Raf mutations has led to accelerated drug development that targets Raf signaling in cancer. However, the effort has not proved as effective as anticipated, inasmuch as the mechanism of Raf activation involves multiple steps, factors and phosphorylation of different sites, as well as complex interactions between Raf isoforms. In this review, we will focus on the physiological complexity of the regulation of Raf kinases and their connection to the ERK phosphorylation cascade and then discuss the role of Raf in tumorigenesis and the clinical application of Raf inhibitors in the treatment of cancer.

Background: It is commonly believed that cancer development is irreversible, organ-specific as well as systemic malignant disorder, often associated with harmful oxidative stress and inflammation. However, there are also well-documented cases of spontaneous cancer regression, the causative mechanisms of which are not understood. It is known that inflammation is a negative pathophysiological process that may support the development of cancer, but it is also believed that the immune system as well as oxidative stress play important roles in prevention of cancer development and defense against tumor progression. Hence, in animal models spontaneous regression of cancer could be mediated by rapid inflammatory response of granulocytes, acting against cancer mostly as innate immune response. In addition, the administration of granulocytes at the site of solid tumors can lead to tumor regression or can slow down tumor growth and extend the overall survival of animals. In both cases, similar to the radiotherapy, surgery and various chemotherapies, oxidative stress occurs generating lipid peroxidation product 4-hydroxynonenal (4-HNE). This "second messenger of free radicals" acts as growth regulating signaling molecule that exerts relatively selective cytotoxicity against cancer cells., Conclusions: We hypothesize that abundant inflammation and metabolic changes caused by cancer and oxidative stress producing of 4-HNE may be crucial mechanisms for spontaneous cancer regression., Competing Interests: The authors declare no conflict of interest. NŽ is serving as the editorial board member of this journal. We declare that NŽ had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to GP., (© 2022 The Author(s). Published by IMR Press.)

During development, multicellular organisms undergo stereotypical patterns of tissue growth in space and time. How developmental growth is orchestrated remains unclear, largely due to the difficulty of observing and quantitating this process in a living organism. Drosophila histoblast nests are small clusters of progenitor epithelial cells that undergo extensive growth to give rise to the adult abdominal epidermis and are amenable to live imaging. Our quantitative analysis of histoblast proliferation and tissue mechanics reveals that tissue growth is driven by cell divisions initiated through basal extracellular matrix degradation by matrix metalloproteases secreted by the neighboring larval epidermal cells. Laser ablations and computational simulations show that tissue mechanical tension does not decrease as the histoblasts fill the abdominal epidermal surface. During tissue growth, the histoblasts display oscillatory cell division rates until growth termination occurs through the rapid emergence of G0/G1 arrested cells, rather than a gradual increase in cell-cycle time as observed in other systems such as the Drosophila wing and mouse postnatal epidermis. Different developing tissues can therefore achieve their final size using distinct growth termination strategies. Thus, adult abdominal epidermal development is characterized by changes in the tissue microenvironment and a rapid exit from the cell cycle., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Organ and tissue growth result from an integration of biophysical communication across biological scales, both in time and space. In this review, we highlight new insight into the dynamic connections between control mechanisms operating at different length scales. First, we consider how the dynamics of chemical and electrical signaling in the shape of gradients or waves affect spatiotemporal signal interpretation. Then, we discuss the mechanics underlying dynamic cell behavior during oriented tissue growth, followed by the connections between signaling at the tissue and organismal levels., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The size and proportions of animals are tightly controlled during development. How this is achieved remains poorly understood. The control of organ size entails coupling of cellular growth and cell division on one hand, and the measure of organ size on the other. In this review we focus on three layers of growth control consisting of genetic patterning, notably chemical gradients, mechanics and energetics which are complemented by a systemic control unit that modulates growth in response to the nutritional conditions and coordinates growth between different organs so as to maintain proportions. Growth factors, often present as concentration dependent chemical gradients, are positive inducers of cellular growth that may be considered as deterministic cues, hence acting as organ-intrinsic controllers of growth. However, the exponential growth dynamics in many developing tissues necessitate more stringent growth control in the form of negative feedbacks. Feedbacks endow biological systems with the capacity to quickly respond to perturbations and to correct the growth trajectory to avoid overgrowth. We propose to integrate chemical, mechanical and energetic control over cellular growth in a framework that emphasizes the self-organizing properties of organ-autonomous growth control in conjunction with systemic organ non-autonomous feedback on growth., (Copyright © 2021. Published by Elsevier B.V.)

Background: Microbial co-cultures and consortia are of interest in cell-based molecular production and even as "smart" therapeutics in that one can take advantage of division of labor and specialization to expand both the range of available functions and mechanisms for control. The development of tools that enable coordination and modulation of consortia will be crucial for future application of multi-population cultures. In particular, these systems would benefit from an expanded toolset that enables orthogonal inter-strain communication., Results: We created a co-culture for the synthesis of a redox-active phenazine signaling molecule, pyocyanin (PYO), by dividing its synthesis into the generation of its intermediate, phenazine carboxylic acid (PCA) from the first strain, followed by consumption of PCA and generation of PYO in a second strain. Interestingly, both PCA and PYO can be used to actuate gene expression in cells engineered with the soxRS oxidative stress regulon, although importantly this signaling activity was found to depend on growth media. That is, like other signaling motifs in bacterial systems, the signaling activity is context dependent. We then used this co-culture's phenazine signals in a tri-culture to modulate gene expression and production of three model products: quorum sensing molecule autoinducer-1 and two fluorescent marker proteins, eGFP and DsRed. We also showed how these redox-based signals could be intermingled with other quorum-sensing (QS) signals which are more commonly used in synthetic biology, to control complex behaviors. To provide control over product synthesis in the tri-cultures, we also showed how a QS-induced growth control module could guide metabolic flux in one population and at the same time guide overall tri-culture function. Specifically, we showed that phenazine signal recognition, enabled through the oxidative stress response regulon soxRS, was dependent on media composition such that signal propagation within our parsed synthetic system could guide different desired outcomes based on the prevailing environment. In doing so, we expanded the range of signaling molecules available for coordination and the modes by which they can be utilized to influence overall function of a multi-population culture., Conclusions: Our results show that redox-based signaling can be intermingled with other quorum sensing signaling in ways that enable user-defined control of microbial consortia yielding various outcomes defined by culture medium. Further, we demonstrated the utility of our previously designed growth control module in influencing signal propagation and metabolic activity is unimpeded by orthogonal redox-based signaling. By exploring novel multi-modal strategies for guiding communication and consortia outcome, the concepts introduced here may prove to be useful for coordination of multiple populations within complex microbial systems., (© 2021. The Author(s).)

There is a lot of evidence showing that lipid peroxidation plays very important role in development of various diseases, including neurodegenerative diseases and brain tumors. Lipid peroxidation is achieved by two main pathways, by enzymatic or by non-enzymatic oxidation, respectively. In this paper, we focus on non-enzymatic, self-catalyzed chain reaction of poly-unsaturated fatty acid (PUFA) peroxidation generating reactive aldehydes, notably 4-hydroxynonenal (4-HNE), which acts as second messenger of free radicals and as growth regulating factor. It might originate from astrocytes as well as from blood vessels, even within the blood-brain barrier (BBB), which is in case of brain tumors transformed into the blood-brain-tumor barrier (BBTB). The functionality of the BBB is strongly affected by 4-HNE because it forms relatively stable protein adducts thus allowing the persistence and the spread of lipid peroxidation, as revealed by immunohistochemical findings. Because 4-HNE can act as a regulator of vital functions of normal and of malignant cells acting in the cell type- and concentration-dependent manners, the bioactivities of this product of lipid peroxidation be should further studied to reveal if it acts as a co-factor of carcinogenesis or as natural factor of defense against primary brain tumors and metastatic cancer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Growth is a widely used term in plant science and ecology, but it can have different meanings depending on the context and the spatiotemporal scale of analysis. At the meristem level, growth is associated with the production of cells and initiation of new organs. At the organ or plant scale and over short time periods, growth is often used synonymously with tissue expansion, while over longer time periods the increase in biomass is a common metric. At even larger temporal and spatial scales, growth is mostly described as net primary production. Here, we first address the question 'what is growth?'. We propose a general framework to distinguish between the different facets of growth, and the corresponding physiological processes, environmental drivers and mathematical formalisms. Based on these different definitions, we then review how plant growth can be measured and analysed at different organisational, spatial and temporal scales. We conclude by discussing why gaining a better understanding of the different facets of plant growth is essential to disentangle genetic and environmental effects on the phenotype, and to uncover the causalities around source or sink limitations of plant growth., (© 2021 The Authors. New Phytologist © 2021 New Phytologist Foundation.)

We designed a novel growth controller regulated by feeding of an unnatural amino acid, N ε -benzyloxycarbonyl-l-lysine (ZK), using a specific incorporation system at a sense codon. This system is constructed by a pair of modified pyrrolisyl-tRNA synthetase (PylRS) and its cognate tRNA (tRNA pyl ). Although ZK is non-toxic for normal organisms, the growth of Escherichia coli carrying the ZK incorporation system was inhibited in a ZK concentration-dependent manner without causing rapid bacterial death, presumably due to generation of non-functional or toxic proteins. The extent of growth inhibition strongly depended on the anticodon sequence of the tRNA pyl gene. Taking advantage of the low selectivity of PylRS for tRNA pyl anticodons, we experimentally determined the most effective anticodon sequence among all 64 nucleotide sequences in the anticodon region of tRNA pyl gene. The results suggest that the ZK-regulated growth controller is a simple, target-specific, environmental noise-resistant and titratable system. This technique may be applicable to a wide variety of organisms because the growth inhibitory effects are caused by "informational disturbance", in which the highly conserved system for transmission of information from DNA to proteins is perturbed.

Understanding how extrinsic factors modulate genetically encoded information to produce a specific phenotype is of prime scientific interest. In particular, the feedback mechanism between abiotic forces and locomotory organs during morphogenesis to achieve efficient movement is a highly relevant example of such modulation. The study of this developmental process can provide unique insights on the transduction of cues at the interface between physics and biology. Here, we take advantage of the natural ability of adult zebrafish to regenerate their amputated fins to assess its morphogenic plasticity upon external modulations. Using a variety of surgical and chemical treatments, we could induce phenotypic responses to the structure of the fin. Through the ablation of specific rays in regenerating caudal fins, we generated artificially narrowed appendages in which the fin cleft depth and the positioning of rays bifurcations were perturbed compared with normal regenerates. To dissect the role of mechanotransduction in this process, we investigated the patterns of hydrodynamic forces acting on the surface of a zebrafish fin during regeneration by using particle tracking velocimetry on a range of biomimetic hydrofoils. This experimental approach enabled us to quantitatively compare hydrodynamic stress distributions over flapping fins of varying sizes and shapes. As a result, viscous shear stress acting on the distal margin of regenerating fins and the resulting internal tension are proposed as suitable signals for guiding the regulation of ray growth dynamics and branching pattern. Our findings suggest that mechanical forces are involved in the fine-tuning of the locomotory organ during fin morphogenesis., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

A fundamental biological question is how diverse and complex signaling and patterning is controlled correctly to generate distinct tissues, organs, and body plans, but incorrectly in diseased cells and tissues. Signaling pathways important for growth control have been identified, but to identify the mechanisms their transient and context-dependent interactions encode is more difficult. Currently computational systems biology aims to infer the control mechanisms by investigating quantitative changes of gene expression and protein concentrations, but this inference is difficult in nature. We propose it is desirable to explicitly simulate events and orders of gene regulation and protein interactions, which better elucidate control mechanisms, and report a method and tool with three examples. The Drosophila wing model includes Wnt, PCP, and Hippo pathways and mechanical force, incorporates well-confirmed experimental findings, and generates novel results. The other two examples illustrate the building of three-dimensional and large-scale models. These examples support that reconstructed spatiotemporal distributions of key signaling events help elucidate growth control mechanisms. As biologists pay increasing attention to disordered signaling in diseased cells, to develop new modeling methods and tools for conducting new computational studies is important., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Modern analytical methods combined with the modern concepts of redox signaling revealed 4-hydroxy-2-nonenal (4-HNE) as particular growth regulating factor involved in redox signaling under physiological and pathophysiological circumstances. In this review current knowledge of the relevance of 4-HNE as "the second messenger of reactive oxygen species" (ROS) in redox signaling of representative major stress-associated diseases is briefly summarized. The findings presented allow for 4-HNE to be considered not only as second messenger of ROS, but also as one of fundamental factors of the stress- and age-associated diseases. While standard, even modern concepts of molecular medicine and respective therapies in majority of these diseases target mostly the disease-specific symptoms. 4-HNE, especially its protein adducts, might appear to be the bioactive markers that would allow better monitoring of specific pathophysiological processes reflecting their complexity. Eventually that could help development of advanced integrative medicine approach for patients and the diseases they suffer from on the personalized basis implementing biomedical remedies that would optimize beneficial effects of ROS and 4-HNE to prevent the onset and progression of the illness, perhaps even providing the real cure., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aminoacyl-tRNA synthetases (aaRSs) serve a dual role in charging tRNAs. Their enzymatic activities both provide protein synthesis flux and reduce uncharged tRNA levels. Although uncharged tRNAs can negatively impact bacterial growth, substantial concentrations of tRNAs remain deacylated even under nutrient-rich conditions. Here, we show that tRNA charging in Bacillus subtilis is not maximized due to optimization of aaRS production during rapid growth, which prioritizes demands in protein synthesis over charging levels. The presence of uncharged tRNAs is alleviated by precisely tuned translation kinetics and the stringent response, both insensitive to aaRS overproduction but sharply responsive to underproduction, allowing for just enough aaRS production atop a "fitness cliff." Notably, we find that the stringent response mitigates fitness defects at all aaRS underproduction levels even without external starvation. Thus, adherence to minimal, flux-satisfying protein production drives limited tRNA charging and provides a basis for the sensitivity and setpoints of an integrated growth-control network., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Gradients of decapentaplegic (Dpp) pattern Drosophila wing imaginal discs, establishing gene expression boundaries at specific locations. As discs grow, Dpp gradients expand, keeping relative boundary positions approximately stationary. Such scaling fails in mutants for Pentagone (pent), a gene repressed by Dpp that encodes a diffusible protein that expands Dpp gradients. Although these properties fit a recent mathematical model of automatic gradient scaling, that model requires an expander that spreads with minimal loss throughout a morphogen field. Here, we show that Pent's actions are confined to within just a few cell diameters of its site of synthesis and can be phenocopied by manipulating non-diffusible Pent targets strictly within the Pent expression domain. Using genetics and mathematical modeling, we develop an alternative model of scaling driven by feedback downregulation of Dpp receptors and co-receptors. Among the model's predictions is a size beyond which scaling fails-something we observe directly in wing discs., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The Drosophila wing has served as a paradigm to mechanistically characterize the role of morphogens in patterning and growth. Wingless (Wg) and Decapentaplegic (Dpp) are expressed in two orthogonal signaling centers, and their gradients organize patterning by regulating the expression of well-defined target genes. By contrast, graded activity of these morphogens is not an absolute requirement for wing growth. Despite their permissive role in regulating growth, here we show that Wg and Dpp are utilized in a non-interchangeable manner by the two existing orthogonal signaling centers to promote preferential growth along the two different axes of the developing wing. Our data indicate that these morphogens promote anisotropic growth by making use of distinct and non-interchangeable molecular mechanisms. Whereas Dpp drives growth along the anterior-posterior axis by maintaining Brinker levels below a growth-repressing threshold, Wg exerts its action along the proximal-distal axis through a double repression mechanism involving T cell factor (TCF)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The expression of multiple growth-promoting genes is coordinated by the transcriptional co-activator Yorkie with its major regulatory input provided by the Hippo-Warts kinase cascade. Here, we identify Atg1/ULK1-mediated phosphorylation of Yorkie as an additional inhibitory input independent of the Hippo-Warts pathway. Two serine residues in Yorkie, S74 and S97, are Atg1/ULK1 consensus target sites and are phosphorylated by ULK1 in vitro, thereby preventing its binding to Scalloped. In vivo, gain of function of Atg1, or its activator Acinus, caused elevated Yorkie phosphorylation and inhibited Yorkie's growth-promoting activity. Loss of function of Atg1 or Acinus raised expression of Yorkie target genes and increased tissue size. Unlike Atg1's role in autophagy, Atg1-mediated phosphorylation of Yorkie does not require Atg13. Atg1 is activated by starvation and other cellular stressors and therefore can impose temporary stress-induced constraints on the growth-promoting gene networks under the control of Hippo-Yorkie signaling., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A newly discovered mechanism that causes the 'Minute' phenotype in fruit flies can explain how organisms are able to eliminate the mutant cells that arise occasionally during development., Competing Interests: SM, DB No competing interests declared, (© 2020, Mello and Bohmann.)

Reduced copy number of ribosomal protein ( Rp ) genes adversely affects both flies and mammals. Xrp1 encodes a reportedly Drosophila -specific AT-hook, bZIP protein responsible for many of the effects including the elimination of Rp mutant cells by competition with wild type cells. Irbp18, an evolutionarily conserved bZIP gene, heterodimerizes with Xrp1 and with another bZip protein, dATF4. We show that Irbp18 is required for the effects of Xrp1, whereas dATF4 does not share the same phenotype, indicating that Xrp1/Irbp18 is the complex active in Rp mutant cells, independently of other complexes that share Irbp18. Xrp1 and Irbp18 transcripts and proteins are upregulated in Rp mutant cells by auto-regulatory expression that depends on the Xrp1 DNA binding domains and is necessary for cell competition. We show that Xrp1 is conserved beyond Drosophila , although under positive selection for rapid evolution, and that at least one human bZip protein can similarly affect Drosophila development., Competing Interests: JB, JC, NB No competing interests declared, (© 2020, Blanco et al.)

The Hippo signaling pathway regulates diverse physiological processes, and its dysfunction has been implicated in an increasing number of human diseases, including cancer. Here, we provide an updated review of the Hippo pathway; discuss its roles in development, homeostasis, regeneration, and diseases; and highlight outstanding questions for future investigation and opportunities for Hippo-targeted therapies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In vitro cultured neuronal networks with defined connectivity are required to improve neuronal cell culture models. However, most protocols for their formation do not provide sufficient control of the direction and timing of neurite outgrowth with simultaneous access for analytical tools such as immunocytochemistry or patch-clamp recordings. Here, we present a proof-of-concept for the dynamic (i.e., time-gated) control of neurite outgrowth on a cell culture substrate based on 2D-micropatterned coatings of thermoresponsive polymers (TRP). The pattern consists of uncoated microstructures where neurons can readily adhere and neurites can extend along defined pathways. The surrounding regions are coated with TRP that does not facilitate cell or neurite growth at 33 °C. Increasing the ambient temperature to 37 °C renders the TRP coating cell adhesive and enables the crossing of gaps coated with TRP by neurites to contact neighboring cells. Here, we demonstrate the realization of this approach employing human neuronal SH-SY5Y cells and human induced neuronal cells. Our results suggest that this approach may help to establish a spatiotemporal control over the connectivity of multinodal neuronal networks.

Wnt/Wingless (Wg) signaling controls many aspects of animal development and is deregulated in different human cancers. The transcription factor dTcf/Pangolin (Pan) is the final effector of the Wg pathway in Drosophila and has a dual role in regulating the expression of Wg target genes. In the presence of Wg, dTcf/Pan interacts with β-catenin/Armadillo (Arm) and induces the transcription of Wg targets. In absence of Wg, dTcf/Pan partners with the transcriptional corepressor TLE/Groucho (Gro) and inhibits gene expression. Here, we use the wing imaginal disk of Drosophila as a model to examine the functions that dTcf/Pan plays in a proliferating epithelium. We report a function of dTcf/Pan in growth control and tumorigenesis. Our results show that dTcf/Pan can limit tissue growth in normal development and suppresses tumorigenesis in the context of oncogene up-regulation. We identify the conserved transcription factors Sox box protein 15 ( Sox15 ) and Ftz transcription factor 1 ( Ftz-f1 ) as genes controlled by dTcf/Pan involved in tumor development. In conclusion, this study reports a role for dTcf/Pan as a repressor of normal and oncogenic growth and identifies the genes inducing tumorigenesis downstream of dTcf/Pan., Competing Interests: The authors declare no conflict of interest.

Coordination of cell proliferation, cell expansion, and differentiation underpins plant growth. To maximise reproductive success, growth needs to be fine-tuned in response to endogenous and environmental cues. This developmental plasticity relies on a cellular machinery that integrates diverse signals and coordinates the downstream responses. In arabidopsis, the BAP regulatory module, which includes the BRASSINAZOLE RESISTANT 1 (BZR1), AUXIN RESPONSE FACTOR 6 (ARF6), and PHYTOCHROME INTERACTING FACTOR 4 (PIF4) transcription factors (TFs), has been shown to coordinate growth in response to multiple growth-regulating signals. In this Opinion article, we provide an integrative view on the BAP module control of cell expansion and discuss whether its function is conserved or diversified, thus providing new insights into the molecular control of growth., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Engineered systems that control cellular differentiation and pattern formation are essential for applications like tissue engineering, biomaterial fabrication, and synthetic ecosystems. Synthetic circuits that can take on multiple states have been made to engineer multicellular systems. However, how to use these states to drive interesting cellular behavior remains challenging. Here, we present a cellular differentiation program involving a novel synthetic bistable switch coupled to an antibiotic resistance gene that affects growth in yeast ( S. cerevisiae). The switch is composed of a positive feedback loop involving a novel transcription factor and can be switched ON and OFF via two different transient inducer inputs. By further coupling the bistable switch with an antibiotic resistance gene, we obtained a growth differentiation circuit, where yeast cells can be switched to stable HIGH or LOW growth rate states via transient inducer inputs. This work demonstrates a rationally designed and experimentally validated cellular differentiation behavior in yeast.

The evolutionarily conserved Target of Rapamycin (TOR) complex-2 (TORC2) is an essential regulator of plasma membrane homeostasis in budding yeast ( Saccharomyces cerevisiae ). In this yeast, TORC2 phosphorylates and activates the effector protein kinase Ypk1 and its paralog Ypk2. These protein kinases, in turn, carry out all the crucial functions of TORC2 by phosphorylating and thereby controlling the activity of at least a dozen downstream substrates. A previously uncharacterized interplay between the Rab5 GTPases and TORC2 signaling was uncovered through analysis of a newly suspected Ypk1 target. Muk1, one of two guanine nucleotide exchange factors for the Rab5 GTPases, was found to be a physiologically relevant Ypk1 substrate; and, genetic analysis indicates that Ypk1-mediated phosphorylation activates the guanine nucleotide exchange activity of Muk1. Second, it was demonstrated both in vivo and in vitro that the GTP-bound state of the Rab5 GTPase Vps21/Ypt51 physically associates with TORC2 and acts as a direct positive effector required for full TORC2 activity. These interrelationships provide a self-reinforcing control circuit for sustained up-regulation of TORC2-Ypk1 signaling. In this overview, we summarize the experimental basis of these findings, their implications, and speculate as to the molecular basis for Rab5-mediated TORC2 activation.

Body size in holometabolous insects is determined by the size at which the juvenile larva undergoes metamorphosis to the pupal stage. To undergo larva-pupa transition, larva must reach a critical developmental checkpoint, the threshold size (TS); however, the molecular mechanisms through which the TS cues this transition remain to be fully characterized. Here, we use the flour beetle Tribolium castaneum to characterize the molecular mechanisms underlying entry into metamorphosis. We found that T. castaneum reaches a TS at the beginning of the last larval instar, which is associated with the downregulation of TcKr-h1 and the upregulation of TcE93 and TcBr-C. Unexpectedly, we found that while there is an association between TS and TcE93 upregulation, it is the latter that constitutes the molecular trigger for metamorphosis initiation. In light of our results, we evaluate the interactions that control the larva-pupa transition and suggest alternative models., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

: Although granulocytes are the most abundant leukocytes in human blood, their involvement in the immune response against cancer is not well understood. While granulocytes are known for their "oxidative burst" when challenged with tumor cells, it is less known that oxygen-dependent killing of tumor cells by granulocytes includes peroxidation of lipids in tumor cell membranes, yielding formation of reactive aldehydes like 4-hydroxynonenal (4-HNE) and acrolein. In the present work, we investigate the role of reactive aldehydes on cellular redox homeostasis and surface toll-like receptor 4 (TLR4) expression. We have further study the granulocyte-tumor cell intercellular redox signaling pathways. The data obtained show that granulocytes in the presence of 4-HNE and acrolein induce excessive ROS formation in tumor cells. Acrolein was also shown to induce granulocyte TLR4 expression. Furthermore, granulocyte-mediated antitumor effects were shown to be mediated via HOCl intracellular pathway by the action of NADPH oxidase. However, further studies are needed to understand interaction between TLR4 and granulocyte-tumor cell intercellular signaling pathways., Competing Interests: The authors have declared that no conflict of interest exists.

The eukaryotic TORC1 kinase is a homeostatic controller of growth that integrates nutritional cues and mediates signals primarily from the surface of lysosomes or vacuoles. Amino acids activate TORC1 via the Rag GTPases that combine into structurally conserved multi-protein complexes such as the EGO complex (EGOC) in yeast. Here we show that Ego1, which mediates membrane-anchoring of EGOC via lipid modifications that it acquires while traveling through the trans-Golgi network, is separately sorted to vacuoles and perivacuolar endosomes. At both surfaces, it assembles EGOCs, which regulate spatially distinct pools of TORC1 that impinge on functionally divergent effectors: vacuolar TORC1 predominantly targets Sch9 to promote protein synthesis, whereas endosomal TORC1 phosphorylates Atg13 and Vps27 to inhibit macroautophagy and ESCRT-driven microautophagy, respectively. Thus, the coordination of three key regulatory nodes in protein synthesis and degradation critically relies on a division of labor between spatially sequestered populations of TORC1., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Among the various synthetic techniques, the sonochemical method has emerged as an interesting method for fabricating different photocatalysis materials with unique photoelectrochemical (PEC) properties. In comparison with the classical method without sonication, this study examines the promoting effect of ultrasonic irradiation during the synthesis of tungsten oxide (WO 3 ) nanoplates within short reaction times (15 and 30 min). The shorter ultrasonic reaction time (15 min) was sufficient for the uniform growth of thin and compact layers of WO 3 nanoparticles (NPs) on the surface of a tungsten foil. In the classical method, however, partial cracks or patches formed when WO 3 samples underwent acid treatment for either 15 min or 30 min at 90° C. The WO 3 nanoplates fabricated with 15- or 30-min sonication followed by 15- or 30-min deposition (U-15/30-15/30) showed much higher photocurrent density than the WO 3 samples fabricated with the classical method without sonication (C-15/30) at 90 °C. The as-prepared monoclinic WO 3 with 30-min ultrasonication and 30-min deposition (U-30/30) showed a maximum photocurrent density of ∼6.51 mA/cm 2 under simulated solar light at 1.8 V vs. Ag/AgCl, which was 2.12- to 2.93-fold higher than that of the two classical samples. The ultrasonic samples exhibited extraordinarily high stability for water oxidation by maintaining 98% of their initial photoactivity for 2200 sec, as compared to the low stability (66-61%) of both classical samples. The WO 3 nanoplates prepared by sonication method had many advantages, such as facile synthetic route, compact, porous and uniform nanoplate morphology, decreased electron-hole pairs recombination rate and controlled oxygen vacancies for greatly enhanced PEC water splitting performance and stability over extended time., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The considerable amount of experimental evidence has defined the Hippo pathway as a tumor suppressive pathway and increased expression and/or activity of its oncogenic effectors is frequently observed in cancer. However, clinical studies have failed to attribute cancer development and progression to mutations in the pathway. In explaining this conundrum, we investigated the expression and functions of a C-terminally truncated isoform of large tumor suppressor kinase 1 (LATS1) called short LATS1 (sLATS1) in human cell lines and Drosophila. Intriguingly, through overexpression of sLATS1, we demonstrated that sLATS1 either activates or suppresses the activity of Yes-associated protein (YAP), one of the effectors of the Hippo pathway, in a cell type-specific manner. The activation is mediated through inhibition of full-length LATS1, whereas suppression of YAP is accomplished through sLATS1-YAP interaction. In HEK293T cells, the former mechanism may affect the cellular response more dominantly, whereas in U2OS cells and developing tissues in Drosophila, the latter mechanism may be solely carried out. Finally, to find the clinical relevance of this molecule, we examined the expression of sLATS1 in breast cancer patients. The transcriptome analysis showed that the ratio of sLATS1 to LATS1 was increased in tumor tissues comparing to their adjacent normal tissues.

In this research, pure anatase phase titanium dioxide thin films were successfully fabricated for the first time using the mist chemical vapor deposition method, and optional values for deposition temperature and concentration of titanium tetraisopropoxide were established. It was found that the crystallinity of the titanium dioxide film was significantly improved by increasing the deposition temperature. The best crystallinity of titanium dioxide film was obtained at 400 °C. It was confirmed that pure anatase phase titanium dioxide films could be obtained using different concentrations of titanium tetraisopropoxide. The lower concentration of titanium tetraisopropoxide produced better crystallinity in the resultant titanium dioxide film. The morphologies of the titanium dioxide thin films were also significantly influenced by the concentration of titanium tetraisopropoxide in the precursor solution.

Stress tolerance and rapid growth are often competing interests in cells. Upon severe environmental stress, many organisms activate defense systems concurrent with growth arrest. There has been debate as to whether aspects of the stress-activated transcriptome are regulated by stress or an indirect byproduct of reduced proliferation. For example, stressed Saccharomyces cerevisiae cells mount a common gene expression program called the environmental stress response (ESR) [1] comprised of ∼300 induced (iESR) transcripts involved in stress defense and ∼600 reduced (rESR) mRNAs encoding ribosomal proteins (RPs) and ribosome biogenesis factors (RiBi) important for division. Because ESR activation also correlates with reduced growth rate in nutrient-restricted chemostats and prolonged G1 in slow-growing mutants, an alternate proposal is that the ESR is simply a consequence of reduced division [2-5]. A major challenge is that past studies did not separate effects of division arrest and stress defense; thus, the true responsiveness of the ESR-and the purpose of stress-dependent rESR repression in particular-remains unclear. Here, we decoupled cell division from the stress response by following transcriptome, proteome, and polysome changes in arrested cells responding to acute stress. We show that the ESR cannot be explained by changes in growth rate or cell-cycle phase during stress acclimation. Instead, failure to repress rESR transcripts reduces polysome association of induced transcripts, delaying production of their proteins. Our results suggest that stressed cells alleviate competition for translation factors by removing mRNAs and ribosomes from the translating pool, directing translational capacity toward induced transcripts to accelerate protein production., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The Hippo signaling pathway is an evolutionarily conserved mechanism that controls organ size in animals. Yorkie is well known as a transcriptional co-activator that functions downstream of the Hippo pathway to positively regulate transcription of genes that promote tissue growth. Recent studies have shown that increased myosin activity activates both Yorkie and its vertebrate orthologue YAP, resulting in increased nuclear localization and tissue growth. Here we show that Yorkie also can accumulate at the cell cortex in the apical junctional region. Moreover, Yorkie functions at the cortex to promote activation of myosin through a myosin regulatory light chain kinase, Stretchin-Mlck. This Yorkie function is not dependent on its transcriptional activity and is required for larval and adult tissues to achieve appropriate size. Based on these results, we suggest that Yorkie functions in a feedforward "amplifier" loop that promotes myosin activation, and thereby greater Yorkie activity, in response to tension., (Copyright © 2018 Elsevier Inc. All rights reserved.)