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1
Fritz, Rafael Dominik, i Olivier Pertz. "The dynamics of spatio-temporal Rho GTPase signaling: formation of signaling patterns". F1000Research 5 (26.04.2016): 749. http://dx.doi.org/10.12688/f1000research.7370.1.
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Rho GTPases are crucial signaling molecules that regulate a plethora of biological functions. Traditional biochemical, cell biological, and genetic approaches have founded the basis of Rho GTPase biology. The development of biosensors then allowed measuring Rho GTPase activity with unprecedented spatio-temporal resolution. This revealed that Rho GTPase activity fluctuates on time and length scales of tens of seconds and micrometers, respectively. In this review, we describe Rho GTPase activity patterns observed in different cell systems. We then discuss the growing body of evidence that upstream regulators such as guanine nucleotide exchange factors and GTPase-activating proteins shape these patterns by precisely controlling the spatio-temporal flux of Rho GTPase activity. Finally, we comment on additional mechanisms that might feed into the regulation of these signaling patterns and on novel technologies required to dissect this spatio-temporal complexity.
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Bakhsh, A., K. Shahzad i T. Husnain. "Variation in the spatio-temporal expression of insecticidal genes in cotton". Czech Journal of Genetics and Plant Breeding 47, No. 1 (18.03.2011): 1–9. http://dx.doi.org/10.17221/131/2010-cjgpb.
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The most significant breakthrough in plant biotechnology is the development of the techniques to transform genes from unrelated sources into commercially important crop plants to develop resistance against targeted insect pests. The spatio-temporal expression of insecticidal genes in transgenic cotton varies with plant age, plant parts and environmental conditions. The understanding of this temporal and spatial variation in efficacy and the resulting mechanisms is essential for cotton protection and production. This review summarizes variations in the efficacy of introduced insecticidal genes in cotton crop. The factors contributing to the variability of endotoxins have also been highlighted. The reduction in Bt protein biosynthesis in late-season cotton tissues could be attributed to the overexpression of the Bt gene at earlier stages, which leads to gene regulation at post-transcription levels and consequently results in gene silencing at a later stage. Methylation of the promoter may also play a role in the declined expression of endotoxin proteins. In genetically modified crops several environmental factors have been reported to affect the expression of transgenes. Among environmental factors nitrogen metabolism, inhibition of synthesis, degradation, remobilization and high temperature are attributable to the quantitative reduction in Bt proteins. Applying plant growth regulators or protein enhancers such as Chaperone<sup>TM</sup> may improve Bt cotton efficacy through enhancing the synthesis of proteins. Also some agronomic practices such as nitrogen fertilization and timely irrigation favour the endotoxin expression. Thus, variations in the efficacy of insecticidal genes in transgenic cotton and the involved mechanisms need to be understood fully so as to plan rational resistance management strategies to retard the rate of resistance development and to control target pests effectively by enhancing the endotoxin expression through genetic or agronomic management.
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Hill, Robert E., i Laura A. Lettice. "Alterations to the remote control of Shh gene expression cause congenital abnormalities". Philosophical Transactions of the Royal Society B: Biological Sciences 368, nr 1620 (19.06.2013): 20120357. http://dx.doi.org/10.1098/rstb.2012.0357.
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Multi-species conserved non-coding elements occur in the vertebrate genome and are clustered in the vicinity of developmentally regulated genes. Many are known to act as cis -regulators of transcription and may reside at long distances from the genes they regulate. However, the relationship of conserved sequence to encoded regulatory information and indeed, the mechanism by which these contribute to long-range transcriptional regulation is not well understood. The ZRS, a highly conserved cis -regulator, is a paradigm for such long-range gene regulation. The ZRS acts over approximately 1 Mb to control spatio-temporal expression of Shh in the limb bud and mutations within it result in a number of limb abnormalities, including polydactyly, tibial hypoplasia and syndactyly. We describe the activity of this developmental regulator and discuss a number of mechanisms by which regulatory mutations in this enhancer function to cause congenital abnormalities.
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Sun, Shuo, Changyu Yi, Jing Ma, Shoudong Wang, Marta Peirats-Llobet, Mathew G. Lewsey, James Whelan i Huixia Shou. "Analysis of Spatio-Temporal Transcriptome Profiles of Soybean (Glycine max) Tissues during Early Seed Development". International Journal of Molecular Sciences 21, nr 20 (14.10.2020): 7603. http://dx.doi.org/10.3390/ijms21207603.
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Soybean (Glycine max) is an important crop providing oil and protein for both human and animal consumption. Knowing which biological processes take place in specific tissues in a temporal manner will enable directed breeding or synthetic approaches to improve seed quantity and quality. We analyzed a genome-wide transcriptome dataset from embryo, endosperm, endothelium, epidermis, hilum, outer and inner integument and suspensor at the global, heart and cotyledon stages of soybean seed development. The tissue specificity of gene expression was greater than stage specificity, and only three genes were differentially expressed in all seed tissues. Tissues had both unique and shared enriched functional categories of tissue-specifically expressed genes associated with them. Strong spatio-temporal correlation in gene expression was identified using weighted gene co-expression network analysis, with the most co-expression occurring in one seed tissue. Transcription factors with distinct spatiotemporal gene expression programs in each seed tissue were identified as candidate regulators of expression within those tissues. Gene ontology (GO) enrichment of orthogroup clusters revealed the conserved functions and unique roles of orthogroups with similar and contrasting expression patterns in transcript abundance between soybean and Arabidopsis during embryo proper and endosperm development. Key regulators in each seed tissue and hub genes connecting those networks were characterized by constructing gene regulatory networks. Our findings provide an important resource for describing the structure and function of individual soybean seed compartments during early seed development.
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Pintard, Lionel, i Vincent Archambault. "A unified view of spatio-temporal control of mitotic entry: Polo kinase as the key". Open Biology 8, nr 8 (sierpień 2018): 180114. http://dx.doi.org/10.1098/rsob.180114.
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The Polo kinase is an essential regulator of cell division. Its ability to regulate multiple events at distinct subcellular locations and times during mitosis is remarkable. In the last few years, a much clearer mechanistic understanding of the functions and regulation of Polo in cell division has emerged. In this regard, the importance of coupling changes in activity with changes in localization is striking, both for Polo itself and for its upstream regulators. This review brings together several new pieces of the puzzle that are gradually revealing how Polo is regulated, in space and time, to enable its functions in the early stages of mitosis in animal cells. As a result, a unified view of how mitotic entry is spatio-temporally regulated is emerging.
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Pang, Junling, Xia Zhang, Xuhui Ma i Jun Zhao. "Spatio-Temporal Transcriptional Dynamics of Maize Long Non-Coding RNAs Responsive to Drought Stress". Genes 10, nr 2 (13.02.2019): 138. http://dx.doi.org/10.3390/genes10020138.
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Long non-coding RNAs (lncRNAs) have emerged as important regulators in plant stress response. Here, we report a genome-wide lncRNA transcriptional analysis in response to drought stress using an expanded series of maize samples collected from three distinct tissues spanning four developmental stages. In total, 3488 high-confidence lncRNAs were identified, among which 1535 were characterized as drought responsive. By characterizing the genomic structure and expression pattern, we found that lncRNA structures were less complex than protein-coding genes, showing shorter transcripts and fewer exons. Moreover, drought-responsive lncRNAs exhibited higher tissue- and development-specificity than protein-coding genes. By exploring the temporal expression patterns of drought-responsive lncRNAs at different developmental stages, we discovered that the reproductive stage R1 was the most sensitive growth stage with more lncRNAs showing altered expression upon drought stress. Furthermore, lncRNA target prediction revealed 653 potential lncRNA-messenger RNA (mRNA) pairs, among which 124 pairs function in cis-acting mode and 529 in trans. Functional enrichment analysis showed that the targets were significantly enriched in molecular functions related to oxidoreductase activity, water binding, and electron carrier activity. Multiple promising targets of drought-responsive lncRNAs were discovered, including the V-ATPase encoding gene, vpp4. These findings extend our knowledge of lncRNAs as important regulators in maize drought response.
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Warmerdam, Daniël O., Roland Kanaar i Veronique A. J. Smits. "Differential Dynamics of ATR-Mediated Checkpoint Regulators". Journal of Nucleic Acids 2010 (2010): 1–16. http://dx.doi.org/10.4061/2010/319142.
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The ATR-Chk1 checkpoint pathway is activated by UV-induced DNA lesions and replication stress. Little was known about the spatio and temporal behaviour of the proteins involved, and we, therefore, examined the behaviour of the ATRIP-ATR and Rad9-Rad1-Hus1 putative DNA damage sensor complexes and the downstream effector kinase Chk1. We developed assays for the generation and validation of stable cell lines expressing GFP-fusion proteins. Photobleaching experiments in living cells expressing these fusions indicated that after UV-induced DNA damage, ATRIP associates more transiently with damaged chromatin than members of the Rad9-Rad1-Hus1 complex. Interestingly, ATRIP directly associated with locally induced UV damage, whereas Rad9 bound in a cooperative manner, which can be explained by the Rad17-dependent loading of Rad9 onto damaged chromatin. Although Chk1 dissociates from the chromatin upon UV damage, no change in the mobility of GFP-Chk1 was observed, supporting the notion that Chk1 is a highly dynamic protein.
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Shan, Xiaotong, Yueqing Li, Song Yang, Zhongzhou Yang, Meng Qiu, Ruifang Gao, Taotao Han i in. "The spatio‐temporal biosynthesis of floral flavonols is controlled by differential phylogenetic MYB regulators in Freesia hybrida". New Phytologist 228, nr 6 (18.08.2020): 1864–79. http://dx.doi.org/10.1111/nph.16818.
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Botti, Gerardo, Clemente Cillo, Rossella De Cecio, Maria Gabriella Malzone i Monica Cantile. "Paralogous HOX13 Genes in Human Cancers". Cancers 11, nr 5 (20.05.2019): 699. http://dx.doi.org/10.3390/cancers11050699.
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Hox genes (HOX in humans), an evolutionary preserved gene family, are key determinants of embryonic development and cell memory gene program. Hox genes are organized in four clusters on four chromosomal loci aligned in 13 paralogous groups based on sequence homology (Hox gene network). During development Hox genes are transcribed, according to the rule of “spatio-temporal collinearity”, with early regulators of anterior body regions located at the 3’ end of each Hox cluster and the later regulators of posterior body regions placed at the distal 5’ end. The onset of 3’ Hox gene activation is determined by Wingless-type MMTV integration site family (Wnt) signaling, whereas 5’ Hox activation is due to paralogous group 13 genes, which act as posterior-inhibitors of more anterior Hox proteins (posterior prevalence). Deregulation of HOX genes is associated with developmental abnormalities and different human diseases. Paralogous HOX13 genes (HOX A13, HOX B13, HOX C13 and HOX D13) also play a relevant role in tumor development and progression. In this review, we will discuss the role of paralogous HOX13 genes regarding their regulatory mechanisms during carcinogenesis and tumor progression and their use as biomarkers for cancer diagnosis and treatment.
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Gao, Yuanhui, Hui Cao, Denggao Huang, Linlin Zheng, Zhenyu Nie i Shufang Zhang. "RNA-Binding Proteins in Bladder Cancer". Cancers 15, nr 4 (10.02.2023): 1150. http://dx.doi.org/10.3390/cancers15041150.
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RNA-binding proteins (RBPs) are key regulators of transcription and translation, with highly dynamic spatio-temporal regulation. They are usually involved in the regulation of RNA splicing, polyadenylation, and mRNA stability and mediate processes such as mRNA localization and translation, thereby affecting the RNA life cycle and causing the production of abnormal protein phenotypes that lead to tumorigenesis and development. Accumulating evidence supports that RBPs play critical roles in vital life processes, such as bladder cancer initiation, progression, metastasis, and drug resistance. Uncovering the regulatory mechanisms of RBPs in bladder cancer is aimed at addressing the occurrence and progression of bladder cancer and finding new therapies for cancer treatment. This article reviews the effects and mechanisms of several RBPs on bladder cancer and summarizes the different types of RBPs involved in the progression of bladder cancer and the potential molecular mechanisms by which they are regulated, with a view to providing information for basic and clinical researchers.
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Lomov, Viktor, Maria Grechushnikova, Vladimir Kazantsev i Irina Repina. "Reasons and patterns of spatio-temporal variability of methane emission from the Mozhaysk reservoir in summer period". E3S Web of Conferences 163 (2020): 03010. http://dx.doi.org/10.1051/e3sconf/202016303010.
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Anthropogenic reservoirs are not only sources of clean energy, flow regulators, recreational and food resources, but also sources of greenhouse gases such as methane. The studies presented in this work, done on a well-studied low-flowing valley reservoir mainly in the summer, when the greatest variability of methane fluxes was observe. Depending on synoptic conditions, the temporal variability of methane fluxes varies greatly. Methane fluxes increase during the summer period and huge methane emissions observed before the autumn mixing stage. Emissions can occur during the destruction of temperature stratification, as a result of stormy weather. With such emissions, methane fluxes into the atmosphere can reach about 20 mgC*m-2*d-1, which is higher than the emission during convection. Revealing the patterns of spatio-temporal distribution of methane fluxes will help to determine the contribution of water bodies (in particular reservoirs) to the total methane budget of the atmosphere more accurately.
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Vaid, Samir, i Wieland B. Huttner. "Transcriptional Regulators and Human-Specific/Primate-Specific Genes in Neocortical Neurogenesis". International Journal of Molecular Sciences 21, nr 13 (29.06.2020): 4614. http://dx.doi.org/10.3390/ijms21134614.
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During development, starting from a pool of pluripotent stem cells, tissue-specific genetic programs help to shape and develop functional organs. To understand the development of an organ and its disorders, it is important to understand the spatio-temporal dynamics of the gene expression profiles that occur during its development. Modifications in existing genes, the de-novo appearance of new genes, or, occasionally, even the loss of genes, can greatly affect the gene expression profile of any given tissue and contribute to the evolution of organs or of parts of organs. The neocortex is evolutionarily the most recent part of the brain, it is unique to mammals, and is the seat of our higher cognitive abilities. Progenitors that give rise to this tissue undergo sequential waves of differentiation to produce the complete sets of neurons and glial cells that make up a functional neocortex. We will review herein our understanding of the transcriptional regulators that control the neural precursor cells (NPCs) during the generation of the most abundant class of neocortical neurons, the glutametergic neurons. In addition, we will discuss the roles of recently-identified human- and primate-specific genes in promoting neurogenesis, leading to neocortical expansion.
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Collins, Emma M., i Alexander Thompson. "HOX genes in normal, engineered and malignant hematopoiesis". International Journal of Developmental Biology 62, nr 11-12 (2018): 847–56. http://dx.doi.org/10.1387/ijdb.180206at.
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Advanced technologies and models systems are improving our understanding of developmental processes. A primary example, hematopoiesis, classically represented by a hierarchical tree with a stem cell at the apex and more lineage restricted cells following each bifurcation has recently been shown to be capable of more adaptable fate decisions. Future research will identify key molecules underpinning this more adaptable or continuous model of hematopoiesis potentially leading to improved engineering of blood cells and therapies for malignant disease. The spatio-temporal, cell specific and exquisite reliance on gene dosage attributed to the HOX family promoted them as candidate master regulators of hierarchical hematopoiesis. Recent discoveries in the need to stimulate or retain HOX expression during engineered human hematopoiesis, supported by similar studies in mice and other developmental models, reinforces their importance at the single cell level. Likewise, dysregulation of HOX in single cells can result in blood cancers such as leukemia. It will be of interest to see what additional roles HOX family members and their regulators including morphogens, epigenetic modifiers and noncoding RNAs play in this evolving field and if these master regulators can be further harnessed for clinical benefit.
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Liu, Yang, Ya-Jie Hu, Wen-Xuan Fan, Xin Quan, Bin Xu i Shi-Ze Li. "O-GlcNAcylation: The Underestimated Emerging Regulators of Skeletal Muscle Physiology". Cells 11, nr 11 (30.05.2022): 1789. http://dx.doi.org/10.3390/cells11111789.
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O-GlcNAcylation is a highly dynamic, reversible and atypical glycosylation that regulates the activity, biological function, stability, sublocation and interaction of target proteins. O-GlcNAcylation receives and coordinates different signal inputs as an intracellular integrator similar to the nutrient sensor and stress receptor, which target multiple substrates with spatio-temporal analysis specifically to maintain cellular homeostasis and normal physiological functions. Our review gives a brief description of O-GlcNAcylation and its only two processing enzymes and HBP flux, which will help to better understand its physiological characteristics of sensing nutrition and environmental cues. This nutritional and stress-sensitive properties of O-GlcNAcylation allow it to participate in the precise regulation of skeletal muscle metabolism. This review discusses the mechanism of O-GlcNAcylation to alleviate metabolic disorders and the controversy about the insulin resistance of skeletal muscle. The level of global O-GlcNAcylation is precisely controlled and maintained in the “optimal zone”, and its abnormal changes is a potential factor in the pathogenesis of cancer, neurodegeneration, diabetes and diabetic complications. Although the essential role of O-GlcNAcylation in skeletal muscle physiology has been widely studied and recognized, it still is underestimated and overlooked. This review highlights the latest progress and potential mechanisms of O-GlcNAcylation in the regulation of skeletal muscle contraction and structural properties.
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Li, Xiaoran, Yanping Zhong, Xudong Zhang, Anil Sood i Jinsong Liu. "Abstract 108: Spatio-temporal view of malignant histogenesis and cancer evolution via formation of polyploid giant cancer cell". Cancer Research 83, nr 7_Supplement (4.04.2023): 108. http://dx.doi.org/10.1158/1538-7445.am2023-108.
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Abstract To understand how malignant tumors develop from single cells, we used long-term, time-lapse, live-cell imaging to track the dynamics of the cell membrane, nucleus, spindle, and cell cycle regulators during the development of high-grade, serous, carcinoma-derived organoids. Organoids are highly heterogeneous and include 2 major subtypes. Type-1 organoids are relatively homogeneous and develop via traditional mitosis, whereas type-2 organoids are highly heterogenous and are composed of differently sized polyploid giant cancer cells (PGCCs). Tracking the origin of PGCCs in type-2 organoids shows single cells first undergo asymmetric mitosis and nuclear fusion, followed by endoreplication, multipolar restitution mitosis, multipolar endomitosis, and karyokinesis. At the cellular level, the formation of PGCCs was associated with the formation of transient intracellular cells, termed fecundity cells. The fecundity cells underwent decellularization via the dissolution of the cell membrane, which allowed a giant nucleus to form via nuclear fusion. Different PGCCs underwent nuclear budding, decellularization, or entosis to form Russian doll-like tissue structures that facilitated rapid tumor growth and evolution. The uncoupling of nuclear augmentation from cytokinesis led to a rapid increase in the nuclear-to-cytoplasmic ratio and increased the genomic content of PGCCs, which facilitated macro-genomic evolution during tumor development. Our live-cell imaging evidence allows us to link nuclear replication and cancer evolution to the nuclear morphologies observed by pathologists under the microscope. PGCCs may be the central regulators of malignant histogenesis, cancer evolution, and physical barriers conferring resistance to immune therapy. Citation Format: Xiaoran Li, Yanping Zhong, Xudong Zhang, Anil Sood, Jinsong Liu. Spatio-temporal view of malignant histogenesis and cancer evolution via formation of polyploid giant cancer cell [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 108.
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Mass, Elvira, Ivan Ballesteros, Matthias Farlik, Florian Halbritter, Johanna Klughammer, Christoph Bock i Frederic Geissmann. "Establishment of tissue-resident macrophage core and tissue specific programs during embryogenesis". Journal of Immunology 196, nr 1_Supplement (1.05.2016): 52.14. http://dx.doi.org/10.4049/jimmunol.196.supp.52.14.
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Abstract Tissue resident macrophages develop during embryogenesis, are maintained independently of hematopoietic stem cells during adulthood, and display tissue-specific functions and phenotypes. To understand the genetic program that drives macrophage differentiation from distinct progenitors and their tissue-specific identity, we performed a systematic spatio-temporal analysis of macrophage development in mice. Transcriptional and in situ analyses revealed that a core macrophage program is established very early and within a short time window and is conserved throughout fetal development and in adult macrophages. A new genetic mouse model supports the transcriptional data as it allows to specifically label differentiating macrophages, and therefore targets adult macrophages in all tissues. Interestingly, immediately after colonization of the target tissue, we could identify tissue-specific macrophage programs that are maintained until adulthood. Additionally, we identified a novel transcriptional regulator, which is expressed in early fetal liver macrophages, and whose inactivation results in an impaired Kupffer cell development. In summary, we present a macrophage developmental atlas, identify novel tissue-specific markers and transcriptional regulators, and show that tissue specialization is mainly influenced by ontogenetic gene expression programs.
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Jorgensen, A., J. E. Nielsen, M. Blomberg Jensen, N. Graem i E. Rajpert-De Meyts. "Analysis of meiosis regulators in human gonads: a sexually dimorphic spatio-temporal expression pattern suggests involvement of DMRT1 in meiotic entry". Molecular Human Reproduction 18, nr 11 (16.08.2012): 523–34. http://dx.doi.org/10.1093/molehr/gas030.
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Serrano-Durán, Rafael, Diana López-Farfán i Elena Gómez-Díaz. "Epigenetic and Epitranscriptomic Gene Regulation in Plasmodium falciparum and How We Can Use It against Malaria". Genes 13, nr 10 (27.09.2022): 1734. http://dx.doi.org/10.3390/genes13101734.
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Malaria, caused by Plasmodium parasites, is still one of the biggest global health challenges. P. falciparum is the deadliest species to humans. In this review, we discuss how this parasite develops and adapts to the complex and heterogenous environments of its two hosts thanks to varied chromatin-associated and epigenetic mechanisms. First, one small family of transcription factors, the ApiAP2 proteins, functions as master regulators of spatio-temporal patterns of gene expression through the parasite life cycle. In addition, chromatin plasticity determines variable parasite cell phenotypes that link to parasite growth, virulence and transmission, enabling parasite adaptation within host conditions. In recent years, epitranscriptomics is emerging as a new regulatory layer of gene expression. We present evidence of the variety of tRNA and mRNA modifications that are being characterized in Plasmodium spp., and the dynamic changes in their abundance during parasite development and cell fate. We end up outlining that new biological systems, like the mosquito model, to decipher the unknowns about epigenetic mechanisms in vivo; and novel methodologies, to study the function of RNA modifications; are needed to discover the Achilles heel of the parasite. With this new knowledge, future strategies manipulating the epigenetics and epitranscriptomic machinery of the parasite have the potential of providing new weapons against malaria.
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Héraud, Pinault, Lagrée i Moreau. "p190RhoGAPs, the ARHGAP35- and ARHGAP5-Encoded Proteins, in Health and Disease". Cells 8, nr 4 (12.04.2019): 351. http://dx.doi.org/10.3390/cells8040351.
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Small guanosine triphosphatases (GTPases) gathered in the Rat sarcoma (Ras) superfamily represent a large family of proteins involved in several key cellular mechanisms. Within the Ras superfamily, the Ras homolog (Rho) family is specialized in the regulation of actin cytoskeleton-based mechanisms. These proteins switch between an active and an inactive state, resulting in subsequent inhibiting or activating downstream signals, leading finally to regulation of actin-based processes. The On/Off status of Rho GTPases implicates two subsets of regulators: GEFs (guanine nucleotide exchange factors), which favor the active GTP (guanosine triphosphate) status of the GTPase and GAPs (GTPase activating proteins), which inhibit the GTPase by enhancing the GTP hydrolysis. In humans, the 20 identified Rho GTPases are regulated by over 70 GAP proteins suggesting a complex, but well-defined, spatio-temporal implication of these GAPs. Among the quite large number of RhoGAPs, we focus on p190RhoGAP, which is known as the main negative regulator of RhoA, but not exclusively. Two isoforms, p190A and p190B, are encoded by ARHGAP35 and ARHGAP5 genes, respectively. We describe here the function of each of these isoforms in physiological processes and sum up findings on their role in pathological conditions such as neurological disorders and cancers.
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Klett, Hagen, Lonny Jürgensen, Patrick Most, Martin Busch, Fabian Günther, Gergana Dobreva, Florian Leuschner, David Hassel, Hauke Busch i Melanie Boerries. "Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration". Biomolecules 9, nr 1 (28.12.2018): 11. http://dx.doi.org/10.3390/biom9010011.
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Heart diseases are the leading cause of death for the vast majority of people around the world, which is often due to the limited capability of human cardiac regeneration. In contrast, zebrafish have the capacity to fully regenerate their hearts after cardiac injury. Understanding and activating these mechanisms would improve health in patients suffering from long-term consequences of ischemia. Therefore, we monitored the dynamic transcriptome response of both mRNA and microRNA in zebrafish at 1–160 days post cryoinjury (dpi). Using a control model of sham-operated and healthy fish, we extracted the regeneration specific response and further delineated the spatio-temporal organization of regeneration processes such as cell cycle and heart function. In addition, we identified novel (miR-148/152, miR-218b and miR-19) and previously known microRNAs among the top regulators of heart regeneration by using theoretically predicted target sites and correlation of expression profiles from both mRNA and microRNA. In a cross-species effort, we validated our findings in the dynamic process of rat myoblasts differentiating into cardiomyocytes-like cells (H9c2 cell line). Concluding, we elucidated different phases of transcriptomic responses during zebrafish heart regeneration. Furthermore, microRNAs showed to be important regulators in cardiomyocyte proliferation over time.
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Schweizer, Nina, Nisha Pawar, Matthias Weiss i Helder Maiato. "An organelle-exclusion envelope assists mitosis and underlies distinct molecular crowding in the spindle region". Journal of Cell Biology 210, nr 5 (24.08.2015): 695–704. http://dx.doi.org/10.1083/jcb.201506107.
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The mitotic spindle is a microtubular assembly required for chromosome segregation during mitosis. Additionally, a spindle matrix has long been proposed to assist this process, but its nature has remained elusive. By combining live-cell imaging with laser microsurgery, fluorescence recovery after photobleaching, and fluorescence correlation spectroscopy in Drosophila melanogaster S2 cells, we uncovered a microtubule-independent mechanism that underlies the accumulation of molecules in the spindle region. This mechanism relies on a membranous system surrounding the mitotic spindle that defines an organelle-exclusion zone that is conserved in human cells. Supported by mathematical modeling, we demonstrate that organelle exclusion by a membrane system causes spatio-temporal differences in molecular crowding states that are sufficient to drive accumulation of mitotic regulators, such as Mad2 and Megator/Tpr, as well as soluble tubulin, in the spindle region. This membranous “spindle envelope” confined spindle assembly, and its mechanical disruption compromised faithful chromosome segregation. Thus, cytoplasmic compartmentalization persists during early mitosis to promote spindle assembly and function.
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Sasaki, T., J. Sasaki, K. Watanabe i A. Suzuki. "Non-invasive visualization of the lipid product of class I PI3K in transgenic mouse models". Biochemical Society Transactions 35, nr 2 (20.03.2007): 215–18. http://dx.doi.org/10.1042/bst0350215.
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PI3Ks (phosphoinositide 3-kinases) regulate many critical cellular responses by producing PI(3,4,5)P3 (phosphatidylinositol 3,4,5-trisphosphate). To facilitate the spatio-temporal characterization of PI(3,4,5)P3 in living primary cells, we generated a novel strain of transgenic mice [AktPH (Akt pleckstrin homology domain)–GFP (green fluorescent protein) Tg (transgenic) mice] that express a fluorescent bioprobe for PI(3,4,5)P3/PI(3,4)P2 (phosphatidylinositol 3,4-bisphosphate). By crossing AktPH–GFP Tg mice with strains of gene-targeted ‘knockout’ mice lacking a particular phosphoinositide-metabolizing enzyme, we have been able to evaluate the contribution of each enzyme to PI(3,4,5)P3 localization in migrating neutrophils. Our results indicate that PI3Kγ and the PI(3,4,5)P3 phosphatase SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase-1] are the key regulators of PI(3,4,5)P3 dynamics during fMet-Leu-Phe (N-formylmethionyl-leucylphenylalanine; ‘chemotactic peptide’)-stimulated neutrophil migration. Our study has also validated the fluorescent transgenic strategy for studying PI(3,4,5)P3 metabolism in physiological and pathological situations.
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Salameh, Ala A. M., Matilde García-Valdecasas Ojeda, María Jesús Esteban-Parra, Yolanda Castro-Díez i Sonia R. Gámiz-Fortis. "Extreme Rainfall Indices in Southern Levant and Related Large-Scale Atmospheric Circulation Patterns: A Spatial and Temporal Analysis". Water 14, nr 23 (22.11.2022): 3799. http://dx.doi.org/10.3390/w14233799.
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This study aims to provide a comprehensive spatio-temporal analysis of the annual and seasonal extreme rainfall indices over the southern Levant from 1970 to 2020. For this, temporal and spatial trends of 15 climate extreme indices based on daily precipitation at 66 stations distributed across Israel and Palestine territories were annually and seasonally analyzed through the nonparametric Mann–Kendall test and the Sen’s slope estimator. The annual averages for frequency-based extreme indices exhibited decreasing trends, significantly for the Consecutive Dry Days. In contrast, the percentiles- and intensity-based extreme indices showed increasing trends, significant for extremely wet days, Max 1- and 3-day precipitation amount indices. The study area had expanding periods of extreme dry spells for spring and correspondingly shortening extreme wet spells for spring, winter and the combined winter–spring. Moreover, most of spring indices showed negative trends. Conversely, most winter indices displayed positive trends. Regarding the influence of large-scale circulation patterns, the North Sea Caspian pattern, the Western Mediterranean Oscillation, and ENSO were the primary regulators of the winter, spring, and autumn extreme indices, respectively. These findings contribute to a better understanding of extreme rainfall variability in the Levant region and could be utilized in the management of water resources, drought monitoring, and flood control.
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Patsoukis, Nikolaos, Esther M. Lafuente, Paul Meraner, Lequn Li, David Dombkowski, Anjana Rao i Vassiliki Boussiotis. "RIAM Regulate Spatio-Temporal Distribution of PLC-γ1 and Calcium Mobilization during T Cell Activation". Blood 112, nr 11 (16.11.2008): 673. http://dx.doi.org/10.1182/blood.v112.11.673.673.
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Abstract T cell receptor (TCR) ligation induces rapid polarization of the actin cytoskeleton resulting in the formation of the immunological synapse (IS), recruitment of signaling molecules, and initiation of signaling cascades leading to T cell activation. Specific recruitment, redistribution and organization of signaling molecules in the IS is facilitated by lipid raft microdomains, which provide a scaffold for focal protein assembly. Fyn and ZAP-70 are the most proximal TCR signaling molecules that localize in the IS and are redistributed in the lipid rafts during T cell activation. Currently, it is poorly understood how signals originating from the TCR are linked to specific mechanisms that regulate T cell activation. We have identified RIAM, an adaptor molecule that contains a RA (Ras Association) domain, a PH (Plekstrin Homology) domain and proline-rich motifs. RIAM interacts with active GTP-bound Rap1 and with regulators of the actin cytoskeleton Evl, VASP and Profilin. RIAM also interacts with ADAP/SKAP-55 and, thereby, is recruited to the plasma membrane during T cell activation. We have previously determined that, during TCR ligation by antigen, RIAM localizes at the IS and the lipid rafts and serves as a substrate for Fyn and ZAP-70. Because of these properties, we examined whether RIAM might be involved in regulating the molecular and functional outcome of T cell activation. Using RIAM-knock down (KD) T cells in which endogenous RIAM was depleted by siRNA, we determined that RIAM was necessary for IL-2 transcription and RIAM-KD cells had impaired capacity for IL-2 production in response to stimulation with SEE-loaded APC or to TCR/CD3-plus-CD28 crosslinking. However, despite the impaired IL-2 production, analysis of TCR-proximal signaling events did not show impairment of ZAP-70 phosphorylation or formation of the LAT signalosome comprised of phosphorylated PLC-γ1, SLP-76 and Vav1. TCR triggering of both control and RIAM-KD cells also resulted in similar phosphorylation of PLC-γ1. Activation of PLC-γ1 leads to the generation of InsP3 and diacylglycerol from phosphatidylinositol-4,5-bisphosphate (PtdIns (4,5)P2). InsP3 binds to InsP3 receptors and triggers Ca2+ release from intracellular stores. Strikingly, TCR triggering of RIAM-KD cells resulted in markedly reduced upregulation of InsP3 compared to that in control T cells. Consistent with the defective upregulation of InsP3, calcium flux of RIAM-KD cells was dramatically impaired. This event was due to the impaired InsP3-mediated calcium release from the endoplasmic reticulum and not due to impaired store content or impaired calcium release-activated calcium (CRAC) channel entry as determined by using the Ca2+ ATPase blocker thapsigargin, which resulted in abundant calcium release in RIAM-KD cells. To analyze the consequences of deregulated InsP3 production and to investigate whether RIAM is specifically involved in PLC-γ1-mediated processes we evaluated activation of several signaling events on which PLC-γ1 activation has distinct effects. Whereas activation of the extracellular signal regulated kinases MEK1/2 and Erk1/2 that are PLC-γ1 and Ca2+-dependent, was impaired in the absence of RIAM, activation of p38 and IKK was unaltered compared to control T cells. These results are consistent with a specific role of RIAM in InsP3-mediated Ca2+ release and indicate that deletion of RIAM does not result in a generalized defect in TCR-mediated signaling. Activation of PLC-γ1 at the cell membrane for proper generation of InsP3 requires appropriate docking and positioning of PLC-γ1. For this reason, we examined whether RIAM interacted with PLC-γ1 and regulated its subcellular localization after T cell activation. Detailed analysis by in vivo co-precipitation experiments in cell lysates and by in vitro association assays of purified proteins revealed a direct RIAM-PLC-γ1 interaction that was mediated via the SH3 domain of PLC-γ1. Furthermore, subcellular fractionation into cytoplasmic and cytoskeletal fractions revealed that PLC-γ1 translocated to the cytoskeleton upon T cell activation and this event was abrogated in RIAM-KD cells. These results indicate a novel and unexpected role of RIAM in T cell responses that involves regulation of spatio-temporal distribution and activation of PLC-γ1, leading to generation of InsP3 and Ca2+ mobilization after T cell receptor triggering.
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Emig, Ramona, Callum M. Zgierski-Johnston, Viviane Timmermann, Andrew J. Taberner, Martyn P. Nash, Peter Kohl i Rémi Peyronnet. "Passive myocardial mechanical properties: meaning, measurement, models". Biophysical Reviews 13, nr 5 (październik 2021): 587–610. http://dx.doi.org/10.1007/s12551-021-00838-1.
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AbstractPassive mechanical tissue properties are major determinants of myocardial contraction and relaxation and, thus, shape cardiac function. Tightly regulated, dynamically adapting throughout life, and affecting a host of cellular functions, passive tissue mechanics also contribute to cardiac dysfunction. Development of treatments and early identification of diseases requires better spatio-temporal characterisation of tissue mechanical properties and their underlying mechanisms. With this understanding, key regulators may be identified, providing pathways with potential to control and limit pathological development. Methodologies and models used to assess and mimic tissue mechanical properties are diverse, and available data are in part mutually contradictory. In this review, we define important concepts useful for characterising passive mechanical tissue properties, and compare a variety of in vitro and in vivo techniques that allow one to assess tissue mechanics. We give definitions of key terms, and summarise insight into determinants of myocardial stiffness in situ. We then provide an overview of common experimental models utilised to assess the role of environmental stiffness and composition, and its effects on cardiac cell and tissue function. Finally, promising future directions are outlined.
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Noatynska, Anna, Nicolas Tavernier, Monica Gotta i Lionel Pintard. "Coordinating cell polarity and cell cycle progression: what can we learn from flies and worms?" Open Biology 3, nr 8 (sierpień 2013): 130083. http://dx.doi.org/10.1098/rsob.130083.
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Spatio-temporal coordination of events during cell division is crucial for animal development. In recent years, emerging data have strengthened the notion that tight coupling of cell cycle progression and cell polarity in dividing cells is crucial for asymmetric cell division and ultimately for metazoan development. Although it is acknowledged that such coupling exists, the molecular mechanisms linking the cell cycle and cell polarity machineries are still under investigation. Key cell cycle regulators control cell polarity, and thus influence cell fate determination and/or differentiation, whereas some factors involved in cell polarity regulate cell cycle timing and proliferation potential. The scope of this review is to discuss the data linking cell polarity and cell cycle progression, and the importance of such coupling for asymmetric cell division. Because studies in model organisms such as Caenorhabditis elegans and Drosophila melanogaster have started to reveal the molecular mechanisms of this coordination, we will concentrate on these two systems. We review examples of molecular mechanisms suggesting a coupling between cell polarity and cell cycle progression.
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Zibetti, Cristina. "Deciphering the Retinal Epigenome during Development, Disease and Reprogramming: Advancements, Challenges and Perspectives". Cells 11, nr 5 (25.02.2022): 806. http://dx.doi.org/10.3390/cells11050806.
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Retinal neurogenesis is driven by concerted actions of transcription factors, some of which are expressed in a continuum and across several cell subtypes throughout development. While seemingly redundant, many factors diversify their regulatory outcome on gene expression, by coordinating variations in chromatin landscapes to drive divergent retinal specification programs. Recent studies have furthered the understanding of the epigenetic contribution to the progression of age-related macular degeneration, a leading cause of blindness in the elderly. The knowledge of the epigenomic mechanisms that control the acquisition and stabilization of retinal cell fates and are evoked upon damage, holds the potential for the treatment of retinal degeneration. Herein, this review presents the state-of-the-art approaches to investigate the retinal epigenome during development, disease, and reprogramming. A pipeline is then reviewed to functionally interrogate the epigenetic and transcriptional networks underlying cell fate specification, relying on a truly unbiased screening of open chromatin states. The related work proposes an inferential model to identify gene regulatory networks, features the first footprinting analysis and the first tentative, systematic query of candidate pioneer factors in the retina ever conducted in any model organism, leading to the identification of previously uncharacterized master regulators of retinal cell identity, such as the nuclear factor I, NFI. This pipeline is virtually applicable to the study of genetic programs and candidate pioneer factors in any developmental context. Finally, challenges and limitations intrinsic to the current next-generation sequencing techniques are discussed, as well as recent advances in super-resolution imaging, enabling spatio-temporal resolution of the genome.
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Rezki, Samir, Claire Campion, Beatrice Iacomi-Vasilescu, Anne Preveaux, Youness Toualbia, Sophie Bonneau, Martial Briand i in. "Differences in stability of seed-associated microbial assemblages in response to invasion by phytopathogenic microorganisms". PeerJ 4 (11.04.2016): e1923. http://dx.doi.org/10.7717/peerj.1923.
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Seeds are involved in the vertical transmission of microorganisms from one plant generation to another and consequently act as reservoirs for the plant microbiota. However, little is known about the structure of seed-associated microbial assemblages and the regulators of assemblage structure. In this work, we have assessed the response of seed-associated microbial assemblages ofRaphanus sativusto invading phytopathogenic agents, the bacterial strainXanthomonas campestrispv.campestris(Xcc) 8004 and the fungal strainAlternaria brassicicolaAbra43. According to the indicators of bacterial (16S rRNA gene andgyrBsequences) and fungal (ITS1) diversity employed in this study, seed transmission of the bacterial strainXcc8004 did not change the overall composition of resident microbial assemblages. In contrast seed transmission of Abra43 strongly modified the richness and structure of fungal assemblages without affecting bacterial assemblages. The sensitivity of seed-associated fungal assemblage to Abra43 is mostly related to changes in relative abundance of closely related fungal species that belong to theAlternariagenus. Variation in stability of the seed microbiota in response toXccand Abra43 invasions could be explained by differences in seed transmission pathways employed by these micro-organisms, which ultimately results in divergence in spatio-temporal colonization of the seed habitat.
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Pichura, Vitalii, Yevhenii Domaratskiy, Larisa Potravka, Oleksandra Biloshkurenko i Andrey Dobrovol’skiy. "Application of the Research on Spatio-Temporal Differentiation of a Vegetation Index in Evaluating Sunflower Hybrid Plasticity and Growth-Regulators in the Steppe Zone of Ukraine". Journal of Ecological Engineering 24, nr 6 (1.06.2023): 144–65. http://dx.doi.org/10.12911/22998993/162782.
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Miro, Julie, Anne-Laure Bougé, Eva Murauer, Emmanuelle Beyne, Dylan Da Cunha, Mireille Claustres, Michel Koenig i Sylvie Tuffery-Giraud. "First Identification of RNA-Binding Proteins That Regulate Alternative Exons in the Dystrophin Gene". International Journal of Molecular Sciences 21, nr 20 (21.10.2020): 7803. http://dx.doi.org/10.3390/ijms21207803.
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The Duchenne muscular dystrophy (DMD) gene has a complex expression pattern regulated by multiple tissue-specific promoters and by alternative splicing (AS) of the resulting transcripts. Here, we used an RNAi-based approach coupled with DMD-targeted RNA-seq to identify RNA-binding proteins (RBPs) that regulate splicing of its skeletal muscle isoform (Dp427m) in a human muscular cell line. A total of 16 RBPs comprising the major regulators of muscle-specific splicing events were tested. We show that distinct combinations of RBPs maintain the correct inclusion in the Dp427m of exons that undergo spatio-temporal AS in other dystrophin isoforms. In particular, our findings revealed the complex networks of RBPs contributing to the splicing of the two short DMD exons 71 and 78, the inclusion of exon 78 in the adult Dp427m isoform being crucial for muscle function. Among the RBPs tested, QKI and DDX5/DDX17 proteins are important determinants of DMD exon inclusion. This is the first large-scale study to determine which RBP proteins act on the physiological splicing of the DMD gene. Our data shed light on molecular mechanisms contributing to the expression of the different dystrophin isoforms, which could be influenced by a change in the function or expression level of the identified RBPs.
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Li, Qiaowei, Liyuan Wang, Kai Xing, Yalan Yang, Adeyinka Abiola Adetula, Yuwen Liu, Guoqiang Yi, Hongfu Zhang, Torres Sweeney i Zhonglin Tang. "Identification of circRNAs Associated with Adipogenesis Based on RNA-seq Data in Pigs". Genes 13, nr 11 (7.11.2022): 2062. http://dx.doi.org/10.3390/genes13112062.
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Adipocytes or fat cells play a vital role in the storage and release of energy in pigs, and many circular RNAs (circRNAs) have emerged as important regulators in various tissues and cell types in pigs. However, the spatio-temporal expression pattern of circRNAs between different adipose deposition breeds remains elusive. In this study, RNA sequencing (RNA-seq) produced transcriptome profiles of Western Landrace (lean-type) and Chinese Songliao black pigs (obese-type) with different thicknesses of subcutaneous fat tissues and were used to identify circRNAs involved in the regulation of adipogenesis. Gene expression analysis revealed 883 circRNAs, among which 26 and 11 circRNAs were differentially expressed between Landrace vs. Songliao pigs and high- vs. low-thickness groups, respectively. We also analyzed the interaction between circRNAs and microRNAs (miRNAs) and constructed their interaction network in adipogenesis; gene ontology classification and pathway analysis revealed two vital circRNAs, with the majority of their target genes enriched in biological functions such as fatty acids biosynthesis, fatty acid metabolism, and Wnt/TGF-β signaling pathways. These candidate circRNAs can be taken as potential targets for further experimental studies. Our results show that circRNAs are dynamically expressed and provide a valuable basis for understanding the molecular mechanism of circRNAs in pig adipose biology.
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Park, Jiwon, i Carsten Gram Hansen. "Cellular feedback dynamics and multilevel regulation driven by the hippo pathway". Biochemical Society Transactions 49, nr 4 (10.08.2021): 1515–27. http://dx.doi.org/10.1042/bst20200253.
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The Hippo pathway is a dynamic cellular signalling nexus that regulates differentiation and controls cell proliferation and death. If the Hippo pathway is not precisely regulated, the functionality of the upstream kinase module is impaired, which increases nuclear localisation and activity of the central effectors, the transcriptional co-regulators YAP and TAZ. Pathological YAP and TAZ hyperactivity consequently cause cancer, fibrosis and developmental defects. The Hippo pathway controls an array of fundamental cellular processes, including adhesion, migration, mitosis, polarity and secretion of a range of biologically active components. Recent studies highlight that spatio-temporal regulation of Hippo pathway components are central to precisely controlling its context-dependent dynamic activity. Several levels of feedback are integrated into the Hippo pathway, which is further synergized with interactors outside of the pathway that directly regulate specific Hippo pathway components. Likewise, Hippo core kinases also ‘moonlight’ by phosphorylating multiple substrates beyond the Hippo pathway and thereby integrates further flexibility and robustness in the cellular decision-making process. This topic is still in its infancy but promises to reveal new fundamental insights into the cellular regulation of this therapeutically important pathway. We here highlight recent advances emphasising feedback dynamics and multilevel regulation of the Hippo pathway with a focus on mitosis and cell migration, as well as discuss potential productive future research avenues that might reveal novel insights into the overall dynamics of the pathway.
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Sello, Cornelius Tlotliso, Chang Liu, Hongtao Lu, Ziqiu Wang, Petunia Msuthwana, Thobela Louis Tyasi, Yue Sun i in. "Variations in the Expression Pattern of HSP27 and MSK1 Genes During the Development of Prehierarchical Follicles in the Zi Geese (Anser Cygnoides)". Annals of Animal Science 20, nr 1 (1.01.2020): 43–53. http://dx.doi.org/10.2478/aoas-2019-0048.
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AbstractThe p38MAPKs (mitogen-activated protein kinases) signaling contributes a pivotal role in mammalian ovarian follicular development; however, the knowledge regarding their expression in geese remains unresolved. The objective of the current study was to determine the spatio-temporal expression of heat shock protein 27 (HSP27) and mitogen- and stress-activated protein kinase 1 (MSK1) genes in the prehierarchical follicles during geese ovarian development. The prehierarchical follicles samples were harvested from 35- to 37-week-old healthy laying geese. HSP27 and MSK1 relative expression in various sized prehierachical follicles was detected by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. Follicular wall localization of HSP27 and MSK1 was examined by using immunohistochemistry. Our results at mRNA level indicated that HSP27 was highly expressed in middle white follicles whereas MSK1 was predominantly expressed in small white follicles. The western blotting results for HSP27 and MSK1 were inconsistent with the RT-qPCR results in various stages of prehierachical follicular development but noticeably, HSP27 proteins were still expressed more in middle white follicles while MSK1 proteins were more abundant in primary follicles. At different stages of prehierarchical development, immunodetections in the granulosa and theca cells revealed that HSP27 was intensively localized in middle white follicles while strong detections of MSK1 were observed in large white follicles. These results indicate HSP27 and MSK1 might be associated to the key regulators of folliculogenesis in geese.
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Ramezanidoraki, Nasim, Driss El Ouardi, Margaux Le, Stéphanie Moriceau, Mahboubeh Ahmadi, Dossi Elena, Danae Rolland i in. "Activation of the PI3K/AKT/mTOR Pathway in Cajal–Retzius Cells Leads to Their Survival and Increases Susceptibility to Kainate-Induced Seizures". International Journal of Molecular Sciences 24, nr 6 (11.03.2023): 5376. http://dx.doi.org/10.3390/ijms24065376.
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Cajal–Retzius cells (CRs) are a class of transient neurons in the mammalian cortex that play a critical role in cortical development. Neocortical CRs undergo almost complete elimination in the first two postnatal weeks in rodents and the persistence of CRs during postnatal life has been detected in pathological conditions related to epilepsy. However, it is unclear whether their persistence is a cause or consequence of these diseases. To decipher the molecular mechanisms involved in CR death, we investigated the contribution of the PI3K/AKT/mTOR pathway as it plays a critical role in cell survival. We first showed that this pathway is less active in CRs after birth before massive cell death. We also explored the spatio-temporal activation of both AKT and mTOR pathways and reveal area-specific differences along both the rostro–caudal and medio–lateral axes. Next, using genetic approaches to maintain an active pathway in CRs, we found that the removal of either PTEN or TSC1, two negative regulators of the pathway, lead to differential CR survivals, with a stronger effect in the Pten model. Persistent cells in this latter mutant are still active. They express more Reelin and their persistence is associated with an increase in the duration of kainate-induced seizures in females. Altogether, we show that the decrease in PI3K/AKT/mTOR activity in CRs primes these cells to death by possibly repressing a survival pathway, with the mTORC1 branch contributing less to the phenotype.
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Bianchi, Greta, Stefania Brocca, Sonia Longhi i Vladimir N. Uversky. "Liaisons dangereuses: Intrinsic Disorder in Cellular Proteins Recruited to Viral Infection-Related Biocondensates". International Journal of Molecular Sciences 24, nr 3 (21.01.2023): 2151. http://dx.doi.org/10.3390/ijms24032151.
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Liquid–liquid phase separation (LLPS) is responsible for the formation of so-called membrane-less organelles (MLOs) that are essential for the spatio-temporal organization of the cell. Intrinsically disordered proteins (IDPs) or regions (IDRs), either alone or in conjunction with nucleic acids, are involved in the formation of these intracellular condensates. Notably, viruses exploit LLPS at their own benefit to form viral replication compartments. Beyond giving rise to biomolecular condensates, viral proteins are also known to partition into cellular MLOs, thus raising the question as to whether these cellular phase-separating proteins are drivers of LLPS or behave as clients/regulators. Here, we focus on a set of eukaryotic proteins that are either sequestered in viral factories or colocalize with viral proteins within cellular MLOs, with the primary goal of gathering organized, predicted, and experimental information on these proteins, which constitute promising targets for innovative antiviral strategies. Using various computational approaches, we thoroughly investigated their disorder content and inherent propensity to undergo LLPS, along with their biological functions and interactivity networks. Results show that these proteins are on average, though to varying degrees, enriched in disorder, with their propensity for phase separation being correlated, as expected, with their disorder content. A trend, which awaits further validation, tends to emerge whereby the most disordered proteins serve as drivers, while more ordered cellular proteins tend instead to be clients of viral factories. In light of their high disorder content and their annotated LLPS behavior, most proteins in our data set are drivers or co-drivers of molecular condensation, foreshadowing a key role of these cellular proteins in the scaffolding of viral infection-related MLOs.
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Pollard, Alison J., Colette Sparey, Stephen C. Robson, Adrian R. Krainer i G. Nicholas Europe-Finner. "Spatio-Temporal Expression of the Trans-Acting Splicing Factors SF2/ASF and Heterogeneous Ribonuclear Proteins A1/A1B in the Myometrium of the Pregnant Human Uterus: A Molecular Mechanism for Regulating Regional Protein Isoform Expression in Vivo*". Journal of Clinical Endocrinology & Metabolism 85, nr 5 (1.05.2000): 1928–36. http://dx.doi.org/10.1210/jcem.85.5.6537.
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Abstract Many of the human myometrial proteins associated with uterine quiescence and the switch to coordinated contractions at the onset of labor exist as alternatively spliced isoforms. There is now extensive evidence to indicate that the nuclear concentrations of the trans-acting splicing regulators SF2/ASF and hnRNP A1/A1B are fundamental in regulating the expression of specific protein isoforms derived from alternative splicing of single precursor messenger ribonucleic acid transcripts. The question thus arose as to whether these factors were also involved in regulating the expression of specific myometrial protein species within different uterine regions during human gestation and parturition. SF2/ASF and hnRNP A1/A1B expression was therefore determined in paired upper (corpus) and lower segment myometrial samples taken from individual women at term/during spontaneous labor and compared with nonpregnant control samples using specific monoclonal antibodies. We report that SF2/ASF levels were substantially increased in the lower uterine region, and this was associated with a parallel decrease in levels of hnRNP A1/A1B during gestation. Conversely, the opposite pattern was observed within the upper uterine region during pregnancy, where hnRNP A1/A1B was significantly up-regulated and SF2/ASF levels were much less than those found in the lower uterine segment. The differential expression of hnRNP A1/A1B and SF2/ASF in the upper and lower uterine segments may have a primary role in defining the formation of specific myometrial protein species associated with the known contractile and relaxatory properties of these regions before and during parturition.
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Zinzen, Robert P., Charles Girardot, Julien Gagneur, Martina Braun i Eileen E. M. Furlong. "Combinatorial binding predicts spatio-temporal cis-regulatory activity". Nature 462, nr 7269 (listopad 2009): 65–70. http://dx.doi.org/10.1038/nature08531.
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Zhou, Li-hua, Yu-qin Li, Yong-quan Li i Dan Wu. "Spatio-temporal expression of the pathway−specific regulatory generedDinS. coelicolor". Journal of Zhejiang University SCIENCE 6B, nr 6 (czerwiec 2005): 464–69. http://dx.doi.org/10.1631/jzus.2005.b0464.
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Scacchi, E., P. Salinas, B. Gujas, L. Santuari, N. Krogan, L. Ragni, T. Berleth i C. S. Hardtke. "Spatio-temporal sequence of cross-regulatory events in root meristem growth". Proceedings of the National Academy of Sciences 107, nr 52 (13.12.2010): 22734–39. http://dx.doi.org/10.1073/pnas.1014716108.
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Juillot, Samuel, Hannes M. Beyer, Josef Madl, Wilfried Weber, Matias D. Zurbriggen i Winfried Römer. "Signalling to the nucleus under the control of light and small molecules". Molecular BioSystems 12, nr 2 (2016): 345–49. http://dx.doi.org/10.1039/c5mb00763a.
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One major regulatory mechanism in cell signalling is the spatio-temporal control of the localization of signalling molecules. We synthetically designed an entire cell signalling pathway, which allows controlling the transport of signalling molecules from the plasma membrane to the nucleus, by using light and small molecules.
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Rashkov, Peter, Bernhard A. Schmitt, Daniela Keilberg, Lotte Søgaard-Andersen i Stephan Dahlke. "A model for spatio-temporal dynamics in a regulatory network for cell polarity". Mathematical Biosciences 258 (grudzień 2014): 189–200. http://dx.doi.org/10.1016/j.mbs.2014.10.005.
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Kim, Yujin, i Joon-Yong An. "Spatio-Temporal Roles of ASD-Associated Variants in Human Brain Development". Genes 11, nr 5 (11.05.2020): 535. http://dx.doi.org/10.3390/genes11050535.
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Transcriptional regulation of the genome arguably provides the basis for the anatomical elaboration and dynamic operation of the human brain. It logically follows that genetic variations affecting gene transcription contribute to mental health disorders, including autism spectrum disorder (ASD). A number of recent studies have shown the role of de novo variants (DNVs) in disrupting early neurodevelopment. However, there is limited knowledge concerning the role of inherited variants during the early brain development of ASD. In this study, we investigate the role of rare inherited variations in neurodevelopment. We conducted co-expression network analyses using an anatomically comprehensive atlas of the developing human brain and examined whether rare coding and regulatory variants, identified from our genetic screening of Australian families with ASD, work in different spatio-temporal functions.
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Guimond, S., K. Turner, M. Kita, M. Ford-Perriss i J. Turnbull. "Dynamic biosynthesis of heparan sulphate sequences in developing mouse brain: a potential regulatory mechanism during development". Biochemical Society Transactions 29, nr 2 (1.05.2001): 177–81. http://dx.doi.org/10.1042/bst0290177.
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Over recent years our understanding of the functions of the heparan sulphate (HS) family of complex polysaccharides has shifted dramatically. Once seen as simply structural scaffolding in the extracellular matrix, they are now viewed as critical players in the regulatory network of cells. They are strategically located at the cell surface and in the extracellular matrix, and there has been an increasing realization that specific sequences in the HS chains are designed for selective interactions with many proteins. Functionally, these interactions result in regulation of the protein activities. It is becoming clear that HS functions as a new class of multifunctional cell regulator. There is also growing evidence that cells can dynamically alter the structure of HS sequences that they express. Here we review recent developments and describe evidence for regulated changes in the synthesis and structure of HS chains expressed during early mouse brain development. The data suggest a new concept in which dynamic changes in biosynthesis of different HS sequences create distinct cellular HS repertoires, the heparanome [1]. Their expression, in specific spatio-temporal patterns, is likely to endow organisms with novel regulatory mechanisms for controlling the activity of specific HS-binding proteins.
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Dong, Peng, i Zhe Liu. "Shaping development by stochasticity and dynamics in gene regulation". Open Biology 7, nr 5 (maj 2017): 170030. http://dx.doi.org/10.1098/rsob.170030.
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Animal development is orchestrated by spatio-temporal gene expression programmes that drive precise lineage commitment, proliferation and migration events at the single-cell level, collectively leading to large-scale morphological change and functional specification in the whole organism. Efforts over decades have uncovered two ‘seemingly contradictory’ mechanisms in gene regulation governing these intricate processes: (i) stochasticity at individual gene regulatory steps in single cells and (ii) highly coordinated gene expression dynamics in the embryo. Here we discuss how these two layers of regulation arise from the molecular and the systems level, and how they might interplay to determine cell fate and to control the complex body plan. We also review recent technological advancements that enable quantitative analysis of gene regulation dynamics at single-cell, single-molecule resolution. These approaches outline next-generation experiments to decipher general principles bridging gaps between molecular dynamics in single cells and robust gene regulations in the embryo.
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Vannoppen, Astrid, Jeroen Degerickx, Niels Souverijns i Anne Gobin. "Spatio-Temporal Dynamics in Grasslands Using the Landsat Archive". Land 12, nr 4 (21.04.2023): 934. http://dx.doi.org/10.3390/land12040934.
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Grasslands are an important biotope in Europe, not only because they are widespread, but also because they provide valuable ecosystem services. The ecological value of a grassland parcel is directly proportional to the number of uninterrupted years of grassland cover. However, the area of long-term grassland (i.e., grassland of 5 years or older) is decreasing, limiting its ability to provide ecosystem services. To prevent the further disappearance of long-term grasslands, Europe developed an agricultural policy instrument in 2003 to protect grasslands of 5 years or older. Nature policy instruments aim to protect grasslands that have existed for more than 10 years to support their high environmental value. However, there is currently no multi-annual information on the location and age of grasslands at a high spatial and temporal resolution, which makes it difficult to assess the effectiveness of the current grassland protection regulations. Multi-annual satellite-based land cover classification can provide a solution for grassland area and age monitoring, which we tested by producing a series of Landsat-based land cover classification maps from 2005 to 2019 for the region of Flanders, Belgium. Historical land cover classification maps proved useful for evaluating past and present planning and policy to ensure grassland conservation, linking spatial and temporal changes in the area of long-term grasslands with policy changes and landscape dynamics. We were able to locate grasslands that were grassland between 2005 and 2014 but were converted to arable land between 2015 and 2019, identify the year in which these grasslands were converted to arable land, and demonstrate regional differences in the conservation of long-term grassland aged 5–9 years and 10 years or more. Long-term grassland aged 10 years or more disappeared faster in urban than in rural areas in Flanders between 2014 and 2019. Our study shows that multi-annual high-resolution satellite imagery provides objective and quantitative information on long-term grassland to support climate, agricultural, environmental, and nature policies.
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Kim, Juhuhn, Michael T. M. Emmerich, Robert Voors, Barend Ording i Jong-Seok Lee. "A Systematic Approach to Identify Shipping Emissions Using Spatio-Temporally Resolved TROPOMI Data". Remote Sensing 15, nr 13 (7.07.2023): 3453. http://dx.doi.org/10.3390/rs15133453.
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Stringent global regulations aim to reduce nitrogen dioxide (NO2) emissions from maritime shipping. However, the lack of a global monitoring system makes compliance verification challenging. To address this issue, we propose a systematic approach to monitor shipping emissions using unsupervised clustering techniques on spatio-temporal georeferenced data, specifically NO2 measurements obtained from the TROPOspheric Monitoring Instrument (TROPOMI) on board the Copernicus Sentinel-5 Precursor satellite. Our method involves partitioning spatio-temporally resolved measurements based on the similarity of NO2 column levels. We demonstrate the reproducibility of our approach through rigorous testing and validation using data collected from multiple regions and time periods. Our approach improves the spatial correlation coefficients between NO2 column clusters and shipping traffic frequency. Additionally, we identify a temporal correlation between NO2 column levels along shipping routes and the global container throughput index. We expect that our approach may serve as a prototype for a tool to identify anthropogenic maritime emissions, distinguishing them from background sources.
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Alzahrani, Talal. "Spatio-Temporal Modeling of Immune Response to SARS-CoV-2 Infection". Mathematics 9, nr 24 (16.12.2021): 3274. http://dx.doi.org/10.3390/math9243274.
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COVID-19 is a disease occurring as a result of infection by a novel coronavirus called SARS-CoV-2. Since the WHO announced COVID-19 as a global pandemic, mathematical works have taken place to simulate infection scenarios at different scales even though the majority of these models only consider the temporal dynamics of SARS-COV-2. In this paper, we present a new spatio-temporal within-host mathematical model of COVID-19, accounting for the coupled dynamics of healthy cells, infected cells, SARS-CoV-2 molecules, chemokine concentration, effector T cells, regulatory T cells, B-lymphocytes cells and antibodies. We develop a computational framework involving discretisation schemes for diffusion and chemotaxis terms using central differences and midpoint approximations within two dimensional space combined with a predict–evaluate–correct mode for time marching. Then, we numerically investigate the model performance using a list of values simulating the baseline scenario for viral infection at a cellular scale. Moreover, we explore the model sensitivity via applying certain conditions to observe the model validity in a comparison with clinical outcomes collected from recent studies. In this computational investigation, we have a numerical range of 104 to 108 for the viral load peak, which is equivalent to what has been obtained from throat swab samples for many patients.
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Lee, Bogyeong, Sungkook Hong i Hyunsoo Kim. "Determination of workers' compliance to safety regulations using a spatio-temporal graph convolution network". Advanced Engineering Informatics 56 (kwiecień 2023): 101942. http://dx.doi.org/10.1016/j.aei.2023.101942.
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Alzein, Mohamad, Estefanía Lozano-Velasco, Francisco Hernández-Torres, Carlos García-Padilla, Jorge N. Domínguez, Amelia Aránega i Diego Franco. "Differential Spatio-Temporal Regulation of T-Box Gene Expression by microRNAs during Cardiac Development". Journal of Cardiovascular Development and Disease 8, nr 5 (14.05.2021): 56. http://dx.doi.org/10.3390/jcdd8050056.
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Cardiovascular development is a complex process that starts with the formation of symmetrically located precardiac mesodermal precursors soon after gastrulation and is completed with the formation of a four-chambered heart with distinct inlet and outlet connections. Multiple transcriptional inputs are required to provide adequate regional identity to the forming atrial and ventricular chambers as well as their flanking regions; i.e., inflow tract, atrioventricular canal, and outflow tract. In this context, regional chamber identity is widely governed by regional activation of distinct T-box family members. Over the last decade, novel layers of gene regulatory mechanisms have been discovered with the identification of non-coding RNAs. microRNAs represent the most well-studied subcategory among short non-coding RNAs. In this study, we sought to investigate the functional role of distinct microRNAs that are predicted to target T-box family members. Our data demonstrated a highly dynamic expression of distinct microRNAs and T-box family members during cardiogenesis, revealing a relatively large subset of complementary and similar microRNA–mRNA expression profiles. Over-expression analyses demonstrated that a given microRNA can distinctly regulate the same T-box family member in distinct cardiac regions and within distinct temporal frameworks, supporting the notion of indirect regulatory mechanisms, and dual luciferase assays on Tbx2, Tbx3 and Tbx5 3′ UTR further supported this notion. Overall, our data demonstrated a highly dynamic microRNA and T-box family members expression during cardiogenesis and supported the notion that such microRNAs indirectly regulate the T-box family members in a tissue- and time-dependent manner.
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Da Rocha, Martine, Caroline Bournaud, Julie Dazenière, Peter Thorpe, Marc Bailly-Bechet, Clément Pellegrin, Arthur Péré i in. "Genome Expression Dynamics Reveal the Parasitism Regulatory Landscape of the Root-Knot Nematode Meloidogyne incognita and a Promoter Motif Associated with Effector Genes". Genes 12, nr 5 (18.05.2021): 771. http://dx.doi.org/10.3390/genes12050771.
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Root-knot nematodes (genus Meloidogyne) are the major contributor to crop losses caused by nematodes. These nematodes secrete effector proteins into the plant, derived from two sets of pharyngeal gland cells, to manipulate host physiology and immunity. Successful completion of the life cycle, involving successive molts from egg to adult, covers morphologically and functionally distinct stages and will require precise control of gene expression, including effector genes. The details of how root-knot nematodes regulate transcription remain sparse. Here, we report a life stage-specific transcriptome of Meloidogyne incognita. Combined with an available annotated genome, we explore the spatio-temporal regulation of gene expression. We reveal gene expression clusters and predicted functions that accompany the major developmental transitions. Focusing on effectors, we identify a putative cis-regulatory motif associated with expression in the dorsal glands, providing an insight into effector regulation. We combine the presence of this motif with several other criteria to predict a novel set of putative dorsal gland effectors. Finally, we show this motif, and thereby its utility, is broadly conserved across the Meloidogyne genus, and we name it Mel-DOG. Taken together, we provide the first genome-wide analysis of spatio-temporal gene expression in a root-knot nematode and identify a new set of candidate effector genes that will guide future functional analyses.