Auxin is a multifunctional hormone essential for plant development and pattern formation. A nuclear auxin-signaling system controlling auxin-induced gene expression is well established, but ...cytoplasmic auxin signaling, as in its coordination of cell polarization, is unexplored. We found a cytoplasmic auxin-signaling mechanism that modulates the interdigitated growth of Arabidopsis leaf epidermal pavement cells (PCs), which develop interdigitated lobes and indentations to form a puzzle-piece shape in a two-dimensional plane. PC interdigitation is compromised in leaves deficient in either auxin biosynthesis or its export mediated by PINFORMED 1 localized at the lobe tip. Auxin coordinately activates two Rho GTPases, ROP2 and ROP6, which promote the formation of complementary lobes and indentations, respectively. Activation of these ROPs by auxin occurs within 30 s and depends on AUXIN-BINDING PROTEIN 1. These findings reveal Rho GTPase-based auxin-signaling mechanisms, which modulate the spatial coordination of cell expansion across a field of cells.
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► Auxin controls interdigitated pavement cell growth ► Auxin does so by coordinately activating two antagonistic GTPases, ROP2 and ROP6 ► The auxin signal is produced by its exporter PIN1 at the site of ROP2 activation ► The auxin signal is perceived by ABP1 acting upstream of both ROP2 and ROP6
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
IMPORTANCE: Population-based studies following trajectories of depression in autism spectrum disorders (ASD) from childhood into early adulthood are rare. The role of genetic confounding and of ...potential environmental intermediaries, such as bullying, in any associations is unclear. OBJECTIVES: To compare trajectories of depressive symptoms from ages 10 to 18 years for children with or without ASD and autistic traits, to assess associations between ASD and autistic traits and an International Statistical Classification of Diseases, 10th Revision (ICD-10) depression diagnosis at age 18 years, and to explore the importance of genetic confounding and bullying. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal study of participants in the Avon Longitudinal Study of Parents and Children birth cohort in Bristol, United Kingdom, followed up through age 18 years. Data analysis was conducted from January to November 2017. MAIN OUTCOMES AND MEASURES: Depressive symptoms were assessed using the Short Mood and Feelings Questionnaire (SMFQ) at 6 time points between ages 10 and 18 years. An ICD-10 depression diagnosis at age 18 years was established using the Clinical Interview Schedule–Revised. Exposures were ASD diagnosis and 4 dichotomized autistic traits (social communication, coherence, repetitive behavior, and sociability). An autism polygenic risk score was derived using the Psychiatric Genomics Consortium autism discovery genome-wide association study summary data. Bullying was assessed at ages 8, 10, and 13 years. RESULTS: The maximum sample with complete data was 6091 for the trajectory analysis (48.8% male) and 3168 for analysis of depression diagnosis at age 18 years (44.4% male). Children with ASD and autistic traits had higher average SMFQ depressive symptom scores than the general population at age 10 years (eg, for social communication 5.55 95% CI, 5.16-5.95 vs 3.73 95% CI, 3.61-3.85, for ASD 7.31 95% CI, 6.22-8.40 vs 3.94 95% CI, 3.83-4.05, remaining elevated in an upward trajectory until age 18 years (eg, for social communication 7.65 95% CI, 6.92-8.37 vs 6.50 95% CI, 6.29-6.71, for ASD 7.66 95% CI, 5.96-9.35 vs 6.62 95% CI, 6.43-6.81). Social communication impairments were associated with depression at age 18 years (adjusted relative risk, 1.68; 95% CI, 1.05-2.70), and bullying explained a substantial proportion of this risk. There was no evidence of confounding by the autism polygenic risk score. Analysis in larger samples using multiple imputation led to similar but more precise results. CONCLUSIONS AND RELEVANCE: Children with ASD and ASD traits have higher depressive symptom scores than the general population by age 10 years, which persist to age 18 years, particularly in the context of bullying. Social communication impairments are an important autistic trait in relation to depression. Bullying, as an environmental intermediary, could be a target for interventions.
The plant G-protein network, comprising Gα, Gβ, and Gγ core subunits, regulates development, senses sugar, and mediates biotic and abiotic stress responses. Here, we report G-protein signalling in ...the salt stress response using two crop models, rice and maize. Loss-of-function mutations in the corresponding genes encoding the Gα subunit attenuate growth inhibition and cellular senescence caused by sodium chloride (NaCl). Gα null mutations conferred reduced leaf senescence, chlorophyll degradation, and cytoplasm electrolyte leakage under NaCl stress. Sodium accumulated in both wild-type and Gα-mutant shoots to the same levels, suggesting that Gα signalling controls cell death in leaves rather than sodium exclusion in roots. Growth inhibition is probably initiated by osmotic change around root cells, because KCl and MgSO4 also suppressed seedling growth equally as well as NaCl. NaCl lowered rates of cell division and elongation in the wild-type leaf sheath to the level of the Gα-null mutants; however there was no NaCl-induced decrease in cell division in the Gα mutant, implying that the osmotic phase of salt stress suppresses cell proliferation through the inhibition of Gα-coupled signalling. These results reveal two distinct functions of Gα in NaCl stress in these grasses: attenuation of leaf senescence caused by sodium toxicity in leaves, and cell cycle regulation by osmotic/ionic stress.
Highlight textThis work reveals two distinct functions of Gα in NaCl stress in rice and maize: attenuation of leaf senescence caused by sodium toxicity in leaves, and cell cycle regulation by osmotic/ionic stress.
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Auxin-binding protein 1 (ABP1) was discovered nearly 40 years ago and was shown to be essential for plant development and morphogenesis, but its mode of action remains unclear. Here, we report that ...the plasma membrane–localized transmembrane kinase (TMK) receptor–like kinases interact with ABP1 and transduce auxin signal to activate plasma membrane–associated ROPs Rho-like guanosine triphosphatases (GTPase) from plants, leading to changes in the cytoskeleton and the shape of leaf pavement cells in Arabidopsis. The interaction between ABP1 and TMK at the cell surface is induced by auxin and requires ABP1 sensing of auxin. These findings show that TMK proteins and ABP1 form a cell surface auxin perception complex that activates ROP signaling pathways, regulating nontranscriptional cytoplasmic responses and associated fundamental processes.
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An Arabidopsis cell-surface auxin receptor that mediates rapid elongation consists of transmembrane kinases (TMKs) and an auxin-binding co-receptor. Auxin-binding protein 1 (ABP1) is one identified ...TMK co-receptor, but abp1 mutants have no elongation phenotypes. Yu et al. use structural analysis of the ABP1-binding pocket to identify functional ABP1-like (ABL) TMK co-receptors that regulate rapid growth.
An Arabidopsis cell-surface auxin receptor that mediates rapid elongation consists of transmembrane kinases (TMKs) and an auxin-binding co-receptor. Auxin-binding protein 1 (ABP1) is one identified TMK co-receptor, but abp1 mutants have no elongation phenotypes. Yu et al. use structural analysis of the ABP1-binding pocket to identify functional ABP1-like (ABL) TMK co-receptors that regulate rapid growth.
Heterotrimeric GTP-binding proteins (G proteins), consisting of Gα, Gβ and Gγ subunits, transduce signals from a diverse range of extracellular stimuli, resulting in the regulation of numerous ...cellular and physiological functions in Eukaryotes. According to the classic G protein paradigm established in animal models, the bound guanine nucleotide on a Gα subunit, either guanosine diphosphate (GDP) or guanosine triphosphate (GTP) determines the inactive or active mode, respectively. In plants, there are two types of Gα subunits: canonical Gα subunits structurally similar to their animal counterparts and unconventional extra-large Gα subunits (XLGs) containing a C-terminal domain homologous to the canonical Gα along with an extended N-terminal domain. Both Gα and XLG subunits interact with Gβγ dimers and regulator of G protein signalling (RGS) protein. Plant G proteins are implicated directly or indirectly in developmental processes, stress responses, and innate immunity. It is established that despite the substantial overall similarity between plant and animal Gα subunits, they convey signalling differently including the mechanism by which they are activated. This review emphasizes the unique characteristics of plant Gα subunits and speculates on their unique signalling mechanisms.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Our understanding of cancer biology has increased substantially over the past 30 years. Despite this, and an increasing pharmaceutical company expenditure on research and development, the approval of ...novel oncology drugs during the past decade continues to be modest. In addition, the attrition of agents during clinical development remains high. This attrition can be attributed, at least in part, to the clinical development being underpinned by the demonstration of predictable efficacy in experimental models of human tumours. This review will focus on the range of models available for the discovery and development of anticancer drugs, from traditional subcutaneous injection of tumour cell lines to mice genetically engineered to spontaneously give rise to tumours. It will consider the best time to use the models, along with practical applications and shortcomings. Finally, and most importantly, it will describe how these models reflect the underlying cancer biology and how well they predict efficacy in the clinic. Developing a line of sight to the clinic early in a drug discovery project provides clear benefit, as it helps to guide the selection of appropriate preclinical models and facilitates the investigation of relevant biomarkers.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Plastid Genome Assembly Using Long‐read data Zhou, Wenbin; Armijos, Carolina E.; Lee, Chaehee ...
Molecular ecology resources,
August 2023, Volume:
23, Issue:
6
Journal Article
Peer reviewed
Open access
Although plastid genome (plastome) structure is highly conserved across most seed plants, investigations during the past two decades have revealed several disparately related lineages that ...experienced substantial rearrangements. Most plastomes contain a large inverted repeat and two single‐copy regions, and a few dispersed repeats; however, the plastomes of some taxa harbour long repeat sequences (>300 bp). These long repeats make it challenging to assemble complete plastomes using short‐read data, leading to misassemblies and consensus sequences with spurious rearrangements. Single‐molecule, long‐read sequencing has the potential to overcome these challenges, yet there is no consensus on the most effective method for accurately assembling plastomes using long‐read data. We generated a pipeline, plastid Genome Assembly Using Long‐read data (ptGAUL), to address the problem of plastome assembly using long‐read data from Oxford Nanopore Technologies (ONT) or Pacific Biosciences platforms. We demonstrated the efficacy of the ptGAUL pipeline using 16 published long‐read data sets. We showed that ptGAUL quickly produces accurate and unbiased assemblies using only ~50× coverage of plastome data. Additionally, we deployed ptGAUL to assemble four new Juncus (Juncaceae) plastomes using ONT long reads. Our results revealed many long repeats and rearrangements in Juncus plastomes compared with basal lineages of Poales. The ptGAUL pipeline is available on GitHub: https://github.com/Bean061/ptgaul.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
G-proteins are molecular on-off switches that are involved in transmitting a variety of extracellular signals to their intracellular targets. In animal and yeast systems, the switch property is ...encoded through nucleotides: a GDP-bound state is the "off-state" and the GTP-bound state is the "on-state". The G-protein cycle consists of the switch turning on through nucleotide exchange facilitated by a G-protein coupled receptor and the switch turning off through hydrolysis of GTP back to GDP, facilitated by a protein designated REGULATOR OF G SIGNALING 1 (RGS). In plants, G-protein signaling dramatically differs from that in animals and yeast. Despite stringent conservation of the nucleotide binding and catalytic structures over the 1.6 billion years that separate the evolution of plants and animals, genetic and biochemical data indicate that nucleotide exchange is less critical for this switch to operate in plants. Also, the loss of the single RGS protein in Arabidopsis (Arabidopsis thaliana) confers unexpectedly weaker phenotypes consistent with a diminished role for the G cycle, at least under static conditions. However, under dynamic conditions, genetic ablation of RGS in Arabidopsis results in a strong phenotype. We explore explanations to this conundrum by formulating a mathematical model that takes into account the accruing evidence for the indispensable role of phosphorylation in G-protein signaling in plants and that the G-protein cycle is needed to process dynamic signal inputs. We speculate that the plant G-protein cycle and its attendant components evolved to process dynamic signals through signaling modulation rather than through on-off, switch-like regulation of signaling. This so-called change detection may impart greater fitness for plants due to their sessility in a dynamic light, temperature, and pest environment.
The study of organosulfates is a burgeoning area in biology, yet there are significant challenges with their synthesis. We report the development of a tributylsulfoammonium betaine as a high yielding ...route to organosulfates. The optimised reaction conditions were interrogated with a diverse range of alcohols, including natural products and amino acids.