Phosphorus (P) is an essential element to all living cells, yet fluctuations in P concentrations are recurrent in the marine environment. Diatoms are amongst the most successful phytoplankton groups, ...adapting to and surviving periods of suboptimal conditions and resuming growth as soon as nutrient concentrations permit. A knowledge of the molecular underpinnings of diatom ecological success is, however, still very incomplete. By strand‐specific RNA sequencing, we analyzed the global transcriptome changes of the diatom Phaeodactylum tricornutum in response to P fluctuations over a course of 8 d, defining five distinct physiological states. This study reports previously unidentified genes highly responsive to P stress in P. tricornutum. Our data also uncover the complexity of the P. tricornutum P‐responsive sensory and signaling system that combines bacterial two‐component systems with more complex pathways reminiscent of metazoans. Finally, we identify a multitude of novel long intergenic nonprotein coding RNAs (lincRNAs) specifically responsive to P depletion, suggesting putative regulatory roles in the regulation of P homeostasis. Our work provides additional molecular insights into the resilience of diatoms and their ecological success, and opens up novel routes to address and explore the function and regulatory roles of P. tricornutum lincRNAs in the context of nutrient stress.
The plant immune response is a complex process involving transcriptional and posttranscriptional regulation of gene expression. Responses to plant immunity are initiated upon the perception of ...pathogen-associated molecular patterns, including peptide fragment of bacterial flagellin (flg22) or translation elongation factor Tu (elf18). Here, we identify an Arabidopsis thaliana long-noncoding RNA, designated ELF18-INDUCED LONG-NONCODING RNA1 (ELENA1), as a factor enhancing resistance against Pseudomonas syringe pv tomato DC3000. ELENA1 knockdown plants show decreased expression of PATHOGENESIS-RELATED GENE1 (PR1) and the plants are susceptible to pathogens. By contrast, plants overexpressing ELENA1 show elevated PR1 expression after elf18 treatment and display a pathogen resistance phenotype. RNA-sequencing analysis of ELENA1-overexpressing plants after elf18 treatment confirms increased expression of defenserelated genes compared with the wild type. ELENA1 directly interacts with Mediator subunit 19a (MED19a) and affects enrichment of MED19a on the PR1 promoter. These results show that MED19a regulates PR1 expression through ELENA1. Our findings uncover an additional layer of complexity, implicating long-noncoding RNAs in the transcriptional regulation of plant innate immunity.
Identifying active prophages is critical for studying coevolution of phage and bacteria, investigating phage physiology and biochemistry, and engineering designer phages for diverse applications. We ...present Prophage Hunter, a tool aimed at hunting for active prophages from whole genome assembly of bacteria. Combining sequence similarity-based matching and genetic features-based machine learning classification, we developed a novel scoring system that exhibits higher accuracy than current tools in predicting active prophages on the validation datasets. The option of skipping similarity matching is also available so that there's higher chance for novel phages to be discovered. Prophage Hunter provides a one-stop web service to extract prophage genomes from bacterial genomes, evaluate the activity of the prophages, identify phylogenetically related phages, and annotate the function of phage proteins. Prophage Hunter is freely available at https://pro-hunter.bgi.com/.
Pd-catalyzed C–H functionalizations promoted by transient directing groups remain largely limited to C–H arylation only. Herein, we report a diverse set of ortho-C(sp2)–H functionalizations of ...benzaldehyde substrates using the transient directing group strategy. Without installing any auxiliary directing group, Pd(II)-catalyzed C–H arylation, chlorination, bromination, and Ir(III)-catalyzed amidation, could be achieved on benzaldehyde substrates. The transient directing groups formed in situ via imine linkage can override other coordinating functional groups capable of directing C–H activation or catalyst poisoning, significantly expanding the scope for metal-catalyzed C–H functionalization of benzaldehydes. The utility of this approach is demonstrated through multiple applications, including late-stage diversification of a drug analogue.
The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report ...the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.
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•We generated a single-cell atlas of PBMCs in both COVID-19 and influenza patients•Plasma cells increase significantly in both COVID-19 and influenza patients•COVID-19 is featured with XAF1-, TNF-, and FAS-induced T cell apoptosis•COVID-19 activates distinct pathway (STAT1/IRF3) versus influenza (STAT3/NFκB)
COVID-19 and influenza are both respiratory infections with cytokine release syndrome. Zhu et al. use single-cell RNA sequencing of longitudinally collected PBMCs in both patients to reveal distinct immune response landscapes of the two diseases and identify virus-specific cell composition and immune response pathways.
Dynamic pluripotent stem cell (PSC) states are in vitro adaptations of pluripotency continuum in vivo. Previous studies have generated a number of PSCs with distinct properties. To date, however, no ...known PSCs have demonstrated dual competency for chimera formation and direct responsiveness to primordial germ cell (PGC) specification, a unique functional feature of formative pluripotency. Here, by modulating fibroblast growth factor (FGF), transforming growth factor β (TGF-β), and WNT pathways, we derived PSCs from mice, horses, and humans (designated as XPSCs) that are permissive for direct PGC-like cell induction in vitro and are capable of contributing to intra- or inter-species chimeras in vivo. XPSCs represent a pluripotency state between naive and primed pluripotency and harbor molecular, cellular, and phenotypic features characteristic of formative pluripotency. XPSCs open new avenues for studying mammalian pluripotency and dissecting the molecular mechanisms governing PGC specification. Our method may be broadly applicable for the derivation of analogous stem cells from other mammalian species.
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•Derivation of intermediate XPSCs by modulating FGF, TGF-β, and WNT pathways•XPSCs can be generated from mice, horses, and humans•XPSCs harbor formative pluripotency features•XPSCs show chimera and primordial germ cell specification dual competency
Yu, Wu, and colleagues report the derivation of intermediate PSCs from mice, horses, and humans (designated as XPSCs) that are permissive for direct PGC-like cell induction in vitro and capable of contributing to intra- or inter-species chimeras in vivo. XPSCs harbor molecular, cellular, and phenotypic features characteristic of formative pluripotency.
Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 ...macrophages. We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines. The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro, the expression of cytokines and chemokines were detected by microarray, real-time PCR, ELISA and multiple colors flow cytometry. Adoptive transfer of macrophages and imiquimod-induced psoriasis mice were used. In contrast to M1- and M2-polarized macrophages, IL-23-treated macrophages produce large amounts of IL-17A, IL-22 and IFN-γ. Biochemical and molecular studies showed that IL-23 induces IL-17A expression in macrophages through the signal transducer and activator of transcription 3 (STAT3)-retinoid related orphan receptor-γ T (RORγT) pathway. T-bet mediates the IFN-γ production in IL-23-treated macrophages. Importantly, IL-23-treated macrophages significantly promote the dermatitis pathogenesis in a psoriasis-like mouse model. IL-23-treated resting macrophages express a distinctive gene expression prolife compared with M1 and M2 macrophages. The identification of IL-23-induced macrophage polarization may help us to understand the contribution of macrophage subpopulation in Th17-cytokines-related pathogenesis.
microRNAs may function as oncogenes or tumor suppressor genes that play crucial roles in human carcinogenesis and cancer development. Growing evidence revealed that the tumor suppressor Id3 is ...involved in tumor progression, carcinogenesis, and the tumor microenvironment. We identified miR‐212‐5p as a negative posttranscriptional modulator of Id3. Dual luciferase reporter assay was used to verify that Id3 is a direct target gene of miR‐212‐5p. Id3 was lowly expressed and miR‐212‐5p was highly expressed in non‐small‐cell lung cancer (NSCLC) tissues and cells. In addition, we found that NSCLC patients having a higher level of miR‐212‐5p expression had a shorter survival time. Besides this, miR‐212‐5p could directly target Id3 and reduce its expression. miR‐212‐5p overexpression significantly accelerated cell proliferation, migration, and invasion by reversing the effects of Id3. Id3 overexpression by silencing miR‐212‐5p expression suppressed phosphatidylinositol 3 kinase (PI3K)/Akt activity and consequently promoted apoptosis and inhibited cell proliferation in lung cancer cells. Consistent with the in vitro results, a xenograft mouse model was used to validate the fact that miR‐212‐5p could promote tumorigenesis by targeting Id3 and activate the PI3K/Akt pathway in vivo as well. Taken together, the present results indicated that miR‐212‐5p may be involved in progression of NSCLC through the PI3K/Akt signaling pathway by targeting Id3.
Non‐small‐cell lung cancer (NSCLC) patients having a higher level of miR‐212‐5p expression had a shorter survival time. miR‐212‐5p could directly target Id3 and significantly accelerated cell proliferation, migration, and invasion by reversing the effects of Id3. miR‐212‐5p may be involved in progression of NSCLC through the phosphatidylinositol 3 kinase (PI3K)/Akt signaling pathway by targeting Id3.
Understanding the complex functions of plant leaves requires a thorough characterization of discrete cell features. Although single-cell gene expression profiling technologies have been developed, ...their application in characterizing cell subtypes has not been achieved yet. Here, we present scStereo-seq (single-cell spatial enhanced resolution omics sequencing) that enabled us to show the bona fide single-cell spatial transcriptome profiles of Arabidopsis leaves. Subtle but significant transcriptomic differences between upper and lower epidermal cells have been successfully distinguished. Furthermore, we discovered cell-type-specific gene expression gradients from the main vein to the leaf edge, which led to the finding of distinct spatial developmental trajectories of vascular cells and guard cells. Our study showcases the importance of physical locations of individual cells for exerting complex biological functions in plants and demonstrates that scStereo-seq is a powerful tool to integrate single-cell location and transcriptome information for plant biology study.
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•Establishing an in situ single-cell spatial transcriptome method in plant•Identification of cell subtypes and subtle transcriptional differences•Cell-type-specific gene expression gradients from the main vein to the leaf edge•scStereo-seq enables the construction of spatially resolved developmental trajectories
Xia et al. establish the single-cell spatial transcriptome technique (scStereo-seq) in Arabidopsis leaves and discover subtle but significant transcriptional differences between cell subtypes, demonstrating that scStereo-seq is a powerful tool to integrate single-cell location and transcriptome information for plant biology study.
Pulmonary infection due to Mycobacterium abscessus complex (MABC) usually occurs in children with underlying risk factors including cystic fibrosis (CF), chronic lung disease, and immunocompromised ...status, but rarely in immunocompetent children without underlying lung disease, especially in infants. We present a case of MABC pulmonary disease (MABC-PD) in an otherwise healthy 53-day-old male infant with one week of cough and respiratory distress. Computed tomography showed multiple masses across both lungs. Isolated mycobacteria from his bronchoalveolar lavage fluid were identified as MABC. We describe our complete evaluation, including immunodeficiency evaluation incorporating whole exome sequencing and our therapeutic process given complicated susceptibility pattern of the M. abscessus isolate, and review literature for MABC-PD in immunocompetent children. The infant was successfully treated through prolonged treatment with parenteral Amikacin, Cefoxitin, Linezolid, and Clarithromycin, combined with inhaled Amikacin.
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