Sensory experience and perceptual learning changes receptive field properties of cortical pyramidal neurons (PNs), largely mediated by synaptic long-term potentiation (LTP). The circuit mechanisms ...underlying cortical LTP remain unclear. In the mouse somatosensory cortex, LTP can be elicited in layer 2/3 PNs by rhythmic whisker stimulation. We dissected the synaptic circuitry underlying this type of plasticity in thalamocortical slices. We found that projections from higher-order, posterior medial thalamic complex (POm) are key to eliciting N-methyl-D-aspartate receptor (NMDAR)-dependent LTP of intracortical synapses. Paired activation of cortical and higher-order thalamocortical inputs increased vasoactive intestinal peptide (VIP) and parvalbumin (PV) interneuron (IN) activity and decreased somatostatin (SST) IN activity, which together disinhibited the PNs. VIP IN-mediated disinhibition was critical for inducing LTP. This study reveals a circuit motif in which higher-order thalamic inputs gate synaptic plasticity via disinhibition. This motif may allow contextual feedback to shape synaptic circuits that process first-order sensory information.
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•Activation of higher-order (HO) thalamic inputs facilitates intracortical LTP•HO inputs increase VIP and PV interneuron (IN) activity and decrease SST IN activity•The activation of VIP INs disinhibits L2/3 pyramidal neurons (PNs)•The HO-to-VIP circuit gates the intracortically driven LTP on PNs
Using ex vivo patch-clamp recordings, optogenetics, and chemogenetics, Williams and Holtmaat dissect the circuits underlying sensory-driven LTP in the cortex. This reveals a circuit motif in which higher-order thalamocortical input gates plasticity of intracortical synapses via VIP-mediated disinhibition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Various ways of disclosing or delivering communication in the form of expressing warnings and expressing prohibitions or delivering information this study aims to determine the differences between ...warning and prohibition expressions in Indonesia and English and the forms of these expressions. This research process used qualitative research methods and literature studies. To collect the data, this research employed textual observation. Meanwhile, to analyze the data this study employed cultural analysis. The result can be seen that expressing warnings and expressing prohibitions declared in Indonesia and abroad are not much different, both in terms of expression and form, such as no smoking, no food and drink in this area, etc.
Aims
The basal forebrain (BF) plays an essential role in wakefulness and cognition. Two subtypes of BF gamma‐aminobutyric acid (GABA) neurons, including somatostatin‐expressing (GABASOM) and ...parvalbumin‐positive (GABAParv) neurons, function differently in mediating the natural sleep–wake cycle. Since the loss of consciousness induced by general anesthesia and the natural sleep–wake cycle probably share similar mechanisms, it is important to clarify the accurate roles of these neurons in general anesthesia procedure.
Methods
Based on two transgenic mouse lines expressing SOM‐IRES‐Cre and PV‐IRES‐Cre, we used a combination of genetic activation, inactivation, and chronic ablation approaches to further explore the behavioral and electroencephalography (EEG) roles of BFSOM and BFParv neurons in general anesthesia. After a single intravenous injection of propofol and the induction and recovery times of isoflurane anesthesia, the anesthesia time was compared. The changes in cortical EEG under different conditions were also compared.
Results
Activation of BF GABASOM neurons facilitates both the propofol and isoflurane anesthesia, manifesting as a longer anesthesia duration time with propofol anesthesia and a fast induction time and longer recovery time with isoflurane anesthesia. Moreover, BF GABASOM‐activated mice displayed a greater suppression of cortical electrical activity during anesthesia, showing an increase in δ power bands or a simultaneous decrease in high‐frequency power bands. However, only a limited and nuanced effect on propofol and isoflurane anesthesia was observed with the manipulated BF GABAParv neurons.
Conclusions
Our results suggested that BF GABASOM neurons play a critical role in propofol and isoflurane general anesthesia, while BF GABAParv neurons appeared to have little effect.
BF GABASOM neurons play a critical role in propofol and isoflurane general anesthesia, while BF GABAParv neurons appeared to have little effect.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
The rapid development of omics sequencing technology has facilitated the identification of thousands of long non‐coding (lnc)RNAs in plant species, but the role of lncRNAs in plant–pathogen ...interactions remains largely unexplored. We used comparative transcriptome analysis of Phytophthora infestans‐resistant and ‐susceptible tomatoes to identify differentially expressed genes (DEGs) and lncRNAs (DELs), and examine lncRNA‐mRNA networks. A total of 1037 DEGs and 688 DELs were identified between P. infestans‐resistant and ‐susceptible tomatoes. The co‐localization networks, including 128 DEGs and 127 DELs, were performed. We found that lncRNA16397 acted as an antisense transcript of SlGRX22 to regulate its expression, and also induced SlGRX21 expression when lncRNA16397 was overexpressed. In addition, disease symptoms and reactive oxygen species (ROS) accumulation in tomatoes overexpressing lncRNA16397 and SpGRX were fewer and lower than those in wild‐type after P. infestans infection. This result suggests that tomato lncRNA16397 induces SlGRX expression to reduce ROS accumulation and alleviate cell membrane injury, resulting in enhanced resistance to P. infestans. Our results provide insight into lncRNAs involved in the response of tomato to P. infestans infection, demonstrate that the lncRNA16397‐GRXs network is an important component of the P. infestans network in tomato, and provide candidates for breeding to enhance biotic stress‐resistance in tomato.
Significance Statement
There are thousands of lncRNAs in plants, but their role in plant‐pathogen interactions remains largely unexplored. Here, by using comparative transcriptome analysis of Phytophthora infestans‐resistant and susceptible tomato, we show that lncRNA16397 can induce gene expression to reduce ROS accumulation and alleviate cell membrane injury, thus enhancing resistance to P. infestans. We also pinpoint other candidate genes that can be used to breed for enhanced biotic stress‐resistance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Mesenchymal stem cells (MSCs) are multipotent stromal cells with immunosuppressive properties. They have emerged as a very promising treatment for autoimmunity and inflammatory diseases such as ...rheumatoid arthritis. Recent data have identified that GM‐CSF‐expressing CD4 T cells and Th17 cells have critical roles in the pathogenesis of arthritis and other inflammatory diseases. Although many studies have demonstrated that MSCs can either prevent or suppress inflammation, no studies have addressed their modulation on GM‐CSF‐expressing CD4 T cells and on the plasticity of Th17 cells. To address this, a single dose of human expanded adipose‐derived mesenchymal stem cells (eASCs) was administered to mice with established collagen‐induced arthritis. A beneficial effect was observed soon after the infusion of the eASCs as shown by a significant decrease in the severity of arthritis. This was accompanied by reduced number of pathogenic GM‐CSF+CD4+ T cells in the spleen and peripheral blood and by an increase in the number of different subsets of regulatory T cells like FOXP3+CD4+ T cells and IL10+IL17−CD4+ T cells in the draining lymph nodes (LNs). Interestingly, increased numbers of Th17 cells coexpressing IL10 were also found in draining LNs. These results demonstrate that eASCs ameliorated arthritis after the onset of the disease by reducing the total number of pathogenic GM‐CSF+CD4+ T and by increasing the number of different subsets of regulatory T cells in draining LNs, including Th17 cells expressing IL10. All these cellular responses, ultimately, lead to the reestablishment of the regulatory/inflammatory balance in the draining LNs. Stem Cells 2015;33:3493–3503
The development of intestinal‐type gastric cancer is preceded by the emergence of metaplastic cell lineages in the gastric mucosa. In particular, intestinal metaplasia and spasmolytic ...polypeptide‐expressing metaplasia (SPEM) have been associated with the pathological progression to intestinal‐type gastric cancer. The development of SPEM represents a physiological response to damage that recruits reparative cells to sites of mucosal injury. Metaplastic cell lineages are characterized by mucus secretion, adding a protective barrier to the epithelium. Increasing evidence indicates that the influence of alarmins and cytokines is required to initiate the process of metaplasia development. In particular, IL‐33 derived from epithelial cells stimulates IL‐13 production by specialized innate immune cells to induce chief cell transdifferentiation into SPEM following the loss of parietal cells from the corpus of the stomach. While SPEM represents a physiological healing response to acute injury, persistent injury and chronic inflammation can perpetuate a recurring pattern of reprogramming and metaplasia that is a risk factor for gastric cancer development. The transdifferentiation of zymogen secreting cells into mucous cell metaplasia may represent both a general repair mechanism in response to mucosal injury in many epithelia as well as a common pre‐neoplastic pathway associated with chronic injury and inflammation.
A signalling cascade of IL‐33 to IL‐13 regulates SPEM development, mucus hypersecretion, and alternative activation of macrophages in the face of acute damage to the gastric mucosa.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Leaves are the main places for photosynthesis and organic synthesis of cotton. Leaf shape has important effects on the photosynthetic efficiency and canopy formation, thereby affecting cotton yield. ...Previous studies have shown that LMI1 is the main gene regulating leaf shape. In this study, the LMI1 gene (LATE MERISTEM IDENTITY1) was inserted into the 35S promoter expression vector, and cotton plants overexpressing LMI1(OE) were obtained through genetical transformation. Statistical analysis of the biological traits of T1 and T2 populations showed that compared to wild type (WT), OE plants had significant larger leaves, thicker stems and significantly increased dry weight. Furthermore, plant sections of the main vein and petiole showed that the number of cell in those tissues of OE plants increased significantly. In addition, RNA-seq analysis revealed differential expression of genes related to gibberellin synthesis and NAC gene family (genes containing the NAC domain) in OE and WT plants, suggesting that LMI1 is involved in secondary wall formation and cell proliferation, and promotes stem thickening. Moreover, GO (Gene Ontology) analysis enriched the terms of calcium ion binding, and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis enriched the terms of fatty acid degradation, phosphatidylinositol signal transduction system, and cAMP signal pathway. These results suggested that LMI1 OE plants were responsive to gibberellin hormone signals, and altered messenger signal (cAMP, Ca2+) which amplified this function, to promote the stronger above ground vegetative growth. This study found the LMI1 soared the nutrient growth in cotton, which is the basic for higher yield.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Endometriosis, a common cause of pelvic pain and female infertility, depends on the growth of vascularized endometrial tissue at ectopic sites. Endometrial fragments reach the peritoneal cavity ...during the fertile years: local cues decide whether they yield endometriotic lesions. Macrophages are recruited at sites of hypoxia and tissue stress, where they clear cell debris and heme-iron and generate pro-life and pro-angiogenesis signals. Macrophages are abundant in endometriotic lesions, where are recruited and undergo alternative activation. In rodents macrophages are required for lesions to establish and to grow; bone marrow-derived Tie-2 expressing macrophages specifically contribute to lesions neovasculature, possibly because they concur to the recruitment of circulating endothelial progenitors, and sustain their survival and the integrity of the vessel wall. Macrophages sense cues (hypoxia, cell death, iron overload) in the lesions and react delivering signals to restore the local homeostasis: their action represents a necessary, non-redundant step in the natural history of the disease. Endometriosis may be due to a misperception of macrophages about ectopic endometrial tissue. They perceive it as a wound, they activate programs leading to ectopic cell survival and tissue vascularization. Clearing this misperception is a critical area for the development of novel medical treatments of endometriosis, an urgent and unmet medical need.
Differentiated cells across multiple species and organs can re‐enter the cell cycle to aid in injury‐induced tissue regeneration by a cellular program called paligenosis. Here, we show that ...activating transcription factor 3 (ATF3) is induced early during paligenosis in multiple cellular contexts, transcriptionally activating the lysosomal trafficking gene Rab7b. ATF3 and RAB7B are upregulated in gastric and pancreatic digestive‐enzyme‐secreting cells at the onset of paligenosis Stage 1, when cells massively induce autophagic and lysosomal machinery to dismantle differentiated cell morphological features. Their expression later ebbs before cells enter mitosis during Stage 3. Atf3–/– mice fail to induce RAB7‐positive autophagic and lysosomal vesicles, eventually causing increased death of cells en route to Stage 3. Finally, we observe that ATF3 is expressed in human gastric metaplasia and during paligenotic injury across multiple other organs and species. Thus, our findings indicate ATF3 is an evolutionarily conserved gene orchestrating the early paligenotic autodegradative events that must occur before cells are poised to proliferate and contribute to tissue repair.
Synopsis
Pancreatic and gastric exocrine cells regenerate after injury through a process called paligenosis. Injury‐induced ATF3 promotes cell autodegradation via transcriptional activation of Rab7b, a regulator of late endosomal and lysosomal trafficking. Atf3 upregulation in injury across diverse organs and species suggests a conserved role in governing the cell plasticity program of paligenosis.
ATF3 transcriptionally activates Rab7b during paligenotic autodegradation of exocrine cells of the stomach and pancreas.
Atf3 is required for lysosome and autophagy induction in paligenosis.
Atf3 loss leads to increased cell death during paligenosis and decreased tissue repair following injury.
Pancreatic and gastric exocrine cells regenerate after injury through a process called paligenosis. Injury‐induced ATF3 promotes autophagy and cell autodegradation via transcriptional activation of Rab7.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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