scholarly journals 3D micro-environment regulates NF–κβ dependent adhesion to induce monocyte differentiation

2018 ◽  
Author(s):  
Anindita Bhattacharya ◽  
Mahesh Agarwal ◽  
Rachita Mukherjee ◽  
Prosenjit Sen ◽  
Deepak Kumar Sinha
Keyword(s):  
Positive Feedback ◽  
Feedback Loop ◽  
The Novel ◽  
Monocyte Adhesion ◽  
Cellular Functions ◽  
Monocyte Differentiation ◽  
Summary Statement ◽  
Necessary And Sufficient ◽  
Multiple Signaling ◽  
Insight Into

AbstractDifferentiation of monocytes entails their relocation from blood to the tissue, hence accompanied by an altered physicochemical micro-environment. While the mechanism by which the biochemical make-up of the micro-environment induces differentiation is known, the fluid-like to gel-like transition in the physical micro-environment is not well understood. Monocytes maintain non-adherent state to prevent differentiation. We establish that irrespective of the chemical makeup, a 3D gel-like micro-environment induces a positive-feedback loop of adhesion-MAPK-NF-κβ activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signalling. Chemical inducer treatment in fluid-like micro-environment, increases the propensity of monocyte adhesion via a brief pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing that adhesion is both necessary and sufficient to induce differentiation in 2D/3D micro-environment. Our findings challenge the notion that adhesion is a result of monocyte differentiation. Rather it’s the adhesion which triggers the differentiation of monocytes. MAPK, and NF-κβ being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.Summary statementThis article brings out a new insight into the novel mechanisms of monocyte differentiation solely driven by physical micro-environment and adhesion.

scholarly journals Anterograde and retrograde signaling by an Aplysia neurotrophin forms a transsynaptic functional unit

2018 ◽  
Vol 115 (46) ◽  
pp. E10951-E10960 ◽  
Author(s):  
Iksung Jin ◽  
Hiroshi Udo ◽  
Stefan Kassabov ◽  
Stylianos Kosmidis ◽  
Huixiang Zhu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Functional Unit ◽  
Companion Paper ◽  
Retrograde Signaling ◽  
Autocrine Signaling ◽  
Cellular Functions ◽  
Short Term ◽  
Positive Feedback Loop

Whereas short-term synaptic plasticity is often either pre- or postsynaptic, intermediate- and long-term plasticity generally require coordinated pre- and postsynaptic mechanisms. Thus, the transition from presynaptic short-term facilitation (STF) to intermediate-term facilitation (ITF) induced by 5HT at Aplysia sensory-to-motor neuron synapses requires the recruitment of postsynaptic mechanisms and activation of protein synthesis in both neurons. In the companion paper to this report, we found that presynaptic autocrine signaling by an Aplysia neurotrophin (ApNT) forms a positive feedback loop that drives the synapses from STF to ITF. Here we report that ApNT also acts through both anterograde and retrograde signaling to form a transsynaptic positive feedback loop that orchestrates cellular functions in both the presynaptic and postsynaptic neurons during the induction of ITF. These two feedback loops activate protein synthesis in each synaptic compartment, which in both cases depends on signaling from the other synaptic compartment. These results suggest that the pre- and postsynaptic compartments act as one functional unit during the consolidation of learning-related facilitation induced by 5HT.

The Monk

2016 ◽  
Author(s):  
Matthew Lewis
Keyword(s):  
French Revolution ◽  
English Literature ◽  
Young Girl ◽  
The Novel ◽  
Reading Public ◽  
Ghost Stories ◽  
Gothic Fiction ◽  
Black Magic ◽  
Insight Into ◽  
Profound Insight

‘He was deaf to the murmurs of conscience, and resolved to satisfy his desires at any price.’ The Monk (1796) is a sensational story of temptation and depravity, a masterpiece of Gothic fiction and the first horror novel in English literature. The respected monk Ambrosio, the Abbot of a Capuchin monastery in Madrid, is overwhelmed with desire for a young girl; once having abandoned his monastic vows he begins a terrible descent into immorality and violence. His appalling fall from grace embraces blasphemy, black magic, torture, rape, and murder, and places his very soul in jeopardy. Lewis’s extraordinary tale drew on folklore, legendary ghost stories, and contemporary dread inspired by the terrors of the French Revolution. Its excesses shocked the reading public and it was condemned as obscene. The novel continues to beguile and shock readers today with its gruesome catalogue of iniquities, while at the same time giving a profound insight into the deep anxieties experienced by British citizens during one of the most turbulent periods in the nation’s history.

scholarly journals LncRNA MIR17HG promotes colorectal cancer liver metastasis by mediating a glycolysis-associated positive feedback circuit

Oncogene ◽  
2021 ◽  
Author(s):  
Senlin Zhao ◽  
Bingjie Guan ◽  
Yushuai Mi ◽  
Debing Shi ◽  
Ping Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Metastatic Tumor ◽  
Feedback Circuit ◽  
Colorectal Cancer Liver Metastasis ◽  
Positive Feedback Circuit

AbstractGlycolysis plays a crucial role in reprogramming the metastatic tumor microenvironment. A series of lncRNAs have been identified to function as oncogenic molecules by regulating glycolysis. However, the roles of glycolysis-related lncRNAs in regulating colorectal cancer liver metastasis (CRLM) remain poorly understood. In the present study, the expression of the glycolysis-related lncRNA MIR17HG gradually increased from adjacent normal to CRC to the paired liver metastatic tissues, and high MIR17HG expression predicted poor survival, especially in patients with liver metastasis. Functionally, MIR17HG promoted glycolysis in CRC cells and enhanced their invasion and liver metastasis in vitro and in vivo. Mechanistically, MIR17HG functioned as a ceRNA to regulate HK1 expression by sponging miR-138-5p, resulting in glycolysis in CRC cells and leading to their invasion and liver metastasis. More interestingly, lactate accumulated via glycolysis activated the p38/Elk-1 signaling pathway to promote the transcriptional expression of MIR17HG in CRC cells, forming a positive feedback loop, which eventually resulted in persistent glycolysis and the invasion and liver metastasis of CRC cells. In conclusion, the present study indicates that the lactate-responsive lncRNA MIR17HG, acting as a ceRNA, promotes CRLM through a glycolysis-mediated positive feedback circuit and might be a novel biomarker and therapeutic target for CRLM.

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