A reprogrammable mechanical metamaterial with stable memory

Nature ◽  
2021 ◽  
Vol 589 (7842) ◽  
pp. 386-390
Author(s):  
Tian Chen ◽  
Mark Pauly ◽  
Pedro M. Reis
Keyword(s):  
2020 ◽  
Vol 27 (5) ◽  
pp. 177-189
Author(s):  
Cuihong Li ◽  
Zhongyu Hu ◽  
Jiongjiong Yang

2020 ◽  
Author(s):  
Igor L. Bado ◽  
Hai Wang ◽  
Poonam Sarkar ◽  
Jun Liu ◽  
William Wu ◽  
...  

SummaryER+ breast cancer exhibits a strong bone-tropism in metastasis. How the bone microenvironment impacts the ER signaling and endocrine therapies remains poorly understood. Here, we discover that the osteogenic niche transiently reduces ER expression and activities specifically in bone micrometastases (BMMs), leading to endocrine resistance. This is mediated by gap junctions and paracrine FGF/PDGF signaling, which together generate a stable “memory”: cancer cells extracted from bone remain resistant to endocrine therapies for several generations. Using single cell-derived populations (SCPs), we demonstrated that this process is independent of clonal selection, and represents an EZH2-mediated epigenomic reprogramming. EZH2 drives ER+ BMMs toward a basal and stem-like state. EZH2 inhibition reverses endocrine resistance. Our data demonstrates how epigenomic adaptation to the bone microenvironment drives phenotypic plasticity of metastatic seeds and alters their therapeutic responses together with clonal selection, and provides insights into the clinical enigma of ER+ metastatic recurrences despite endocrine therapies.


1983 ◽  
Vol 17 (1) ◽  
pp. 16-16 ◽  
Author(s):  
R. M. Needham ◽  
A. J. Herbert ◽  
J. G. Mitchell
Keyword(s):  

2020 ◽  
Author(s):  
Zhe Zhao ◽  
Mai Shi ◽  
Tianyuan Zhu ◽  
Huimeng Wang ◽  
Troi Pediongco ◽  
...  

Abstract Mucosal-Associated Invariant T (MAIT) cells have potent antibacterial functions. Their protective capacity, in vivo, has been demonstrated in mouse models, particularly of respiratory infections. We now show that during systemic infection of mice with Francisella tularensis Live Vaccine Strain (LVS), MAIT cell expansion was evident in the liver, lungs, kidney, spleen and blood. MAIT cells manifested a polarised Th1-like (termed “MAIT-1”) phenotype and cytokine profile that conferred a critical role in controlling bacterial load. After resolution of the primary infection, the expanded MAIT cells developed to a stable memory-like MAIT-1 cell population, suggesting a basis for vaccination and protection against subsequent challenge. Indeed, a systemic vaccination with synthetic ligand (5-OP-RU) in combination with CpG adjuvant boosted MAIT-1 cells and resulted in enhanced protection against systemic and local infections with F. tularensis and Legionella longbeachae. Our study highlights the potential utility of targeting MAIT cells to combat multiple bacterial pathogens.


2021 ◽  
Author(s):  
Peter Vavra ◽  
Leo Sokolovič ◽  
Emanuele Porcu ◽  
Pablo Ripollés ◽  
Antoni Rodríguez-Fornells ◽  
...  

Recently, we provided causal evidence that self-regulated dopamine signaling enhanced long-term memory formation in the absence of any external feedback or reward (Ripollés et al., 2016, 2018) if a congruent meaning inferred from semantic context (DA-dependent learning), while DA-signals were absent if no congruent meaning could be inferred (DA-independent learning). Here, we investigated the interaction of self-regulated learning with externally-regulated DA-signalling by providing external performance feedback in the first or second half of trials. We found that removing feedback during DA-dependent learning lowered subsequent recognition rates a day later, whereas recognition remained high in the group which received feedback only in the second half. In contrast, feedback modestly enhanced recognition rates for both groups for DA-independent learning. Our findings suggest that external reinforcers can selectively impair DA-dependent memories if internal DA-dependent processes are not already established and highlights the relevance of self-regulated learning in education to support stable memory formation.


2011 ◽  
Vol 99 (4) ◽  
pp. 042109 ◽  
Author(s):  
Emil B. Song ◽  
Bob Lian ◽  
Sung Min Kim ◽  
Sejoon Lee ◽  
Tien-Kan Chung ◽  
...  

2015 ◽  
Vol 112 (13) ◽  
pp. 4146-4151 ◽  
Author(s):  
Andrew Angel ◽  
Jie Song ◽  
Hongchun Yang ◽  
Julia I. Questa ◽  
Caroline Dean ◽  
...  

A fundamental property of many organisms is an ability to sense, evaluate, and respond to environmental signals. In some situations, generation of an appropriate response requires long-term information storage. A classic example is vernalization, where plants quantitatively sense long-term cold and epigenetically store this cold-exposure information to regulate flowering time. In Arabidopsis thaliana, stable epigenetic memory of cold is digital: following long-term cold exposure, cells respond autonomously in an all-or-nothing fashion, with the fraction of cells that stably silence the floral repressor FLOWERING LOCUS C (FLC) increasing with the cold exposure duration. However, during cold exposure itself it is unknown whether vernalizing cold is registered at FLC in individual cells in an all-or-nothing (digital) manner or is continuously varying (analog). Using mathematical modeling, we found that analog registration of cold temperature is problematic due to impaired analog-to-digital conversion into stable memory. This disadvantage is particularly acute when responding to short cold periods, but is absent when cold temperatures are registered digitally at FLC. We tested this prediction experimentally, exposing plants to short periods of cold interrupted with even shorter warm breaks. For FLC expression, we found that the system responds similarly to both interrupted and uninterrupted cold, arguing for a digital mechanism integrating long-term temperature exposure.


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