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The plant cell wall is an important factor for determining cell shape, function and response to the environment. Secondary cell walls, such as those found in xylem, are composed of cellulose, hemicelluloses and lignin and account for the bulk of plant biomass. The coordination between transcriptional regulation of synthesis for each polymer is complex and vital to cell function. A regulatory hierarchy of developmental switches has been proposed, although the full complement of regulators remains unknown. Here we present a protein-DNA network between Arabidopsis thaliana transcription factors and secondary cell wall metabolic genes with gene expression regulated by a series of feed-forward loops. This model allowed us to develop and validate new hypotheses about secondary wall gene regulation under abiotic stress. Distinct stresses are able to perturb targeted genes to potentially promote functional adaptation. These interactions will serve as a foundation for understanding the regulation of a complex, integral plant component.

Metamaterials are designed to realize exotic physical properties through the geometric arrangement of their underlying structural layout 1,2 . Traditional mechanical metamaterials achieve functionalities such as a target Poisson's ratio 3 or shape transformation 4-6 through unit-cell optimization 7-9 , often with spatial heterogeneity 10-12 . These functionalities are programmed into the layout of the metamaterial in a way that cannot be altered. Although recent efforts have produced means of tuning such properties post-fabrication 13-19 , they have not demonstrated mechanical reprogrammability analogous to that of digital devices, such as hard disk drives, in which each unit can be written to or read from in real time as required. Here we overcome this challenge by using a design framework for a tileable mechanical metamaterial with stable memory at the unit-cell level. Our design comprises an array of physical binary elements (m-bits), analogous to digital bits, with clearly delineated writing and reading phases. Each m-bit can be independently and reversibly switched between two stable states (acting as memory) using magnetic actuation to move between the equilibria of a bistable shell 20-25 . Under deformation, each state is associated with a distinctly different mechanical response that is fully elastic and can be reversibly cycled until the system is reprogrammed. Encoding a set of binary instructions onto the tiled array yields markedly different mechanical properties; specifically, the stiffness and strength can be made to range over an order of magnitude. We expect that the stable memory and on-demand reprogrammability of mechanical properties in this design paradigm will facilitate the development of advanced forms of mechanical metamaterials.

Germline activating mutations of the protein tyrosine phosphatase SHP2 (encoded by PTPN11), a positive regulator of the RAS signalling pathway, are found in 50% of patients with Noonan syndrome. These patients have an increased risk of developing leukaemia, especially juvenile myelomonocytic leukaemia (JMML), a childhood myeloproliferative neoplasm (MPN). Previous studies have demonstrated that mutations in Ptpn11 induce a JMML-like MPN through cell-autonomous mechanisms that are dependent on Shp2 catalytic activity. However, the effect of these mutations in the bone marrow microenvironment remains unclear. Here we report that Ptpn11 activating mutations in the mouse bone marrow microenvironment promote the development and progression of MPN through profound detrimental effects on haematopoietic stem cells (HSCs). Ptpn11 mutations in mesenchymal stem/progenitor cells and osteoprogenitors, but not in differentiated osteoblasts or endothelial cells, cause excessive production of the CC chemokine CCL3 (also known as MIP-1α), which recruits monocytes to the area in which HSCs also reside. Consequently, HSCs are hyperactivated by interleukin-1β and possibly other proinflammatory cytokines produced by monocytes, leading to exacerbated MPN and to donor-cell-derived MPN following stem cell transplantation. Remarkably, administration of CCL3 receptor antagonists effectively reverses MPN development induced by the Ptpn11-mutated bone marrow microenvironment. This study reveals the critical contribution of Ptpn11 mutations in the bone marrow microenvironment to leukaemogenesis and identifies CCL3 as a potential therapeutic target for controlling leukaemic progression in Noonan syndrome and for improving stem cell transplantation therapy in Noonan-syndrome-associated leukaemias.