Computers from plants we never made. Speculations

We discuss possible designs and prototypes of computing systems that could be based on morphological development of roots, interaction of roots, and analog electrical computation with plants, and plant-derived electronic components. In morphological plant processors data are represented by initial configuration of roots and configurations of sources of attractants and repellents; results of computation are represented by topology of the roots' network. Computation is implemented by the roots following gradients of attractants and repellents, as well as interacting with each other. Problems solvable by plant roots, in principle, include shortest-path, minimum spanning tree, Voronoi diagram, $\alpha$-shapes, convex subdivision of concave polygons. Electrical properties of plants can be modified by loading the plants with functional nanoparticles or coating parts of plants of conductive polymers. Thus, we are in position to make living variable resistors, capacitors, operational amplifiers, multipliers, potentiometers and fixed-function generators. The electrically modified plants can implement summation, integration with respect to time, inversion, multiplication, exponentiation, logarithm, division. Mathematical and engineering problems to be solved can be represented in plant root networks of resistive or reaction elements. Developments in plant-based computing architectures will trigger emergence of a unique community of biologists, electronic engineering and computer scientists working together to produce living electronic devices which future green computers will be made of.Comment: The chapter will be published in "Inspired by Nature. Computing inspired by physics, chemistry and biology. Essays presented to Julian Miller on the occasion of his 60th birthday", Editors: Susan Stepney and Andrew Adamatzky (Springer, 2017

Irradiation leads to apoptosis of Kupffer cells by a Hsp27-dependant pathway followed by release of TNF-α

In a previous publication, we were able to show that irradiation of Kupffer cells, the liver resident macrophages, leads to an increased TNF-α concentration in the culture medium. The pathomechanisms underlying this phenomenon, however, remained to be elucidated. Here, we show that following irradiation of Kupffer cells, the apoptosis rate increased drastically within 48 h. At the same time, the total TNF-α concentration in cell lysates of Kupffer cells attached to the culture plate decreased. However, normalization of the TNF-α concentration with respect to cell number revealed that TNF-α concentration per attached cell remained constant during the observation period. Western blot analysis showed that heat shock protein 27 (Hsp27) is strongly downregulated and bax is upregulated in irradiated Kupffer cells as compared to sham-irradiated cells. Overexpression of Hsp27 in Kupffer cells was shown to prevent the effect of irradiation on bax expression, apoptosis and, at the same time, on increase of TNF-α concentration in the Kupffer cell medium. We conclude that irradiation of Kupffer cells leads to apoptosis because of downregulation of Hsp27 and consecutive upregulation of bax expression. Furthermore, we suggest that apoptosis of Kupffer cells leads to an increase of TNF-α concentration in the culture medium which may be due to cell death rather than active release or synthesis

Targeting aberrant DNA double strand break repair in triple negative breast cancer with alpha particle emitter radiolabeled anti-EGFR antibody

The greater potential efficacy of alpha-particle emitter radiopharmaceutical therapy lies in the 3 to 8-fold greater biological effectiveness (RBE) of alpha particles relative to photon or beta-particle radiation. The greater RBE, however, generally applies to both tumor and normal tissue, thereby reducing efficacy. Since alpha particles typically cause DNA double strand breaks (DSBs), targeting tumors that are defective in DNA DSB repair would effectively increase the RBE, yielding a secondary, RBE-based differentiation between tumor and normal tissue that is complementary to conventional, delivery-based tumor targeting. In some triple negative breast cancer (ER-/PR-/HER-2-, TNBC) patients, both germline predisposed mutation or sporadic gene silencing in BRCA-1, a key gene in homologous recombination (HR) DSB repair, are well established. Such patients have few treatment options once the cancer has metastasized. In this study, we investigated the efficacy of alpha particle emitter, 213Bi labeled anti-EGFR antibody, Cetuximab, in TNBC cells that are defective in DNA DSB repair. 213Bi-Cetuximab was found to be significantly more effective in BRCA-1 mutated TNBC cell HCC1937. siRNA knockdown of BRCA-1 or DNA-PKcs, a key gene in non-homologous end joining (NHEJ) DSB repair, sensitized TNBC cells to 213Bi-Cetuximab. Furthermore, the small molecule inhibitor of DNA-PKcs, NU7441, also sensitized TNBC cells to alpha radiation. Both immunofluorescent staining of H2AX foci and Comet assay confirmed that enhanced RBE is caused by impaired DNA DSB repair. These data suggest a strategy for enhancing conventional receptor-mediated targeting with an additional, potentially synergistic radiobiological alpha-emitter targeting that could be applied to TNBC metastases.JRC.E.5-Nuclear chemistr