Constructing living buildings: a review of relevant technologies for a novel application of biohybrid robotics

Biohybrid robotics takes an engineering approach to the expansion and exploitation of biological behaviours for application to automated tasks. Here, we identify the construction of living buildings and infrastructure as a high-potential application domain for biohybrid robotics, and review technological advances relevant to its future development. Construction, civil infrastructure maintenance and building occupancy in the last decades have comprised a major portion of economic production, energy consumption and carbon emissions. Integrating biological organisms into automated construction tasks and permanent building components therefore has high potential for impact. Live materials can provide several advantages over standard synthetic construction materials, including self-repair of damage, increase rather than degradation of structural performance over time, resilience to corrosive environments, support of biodiversity, and mitigation of urban heat islands. Here, we review relevant technologies, which are currently disparate. They span robotics, self-organizing systems, artificial life, construction automation, structural engineering, architecture, bioengineering, biomaterials, and molecular and cellular biology. In these disciplines, developments relevant to biohybrid construction and living buildings are in the early stages, and typically are not exchanged between disciplines. We, therefore, consider this review useful to the future development of biohybrid engineering for this highly interdisciplinary application.publishe

Proinflammatory and Cytotoxic Effects of Hexadecylphosphocholine (Miltefosine) against Drug-Resistant Strains of Trypanosoma cruzi

The increased resistance of the protozoan parasite Trypanosoma cruzi to nitro derivatives is one of the major problems for the successful treatment of Chagas' disease. In the present study, we have tested the effects of 1-O-hexadecylphosphocholine (miltefosine) against strains of T. cruzi that are partially resistant (strain Y) and highly resistant (strain Colombiana) to the drugs in clinical use. As expected, epimastigotes of strain Colombiana showed higher levels of resistance to benznidazole than those of strain Y. However, the level of resistance to miltefosine was the same for both strains. This alkylphospholipid was also extremely toxic against intracellular amastigotes of both strains. This ether-lipid analogue induced in a dose-dependent manner the production of tumor necrosis factor alpha and nitric oxide (NO) radicals by infected and noninfected macrophages, suggesting that miltefosine may activate macrophages in vitro. Nevertheless, the cytotoxic effect of miltefosine against intracellular amastigotes was independent of the amount of NO produced by the infected macrophages since the same dose-response curves for miltefosine were observed when the NO production was blocked by the NO synthase inhibitor N(G)-monomethyl-l-arginine monoacetate. Preliminary in vivo studies with BALB/c mice infected with strain Y indicated that oral miltefosine promoted survival and reduced the parasitemia to levels comparable to those observed when benznidazole was used. Four months after treatment, no parasites were detected in the blood or spleen tissue sections maintained in culture. Together, these results support the hypothesis that miltefosine may be used for the treatment of Chagas' disease, including cases caused by resistant strains of T. cruzi

Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response

Submitted by sandra infurna ([email protected]) on 2016-04-28T14:57:30Z No. of bitstreams: 1 isabela_pereira_etal_IOC_2015.pdf: 6043084 bytes, checksum: 03af83923a25cfd4e95c3be608b6e3b2 (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-04-28T15:07:54Z (GMT) No. of bitstreams: 1 isabela_pereira_etal_IOC_2015.pdf: 6043084 bytes, checksum: 03af83923a25cfd4e95c3be608b6e3b2 (MD5)Made available in DSpace on 2016-04-28T15:07:54Z (GMT). No. of bitstreams: 1 isabela_pereira_etal_IOC_2015.pdf: 6043084 bytes, checksum: 03af83923a25cfd4e95c3be608b6e3b2 (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Cardiologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.BACKGROUND: Chronic chagasic cardiomyopathy (CCC), the main clinical sign of Chagas disease, is associated with systemic CD8+ T-cell abnormalities and CD8-enriched myocarditis occurring in an inflammatory milieu. Pentoxifylline (PTX), a phosphodiesterase inhibitor, has immunoregulatory and cardioprotective properties. Here, we tested PTX effects on CD8+ T-cell abnormalities and cardiac alterations using a model of experimental Chagas' heart disease. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 mice chronically infected by the Colombian Trypanosoma cruzi strain and presenting signs of CCC were treated with PTX. The downmodulation of T-cell receptors on CD8+ cells induced by T. cruzi infection was rescued by PTX therapy. Also, PTX reduced the frequency of CD8+ T-cells expressing activation and migration markers in the spleen and the activation of blood vessel endothelial cells and the intensity of inflammation in the heart tissue. Although preserved interferon-gamma production systemically and in the cardiac tissue, PTX therapy reduced the number of perforin+ cells invading this tissue. PTX did not alter parasite load, but hampered the progression of heart injury, improving connexin 43 expression and decreasing fibronectin overdeposition. Further, PTX reversed electrical abnormalities as bradycardia and prolonged PR, QTc and QRS intervals in chronically infected mice. Moreover, PTX therapy improved heart remodeling since reduced left ventricular (LV) hypertrophy and restored the decreased LV ejection fraction. CONCLUSIONS/SIGNIFICANCE: PTX therapy ameliorates critical aspects of CCC and repositioned CD8+ T-cell response towards homeostasis, reinforcing that immunological abnormalities are crucially linked, as cause or effect, to CCC. Therefore, PTX emerges as a candidate to treat the non-beneficial immune deregulation associated with chronic Chagas' heart disease and to improve prognosis

CCL3/Macrophage Inflammatory Protein-1α Is Dually Involved in Parasite Persistence and Induction of a TNF- and IFNγ-Enriched Inflammatory Milieu in Trypanosoma cruzi-Induced Chronic Cardiomyopathy

Submitted by Sandra Infurna ([email protected]) on 2020-03-29T17:24:07Z No. of bitstreams: 1 JoseliLVieira_GlauciaPereira_etal_IOC_2020.pdf: 4148062 bytes, checksum: 271051d3a2e4d93789b5f0c58b65f292 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2020-03-29T17:46:56Z (GMT) No. of bitstreams: 1 JoseliLVieira_GlauciaPereira_etal_IOC_2020.pdf: 4148062 bytes, checksum: 271051d3a2e4d93789b5f0c58b65f292 (MD5)Made available in DSpace on 2020-03-29T17:46:56Z (GMT). No. of bitstreams: 1 JoseliLVieira_GlauciaPereira_etal_IOC_2020.pdf: 4148062 bytes, checksum: 271051d3a2e4d93789b5f0c58b65f292 (MD5) Previous issue date: 2020Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Laboratório de Hematologia. Niterói, RJ, Brasil.Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Cardiologia Celular e Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro; Centro de Ciências da Saúde. Centro Nacional de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.CCL3, a member of the CC-chemokine family, has been associated with macrophage recruitment to heart tissue and parasite control in the acute infection of mouse with Trypanosoma cruzi, the causative agent of Chagas disease. Here, we approached the participation of CCL3 in chronic chagasic cardiomyopathy (CCC), the main clinical form of Chagas disease. We induced CCC in C57BL/6 (ccl3+/+) and CCL3-deficient (ccl3-/-) mice by infection with the Colombian Type I strain. In ccl3+/+ mice, high levels of CCL3 mRNA and protein were detected in the heart tissue during the acute and chronic infection. Survival was not affected by CCL3 deficiency. In comparison with ccl3+/+, chronically infected ccl3-/- mice presented reduced cardiac parasitism and inflammation due to CD8+ cells and macrophages. Leukocytosis was decreased in infected ccl3-/- mice, paralleling the accumulation of CD8+ T cells devoid of activated CCR5+ LFA-1+ cells in the spleen. Further, T. cruzi-infected ccl3-/-mice presented reduced frequency of interferon-gamma (IFNγ)+ cells and numbers of parasite-specific IFNγ-producing cells, while the T. cruzi antigen-specific cytotoxic activity was increased. Stimulation of CCL3-deficient macrophages with IFNγ improved parasite control, in a milieu with reduced nitric oxide (NOx) and tumor necrosis factor (TNF), but similar interleukin-10 (IL-10), concentrations. In comparison with chronically T. cruzi-infected ccl3+/+ counterparts, ccl3-/- mice did not show enlarged heart, loss of left ventricular ejection fraction, QTc prolongation and elevated CK-MB activity. Compared with ccl3+/+, infected ccl3-/- mice showed reduced concentrations of TNF, while IL-10 levels were not affected, in the heart milieu. In spleen of ccl3+/+ NI controls, most of the CD8+ T-cells expressing the CCL3 receptors CCR1 or CCR5 were IL-10+, while in infected mice these cells were mainly TNF+. Lastly, selective blockage of CCR1/CCR5 (Met-RANTES therapy) in chronically infected ccl3+/+ mice reversed pivotal electrical abnormalities (bradycardia, prolonged PR, and QTc interval), in correlation with reduced TNF and, mainly, CCL3 levels in the heart tissue. Therefore, in the chronic T. cruzi infection CCL3 takes part in parasite persistence and contributes to form a CD8+ T-cell and macrophage-enriched cardiac inflammation. Further, increased levels of CCL3 create a scenario with abundant IFNγ and TNF, associated with cardiomyocyte injury, heart dysfunction and QTc prolongation, biomarkers of severity of Chagas' heart disease

Additional File 4: Figure S4.

Pre-treatment of fibroblast with rTNF does not affect infection by Trypanosoma cruzi. (a) Experimental scheme showing that L-929 fibroblasts were pre-treated with TNF (1 ng/mL) and subsequently infected with trypomastigote forms of the Colombian T. cruzi strain. (b-c) The percentage of infected cells and the number of parasites per cells were analyzed at 4 h (b) and 24 h (c) of infection, at a MOI of 1:1 or 10:1. Data are presented as mean ± SEM of duplicates. (TIFF 1430 kb