Burden-driven feedback control of gene expression

Cells use feedback regulation to ensure robust growth despite fluctuating demands for resources and differing environmental conditions. However, the expression of foreign proteins from engineered constructs is an unnatural burden that cells are not adapted for. Here we combined RNA-seq with an in vivo assay to identify the major transcriptional changes that occur in Escherichia coli when inducible synthetic constructs are expressed. We observed that native promoters related to the heat-shock response activated expression rapidly in response to synthetic expression, regardless of the construct. Using these promoters, we built a dCas9-based feedback-regulation system that automatically adjusts the expression of a synthetic construct in response to burden. Cells equipped with this general-use controller maintained their capacity for native gene expression to ensure robust growth and thus outperformed unregulated cells in terms of protein yield in batch production. This engineered feedback is to our knowledge the first example of a universal, burden-based biomolecular control system and is modular, tunable and portable

Synthesis, characterization and application of novel MnO and CuO impregnated biochar composites to sequester arsenic (As) from water: Modeling, thermodynamics and reusability

© 2020 Elsevier B.V. The present study aimed at enhancing the adsorption potential of novel nanocomposites of Sesbania bispinosa biochar (SBC) with copper oxide (SBC/CuO) and manganese oxide nanoparticles (SBC/MnO) for the efficient and inexpensive removal of environmentally concerned contaminant arsenic (As) from contaminated water at batch scale. The scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, energy dispersive X-ray (EDX), X-ray diffraction (XRD) and point of zero charge (PZC) analyses proved successful impregnation of the metallic nanoparticles on SBC surface. The results revealed the maximum As removal (96 %) and adsorption (12.47 mg/g) by SBC/CuO composite at 10 mg As/L, optimum pH-4, dose 1.0 g/L and ambient temperature (25 ± 1.5 °C) as compared with SBC (7.33 mg/g) and SBC/MnO (7.34 mg/g). Among four types of adsorption isotherms, Freundlich isotherm demonstrated best fit with R2 \u3e 0.997. While pseudo second-order kinetic model revealed better agreement with kinetic experimental data as matched with other kinetic models. The thermodynamic results depicted that As adsorption on the as-synthesized adsorbents was endothermic and spontaneous in nature with increased randomness. The SBC/CuO displayed excellent reusability and stability over four adsorption/desorption cycles and proved that the as-synthesized SBC/CuO composite may be the efficient adsorbent for practical removal of As from contaminated water

Graphene-based fabrics and their applications: a review

[EN] Graphene has emerged as a revolutionary material in different fields of science and engineering due to its extraordinary properties such as: high electron mobility, high thermal conductivity, mechanical properties, easy functionalization, etc. The field of textiles is continuously integrating new materials to provide fabrics with new functionalities, hence its incorporation on fabrics was a logical step. Its application to the field of textiles has been recently reported, which has allowed the development of textiles with different functionalities such as: antistatic, UV-protecting, electroconductive, photocatalytic, antibacterial, thermal conductivity, energy storage in flexible supercapacitors, electrodes for batteries, sensors, etc. Up to date no review has been written regarding graphene-based fabrics and their applications. The present review aims to fill the existing gap and provide perspectives into the preparation and applications of graphene-based fabrics and yarns.J. Molina wishes to thank to the Spanish Ministerio de Ciencia e Innovacion (contract CTM2011-23583) for the financial support. J. Molina is grateful to the Conselleria d'Educacio, Formacio i Ocupacio (Generalitat Valenciana) for the Programa VALi + D Postdoctoral Fellowship (APOSTD/2013/056).Molina Puerto, J. (2016). Graphene-based fabrics and their applications: a review. RSC Advances. 6:68261-68291. https://doi.org/10.1039/c6ra12365aS6826168291

Casual Compressive Sensing for Gene Network Inference

We propose a novel framework for studying causal inference of gene interactions using a combination of compressive sensing and Granger causality techniques. The gist of the approach is to discover sparse linear dependencies between time series of gene expressions via a Granger-type elimination method. The method is tested on the Gardner dataset for the SOS network in E. coli, for which both known and unknown causal relationships are discovered

Spinal Astrocytic Activation Is Involved in a Virally-Induced Rat Model of Neuropathic Pain

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and “NO-Astrocyte-Cytokine-NMDAR-Neuron” pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN

Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics

We have noted in previous work, in a variety of inflammatory diseases, where iron dysregulation occurs, a strong tendency for erythrocytes to lose their normal discoid shape and to adopt a skewed morphology (as judged by their axial ratios in the light microscope and by their ultrastructure in the SEM). Similarly, the polymerization of fibrinogen, as induced in vitro by added thrombin, leads not to the common ‘spaghetti-like’ structures but to dense matted deposits. Type 2 diabetes is a known inflammatory disease. In the present work, we found that the axial ratio of the erythrocytes of poorly controlled (as suggested by increased HbA1c levels) type 2 diabetics was significantly increased, and that their fibrin morphologies were again highly aberrant. As judged by scanning electron microscopy and in the atomic force microscope, these could be reversed, to some degree, by the addition of the iron chelators deferoxamine (DFO) or deferasirox (DFX). As well as their demonstrated diagnostic significance, these morphological indicators may have prognostic value.Biotechnology and Biological Sciences Research Council (grant BB/L025752/1) as well as the National Research Foundation (NRF) of South Africa.http://www.cardiab.com/hb201

Global burden of cardiovascular diseases and risk factors, 1990-2019 : Update from the GBD 2019 Study

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases