Up-scale challenges on biopolymer production from waste streams by Purple Phototrophic Bacteria mixed cultures: A critical review

Financial support from the Regional Government of Madrid through the project S2018/EMT-4344 BIOTRES-CM is gratefully acknowledged. D. Puyol wishes to thank the Spanish Ministry of Economy for the Ramon y Cajal grant. J. FThe increasing volume of waste streams require new biological technologies that can address pollution concerns while offering sustainable products. Purple phototrophic bacteria (PPB) are very versatile organisms that present a unique metabolism that allows them to adapt to a variety of environments, including the most complex waste streams. Their successful adaptation to such demanding conditions is partly the result of internal polymers accumulation which can be stored for electron/energy balance or as carbon and nutrients reserves for deprivation periods. Polyhydroxyalkanoates, glycogen, sulphur and polyphosphate are examples of polymers produced by PPB that can be economically explored due to their applications in the plastic, energy and fertilizers sectors. Their large-scale production implies the outdoor operation of PPB systems which brings new challenges, identified in this review. An overview of the current PPB polymer producing technologies and prospects for their future development is also provided.publishersversionpublishe

A mechanistic model for anaerobic phototrophs in domestic wastewater applications: photo-anaerobic model (PAnM)

Purple phototrophic bacteria (PPB) have been recently proposed as a key potential mechanism for accumulative biotechnologies for wastewater treatment with total nutrient recovery, low greenhouse gas emissions, and a neutral to positive energy balance. Purple phototrophic bacteria have a complex metabolism which can be regulated for process control and optimization. Since microbial processes governing PPB metabolism differ from traditional processes used for wastewater treatment (e.g., aerobic and anaerobic functional groups in ASM and ADM1), a model basis has to be developed to be used as a framework for further detailed modelling under specific situations. This work presents a mixed population phototrophic model for domestic wastewater treatment in anaerobic conditions. The model includes photoheterotrophy, which is divided into acetate consumption and other organics consumption, chemoheterotrophy (including simplified fermentation and anaerobic oxidation) and photoautotrophy (using hydrogen as an electron donor), as microbial processes, as well as hydrolysis and biomass decay as biochemical processes, and is single-biomass based. The main processes have been evaluated through targeted batch experiments, and the key kinetic and stoichiometric parameters have been determined. The process was assessed by analyzing a continuous reactor simulation scenario within a long-term wastewater treatment system in a photo-anaerobic membrane bioreactor

Probabilistic 3D surface reconstruction from sparse MRI information

Surface reconstruction from magnetic resonance (MR) imaging data is indispensable in medical image analysis and clinical research. A reliable and effective reconstruction tool should: be fast in prediction of accurate well localised and high resolution models, evaluate prediction uncertainty, work with as little input data as possible. Current deep learning state of the art (SOTA) 3D reconstruction methods, however, often only produce shapes of limited variability positioned in a canonical position or lack uncertainty evaluation. In this paper, we present a novel probabilistic deep learning approach for concurrent 3D surface reconstruction from sparse 2D MR image data and aleatoric uncertainty prediction. Our method is capable of reconstructing large surface meshes from three quasi-orthogonal MR imaging slices from limited training sets whilst modelling the location of each mesh vertex through a Gaussian distribution. Prior shape information is encoded using a built-in linear principal component analysis (PCA) model. Extensive experiments on cardiac MR data show that our probabilistic approach successfully assesses prediction uncertainty while at the same time qualitatively and quantitatively outperforms SOTA methods in shape prediction. Compared to SOTA, we are capable of properly localising and orientating the prediction via the use of a spatially aware neural network.Comment: MICCAI 202

Plant-Inspired Polyaleuritate–Nanocellulose Composite Photonic Films

Plant epidermis is a complex composite material composed by the cuticle and the epidermal cells. In order to prevent dehydration the cuticle is a water barrier composed of an outer layer (proper cuticle) connected to the cell wall of the epidermal cells via a complex matrix often referred to as cutinised cell wall, that acts as compatibilizer for the water repellent cutin and the hydrophilic polysaccharides in the cell walls. Here, biomimetic plant epidermis-inspired films with selective reflection properties were prepared by formation of an aliphatic polyester coating on chiral nematic cellulose nanocrystal (CNC) films. Aleuritic acid, a polyhydroxylated fatty acid, was sprayed on CNC films and polymerized by hot-pressing. The micromorphology of the resultant samples was characterized by scanning electron microscopy (SEM). Polarised optical microscopy confirmed the CNCs helicoidal organization in the films, responsible for the reflection of circularly polarised light, before and after the hot-pressing. The chemical analysis by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) confirmed the polymerization of aleuritic acid into polyaleuritate with differences between filter paper and woodpulp substrates that were ascribed to water elimination during polycondensation. The characterization of the mechanical (Young’s modulus and hardness from nanoindentation tests) and hydrodynamic (water uptake and water vapor transmission rate) properties indicated that this process enhances the robustness and waterproof behaviour of CNC films. These properties were comparable to those of commercial and biodegradable materials commonly used in packaging such as polyesters and cellulose derivatives, thus making these natural composite ideal for optically responsive packaging applications.J.A.H.-G. acknowledges the funding by the Spanish “Ministerio de Ciencia, Innovación y Universidades”, project numbers RTI2018-096896-J-I00 and RYC2018-025079-I

Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity

Dysfunction of either the right or left ventricle can lead to heart failure (HF) and subsequent morbidity and mortality. We performed a genome-wide association study (GWAS) of 16 cardiac magnetic resonance (CMR) imaging measurements of biventricular function and structure. Cis-Mendelian randomization (MR) was used to identify plasma proteins associating with CMR traits as well as with any of the following cardiac outcomes: HF, non-ischemic cardiomyopathy, dilated cardiomyopathy (DCM), atrial fibrillation, or coronary heart disease. In total, 33 plasma proteins were prioritized, including repurposing candidates for DCM and/or HF: IL18R (providing indirect evidence for IL18), I17RA, GPC5, LAMC2, PA2GA, CD33, and SLAF7. In addition, 13 of the 25 druggable proteins (52%; 95% confidence interval, 0.31 to 0.72) could be mapped to compounds with known oncological indications or side effects. These findings provide leads to facilitate drug development for cardiac disease and suggest that cardiotoxicities of several cancer treatments might represent mechanism-based adverse effects

CDK1 is a synthetic lethal target for KRAS mutant tumours.

Activating KRAS mutations are found in approximately 20% of human cancers but no RAS-directed therapies are currently available. Here we describe a novel, robust, KRAS synthetic lethal interaction with the cyclin dependent kinase, CDK1. This was discovered using parallel siRNA screens in KRAS mutant and wild type colorectal isogenic tumour cells and subsequently validated in a genetically diverse panel of 26 colorectal and pancreatic tumour cell models. This established that the KRAS/CDK1 synthetic lethality applies in tumour cells with either amino acid position 12 (p.G12V, pG12D, p.G12S) or amino acid position 13 (p.G13D) KRAS mutations and can also be replicated in vivo in a xenograft model using a small molecule CDK1 inhibitor. Mechanistically, CDK1 inhibition caused a reduction in the S-phase fraction of KRAS mutant cells, an effect also characterised by modulation of Rb, a master control of the G1/S checkpoint. Taken together, these observations suggest that the KRAS/CDK1 interaction is a robust synthetic lethal effect worthy of further investigation

First results of the CAST-RADES haloscope search for axions at 34.67 μeV

We present results of the Relic Axion Dark-Matter Exploratory Setup (RADES), a detector which is part of the CERN Axion Solar Telescope (CAST), searching for axion dark matter in the 34.67μeV mass range. A radio frequency cavity consisting of 5 sub-cavities coupled by inductive irises took physics data inside the CAST dipole magnet for the first time using this filter-like haloscope geometry. An exclusion limit with a 95% credibility level on the axion-photon coupling constant of gaγ & 4 × 10−13 GeV−1 over a mass range of 34.6738μeV < ma < 34.6771μeV is set. This constitutes a significant improvement over the current strongest limit set by CAST at this mass and is at the same time one of the most sensitive direct searches for an axion dark matter candidate above the mass of 25μeV. The results also demonstrate the feasibility of exploring a wider mass range around the value probed by CAST-RADES in this work using similar coherent resonant cavitiesWe wish to thank our colleagues at CERN, in particular Marc Thiebert from the coating lab, as well as the whole team of the CERN Central Cryogenic Laboratory for their support and advice in speci c aspects of the project. We thank Arefe Abghari for her contributions as the project's summer student during 2018. This work has been funded by the Spanish Agencia Estatal de Investigacion (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) under project FPA-2016-76978-C3-2-P and PID2019-108122GB-C33, and was supported by the CERN Doctoral Studentship programme. The research leading to these results has received funding from the European Research Council and BD, JG and SAC acknowledge support through the European Research Council under grant ERC-2018-StG-802836 (AxScale project). BD also acknowledges fruitful discussions at MIAPP supported by DFG under EXC-2094 { 390783311. IGI acknowledges also support from the European Research Council (ERC) under grant ERC-2017-AdG-788781 (IAXO+ project). JR has been supported by the Ramon y Cajal Fellowship 2012-10597, the grant PGC2018-095328-B-I00(FEDER/Agencia estatal de investigaci on) and FSE-GA2017-2019-E12/7R (Gobierno de Aragón/FEDER) (MINECO/FEDER), the EU through the ITN \Elusives" H2020-MSCA-ITN-2015/674896 and the Deutsche Forschungsgemeinschaft under grant SFB-1258 as a Mercator Fellow. CPG was supported by PROMETEO II/2014/050 of Generalitat Valenciana, FPA2014-57816-P of MINECO and by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreements 690575 and 674896. AM is supported by the European Research Council under Grant No. 742104. Part of this work was performed under the auspices of the US Department of Energy by Lawrence Livermore National Laboratory under Contract No. DE-AC52-07NA27344

Twist1 Suppresses Senescence Programs and Thereby Accelerates and Maintains Mutant Kras-Induced Lung Tumorigenesis

KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with KrasG12D to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy