Bioreactor Mixing: a Comparison of Computational Fluid Dynamics and Experimental Approaches in the Pursuit of Sustainable Bioprocessing for the Bioeconomy

This paper highlights the importance of bioreactors in the bioeconomy, focusing on the role of mechanical mixing in promoting optimal conditions for microorganism growth and productivity. Computational fluid dynamics (CFD) simulations are increasingly used in bioreactor design to predict fluid dynamics and mixing characteristics. This study utilizes CFD simulations with OpenFOAM® to predict the power number of various stirring devices in a lab-scale reactor. The torque and power number results of three different stirrers were compared through experimental and simulation methods. The pitched blade and cage impeller showed an increase in experimental torque and power number with rotational speed, while the paddle impeller had much higher experimental values than the simulated values at all speeds. The study demonstrates the value of CFD models for predicting bioreactor performance, despite some inaccuracies in simulations. These findings are important for industries seeking to optimize bioreactor design and increase productivity through better mixing processes

Calibration of TCCON column-averaged CO2: the first aircraft campaign over European TCCON sites

The Total Carbon Column Observing Network (TCCON) is a ground-based network of Fourier Transform Spectrometer (FTS) sites around the globe, where the column abundances of CO2, CH4, N2O, CO and O2 are measured. CO2 is constrained with a precision better than 0.25% (1-σ). To achieve a similarly high accuracy, calibration to World Meteorological Organization (WMO) standards is required. This paper introduces the first aircraft calibration campaign of five European TCCON sites and a mobile FTS instrument. A series of WMO standards in-situ profiles were obtained over European TCCON sites via aircraft and compared with retrievals of CO2 column amounts from the TCCON instruments. The results of the campaign show that the FTS measurements are consistently biased 1.1% ± 0.2% low with respect to WMO standards, in agreement with previous TCCON calibration campaigns. The standard a priori profile for the TCCON FTS retrievals is shown to not add a bias. The same calibration factor is generated using aircraft profiles as a priori and with the TCCON standard a priori. With a calibration to WMO standards, the highly precise TCCON CO2 measurements of total column concentrations provide a suitable database for the calibration and validation of nadir-viewing satellite

Synergetic use of IASI and TROPOMI space borne sensors for generating a tropospheric methane profile product

The thermal infrared nadir spectra of IASI (Infrared Atmospheric Sounding Interferometer) are successfully used for retrievals of different atmospheric trace gas profiles. However, these retrievals offer generally reduced information about the lowermost tropospheric layer due to the lack of thermal contrast close to the surface. Spectra of scattered solar radiation observed in the near and/or short wave infrared, for instance by TROPOMI (TROPOspheric Monitoring Instrument) offer higher sensitivity near ground and are used for the retrieval of total column averaged mixing ratios of a variety of atmospheric trace gases. Here we present a method for the synergetic use of IASI profile and TROPOMI total column data. Our method uses the output of the individual retrievals and consists of linear algebra a posteriori calculations (i.e. calculation after the individual retrievals). We show that this approach is largely equivalent to applying the spectra of the different sensors together in a single retrieval procedure, but with the substantial advantage of being applicable to data generated with different individual retrieval processors, of being very time efficient, and of directly benefiting from the high quality and most recent improvements of the individual retrieval processors.This research has largely benefit from funds of the Deutsche Forschungsgemeinschaft (provided for the two projects MOTIV and TEDDY with IDs/Geschäftszeichen 290612604/GZ:SCHN1126/2-1 and 416767181/GZ:SCHN1126/5-1, respectively) and from support by the European Space Agency in the context the "Sentinel-5p+Innovation (S5p+I) - Water Vapour Isotopologues (H2O-ISO)" activities. Furthermore, we acknowledge funds from the Ministerio de Economía y Competividad from Spain for the project INMENSE (CGL2016-80688-P)

SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease

Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10−12). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10−5), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10−3). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-4

Global CO2 fluxes inferred from surface air-sample measurements and from TCCON retrievals of the CO2 total column

We present the first estimate of the global distribution of CO2surface fluxes from 14 stations of the Total Carbon Column Observing Network (TCCON). The evaluation of this inversion is based on 1) comparison with the fluxes from a classical inversion of surface air-sample-measurements, and 2) comparison of CO2mixing ratios calculated from the inverted fluxes with independent aircraft measurements made during the two years analyzed here, 2009 and 2010. The former test shows similar seasonal cycles in the northern hemisphere and consistent regional carbon budgets between inversions from the two datasets, even though the TCCON inversion appears to be less precise than the classical inversion. The latter test confirms that the TCCON inversion has improved the quality (i.e., reduced the uncertainty) of the surface fluxes compared to the assumed or prior fluxes. The consistency between the surface-air-sample-based and the TCCON-based inversions despite remaining flaws in transport models opens the possibility of increased accuracy and robustness of flux inversions based on the combination of both data sources and confirms the usefulness of space-borne monitoring of the CO2 column.It was co-funded by the European Commission under the EU Seventh Research Framework Programme (grants agreements 218793, MACC, and 212196, COCOS

Dopaminergic Neuronal Loss, Reduced Neurite Complexity and Autophagic Abnormalities in Transgenic Mice Expressing G2019S Mutant LRRK2

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant familial Parkinson's disease (PD) and also contribute to idiopathic PD. LRRK2 mutations represent the most common cause of PD with clinical and neurochemical features that are largely indistinguishable from idiopathic disease. Currently, transgenic mice expressing wild-type or disease-causing mutants of LRRK2 have failed to produce overt neurodegeneration, although abnormalities in nigrostriatal dopaminergic neurotransmission have been observed. Here, we describe the development and characterization of transgenic mice expressing human LRRK2 bearing the familial PD mutations, R1441C and G2019S. Our study demonstrates that expression of G2019S mutant LRRK2 induces the degeneration of nigrostriatal pathway dopaminergic neurons in an age-dependent manner. In addition, we observe autophagic and mitochondrial abnormalities in the brains of aged G2019S LRRK2 mice and markedly reduced neurite complexity of cultured dopaminergic neurons. These new LRRK2 transgenic mice will provide important tools for understanding the mechanism(s) through which familial mutations precipitate neuronal degeneration and PD

High LRRK2 Levels Fail to Induce or Exacerbate Neuronal Alpha-Synucleinopathy in Mouse Brain

The G2019S mutation in the multidomain protein leucine-rich repeat kinase 2 (LRRK2) is one of the most frequently identified genetic causes of Parkinson’s disease (PD). Clinically, LRRK2(G2019S) carriers with PD and idiopathic PD patients have a very similar disease with brainstem and cortical Lewy pathology (α-synucleinopathy) as histopathological hallmarks. Some patients have Tau pathology. Enhanced kinase function of the LRRK2(G2019S) mutant protein is a prime suspect mechanism for carriers to develop PD but observations in LRRK2 knock-out, G2019S knock-in and kinase-dead mutant mice suggest that LRRK2 steady-state abundance of the protein also plays a determining role. One critical question concerning the molecular pathogenesis in LRRK2(G2019S) PD patients is whether α-synuclein (aSN) has a contributory role. To this end we generated mice with high expression of either wildtype or G2019S mutant LRRK2 in brainstem and cortical neurons. High levels of these LRRK2 variants left endogenous aSN and Tau levels unaltered and did not exacerbate or otherwise modify α-synucleinopathy in mice that co-expressed high levels of LRRK2 and aSN in brain neurons. On the contrary, in some lines high LRRK2 levels improved motor skills in the presence and absence of aSN-transgene-induced disease. Therefore, in many neurons high LRRK2 levels are well tolerated and not sufficient to drive or exacerbate neuronal α-synucleinopathy

Molecular changes in the postmortem parkinsonian brain

Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease. Although PD has a relatively narrow clinical phenotype, it has become clear that its etiological basis is broad. Post-mortem brain analysis, despite its limitations, has provided invaluable insights into relevant pathogenic pathways including mitochondrial dysfunction, oxidative stress and protein homeostasis dysregulation. Identification of the genetic causes of PD followed the discovery of these abnormalities, and reinforced the importance of the biochemical defects identified post-mortem. Recent genetic studies have highlighted the mitochondrial and lysosomal areas of cell function as particularly significant in mediating the neurodegeneration of PD. Thus the careful analysis of post-mortem PD brain biochemistry remains a crucial component of research, and one that offers considerable opportunity to pursue etiological factors either by ‘reverse biochemistry’ i.e. from defective pathway to mutant gene, or by the complex interplay between pathways e.g. mitochondrial turnover by lysosomes. In this review we have documented the spectrum of biochemical defects identified in PD post-mortem brain and explored their relevance to metabolic pathways involved in neurodegeneration. We have highlighted the complex interactions between these pathways and the gene mutations causing or increasing risk for PD. These pathways are becoming a focus for the development of disease modifying therapies for PD. Parkinson's is accompanied by multiple changes in the brain that are responsible for the progression of the disease. We describe here the molecular alterations occurring in postmortem brains and classify them as: Neurotransmitters and neurotrophic factors; Lewy bodies and Parkinson's-linked genes; Transition metals, calcium and calcium-binding proteins; Inflammation; Mitochondrial abnormalities and oxidative stress; Abnormal protein removal and degradation; Apoptosis and transduction pathways