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Background: Human and microbial metabolism are distinct disciplines. Terminology, metrics, and methodologies have been developed separately. Therefore, combining the 2 fields to study energetic processes simultaneously is difficult.Objectives: When developing a mechanistic framework describing gut microbiome and human metabolism interactions, energy values of food and digestive materials that use consistent and compatible metrics are required. As an initial step toward this goal, we developed and validated a model to convert between chemical oxygen demand (COD) and gross energy (${E_g}$) for >100 food items and ingredients.Methods: We developed linear regression models to relate (and be able to convert between) theoretical gross energy (${E_g}^{\prime}$) and chemical oxygen demand (COD'); the latter is a measure of electron equivalents in the food's carbon. We developed an overall regression model for the food items as a whole and separate regression models for the carbohydrate, protein, and fat components. The models were validated using a sample set of computed ${E_g}^{\prime}$ and COD' values, an experimental sample set using measured ${E_g}$ and COD values, and robust statistical methods.Results: The overall linear regression model and the carbohydrate, protein, and fat regression models accurately converted between COD and ${E_g}$, and the component models had smaller error. Because the ratios of COD per gram dry weight were greatest for fats and smallest for carbohydrates, foods with a high fat content also had higher ${E_g}$ values in terms of kcal · g dry weight-1.Conclusion: Our models make it possible to analyze human and microbial energetic processes in concert using a single unit of measure, which fills an important need in the food-nutrition-metabolism-microbiome field. In addition, measuring COD and using the regressions to calculate ${E_g}$ can be used instead of measuring ${E_g}$ directly using bomb calorimetry, which saves time and money. [ABSTRACT FROM AUTHOR]

Abstract Rapid uptake of inorganic phosphate (Pi) by microalgae should occur through two processes operating in parallel: onto extracellular polymeric substances (EPS) and intracellular polymeric substances (IPS). Most previous studies focused only on overall Pi uptake and ignored the roles of EPS. We investigated the two-step removal of Pi by Synechocystis sp. PCC 6803 in dark conditions (i.e., without incorporation of Pi into newly synthesized biomass). We also developed a model to simulate both steps. Experimental results with Synechocystis confirmed that Pi in the bulk solution was removed by the two uptake mechanisms operating in parallel, but with different kinetics. All uptake rates decreased with time, and the Pi uptake rate by IPS was much higher than that by EPS at all times, but EPS had a larger maximum Pi-storage capacity -- 33–48 mgP/gCOD EPS versus 15–17 mgP/gCOD IPS. Synechocystis had a maximum Pi-storage capacity in the range of 22–28 mgP/g dry biomass. Protein in EPS and IPS played the key role for binding Pi, and biomass with higher protein content had greater Pi-storage capacity. Furthermore, biomass with low initial stored Pi had faster Pi-uptake kinetics, leading to more Pi removed from the bulk solution. This work lays the foundation for using microalgae as a means to remove Pi from polluted water and for understanding competition for Pi in microbial communities. Graphical abstract Image 1 Highlights • Uptake of Pi by Synechocystis sp. PCC 6803 in dark conditions is investigated. • Uptake of Pi BS by EPS and IPS were operated in parallel but with different kinetics. • EPS had a slower Pi-uptake rate but a larger maximum Pi-storage capacity than IPS. • Protein in EPS and IPS played a key role for binding Pi due to its amine functional groups. • Biomass with low initial stored Pi had faster Pi-uptake kinetics. [ABSTRACT FROM AUTHOR]

Mineralocorticoid receptor (MR) antagonists continue to be a prevalent area of research in the pharmaceutical industry. Herein we report the discovery of various spirooxindole and dibenzoxazepine constructs as potent MR antagonists. SAR analysis of our spirooxindole hit led to highly potent compounds containing polar solubilizing groups, which interact with the helix-11 region of the MR ligand binding domain (LBD). Various dibenzoxazepine moieties were also prepared in an effort to replace a known dibenzoxepane system which interacts with the hydrophobic region of the MR LBD. In addition, an X-ray crystal structure was obtained from a highly potent compound which was shown to exhibit both partial agonist and antagonist modes of action against MR. [ABSTRACT FROM AUTHOR]

Abstract: The Combined Activated Sludge-Anaerobic Digestion Model (CASADM) quantifies the effects of recycling anaerobic-digester (AD) sludge on the performance of a hybrid activated sludge (AS)-AD system. The model includes nitrification, denitrification, hydrolysis, fermentation, methanogenesis, and production/utilization of soluble microbial products and extracellular polymeric substances (EPS). A CASADM example shows that, while effluent COD and N are not changed much by hybrid operation, the hybrid system gives increased methane production in the AD and decreased sludge wasting, both caused mainly by a negative actual solids retention time in the hybrid AD. Increased retention of biomass and EPS allows for more hydrolysis and conversion to methane in the hybrid AD. However, fermenters and methanogens survive in the AS, allowing significant methane production in the settler and thickener of both systems, and AD sludge recycle makes methane formation greater in the hybrid system. [Copyright &y& Elsevier]

Abstract: Novel in vitro mGlu5 positive allosteric modulators with good potency, solubility, and low lipophilicity are described. Compounds were identified which did not rely on the phenylacetylene and carbonyl functionalities previously observed to be required for in vitro activity. Investigation of the allosteric binding requirements of a series of dihydroquinolinone analogs led to phenylacetylene azachromanone 4 (EC50 11.5nM). Because of risks associated with potential metabolic and toxicological liabilities of the phenylacetylene, this moiety was successfully replaced with a phenoxymethyl group (27; EC50 156.3nM). Derivation of a second-generation of mGlu5 PAMs lacking a ketone carbonyl resulted in azaindoline (33), azabenzimidazole (36), and N-methyl 8-azaoxazine (39) phenylacetylenes. By scoping nitrogen substituents and phenylacetylene replacements in 39, we identified phenoxymethyl 8-azaoxazine 47 (EC50 50.1nM) as a potent and soluble mGlu5 PAM devoid of both undesirable phenylacetylene and carbonyl functionalities. [Copyright &y& Elsevier]

Abstract: Common to all microbial electrochemical cells (MXCs) are the anode-respiring bacteria (ARB), which transfer electrons to an anode and release protons that must transport out of the biofilm. Here, we develop a novel modeling platform, Proton Condition in BIOFILM (PCBIOFILM), with a structure geared towards mechanistically explaining: (1) how the ARB half reaction produces enough acid to inhibit the ARB by low pH; (2) how the diffusion of alkalinity carriers (phosphates and carbonates) control the pH gradients in the biofilm anode; (3) how increasing alkalinity attenuates pH gradients and increases current; and (4) why carbonates enable higher current density than phosphates. Analysis of literature data using PCBIOFILM supports the hypothesis that alkalinity limits the maximum current density for MXCs. An alkalinity criterion for eliminating low-pH limitation – 12mgCaCO3/mgBOD – implies that a practical MXC can achieve a maximum current density with an effluent quality comparable to anaerobic digestion. [ABSTRACT FROM AUTHOR]

Abstract: Microbial electrochemical cells depend on the reaction by anode-respiring bacteria (ARB). The ARB reaction generates multiple e− and H+, which take diverging paths, creating a charge imbalance. An electric field must migrate ions to restore electrical neutrality. Here, the model proton condition in bioflim (PCBIOFILM) expands for evaluating the impact of migration on the biofilm anode: the expansion makes the proton condition (PC) work in tandem with the electrical-neutrality condition, which is a novel methodological advancement. The analysis with PCBIOFILM examines relevant scenarios of phosphate- and carbonate-buffered biofilm anodes using established parameters. The analysis demonstrates how: (1) the proton condition (PC) maintains electrical neutrality by achieving charge balance; (2) migration influences the biofilm anode more than non-ARB biofilms; (3) migration increases the overall current density, but by less than 15 percent; and (4) PCBIOFILM without migration accurately captures large-scale trends in biofilm anodes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Multiple innovative intensification technologies for anaerobic digestion were reviewed. • The mechanisms and efficiency gains of each technology were discussed. • A comparison between the advantages and challenges of each technology was presented. • Possible integration of the technologies with existing infrastructure was highlighted. • The technology readiness level (TRL) of each technology was quantified. Anaerobic digestion (AD) is an established technology that plays a crucial role in breaking down the organic compounds and biomass during the sludge treatment processes. However, there are multiple challenges associated with the application of AD on different feedstocks and under various operational conditions. The AD process is highly sensitive to operational conditions (e.g., temperature and pH) with relatively slow reactions rates especially during the hydrolysis and methanogenesis stages. These limitations can significantly affect the performance of anaerobic digesters and the biogas production rate. Therefore, various intensification technologies were proposed and investigated in the literature to upgrade the biogas production and yield as well as enhancing the removal of organics and biomass during the sludge treatment processes. Although different review studies have examined some of these intensification technologies such as physical and chemical pretreatment techniques, limited studies have focused on reviewing the innovative intensification technologies, such as microbial electrolysis cells (MEC) and micro-aeration, in AD applications. Moreover, there are no systematic investigations that compared the performance, mechanisms, advantages, and challenges of these innovative technologies to draw strong conclusions about the applicability of each technology with different wastes, feedstocks, and operation conditions. In addition, the quantification of possible integration of these technologies with the current infrastructure and the technology readiness level were not well-investigated in literature. Therefore, in the current study, seven different innovative intensification technologies were reviewed including MEC-assisted AD, conductive functional materials, micro-aeration, anaerobic membrane bioreactors, hydrogen injection, IntensiCarb, and microbial hydrolysis process using Caldicellulosiruptor bescii. A detailed description of these technologies for increasing biogas yields was presented, with a special focus on the performance, reliability, efficiency gains, and applicability of each technology. The major insights of this review can serve as a reference for the potential intensification technologies that can be integrated with existing AD systems for enhanced biogas production and removal of organics and biomass. [ABSTRACT FROM AUTHOR]

Abstract: We established the first complete electron-equivalent balances in microbial fuel cells (MFCs) fed with non-fermentable (acetate) and fermentable (glucose) electron donors by experimentally quantifying current, biomass, residual organic compounds, H2, and CH4 gas. The comparison of the two donors allowed us to objectively evaluate the diversion of electron flow to non-electricity sinks for fermentable donors, leading to different behaviors in energy-conversion efficiency (ECE) and potential efficiency (PE). Electrical current was the most significant electron sink in both MFCs, being 71% and 49%, respectively, of the initial COD applied. Biomass and residual organic compounds, the second and third greatest sinks, respectively, were greater in the glucose-fed MFC than in the acetate-fed MFC. We detected methane gas only in the glucose-fed MFC, and this means that anode-respiring bacteria (ARB) could out-compete acetoclastic methanogens. The ECE was 42% with acetate, but was only 3% with glucose. The very low ECE for glucose was mostly due to a large increase of the anode potential, giving a PE of only 6%. Although the glucose-fed MFC had the higher biomass density on its anode, it had a very low current density, which supports the fact that the density of ARB was very low. This led to slow kinetics for electron transfer to the anode and accentuated loss due to the substrate-concentration gradient in the anode-biofilm. The large drop of PE with low current, probably caused by a low ARB density and electron (e−) donor concentration, resulted in a poor maximum power density (9.8mW/m2) with glucose. In contrast, PE reached 59% along with high current for acetate and the maximum power density was 360mW/m2. [Copyright &y& Elsevier]

Abstract: This paper describes a new methodology to detect small anomalies in high resolution hyperspectral imagery, which involves successively: (1) a multivariate statistical analysis (principal component analysis, PCA) of all spectral bands; (2) a geostatistical filtering of noise and regional background in the first principal components using factorial kriging; and finally (3) the computation of a local indicator of spatial autocorrelation to detect local clusters of high or low reflectance values and anomalies. The approach is illustrated using 1 m resolution data collected in and near northeastern Yellowstone National Park. Ground validation data for tarps and for disturbed soils on mine tailings demonstrate the ability of the filtering procedure to reduce the proportion of false alarms (i.e., pixels wrongly classified as target), and its robustness under low signal to noise ratios. In almost all scenarios, the proposed approach outperforms traditional anomaly detectors (i.e., RX detector which computes the Mahalanobis distance between the vector of spectral values and the vector of global means), and fewer false alarms are obtained when using a novel statistic S 2 (average absolute deviation of p-values from 0.5 through all spectral bands) to summarize information across bands. Image degradation through addition of noise or reduction of spectral resolution tends to blur the detection of anomalies, increasing false alarms, in particular for the identification of the least pure pixels. Results from a mine tailings site demonstrate the approach performs reasonably well for highly complex landscape with multiple targets of various sizes and shapes. By leveraging both spectral and spatial information, the technique requires little or no input from the user, and hence can be readily automated. [Copyright &y& Elsevier]

[Display omitted] • Redox mediators with various potentials change energy distribution between microbes. • Bioelectrochemical equations and concepts are currently being used for IET modeling. • Models confirm the potential of DIET to improve electron transfer rates. • Fundamental knowledge on the characteristics of IET is needed for adequate modeling. Interspecies electron transfer (IET) is a key phenomenon in anaerobic ecosystems, which is traditionally modeled as hydrogen transfer. Recently discovered alternative mediated IET (MIET) or direct IET (DIET) offer exciting alternative mechanisms of microbial partnerships that could lead to new strategies for the improvement of biotechnologies. Here, we analyze mathematical modeling of DIET and MIET in anaerobic ecosystems. Bioenergetics approaches already enable the evaluation of different energy sharing scenarios between microorganisms and give interesting clues on redox mediators and on possible ways of driving microbial communities relying on IET. The modeling of DIET kinetics however is currently only in its infancy. Recent concepts introduced for the modeling of electroactive biofilms should be further exploited. Recent modeling examples confirms the potential of DIET to increase the IET rates compared to H 2 -MIET, but also point out the need for additional characterizations of biological components supporting IET to improve predictions. [ABSTRACT FROM AUTHOR]

Liver X receptor (LXR) agonists have been reported to lower brain amyloid beta (Aβ) and thus to have potential for the treatment of Alzheimer’s disease. Structure and property based design led to the discovery of a series of orally bioavailable, brain penetrant LXR agonists. Oral administration of compound 18 to rats resulted in significant upregulation of the expression of the LXR target gene ABCA1 in brain tissue, but no significant effect on Aβ levels was detected. [ABSTRACT FROM AUTHOR]

Abstract: The evaluation of the CXCR3 antagonist AMG 487 in clinic trials was complicated due to the formation of an active metabolite. In this Letter, we will discuss the further optimization of the quinazolinone series that led to the discovery of compounds devoid of the formation of the active metabolite that was seen with AMG 487. In addition, these compounds also feature increased potency and good pharmacokinetic properties. We will also discuss the efficacy of the lead compound 34 in a mouse model of cellular recruitment induced by bleomycin. [Copyright &y& Elsevier]

Abstract: A series of six–six and six–five fused heterocyclic CXCR3 antagonists has been synthesized and their activities evaluated in an [125I]-IP-10 displacement assay and an ITAC mediated in vitro cell migration assay. The pharmacokinetic properties of several top compounds have also been studied. This effort led to the discovery of compounds with increased potency and improved pharmacokinetic properties that could serve as useful tools to study the role of the CXCR3 receptor in vivo. [Copyright &y& Elsevier]

Abstract: A series of quinazolinone-derived inhibitors of the CXCR3 receptor have been synthesized and their affinity for the receptor evaluated. Compounds were evaluated in a 125I-IP10 displacement assay and in in vitro cell migration assays to IP10, ITAC, and MIG using human peripheral blood mononuclear cells. [Copyright &y& Elsevier]

The mitochondrion within human cells in tissue culture is pleomorphic and highly dynamic. The organelle mass can exist as thousands of small ovoids or as one continuous reticulum. In either state, the mitochondrial mass is in constant thermal motion, as well as moving in ≈0.8-μm jumps that are determined by, and related to, attachments with cytoskeletal elements. Many protein complexes, such as the pyruvate dehydrogenase (PDH) complex and DNA containing nucleoids, are dispersed through the mass and as though fixed by attachments to membranes, such that they can become distributed to all of the individual small ovoid mitochondria when the reticulum becomes fragmented. This leads us to propose that a replicating module is the repeating unit of mitochondrial structure. Studies to examine heterogeneity of functioning within the organelle mass are briefly reviewed. [Copyright &y& Elsevier]

A fusion protein between GFP and the E1α subunit of the pyruvate dehydrogenase (PDH) complex was created and shown to assemble into functional PDH complexes using immunoprecipitation and activity assays. The expression of this GFP-E1α chimera is specific to mitochondria and results in two different fluorescence patterns. These patterns have been distinguished by immunolabeling experiments using monoclonal antibodies against PDH subunits and GFP. The bright, localized fluorescent spots represent the assembled form of the GFP-E1α in PDH complexes. The uniform, dim fluorescence is given by the unassembled chimera free to diffuse throughout the mitochondrial reticulum. This study reveals a discrete, heterogeneous distribution of PDH complexes in the matrix of mitochondria, both in cells with normal and reduced levels of PDH. The uneven arrangement of PDH complexes is maintained over time and most likely reflects the structural and metabolic compartmentalization of mitochondria. [Copyright &y& Elsevier]