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The gasdermins are a family of pore-forming proteins that has recently been suggested to play a central role in pyroptosis. In this study, we describe the novel roles of gasdermins in the biogenesis of apoptotic cell–derived exosomes. In apoptotic human HeLa and HEK293 cells, GSDMA, GSDMC, GSDMD, and GSDME increased the release of apoptotic exosomes. GSDMB and DFNB59, in contrast, negatively affected the release of apoptotic exosomes. GSDME at its full-length and cleaved forms was localized in the exosomes and exosomal membrane. Full-length and cleaved forms of GSDME are suggested to increase Ca2+ influx to the cytosol through endosomal pores and thus increase the biogenesis of apoptotic exosomes. In addition, the GSDME-mediated biogenesis of apoptotic exosomes depended on the ESCRT-III complex and endosomal recruitment of Ca2+-dependent proteins, that is, annexins A2 and A7, the PEF domain family proteins sorcin and grancalcin, and the Bro1 domain protein HD-PTP. Therefore, we propose that the biogenesis of apoptotic exosomes begins when gasdermin-mediated endosomal pores increase cytosolic Ca2+, continues through the recruitment of annexin-sorcin/grancalcin-HD-PTP, and is completed when the ESCRT-III complex synthesizes intraluminal vesicles in the multivesicular bodies of dying cells. Finally, we found that GSDME-bearing tumors released apoptotic exosomes to induce inflammatory responses in the in vivo mouse 4T1 orthotropic model of BALB/c breast cancer. The data indicate that the switch from apoptosis to pyroptosis could drive the transfer of mass signals to nearby or distant living cells and tissues by way of extracellular vesicles, and that gasdermins play critical roles in that process.

Although the etiology of obesity is not well-understood, genetic, environmental, and microbiome elements are recognized as contributors to this rising pandemic. It is well documented that Roux-en-Y gastric bypass (RYGB) surgery drastically alters the fecal microbiome, but data are sparse on temporal and spatial microbiome and metabolome changes, especially in human populations. We characterized the structure and function (through metabolites) of the microbial communities in the gut lumen and structure of microbial communities on mucosal surfaces in nine morbidly obese individuals before, 6 months, and 12 months after RYGB surgery. Moreover, using a comprehensive multi-omic approach, we compared this longitudinal cohort to a previously studied cross-sectional cohort (n = 24). In addition to the expected weight reduction and improvement in obesity-related comorbidities after RYGB surgery, we observed that the impact of surgery was much greater on fecal communities in comparison to mucosal ones. The changes in the fecal microbiome were linked to increased concentrations of branched-chain fatty acids and an overall decrease in secondary bile acid concentrations. The microbiome and metabolome data sets for this longitudinal cohort strengthen our understanding of the persistent impact of RYGB on the gut microbiome and its metabolism. Our findings highlight the importance of changes in mucosal and fecal microbiomes after RYGB surgery. The spatial modifications in the microbiome after RYGB surgery corresponded to persistent changes in fecal fermentation and bile acid metabolism, both of which are associated with improved metabolic outcomes.

Reverse osmosis (RO) membrane biofouling is a critical issue in seawater desalination. However, biofouling characteristics are not fully understood owing to the complex structure of the fouling layer. Therefore, the objective of this study is to investigate how the biofouling characteristics of RO membranes are associated with bacterial and archaeal communities and their physiological (surface structure, elemental composition, and thickness) and metabolic characteristics in different locations of the RO membrane element. Raw seawater, feedwater, first- and last-located RO membrane elements, and brine were collected from a full-scale (50 m3 per day) intermittently operated seawater reverse osmosis (SWRO) desalination plant. Bacteria were found to be the most dominant biofouling microorganism on the RO membrane surface rather than archaea or diatoms. This study highlights that the very first element of the RO membrane receiving inflow had fouled biofilm with more heterogeneous morphologies and chemical composition compared with the very last element of the RO membrane where the outflow is discharged. In contrast, the microbial communities in both biofilms were similar to each other during the period of desalination operation. The most dominant bacterial species in the biofilm of RO membranes were Pelagibius, Parvibaculum, Legionella, Hyphomicrobium, and Sphingomonas. Moreover, their physiological and metabolic characteristics, such as salt tolerance, high pressure tolerance, and/or oligotrophic properties may provide advantages for their adaptation and dominance in RO membrane biofilms. A substantial difference in microbial diversity was observed between the feedwater and RO membranes, suggesting that more attention should be given to the biofilm, rather than the feedwater, when investigating how biofouling is developed and eventually controlled.

This paper proposes a systematic design procedure with comprehensive consideration of the internal and external dynamics in modular multilevel converter high voltage direct current (MMC-HVDC) transmission system. Previous studies on MMC parameter selection separately deal with each specific component such as energy storage capacity for voltage ripple of sub-module (SM) capacitor, arm inductance for second harmonic circulating current reduction, maximum allowable modulation index for MMC operating condition, which considered only a single purpose. However, the parameters respond dynamically to their characteristics and interact directly with the MMC performance, power system conditions, and specific requirements. In this study, we investigate the mutual relationships between the parameters and their performance. Then, we determine the parameter values based on a proposed systematic design procedure with the desired objectives and restricted conditions, which could be cumbersome and time-consuming to approach proper and acceptable parameter values. Therefore, this study could provide engineering evaluations and insights to help MMC-HVDC system engineers and project developers in intuitive approaches regarding the design aspects of the technology requirement challenges. The efficacy and accuracy of the analysis and design method for the MMC-HVDC system parameters were validated by PSCAD/EMTDC time-domain simulation and real-time digital simulation with hardware-in-loop system.

The application of bioaugmentation (i.e., injection of contaminant-degrading microorganisms) has shown its potential to remove harmful cyanotoxins like microcystin-LR (MC-LR) from drinking water sources. However, the natural organic matter (NOM) present in both natural and engineered water systems might affect the bacterial biodegradation of MC-LR. Therefore, for the successful application of bioaugmentation for MC-LR removal in water treatment, it is important to understand NOM effects on MC-LR biodegradation. In this study, the impact of NOM [algal organic matter (AOM) and humic substances (HS)] on MC-LR biodegradation was evaluated in the presence of varying concentrations of NOM by monitoring MC-LR biodegradation kinetics. The changes in NOM composition during MC-LR biodegradation were also characterized by a five-component Parallel factor (PARAFAC) model using 336 excitation-emission matrix (EEM) spectra collected at different sampling points. Our results showed decreases in MC-LR biodegradation rate of 1.6-and 3.4-fold in the presence of AOM and HS, respectively. The expression of the functional mlrA gene exhibited a similar trend to the MC-LR degradation rate at different NOM concentrations. EEM-PARAFAC analyses and NOM molecular size fractionation results indicated a relatively greater production of terrestrial humic-like components (57%) and a decrease of protein-like components. Two-dimensional correlation spectroscopy (2D-COS) analyses further confirmed that low molecular weight protein-like components were initially utilized by bacteria, followed by the formation of higher molecular weight humic-like components, likely due to microbial metabolism.

The gasdermins are a family of pore-forming proteins that has recently been suggested to play a central role in the pyroptosis and the release of inflammatory cytokines. Here, we describe the novel roles of gasdermins in the biogenesis of apoptotic cell–derived exosomes. In apoptotic cells, GADMA, GSDMC, GSDMD, and GSDME increased the release of ApoExos, and both their full-length and cleaved forms were localized in the exosomal membrane. GSDMB and DFNB59, on the other hand, negatively affected the release of ApoExos. The caspase-mediated cleavage of gasdermins, especially GSDME, is suggested to increase Ca2+ influx to cytosol through endosomal pores and thus increase the biogenesis of ApoExos. In addition, the GSDME-mediated biogenesis of ApoExos depended on the ESCRT-III complex and endosomal recruitment of Ca2+-dependent proteins: annexins A2 and A7, the PEF domain family proteins sorcin and grancalcin, and the Bro1 domain protein HD-PTP. Therefore, we propose that the biogenesis of ApoExos begins when gasdermin-mediated endosomal pores increase cytosolic Ca2+, continues through the recruitment of annexin-sorcin/grancalcin-HD-PTP, and is completed when the ESCRT-III complex synthesizes intraluminal vesicles in the multivesicular bodies of dying cells. Finally, we found that GSDME-bearing tumors released ApoExos to induce inflammatory responses in the in vivo 4T1 orthotropic model of breast cancer. The data presented in this study indicate that the switch from apoptosis to pyroptosis could drive the transfer of mass signals to nearby or distant living cells and tissues by way of extracellular vesicles, and that gasdermins play critical roles in that process.

Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these links, microbiome therapies have been proposed to improve gastrointestinal (GI) and ASD symptoms in ASD individuals. Previously, our open-label microbiota transfer therapy (MTT) study provided insight into the changes in the gut microbial community of children with ASD after MTT and showed significant and long-term improvement in ASD and GI symptoms. Using samples from the same study, the objective of this work was to perform a deeper taxonomic and functional analysis applying shotgun metagenomic sequencing. Taxonomic analyses revealed that ASD Baseline had many bacteria at lower relative abundances, and their abundance increased after MTT. The relative abundance of fiber consuming and beneficial microbes including Prevotella (P. dentalis, P. enoeca, P. oris, P. meloninogenica), Bifidobacterium bifidum, and a sulfur reducer Desulfovibrio piger increased after MTT-10wks in children with ASD compared to Baseline (consistent at genus level with the previous 16S rRNA gene study). Metabolic pathway analysis at Baseline compared to typically developing (TD) children found an altered abundance of many functional genes but, after MTT, they became similar to TD or donors. Important functional genes that changed included: genes encoding enzymes involved in folate biosynthesis, sulfur metabolism and oxidative stress. These results show that MTT treatment not only changed the relative abundance of important genes involved in metabolic pathways, but also seemed to bring them to a similar level to the TD controls. However, at a two-year follow-up, the microbiota and microbial genes shifted into a new state, distinct from their levels at Baseline and distinct from the TD group. Our current findings suggest that microbes from MTT lead to initial improvement in the metabolic profile of children with ASD, and major additional changes at two years post-treatment. In the future, larger cohort studies, mechanistic in vitro experiments and metatranscriptomics studies are recommended to better understand the role of these specific microbes, functional gene expression, and metabolites relevant to ASD.

Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.

Research relating gut microbiome composition to autism spectrum disorders (ASD) has produced inconsistent results, indicative of the disorder’s complexity and the need for more sophisticated experimental designs. We address this need by (i) comparing gut microbiome composition between individuals with ASD and neurotypical controls in Arizona and Colorado using standardized DNA extraction and sequencing methods at both locations and (ii) longitudinally evaluating the gut microbiome’s relationship to autism behavioral severity, diet, and gastrointestinal symptoms. Gut microbiome composition differed between individuals in Arizona and individuals in Colorado, and gastrointestinal symptoms were significantly higher in ASD individuals than in neurotypical individuals in Arizona but not in Colorado. Gut microbiome composition was significantly associated with ASD while controlling for study-site location but not when controlling for gastrointestinal symptoms. This suggests that non-ASD-related study site differences in gut microbiome composition and different degrees of gastrointestinal symptoms involvement with ASD between sites may contribute to inconsistent results in the literature regarding the association between gut microbiome composition and ASD. In the longitudinal analysis, we found that difference in levels of lethargy/social withdrawal measured in individuals at different time points correlated with the degree of change in gut microbiome composition and that a worsening of inappropriate speech between time points was associated with decreased gut microbiome diversity. This relationship between changes in the gut microbiome composition within individuals and ASD behavioral severity metrics indicates that longitudinal study designs may be useful for exploring microbial drivers of ASD severity when substantial variability exists in baseline microbiome compositions across individuals and geographical regions. IMPORTANCE Autism spectrum disorder (ASD) is a brain developmental disorder with varying behavioral symptom severity both across individuals and within individuals over time. There have been promising but also inconsistent literature results regarding how the gut microbiota (microbiome) may be involved. We found that the gut microbiome in individuals with ASD is affected by study-site location as well as gastrointestinal symptom severity. When we sampled some individuals with ASD at several different time points, we found that some behaviors, such as lethargy/social withdrawal and inappropriate speech, changed along with changes in the gut microbiota composition. This is the first study to relate severity of behavior symptoms to gut microbiome composition within individuals over time and suggests a dynamic relationship between ASD-associated symptoms and gut microbes. Longitudinal study designs as well as collaborative efforts across multiple centers are needed to fully characterize the relationship between ASD and gut microbes.

Fecal microbiota transplant (FMT) holds significant promise for patients with Autism Spectrum Disorder (ASD) and gastrointestinal (GI) symptoms. Prior work has demonstrated that plasma metabolite profiles of children with ASD become more similar to those of their typically developing (TD) peers following this treatment. This work measures the concentration of 669 biochemical compounds in feces of a cohort of 18 ASD and 20 TD children using ultrahigh performance liquid chromatography-tandem mass spectroscopy. Subsequent measurements were taken from the ASD cohort over the course of 10-week Microbiota Transfer Therapy (MTT) and 8 weeks after completion of this treatment. Univariate and multivariate statistical analysis techniques were used to characterize differences in metabolites before, during, and after treatment. Using Fisher Discriminant Analysis (FDA), it was possible to attain multivariate metabolite models capable of achieving a sensitivity of 94% and a specificity of 95% after cross-validation. Observations made following MTT indicate that the fecal metabolite profiles become more like those of the TD cohort. There was an 82&ndash, 88% decrease in the median difference of the ASD and TD group for the panel metabolites, and among the top fifty most discriminating individual metabolites, 96% report more comparable values following treatment. Thus, these findings are similar, although less pronounced, as those determined using plasma metabolites.

To address the adverse effects of harmful algal blooms, there are increased demands over the implementation of ozone coupled with biologically active carbon (BAC) filters in the drinking water treatment plants. Although the microbial biofilms are vital elements to support the proper performance of BAC filters, except for taxonomic affiliations, little is known about the assembly mechanisms of microbial communities in the full-scale BAC filters. This study aimed to examine how the assembly processes and their associated factors (e.g., influent characteristics, biological interactions) drive the temporal dynamics of bacterial communities in full-scale BAC filters, which underwent ozone implementation (five consecutive seasons from 2017 to 2018). The results revealed that along with the increase of bacterial taxonomic richness and evenness, stochastic processes became more crucial to determine the bacterial community assembly in the summer and autumn after ozone implementation (relative contribution: 61.23% and 83.75%, respectively). Moreover, their corresponding networks possessed simple network structures with lower modularity than other seasons, which implied lesser biological interactions among bacterial populations. The correlation between taxonomic and predicted functional diversities using functional redundancy index indicated that relatively high levels of bacterial functional redundancy (>0.83) were generally present in BAC filters. However, compared to other seasons, significantly higher degrees of functional redundancy existed in the summer and autumn after ozone implementation (0.85 ± 0.01 and 0.86 ± 0.01, respectively). Overall, this work improves our understanding of the microbial ecology of full-scale BAC filters by providing a conceptual framework that characterizes bacterial biofilm assembly processes relevant to performance optimization of full-scale BAC filters.

Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) are anatomically different bariatric operations. RYGB achieves greater weight loss compared with LAGB. Changes in the gut microbiome have been documented after RYGB, but not LAGB, and the microbial contribution to sustainable surgical weight loss warrants further evaluation. We hypothesized that RYGB imposes greater changes on the microbiota and its metabolism than LAGB, and that the altered microbiota may contribute to greater weight loss. Using multi-omic approaches, we analyzed fecal microbial community structure and metabolites of pre-bariatric surgery morbidly obese (PreB-Ob), normal weight (NW), post-RYGB, and post-LAGB participants. RYGB microbiomes were significantly different from those from NW, LAGB and PreB-Ob. Microbiome differences between RYGB and PreB-Ob populations were mirrored in their metabolomes. Diversity was higher in RYGB compared with LAGB, possibly because of an increase in the abundance of facultative anaerobic, bile-tolerant and acid-sensible microorganisms in the former. Possibly because of lower gastric acid exposure, phylotypes from the oral cavity, such as Escherichia, Veillonella and Streptococcus, were in greater abundance in the RYGB group, and their abundances positively correlated with percent excess weight loss. Many of these post-RYGB microorganisms are capable of amino-acid fermentation. Amino-acid and carbohydrate fermentation products—isovalerate, isobutyrate, butyrate and propionate—were prevalent in RYGB participants, but not in LAGB participants. RYGB resulted in greater alteration of the gut microbiome and metabolome than LAGB, and RYGB group exhibited unique microbiome composed of many amino-acid fermenters, compared with nonsurgical controls.

Introduction: The purpose of this review is to discuss Microbiota Transplant Therapy (MTT), a type of intensive intestinal microbiota transplantation (IMT), for people with autism spectrum disorders (ASD) and chronic gastrointestinal disorders (constipation and/or diarrhea).Areas covered: This paper briefly reviews IMT, gastrointestinal symptoms and gastrointestinal bacteria in children with ASD, and results and lessons learned from intensive MTT for autism.Expert opinion: An open-label study and a two-year follow-up suggest that MTT is relatively safe and effective in significantly reducing gastrointestinal disorders and autism symptoms, changing the gut microbiome structure, and increasing gut microbial diversity. Further research with larger, randomized, double-blind, placebo-controlled studies is warranted.

Autism spectrum disorder (ASD) manifests as alterations in complex human behaviors including social communication and stereotypies. In addition to genetic risks, the gut microbiome differs between typically-developing (TD) and ASD individuals, though it remains unclear whether the microbiome contributes to symptoms. We transplanted gut microbiota from human donors with ASD or TD controls into germ-free mice, and reveal that colonization with ASD microbiota is sufficient to induce hallmark autistic behaviors. The brains of mice colonized with ASD microbiota display alternative splicing of ASD-relevant genes. Microbiome and metabolome profiles of mice harboring human microbiota predict that specific bacterial taxa and their metabolites modulate ASD behaviors. Indeed, treatment of an ASD mouse model with candidate microbial metabolites improves behavioral abnormalities and modulates neuronal excitability in the brain. We propose that the gut microbiota regulates behaviors in mice via production of neuroactive metabolites, suggesting that gut-brain connections contribute to the pathophysiology of ASD.

This paper introduces the design methodology of MMC-HVDC control system based on Field-Programmable Gate Array (FPGA), which has advantages of high-speed parallel operation, and verify accuracy of control performance using this control system and RTDS (Real-Time Digital Simulator). Finally, this paper compares the characteristics of LVRT (Low-Voltage-Ride-Through) of MMC-HVDC system composed of physical control system and RTDS.

Accurately monitoring health condition of individual lithium-ion (Li-ion) cells such as state of charge (SOC) and state of health (SOH) in multicell batteries is crucial to build high-performance and safety-critical battery systems. However, this involves considerable computational burden to embedded battery management systems (BMSs), as number of battery cells increases. This paper proposes an efficient on-board health monitoring method for multicell Li-ion battery systems consisting of large number of cells using the proposed Gaussian process clustering. The Gaussian process clustering method first preprocesses all cell voltages using Z-score standardization and classifies a normal cell cluster and an abnormal cell cluster using outlier scoring vector. Then, a representative of the normal cell cluster and abnormal cells are carefully monitored using the threads of a condition monitoring algorithm. Instead of using cell-based method for all cells in a pack, the proposed method can significantly reduce the computation cost for onboard implementation. We show the usefulness of the proposed health monitoring algorithm through simulation results.

Fault diagnosis for lithium-ion batteries involves detecting faulty cells and identifying types of faults. It is crucial to build safety-critical battery systems, which has not been fully integrated in conventional battery management systems. This paper proposes a novel data mining-based real-time fault diagnosis for multicell lithium-ion batteries using a microcontroller. The proposed fault diagnosis algorithm includes: 1) a model-based battery condition monitoring algorithm that estimates physical model parameters and operational states and 2) an outlier detection algorithm that detects abnormal battery cells based on the outcomes of the condition monitoring and identifies the types of faults such as internally shorted cells and anomaly aged cells. The proposed fault diagnosis method is implemented in a low-priced microcontroller and validated by experiments in a multicell battery simulation testbed.

This paper proposes an enhanced control method for a high-voltage direct-current (HVDC) modular multilevel converter (MMC). To control an MMC-HVDC system properly, the ac current, circulating current, and submodule (SM) capacitor voltage are considered. The ac-side current is a fundamental frequency component, and the circulating current is a double-line frequency component. Existing control methods control the ac current and circulating current by separating each component. However, the existing methods have a disadvantage in that the ac-side current must be separated into the positive and negative sequences for control under an unbalanced voltage condition. The circulating current consists of not only negative-sequence components but also positive- and zero-sequence components under an unbalanced voltage condition. Therefore, an additional control method is necessary to consider the positive- and zero-sequence components of the circulating current. The proposed control method has the advantage of controlling not only the ac-side current of the MMC but also the circulating current without separating each of the current components to control each arm current of the MMC. In addition, it can stably control the positive- and zero-sequence components of the circulating current under the unbalanced voltage condition.

This paper proposes a model predictive control (MPC) method for modular-multilevel-converter (MMC) high-voltage direct current (HVDC). To control the MMC-HVDC system properly, the ac current, circulating current, and submodule (SM) capacitor voltage are taken into consideration. The existing MPC methods for the MMC-HVDC system utilize weighting factors to configure the cost function in combinations of the SM capacitor voltage balancing algorithm, ac current control, and circulating current control. Because all combinations of the switch states are considered in order to minimize the cost function, their possible combinations increase geometrically according to the increase of the level of the MMC, which is a significant disadvantage. This paper proposes a new MPC method with a reduced number of states for ac current control, circulating current control, and the SM capacitor voltage-balancing algorithm. The proposed cost functions are divided into three types according to their control purposes. Each cost function determines the minimum number of states for controlling the ac current, circulating current, and SM capacitor voltage. The efficacy of the proposed controlling method is verified through simulation results using PSCAD/EMTDC.

Model-based condition monitoring for lithium-ion (Li-ion) batteries involves estimating physical model parameters and operational states such state of charge (SOC) and state of health (SOH), and is crucial for building high-performance and safety-critical battery systems. This paper proposes a real-time model-based condition monitoring algorithm based on a second-order RC electrical circuit battery model. The proposed method consists of an extended Kalman filter (EKF)-based online parameter identification algorithm and a smooth variable structure filter (SVSF)-based state estimation algorithm. The two filters are systematically integrated to cooperate each other and named hybrid filter (HF). The HF is not only compared with a dual extended Kalman filter (DEKF) in numerical simulation studies, but also implemented in a low-priced microcontroller with a real-time battery cell simulation testbed for a high-power Li-ion battery cell. The results show that the proposed HF can have less computational complexity and higher accuracy of SOC and capacity estimation than those of the conventional DEKF. Therefore, the proposed HF can be the alternative of DEKF as well as suitable for the real-time embedded battery management system (BMS) applications.

Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using 1H-NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites-caprate, nicotinate, glutamine, thymine, and aspartate-may potentially function as a modest biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of phylotypes most closely related to Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. Despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further investigation of metabolites in larger cohorts.

This paper proposes a novel online condition monitoring algorithm estimating battery states and model parameters. The proposed method includes: 1) an electrical circuit battery model incorporating the hysteresis effect, 2) an extended Kalman Filter-based online parameter identification algorithm for the electrical battery model, and 3) a smooth variable structure filter (SVSF)-based state estimation algorithm for state of charge (SOC) estimation. The proposed method enables an accurate and robust condition monitoring for lithium-ion batteries. Since the proposed hybrid filter further reduces the complexity compared to existing dual extended Kalman filter (DEKF), it is much more suitable for the real-time embedded battery management system (BMS) application. Simulation studies validate the effectiveness of the proposed strategy.

Characteristics of study participants and their medical and diet history. All values are median ± median absolute deviation (MAD). p values are either by Mann-Whitney U test or Fisher’s exact probability test. n.s., not-significant. Table S2. Percent days of no stool, stool hardness, and softness based on the daily stool record (DSR) and the Bristol Stool Form Scale (p values by two-tailed Wilcoxon signed-rank test). Table S3. Adverse effects. (PDF 72 kb)

Background Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. Results MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7–8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). Conclusions This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. Trial registration This trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554 Electronic supplementary material The online version of this article (doi:10.1186/s40168-016-0225-7) contains supplementary material, which is available to authorized users.

Subscores of GI- and ASD-related symptoms in 18 children with ASD. Figure S2. Correlation between percentage change in GSRS and overall PGI-III scores (based on the data shown in Fig. 2a, b) for the 18 weeks of the study. Figure S3. Vineland developmental age (in years) for individual subscales and for the average of all subscales, measured at baseline and at the end of observation 4 months later. Figure S4. Stool microbiota changes in community richness with fecal microbiota transplant. Figure S5. Gut phageome taxonomy is still mostly unknown. Figure S6. Subscores of the PGI-III at end of treatment (week 10). Figure S7. Microbiota changes with fecal microbiota transplant based on swab samples (analog of Fig 3a–d). Figure S8. Stool microbiota changes with fecal microbiota transplant. Figure S9. Engraftment plots with four diversity metrics (stool samples). Figure S10. Stool microbiota changes with fecal microbiota transplant. (PDF 1964 kb)

Renewable energy is being spotlighted as the electric power generating source for the next generation. Due to an increase in renewable energy systems in the grid system, their impact on the grid has become non-negligible. Thus, many countries in the world, including Europe, present their own grid codes for grid power conversion devices. In order to experiment with these grid codes, grid fault test equipment is required. This paper proposes both equipment and a control method, which are constructed with a 7-level cascaded H-bridge converter, that are capable of generating various grid faults. In addition, the Pulse Width Modulation (PWM) method for multilevel converters is compared and analyzed. The proposed structure, the control method, and the PWM method are verified through simulation and experimental results.

Microbial electrolysis cells (MECs) can be used as a downstream process to dark fermentation to further capture electron in volatile fatty acids that remain after fermentation, improving this way the viability of the overall process. Acetic and propionic acid are common products of dark fermentation. The main objective of this work was to investigate the effect of different initial concentrations of a mixture of acetic and propionic acids on MECs microbial ecology and hydrogen production performance. To link microbial structure and function, we characterized the anode respiring biofilm communities using pyrosequencing and quantitative-PCR. The best hydrogen production rates (265 mL/d/Lreactor) were obtained in the first block of experiments by MEC fed with 1500 mg/L acetic acid and 250 mg/L propionic acid. This reactor presents in the anode biofilm an even distribution of Proteobacteria, Firmicutes and Bacteroidetes and Arcobacter was the dominant genera. The above fact also correlated to the highest electron load among all the reactors. It was evidenced that although defined acetic and propionic acid concentrations fed affected the structure of the microbial consortia that developed at the anode, the initial inoculum played a major role in the development of MEC microbial consortia.

Enhanced biological phosphorus removal (EBPR) is an effective nutrient removal process that has been engineered and successfully applied in wastewater treatment for decades. Although the prevalent microorganism performing EBPR in full-scale activated sludge plants was identified nearly a decade ago as Candidatus Accumulibacter phosphatis, it still remains an unculturable organism. In this paper, the authors describe research that has been aimed at identifying and isolating microorganisms responsible for EBPR, along with the fundamental metabolic, genetic, and ecological advances that have been recently made in the characterization of Cand. A. phosphatis. Furthermore, evidence is presented that Cand. A. phosphatis can perform the EBPR cycle under nitrogen-limiting conditions, a characteristic that could be potentially incorporated into strategies to obtain pure cultures of this organism. Finally, possible research directions that could be enabled when a pure culture of this organism is obtained wer...

Current diagnosis of autism spectrum disorder (ASD) is based on assessment of behavioral symptoms, although there is strong evidence that ASD affects multiple organ systems including the gastrointestinal (GI) tract. This study used Fisher discriminant analysis (FDA) to evaluate plasma metabolites from 18 children with ASD and chronic GI problems (ASD + GI cohort) and 20 typically developing (TD) children without GI problems (TD &minus, GI cohort). Using three plasma metabolites that may represent three general groups of metabolic abnormalities, it was possible to distinguish the ASD + GI cohort from the TD &minus, GI cohort with 94% sensitivity and 100% specificity after leave-one-out cross-validation. After the ASD + GI participants underwent Microbiota Transfer Therapy with significant improvement in GI and ASD-related symptoms, their metabolic profiles shifted significantly to become more similar to the TD &minus, GI group, indicating potential utility of this combination of plasma metabolites as a biomarker for treatment efficacy. Two of the metabolites, sarcosine and inosine 5&prime, monophosphate, improved greatly after treatment. The third metabolite, tyramine O-sulfate, showed no change in median value, suggesting it and correlated metabolites to be a possible target for future therapies. Since it is unclear whether the observed differences are due to metabolic abnormalities associated with ASD or with GI symptoms (or contributions from both), future studies aiming to classify ASD should feature TD participants with GI symptoms and have larger sample sizes to improve confidence in the results.

This study demonstrated the utility in correlating performance and community structure of a trichloroethene (TCE)-dechlorinating microbial consortium; specifically dechlorinators, fermenters, homoacetogens, and methanogens. Two complementary approaches were applied: predicting trends in the microbial community structure based on an electron balance analysis and experimentally assessing the community structure via pyrosequencing and quantitative polymerase chain reaction (qPCR). Fill-and-draw reactors inoculated with the DehaloR^2 consortium were operated at five TCE-pulsing rates between 14 and 168 µmol/10-day-SRT, amended with TCE every 2 days to give peak concentrations between 0.047 and 0.56 mM (6-74 ppm) and supplied lactate and methanol as sources of e(-) donor and carbon. The complementary approaches demonstrated the same trends: increasing abundance of Dehalococcoides and Geobacter and decreasing abundance of Firmicutes with increasing TCE pulsing rate, except for the highest pulsing rate. Based on qPCR, the abundance of Geobacter and Dehalococcoides decreased for the highest TCE pulsing rate, and pyrosequencing showed this same trend for the latter. This deviation suggested decoupling of Dehalococcoides growth from dechlorination. At pseudo steady-state, methanogenesis was minimal for all TCE pulsing rates. Pyrosequencing and qPCR showed suppression of the homoacetogenic genera Acetobacterium at the two highest pulsing rates, and it was corroborated by a decreased production of acetate from lactate fermentation and increased propionate production. Suppression of Acetobacterium, which can provide growth factors to Dehalococcoides, may have contributed to the decoupling for the highest TCE-pulsing rate.

Malnutrition may manifest as either obesity or undernutrition. Accumulating evidence suggests that the gut microbiota plays an important role in the harvest, storage, and expenditure of energy obtained from the diet. The composition of the gut microbiota has been shown to differ between lean and obese humans and mice; however, the specific roles that individual gut microbes play in energy harvest remain uncertain. The gut microbiota may also influence the development of conditions characterized by chronic low-level inflammation, such as obesity, through systemic exposure to bacterial lipopolysaccharide derived from the gut microbiota. In this review, the role of the gut microbiota in energy harvest and fat storage is explored, as well as differences in the microbiota in obesity and undernutrition.

We evaluated the consumption of hydrogen gas at the anode of a microbial electrolysis cell (MEC) and characterized the significance of new interactions between anode respiring bacteria (ARB) and homo-acetogens. We demonstrated the significance of biofilm limitation for direct consumption of H2 over acetate by ARB, using the deep biofilm model. Selective inhibition of the major competing hydrogen sink at the biofilm anode, methanogenesis, resulted in significant increase in electron recovery as electric current (∼10–12 A/m2). The presence of acetate at high concentration in the anode compartment and detection of formate, a known intermediate of the acetyl-CoA pathway, provide evidence towards the role of homoacetogenic bacteria. We also assessed the activity of homoacetogens with reverse transcription quantitative PCR targeting formyltetrahydrofolate synthetase (FTHFS) transcripts, and observed a comparable decrease in the FTHFS transcript numbers with current density and acetate concentrations as we decreased the HRT below 4.5 h. The biofilm anode community was predominated by Deltaproteobacteria (70% of total readouts) along with a fraction of the homoacetogenic genus, Acetobacterium (4% of total readouts), established by pyrosequencing targeting the V6 region of the 16S rRNA. Homoacetogens seem to play a major role as syntrophic members of the biofilm anode community when electron recovery is high.

A novel anaerobic consortium, named DehaloR^2, that performs rapid and complete reductive dechlorination of trichloroethene (TCE) to ethene is described. DehaloR^2 was developed from estuarine sediment from the Back River of the Chesapeake Bay and has been stably maintained in the laboratory for over 2 years. Initial sediment microcosms showed incomplete reduction of TCE to DCE with a ratio of trans- to cis- isomers of 1.67. However, complete reduction to ethene was achieved within 10 days after transfer of the consortium to sediment-free media and was accompanied by a shift to cis-DCE as the prevailing intermediate metabolite. The microbial community shifted from dominance of the Proteobacterial phylum in the sediment to Firmicutes and Chloroflexi in DehaloR^2, containing the genera Acetobacterium, Clostridium, and the dechlorinators Dehalococcoides. Also present were Spirochaetes, possible acetogens, and Geobacter which encompass previously described dechlorinators. Rates of TCE to ethene reductive dechlorination reached 2.83 mM Cl- d(-1) in batch bottles with a Dehalococcoides sp. density of 1.54E+11 gene copies per liter, comparing favorably to other enrichment cultures described in the literature and identifying DehaloR^2 as a promising consortium for use in bioremediation of chlorinated ethene-impacted environments.