Characterization of Proton Production and Consumption Associated with Microbial Metabolism

BACKGROUND: Production or consumption of protons in growth medium during microbial metabolism plays an important role in determining the pH of the environment. Such pH changes resulting from microbial metabolism may influence the geochemical speciation of many elements in subsurface environments. Protons produced or consumed during microbial growth were measured by determining the amount of acid or base added in a 5 L batch bioreactor equipped with pH control for different species including Escherichia coli, Geobacter sulfurreducens, and Geobacter metallireducens. RESULTS: An in silico model was used to predict the proton secretion or consumption rates and the results were compared with the data. The data was found to confirm predictions of proton consumption during aerobic growth of E. coli with acetate as the carbon source. However, in contrast to proton consumption observed during aerobic growth of E. coli with acetate, proton secretion was observed during growth of Geobacter species with acetate as the donor and Fe(III) as the extracellular electron acceptor. CONCLUSIONS: In this study, we have also shown that the final pH of the medium can be either acidic or basic depending on the choice of the electron acceptor for the same electron donor. In all cases, the in silico model could predict qualitatively the proton production/consumption rates obtained from the experimental data. Therefore, measurements of pH equivalents generated or consumed during growth can help characterize the microbial physiology further and can be valuable for optimizing practical applications such as microbial fuel cells, where growth associated pH changes can limit current generation rates

Model based code generation for distributed embedded systems

Embedded systems are becoming increasingly complex and more distributed. Cost and quality requirements necessitate reuse of the functional software components for multiple deployment architectures. An important step is the allocation of software components to hardware. During this process the differences between the hardware and application software architectures must be reconciled. In this paper we discuss an architecture driven approach involving model-based techniques to resolve these differences and integrate hardware and software components. The system architecture serves as the underpinning based on which distributed real-time components can be generated. Generation of various embedded system architectures using the same functional architecture is discussed. The approach leverages the following technologies – IME (Integrated Modeling Environment), the SAE AADL (Architecture Analysis and Design Language), and Ocarina. The approach is illustrated using the electronic throttle control system as a case study

Studies on AP-1 Sorting Function and Regulation of Membrane Binding

Der Adaptor-Protein Komplex 1 (AP-1) vermittelt die Bildung von transportvesikeln am trans-Golgi Netzwerk und ist Bestandteil Clathrin umhüllter transportvesikel. AP-1 vermittelt die Clathrin Bindung an Vesikel und bindet zudem an Sequenzmotive in zytoplasmatischen Domänen von transmembranproteinen. Seine Funktion wird in der Sortierung von Proteinen in Clathrin-transportvesikel gesehen. Der AP-1 Komplex besteht aus 4 Untereinheiten, deren Funktionen für die Proteinsortierung und die Vesikelbildung nur in Teilen verstanden sind. Die beiden grossen Untereinheiten γ1 und β1 bestehen jeweils aus einer N-terminalen globulären Domäne und einer C-terminalen globulären Domäne, die eine Vielzahl von Proteinen binden, deren Funktionen bei der Vesikelbildung nicht verstanden sind. Die μ1A Untereinheit des Komplexes ist essentiel für die Membranbindung des AP-1 und bindet transmembranproteine, die durch den AP-1 Komplex transportiert werden. Mit Ausnahme des β 1 Adaptin existieren von allen Untereinheiten des AP-1 Isoformen, von denen die Mehrzahl gewebsspezifisch expremiert werden. Die Funktionsanalyse von μ2/μ1A-Adaptin Chimären zeigte, dass der Bereich geringster Sequenzhomologie eine Bedeutung für die AP-1 vermittelte Proteinsortierung hat. Die Membranbindung des AP-1 Komplexes mit dem μ2/μ1A Chimären ist stabiler. Mittels des Y2H Verfahrens wurde ein bislang nicht charakterisiertes Protein identifiziert, das mit hoher Affinität und Spezifität an diese Domäne bindet. Seine Überexpression führt zu einer verminderten Membranbindung des AP-1, nicht des chimären Komplexes. Vom σ1-Adaptin existieren drei Isoformen σ1A, σB und σC. Das σ1B transskript wird zudem gewebsspezifisch alternativ gespleisst. Es sollten spezifische Funktionen für σ1 Isoformen identifiziert werden. Da ein γ1 Adaptin Bindemotif in der Isoform σ1B-3 existiert, nicht aber in den anderen, wurde dieses Motif analysiert. Es interagierte nicht mit γ1, jedoch lies sich durch Änderung einer einzigen flankierenden Aminosäure, eine Bindung erreichen.Es wurde die Sortierung des Sortilin Rezeptors in μ1A-sowie σ1B Adaptin-defizienten Zellen untersucht. In μ1A -/- zellen ist Sortilin von seiner normalen trans-Golgi Netzwerk Lokalisation in frühe Endosomen umverteilt. Daraufhin wurde die Bindung zweier Sortierungsmotife des Sortilin überprüft. Das Tyrosin-basierende Motif zeigte eine Interaktion mit dem μ1A Adaptin. Das di-Leucin-basierende Motif zeigte die höchste Affinität zu γ1/σ1B Hemikomplexen. Embryonale Fibroblasten einer σ1B "knock-out" Maus zeigten jedoch keine Sortilinfehlsortierung. Die Interaktion des Sortilins mit μ1A Adaptin scheint daher für eine Sortierung zwischen dem trans-Golgi Netzwerk und Endosomen in diesen Zellen ausreichend zu sein. Adipocyten von σ1B-defizienten Mäusen hatten jedoch eine vierfach höhere Menge an Sortilin. σ1B-Adaptin vermittelt daher in Adipocyten die Sortierung entlang eines gewebsspezifischen transportweges

Multiple Sulfatase Deficiency: A Disease Comprising Mucopolysaccharidosis, Sphingolipidosis, and More Caused by a Defect in Posttranslational Modification.

Schlotawa L, Adang LA, Radhakrishnan K, Ahrens-Nicklas RC. Multiple Sulfatase Deficiency: A Disease Comprising Mucopolysaccharidosis, Sphingolipidosis, and More Caused by a Defect in Posttranslational Modification. International journal of molecular sciences. 2020;21(10):3448.Multiple sulfatase deficiency (MSD, MIM #272200) is an ultra-rare disease comprising pathophysiology and clinical features of mucopolysaccharidosis, sphingolipidosis and other sulfatase deficiencies. MSD is caused by impaired posttranslational activation of sulfatases through the formylglycine generating enzyme (FGE) encoded by the sulfatase modifying factor 1 (SUMF1) gene, which is mutated in MSD. FGE is a highly conserved, non-redundant ER protein that activates all cellular sulfatases by oxidizing a conserved cysteine in the active site of sulfatases that is necessary for full catalytic activity. SUMF1 mutations result in unstable, degradation-prone FGE that demonstrates reduced or absent catalytic activity, leading to decreased activity of all sulfatases. As the majority of sulfatases are localized to the lysosome, loss of sulfatase activity induces lysosomal storage of glycosaminoglycans and sulfatides and subsequent cellular pathology. MSD patients combine clinical features of all single sulfatase deficiencies in a systemic disease. Disease severity classifications distinguish cases based on age of onset and disease progression. A genotype- phenotype correlation has been proposed, biomarkers like excreted storage material and residual sulfatase activities do not correlate well with disease severity. The diagnosis of MSD is based on reduced sulfatase activities and detection of mutations in SUMF1. No therapy exists for MSD yet. This review summarizes the unique FGE/ sulfatase physiology, pathophysiology and clinical aspects in patients and their care and outlines future perspectives in MSD

Multi-Criteria Service Selection Agent for Federated Cloud

Federated cloud interconnects small and medium-sized cloud service providers for service enhancement to meet demand spikes. The service bartering technique in the federated cloud enables service providers to exchange their services. Selecting an optimal service provider to share services is challenging in the cloud federation. Agent-based and Reciprocal Resource Fairness (RRF) based models are used in the federated cloud for service selection. The agent-based model selects the best service provider using Quality of Service (quality of service). RRF model chooses fair service providers based on service providers\u27 previous service contribution to the federation. However, the models mentioned above fail to address free rider and poor performer problems during the service provider selection process. To solve the above issue, we propose a Multi-criteria Service Selection (MCSS) algorithm for effectively selecting a service provider using quality of service, Performance-Cost Ratio (PCR), and RRF. Comprehensive case studies are conducted to prove the effectiveness of the proposed algorithm. Extensive simulation experiments are conducted to compare the proposed algorithm performance with the existing algorithm. The evaluation results demonstrated that MCSS provides 10% more services selection efficiency than Cloud Resource Bartering System (CRBS) and provides 16% more service selection efficiency than RPF

A comprehensive review on Nipah virus infection control measures

Nipah virus (NiV) has emerged as a deadly zoonotic pathogen, causing sporadic outbreaks with high mortality rates. The patient typically exhibits thrombocytopenia, leukopenia, and transaminitis along with fever, encephalitis, and/or respiratory involvement. This comprehensive review delves into the multifaceted realm of Nipah virus infection control measures. We explore the latest research, strategies, and practices aimed at preventing, containing, and mitigating the impact of NiV outbreaks. From surveillance and diagnosis to treatment and public health interventions, this review offers a holistic perspective on the ongoing efforts to combat this deadly virus

Recognition and ER Quality Control of Misfolded Formylglycine-Generating Enzyme by Protein Disulfide Isomerase

Schlotawa L, Wachs M, Bernhard O, et al. Recognition and ER Quality Control of Misfolded Formylglycine-Generating Enzyme by Protein Disulfide Isomerase. Cell Reports. 2018;24(1):27-37.e4.Multiple sulfatase deficiency (MSD) is a fatal, inherited lysosomal storage disorder characterized by reduced activities of all sulfatases in patients. Sulfatases require a unique post-translational modification of an active-site cysteine to formylglycine that is catalyzed by the formylglycine-generating enzyme (FGE). FGE mutations that affect intracellular protein stability determine residual enzyme activity and disease severity in MSD patients. Here, we show that protein disulfide isomerase (PDI) plays a pivotal role in the recognition and quality control of MSD-causing FGE variants. Overexpression of PDI reduces the residual activity of unstable FGE variants, whereas inhibition of PDI function rescues the residual activity of sulfatases in MSD fibroblasts. Mass spectrometric analysis of a PDI+FGE variant covalent complex allowed determination of the molecular signature for FGE recognition by PDI. Our findings highlight the role of PDI as a disease modifier in MSD, which may also be relevant for other ER-associated protein folding pathologies

Myocardial infarction protective effect of xyloglucan on Drosophila melanogaster: A review

Myocardial infarction, more often known as cardiac arrest, occurs when the supply of blood to the heart’s coronary artery decreases or ceases, causing damage to the heart muscle. Xyloglucan is a plant polysaccharide. Xyloglucan has been proven in several studies utilizing model organisms to reduce the risk of coronary heart disease by avoiding post-occlusion phases inhibiting apoptosis and enhancing energy metabolism. Many studies utilize Drosophila melanogaster because its SRY-related HMG-box 5 (SOX5) gene encodes a SOX family transcription factor; the human SOX5 ortholog, Sox102F, is well conserved in Drosophila melanogaster. Suppressing Sox102F in flies resulted in significant heart dysfunction, structural defects, and a disturbance in notch signal transduction. This demonstrates that SOX5 serves an important functional part in the heart and that variations in SOX5 concentrations may contribute to the possibility of myocardial infarction. Xyloglucan activity is significant in myocardial infarction and may be lowered in the myocardium after H/R damage by stimulating Notch signaling, which may benefit myocardial survival, angiogenesis, and cardiac function. This review discusses the roles of the human SOX5 and Drosophila SOX102F genes, the notch signaling system, and how xyloglucan in tamarind seeds may defend against heart damage by preventing apoptosis along with improving energy metabolism

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries