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S136952742030031X | A primary goal of synthetic biology is to develop gene circuits that perform their intended functions despite variations in the growth conditions . However this has turned out to be more complicated than it originally seemed because there is a complex interplay between the operation of synthetic gene circuits and the global physiology of host cells . Mathematical models provide an avenue to disentangle the intricacies of this phenomenon and guide the design of synthetic circuits that robustly perform in a variety of conditions . In this work we review quantitative modeling approaches that have been used to rationalize and predict experimental observations resulting from circuit to circuit and circuithost interactions in bacteria . | The lack of predictive understanding of circuit behavior limits synthetic biology. A major reason for this is the complex interplay between circuit and host state. Quantitative models promise to unravel this phenomenon and overcome this limitation. |
S1369527420300321 | With more than one million bacterial genome sequences uploaded to public databases in the last 25 years genomics has become a powerful tool for studying bacterial biology . Here we review recent approaches that leverage large numbers of whole genome sequences to decipher the spread and pathogenesis of bacterial infectious diseases . | 72 of the available 1. None. 067. None. 277 bacterial genomes on NCBI are from only 10 species. WGS is a new gold standard for detection of clonal outbreaks and transmission events. WGS ancestral reconstruction and GWAS allow unbiased functional prediction. WGS of longitudinal infection can be used to detect host adaptations. The data loss common in WGS methods may be tackled with database driven approaches. |
S1369527420300333 | is known for its intrinsic resistance to conventional antibiotic treatment and hypervirulence during infection . This coupled with its extraordinary capacity to survive in myriad harsh environments has led to increasing rates of infection in clinical settings . Numerous studies have characterized the virulence factors and resistance genes in | encodes a variety of transcription factors two component systems and small RNAs that influence survival during infection. ABUW 1645 is a novel regulator that serves as a switch between avirulent and virulent phenotypes during infection within the host. The two component system BfmRS regulates pathways involved in cell division and wall synthesis and consequently has a profound influence on pathogenic potential. The global regulator Zur is essential for. pathogenicity as it helps circumvent host nutritional immunity during. infection. The TF AceR regulates the AceI efflux pump which is responsible for resistance to the commonly used antiseptic chlorohexidine. |
S1369527420300370 | Invasive fungal infections are responsible for a significant disease burden worldwide . Drugs to treat these infections are limited to only four unique classes and despite these available treatments mortality rates remain unacceptably high . In this review we will discuss antifungal drug screening and how the approach to identifying novel compounds needs move away from traditional growth based assays in order to meet the demand for new drugs . We highlight specific examples of creative screening strategies that increase the likelihood of identifying compounds with desired activities and provide perspective to inspire development of novel screens for the identification of first in class antifungals . | There is an urgent need for the development of novel antifungals. Repeating the same growth assays leads to reidentification of the same molecules. Designing creative screening strategies will diversify leads identified for antifungal development. |
S1369527420300394 | Introduction of antibiotics into clinical use has contributed to some of the greatest improvements to public health in the 20th century . Most antibiotics are based on antimicrobials that were isolated from environmental microorganisms over 50 years ago but emerging resistance requires discovery of new molecules and development of these molecules into therapeutics . Bioinformatic analyses of microbial genomes indicate that many more microbial bioactive molecules remain undiscovered . Understanding when where and why these molecules are produced informs efforts to tap into the hidden unexplored chemical diversity . Expanding the search to undersampled ecological niches and improving culturing techniques will ensure discovery of new antibiotics . | Most antibiotics are derived from antimicrobials produced by soil microorganisms. Genetic potential of microbes far exceeds their small molecule output in the lab. Microbial ecology informs strategies to discover new antimicrobials. Organisms from non conventional habitats may serve as a source of new antimicrobials. Better models are needed to study the role of antimicrobials in microbial ecology. |
S1369527420300400 | is both a member of the human mucosal microbiota and a common agent of invasive fungal disease . Systems biology approaches allow for analysis of the interactions between this fungus and its mammalian host . Framing these studies by considering how | Interactions between. and human hosts shape each others biology. Systems biology provides tools to interrogate these interactions at multiple scales. Microscopy transcriptomics and proteomics illustrate individual cell responses. Functional genomics screens and experimental evolution reveal genotypes that impact fitness. Microbial community interactions can modify each other and host health. |
S1369527420300412 | Many bacterial pathogens rely on dedicated secretion systems to translocate virulence proteins termed effectors into host cells . These effectors engage and manipulate host cellular functions to support bacterial colonization and propagation . The secretion systems are molecular machines that recognize targeting features in these effector proteins | Effector arsenal expansion may facilitate bacterial infection of a broader range of hosts. Computational machine learning has facilitated large scale effector discovery. Substantiating the biological significance of. identified effectors remains challenging. |
S1369527420300552 | Anti fungal immunity is characterized by the continuous interplay between immune activation and immune regulation processes . These processes have now been clearly shown not only in animal pre clinical models but also in humans . To create and maintain this immune homeostasis reciprocal interactions among the host immune system fungal pathogens and the microbiome are crucial . Notably the microbiome exerts multiple direct and indirect antifungal effects that are particularly aimed at minimizing host tissue damage . Thus in this microbiome era the architecture of 3D culture system or tissue organoids might finally represent a simple but effective | The increased incidence of human fungal infections is related to immune disorders. Humans are holobionts maintaining balanced interactions with pathobionts and the microbiome. The host microbiome contributes to both antifungal resistance and tolerogenic strategies. Organoids may be used as mini holobionts systems to model the host fungus microbiome disease triangle. |
S1369527420300631 | Compared to bacteria fungi often exhibit a lower abundance and a higher temporal volatility in the intestinal microbiota . Analysis of fungi in the microbiota faces technical limitations with tools that were originally developed for analyzing bacteria . Dysbiotic states of the intestinal mycobiota often associated with disruption of the healthy bacterial microbiota are characterized by overgrowth of specific fungal taxa and loss of diversity . Intestinal domination by | The human mycobiota contains clinically relevant fungal species. Longitudinal sampling provides robust insights into the human mycobiota. Simultaneous analysis of intestinal fungi and bacteria is critical in clinical studies. The intestinal mycobiota is an important source of fungal bloodstream infections. The mycobiota may play a role in bacterial or viral systemic infections. |
S1369527420300643 | is a major cause of fungal nosocomial infections . Host defense against disseminated infections caused by this yeast strongly relies on myeloid cells of the innate immune system . Recently several breakthroughs have been made that significantly improved our understanding of the role of macrophages during candidiasis and how | Tissue resident macrophages are central to counteract systemic candidiasis. Macrophages engulf yeast but struggle with hypha forming frustrated phagosomes. evolved strategies to counteract the microbicidal phagosomal environment. can employ four distinct mechanisms to escape from macrophages. Modulation of macrophage activity may improve the outcome of systemic candidiasis. |
S1369527420300655 | Although soluble mediators of our innate immune system have a substantial impact on invading microbes their role against fungal pathogens has been underexplored . Constituting the humoral immunity soluble mediators comprise the complement system collectins acute phase proteins antibodies and antimicrobial peptides . These components can prevent fungal infection either by directly interacting with invading microbes leading to their aggregation destruction or linking them to cellular immunity . The composition of soluble mediator varies with human body fluids resulting in different antifungal mechanisms . Moreover cellular immune system deploys both oxidative and non oxidative mechanisms to destroy extracellular or internalized fungal pathogens however cellular immune activation is mainly influenced as well as regulated by soluble mediators . This review outlines the antifungal mechanism employed directly or indirectly by soluble mediators and in response the evading strategies of the fungal pathogens . | Soluble mediators exert antifungal properties directly or indirectly. They are unaffected or partially affected by immunosuppression unlike cellular immunity. Most soluble mediators are pattern recognition receptors linking fungi to phagocytes. Soluble mediator based antifungal immunotherapies are gaining attention. Immune based antifungal strategies should exploit properties of soluble mediators. |
S1369527420300679 | Impaired microbiome diversity and composition can develop into a potent etiological agent of disease and increase susceptibility to infection . Given this interventions targeting the microbiome have developed rapidly with healthy donor feces being a | Fecal transplants despite associated risks are now a widely accepted therapeutic. Bacterial species and functions consistently associated with efficacy have been identified. Recent research indicates fungi and viruses are associated with therapy outcomes. Limited data exists on the influence of host diet and genetics on therapy efficacy. Modified fecal communities and lab based microbial therapies have been tested. |
S1369527420300680 | Bacterial pathogens need to sense and respond to their environments during infection to align cell metabolism and virulence factor production to survive and battle host defenses . Complex regulatory networks including ligand binding transcription factors two component systems RNA binding proteins and small non coding regulatory RNAs adjust gene expression programs in response to changes in metabolic fluxes environmental cues and nutrient availability . Recent studies underlined that these different layers of regulation occur along varying spatial and temporal scales leading to changes in cell behavior and heterogeneity among the bacterial community . This brief review will highlight current research emphasizing that cell metabolism and pathogenesis are inextricably intertwined in both Gram positive and Gram negative bacteria . | Regulators act as genetic time circuits to adjust metabolism and virulence. Altered metabolic flux has profound effects on survival and pathogenic potential. Host signals or nutrients can affect gene expression on various spatial scales. Spatial and temporal cues result in metabolic and phenotypic heterogeneity. |
S1369527420300692 | Directed evolution allows the effective engineering of proteins biosynthetic pathways and cellular functions . Traditional plasmid based methods generally subject one or occasionally multiple genes of interest to mutagenesis require time consuming manual interventions and the genes that are subjected to mutagenesis are outside of their native genomic context . Other methods mutagenize the whole genome unselectively which may distort the outcome . Recent recombineering and CRISPR based technologies radically change this field by allowing exceedingly high mutation rates at multiple predefined loci in their native genomic context . In this review we focus on recent technologies that potentially allow accelerated tunable mutagenesis at multiple genomic loci in the native genomic context of these target sequences . These technologies will be compared by four main criteria including the scale of mutagenesis portability to multiple microbial species off target mutagenesis and cost effectiveness . Finally we discuss how these technical advances open new avenues in basic research and biotechnology . | Methods for targeted microbial mutagenesis enable the massively parallel engineering of proteins biosynthetic pathways and cellular functions. ssDNA based recombineering and CRISPR Cas9 genome editing allow for precise saturation mutagenesis at user defined genomic sequences. Recombineering allows the most extensive and controllable mutagenesis at multiple loci and thus serves as enabling technology for new applications. |
S1369527420300709 | Early life is a critical time window for the neonatal gut to be progressively populated with different bacterial species that collectively promote gut maturation . A fully developed and healthy gut microbiome in neonates is an important driver for the development of other aspects of health . Unlike the relatively stable gut microbiome in adults the developing gut microbiome in neonates exhibits higher plasticity and adaptability . This also underscores the unique window of opportunity for intervention or preventive measures to improve long term health through modulations of the gut microbiome in early life . Better understanding of the neonatal gut microbiome how it arises and how it impacts immune cell development will help us appreciate the underpinnings of immune related diseases . Here we examine recent findings on the neonatal gut microbiome and discuss their implications for understanding this important driver of the maturation of the immune system and immunity against infections in early life . | microbial stimulation modulates both prenatal and postnatal immune cell development. Unique neonatal gut microenvironment allows for progressive colonization of selective bacteria before stabilization of the gut microbiome. Both mode of delivery and nutritional availability heavily shape postnatal colonization of gut bacteria. Gut microbial signals prime innate immune cells while minimizing overactivation of helper T cells through induction of regulatory T cells and sIgA. Dysbiotic gut microbiome leads to pathobiont expansion and potential detrimental sepsis in neonates. |
S1369527420300710 | Antibiotics used in combination are an effective strategy for combatting numerous infectious diseases in clinical and veterinary settings particularly as a last line therapy for difficult to treat cases . Combination therapy can either increase or slow the rate of killing broaden the antibiotic spectrum reduce dosage and unwanted side effects and even control the emergence of resistance . The administration of antibiotics in combination has been used effectively against bacterial infections for 70 years first used to treat tuberculosis . However effective antibiotic combinations and their dosage regimes have been largely determined empirically in the clinic and the molecular mechanisms underpinning how these combinations work remains surprisingly elusive . This review focuses on studies that have outlined the genetics and molecular mechanisms of action underlying antibiotic combinations as well as those that examine how resistance develops . We highlight the need for further experimentation and genetic validation to fully realise the potential of combination therapy . | Combination therapy is an important tool for tackling antibiotic resistance. In depth molecular studies for combination therapy are lacking. We summarise six major mechanisms mediating the effects seen in synergy and antagony. Combination therapy resistance mechanisms are complex on a population level. Resistance mutations relate to general as well as specific resistance strategies. |
S1369527420300734 | Phage satellites are genetic elements that depend on helper phages for induction packaging and transfer . To promote their lifestyles they have evolved elegant and sophisticated strategies to inhibit phage reproduction which will be reviewed here . We will principally focus on the convergent interference mechanisms used by phage inducible chromosomal islands which are a family of satellite phages present in both Gram positive and Gram negative bacteria . While some PICI elements have been extensively studied for their roles in virulence and antibiotic resistance recent studies have highlighted their relevance in controlling phage ecology and diversity . In many cases these interference mechanisms are complemented by additional strategies that promote the preferential PICI packaging and dissemination of these elements in nature . Since the PICI encoded mechanisms target conserved phage mechanisms we propose here that the PICIs form part of the initial innate immune system that phages must overcome to infect their bacterial host . | Phage satellites have evolved multiple and convergent strategies to inhibit phage reproduction. Production of small phage capsids is a universal mechanism used by satellite phages to inhibit phage maturation. Satellite phages have evolved mechanisms that promote their own packaging and transfer. |
S1369527420300746 | Once overlooked as passive bystanders of the human intestinal microbiota new evidence is shedding light on the importance of enterococci and their bacteriophages in shaping human health . Natural predators of enterococci phages represent a narrow spectrum precision targeting modality for the eradication of problematic enterococci within the microbiota or infected tissue . The identification of enterococcal phage receptors absorption factors and transcriptional responses following phage infection reveals a complex predator prey relationship that modulates enterococcal cell surface architecture susceptibility to antibiotics and adaptation to host associated environments . Considering the dry up of contemporary antibiotic discovery pipelines in the pharmaceutical industry and a continued emergence of multidrug resistant enterococci enterococcal phages may serve as bonafide therapeutics . We highlight current advances in enterococcal phage biology with emphasis on recent breakthroughs in potential therapeutic applications that place enterococcal phages at the forefront of next generation biologics . | Phage bacteria interactions drive key fitness tradeoffs in enterococci. Discovery of novel phage receptors will aid in the future therapeutic development of enterococcal phages. Enterococcal phage therapy demonstrates efficacy in animal models yet studies in humans are currently lacking. Enterococcal gut dysbiosis exacerbates several human diseases that may be mitigated by phage therapy. |
S1369527420300758 | To this day malaria remains a global burden affecting millions of people especially those in sub Saharan Africa and Asia . The rise of drug resistance to current antimalarial treatments including artemisinin based combination therapies has made discovering new small molecule compounds with novel modes of action an urgent matter . The concerted effort to construct enormous compound libraries and develop high throughput phenotypic screening assays to find compounds effective at specifically clearing malaria causing | evolution and whole genome sequencing elucidates genedrug interactions. Cellular thermal shift assay and mass spectrometry directly reveals small molecule compoundprotein interactions. Metabolomic profiling complements target identification with broad mode of action. |
S136952742030076X | Transfer RNAs are non coding RNAs essential for protein synthesis . tRNAs are heavily decorated with a variety of post transcriptional modifications . Recent methodological advances provide new tools for rapid profiling of tRNA modifications and have led to discoveries of novel modifications and their regulation . Here we provide an overview of the techniques for investigating tRNA modifications and of the expanding knowledge of their chemistry and regulation . | Diverse chemical modifications of tRNAs tRNA modifications modulate protein synthesis. tRNA sequencing and RNA mass spectrometry enable rapid identification of the structures and sites of tRNA modifications.. Novel modifications have been discovered in a variety of organisms. tRNA modification frequencies are regulated by environmental conditions. |
S1369527420300771 | The lung is a central organ for immune environmental interactions ranging from tolerance against harmless substances to protection against pathogens which are particularly sensitive to regulation by the intestinal microbiota . Airborne fungi can cause variety of diseases including allergies and inflammatory disorders as well as life threatening invasive infections . Remarkable differences exist between ubiquitous fungal species with regard to protective immune mechanisms . Recent data have surprisingly identified Aspergillus specific regulatory T cells as an essential tolerance checkpoint and provided mechanistic insight for the loss of tolerance in the course of immune pathologies . Furthermore pathogenic Th17 cells in Aspergillus associated inflammatory disease seem to be induced by cross reactivity to the intestinal commensal | Ubiquitous airborne fungi differentially induce protective immunity or tolerance. Chronic exposure to. induces primarily Treg mediated tolerance. The majority of. associated diseases resemble immune pathologies. Microbiota exert antigen specific and non specific innate immune modulation. |
S1369527420300801 | The complex communities of microbes that constitute the human microbiome are influenced by host and environmental factors . Here we address how a fundamental aspect of human biology blood type contributes to shaping this microscopic ecosystem . Although this question remains largely unexplored we glean insights from decades of work describing relationships between pathogens and blood type . The bacterial strategies molecular mechanisms and host responses that shaped those relationships may parallel those that characterize how blood type and commensals interact . Understanding these nuanced interactions will expand our capacity to analyze and manipulate the human microbiome . | A historical perspective on associations between ABO blood type and bacteria. Mechanisms that drive relationships between host blood type and commensal and pathogenic bacteria. Review of conflicting evidence for an influence of host blood type on the intestinal microbiome. How this knowledge may inform the development of microbiome targeted intervention strategies. |
S1369527420300813 | Antimicrobial resistance is an urgent public health threat and continues to be on the rise . Basic microbiological research is the foundation for addressing knowledge gaps both for the development of new antibiotics diagnostics and preventives but also to inform strategies to mitigate the transmission of resistance and drug resistant microorganisms . Translating this research into new products to reinvigorate dwindling pipelines especially for new antibiotics is one of the main challenges faced in addressing AMR . The scientific complexity is compounded by the market uncertainty of any new products leading to a large proportion of pharmaceutical companies exiting the market . Consequently a number of initiatives were developed to reinvigorate the AMR research and development landscape . Despite all these efforts the antibiotic pipeline remains inadequate to keep up with the increasing rates of resistance globally . Given the number of individual and multilateral actions there is an urgent need for a common platform and coordination to ensure that resources are adequately used to address the critical challenges posed by AMR globally hence the founding of the Global AMR R D Hub to take on this role . | Antimicrobial resistance is on the rise globally. The pipeline for new antibiotics is weak due to market failure. New initiatives have been put in place to replenish the antibiotic R D pipeline. The Global Antimicrobial Research and Development Hub was founded to coordinate the R D space. |
S1369527420300849 | Myxobacteria conduct complex social traits that requires populations to be highly related and devoid of exploiters . To enrich for clonal cells in populations they employ kin discrimination mechanisms . One key system involves a polymorphic cell surface receptor TraA which recognizes self by homotypic interactions with neighboring myxobacterial cells . Recent studies revealed that TraA and its partner TraB are fluid outer membrane proteins that coalesce into foci upon recognition of kin . The formation of foci leads to transient membrane fusion junctions and the bidirectional exchange of outer membrane components that facilitates cooperative behaviors . Additionally expansive suites of polymorphic lipoprotein toxins are exchanged which act as self identity barcodes that exquisitely discriminate against nonself to assemble homogenous populations . | Self recognition mediated by homotypic binding of a dynamic polymorphic cell surface receptor. TraA and TraB function as a fusogen that mediates outer membrane cargo exchange and homeostasis in. Polymorphic toxin exchange function as self identity barcodes. Experimental complexities in distinguishing greenbeard recognition from kin recognition. |
S1369527420300904 | Recent advances in genomics have uncovered the tremendous diversity and richness of microbial ecosystems . New functional genomics methods are now needed to probe gene function in high throughput and provide mechanistic insights . Here we review how the CRISPR toolbox can be used to inactivate repress or overexpress genes in a sequence specific manner and how this offers diverse attractive solutions to identify gene function in high throughput . Developed both in eukaryotes and prokaryotes CRISPR screening technologies have already provided meaningful insights in microbiology and host pathogen interactions . In the era of microbiomes the versatility and the functional diversity of CRISPR derived tools has the potential to significantly improve our understanding of microbial communities and their interaction with the host . | CRISPR screens enable the investigation of gene function in high throughput. CRISPR screens can be performed on bacteria or host cells. Cas9 and dCas9 are used to mutate genes or inhibit their expression respectively. Pooled and arrayed screens can access different phenotypes. New CRISPR technologies such as base editing have a great potential for screening. |
S1369527420300928 | As the incidence rate of invasive fungal infections has increased with the use of modern medical interventions so too has the occurrence of fungi invading the brain . Fungi such as | Brain fungal infections are a growing problem affecting both immunocompromised and putatively immunocompetent individuals. Fungi enter the brain by crossing the bloodbrain barrier or by direct inoculation. Resident and recruited immune cells are required to clear or contain brain fungal infection. Immune response often results in neurotoxicity and lack of subsequent tissue repair. |
S1369527420300977 | Antibiotics profoundly reduced worldwide mortality . However the emergence of resistance to the growth inhibiting effects of these drugs occurred . New approaches to treat infectious disease that reduce the likelihood for resistance are needed . In bacterial pathogens complex signaling networks regulate virulence . Anti virulence therapies aim to disrupt these networks to attenuate virulence without affecting growth . Quorum sensing a cell to cell communication system represents an attractive anti virulence target because it often activates virulence . The challenge is to identify druggable targets that inhibit virulence while also minimizing the likelihood of mutations promoting resistance . Moreover given the ubiquity of quorum sensing systems in commensals any potential effects of anti virulence therapies on microbiome function should also be considered . Here we highlight the efficacy and drawbacks of anti virulence approaches . | Anti virulence therapies target intercellular signaling networks essential for acute infection. Quorum sensing QS mediates the transition from human commensal to opportunistic pathogen. Microbiota interference of pathogen signaling can be exploited to inhibit virulence. In chronic disease host selective pressures may modulate QS systems through genetic mutations. |
S1369527420300989 | Clonal cell populations often display significant cell to cell phenotypic heterogeneity even when maintained under constant external conditions . This variability can result from the inherently stochastic nature of transcription and translation processes which leads to varying numbers of transcripts and proteins per cell . Here we showcase studies that reveal links between stochastic cellular events and biological functions in isogenic microbial populations . Then we highlight emerging tools from engineering computation and synthetic and molecular biology that enable precise measurement control and analysis of gene expression noise in microorganisms . The capabilities offered by this sophisticated toolbox will shape future directions in the field and generate insight into the behavior of living systems at the single cell level . | Phenotypic heterogeneity is an inevitable consequence of gene expression. Gene expression noise has functional consequences e.g. survival differentiation . Emerging tools offer the potential to quantify and control noise in single cells. |
S1369527420300990 | The trillions of microbes that constitutively colonize the intestine impact diverse aspects of human physiology in health and disease . Immunoglobulin A is the most abundant antibody isotype produced at mucosal surfaces and nearly two grams of IgA is secreted into the intestine every day . Secretory IgA provides critical protection against pathogens and toxins but can also directly bind to and coat commensal bacteria in the gut . Commensal targeting by SIgA shapes gut microbiota composition modulates bacterial behaviors and enforces host microbiota homeostasis in both mice and humans . | Secretory immunoglobulin A SIgA is the dominant antibody at mucosal surfaces. Gut commensals are coated by SIgA at varied levels. SIgA targeting regulates bacterial activities and shapes gut microbiota composition. SIgA enforces host microbiota homeostasis throughout the lifespan. |
S1369527420301004 | The mammalian immune system can tune its inflammatory response to the threat level posed by an invading pathogen . It is well established that the host utilizes numerous patterns of pathogenicity such as microbial growth invasion and viability to achieve this tuning during bacterial infections . This review discusses how this notion fits during fungal infection particularly regarding | Host fungal interactions tune the innate inflammatory response to maintain host resistance against distinct fungal isolates. Growth viability phagosome escape and cell wall changes are critical patterns of pathogenesis during fungal infection. Environmental evolution and growth conditions drive isolate specific virulence traits. |
S1369527420301016 | Environmental triggers in the context of genetic susceptibility drive phenotypes of complex immune disorders such as Inflammatory bowel disease . One such trigger of IBD is perturbations in enteric commensal bacteria fungi or viruses that shape both immune and neuronal state . The epigenome acts as an interface between microbiota and context specific gene expression and is thus emerging as a third key contributor to IBD . Here we review evidence that the host epigenome plays a significant role in orchestrating the bidirectional crosstalk between mammals and their commensal microorganisms . We discuss disruption of chromatin regulatory regions and epigenetic enzyme mutants as a causative factor in IBD patients and mouse models of intestinal inflammation and consider the possible translation of this knowledge . Furthermore we present emerging insights into the intricate connection between the microbiome and epigenetic enzyme activity via host or bacterial metabolites and how these interactions fine tune the microorganism host relationship . | Epigenetics is a therapeutically tractable mechanism linking genetics and environmental cues in IBD. Variants of human epigenetic regulators or regulatory regions associate with IBD susceptibility. Individual epigenetic enzymes exacerbate or protect mouse models of colitis. Intestinal bacteria modulate DNA histone modifications and chromatin accessibility. Cellular and bacteria derived metabolites are major determinants of epigenetic enzyme function. |
S1369527420301028 | Malaria continues to pose a severe threat to over half of the worlds population each year . With no long term effective vaccine available and a growing resistance to antimalarials there is a need for innovative methods of | Gut microbiota is associated with malaria in rodents and humans. Gut microbiota influences systemic adaptive immune responses. Probiotic treatment in infants can decrease infection related mortality. |
S1369527420301053 | A myriad of microbes living together with the host constitute microbiota which possesses very diverse functions in regulation of host physiology . Recently it has been unequivocally demonstrated that microbiota regulates cancer initiation progression and responses to therapy . Here we review known pro tumorigenic and anti tumorigenic function of microbiota and mechanisms how microbes can regulate cancer cells and immune and stromal cells within the tumor microenvironment . | Microbiota is important in various aspects of host physiology including regulation of cancer development and progression. Microbiota can play negative or positive effects on tumorigenesis and efficacy of therapies. Microbiota regulates tumorigenesis via few distinct mechanisms including interactions with cancer cells and tumor microenvironment. Pro tumorigenic microbiota stimulates tumor elicited inflammation alters metabolism hinder therapies and can promote genotoxicity. Anti tumorigenic microbiota outcompetes pathogenic microbes metabolically suppresses cancer facilitates immunity and therapies. |
S1369527420301065 | Human fungal diseases are a significant global health problem affecting both immunocompromised and immunocompetent patients . Although patients with single gene inborn errors account for only a small part of patients developing fungal infections studies of these diseases significantly promoted our understanding of the general mechanisms involved in human antifungal immunity . Recently substantial breakthroughs in monogenetic causes of fungal infections have been made which have furthered our knowledge of both new genes of known infections and new phenotypes of reported genes . This review describes recent insights into the human monogenetic errors that cause fungal susceptibility alongside novel genes phenotypes and mechanisms of both innate and adaptive immunity . We hope that this review raises awareness of the recently identified monogenetic causes of fungal diseases to facilitate the development of new diagnostic and therapeutic approaches . | Monogenetic causes of fungal disease promoted studies of antifungal immunity. Advances have been achieved in both novel genes and novel phenotypes. Defects in either innate or adaptive immune response underlie fungal susceptibility. Genetic causes should be considered in immunocompetent patients of unusual mycosis. |
S1369703X19301354 | Two lab scale sequencing batch biofilm reactors with no salt and 10.0g L salt were operated to explore the simultaneous COD nitrogen phosphorus removal behavior and the microbial diversity as well as tridimensional key functional microbial groups responses to varying C N P ratios from 125 8.3 1 to 33.3 8.3 1 . The simultaneous nitrification and denitrification process and denitrifying phosphorus removal process were observed in this SBBR system . The N SBBR showed better adaptation to low C N P compared with the performance in S SBBR removal efficiency of ammonia nitrogen and phosphorus in N SBBR showed 15 and 30 enhancement . The sludge samples from N SBBR collected at the C N P ratio of 70.0 7.0 1 had the highest bacterial richness and diversity . The abundance of bacterial in suspended sludge exterior biofilm and interior biofilm were different the interior biofilm tends to favour the growth of denitrifying phosphorus bacteria | Simultaneous nutrients removal in SBBRs were evaluated at varying C N P ratios. Lower C N P inhibited S SBBR more severely in terms of TP removal. Both the microbial diversity and richness were effected by C N P ratios. Microorganism in suspended sludge and biofilm showed different characteristics. PAOs and DNPAOs enriched at the C N P of 33.3 8.3 1. |
S1369703X19302694 | Limiting nitrogen and excess carbon sources induce accumulation of the bioplastic Poly as inclusion bodies in microbes . Here we designed a co culture | Poly 3 hydroxybutyrate synthesis was increased using co culture strategy. Aeration and agitation optimization studies showed improved kLa. Metabolic heat released and yield coefficients were calculated. Synergy seen in co culture gave higher PHB yield compared to monocultures. |
S1369703X19303304 | The dissolved carbon dioxide effect on succinic acid production by A. succinogenes has been investigated and a double substrate mechanistic model has been developed to describe the bioconversion of glycerol under CO | We develop a new experimentally validated double substrate succinic acid fermentation model. The model accounts for multi phase mass transfer phenomena in the fermentation medium. Mass transfer effects of solid MgCO3 on the fermentation system are quantified. System dynamics including liquid and gaseous substrates are successfully predicted. Model can be used to design batch continuous and scale up fermentation systems. |
S1369703X19303316 | Shaken microwell plates are widely used for early bioprocess development as they allow a large number of experiments to be performed in parallel by using small amount of materials . Despite their widespread use microwell plates have not been characterised from an engineering viewpoint . In this study mixing time measurements were carried out in two wells of square and cylindrical cross sections for small orbital diameter shaker | Reduced free surface oscillation leads to reduced mixing time in square microwell geometry. Surface tension plays a critical role in the mixing process in square microwell plates. Mixing times are longer in cylinder wells at low shaken speeds when compared to square microwells. Natural frequency is a promising scaling parameter for microwells and larger reactors. |
S1369703X1930333X | sp . has been reported to synthesize polyhydroxyalkanoates with different monomers such as 3 hydroxybutyrate and 3 hydroxyvalerate . In this study the PHA synthase gene of | Heterologous expression of. Kad1. gene into. PHB4. Transformant. Cn Kad1 harboring. produces P 3HB. 4HB . 4HB monomer increased with higher concentration of sodium 4HB as the carbon source. Produced copolymer with higher 4HB significantly reduced the melting temperature. |
S1369703X19303353 | Microalgal biorefineries have recently emerged as a potentially economically viable option for the co production of value added products and fuels such as biodiesel and biobutanol . Whilst microalgal biodiesel has been studied extensively microalgal biobutanol has received less attention due to the low product yields of the biochemical process from which biobutanol is obtained the Acetone Butanol Ethanol fermentation . In this work we evaluate the potential of a microalgae based biorefinery by i quantifying biobutanol production via ABE fermentation of microalgae using a medium optimised via surface response analysis methodology ii quantifying biodiesel production via transesterification of microalgae . Using SRA optimised medium butanol fermentation yields of 10.31 g g | We present a biorefinery approach for dual biofuel production from microalgae. Biobutanol production was achieved with both raw and hydrolysed biomass. Biodiesel extraction was enhanced by increased cell disruption treatments. ABE process was optimized by supplementing butyric acid to the fermentation medium. |
S1369703X19303365 | Fumaric acid is an industrially important platform chemical which has been widely used in food chemicals agriculture and pharmaceutical industries . Due to the rising price of raw materials in traditional petrochemical method and demand for sustainable development fermentative fumaric acid production has attracted great attention . In this context various strains with enhanced fumaric acid production or elimination of by products were developed through mutagenesis or metabolic engineering . In addition renewable organic wastes together with the fermentation process optimization have also been widely investigated . Accordingly this review will comprehensively summarize the achievements of fermentative fumaric acid production in recent years and major obstacles occurring in industrialization to provide insights and perspective for future microbial fermentation of fumaric acid . | This review provides an overview of metabolic pathways for fumaric acid production. Different fumaric acid producers and strain improvement strategies involved were introduced. Alternative substrates for fumaric acid production and their fermentation performances were shown. The optimization of fermentation conditions was discussed. |
S1369703X19303377 | Robust microalgae cultivation at industrial scale needs complex scale up of photobioreactors since the same yields obtained at lab scale are hardly reached during pilot or industrial production . In this paper we propose a procedure based on Buckingham theorem to perform the scale up of photobioreactors used to cultivate | Theoretical scale up of photobioreactors by Buckingham theorem. Dimensionless numbers evaluated by experimental campaign at different scales. Airlift reactors for cultivation of Chlorella Vulgaris at pilot scale. Set up and tuning of operating conditions for integration in biorefineries. |
S1369703X19303389 | Calcitonin gene related peptide promotes proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells which influence bone regeneration and reconstruction . We previously established CGRP modified BMSCs that express the CGRP gene and demonstrated that this elevated CGRP expression promotes osteogenic differentiation of BMSCs . The current study investigated the therapeutic effects of CGRP modified BMSCs combined with autogenous bone grafting for the treatment of osteonecrosis of the femoral head in rabbits . ONFH model rabbits were divided into three groups CGRP BMSCs pLV5 CGRP combined with autogenous bone grafting NC BMSCs pLV5 NC combined with autogenous bone grafting and Blank BMSCs combined with autogenous bone grafting . After autogenous bone grafting mRNA and protein expression levels of osteogenesis related genes were measured in the femoral head as were ALP laminin and collagen type I contents . The fraction of trabecular bone area percentage of empty osteocyte lacunae maximum compressive strength and mean elasticity modulus of the femoral head were also determined . Our results demonstrated that CGRP modified BMSCs combined with autogenous bone grafting accelerated osteogenic differentiation of BMSCs improved osteogenesis efficiency and promoted the repair and reconstruction of bone tissue in the femoral head which significantly improved the success rate of ONFH treatment . | CGRP could promotes the proliferation and osteogenic differentiation of BMSCs. CGRP modified BMSCs may promote bone formation and repair in the femoral head. CGRP modified BMSCs combined with autogenous bone grafting improved the success of treatment for ONFH. |
S1369703X19303390 | In this study the combined effect of dissolved oxygen and COD N on nitrogen removal as well as the corresponding mechanisms were investigated in aerated constructed wetlands . At each investigated COD N level the ammonium removal efficiency increased as DO concentration increased . However the highest total N removal efficiency occurred at different DO concentration at each COD N level . The results of functional gene analysis and cyclic N profile studies indicated that DO supply and COD N influence the N removal performance which is not only exert a direct effect on nitrification denitrification process but also change N removal pathway in intermittent aerated CWs . At a relatively high influent COD N of 20 the simultaneous nitrification and denitrification via nitrite was almost the exclusive N removal pathway at all investigated DO concentration . With the decrease of COD N from 20 to 2 at DO of 1.8 3.5 and 6.0mg L SND efficiency all decreased however its decreasing rate was much higher at relatively high DO level of 6.0mg L than that at DO levels of 1.8 and 3.5mg L. In comparison a simultaneously partial nitrification anammox and denitrification was established at DO of 0.8mg L along with reducing influent COD N . | DO and COD N had a combined effect on nitrogen removal pathway in aerated CWs. SND was dominant N removal routine in a broad range of DO and COD N condition. SNAD was dominant N removal pathway at low DO along with low COD N levels. Optimal DO for TN removal should be adjusted according to influent COD N. |
S1369703X19303419 | Manganese peroxidase which is an extracellular glycosylated heme protein produced by various basidiomycetous fungi shows attractive potential in various biotechnological applications . A novel MnP gene | A novel MnP gene. from. BBP6 was cloned. Gene. was functionally expressed in. rMnP3 BBP6 had great potential in dye decolorization and denim bleaching. The first report on denim bleaching and PAH degradation using a recombinant WRF MnP. |
S1369703X19303420 | Eco friendly cost efficient and effective extraction methods have become significant for the industries applying zero waste principles . The two main objectives of this study were to examine fucoxanthin extraction from wet | SFE was performed to extract fucoxanthin from. Extraction was conducted directly from wet microalga to reduce energy and cost. A solvent to solid ratio of 200 1 20MPa 35C at 120rpm 60min yielded 0.69mg g. Residual biomass was characterized using light microscopy and SEM EDS analysis. Residual cells could be potential candidate for different commercial applications. |
S1369703X19303432 | This research aimed at comparing the single stage and two stage co digestion of end of life dairy products with a mixture of agro industrial wastes . The two systems were operated in parallel and operational parameters including hydraulic retention time and organic loading rate were tested for their effect on bio hydrogen and bio methane production . During acidogenic fermentation of EoL DPs HRT of 3 days led to process instability due to lactate accumulation whereas HRT of 6 days resulted in maximum hydrogen yield of 0.676mol H | End of life dairy products EoL DP can be efficiently co digested with agro waste. The two stage system yielded 30 higher energy productivity than the single stage. EoL DP fermentation in 3 days HRT resulted in lactate accumulation and process failure. The co digestion systems were stable despite the high ammonia concentrations. |
S1369703X19303511 | Porous cellulose beads are widely used in the adsorption field in which enhancing the structure stability and enlarging the specific surface area are the ways to improve the adsorption efficiency . Here a preliminary chemical cross linking strategy is explored to construct the tough and highly porous cellulose beads as high efficient adsorbent . Especially the customized cellulose solution is preliminarily mixed with a cross linking agent for emulsification and followed by cellulose regeneration . The entrapped cross linking agent creates the inner covalent linkages between the neighboring long cellulose chains which accounts for strong mechanical strength of cellulose framework . Meanwhile the entrapped covalent bonds disrupt the normal growth of cellulose crystalline and lead to more amorphousness which conduces to high specific surface area . Finally the proposed cellulose beads after being modified by DEAE were evaluated for protein adsorption . As a result the obtained porous cellulose beads exhibits high adsorption capacities BSA 204.58mgg | Porous cellulose beads were prepared by preliminary chemical cross linking strategy. The inner chemical linkages of neighboring cellulose chains strengthened the mechanical strength of cellulose beads. Porous cellulose beads possessed high specific surface area of 142.96m. The adsorption capacity of adsorbents reached 204.58mgg. for BSA and 144.78mgg. for BHb. |
S1369703X19303560 | When feeding enzymes are consumed by livestock and poultry the stomach is the first organ to come in contact with feeding enzymes . They will face major hazards acidolysis and enzymatic hydrolysis . Therefore it is very important to improve the tolerance of feed enzymes to the gastric juice such as pepsin . However the hydrolysis of amino acids by pepsin is not specific so improving the resistance of enzymes to pepsin is a great challenge . In this paper we have selected cellulase E4 isolated from | Inhibition of the transition state formation can improve the pepsin resistance of cellusase E4. Select proper mutable sites based on the hydrolysis preference of pepsin and rational design. The pepsin resistance of mutants were improved without affecting the enzymology. The universality of methods are fit to improve the tolerance of other protein. |
S1369703X19303572 | Online measurements of off gas streams are often crucial for studying bioconversion processes . However for anaerobic processes options for online off gas analysis are typically restricted to lab scale bioreactors or larger systems while gas measurements at smaller scales typically do not discriminate between different gases . In this work a method for online measurement of CO | System developed to analyze headspace gasses in anaerobic shake flask fermentations. Fermentations in system mirrored those previously reported in stirred tank reactors. Analyses of gaseous and soluble products allowed carbon balances to be performed. Gas transfer rates reflected phenomena such as inhibition and substrate depletion. System allowed using small volumes with multiple conditions analyzed in parallel. |
S1369703X19303584 | The wider application of creatinase an enzyme used to determine renal function is limited by the yield problem and current production can not meet the needs of society . Therefore the work constructed an efficient | Creatinase activity in B. subtilis was up to 141.9 U mL by high density fermentation. Calcein AM PI assays confirmed the cell membrane was damaged. TEM and SEM results found the presence of leakage site on the bacterial cell surface. |
S1369703X19303596 | An optimization workflow is introduced which integrates multi objective optimization of lignocellulolytic enzyme cocktail ingredients with a bioethanol production process where the enzymes are utilized . The workflow integrates data collection via exploratory experiments modeling via Kriging Pareto based multi objective optimization and process simulation . The critical links in the integration are calculation of enzyme cocktail performance and cost . This allows the identification of the best Pareto optimal result depending on process simulation results . The workflow is demonstrated on a case study involving the production of lignocellulolytic enzymes laccase glucosidase and carboxymethyl cellulase by a white rot fungus | growth conditions are optimized for Lac Bet and Cmc activities. A novel workflow integrating experiments and process simulations is offered. Kriging is used to model time profile data from activity measurements. The workflow is demonstrated on a bioethanol production process case study. Significance of Bet activity favors yeast extract dominated optimal growth medium. |
S1369703X19303602 | A valuable monomer in the synthesis of various polyesters is 5 hydroxymethyl 2 furan carboxylic acid . In this work the synthesis of HMFCA using crude HMF obtained from fructose is described . To obtain crude HMF fructose dehydration was performed by thermal treatment with Nb | Crude HMF was transformed to HMFCA by. The HMFCA concentration of 790.2mg L was obtained using the fed batch strategy. Pyridine nucleotide disulfide oxidoreductase gene is related with HMFCA production. |
S1369703X19303614 | This work aims to investigate optimization while running a Recycled Membrane Biofilm Reactor as a sustainable biological treatment for microcystins removal . For this purpose coupons from an end of life seawater reverse osmosis membrane module were extracted and conditioned . The MC degrading biofilm formation on this recycled membrane surface was carried out in a simulator cell on the laboratory scale to study the influence of air supply in this step . Firstly the main results obtained in this work are related to the biofilm formation . Confocal laser scanning microscope demonstrated that air supply provide a higher biomass maximum thickness and lower roughness coefficient . Secondly the air supply also stimulated the MC removal by shortening the lag phase and increasing the MC degradation rate . Finally the developed biofilm with air supply also was able to efficiently remove MC from two different types of polluted water surface natural water and synthetic reclaimed water . These results support the R MBfR technology for treating MC polluted water that could be used for different application especially in nutrient rich water . Therefore this study addresses the lack of sustainable technologies for water treatment while opening an alternative in sustainable solid waste management under a circular economy approach . | Biomass thickness and homogeneity of the biofilm were enhanced by air supply. A stable biofilm with EPS production was achieved on the recycled membrane. The air supply diminished the lag phase and increased the MC removal by the biofilm. MC was more rapidly eliminated in nutrient rich water. |
S1369703X19303626 | Using laccase as a case study an alternative methodology for discrimination of bisubstrate mechanism types useful for Bi Bi reactions when water is one of the products is presented . A purified enzyme from fungal cultures of | AICc and Akaike weights were useful to discriminate bisubstrate models of laccase reactions. The more likely bisubstrate model for ABTS oxidation was ping pong. The more likely bisubstrate model for DMP oxidation was Theorell Chance. Michaelis Menten constants towards dioxygen mean that laccase is not oxygen saturated. |
S1369703X19303638 | During the past two decades cell culture has played an important role in many biochemical and biomedical fields . However finding an alternative to animal serum is an important area in cell culture methods and related biotechnology industries . In a previous study we demonstrated that the platelet rich plasma from specific pathogen free pigs was a rich source of cytokines and growth factors and might serve as a replacement for animal serum . The selection of an activator is a crucial step in PRP activation and affects the availability of bioactive molecules . The present study is the first to demonstrate the ability of ectoine to activate PRP and to investigate the effects of ectoine activated PRP on cell proliferation and biological function . The amounts of bioactive molecules including TGF PDGF AB EGF VEGF KGF and IGF secreted from PRP activated by ectoine were measured . In addition two types of primary cells and three types of cell lines were cultured with various concentrations of ectoine activated PRP under animal serum free conditions . Then the effects of ectoine activated PRP on cell growth kinetics extracellular matrix secretion and melanin synthesis were also determined . Finally our results demonstrated that ectoine is a novel and effective PRP activator and that ectoine activated PRP can serve as an excellent replacement for animal serum in cell culture and related applications . | This study was the first to demonstrate that ectoine is an effective PRP activator. Ectoine is a novel activator with a defined and simple structure. Ectoine activated PRP can release high levels of bioactive molecules. Ectoine activated PRP is an excellent replacement for animal serum in cell ulture. Ectoine activated PRP is speculated to be a safe and excellent melanin inhibitor. |
S1369703X1930364X | The expanding aquaculture industry increases the prices of fishmeal the main protein source in fish diet . A promising alternative is microalgal protein . Therefore we investigated the protein production capacities of green microalgae | Microalgal strains were optimized for protein production as alternative to fishmeal. After optimization the maximum cultivation time of both strains was 2 days. Maximum protein productivity for. CY1 was 0.8560.025g L d. Maximum protein productivity for. ESP 31 was 0.9460.065g L d. |
S1369703X19303651 | As a biocompatible and designer solvents ionic liquids are extensively used for enzymatic conversion of substrates particularly those that are insoluble or sparingly soluble in water and common organic solvents . More than a decade ago the first generation ILs involved in enzymatic reactions generally comprised an imidazolium cation and non coordinating anions such as tetrafluoroborate and hexafluorophosphate . Recently focus has shifted to more environmentally acceptable second and third generation ILs comprising enzyme compatible cations and anions such as amines and amino acids . A wide range of such ILs have been derived from readily available renewable resources and used in biocatalytic reactions . Compared with first generation ILs the use of enzymes in second and third generation ILs provides better activity and stability and they are also attractive from both an environmental and an economic viewpoint . In this review we report the recent advances of enzymatic reactions in second and third generation ILs . The intention of this review is not to cover first generation ILs but rather to update and overview the potential approaches developed within the last ten years for enzymatic reactions in second and third generation ILs . | Overview of second and third generation ionic liquids ILs for enzymes. ILs showed great enhancement of enzyme performance. Novel materials have been developed to stabilize enzymes in ILs. More studies are required to develop cost analysis for ILs bioprocesse |
S1369703X19303699 | Lipid degradation behavior was examined during the Intermittent Contact Oxidation Process for application in in sewer purification . Lipids are known to accumulate in the sewer environment making the study of its degradation behavior relevant for in sewer purification . Changes in the lipid substrate during various flow conditions and the subsequent effect of these transformation on the performance of a channel incorporating ICOP were focused on . Biomass was first developed for 84 days in three types of sponges . Oxygen consumption rates indicative of aerobic lipid degradation were then observed during three flow conditions which were extended no flow condition frequent flow condition and a combination of extended no flow and frequent flow condition . Oxygen consumption rates decreased over time during extended no flow condition while they were generally similar during frequent flow condition for all sponge types . Lipid samples analyzed after treatment revealed that intermittent flow affected the composition of residual free fatty acid species . Overall the study provides insights on the effect of flow intermittency on lipid degradation behavior during the application of the ICOP for in sewer purification . | Lipid degradation occurred during no flow and was enhanced during frequent flow. Oxygen mass transfer was enhanced during flow. Oxygen mass transfer during no flow was affected by retained water volume in the porous media. Oxygen supply affected by flow intermittency affected lipid degradation behavior. |
S1369703X19303705 | A new dynamic model that mimics gastrointestinal function was designed . Elastic and contractile silica gel with gastrointestinal rugae and folds were used to simulate the stomach and large intestine and silica gel with intestinal folds and villi was utilized to simulate small intestines . Mixing times for Newtonian fluids with Reynolds numbers of 105000 and for non Newtonian fluids with Reynolds numbers of 1100 were shortened in the new dynamic model bionic gastrointestinal reactor compared with those in a traditional stirred tank reactor . Gastric pressure of stomach at different digestion phases in the range 20220mm Hg was simulated by adopting different motion models . Maximum force of 0.72N was observed when using agar beads to mimic solid foods . The folds and villi increased the surface area of the modeled small and large intestine walls by 112 and 52 respectively . As a result mixing and grinding in the simulated tract was improved . In the future BGR can be applied for simulated studies on digestion and metabolism of foods and drugs in a mimetic gastrointestinal tract environment . | BGR has better mixing time than traditional STR. The gastric pressure of the stomach can be simulated by adopting different motion models. The maximum crushing force of the BRG is higher than 0.72N. The folds and villi increased the surface area of small and large intestine walls by 112 and 52 . New technology for dynamic digestion model reactor was developed. |
S1369703X19303717 | Indole 3 ethanol is an important pharmaceutical intermediate that possess significant pharmaceutical properties . In this study we established an artificial pathway in engineered | Production of indole 3 ethanol from L tryptophan. De novo biosynthesis of indole 3 ethanol from glucose. De novo biosynthesis of indole 3 ethanol acetate from glucose. |
S1369703X19303729 | As a kind of pyrimidine nucleoside cytidine has been widely recognized as an important precursor for the production of some antiviral and antitumor drugs . In this study the systematic construction of metabolically engineered | Cytidine titer was stepwise increased under the coordination of four modularized metabolic engineering strategies. The metabolic module from UMP toward cytidine was investigated to enhance cytidine formation. The major rate limiting steps and competing pathways of cytidine biosynthesis were identified and fine tuned. A fed batch fermentation was performed in a 5 L reactor to further increase cytidine titer. |
S1369703X19303730 | The aim of this study was to establish a phenomenological model capable of describing the mass transfer and kinetic effects of the | Phenomenological model for the. transesterification of microalgal biomass. The model predicts the mass transfer of the transesterification reaction. The model fits the experimental data and adequately describes the reaction kinetics. The Volume Elements Method was used in the model development |
S1369703X19303754 | Small scale culture of animal cells in suspension is of importance for many applications . At a small scale fed batch is achieved either by manual bolus feeding or the use of liquid handling robots . In this study we report an alternate application of a hydrogel for in situ continuous delivery of a nutrient feed comprising 18 amino acids vitamins antioxidants and trace elements . We show that amino acid release is sustained for at least seven days . Importantly release rates of individual amino acids can be independently modulated by changing their loading . We demonstrate the application of this hydrogel for complete in situ feeding of nutrients to a suspension adapted CHO cell line expressing IgG leading to 2.7 fold and 4 fold improvement in integral viable cell density and volumetric productivity respectively . This is similar to improvements obtained by bolus liquid feeding . Further supplying glucose from the same hydrogel to eliminate manual feeding led to a 1.8 fold increase in IVCD accompanied by a 3 fold increase in volumetric productivity as compared to batch culture . In summary this study provides a proof of concept that hydrogels can enable completely closed in situ feeding for mammalian cell culture requiring no external intervention . Such continuous in situ delivery can potentially enable closed culture systems maintaining nutrients at low levels mimicking physiological concentrations . | In situ delivery of a multi component nutrient feed by hydrogel NutriGel . NutriGel sustains release of amino acids for at least 7 days. Independent modulation of release rates of 16 amino acids demonstrated. NutriGel enables a completely closed system for fed batch culture of animal cells. NutriGel improved IVCD and productivity by 1.8 and 3 fold compared to batch culture. |
S1369703X19303766 | Understanding and modeling of the metabolic pathway of a cell by probing the fraction of extracellular metabolites is gaining much interest in biological reactions . This communication deals with metabolic footprinting technique to understand the effect of static and shake culture conditions on the production of lovastatin by | Metabolic pathway for the biosynthesis of lovastatin was constructed using metabolic footprinting technique. Culture conditions had profound influence on the production of lovastatin as observed through the variation in internal metabolic fluxes. Ethanol and glycerol were produced along with lovastatin by. They were probably utilized back to increase the production of lovastatin in shake culture. The dynamic macroscopic models developed were validated using experimental data. |
S1369703X19303778 | Realization of binding reagents that can perform high fidelity sequential recognition and detection of amino acids is important for the success of many proposed approaches for single molecule protein sequencing . Towards this purpose a variant of the | Engineering thermostable into ClpS protein variants for biotechnology applications. Thermostable ClpS variants retain original N terminal amino acid specificity. Thermostable ClpS variants retain original N terminal amino acid affinity. ClpS affinity and selectivity depend on the second amino acid in the target peptide. |
S1369703X1930378X | Estimations of the facility footprint and fixed capital investment of cell therapy facilities need to consider the unique features of the single use technologies selected for CT manufacture and the product nature that impacts scale out versus scale up approaches . A novel detailed factorial methodology is proposed for estimating FCI and footprint for bespoke stick built cell therapy facilities that accounts for technology specific factors for key cell culture technologies as well as the implications of SUTs open versus closed operations and the commercialisation scenario selected . This was used to derive benchmark values for short cut cost and area factors for typical cell therapy facilities according to the technologies selected . The results provide project specific ratios for equipment purchase costs to facility footprint and for FCI to total equipment purchase costs . Area factors m | Factorial methodology for fixed capital investment FCI of cell therapy facilities. Considers impact of single use technologies SUTs on facility design. Considers the product nature that impacts scale out versus scale up approaches. Benchmark values provided for cost and area factors for cell therapy facilities. Autologous versus allogeneic facility footprints and FCI values compared. |
S1369703X19303791 | 5 hydroxymethylfurfural is a versatile biomass derived chemical for synthesizing useful compounds . In this work an attempt is made to produce HMF by developing a low cost process for doing that using cellulosic waste and deep eutectic solvents . The most effective DES was choline chloride citric acid which provided a greater glucose conversion percentage HMF yield and HMF selectivity than other DESs with 0.1g of pure glucose . To increase the HMF yield further the species of catalyst reaction time and reaction temperature were varied . The highest glucose conversion percentage HMF yield and HMF selectivity were obtained with a reaction time of five minutes a reaction temperature of 130 sulfuric acid as the catalyst and a ChCl citric acid ratio of the DES of 2 1 . These optimal conditions were used with the enzymatic hydrolysate of pretreated wood dusts as a substrate . The experimental results thus obtained revealed a glucose conversion percentage HMF yield and HMF selectivity of 34.86mol 16.46g g and 67.43 respectively under these conditions . These results reveal that using enzymatic hydrolysate from pretreated wood in the production of HMF can yield approximately as much as the use of pure glucose indicating that this low cost process may be commercially feasible . | The composition of wood dust and its byproducts from SE process were identified. The constituents of DESs affect the yield and selectivity of HMF was determined. The reaction conditions affect the yield and selectivity of HMF was explored. Optimal conditions for using pretreated wood dust to produce HMF were identified. |
S1369703X19303808 | The removal of atmospheric methane by methanotrophs is a potential strategy for mitigating global warming . However due to the low mass transfer of methane to methanotrophic cells the conventional bioprocesses require active gas supply with high energy consumption . This study aimed to evaluate methane degradation performance in microbial gas phase reactions using effectively immobilized | Freeze thaw treatment facilitated the immobilization of methanotrophic cells. Methane degradation is higher in microbial gas phase reactions even without agitation. Gel entrapment systems impaired methane degradation in the gas phase reaction. Absence of an aqueous diffusion barrier improved methane degradation efficiency. |
S1369703X1930381X | A lipase gene was identified and isolated from a fosmid metagenomics library constructed from forest topsoil samples . Error prone PCR and saturation mutagenesis were used to generate seven lipase variants S69P R194Q S69G S69P S69E S69P T99S N190S R194Q R194S and R194A by testing five different fatty acids of | Present study report engineering of a metagenome derived lipase gene. Positions R194 and S69 are identified as hot spot residues for improved activity. Reactivity of lipases can be engineered at positions away from the active site. Combining directed evolution with saturation mutagenesis is an effective approach. |
S1369703X19303961 | Since monoclonal antibodies are sensitive to the manufacturing process several mAb variants can be the result of a single batch production . The most critical source of heterogeneity is glycosylation which has a profound impact on safety and efficacy of the final product . Implementation of monitoring and control of the process using the Quality by Design approach may help to ensure mAb specifications although its implementation is limited by the availability of real time specific measurements . All current approaches to elucidate mAb glycoforms require sampling and labour intensive efforts . Thus glycosylation analysis is often performed with the objective of detecting quality defects at the end of the culture process . In this work the capability of Near Infrared spectroscopy and chemometric treatment to accurately monitor mAb glycosylation during CHO cells cultures using | Monitoring of mAb glycosylation during CHO cell processes by. NIR probes. PLS regressions are limited for providing spectrum based glycosylation information. Consideration of the process nature in regression is critical for accurate monitoring. The novel use of LWR allowed to monitor total mAb concentration accurately. Only SVR allowed mAb glycoform concentration monitoring. |
S1369703X19303985 | N acetyllactosamine is an important lactose derived molecule which can act as an effective prebiotic . In this study a process for the enzymatic synthesis and downstream purification of LacNAc was designed based on the use of thermostable galactosidases from | Techno economic analysis of large scale enzymatic production of N acetyllactosamine. Separation processes based on chromatography and crystallization were compared. The process based on selective crystallization and the BgaD D enzyme gave the lowest costs. Production capacity N acetylglucosamine recovery acceptor to donor ratio and yield investigated. |
S1369703X19303997 | In modern aquaculture simple and rapid methods of predicting fish ovulation are needed to produce seedlings in a stable and efficient manner . Ovulation time is variable due to environmental and physiological factors while 17 20 dihydroxy 4 pregnen 3 one an indicator of ovulation increases its concentration rapidly just before spawning . In this paper we developed a biosensor system in which immune and enzymatic reaction assays were combined to monitor DHP levels with low environmental loads . We attempted to quantify DHP by analyzing the decrease rate in the output current after the immunoreaction using the amperometric method as a transfer inhibition degree of the enzyme generated electrons generated by the formation of the antigen antibody complex . DHP standard samples were measured under investigated optimal conditions and a specific response with a good linear correlation was obtained between the current decrease rate of the sensor system and the DHP concentration in a range of 7.81500pg ml | An amperometry immunosensor was developed for simple and fast monitoring 17 20 dihydroxy 4 pregnen 3 one DHP . The proposed sensor system is eco friendly because it used non toxic glucose as a source of sensor output. The sensor system may help us to predict fish ovulation which can improve the efficiency of modern aquaculture industry. |
S1369703X19304000 | In this study anaerobic membrane bioreactor was applied for the treatment of a model slurry of high strength organic solid waste . Continuous monitoring of reactor performances by chemical analyses and fine scale tracing of the AnMBR sludge microbiome by high throughput 16S rRNA gene sequencing were conducted during the long term operation with increased organic loading rates up to 5.26 kgCOD m | Long term acclimatization of AnMBR sludge to treat organic solid waste was performed. SRT control to optimize MLSS in AnMBR improved reactor performances. High resolution dynamics of the AnMBR sludge microbiome were revealed. Constitution of methanogens was changed with the OLR increase and SRT control. Syntrophic methanogenesis was responsible for AnMBR treatment of organic solid waste. |
S1369703X19304012 | Environmental concerns and the depletion of fossil resources are the major factors that boost modern society towards bio based and circular economy . To this end the development of mathematical tools that can be used to perform rapid comparative analysis across multiple technology options is necessary . The aim of this work is to present a simple and accurate mathematical model which describes the economics of the bioreaction section of a typical biotransformation technology . The functional dependency of fixed capital investment and utilities consumption from parameters determined experimentally is developed using a regression model . The proposed model which consists only of three equations can be used to compare the economic performance of different bio based technologies that could potentially reach commercialization . More specifically it can be used to estimate at the early stages of process development the effect of final broth concentration fermentation time and aeration rate on overall process economics . | A linear statistical model for comparing the economic performance of different bio based chemicals. Functional dependency of bioprocess economics on fermentation time titer and aeration rate. Fixed capital investment and utilities consumption of a biotransformation technology. |
S1369703X19304036 | We introduce a novel magnetically coupled mixer drive for biotechnological pharmaceutical and chemical applications requiring high grade aseptic conditions . The proposed design enables its application in larger volume bioreactors compared to traditional magnetic drives due to a possibility of introducing higher power quantities per individual rotor while ensuring higher mixing intensity . | The design of the novel magnetically coupled mixer drive is demonstrated. Magnetic field simulations were performed for two magnetic drive scales. The magnetic mixers were built according to the simulated designs. Magnetic mixer performance was evaluated in terms of maximal torque and power input. The magnetic drive was applied during K. marxianus cultivations in 15m3 bioreactor. |
S1369703X19304048 | To scale up a filling process in a cell manufacturing system the impact of the processing time on the final product quality should be evaluated . It is known that the suspended cells in a cryopreservation solution are subjected to various types of stress factors which eventually results in apoptotic or necrotic death . In this study the aim was to investigate a critical factor of cell decay in human induced pluripotent stem cells suspended in a cryopreservation solution and to propose a methodology to maintain the viability of cells for a longer filling process time . Based on experimental results it was determined that the accumulation of intracellular reactive oxygen species induces apoptosis of cells suspended in a cryopreservation solution . In addition treatment with an antioxidant or a low temperature condition was effective in suppressing the induction of apoptosis and subsequent cell death . In particular the treatment at low temperature was able to maintain the attachment efficiency of suspended cells at a higher level compared to the treatment with antioxidants . The appropriate control of redox balance in cells suspended in a cryopreservation solution could improve the viability of cells in the filling process and lead to the successful lot size expansion of cell manufacturing systems . | ROS accumulation induces apoptosis of cells suspended in cryopreservation solution. Treatment with antioxidant or at low temperature suppresses apoptosis induction. Low temperatures alone are sufficient to achieve maximal yield. Control of cellular redox balance is a key factor of a filling process system design. |
S1369703X19304061 | External magnetic field with simple rapid standardized and controllable characters can improve electricity harvesting in bioelectrochemical systems . Herein the fabrication of external magnetic field with microbial electrosynthesis system in which electrotrophic | Magnetic field stimulates. for more production of acetate in MES. Magnetic field induces. for more EPS and bacterial growth. Synergistic stimulating of magnetic field and circuital current for release of EPS. Additive effects of magnetic field and circuital current on. growth. Circuital current was more influential than magnetic field for release of EPS. |
S1369703X19304073 | The carbon release behaviour of polylactic acid starch blends and the correlation between solid phase denitrification performance and solid carbon decomposition were investigated by both batch experiments and numerical simulations . The results showed that the mass ratio of PLA to starch is a key parameter in determining the total organic carbon release rate of the blends . Hydrolysis of the blends contributed more markedly to the fraction of TOC released during denitrification compared with physicochemical leaching . The maximum denitrification rate of the blend supported SPD system was 0.008kg N m | Carbon release behavior of PLA starch based solid carbon was investigated. Mass ratio of the blends is a key parameter governing the TOC release rate. Hydrolysis contributed more to TOC released than the physicochemical leaching. Little TOC will accumulates in the effluent during the SPD process. The PLA starch blend is an ideal solid carbon source for nitrate removal. |
S1369703X19304085 | Numerous micro physiological systems have been reported to successfully mimic the organ microenvironment . However there are currently only a few systems that focus on real time physiological monitoring for preclinical cytotoxicity assessment of drug candidates . We developed a multi sensor lung cancer on chip platform for trans epithelial electrical impedance based cytotoxicity evaluation of drug candidates . The excellent transparency of ITO electrodes allowed for visual monitoring of cells on chip using a 3D printed digital microscope which has not been previously reported . An optical pH sensor was used for online monitoring of media pH . As a proof of concept lung cancer NCI H1437 cells were cultured on glass based microfluidic chip and biosensors data were obtained in real time . The toxicity of different concentrations of drugs doxorubicin and docetaxel was then monitored in real time using the TEER impedance sensor . The TEER impedance response was evaluated in terms of cell index whereas a live dead assay was performed for the comparison of cell viability at the end of the experiments . The cell index assessment suggested that the increasing concentrations of doxorubicin resulted in a higher cell death rate than docetaxel . The pH response and microscopic images were also recorded during drug treatment . The platform we developed here is a promising tool for the cytotoxicity evaluation of novel drug compounds for future micro physiological systems and development of personalized medicine . | A lung cancer on chip platform was developed for real time physiological monitoring. All the biosensors were developed in house including pH and TEER impedance sensors. Transparent ITO electrode allowed for visual monitoring using 3D printed microscope. The toxicity of anticancer drugs doxorubicin and docetaxel was evaluated. A comparison of impedimetric and live dead cell viabilities was also analyzed. |
S1369703X19304218 | The potential of Forward Osmosis technology to up concentrate succinic acid lactic acid and ethanol from fermentation broths was investigated . The aforementioned molecules were obtained from two residual resources | Succinic acid lactic acid and ethanol were produced from residual resources. Forward osmosis was examined to up concentrate fermentation products. Succinic acid concentration factor of 5.0 was achieved. Best results were obtained with NaCl 5.0M as draw solution. Water removals of up to 85 were attained. |
S1369703X1930422X | Paper based diagnostics are rapid robust affordable and user friendly thus have potential for point of care . Modulation of sample flow in these technologies have the advantage of increased exposure between immunoreagents which ensures higher sensitivity and specificity . In this study common membrane types were compared and modified to modulate sample flow . Five different membranes were compared glassfiber polyester nitrocellulose polyvinylidene difluoride and cellulose . Several parameters were tested for their effect on the sample flow membranes absorption capacity immobilization of buffer solution different membrane types as separation layer and sample volume . The effect of separation membrane on the sample flow was tested using a Stack Pad sensor layout . Higher antibody levels could reach the three absorption pads with the use of polyester separation membrane as compared to the glassfiber separation membrane thus potentially increasing the sensor sensitivity . Lastly the effect of the membrane type and its modifications on the detection sensitivity was also compared . The finalized modified setup demonstrated a higher detection sensitivity vs. the initial setup . To conclude the selection of membrane types and their modifications can modulate sample flow and increase the sensitivity of detection in paper diagnostics . | Sample flow modulation in paper diagnostics increase exposure between immunoreagents that may increase sensor performance. Selection of membrane types and their modifications modulate sample flow and may increase the sensitivity of detection. Five different membranes were compared glassfiber polyester nitrocellulose polyvinylidene difluoride and cellulose. Polyester membrane as separation layer and skim milk tween based buffer promotes antibody release and flow in the sensor. Control of membranes type and their modifications inside paper based sensor increased sensing sensitivity and performance. |
S1369703X19304231 | In this work was presented a strategy to produce to concentrate and to apply a cocktail containing cell wall degrading enzymes . The novelties and the differences of this study from the others lie in the fact of defining the entire production process of a second generation biopesticide and in addition an enzyme cocktail will be produced and not a single enzyme as usually studied . Enzymes were produced by solid state fermentation using | High production of cell wall degrading enzymes. Membrane technology was efficient for enzyme enzymes concentration. Concentrated enzymes presented insecticidal activity. |
S1369703X19304243 | The work focuses on the bioelectrochemical treatment of wastewater containing phenol and trichlorophenol in microbial fuel cells with non coated and PANI SnO | Comparative bioremediation of mixed phenolic contaminants under anoxic and oxic conditions. PANI SnO. modified for the treatment of P TCP. Electrochemical polymerisation of PANI SnO. nanocomposite on the surface of carbon cloth electrode. Higher PD and COD removal efficiency for oxic treatment of P TCP. |
S1369703X20300012 | Butane is an abundant side product of oil and gas production and is mostly burned for energy and heat production . The alkane monooxygenase enzyme system | Volumetric productivity is driven by butane gas to liquid mass transfer. Gassing rate dominates volumetric productivity over pressure and temperature. Increasing butane content is no key to significantly rise volume productivity. a transferability demonstrated for different bubble column geometries. |
S1369703X20300024 | The assembly of multiple enzymes has received increasing attention due to the promising application in improving biocatalytic process . In this study supramolecular nanoreactors were engineered by assembly of polyphosphate kinase and bifunctional glutathione synthetase for adenosine triphosphate regeneration in vitro . Tetrameric PPK and dimeric GshF were first self assembled via peptide peptide interaction of fused leucine zipper domains to form multienzyme complexes with plate like morphology . Further under the driving force of polymerization of PPK driven by substrate polyphosphate MECs were assembled into multienzyme nanoreactors with branch like morphology . MENRs were applied to a two enzyme cascade reaction in vitro . The ATP regeneration efficiency of MENRs system was 57 higher than that of unassembled enzymes mixture and the thermal stability was improved by 46 . When reused for ATP regeneration the assemblies retained more than 70 of the initial activity even after seven cycles . This is the first report in which an artificial complex was constructed by substrate driven assembly of multiple enzymes for cascade reaction . The strategy demonstrated potential application of multienzyme assembly in synthetic biotechnology and nanotechnology . | Dimeric GshF and tetrameric family 2 PPK were self assembled into MECs through LZs mediated interaction. MECs were assembled into supramolecular MENRs driven by the substrate polyP. MENRs system showed higher ATP regeneration efficiency and stability than unassembled system. MENRs retained more than 70 of the initial activity after seven cycles for reuse. |
S1369703X20300036 | Lycopene is an antioxidant that can be used as functional food or a high value product for nutraceutical pharmaceutical and cosmetic applications . In this paper the mevalonate and lycopene synthesis pathways were first built in | Biosynthesis of lycopene from metabolically engineered. Capable of using free fatty acids or waste cooking oil to improve lycopene yield. Co feeding with glucose and waste cooking oil to produce 2.7g L lycopene in 40h. Lycopene content in biomass 94mg g is among the highest levels reported so far. |
S1369703X20300048 | Suspended solids are one of major pollutants that deteriorate water quality . The high rate clarifier is commonly used as the tertiary treatment by coagulation to agglomerate particles thus achieving a high SS removal and making effluents acceptable for discharge . Currently the control of average residence time in operation of high rate clarifier is challenging With limited residence time the particles fail to form flocs in the mixing tank causing inefficient solid liquid separation while with prolonged residence time SS sedimentation would accumulate at the bottom of the tank . In this study a liquid solid two phase computational fluid dynamics model has been developed to simulate the distributions of flow field and SS in a high rate clarifier . The CFD model was successfully validated against experimental results in a full scale operation with the normalized standard error on SS less than 1.24 . The results showed that the height of under through channel affected the flow field more significantly rather than its width . This study also indicated that with the height of under through channel decreasing from 2000 to 500mm and the height of baffle increasing from 3300 to 5213mm the average SS concentration at the bottom of reaction tank would decrease by 34.95 and the average residence time would be shortened by 4.77 which can be helpful for prolonging dredging cycle and avoiding unnecessary dredging costs . | Flow field and SS concentration were simulated in a full scale high rate clarifier. SS at the bottom of reaction tank was decreased by 35 to avoid SS sedimentation. Suitable under through channel and baffle heights were obtained by two phase model. The standard error between simulated and measured velocities was less than 6.71 . The error between simulated and measured SS concentration was less than 1.24 . |
S1369703X2030005X | The differentiation of human induced pluripotent stem cells into functional hepatocytes has the potential to solve the shortage of human primary liver cells and would be of use in drug screening . In this frame we developed a hiPSCs maturation strategy in microfluidic biochips using a liver on chip approach a promising technology mimicking | Maturation of hiPSCs derived HLCs is improved by culture in a microfluidic biochip. The tissue formed presents liver specific markers such as Albumin CYP3A4 or the production of urea and cholesterol. Longer maturation might improve the functionality. |
S1369703X20300061 | This work aims to control foaming in a submerged membrane bioreactor by optimizing the organic loading rate and sludge retention time values to decrease the extracellular polymeric substance production used for the pharmaceutical wastewater treatment . Four lab scale SMBRs were operated for a period of more than 8 months to determine the biokinetic coefficients and optimize the SMBR systems operation under the SRT of 5 10 15 20 25 days and OLRs of 0.03 0.32 gCOD L.day . The investigation revealed that the lowest foaming quantity was at an organic loading rate of 0.32 gCOD L.day and a sludge retention time of 15 days related to few protein concentration of EPS . The results also showed that the foaming quality at the OLR of 0.03 gCOD L.day was higher compared to the greater OLRs in all SRTs . It was found that the yield the endogenous decay coefficient k | Quantity and quantify of foaming were evaluated at different SRTs and OLRs. Protein content of EPS can lead to more foam formation than carbohydrate. Foaming phenomenon can be controlled by optimizing OLR values. More OLR is not providing higher values of maximum specific growth rate m . |
S1369703X20300073 | genus is an important biological control agent . Most industrial conidia production processes are based on the use of plastic bags or containers containing 1kg of substrate . Static bioreactors such as packed columns trays and plastic bags are used for different scale conidia production . However the effect of aeration mechanism on conidia production and quality has not been evaluated . Therefore the productivity and quality of conidia produced in three types of bioreactors were evaluated | Conidia production increased threefold in aerated packed column bioreactor. Conidia productivity in columns were twice as high than those in trays and bags. Maximum conidia production was attained when the CO. production rate decreased 50 . Infectivity of conidia was independent of the aeration mechanisms tested. |
S1369703X20300085 | This study was carried out at both laboratory and pilot scale to investigate whether the presence of phosphorus affects the nitrification process during aerobic digestion of aquaculture aquaponic solid waste . Results from the laboratory scale aerobic digestions indicated that nitrification did not occur throughout the entire bioprocessing period in aerobic bioreactors containing phosphorus . The mineralization process in laboratory scale aerobic bioreactors which did not contain phosphorus on the other hand followed the typical non inhibited nitrogen mineralization | Phosphorus affects the bioconversion of organic solid waste into liquid fertilizer. Phosphorus delays the onset of nitrification of aquaculture aquaponic solid waste. Phosphorus should be avoided in bioprocessing of aquaculture aquaponic solid waste. |
S1369703X20300097 | Based on elementary flux mode analysis a novel approach is presented for monoclonal antibody production by GS CHO cells . A kinetic model is developed on the basis of a set of macro reactions which can predict the time dependent concentrations of metabolites cell growth and MAb productivity over a range of culture conditions . The model incorporates energy metabolism with biomass and MAb formation with the specific ATP production rate being decided by the central carbon metabolism and used for estimation of biomass and MAb synthesis rates . The reaction rate expressions are represented by MichaelisMenten kinetics based on extracellular metabolite concentrations which determine ATP production by glycolysis and respiratory chain . Glutamine and asparagine are considered as regulatory metabolites for GS CHO cells . Glutamine determines asparagine utilization route and energetic state of cells while asparagine regulates the uptake rates of aspartate and glutamate . The model was calibrated for glutamine free and glutamine available cases and validated for fed batch cultures supplied with glutamine . Unoptimized fed batch cultures have been simulated for daily and constant feeding . The model predictions are in good agreement with the experimental data reported in literature . | Cell culture kinetic modeling. Metabolic behavior under different culture conditions. The effect of glutamine availability on central carbon metabolism. Model based evaluation of fed batch processes. |
S1369703X20300103 | Changes in microbial communities are observed during the long term operation of activated sludge systems employing an excess sludge reduction technology . Short term changes are also significant to confirm if key microbes are damaged but they have not been investigated due to the absence of an appropriate method . We report a methodology to identify prokaryotic and eukaryotic species damaged almost instantaneously by a high pressure jet device a cost effective sludge reduction technology . 16S rRNA gene amplicon sequencing and microscopic inspection were implemented to identify damaged microorganisms . A sludge injection ratio | A sludge reduction method to damage and identify prokaryotes was proposed. A high pressure jet device HPJD was applied for sludge reduction. Eluted DNA from damaged bacteria was sequenced for taxonomic identification. Nitrifying bacteria were not damaged by HPJD treatment. Protozoa were severely damaged by HPJD treatment. |
S1369703X20300127 | CdSe quantum dots are semiconductor materials and possess unique optical and electronic properties therefore being increasingly used in many fields . Biosynthesis of CdSe QDs has several advantages over the chemical synthesis route . In this study the CdSe QDs were biosynthesized using a yeast | CdSe quantum dots was synthesized by. PA 1 with small size and a narrow size distribution. The concentration of Cd determine CdSe biosynthesis that is a detoxification strategy of Cd in. PA 1. Bio synthesized CdSe quantum dots showed photocatalytic activity toward MG degradation under ultraviolet and visible light. |
S1369703X20300139 | Thalassaemia is an inherited blood disorder with serious complications . Combining the unique advantages of DNA and magnetoelastic materials an ME DNA biosensor was proposed that can wirelessly detect a target DNA sequence that is a 4 bp deletion in codon 41 42 in the globin gene causing thalassaemia . The thiolated capture probe was covalently immobilized on the surface of the gold plated ME chip and then hybridized to tDNA and AuNPs modified with thiolated signal probe DNA serve as the signal amplifier and the direct signal indicator enabling label free detection . The specific hybridization process of sDNA AuNPs to tDNA increased the surface load mass and decreased the resonance frequency of the DNA biosensor . The resonance frequency shift of the DNA biosensor was linear to the logarithmic concentration of tDNA in the range of 1.010 | An ME DNA biosensor was developed to detect a common mutated DNA causing thalassaemia. sDNA AuNPs serve as the signal amplifier. The sandwich type structure enables label free detection. A low detection limit of 0.571pM and high sensitivity of 72.7Hz nM were obtained. The DNA biosensor exhibits excellent sensitivity selectivity and stability. |
S1369703X20300140 | TCCC 13007 was used to produce aminobutyric acid . The fermentation broth was degermed decolorized and deionized before the green style spray drying and the process parameters were optimized . Single factor experiments were carried out to optimize 7 factors to investigate their effects on spray drying . Maltodextrin was found to be a good drying aid that significantly improves the drying process . Response surface methodology was used to assess the combined effects of air inlet temperature spray pressure and amount of maltodextrin to optimize the spray drying process parameters of the aminobutyric acid containing eluent . The optimized variables were applied for the following evaluation of the powder collection rate and comprehensive product score evaluation . Using the optimum parameters of spray drying the powder collection rate reached 62.74 the comprehensive score was 85 and the aminobutyric acid content was 67.5 and the recovery rate of GABA was 60.71 . These results lay the foundation of further industrial scale up of aminobutyric acid production from fermentation broth . | GABA rich powder was prepared from fermentation broth by green style spray drying. Maltodextrin was screened out as best drying aid to help spray drying. The 7 parameters of spray drying were optimized by response surface methodology. The obtained results lightened cleaner GABA preparation for industrial fermentation. |
S1369703X20300152 | Due to the availability of natural gas shale gas and flared gas there is increased interest in converting methane in these gases into commodity chemicals via cost effective and sustainable processes . Recently we have demonstrated an efficient process concept converting methane to lactic acid by methanotrophic bacteria with high carbon flux pivoting potentials for commercialization . Herein we present a first of kind conceptual design and a techno economic analysis of a biorefinery process with calculated minimum selling prices . This study includes both sensitivity analysis and scenario analysis for key cost drivers and for projecting path forwards in research and development . The analyses reveal that the conversion efficiency LA product titer LA productivity and gas flow rate have the most significant impacts on cost . The MSP varies from 5.83 2.17 kg LA depending on these key process attributes . Further a life cycle assessment of this process concept is evaluated and compared to understand the sustainable aspects . In this TEA study the bio upgrading process from natural gas to LA presents a potentially promising approach in terms of the feedstock versatility economic viability and environmental impact . | Four different scenarios of BioGTLA were analyzed in the n. plant. Productivity titer and CCE are identified as the key cost drivers for MSP. A promising MSP of 2.17 kg can be realized in a long term scenario. A preliminary LCA was performed to show environmental considerations. |
S1369703X20300164 | The textile dyeing and printing industry has led to extensive environmental pollution and severely threatens ecosystems . Immobilized laccase is an effective biocatalyst for the biotreatment of dye effluents but is usually restricted by its aerobic requirements . Thus it is desirable to design an efficient reactor that will increase the applicability of IL on an industrial scale . Decolourization efficiency of Reactive Blue 19 selected as a model textile dye was compared between a horizontal rotating reactor and a traditional vertical mixing reactor . The HRR was equipped with strips of bacterial nanocellulose immobilized laccase and the VMR contained wafers of BNC immobilized laccase . The maximum decolourization efficiency of HRR was achieved at the optimized temperature of 55C pH of 4.0 and agitation speed of 20 rpm . Advantages of HRR over VMR include a broader range of enzymatic reacting temperatures greater contact and reacting interfacial area and higher oxygen availability . After reacting RB 19 at optimized conditions for 5 h the decolourization ratios of the VMR and HRR were respectively 45.7 and 88.2 . The HRR provided greater reusability of immobilized enzyme and higher detoxification removal of chemical oxygen demand and total organic carbon indicating great potential in promoted decolourization of dyeing effluents . | An HRR reactor was designed to satisfy the oxygen demand of catalysis of dye by BNC immobilized laccase. Decolourization efficiency of Reactive Blue 19 dye with laccase was compared in reactors HRR and VMR. HRR provides immobilized laccase better thermostability higher oxygen availability and larger contact reacting area. HRR showed approximately two fold higher decolourization efficiency than VWR and greater removal capability of COD and TOC. |
S1369703X20300176 | Carboxylic acids are high added value compounds that can be produced via anaerobic fermentation by using agroindustrial residues as substrates . However different compounds in wastewater impose uncontrolled metabolic pathways in which the acidogenic fermentation kinetics need to be elucidated . This work aimed to assess the potential production of CA from dairy wastewater and to perform the kinetic modeling of the process . The experiments were conducted in quadruplicate batch reactors with inoculum from a brewery UASB at 0.61 0.04 gCOD gVSS | Dairy wastewater DW is a potential substrate to produce carboxylic acids CA . Kinetic modeling is a useful tool to elucidate acidogenic fermentation kinetics. High yield of CA 0.66 mgCA mgCOD. was obtained from DW acidogenic fermentation. Models that describe an exponential phase are suitable to simulate CA production. Low concentrations of a medium chain CA were achieved without e donors addition. |
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