Response Surface Methodology for Understanding Glucose and Xylose Utilization by Clostridium beijerinckii NCIMB 8052

We applied response surface methodology to understand the effect and extend of carbon catabolite repression (CCR) on growth of Clostridium beijerinckii NCIMB 8052 using xylose and glucose as representative lignocellulosic sugars. We performed batch growth experiments based on the central composite design with different concentrations of glucose and xylose, and estimated the respective growth rates as the response. Fitting the quadratic model with interaction coefficient to experimental data gave a good quality of fit (R-squared=0.939). We found that glucose is the most significant factor affecting the growth rate. Interaction between glucose and xylose is another highly significant factor. Response surface illustrated that increasing or decreasing both sugar concentrations at the same time results in a decreasing growth rate, and increasing either sugar concentration while decreasing the other sugar increases the growth rate. It is an important finding as it suggests that CCR can be not only from glucose on xylose but also from xylose on glucose. A transcriptional study will be necessary to understand the repression mechanism and to improve the utilization of sugars in mixed form, thus lignocellulosic fermentation processes.publishedVersio

The Effect of Feeding Strategy on Butanol Production by Clostridium beijerinckii NCIMB 8052 Using Glucose and Xylose

We performed fed-batch fermentations of glucose and xylose mixtures producing butanol. Our aim was to develop a feeding strategy for coping with carbon catabolite repression (CCR) and sequential utilization problems as well as understanding the effect of feeding strategy on fermentation kinetics. Experimental results showed that fermenter 1 with only xylose as the initial carbon source could co-utilize sugars for all mixed sugar feeds. On the other hand, fermenter 2 with only glucose as the initial sugar showed sequential utilization. Xylose in fermenter 2 accumulated while glucose was present; it was only utilized after the glucose was completely exhausted. Besides the sugar utilization profile, the feeding strategy had an impact on the fermentation kinetics. Maximum specific growth rates were 0.68 h-1 and 0.94 h-1, for fermenter 1 and 2,respectively. Fermenter 1 produced 4.98 g/l butanol and yield was 0.28 g/g, while fermenter 2 produced 0.5 g/l butanol with a yield value of 0.05 g/g. Total sugar utilization was also higher for fermenter 1, 81 % and 46 % for fermenter 2. The feeding strategy we proposed showed that wild type Clostridium beijerinckii NCIMB 8052 can co-utilize glucose and xylose, and produce butanol. Our observation suggests that we can tackle sequential utilization problem and enhance fermentation process with the proposed feeding strategy without having to manipulate the strain.publishedVersio

Kinetic Study of Butanol Production from Mixtures of Glucose and Xylose and Investigation of Different Pre-growth Strategies

This study proposes a dynamic model that describes key characteristics of fermentative butanol production from glucose and xylose mixtures. The model has 12 parameters and incorporates noncompetitive inhibitory interaction between sugars as well as inhibitions due to high substrate and butanol concentrations. Different pre-growth strategies to achieve co-utilization of sugars were explored together with their effects on fermentation kinetics. Mixed sugar fermentation by the cultures pre-grown on a mixture of glucose and xylose showed a higher endurance to inhibition, a 2-fold increase in butanol production and a 1.5-fold increase in total sugar consumption compared to cultures pre-grown on xylose only. The average squared correlation coefficients (r2) between experimental observations and model predictions were 0.917 and 0.926 for fermentations done by the cultures pre-grown on xylose only, and pre-grown on a mixture of glucose and xylose, respectively. Sensitivity analysis on the model parameters revealed that the growth parameters were the most critical. The proposed model can serve as a basis for modeling of microbial butanol production from lignocellulosic biomass and be applied to other substrates and microorganisms. © 2019(32 refs)acceptedVersio

Modeling the Growth of Clostridium beijerinckii NCIMB 8052 on Lignocellulosic Sugars

To our knowledge, this is the first growth model of Clostridium beijerinckii NCIMB 8052 on glucose and xylose as representative lignocellulosic sugars, which considers the synergistic effects of sugars on the growth rate. We fitted models with different types of interactions between the substrates to the growth rate data obtained with varying sugar concentrations. Noncompetitive binary substrate growth model gave the best fit with the smallest mean standard errors (MSE), and sum of squares error (SSE), 0.0778 and 0.0071, respectively. Confidence intervals for the parameter estimates showed that the substrate affinity constant for xylose, KsX (g/l) had the largest uncertainty, while the maximum specific growth rate on xylose, µmaxX (h-1) had the smallest. The correlation matrix showed that the model parameters were highly correlated. Carbon cataboliterepression (CCR) effect on the growth rate was of the noncompetitive type. Validation with other sugar concentration values is necessary to evaluate the prediction capability of the proposed model. A transcriptional study will be beneficial to understand global gene regulation mechanisms as guidance for improving the efficiency of lignocellulosic fermentation processes.publishedVersio

Bringing together materials and business ontologies for protective coatings

publishedVersio

Education in Process Systems Engineering: Why it matters more than ever and how it can be structured

This position paper is an outcome of discussions that took place at the third FIPSE Symposium in Rhodes, Greece, between June 20–22, 2016 (http://fi-in-pse.org). The FIPSE objective is to discuss open research challenges in topics of Process Systems Engineering (PSE). Here, we discuss the societal and industrial context in which systems thinking and Process Systems Engineering provide indispensable skills and tools for generating innovative solutions to complex problems. We further highlight the present and future challenges that require systems approaches and tools to address not only ‘grand’ challenges but any complex socio-technical challenge. The current state of Process Systems Engineering (PSE) education in the area of chemical and biochemical engineering is considered. We discuss approaches and content at both the unit learning level and at the curriculum level that will enhance the graduates’ capabilities to meet the future challenges they will be facing. PSE principles are important in their own right, but importantly they provide significant opportunities to aid the integration of learning in the basic and engineering sciences across the whole curriculum. This fact is crucial in curriculum design and implementation, such that our graduates benefit to the maximum extent from their learning

The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders

Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

AbstractBackgroundThe genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder.MethodsWe analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures.ResultsThe SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10–9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10–9).ConclusionsThis large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression

Evidence for Increased Genetic Risk Load for Major Depression in Patients Assigned to Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant depression; disorder severity and unfavorable treatment outcomes are shown to be influenced by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment and response/nonresponse are associated with an increased genetic burden for major depression (MD) using polygenic risk score (PRS), which summarize the contribution of diseaserelated common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive episode underwent ECT. MD-PRS were calculated for these inpatients and a separate population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary statistics from the Psychiatric Genomics Consortium MDD-working group (Cases: n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status between ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higher MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response (50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate that ECT cohorts show an increased genetic burden for MD and are consistent with the hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic risk for MD. Larger samples are needed to better substantiate these findings