pretreatment-of-lignocellulosic-biomass-with-low-cost-ionic-liquids

Pretreatment of Lignocellulosic Biomass with Low-cost Ionic Liquids

A number of ionic liquids (ILs) with economically attractive production costs have recently received growing interest as media for the delignification of ...

Imperial College London

New isolates of solventogenic bacteria exhibited high hemicellulolytic activity. They produced butanol and acetone with high selectivity for butanol (about 80% of butanol from the total solvent yield). Their 16S rDNA sequence was 99% identical to that of Clostridium saccharobutylicum. The genes responsible for the last steps of solventogenesis and encoding crotonase, butyryl-CoA dehydrogenase, electron-transport protein subunits A and B, 3-hydroxybutyryl-CoA dehydrogenase, alcohol dehydrogenase, CoA-transferase (subunits A and B), acetoacetate decarboxylase, and aldehyde dehydrogenase were identified in the new C. saccharobutylicum strain Ox29 and cloned into Escherichia coli. The genes for crotonase, butyryl-CoA dehydrogenase, electron-transport protein subunits A and B, and 3-hydroxybutyryl-CoA dehydrogenase composed the bcs-operon. A monocistronic operon containing the alcohol dehydrogenase gene was located downstream of the bcs-operon. Genes for aldehyde dehydrogenase, CoA-transferase (subunits A and B), and acetoacetate decarboxylase composed the sol-operon. The gene sequences and the gene order within the sol- and bcs-operons of C. saccharobutylicum Ox29 were most similar to those of Clostridium beijerinckii. The activity of some of the bcs-operon genes, expressed in heterologous E. coli, was determined.

Isolation of a new butanol-producing Clostridium strain: high level of hemicellulosic activity and structure of solventogenesis genes of a new Clostridium saccharobutylicum isolate.

A Lactobacillus brevis strain with the ability to synthesize butanol from glucose was constructed by metabolic engineering. The genes crt, bcd, etfB, etfA, and hbd, composing the bcs-operon, and the thl gene encode the enzymes of the lower part of the clostridial butanol pathway (crotonase, butyryl-CoA-dehydrogenase, two subunits of the electron transfer flavoprotein, 3-hydroxybutyryl-CoA dehydrogenase, and thiolase) of Clostridium acetobutylicum. They were cloned into the Gram-positive/Gram-negative shuttle plasmid vector pHYc. The two resulting plasmids pHYc-thl-bcs and pHYc-bcs (respectively, with and without the clostridial thl gene) were transferred to Escherichia coli and L. brevis. The recombinant L. brevis strains were able to synthesize up to 300 mg l(-1) or 4.1 mM of butanol on a glucose-containing medium. A L. brevis strain carrying the clostridial bcs-operon has the ability to synthesize butanol with participation of its own thiolase, aldehyde dehydrogenase, and alcohol dehydrogenase. The particular role of the enzymes involved in butanol production and the suitability of L. brevis as an n-butanol producer are discussed.

Reconstructing the clostridial n-butanol metabolic pathway in Lactobacillus brevis.

The natural history of type 1 diabetes is concerned with the appearance of autoantibodies against antigens of pancreatic beta cells. The last decade revealed some evidence of the participation of T regulatory lymphocytes - cells which suppress immune response - in the pathogenesis of type 1 diabetes and prediabetes.

[Higher percentages of T regulatory cells in children at risk for developing type 1 diabetes mellitus].

Monogenic diabetes caused by mutations in the glucokinase gene (GCK-MODY) is usually characterized by a mild clinical phenotype. The clinical course of diabetes may be, however, highly variable. The authors present a child with diabetes manifesting with ketoacidosis during the neonatal period, born in a large family with ten members bearing a heterozygous p.Gly223Ser mutation in GCK. DNA sequencing and multiplex ligation-dependent probe amplification were used to confirm GCK mutation and exclude other de novo mutations in other known genes associated with monogenic diabetes. Continuous glucose monitoring (CGM) was used to assess daily glycemic profiles. At the onset of diabetes the child had hyperglycemia 765 mg/dl with pH 7.09. Her glycated hemoglobin level was 8.6% (70.5 mmol/mol). The C-peptide level was below normal range (<0.5 pmol/ml) at onset, and the three- and 6-month follow-up examinations. Current evaluation at age 3 still showed unsatisfactory metabolic control with HbA1c level equal to 8.1% (65.0 mmol/mol). CGM data showed glucose concentrations profile similar to poorly controlled type 1 diabetes. The patient was confirmed to be heterozygous for the p.Gly223Ser mutation and did not show any point mutations or deletions within other monogenic diabetes genes. Other family members with p.Gly223Ser mutation had retained C-peptide levels and mild diabetes manageable with diet (five individuals), oral hypoglycemizing agents (five patients), or insulin (one patient). This mutation was absent within all healthy family members. Heterozygous mutations of the GCK gene may result in neonatal diabetes similar to type 1 diabetes, the cause of such phenotype variety is still unknown. The possibility of other additional, unknown mutations seems to be the most likely explanation for the unusual presentation of GCK-MODY.

Phenotype variability and neonatal diabetes in a large family with heterozygous mutation of the glucokinase gene.

Type 1 diabetes is considered as pluricausal disease, whose etiology involves genetic predisposition as well as environmental factors that contribute to disease progression and pathogenesis. Women are believed to be more susceptible to develop autoimmune diseases, which may depend in part on the influence of sex hormones on the immune system. It was shown that estrogens may protect against the development of autoimmune disease by inducing the expansion of regulatory T cell pool and upregulating Foxp3 expression. Foxp3 is a transcription factor that controls the development and suppressive function of naturally occurring regulatory T cells CD4(+)Foxp3(+). Longstanding diabetes type 1 has features of low-grade chronic inflammation which may influence regulatory T cell subset by reducing their numbers or/and inhibiting their suppressive potential. As diabetic type 1 patients are differentiated with regard to metabolic factors, level of glycemic control and systemic inflammatory state, we aimed to examine if this can be associated with IVSI-397T>C estrogen receptor α polymorphism. We examined 93 young regularly menstruating girls with diagnosed type 1 diabetes and 49 healthy age-matched control individuals. The PvuII polymorphism of the ER-α gene was analyzed as well as the serum TNF level and the level of CD4(+)Foxp3(+) regulatory T cells in these individuals. Girls with type 1 diabetes had lower level of CD4(+)Foxp3(+) Tregs than their healthy counterparts. Regulatory T cells from these patients showed also lower expression of Foxp3 than Tregs in healthy, control group. In addition, DM1 girls bearing the CC genotypes showed the highest level of CD4(+)Foxp3(+) Tregs and the lowest TNF serum level in comparison to girls carrying CT or TT genotype. The CC DM1 carriers had also higher serum level of estrogens than girls bearing CT or TT genotype. We propose that different variants of IVS1-397 estrogen receptor α polymorphism may become additional genetic factor that influences regulatory conditions during diabetes type 1 in females.

The association of the IVS1-397T>C estrogen receptor α polymorphism with the regulatory conditions in longstanding type 1 diabetic girls.

A range of methods for the computational prediction of experimentally derived α and β Kamlet-Taft parameters, indicators of hydrogen bond (H-bond) acidity and basicity for ionic liquids (ILs) have been explored. Most usefully, a good correlation has been established between several simple and easily computed quantities which allow for a "quick bench-top" evaluation. More accurate, but also more sophisticated methods employing TD-DFT calculations involving the Kamlet-Taft dyes have been examined and evaluated. Importantly, these techniques open up the opportunity for pre-screening and a priori prediction of properties for ILs not yet synthesised. A key fundamental insight into IL H-bonds has been the determination of an estimate for the energy associated with replacing both neutral molecules in a H-bond with ionic molecules, thus forming the "doubly ionic" H-bond found in ILs.

A step towards the a priori design of ionic liquids.

[Management in familial hypercholesterolaemia in children and adolescents. Position of the Lipid Expert Forum].

The study aimed to investigate the influence of estrogen receptor α (ER-α) genotypes on inflammatory response and development of microvascular complications in girls with type 1 diabetes.

IVS1 -397T>C estrogen receptor α polymorphism is associated with low-grade systemic inflammatory response in type 1 diabetic girls.

Familial hypercholesterolemia (FH) affects on average 1 in 500 individuals in European countries, and it is estimated that FH in Poland may affect more than 80,000 people. However, in Poland, only about 20% of the population is estimated to have been diagnosed with FH, of which only a small number receive adequate treatment. FH results in more rapid development of atherosclerosis and is associated with a high risk of cardiovascular events. Atherosclerosis develops beginning in childhood in patients with FH and reaches advanced stages before clinical manifestations develop. Inadequate diagnostics and treatment of FH in Polish children suggests a need for raising the level of awareness and understanding of the condition in both society and among health professionals. These recommendations present the current epidemiological status, guidelines for diagnosing FH in Polish children and adolescents, and effective treatment options.

Management of familial hypercholesterolemia in children and adolescents. Position paper of the Polish Lipid Expert Forum.

The objective was to compare the impact of clinical and genetic factors on body mass index (BMI) in children with type 1 diabetes (T1DM) without severe obesity. A total of 1,119 children with T1DM (aged 4-18 years) were qualified to take part in the study. All children were genotyped for variants of FTO, MC4R, INSIG2, FASN, NPC1, PTER, SIRT1, MAF, IRT1, and CD36. Results. Variants of FTO showed significant association with BMI-SDS in the T1DM group. The main factors influencing BMI-SDS in children with T1DM included female gender (P = 0.0003), poor metabolic control (P = 0.0001), and carriage of the A allele of the FTO rs9939609 gene (P = 0.02). Conclusion. Our research indicates, when assessing, the risk of overweight and obesity carriage of the A allele in the rs9939609 site of the FTO gene adds to that of female gender and poor metabolic control. This trial is registered with ClinicalTrials.gov (NCT01279161).

Polymorphism of the FTO Gene Influences Body Weight in Children with Type 1 Diabetes without Severe Obesity.

The effect of estrogens is mediated by activation of estrogen receptors (ERs), which are expressed in many tissues. Because ER-α gene polymorphisms may exert different effects in childhood, in the present study we analyzed associations between the IVS1 -397T>C polymorphism and indicators of inflammatory response as well as late complications in boys with type 1 diabetes mellitus (DM1).

Grade of inflammation in boys with type 1 diabetes depends on the IVS1 -397T>C estrogen receptor α polymorphism.

Congenital hyperinsulinism of Infancy (CHI) comprises heterogenic defects of insulin secretion with diverse molecular aetiology, histological features, severity of symptoms, and response to pharmacotherapy. The study aimed to establish the first clinical characteristics of Polish patients with CHI and to propose a novel clinical algorithm allowing the prioritisation of genetic and radiology studies, based on patient's characteristics and response to pharmacotherapy.

Congenital hyperinsulinism in Polish patients--how can we optimize clinical management?

Th17, Th22 and Th9 are recently discovered effector populations that may contribute to the pathogenesis of autoimmune and inflammatory diseases. The presented study aimed to investigate the link between Th22 and Th9 subsets in type 1 diabetes, as this disease involves different subsets of CD4+ T lymphocytes. The study groups consisted of 23 patients with type 1 diabetes and 11 healthy individuals. All subjects had CD4+IL-22 Th22 and CD4+IL-9 Th9 lymphocytes investigated by flow cytometry. In addition, the plasma concentrations of IL-22 as well as IL-9 were analyzed. Our study demonstrated that Th9 and Th22 cell counts as well as their plasma cytokines were upregulated in patients with type 1 and correlated with HbA1c and CRP values. Taking these all into account, one can conclude that Th22 and Th9 lymphocyte activities may contribute to chronic, low-level inflammation that is considered an integral part of type 1 diabetes.

Article	Year
Isolation of a new butanol-producing Clostridium strain: high level of hemicellulosic activity and structure of solventogenesis genes of a new Clostridium saccharobutylicum isolate. Systematic and applied microbiology\| PubMed ID: 19674858	2009
Reconstructing the clostridial n-butanol metabolic pathway in Lactobacillus brevis. Applied microbiology and biotechnology\| PubMed ID: 20195860	2010
[Higher percentages of T regulatory cells in children at risk for developing type 1 diabetes mellitus]. Pediatric endocrinology, diabetes, and metabolism\| PubMed ID: 20529599	2010
Phenotype variability and neonatal diabetes in a large family with heterozygous mutation of the glucokinase gene. Acta diabetologica\| PubMed ID: 21437567	2011
The association of the IVS1-397T>C estrogen receptor α polymorphism with the regulatory conditions in longstanding type 1 diabetic girls. Molecular immunology\| PubMed ID: 21943781	2011
A step towards the a priori design of ionic liquids. Physical chemistry chemical physics : PCCP\| PubMed ID: 23752557	2013
[Management in familial hypercholesterolaemia in children and adolescents. Position of the Lipid Expert Forum]. Kardiologia polska\| PubMed ID: 24197602	2013
IVS1 -397T>C estrogen receptor α polymorphism is associated with low-grade systemic inflammatory response in type 1 diabetic girls. Mediators of inflammation\| PubMed ID: 24523574	2014
Management of familial hypercholesterolemia in children and adolescents. Position paper of the Polish Lipid Expert Forum. Journal of clinical lipidology\| PubMed ID: 24636176	2014
Polymorphism of the FTO Gene Influences Body Weight in Children with Type 1 Diabetes without Severe Obesity. International journal of endocrinology\| PubMed ID: 25214838	2014
Grade of inflammation in boys with type 1 diabetes depends on the IVS1 -397T>C estrogen receptor α polymorphism. Journal of diabetes and its complications\| PubMed ID: 26077347	2015
Congenital hyperinsulinism in Polish patients--how can we optimize clinical management? Endokrynologia Polska\| PubMed ID: 26323469	2015
Th9 and Th22 immune response in young patients with type 1 diabetes. Immunologic research\| PubMed ID: 26659093	2016

Agnieszka Brandt

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