Only VpreB1, but not VpreB2, is expressed at levels which allow normal development of B cells

The surrogate light chain (SLC) consists of the polypeptides λ5 and, in the mouse, either VpreB1 or VpreB2. SLC associates with BILL-Cadherin and other glycoproteins to form the pro-B cell receptor (pro-BCR) at the pre-BI cell stage, and with the immunoglobulin μ heavy chain to form the pre-BCR at the pre-BII cell stage. The function of the pro-BCR, if any, is unknown, whereas the pre-BCR is crucial for proliferative expansion of pre-BII cells. To shed light on the functional properties of VpreB1 and VpreB2 in vivo, mice with either one or two VpreB1, or one or two VpreB2, alleles have been investigated. We show that B cell development in mice with two VpreB1 alleles is indistinguishable from that of normal mice. In contrast, mice with two VpreB2 alleles show an ∼1.6-fold increase in pre-BI and a 35% decrease in pre-BII cell numbers, while mice with only one VpreB2 allele show a reduction in B cell development manifested in a 2-fold enrichment in pre-BI cells and a 75% reduction in pre-BII cells. However, such a gene dosage effect is not observed for VpreB1. Our results suggest that the difference between VpreB1- and VpreB2-deficient mice is due to lower VpreB2 protein expression, thus limiting the formation of pre-BCRs and thereby the number of large, cycling pre-BII cell

Study of the stability of 1alkyl-3-methylimidazolium hexafluoroantimonate(V) based ionic liquids using xray photoelectron spectroscopy

A series of highly pure 1-alkyl-3-methylimidazolium hexafluoroantimonate (V) ionic liquids was firstly investigated by XPS. Reliable binding energy values for all elements within the samples were obtained by applying a C 1s fitting model previously employed for other imidazolium ionic liquids, based on setting the C 1s aliphatic component to 285.0 eV when alkyl chains are longer than 8 carbons. We also observed a straightforward X-ray-mediated photoreduction of Sb (V) to Sb (III) species, i.e. reduction of [SbF6]- anion to volatile SbF3. Thus, binding energies values observed at 542.5 eV and 533.1 eV were attributed to Sb 3d3/2 (V) and Sb 3d5/2 (V), respectively, whereas values at 541.0 eV and 531.7 eV were found for Sb 3d3/2 (III) and Sb 3d5/2 (III), respectively. The SbF3 being formed can be lost either by evaporation and/or redistribution to the bulk. Providing the sample is cooled to freezing temperatures, the SbF3 is prevented from escaping the ionic liquid and it accumulated on the surface of cooled [C4C1Im][SbF6] and [C8C1Im][SbF6]. Particularly in the case of prolonged X-ray exposure of a cooled [C4C1Im][SbF6], an unprecedented further reduction of Sb (III) to Sb (0) was noticed. This study provides fundamental knowledge on the XPS data for antimony compounds as well as providing a step towards the surface analysis of materials composed by antimony species, notably the hexafluoroantimonate (V) anion

Historic Global Commodity Networks: the Research Potential of Rubbish Dumps for the Study of Rural Household Market Access during the late Nineteenth and Early Twentieth Centuries

This article discusses the research potential of rubbish dumps for the study of rural household market access during the late nineteenth and early twentieth centuries. By investigating the global commodity networks associated with four rubbish dumps excavated by the authors in the East Anglian region, at Hempstead (Norfolk), Kirton and Falkenham (Suffolk) and Holme Hale (Norfolk), the article will show how these archives can be used to locate individual rural households within the international capitalist system. This article also discusses the potential challenges faced when analysing the historic rubbish dump archives

Thermal stability of dialkylimidazolium tetrafluoroborate and hexafluorophosphate ionic liquids: ex situ bulk heating to complement in situ mass spectrometry

Thermal decomposition (TD) products of the ionic liquids (ILs) [CnC1Im][BF4] and [CnC1Im][PF6] ([CnC1Im]+ = 1-alkyl-3-methylimidazolium, [BF4]- = tetrafluoroborate, and [PF6]- = hexafluorophosphate) were prepared, ex situ, by bulk heating experiments in a bespoke setup. The respective products, CnC1(C3N2H2)BF3 and CnC1(C3N2H2)PF5 (1-alkyl-3-methylimidazolium-2-trifluoroborate and 1-alkyl-3-methylimidazolium-2-pentafluorophosphate), were then vaporized and analyzed by direct insertion mass spectrometry (DIMS) in order to identify their characteristic MS signals. During IL DIMS experiments we were subsequently able, in situ, to identify and monitor signals due to both IL vaporization and IL thermal decomposition. These decomposition products have not been observed in situ during previous analytical vaporization studies of similar ILs. The ex situ preparation of TD products is therefore perfectly complimentary to in situ thermal stability measurements. Experimental parameters such as sample surface area to volume ratios and heating rates are consequently very important for ILs that show competitive vaporization and thermal decomposition. We have explained these experimental factors in terms of Langmuir evaporation and Knudsen effusion-like conditions, allowing us to draw together observations from previous studies to make sense of the literature on IL thermal stability. Hence, the design of experimental setups are crucial and previously overlooked experimental factors

Normalising Bottle Reuse: Lessons from the Victorians on the Limits of Voluntary Schemes

A policy article, addressing the historical failure of voluntary return schemes for reusable bottles and advising mandatory schemes in future

The putative mevalonate diphosphate decarboxylase from Picrophilus torridus is in reality a mevalonate-3-kinase with high potential for bioproduction of isobutene

Mevalonate diphosphate decarboxylase (MVD) is an ATP-dependent enzyme that catalyzes the phosphorylation/decarboxylation of (R)-mevalonate-5-diphosphate to isopentenyl pyrophosphate in the mevalonate (MVA) pathway.MVD is a key enzyme in engineered metabolic pathways for bioproduction of isobutene, since it catalyzes the conversion of 3-hydroxyisovalerate (3-HIV) to isobutene, an important platform chemical. The putative homologue from Picrophilus torridus has been identified as a highly efficient variant in a number of patents, but its detailed characterization has not been reported. In this study, we have successfully purified and characterized the putative MVD from P. torridus. We discovered that it is not a decarboxylase per se but an ATP-dependent enzyme, mevalonate-3-kinase (M3K), which catalyzes the phosphorylation of MVA to mevalonate-3-phosphate. The enzyme’s potential in isobutene formation is due to the conversion of 3-HIV to an unstable 3-phosphate intermediate that undergoes consequent spontaneous decarboxylation to form isobutene. Isobutene production rates were as high as 507 pmol min-1 g cells-1 using Escherichia coli cells expressing the enzyme and 2,880 pmol min-1 mg protein-1 with the purified histidine-tagged enzyme, significantly higher than reported previously. M3K is a key enzyme of the novel MVA pathway discovered very recently in Thermoplasma acidophilum. We suggest that P. torridus metabolizes MVA by the same pathway

The role of small heat shock proteins in mutant superoxide dismutase-linked familial amyotrophic lateral sclerosis

The mechanisms by which mutations in the gene encoding superoxide dismutase 1 (S0D1) lead to amyotrophic lateral sclerosis (ALS) remain incompletely understood. Mutant SODI inclusions are observed in both ALS patients and animal models of the disease. Chaperone proteins have been shown to reduce mutant S0D1 inclusion formation in both cell and animal systems and, up-regulation of heat shock proteins (HSPs) in a mouse model of ALS increases their life expectancy. The results presented in this thesis are based on an investigation into the role of small heat shock proteins (sHSPs) in mutant SODI inclusion formation, using a model HEK293 cell system. Over-expression of yellow fluorescent protein (YFP)-tagged G85R mutant SODI in HEK293 cells and subsequent treatment with proteasome inhibitor leads to mutant S0D1-inclusion formation, as shown by immunofluorescence (IMF) microscopy. Using this model of mutant S0D1- inclusion formation, we demonstrate that over-expression of sHSPs decreases the proportion of insoluble mutant SODI present within these cells. Mutations in these sHSPs prevent this function, and further increase the proportion of insoluble mutant S0D1. These mutant sHSPs also cause an increase in the insolubility of normally soluble proteins, such as wild-type SODI. Similar results were observed in Neuro 2a cells, where over-expression of sHSPs caused the phenotype of the mutant SODI inclusions to change, from dense, tight structures to more diffuse ones. We have shown that sHSPs decrease the amount of insoluble mutant SODI in HEK2S3 cells, supporting reports that chaperone proteins prevent mutant SODI-inclusion formation and are beneficial in a mouse model Gf AL