Limited oxygen conditions as an approach to scale-up and improve D and L-lactic acid production in mineral media and avocado seed hydrolysates with metabolically engineered Escherichia coli.

The effectiveness of micro-aeration on lactate (LA) production by metabolically engineered Escherichia coli was evaluated in 1 L bioreactors containing mineral media and glucose (70 g/L). Volumetric oxygen transfer coefficients (kLa) between 12.6 and 28.7 h-1 increased the specific growth rate (µ) and volumetric productivity (QLA) by 300 and 400%, respectively, without a significant decrease in lactate yield (YLA), when compared with non-aerated fermentations. A kLa of 12.6 h-1 was successfully used as a criterion to scale-up the production of L and D-lactate from 1 to 11 and 130 L. Approximately constant QLA and YLA values were obtained throughout the fermentation scale-up process. Furthermore, a D-lactogenic fermentation was carried out in 1 L bioreactors using avocado seed hydrolysate as a culture medium under the same kLa value, displaying high QLA and YLA.

A local antigen-driven humoral response is present in the inflammatory myopathies.

The inflammatory myopathies are putative autoimmune disorders characterized by muscle weakness and the presence of intramuscular inflammatory infiltrates. Although inclusion body myositis and polymyositis have been characterized as cytotoxic CD8(+) T cell-mediated diseases, we recently demonstrated high frequencies of CD138(+) plasma cells in the inflamed muscle tissue of patients with these diseases. To gain a deeper understanding of the role these B cell family members play in the disease pathology, we examined the molecular characteristics of the H chain portion of the Ag receptor. Biopsies of muscle tissue were sectioned and tissue regions and individual cells were isolated through laser capture microdissection. Ig H chain gene transcripts isolated from the sections, regions, and cells were used to determine the variable region gene sequences. Analysis of these sequences revealed clear evidence of affinity maturation in that significant somatic mutation, isotype switching, receptor revision, codon insertion/deletion, and oligoclonal expansion had occurred within the B and plasma cell populations. Moreover, analysis of tissue regions isolated by laser capture microdissection revealed both clonal expansion and variation, suggesting that local B cell maturation occurs within muscle. In contrast, sequences from control muscle tissues and peripheral blood revealed none of these characteristics found in inflammatory myopathy muscle tissue. Collectively, these data demonstrate that Ag drives a B cell Ag-specific response in muscle in patients with dermatomyositis, inclusion body myositis, and polymyositis. These findings highlight the need for a revision of the current paradigm of exclusively T cell-mediated intramuscular Ag-specific autoimmunity in inclusion body myositis and polymyositis.