Bioprocess modelling of biohydrogen production by Rhodopseudomonas palustris: Model development and effects of operating conditions on hydrogen yield and glycerol conversion efficiency

This research explores the photofermentation of glycerol to hydrogen by Rhodopseudomonas palus- tris, with the objective to maximise hydrogen production. Two piecewise models are designed to simulate the entire growth phase of R. palustris; a challenge that few dynamic models can accomplish. The parameters in both models were fitted by the present batch experiments through the solution of the underlying optimal control problems by means of stable and accurate discretisation techniques. It was found that an initial glutamate to glycerol ratio of 0.25 was optimal, and was independent of the initial biomass concentration. The glycerol conversion efficiency was found to depend on initial biomass concentration and its computational peak is 64.4%. By optimising a 30-day industrially relevant batch process, the hydrogen productivity was improved to be 37.7 mL·g biomass-1·hr-1 and the glycerol conversion efficiency was maintained at 58%. The models can then be applied as the connection to transfer biohydrogen production from laboratory scale into industrial scale.Authors N. Xiao and Dr. K. T. Mahbubani are funded through the KACST-Cambridge Center for Advanced Material Manufacture, the author E. A. del Rio-Chanona is found by CONACyT scholarship No. 522530 from the Secretariat of Public Education and the Mexican government.This is the accepted manuscript. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0009250915001815

Engaging Cold to Upregulate Cell Proliferation in Alginate-Encapsulated Liver Spheroids.

For many years, the impact of hyper- and hypothermia on mammalian cells has been examined. With the exception of short, low temperature storage, which has uses in areas such as preservation for transplantation or regenerative medicine, advantages for the use of low temperature treatment in hepatocytes have not been previously reported. We have observed that alginate-encapsulated HepG2 liver spheroids that are cryopreserved or experience a cold reduction in temperature (≤10°C) for periods between 1 and 90 min display an enhanced cell proliferation during culture 7-16 days post-treatment compared with untreated samples. Following 8-12 days post-treatment, alginate-encapsulated liver spheroids experienced a cell density of 1.71 ± 0.35 times that of control samples (p < 0.001). This effect occurred in samples with a variety of cold treatments. This low temperature treatment offers a simple method to rapidly increase cell proliferation rates for extended culture systems, such as bioartificial liver devices. This would allow the manufacture of required biomass more rapidly, and to a higher cell density, reducing final required biomass volume. This could enable bioartificial liver devices to be prepared more cheaply, making them a more cost effective treatment.Funding for this work was provided through a Medical Research Council (United Kingdom) Industrial Case Studentship (9203) and by Innovate UK (101103) between University College London and Asymptote Ltd. and a Medical Research Council Proximity to Discovery Grant (RG79366) between University of Cambridge and Asymptote Ltd

Cross-tissue immune cell analysis reveals tissue-specific adaptations and clonal architecture in humans

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. Here, we surveyed the immune compartment of 15 tissues of six deceased adult donors by single-cell RNA sequencing and paired VDJ sequencing. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of 45 finely phenotyped immune cell types and states, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. In summary, our multi-tissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis and antigen receptor sequencing. One Sentence Summary We provide an immune cell atlas, including antigen receptor repertoire profiling, across lymphoid and non-lymphoid human tissues

Cells of the human intestinal tract mapped across space and time

The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung’s disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease