In Silico Insights into the Symbiotic Nitrogen Fixation in Sinorhizobium meliloti via Metabolic Reconstruction

BACKGROUND: Sinorhizobium meliloti is a soil bacterium, known for its capability to establish symbiotic nitrogen fixation (SNF) with leguminous plants such as alfalfa. S. meliloti 1021 is the most extensively studied strain to understand the mechanism of SNF and further to study the legume-microbe interaction. In order to provide insight into the metabolic characteristics underlying the SNF mechanism of S. meliloti 1021, there is an increasing demand to reconstruct a metabolic network for the stage of SNF in S. meliloti 1021. RESULTS: Through an iterative reconstruction process, a metabolic network during the stage of SNF in S. meliloti 1021 was presented, named as iHZ565, which accounts for 565 genes, 503 internal reactions, and 522 metabolites. Subjected to a novelly defined objective function, the in silico predicted flux distribution was highly consistent with the in vivo evidences reported previously, which proves the robustness of the model. Based on the model, refinement of genome annotation of S. meliloti 1021 was performed and 15 genes were re-annotated properly. There were 19.8% (112) of the 565 metabolic genes included in iHZ565 predicted to be essential for efficient SNF in bacteroids under the in silico microaerobic and nutrient sharing condition. CONCLUSIONS: As the first metabolic network during the stage of SNF in S. meliloti 1021, the manually curated model iHZ565 provides an overview of the major metabolic properties of the SNF bioprocess in S. meliloti 1021. The predicted SNF-required essential genes will facilitate understanding of the key functions in SNF and help identify key genes and design experiments for further validation. The model iHZ565 can be used as a knowledge-based framework for better understanding the symbiotic relationship between rhizobia and legumes, ultimately, uncovering the mechanism of nitrogen fixation in bacteroids and providing new strategies to efficiently improve biological nitrogen fixation

Immunological aspects in chronic lymphocytic leukemia (CLL) development

Chronic lymphocytic leukemia (CLL) is unique among B cell malignancies in that the malignant clones can be featured either somatically mutated or unmutated IGVH genes. CLL cells that express unmutated immunoglobulin variable domains likely underwent final development prior to their entry into the germinal center, whereas those that express mutated variable domains likely transited through the germinal center and then underwent final development. Regardless, the cellular origin of CLL remains unknown. The aim of this review is to summarize immunological aspects involved in this process and to provide insights about the complex biology and pathogenesis of this disease. We propose a mechanistic hypothesis to explain the origin of B-CLL clones into our current picture of normal B cell development. In particular, we suggest that unmutated CLL arises from normal B cells with self-reactivity for apoptotic bodies that have undergone receptor editing, CD5 expression, and anergic processes in the bone marrow. Similarly, mutated CLL would arise from cells that, while acquiring self-reactivity for autoantigens—including apoptotic bodies—in germinal centers, are also still subject to tolerization mechanisms, including receptor editing and anergy. We believe that CLL is a proliferation of B lymphocytes selected during clonal expansion through multiple encounters with (auto)antigens, despite the fact that they differ in their state of activation and maturation. Autoantigens and microbial pathogens activate BCR signaling and promote tolerogenic mechanisms such as receptor editing/revision, anergy, CD5+ expression, and somatic hypermutation in CLL B cells. The result of these tolerogenic mechanisms is the survival of CLL B cell clones with similar surface markers and homogeneous gene expression signatures. We suggest that both immunophenotypic surface markers and homogenous gene expression might represent the evidence of several attempts to re-educate self-reactive B cells

Multidisciplinary investigations of the diets of two post-medieval populations from London using stable isotopes and microdebris analysis

This paper presents the first multi-tissue study of diet in post-medieval London using both the stable light isotope analysis of carbon and nitrogen and analysis of microdebris in dental calculus. Dietary intake was explored over short and long timescales. Bulk bone collagen was analysed from humans from the Queen’s Chapel of the Savoy (QCS) (n = 66) and the St Barnabas/St Mary Abbots (SB) (n = 25). Incremental dentine analysis was performed on the second molar of individual QCS1123 to explore childhood dietary intake. Bulk hair samples (n = 4) were sampled from adults from QCS, and dental calculus was analysed from four other individuals using microscopy. In addition, bone collagen from a total of 46 animals from QCS (n = 11) and the additional site of Prescot Street (n = 35) was analysed, providing the first animal dietary baseline for post-medieval London. Overall, isotopic results suggest a largely C3-based terrestrial diet for both populations, with the exception of QCS1123 who exhibited values consistent with the consumption of C4 food sources throughout childhood and adulthood. The differences exhibited in δ15Ncoll across both populations likely reflect variations in diet due to social class and occupation, with individuals from SB likely representing wealthier individuals consuming larger quantities of animal and marine fish protein. Microdebris analysis results were limited but indicate the consumption of domestic cereals. This paper demonstrates the utility of a multidisciplinary approach to investigate diet across long and short timescales to further our understanding of variations in social status and mobility