Long, C. | bioRxiv Science

bioRxiv2019

Iron-deficiency and estrogen are associated with ischemic stroke by up-regulating transferrin to induce hypercoagulability

In the accompanying manuscript, transferrin has been demonstrated to maintain coagulation balance by interacting with clotting factors, suggesting that elevated transferrin causes thromboembolic diseases and factors up-regulating transferrin is associated with thrombosis. Here we show that transferrin and transferrin-thrombin/FXIIa complexes are elevated in plasma and cerebrospinal fluid of ischemic stroke (IS) patients with iron-deficiency anemia (IDA) history, IDA patients and venous thromboembolism patients using combined oral contraceptives (CC) as well as ID mice, suggesting an association of transferrin up-regulation with ID and CC. ID and estrogen up-regulated transferrin through hypoxia and estrogen response elements located at transferrin gene enhancer and promoter region, respectively. ID, exogenous transferrin/estrogen administration or transferrin over-expression promoted hypercoagulability and aggravated IS, while anti-transferrin antibody, transferrin knockdown or designed peptide inhibitors interfering transferrin-thrombin/FXIIa interaction exerted anti-IS effects in vivo. Collectively, the results reveal that factors (i.e., ID and CC) up-regulating transferrin are risk factors of thromboembolic diseases.

biochemistry↗

bioRxiv2019

Microbial biogeography and ecology of the mouth and implications for periodontal diseases

Human-associated microbial communities differ in composition among body sites and between habitats within a site. Patterns of variation in the distribution of organisms across time and space is referred to as biogeography. The human oral cavity is a critical observatory for exploring microbial biogeography because it is spatially structured, easily accessible, and its microbiota has been linked to the promotion of both health and disease. The biogeographic features of microbial communities residing in spatially distinct but ecologically similar environments on the human body, including the subgingival crevice, have not yet been adequately explored. The purpose of this paper is twofold. First, we seek to provide the dental community with a primer on biogeographic theory, highlighting its relevance to the study of the human oral cavity. For this reason, we summarize what is known about the biogeographic variation of dental caries and periodontitis and postulate as to how this may be driven by spatial patterning in oral microbial community composition and structure. Second, we present a number of methods that investigators can use to test specific hypotheses using biogeographic theory. To anchor our discussion, we apply each method to a case study and examine the spatial variation of the human subgingival microbiota of 2 individuals. Our case study suggests that subgingival communities in the aggregate may conform to an anterior-to-posterior gradient in community composition. The gradient appears to be structured both by deterministic and non-deterministic processes, though additional work is needed to test and confirm specific hypotheses. A better understanding of biogeographic patterns and processes will advance our understanding of ways to optimize the efficacy of dental interventions targeting the oral microbiota.

ecology↗