Search

Kerstin Lippl, Anna Boleininger, Michael A McDonough, Martine I Abboud, Hanna Tarhonskaya, Rasheduzzaman Chowdhury, Christoph Loenarz, Christopher J Schofield Chemistry Research Laboratory, University of Oxford, Oxford, UK Background: In humans and other animals, the chronic hypoxic response is mediated by hypoxia inducible transcription factors (HIFs) which regulate the expression of genes that counteract the effects of limiting oxygen. Prolyl hydroxylases (PHDs) act as hypoxia sensors for the HIF system in organisms ranging from humans to the simplest animal Trichoplax adhaerens. Methods: We report structural and biochemical studies on the T. adhaerens HIF prolyl hydroxylase (TaPHD) that inform about the evolution of hypoxia sensing in animals. Results: High resolution crystal structures (≤1.3 Å) of TaPHD, with and without its HIFα substrate, reveal remarkable conservation of key active site elements between T. adhaerens and human PHDs, which also manifest in kinetic comparisons. Conclusion: Conserved structural features of TaPHD and human PHDs include those apparently enabling the slow binding/reaction of oxygen with the active site Fe(II), the formation of a stable 2-oxoglutarate complex, and a stereoelectronically promoted change in conformation of the hydroxylated proline-residue. Comparison of substrate selectivity between the human PHDs and TaPHD provides insights into the selectivity determinants of HIF binding by the PHDs, and into the evolution of the multiple HIFs and PHDs present in higher animals. Keywords: hypoxia, hypoxic response, oxygen sensing, hypoxia-inducible factor (HIF), evolution, dioxygenase, enzyme structure, PHD/EGLN prolyl hydroxylases, 2-oxoglutarate oxygenase, Trichoplax adhaerens

In this study, a sensor based on the development of a planar antenna immersed in sediments dedicated to water content monitoring in this type of material is proposed and experimentally validated. It is produced by a conventional Printed Circuit Board (PCB) manufacturing process on a double-sided metalized FR4 substrate. The sensitivity of the sensor is ensured by the variation of the real part of the complex dielectric permittivity of sediments with water content at around 1 GHz. As shown, in this frequency range, electrode polarization and Maxwell&ndash, Wagner polarization effects become negligible, leading to only a bulk water polarization sensitivity. The sensor operates in the reflection mode by monitoring the variation of the resonant frequency as a function of the sediment density through the S11 reflection measurements. An experimental sensitivity of 820 &nbsp, MHz . g &minus, 1 . cm 3 was achieved. Despite the simplification of data interpretation at the considered frequency, the influence of ionic species such as NaCl in sediments on the real part of the relative complex dielectric permittivity is highlighted. This demonstrates the importance of considering a second parameter such as the S11 level at low frequency or the electrical conductivity to extract the density from the frequency measurements.

Hematopoietic Stem Cell Transplantation (HSCT) activity was evaluated in the African (AFR)/EMRO region and compared to the global activity for the years 2006-2013. Data were obtained from 1570 teams in the 6 WHO continental regions. Of these, 29 (1.85%) of all teams were active in 12 of the 68 AFR/EMRO countries. They reported 2.331 (3.3%) of the worldwide 71.036 HSCT, and a transplant rate of 32.8 (TR; HSCT/10 million inhabitants; worldwide 128.5). This reflects still the lowest regional TR despite an increase of 90% since 2006. HSCT activity in AFR/EMRO countries was characterized by a higher use of allogeneic compared to autologous HSCT, an almost exclusive use of family donors, including haploidentical family donors. These findings contrast with the prevalence of autologous over allogeneic HSCT, and a higher frequency of unrelated HSCT in other parts of the world. Of note, the increase by 200% in HSCT for hemoglobinopathies from 2006 to 2013 (72 per year) in the AFR/EMRO region. This reflects the specific role of HSCT for these disease categories with high prevalence and incidence in the AFR/EMRO region. This report provides information for the competent authorities to foster adequate infrastructure. It urges transplant organization to optimize their cooperation.