Efficient transplacental IgG transfer in women infected with Zika virus during pregnancy

Zika virus (ZIKV) is a newly-identified infectious cause of congenital disease. Transplacental transfer of maternal IgG to the fetus plays an important role in preventing many neonatal infections. However, antibody transfer may also have negative consequences, such as mediating enhancement of flavivirus infections in early life, or trafficking of virus immune complexes to the fetal compartment. ZIKV infection produces placental pathology which could lead to impaired IgG transfer efficiency as occurs in other maternal infections, such as HIV-1 and malaria. In this study, we asked whether ZIKV infection during pregnancy impairs transplacental transfer of IgG. We enrolled pregnant women with fever or rash in a prospective cohort in Vitoria, Brazil during the recent ZIKV epidemic. ZIKV and dengue virus (DENV)-specific IgG, ZIKV and DENV neutralizing antibodies, and routine vaccine antigenspecific IgG were measured in maternal samples collected around delivery and 20 paired cord blood samples. We concluded that 8 of these mothers were infected with ZIKV during pregnancy and 12 were ZIKV-uninfected. The magnitude of flavivirus-specific IgG, neutralizing antibody, and vaccine-elicited IgG were highly correlated between maternal plasma and infant cord blood in both ZIKV-infected and -uninfected mother-infant pairs. Moreover, there was no difference in the magnitude of plasma flavivirus-specific IgG levels between mothers and infants regardless of ZIKV infection status. Our data suggests that maternal ZIKV infection during pregnancy does not impair the efficiency of placental transfer of flavivirus-specific, functional, and vaccine-elicited IgG. These findings have implications for the neonatal outomes of maternal ZIKV infection and optimal administration of antibody-based ZIKV vaccines and therapeutics

A high stability semiconductor laser system for a 88^{88}Sr-based optical lattice clock

We describe a frequency stabilized diode laser at 698 nm used for high resolution spectroscopy of the 1S0-3P0 strontium clock transition. For the laser stabilization we use state-of-the-art symmetrically suspended optical cavities optimized for very low thermal noise at room temperature. Two-stage frequency stabilization to high finesse optical cavities results in measured laser frequency noise about a factor of three above the cavity thermal noise between 2 Hz and 11 Hz. With this system, we demonstrate high resolution remote spectroscopy on the 88Sr clock transition by transferring the laser output over a phase-noise-compensated 200 m-long fiber link between two separated laboratories. Our dedicated fiber link ensures a transfer of the optical carrier with frequency stability of 7 \cdot 10^{-18} after 100 s integration time, which could enable the observation of the strontium clock transition with an atomic Q of 10^{14}. Furthermore, with an eye towards the development of transportable optical clocks, we investigate how the complete laser system (laser+optics+cavity) can be influenced by environmental disturbances in terms of both short- and long-term frequency stability.Comment: 9 pages, 9 figures, submitted to Appl. Phys.

The role of cytokine gene polymorphisms in the pathogenesis of abdominal aortic aneurysms: A case-control study

AbstractBackground: Cytokines are the primary mediators of inflammation and also influence matrix metalloproteinase expression, both of which are important in development of abdominal aortic aneurysm (AAA). A significant, but as yet unknown, familial factor contributes to the pathogenesis of AAA. Many cytokine genes contain polymorphic sites, some of which affect cytokine production in vitro. Cytokine gene polymorphisms may therefore influence the pathogenesis of AAA. The purpose of this study was to determine whether there is any association between cytokine gene polymorphisms and AAA. Methods and Results: This case-control study comprised 100 patients with AAA and 100 age-matched and sex-matched control subjects. For each case and control subject in the study, genotypes at the following cytokine gene polymorphic loci were determined: interleukin (IL)-1β +3953, IL-6 −174, IL-10 −1082, IL-10 −592, and tumor necrosis factors-α −308. Allele and genotype frequencies were compared between AAA and control groups, and odds ratios (OR) were calculated for the presence of AAA with each allele at each locus examined as risk factors. The IL-10 −1082 A allele was significantly more common in the AAA group than the control group (P =.03). The OR for the IL-10 −1082 A allele as a risk factor for AAA was 1.8 (95% confidence interval, 0.9-3.6). Discussion: These associations suggest a significant role for IL-10 in the pathogenesis of AAA. This association of AAA with the IL-10 −1082 A allele is also biologically plausible; the IL-10 −1082 A allele is associated with low IL-10 secretion, and it may be that AAA develops in patients who are unable to mount the same anti-inflammatory response as those who do not have AAA. (J Vasc Surg 2003;37:999-1005.

Correlated response to selection for litter size environmental variability in rabbits' resilience

[EN] Resilience is the ability of an animal to return soon to its initial productivity after facing diverse environmental challenges. This trait is directly related to animal welfare and it plays a key role in fluctuations of livestock productivity. A divergent selection experiment for environmental variance of litter size has been performed successfully in rabbits over ten generations. The objective of this study was to analyse resilience indicators of stress and disease in the divergent lines of this experiment. The high line showed a lower survival rate at birth than the low line (-4.1%). After correcting by litter size, the difference was -3.2%. Involuntary culling rate was higher in the high than in the low line (+12.4%). Before vaccination against viral haemorrhagic disease or myxomatosis, concentration of lymphocytes, C-reactive protein (CRP), complement C3, serum bilirubin, triglycerides and cholesterol were higher in the high line than in the low line (difference between lines +4.5%, +5.6 mu g/ml, +4.6 mg/ml, +7.9 mmol/l, +0.3 mmol/l and +0.4 mmol/l). Immunological and biochemical responses to the two vaccines were similar. After vaccination, the percentage of lymphocytes and CRP concentration were higher in the low line than in the high one (difference between lines +4.0% and +13.1 mu g/ml). The low line also showed a higher increment in bilirubin and triglycerides than the high line (+14.2 v. +8.7 mmol/l for bilirubin and +0.11 v. +0.01 mmol/l for triglycerides); these results would agree with the protective role of bilirubin and triglycerides against the larger inflammatory response found in this line. In relation to stress, the high line had higher basal concentration of cortisol than the low line (+0.2ng/ml); the difference between lines increased more than threefold after the injection of ACTH 1 to 24, the increase being greater in the high line (+0.9 ng/ml) than in the low line (+0.4 ng/ml). Selection for divergent environmental variability of litter size leads to dams with different culling rate for reproductive causes and different kits' neonatal survival. These associations suggest that the observed fitness differences are related to differences in the inflammatory response and the corticotrope response to stress, which are two important components of physiological adaptation to environmental aggressions.This study is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) with the Projects AGL2014-55921, C2-1-P and C2-2-P, and AGL2017-86083, C2-1-P and C2-2-P.Argente, M.; Garcia, M.; Zbynovska, K.; Petruska, P.; Capcarova, M.; Blasco Mateu, A. (2019). Correlated response to selection for litter size environmental variability in rabbits' resilience. Animal. 13(10):2348-2355. https://doi.org/10.1017/S1751731119000302S234823551310Glaser, R., & Kiecolt-Glaser, J. K. (2005). Stress-induced immune dysfunction: implications for health. Nature Reviews Immunology, 5(3), 243-251. doi:10.1038/nri1571Markanday, A. (2015). Acute Phase Reactants in Infections: Evidence-Based Review and a Guide for Clinicians. Open Forum Infectious Diseases, 2(3). doi:10.1093/ofid/ofv098Rauw, W. ., Kanis, E., Noordhuizen-Stassen, E. ., & Grommers, F. . (1998). Undesirable side effects of selection for high production efficiency in farm animals: a review. Livestock Production Science, 56(1), 15-33. doi:10.1016/s0301-6226(98)00147-xPiles, M., García, M. L., Rafel, O., Ramon, J., & Baselga, M. (2006). Genetics of litter size in three maternal lines of rabbits: Repeatability versus multiple-trait models. Journal of Animal Science, 84(9), 2309-2315. doi:10.2527/jas.2005-622Guelfi, G., Zerani, M., Brecchia, G., Parillo, F., Dall’Aglio, C., Maranesi, M., & Boiti, C. (2011). Direct actions of ACTH on ovarian function of pseudopregnant rabbits. Molecular and Cellular Endocrinology, 339(1-2), 63-71. doi:10.1016/j.mce.2011.03.017García ML , Blasco A , García ME and Argente MJ 2018. Body condition and energy mobilisation in rabbits selected for litter size variability. Animal, 1–6, https://doi.org/10.1017/S1751731118002203, Published online by Cambridge University Press 28 August 2018.Furze, R. C., & Rankin, S. M. (2008). Neutrophil mobilization and clearance in the bone marrow. Immunology, 125(3), 281-288. doi:10.1111/j.1365-2567.2008.02950.xMcDade, T. W., Borja, J. B., Kuzawa, C. W., Perez, T. L. L., & Adair, L. S. (2015). C-reactive protein response to influenza vaccination as a model of mild inflammatory stimulation in the Philippines. Vaccine, 33(17), 2004-2008. doi:10.1016/j.vaccine.2015.03.019Blasco, A. (2017). Bayesian Data Analysis for Animal Scientists. doi:10.1007/978-3-319-54274-4Castellini, C., Dal Bosco, A., Arias-Álvarez, M., Lorenzo, P. L., Cardinali, R., & Rebollar, P. G. (2010). The main factors affecting the reproductive performance of rabbit does: A review. Animal Reproduction Science, 122(3-4), 174-182. doi:10.1016/j.anireprosci.2010.10.003Rosa Neto, N. S., & Carvalho, J. F. de. (2009). O uso de provas de atividade inflamatória em reumatologia. Revista Brasileira de Reumatologia, 49(4), 413-430. doi:10.1590/s0482-50042009000400008Argente, M. J., Calle, E. W., García, M. L., & Blasco, A. (2017). Correlated response in litter size components in rabbits selected for litter size variability. Journal of Animal Breeding and Genetics, 134(6), 505-511. doi:10.1111/jbg.12283Mirkena, T., Duguma, G., Haile, A., Tibbo, M., Okeyo, A. M., Wurzinger, M., & Sölkner, J. (2010). Genetics of adaptation in domestic farm animals: A review. Livestock Science, 132(1-3), 1-12. doi:10.1016/j.livsci.2010.05.003García, M. L., Blasco, A., & Argente, M. J. (2016). Embryologic changes in rabbit lines selected for litter size variability. Theriogenology, 86(5), 1247-1250. doi:10.1016/j.theriogenology.2016.04.065Feingold KR and Grunfeld C 2015. The effect of inflammation and infection on lipids and lipoproteins. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F and Vinik A. Endotext, South Dartmouth, MA, USA. Retrieved on 7 June 2018 from https://www.ncbi.nlm.nih.gov/books/NBK326741/.Minemura, M. (2014). Liver involvement in systemic infection. World Journal of Hepatology, 6(9), 632. doi:10.4254/wjh.v6.i9.632Knap, P. W. (2005). Breeding robust pigs. Australian Journal of Experimental Agriculture, 45(8), 763. doi:10.1071/ea05041Barcia, A. M., & Harris, H. W. (2005). Triglyceride-Rich Lipoproteins as Agents of Innate Immunity. Clinical Infectious Diseases, 41(Supplement_7), S498-S503. doi:10.1086/432005Webster, J. I., Tonelli, L., & Sternberg, E. M. (2002). NEUROENDOCRINEREGULATION OFIMMUNITY. Annual Review of Immunology, 20(1), 125-163. doi:10.1146/annurev.immunol.20.082401.104914Fortun-Lamothe, L. (2006). Energy balance and reproductive performance in rabbit does. Animal Reproduction Science, 93(1-2), 1-15. doi:10.1016/j.anireprosci.2005.06.009Cabezas, S., Blas, J., Marchant, T. A., & Moreno, S. (2007). Physiological stress levels predict survival probabilities in wild rabbits. Hormones and Behavior, 51(3), 313-320. doi:10.1016/j.yhbeh.2006.11.004De Nardo, D., Labzin, L. I., Kono, H., Seki, R., Schmidt, S. V., Beyer, M., … Latz, E. (2013). High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. Nature Immunology, 15(2), 152-160. doi:10.1038/ni.2784BURKUŠ, J., KAČMAROVÁ, M., KUBANDOVÁ, J., KOKOŠOVÁ, N., FABIANOVÁ, K., FABIAN, D., … ČIKOŠ, Š. (2015). Stress exposure during the preimplantation period affects blastocyst lineages and offspring development. Journal of Reproduction and Development, 61(4), 325-331. doi:10.1262/jrd.2015-012Posthouwer, D., Voorbij, H. A. M., Grobbee, D. E., Numans, M. E., & van der Bom, J. G. (2004). Influenza and pneumococcal vaccination as a model to assess C-reactive protein response to mild inflammation. Vaccine, 23(3), 362-365. doi:10.1016/j.vaccine.2004.05.035Ibáñez-Escriche, N., Sorensen, D., Waagepetersen, R., & Blasco, A. (2008). Selection for Environmental Variation: A Statistical Analysis and Power Calculations to Detect Response. Genetics, 180(4), 2209-2226. doi:10.1534/genetics.108.091678Colditz, I. G., & Hine, B. C. (2016). Resilience in farm animals: biology, management, breeding and implications for animal welfare. Animal Production Science, 56(12), 1961. doi:10.1071/an15297Blasco, A., Martínez-Álvaro, M., García, M.-L., Ibáñez-Escriche, N., & Argente, M.-J. (2017). Selection for environmental variance of litter size in rabbits. Genetics Selection Evolution, 49(1). doi:10.1186/s12711-017-0323-4Argente MJ , Santacreu MA , Climen A and Blasco A 2000. Genetic correlations between litter size and uterine capacity. In Proceeding of the 8th World Rabbit Congress, 4–7 July 2000, Valencia, Spain, pp. 333–338.Janssens, C. J., Helmond, F. A., & Wiegant, V. M. (1995). Chronic stress and pituitary–adrenocortical responses to corticotropin-releasing hormone and vasopressin in female pigs. European Journal of Endocrinology, 132(4), 479-486. doi:10.1530/eje.0.132047

Establishing the Production of Male Schistosoma mansoni Cercariae for a Controlled Human Infection Model

Medical Microbiolog

Identifying viable regulatory and innovation pathways for regenerative medicine:A case study of cultured red blood cells

The creation of red blood cells for the blood transfusion markets represents a highly innovative application of regenerative medicine with a medium term (5–10 year) prospect for first clinical studies. This article describes a case study analysis of a project to derive red blood cells from human embryonic stem cells, including the systemic challenges arising from (i) the selection of appropriate and viable regulatory protocols and (ii) technological constraints related to stem cell manufacture and scale up to clinical Good Manufacturing Practice (GMP) standard. The method used for case study analysis (Analysis of Life Science Innovation Systems (ALSIS)) is also innovative, demonstrating a new approach to social and natural science collaboration to foresight product development pathways. Issues arising along the development pathway include cell manufacture and scale-up challenges, affected by regulatory demands emerging from the innovation ecosystem (preclinical testing and clinical trials). Our discussion reflects on the efforts being made by regulators to adapt the current pharmaceuticals-based regulatory model to an allogeneic regenerative medicine product and the broader lessons from this case study for successful innovation and translation of regenerative medicine therapies, including the role of methodological and regulatory innovation in future development in the field

What is the Oxygen Isotope Composition of Venus? The Scientific Case for Sample Return from Earth’s “Sister” Planet

Venus is Earth’s closest planetary neighbour and both bodies are of similar size and mass. As a consequence, Venus is often described as Earth’s sister planet. But the two worlds have followed very different evolutionary paths, with Earth having benign surface conditions, whereas Venus has a surface temperature of 464 °C and a surface pressure of 92 bar. These inhospitable surface conditions may partially explain why there has been such a dearth of space missions to Venus in recent years.The oxygen isotope composition of Venus is currently unknown. However, this single measurement (Δ17O) would have first order implications for our understanding of how large terrestrial planets are built. Recent isotopic studies indicate that the Solar System is bimodal in composition, divided into a carbonaceous chondrite (CC) group and a non-carbonaceous (NC) group. The CC group probably originated in the outer Solar System and the NC group in the inner Solar System. Venus comprises 41% by mass of the inner Solar System compared to 50% for Earth and only 5% for Mars. Models for building large terrestrial planets, such as Earth and Venus, would be significantly improved by a determination of the Δ17O composition of a returned sample from Venus. This measurement would help constrain the extent of early inner Solar System isotopic homogenisation and help to identify whether the feeding zones of the terrestrial planets were narrow or wide.Determining the Δ17O composition of Venus would also have significant implications for our understanding of how the Moon formed. Recent lunar formation models invoke a high energy impact between the proto-Earth and an inner Solar System-derived impactor body, Theia. The close isotopic similarity between the Earth and Moon is explained by these models as being a consequence of high-temperature, post-impact mixing. However, if Earth and Venus proved to be isotopic clones with respect to Δ17O, this would favour the classic, lower energy, giant impact scenario.We review the surface geology of Venus with the aim of identifying potential terrains that could be targeted by a robotic sample return mission. While the potentially ancient tessera terrains would be of great scientific interest, the need to minimise the influence of venusian weathering favours the sampling of young basaltic plains. In terms of a nominal sample mass, 10 g would be sufficient to undertake a full range of geochemical, isotopic and dating studies. However, it is important that additional material is collected as a legacy sample. As a consequence, a returned sample mass of at least 100 g should be recovered.Two scenarios for robotic sample return missions from Venus are presented, based on previous mission proposals. The most cost effective approach involves a “Grab and Go” strategy, either using a lander and separate orbiter, or possibly just a stand-alone lander. Sample return could also be achieved as part of a more ambitious, extended mission to study the venusian atmosphere. In both scenarios it is critical to obtain a surface atmospheric sample to define the extent of atmosphere-lithosphere oxygen isotopic disequilibrium. Surface sampling would be carried out by multiple techniques (drill, scoop, “vacuum-cleaner” device) to ensure success. Surface operations would take no longer than one hour.Analysis of returned samples would provide a firm basis for assessing similarities and differences between the evolution of Venus, Earth, Mars and smaller bodies such as Vesta. The Solar System provides an important case study in how two almost identical bodies, Earth and Venus, could have had such a divergent evolution. Finally, Venus, with its runaway greenhouse atmosphere, may provide data relevant to the understanding of similar less extreme processes on Earth. Venus is Earth’s planetary twin and deserves to be better studied and understood. In a wider context, analysis of returned samples from Venus would provide data relevant to the study of exoplanetary systems