Protective immunity to liver-stage malaria

Despite decades of research and recent clinical trials, an efficacious long-lasting preventative vaccine for malaria remains elusive. This parasite infects mammals via mosquito bites, progressing through several stages including the relatively short asymptomatic liver stage followed by the more persistent cyclic blood stage, the latter of which is responsible for all disease symptoms. As the liver acts as a bottleneck to blood-stage infection, it represents a potential site for parasite and disease control. In this review, we discuss immunity to liver-stage malaria. It is hoped that the knowledge gained from animal models of malaria immunity will translate into a more powerful and effective vaccine to reduce this global health problem

Microcanonical finite-size scaling in specific heat diverging 2nd order phase transitions

A Microcanonical Finite Site Ansatz in terms of quantities measurable in a Finite Lattice allows to extend phenomenological renormalization (the so called quotients method) to the microcanonical ensemble. The Ansatz is tested numerically in two models where the canonical specific-heat diverges at criticality, thus implying Fisher-renormalization of the critical exponents: the 3D ferromagnetic Ising model and the 2D four-states Potts model (where large logarithmic corrections are known to occur in the canonical ensemble). A recently proposed microcanonical cluster method allows to simulate systems as large as L=1024 (Potts) or L=128 (Ising). The quotients method provides extremely accurate determinations of the anomalous dimension and of the (Fisher-renormalized) thermal $\nu$ exponent. While in the Ising model the numerical agreement with our theoretical expectations is impressive, in the Potts case we need to carefully incorporate logarithmic corrections to the microcanonical Ansatz in order to rationalize our data.Comment: 13 pages, 8 figure

Comment on "Evidence of Non-Mean-Field-Like Low-Temperature Behavior in the Edwards-Anderson Spin-Glass Model"

A recent interesting paper [Yucesoy et al. Phys. Rev. Lett. 109, 177204 (2012), arXiv:1206:0783] compares the low-temperature phase of the 3D Edwards-Anderson (EA) model to its mean-field counterpart, the Sherrington-Kirkpatrick (SK) model. The authors study the overlap distributions P_J(q) and conclude that the two models behave differently. Here we notice that a similar analysis using state-of-the-art, larger data sets for the EA model (generated with the Janus computer) leads to a very clear interpretation of the results of Yucesoy et al., showing that the EA model behaves as predicted by the replica symmetry breaking (RSB) theory.Comment: Version accepted for publication in PRL. 1 page, 1 figur

Millimagnitude Photometry for Transiting Extrasolar Planetary Candidates. V. Follow-up of 30 OGLE Transits. New Candidates

We used VLT/VIMOS images in the V band to obtain light curves of extrasolar planetary transits OGLE-TR-111 and OGLE-TR-113, and candidate planetary transits: OGLE-TR-82, OGLE-TR-86, OGLE-TR-91, OGLE-TR-106, OGLE-TR-109, OGLE-TR-110, OGLE-TR-159, OGLE-TR-167, OGLE-TR-170, OGLE-TR-171. Using difference imaging photometry, we were able to achieve millimagnitude errors in the individual data points. We present the analysis of the data and the light curves, by measuring transit amplitudes and ephemerides, and by calculating geometrical parameters for some of the systems. We observed 9 OGLE objects at the predicted transit moments. Two other transits were shifted in time by a few hours. For another seven objects we expected to observe transits during the VIMOS run, but they were not detected. The stars OGLE-TR-111 and OGLE-TR-113 are probably the only OGLE objects in the observed sample to host planets, with the other objects being very likely eclipsing binaries or multiple systems. In this paper we also report on four new transiting candidates which we have found in the data.Comment: 11 pages, 17 figures, accepted for publication in A&

Estima de la composición corporal en conejos de 25 a 77 días de edad mediante la técnica de impedancia bioeléctrica (BIA).

El objetivo de este trabajo fue determinar y validar con datos independientes las ecuaciones de predicción obtenidas para estimar in vivo la composición corporal de conejos en crecimiento utilizando la técnica de impedancia bioeléctrica (BIA). Las ecuaciones se calcularon mediante un análisis de regresión múltiple a partir de las medidas de impedancia presentadas en el trabajo anterior (Saiz et al., 2011) y de otras variables independientes que fueron incluidas en el modelo, tras hacer un análisis de selección de variables, como la edad, el peso y la longitud del animal. Los coeficientes de determinación (R2) de las ecuaciones para estimar la humedad (g), la proteína (g), la grasa (g), las cenizas (g) y la energía (MJ) fueron: 0,99, 0,99, 0,97, 0,98 y 0,99, y los errores medios de predicción relativos (EMPR): 2,24, 5,99, 16,3, 8,56 y 7,81%, respectivamente. El R2 y EMPR para estimar el porcentaje de humedad corporal fueron de 0,85 y 1,98%, respectivamente. Para predecir los contenidos, expresados sobre materia seca (MS), de proteína (%), grasa (%), cenizas (%) y energía (kJ/100g), el R2 obtenido fue 0,79, 0,83, 0,71 y 0,86, respectivamente y el EMPR 4,78, 12,2, 8,39 y 3,26%, respectivamente. La reactancia estuvo negativamente correlacionada con el contenido en humedad, cenizas y proteína bruta (r=-0,32, Pmenor que0,0001; r=-0,20, Pmenor que0,05; r=-0,26, Pmenor que0,01) pero positivamente con el de grasa y energía (r=0,23 y r=0,24; Pmenor que0,01). Al contrario ocurrió con la resistencia, que estuvo positivamente correlacionada con el contenido en humedad, cenizas y proteína bruta (r=0,31, Pmenor que0,001; r=0,28, Pmenor que0,001; r=0,37, Pmenor que0,0001) pero negativamente con el de grasa y energía (r=-0,36 y r=-0,35; Pmenor que0,0001). Así mismo, la edad del animal, estuvo negativamente correlacionada con el contenido en humedad, proteína y cenizas (r=-0,79, r=-0,67 y r=-0,80; Pmenor que0,0001) y positivamente con la grasa y energía (r=0,78 y r=0,81; Pmenor que0,0001). Se puede considerar la técnica BIA como una técnica útil para estimar in vivo la composición corporal de los conejos en crecimiento de 25 a 77 días de edad

Interplay between liver and blood stages of Plasmodium infection dictates malaria severity via γδ T cells and IL-17-promoted stress erythropoiesis

© 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Plasmodium replicates within the liver prior to reaching the bloodstream and infecting red blood cells. Because clinical manifestations of malaria only arise during the blood stage of infection, a perception exists that liver infection does not impact disease pathology. By developing a murine model where the liver and blood stages of infection are uncoupled, we showed that the integration of signals from both stages dictated mortality outcomes. This dichotomy relied on liver stage-dependent activation of Vγ4+ γδ T cells. Subsequent blood stage parasite loads dictated their cytokine profiles, where low parasite loads preferentially expanded IL-17-producing γδ T cells. IL-17 drove extra-medullary erythropoiesis and concomitant reticulocytosis, which protected mice from lethal experimental cerebral malaria (ECM). Adoptive transfer of erythroid precursors could rescue mice from ECM. Modeling of γδ T cell dynamics suggests that this protective mechanism may be key for the establishment of naturally acquired malaria immunity among frequently exposed individuals.We would like to acknowledge Freddy Frischknecht (Integrative Parasitology Center for Infectious Diseases, Heidelberg) for providing the Plasmodium berghei lisp2− parasite line, Immo Prinz (Hannover Medical School, Hannover) for providing genetically modified mouse lines, Ana Parreira (iMM-JLA, Portugal) and Geoff McFadden’s lab (School of BioSciences, University of Melbourne, Australia) for mosquito rearing and infection with Plasmodium parasites, Helena Pinheiro (iMM-JLA, Portugal) for assistance with graphical design, Inês Bento and Miguel Prudêncio for critically reviewing this manuscript, and the Flow Cytometry and Rodent Facilities teams (iMM-JLA, Portugal) for their assistance. Work at iMM-JLA was supported by Fundação para a Ciência e a Tecnologia. Portugal (PTDC/MED-IMU/28664/2017) and the “La caixa” Banking Foundation, Spain (HR17-00264-PoEMM) grants attributed to Â.F.C. and M.M.M., respectively. Work at the Department of Microbiology and Immunology, The University of Melbourne, Australia, was funded by the National Health and Medical Research Council, Australia (1113293, 1154457) and the Australian Research Council, Australia (CE140100011). Â.F.C., S.M., J.L.G., M.I.M., R.M.R., and K.S. were supported by Fundação para a Ciência e a Tecnologia, Portugal (DL57/2016/CP1451/CT0004, DL57/2016/CP1451/CT0010, PD/BD/139053/2018, PD/BD/135454/2017, PTDC/MAT-APL/31602/2017, and CEECIND/00697/2018, respectively), P.L. was supported by Conselho Nacional de Desenvolvimento Científico e Tenológico, Brazil (SN/CGEFO/CNPQ 201801/2015-9), and A.T.T. was supported in part by Alfred P. Sloan Foundation Fellowship (FG-2020-12949).info:eu-repo/semantics/publishedVersio

Iberian cured-ham consumption improves endothelial function in healthy subjects

Objectives: Previous studies have shown that dietary components such as oleic acid or polyphenols exert beneficial effects on endothelium. We aimed to assess the impact of regular consumption of Iberian cured-ham (ICH) on endothelial function. Design: An open-label, randomized controlled parallel study. Setting: Volunteers recruited through advertisements at a hospital in Madrid, Spain. Participants: 102 Caucasian adults (76.8% females) aged 25-55 years, and free from cardiometabolic disease. Intervention: Participants were randomized to an ICH-enriched ad libitum diet or an ad libitum diet without ICH for 6 weeks. Subjects in ICH group were randomly provided with either acorn- or mixed-fed ICH, and followed up for an additional 6-week period under their usual diet. Measurements: Clinical parameters, biomarkers of endothelial function and oxidative stress, microvascular vasodilatory response to hyperemia and arterial stiffness were measured before and after the intervention. Results: After 6 weeks, a larger decrease in PAI-1 was observed in subjects consuming ICH compared to the Control group (-6.2±17.7 vs. 0.3±1.4 ng/ml; p=0.020). Similarly, microvascular vasodilatory response to hyperemia showed a significant increase (112.4±391.7 vs. -56.0±327.9%; p=0.007). However, neither oxidative stress, hemodynamic nor clinical parameters differed significantly over the study. Additionally, after stopping ICH consumption, improvements in PAI-1 remained for 6 additional weeks with respect to baseline (p=0.006). Conclusion: The present study demonstrates, for the first time, that regular consumption of ICH improves endothelial function in healthy adults. Strategies aimed to preserve or improve the endothelial function may have implications in vascular aging beyond the prevention of the atherothrombotic disease

CD8⁺ T Cell Activation Leads to Constitutive Formation of Liver Tissue-Resident Memory T Cells that Seed a Large and Flexible Niche in the Liver

Liver tissue-resident memory T (Trm) cells migrate throughout the sinusoids and are capable of protecting against malaria sporozoite challenge. To gain an understanding of liver Trm cell development, we examined various conditions for their formation. Although liver Trm cells were found in naive mice, their presence was dictated by antigen specificity and required IL-15. Liver Trm cells also formed after adoptive transfer of in vitro-activated but not naive CD8+ T cells, indicating that activation was essential but that antigen presentation within the liver was not obligatory. These Trm cells patrolled the liver sinusoids with a half-life of 36 days and occupied a large niche that could be added to sequentially without effect on subsequent Trm cell cohorts. Together, our findings indicate that liver Trm cells form as a normal consequence of CD8+ T cell activation during essentially any infection but that inflammatory and antigenic signals preferentially tailor their development. Holz et al. demonstrate that tissue-resident memory T (Trm) cells routinely develop in the liver after T cell activation. Within the liver, IL-15, antigen, and inflammation aid Trm cell formation, but only IL-15 is essential. Newly formed Trm cells do not displace existing populations, demonstrating a flexible liver niche

A T-PROPER KARHUNEN-LOÈVE EXPANSION AND ITS APPLICATION TO THE PROBLEM OF SIMULATION

The paper addresses the Karhunen-Loeve series representation in the tessarine domain. Based on augmented statistics, a tessarine widely linear Karhunen-Loeve expansion is defined. Then, the impact of T-properness on this representationis analyzed, leading to a T-proper Karhunen-Loeve expansion that means a dimensionality reduction. Furthermore, this series representation serves as a versatile simulation tool, valid for both stationary and non-stationary, Gaussian and non-Gaussian random signals. Finally, the applicability of the simulation technique proposed is examined numerically