Memory Phenotype CD4 T Cells Undergoing Rapid, Nonburst-Like, Cytokine-Driven Proliferation Can Be Distinguished from Antigen-Experienced Memory Cells

Contrary to the current paradigm that nearly all memory T cells proliferate in response to antigenic stimulation, this paper shows that an important population of CD4 T lymphocytes achieves memory/effector status independent of antigenic stimulation

Uterine Gene Expression in the Live-Bearing Lizard, Chalcides ocellatus, Reveals Convergence of Squamate Reptile and Mammalian Pregnancy Mechanisms

Although the morphological and physiological changes involved in pregnancy in live-bearing reptiles are well studied, the genetic mechanisms that underlie these changes are not known. We used the viviparous African Ocellated Skink, Chalcides ocellatus, as a model to identify a near complete gene expression profile associated with pregnancy using RNA-Seq analyses of uterine transcriptomes. Pregnancy in C. ocellatus is associated with upregulation of uterine genes involved with metabolism, cell proliferation and death, and cellular transport. Moreover, there are clear parallels between the genetic processes associated with pregnancy in mammals and Chalcides in expression of genes related to tissue remodeling, angiogenesis, immune system regulation, and nutrient provisioning to the embryo. In particular, the pregnant uterine transcriptome is dominated by expression of proteolytic enzymes that we speculate are involved both with remodeling the chorioallantoic placenta and histotrophy in the omphaloplacenta. Elements of the maternal innate immune system are downregulated in the pregnant uterus, indicating a potential mechanism to avoid rejection of the embryo. We found a downregulation of major histocompatability complex loci and estrogen and progesterone receptors in the pregnant uterus. This pattern is similar to mammals but cannot be explained by the mammalian model. The latter finding provides evidence that pregnancy is controlled by different endocrinological mechanisms in mammals and reptiles. Finally, 88% of the identified genes are expressed in both the pregnant and the nonpregnant uterus, and thus, morphological and physiological changes associated with C. ocellatus pregnancy are likely a result of regulation of genes continually expressed in the uterus rather than the initiation of expression of unique genes

International comparisons of laboratory values from the 4CE collaborative to predict COVID-19 mortality

Given the growing number of prediction algorithms developed to predict COVID-19 mortality, we evaluated the transportability of a mortality prediction algorithm using a multi-national network of healthcare systems. We predicted COVID-19 mortality using baseline commonly measured laboratory values and standard demographic and clinical covariates across healthcare systems, countries, and continents. Specifically, we trained a Cox regression model with nine measured laboratory test values, standard demographics at admission, and comorbidity burden pre-admission. These models were compared at site, country, and continent level. Of the 39,969 hospitalized patients with COVID-19 (68.6% male), 5717 (14.3%) died. In the Cox model, age, albumin, AST, creatine, CRP, and white blood cell count are most predictive of mortality. The baseline covariates are more predictive of mortality during the early days of COVID-19 hospitalization. Models trained at healthcare systems with larger cohort size largely retain good transportability performance when porting to different sites. The combination of routine laboratory test values at admission along with basic demographic features can predict mortality in patients hospitalized with COVID-19. Importantly, this potentially deployable model differs from prior work by demonstrating not only consistent performance but also reliable transportability across healthcare systems in the US and Europe, highlighting the generalizability of this model and the overall approach

C5a Enhances Dysregulated Inflammatory and Angiogenic Responses to Malaria In Vitro: Potential Implications for Placental Malaria

Placental malaria (PM) is a leading cause of maternal and infant mortality. Although the accumulation of parasitized erythrocytes (PEs) and monocytes within the placenta is thought to contribute to the pathophysiology of PM, the molecular mechanisms underlying PM remain unclear. Based on the hypothesis that excessive complement activation may contribute to PM, in particular generation of the potent inflammatory peptide C5a, we investigated the role of C5a in the pathogenesis of PM in vitro and in vivo.Using primary human monocytes, the interaction between C5a and malaria in vitro was assessed. CSA- and CD36-binding PEs induced activation of C5 in the presence of human serum. Plasmodium falciparum GPI (pfGPI) enhanced C5a receptor expression (CD88) on monocytes, and the co-incubation of monocytes with C5a and pfGPI resulted in the synergistic induction of cytokines (IL-6, TNF, IL-1beta, and IL-10), chemokines (IL-8, MCP-1, MIP1alpha, MIP1beta) and the anti-angiogenic factor sFlt-1 in a time and dose-dependent manner. This dysregulated response was abrogated by C5a receptor blockade. To assess the potential role of C5a in PM, C5a plasma levels were measured in malaria-exposed primigravid women in western Kenya. Compared to pregnant women without malaria, C5a levels were significantly elevated in women with PM.These results suggest that C5a may contribute to the pathogenesis of PM by inducing dysregulated inflammatory and angiogenic responses that impair placental function

Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study

Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings: Advanced age (HR 2.77, 95%CI 2.53–3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03–4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55–5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14–1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37–0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17–1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20–1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45–1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80–13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10–1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32–1.67) and 365 days (RR 1.54, 95%CI 1.21–1.96) compared to COVID-19 patients with no AKI. Interpretation: COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery. Funding: Authors are supported by various funders, with full details stated in the acknowledgement section

Molecular reorientations in the two plastic crystalline phases of norbornane. An investigation from incoherent quasielastic neutron scattering

The dynamics of norbornane molecules is studied over the 120 K-348 K temperature range in its ordered (T < 131.5 K) and in its two orientationally disordered solid phases, using the incoherent quasielastic neutron scattering technique. On the time-scale accessible to time-of-flight neutron spectroscopy, (10–11 – 10–12 s), an elastic incoherent structure factor is extracted in the two plastic phases, which corresponds to isotropic rotations of the molecules about their centre of gravity, with apparently no change at the transition between the two phases. A description in terms of an isotropic rotational diffusion model yields a unique Arrhenius law for the diffusion constant through all the temperature range of these two phases. A more sophisticated description based on reorientations about lattice and molecules axes gives a continuous evolution of the correlation times across the transition. A comparison is made with recent NMR results. At the lowest temperatures in the h.c.p. plastic phase, an extra amount of elastic scattering is evidenced. A possible interpretation in terms of either a local ordering of the molecules or a distribution of the correlation times is proposed

LOCAL ORDER AND NON EQUILIBRIUM BEHAVIOUR IN GLASSY CRYSTAL CYANOADAMANTANE

Lors de recuits isothermes en phase plastique trempée, le cyanoadamantane évolue vers une phase métastable dont la structure est différente de celle de la phase stable à la même température. Cette microstructure est décrite. La cinétique de mise en ordre qui est corrélée à une contraction volumique est analysée en terme de relaxation moléculaire.During isothermal annealing in the glassy crystal phase, cyanoadamantane relaxes towards a metastable state. The microstructure of the latter is described. It is different from that of the stable phase at the same temperature. The kinetics of ordering which are coupled to a volume contraction are analyzed in terms of molecular relaxation

Bi-directional cell trafficking between mother and fetus in mouse placenta.

International audienceIt is now well established that cells are exchanged between mother and fetus during gestation. It has been proposed that some of these exchanges take place in the placenta, but it has never been demonstrated. Here, we made use of EGFP (Enhanced Green Fluorescent Protein) transgenic mice to precisely visualize the juxtaposition of maternal and fetal tissues at the implantation site, as well as to describe the bi-directional cell trafficking between mother and fetus at different stages of gestation. The influence of genetic differences between mother and fetus on the cell migration was also addressed by studying various types of matings: syngeneic, allogeneic and outbred. The frequency of maternal-fetal cell exchanges within the placenta is much higher in syngeneic and allogeneic gestations than in outbred ones. Maternal cells were mainly localized in the labyrinth where they were scattered or sometimes grouped in or near blood spaces. Groups of maternal cells could also be observed in maternal blood sinuses of the spongiotrophoblast. Conversely, fetal cells were organized in rings surrounding maternal blood sinuses in the decidua at 10-12 days of gestation. After day 13, they invaded the decidua. Fetal cells could also be detected in maternal peripheral blood and organs by nested PCR and fluorescence microscopy on cryosections, respectively. This suggests a role in the establishment and maintenance of the maternal tolerance to the fetus

Local molecular order in the glassy crystalline phase of cyanoadamantane : diffuse X-ray scattering analysis

This Letter presents the results of X-ray scattering experiments performed on cyanoadamantane in its plastic phase (I) and its « glassy crystal » state (Ig) obtained by the quenching of phase (I). The patterns associated with this latter phase are more structured and are characterized by the presence of narrow spots at the X boundary points. An interpretation is proposed in terms of geared antiferroelectric domains. The coherence length is ξ ≃ 20 A.Dans cette Lettre nous présentons les résultats d'expériences de diffusion de rayons X effectuées sur le cyanoadamantane en phase plastique (I) et en phase « cristal vitreux » (Ig) obtenue par trempe de la phase (I). L'aspect général des figures de diffusion est dans ce dernier cas plus structuré. De plus, il apparait en phase vitreuse, des taches diffuses fines aux points X des zones de Brillouin. Nous proposons une interprétation en termes de domaines antiferroélectriques engrainés. La longueur de corrélation correspondante serait alors d'environ 20 A