Perinatal iron deficiency alters the cardiac proteome and mitochondrial function in neonatal offspring.

Iron deficiency (ID) is common during gestation and early infancy and can alter developmental trajectories with lasting consequences on cardiovascular health. Iron plays a critical role in systemic oxygen transport (via hemoglobin) and aerobic respiration (as a component of mitochondrial complexes). Perinatal ID has been shown to cause cardiac dysfunction in neonates, but the mechanisms underlying these changes have not been characterized.

Maternal ketone supplementation throughout gestation improves neonatal cardiac dysfunction caused by perinatal iron deficiency.

Iron deficiency (ID) is common during gestation and in early infancy and has been shown to adversely affect cardiac development and function, which could lead to lasting cardiovascular consequences. Ketone supplementation has been shown to confer cardioprotective effects in numerous disease models. Here, we tested the hypothesis that maternal ketone supplementation during gestation would mitigate cardiac dysfunction in ID neonates.

The Dictyostelium discoideum FimA protein, unlike yeast and plant fimbrins, is regulated by calcium similar to mammalian plastins.

Plastins, also known as fimbrins, are highly conserved eukaryotic multidomain proteins that are involved in actin-bundling. They all contain four independently folded Calponin Homology-domains and an N-terminal headpiece that is comprised of two calcium-binding EF-hand motifs. Since calcium-binding has been shown to be integral to regulating the activity of the three mammalian plastin proteins, we decided to study the properties of the headpiece regions of fimbrins from the model plant Arabidopsis thaliana, the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe and the amoeba Dictyostelium discoideum.

Perinatal iron restriction is associated with changes in neonatal cardiac function and structure in a sex-dependent manner.

Iron deficiency (ID) is common during gestation and in early infancy and can alter developmental trajectories with lasting consequences on cardiovascular health. While the effects of ID and anemia on the mature heart are well documented, comparatively little is known about their effects and mechanisms on offspring cardiac development and function in the neonatal period. Female Sprague-Dawley rats were fed an iron-restricted or iron-replete diet before and during pregnancy.

Perinatal iron deficiency causes sex-dependent alterations in renal retinoic acid signaling and nephrogenesis.

Long-term alterations in kidney structure and function have been observed in offspring exposed to perinatal stressors such as iron deficiency (ID), albeit the mechanisms underlying these changes remain unclear. Here, we assessed how perinatal ID alters renal vitamin A metabolism, an important contributor to nephrogenesis, in the developing kidney. Pregnant Sprague Dawley rats were fed either an iron-restricted or -replete diet throughout gestation, and offspring were studied on postnatal day (PD)1 and 28.

Generated Randomly and Selected Functionally? The Nature of Enterovirus Recombination.

Genetic recombination in RNA viruses is an important evolutionary mechanism. It contributes to population diversity, host/tissue adaptation, and compromises vaccine efficacy. Both the molecular mechanism and initial products of recombination are relatively poorly understood.

Maternal Iron Deficiency Alters Trophoblast Differentiation and Placental Development in Rat Pregnancy.

Iron deficiency, which occurs when iron demands chronically exceed intake, is prevalent in pregnant women. Iron deficiency during pregnancy poses major risks for the baby, including fetal growth restriction and long-term health complications. The placenta serves as the interface between a pregnant mother and her baby, and it ensures adequate nutrient provisions for the fetus.

Imprecise recombinant viruses evolve via a fitness-driven, iterative process of polymerase template-switching events.

Recombination is a common feature of many positive-strand RNA viruses, playing an important role in virus evolution. However, to date, there is limited understanding of the mechanisms behind the process. Utilising in vitro assays, we have previously shown that the template-switching event of recombination is a random and ubiquitous process that often leads to recombinant viruses with imprecise genomes containing sequence duplications.

Maternal and Cord Blood Hemoglobin as Determinants of Placental Weight: A Cross-Sectional Study.

Background: Both high and low placental weights are associated with adverse pregnancy outcomes. Maternal hemoglobin levels can influence placental weight, but the evidence is conflicting. Since maternal hemoglobin does not invariably correlate with fetal/neonatal blood hemoglobin levels, we sought to determine whether cord blood hemoglobin or maternal hemoglobin status more closely associates with placental weight in women undergoing elective cesarean section at term.

A systematic review and meta-analysis of the correlation between maternal and neonatal iron status and haematologic indices.

Background: Iron deficiency (ID) is the leading single-nutrient deficiency in the world. Anaemia is a common outcome of ID that affects half of pregnancies worldwide with serious consequences for child development. Whether haematologic indices and biomarkers of iron status in pregnant women correlate with those of their neonates is unclear.

RNA-Dependent RNA Polymerase Speed and Fidelity are not the Only Determinants of the Mechanism or Efficiency of Recombination.

Using the RNA-dependent RNA polymerase (RdRp) from poliovirus (PV) as our model system, we have shown that Lys-359 in motif-D functions as a general acid in the mechanism of nucleotidyl transfer. A K359H (KH) RdRp derivative is slow and faithful relative to wild-type enzyme. In the context of the KH virus, RdRp-coding sequence evolves, selecting for the following substitutions: I331F (IF, motif-C) and P356S (PS, motif-D).

More than efficacy revealed by single-cell analysis of antiviral therapeutics.

Because many aspects of viral infection dynamics and inhibition are governed by stochastic processes, single-cell analysis should provide more information than approaches using population averaging. We have developed a microfluidic device composed of ~6000 wells, with each well containing a microstructure to capture single, infected cells replicating an enterovirus expressing a fluorescent reporter protein. We have used this system to characterize enterovirus inhibitors with distinct mechanisms of action.

Perinatal iron deficiency combined with a high salt diet in adulthood causes sex-dependent vascular dysfunction in rats.

Key Points: Perinatal iron deficiency causes changes in offspring mesenteric artery function in adulthood, particularly in males, which can be exacerbated by chronic intake of a high salt diet. Perinatal iron deficient male offspring exhibit enhanced conversion of big endothelin-1 to active endothelin-1, coinciding with decreased nitric oxide levels. Perinatal iron deficient male offspring have reduced nitric oxide-mediated endothelial-dependent vasodilatation coincident with increased vascular superoxide levels following consumption of a high salt diet.

Senecavirus-Specific Recombination Assays Reveal the Intimate Link between Polymerase Fidelity and RNA Recombination.

Senecavirus A (SVA) is a reemerging virus, and recent evidence has emphasized the importance of SVA recombination on virus evolution. In this study, we report the development of an infectious cDNA clone for the SVA/HLJ/CHA/2016 strain. We used this strain to develop a reporter virus expressing enhanced green fluorescent protein (eGFP), which we then used to screen for a recombination-deficient SVA by an eGFP retention assay.

Perinatal iron deficiency and a high salt diet cause long-term kidney mitochondrial dysfunction and oxidative stress.

Aims: Perinatal iron deficiency (ID) alters developmental trajectories of offspring, predisposing them to cardiovascular dysfunction in later life. The mechanisms underlying this long-term programming of renal function have not been defined. We hypothesized perinatal ID causes hypertension and alters kidney metabolic function and morphology in a sex-dependent manner in adult offspring.

Characterization of the EF-Hand Calcium-Binding Domains of Human Plastins.

The three human plastins (L-plastin, T-plastin, and I-plastin) are important regulatory Ca-binding proteins that belong to the family of actin-binding proteins. Plastins are involved in the regulation of the actin cytoskeleton as well as the cross-linking of actin filaments. In addition to four calponin-homology (CH) domains, all three plastins contain two N-terminal EF-hand Ca-binding motifs which together are homologous to a single lobe of the well-known calcium-regulatory protein calmodulin.

Predicting Intraserotypic Recombination in Enterovirus 71.

Enteroviruses are well known for their ability to cause neurological damage and paralysis. The model enterovirus is poliovirus (PV), the causative agent of poliomyelitis, a condition characterized by acute flaccid paralysis. A related virus, enterovirus 71 (EV-A71), causes similar clinical outcomes in recurrent outbreaks throughout Asia.

A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus.

Mutation rates can evolve through genetic drift, indirect selection due to genetic hitchhiking, or direct selection on the physicochemical cost of high fidelity. However, for many systems, it has been difficult to disentangle the relative impact of these forces empirically. In RNA viruses, an observed correlation between mutation rate and virulence has led many to argue that their extremely high mutation rates are advantageous because they may allow for increased adaptability.

Discovery of Enterovirus A71-like nonstructural genomes in recent circulating viruses of the Enterovirus A species.

Enterovirus A71 (EV-A71) is an important nonpolio enterovirus that causes severe neurological complications. In 1998, Taiwan experienced an EV-A71 outbreak that caused 78 deaths. Since then, periodic epidemics of EV-A71 associated with newly emerging strains have occurred.

Foot-and-mouth disease virus type O specific mutations determine RNA-dependent RNA polymerase fidelity and virus attenuation.

Previous studies have shown that the FMDV Asia1/YS/CHA/05 high-fidelity mutagen-resistant variants are attenuated (Zeng et al., 2014). Here, we introduced the same single or multiple-amino-acid substitutions responsible for increased 3D fidelity of type Asia1 FMDV into the type O FMDV O/YS/CHA/05 infectious clone.

Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats.

Single-Cell Virology: On-Chip Investigation of Viral Infection Dynamics.

We have developed a high-throughput, microfluidics-based platform to perform kinetic analysis of viral infections in individual cells. We have analyzed thousands of individual poliovirus infections while varying experimental parameters, including multiplicity of infection, cell cycle, viral genotype, and presence of a drug. We make several unexpected observations masked by population-based experiments: (1) viral and cellular factors contribute uniquely and independently to viral infection kinetics; (2) cellular factors cause wide variation in replication start times; and (3) infections frequently begin later and replication occurs faster than predicted by population measurements.

Modest and Severe Maternal Iron Deficiency in Pregnancy are Associated with Fetal Anaemia and Organ-Specific Hypoxia in Rats.

Prenatal iron-deficiency (ID) is known to alter fetal developmental trajectories, which predisposes the offspring to chronic disease in later life, although the underlying mechanisms remain unclear. Here, we sought to determine whether varying degrees of maternal anaemia could induce organ-specific patterns of hypoxia in the fetuses. Pregnant female Sprague Dawley rats were fed iron-restricted or iron-replete diets to induce a state of moderate (M-ID) or severe ID (S-ID) alongside respective controls.