DNA replication dynamics during erythrocytic schizogony in the malaria parasites Plasmodium falciparum and Plasmodium knowlesi

Malaria parasites are unusual, early-diverging protozoans with non-canonical cell cycles. They do not undergo binary fission, but divide primarily by schizogony. This is a syncytial mode of replication involving asynchronous production of multiple nuclei within the same cytoplasm, culminating in a single mass cytokinesis event. The rate and efficiency of parasite replication is fundamentally important to malarial disease, which tends to be severe in hosts with high parasite loads. Here, we have studied for the first time the dynamics of schizogony in two human malaria parasite species, Plasmodium falciparum and Plasmodium knowlesi. These differ in their cell-cycle length, the number of progeny produced and the genome composition, among other factors. Comparing them could therefore yield new information about the parameters and limitations of schizogony. We report that the dynamics of schizogony differ significantly between these two species, most strikingly in the gap phases between successive nuclear replications, which are longer in P. falciparum and shorter, but more heterogenous, in P. knowlesi. In both species, gaps become longer as schizogony progresses, whereas each period of active replication grows shorter. In both species there is also extreme variability between individual cells, with some schizonts producing many more nuclei than others, and some individual nuclei arresting their replication for many hours while adjacent nuclei continue to replicate. The efficiency of schizogony is probably influenced by a complex set of factors in both the parasite and its host cell.

Left atrial invasion of a lung cancer: a case report

Lung cancer is the leading neoplastic form worldwide for both incidence and mortality and represents the largest contributor to new cancer diagnosis. Cardiac extensions of a pulmonary neoplasm are rare and dramatically under-diagnosed because of the extreme variability of clinical presentation and frequently are expression of an advanced-stage primary lung cancer. The invasion often happens through pulmonary veins in absence of a clear respiratory impairment. Symptoms related to the cardiac involvement as the first presentation of a malignant pulmonary neoplasm are very uncommon and related with poor outcome. Here we present a case of invasion of the left atrium of a pulmonary neoplasm with initial cardiac manifestations and a laboratory finding of hypercalcemia.

Towards a Living Lab for Enhanced Thermal Comfort and Air Quality: Analyses of Standard Occupancy, Weather Extremes, and COVID-19 Pandemic

Maintaining indoor environmental (IEQ) quality is a key priority in educational buildings. However, most studies rely on outdoor measurements or evaluate limited spatial coverage and time periods that focus on standard occupancy and environmental conditions which makes it hard to establish causality and resilience limits. To address this, a fine-grained, low-cost, multi-parameter IOT sensor network was deployed to fully depict the spatial heterogeneity and temporal variability of environmental quality in an educational building in Sydney. The building was particularly selected as it represents a multi-use university facility that relies on passive ventilation strategies, and therefore suitable for establishing a living lab for integrating innovative IoT sensing technologies. IEQ analyses focused on 15 months of measurements, spanning standard occupancy of the building as well as the Black Summer bushfires in 2019, and the COVID-19 lockdown. The role of room characteristics, room use, season, weather extremes, and occupancy levels were disclosed via statistical analysis including mutual information analysis of linear and non-linear correlations and used to generate site-specific re-design guidelines. Overall, we found that 1) passive ventilation systems based on manual interventions are most likely associated with sub-optimum environmental quality and extreme variability linked to occupancy patterns, 2) normally closed environments tend to get very unhealthy under periods of extreme pollution and intermittent/protracted disuse, 3) the elevation and floor level in addition to room use were found to be significant conditional variables in determining heat and pollutants accumulation, presumably due to the synergy between local sources and vertical transport mechanisms. Most IEQ inefficiencies and health threats could be likely mitigated by implementing automated controls and smart logics to maintain adequate cross ventilation, prioritizing building airtightness improvement, and appropriate filtration techniques. This study supports the need for continuous and capillary monitoring of different occupied spaces in educational buildings to compensate for less perceivable threats, identify the room for improvement, and move towards healthy and future-proof learning environments.

Numerical uncertainty in analytical pipelines lead to impactful variability in brain networks

The analysis of brain-imaging data requires complex processing pipelines to support findings on brain function or pathologies. Recent work has shown that variability in analytical decisions, small amounts of noise, or computational environments can lead to substantial differences in the results, endangering the trust in conclusions. We explored the instability of results by instrumenting a structural connectome estimation pipeline with Monte Carlo Arithmetic to introduce random noise throughout. We evaluated the reliability of the connectomes, the robustness of their features, and the eventual impact on analysis. The stability of results was found to range from perfectly stable (i.e. all digits of data significant) to highly unstable (i.e. 0 − 1 significant digits). This paper highlights the potential of leveraging induced variance in estimates of brain connectivity to reduce the bias in networks without compromising reliability, alongside increasing the robustness and potential upper-bound of their applications in the classification of individual differences. We demonstrate that stability evaluations are necessary for understanding error inherent to brain imaging experiments, and how numerical analysis can be applied to typical analytical workflows both in brain imaging and other domains of computational sciences, as the techniques used were data and context agnostic and globally relevant. Overall, while the extreme variability in results due to analytical instabilities could severely hamper our understanding of brain organization, it also affords us the opportunity to increase the robustness of findings.

The effects of age, sex, weight and breed on canid methylomes

Unlike genomes, which are static throughout the lifespan of an organism, DNA methylomes are dynamic. To study these dynamics we developed quantitative models that measure the effect of multiple factors on DNA methylomes including, age, sex, weight and genetics. We conducted our study in canids, which prove to be an ideal species to assess epigenetic moderators due to their extreme variability in size and well-characterized genetic structure. We collected buccal swabs from 217 canids (207 domestic dogs and 10 gray wolves) and used targeted bisulfite sequencing to measure methylomes. We also measured genotypes at over one thousand single nucleotide polymorphisms (SNPs). We found that DNA methylomes are strongly associated with age, enabling the construction of epigenetic clocks. We also show that methylomes are strongly impacted by sex, weight and sterilization status, leading to accurate predators of these factors. Methylomes are also affected by genetics and we observe multiple associations between SNP loci and methylated CpGs. Finally, we show that several factors moderate the relationship between epigenetic ages and real ages, such as body weight, which increases epigenetic aging. In conclusion, we demonstrate that the plasticity of DNA methylomes is impacted by myriad genetic and physiological factors, and that DNA methylation biomarkers are accurate predictors of age, sex and sterilization status.

Host galaxy line diagnostics for the candidate tidal disruption events XMMSL1 J111527.3+180638 and PTF09axc

We present results of our analysis of spectra of the host galaxies of the candidate Tidal Disruption Events (TDEs) XMMSL1 J111527.3+180638 and PTF09axc to determine the nature of these transients. We subtract the starlight component from the host galaxy spectra to determine the origin of the nuclear emission lines. Using a Baldwin–Phillips–Terlevich (BPT) diagram we conclude that the host galaxy of XMMSL1 J111527.3+180638 is classified as a Seyfert galaxy, suggesting this transient is likely to be caused by (extreme) variability in the active galactic nucleus. We find that the host of PTF09axc falls in the ’star-forming’ region of the BPT-diagram, implying that the transient is a strong TDE candidate. For both galaxies we find a WISE-colour difference of W1 − W2 < 0.8, which means there is no indication of a dusty torus and therefore an active galactic nucleus, seemingly contradicting our BPT finding for the host of XMMSL1 J111527.3+180638. We discuss possible reasons for the discrepant results obtained through the two methods.

Multimodality Imaging of the Anatomy of Tricuspid Valve

Even though the tricuspid valve is no longer “forgotten”, it still remains poorly understood. In this review, we focus on some controversial and still unclear aspects of tricuspid anatomy as illustrated by noninvasive imaging techniques. In particular, we discuss the anatomical architecture of the so-called tricuspid annulus with its two components (i.e., the mural and the septal annulus), emphasizing the absence of any fibrous “ring” around the right atrioventricular junction. Then we discussed the extreme variability in number and size of leaflets (from two to six), highlighting the peculiarities of the septal leaflet as part of the septal atrioventricular junction (crux cordis). Finally, we describe the similarities and differences between the tricuspid and mitral valve, suggesting a novel terminology for tricuspid leaflets.