A cryptic cycle in haematopoietic niches promotes initiation of malaria transmission and evasion of chemotherapy

Blood stage human malaria parasites may exploit erythropoietic tissue niches and colonise erythroid progenitors; however, the precise influence of the erythropoietic environment on fundamental parasite biology remains unknown. Here we use quantitative approaches to enumerate Plasmodium infected erythropoietic precursor cells using an in vivo rodent model of Plasmodium berghei. We show that parasitised early reticulocytes (ER) in the major sites of haematopoiesis establish a cryptic asexual cycle. Moreover, this cycle is characterised by early preferential commitment to gametocytogenesis, which occurs in sufficient numbers to generate almost all of the initial population of circulating, mature gametocytes. In addition, we show that P. berghei is less sensitive to artemisinin in splenic ER than in blood, which suggests that haematopoietic tissues may enable origins of recrudescent infection and emerging resistance to antimalarials. Continuous propagation in these sites may also provide a mechanism for continuous transmission and infection in malaria endemic regions

The effect of weak inertia in rotating high-aspect-ratio vessel bioreactors

One method to grow artificial body tissue is to place a porous scaffold seeded with cells, known as a tissue construct, into a rotating bioreactor filled with a nutrient-rich fluid. The flow within the bioreactor is affected by the movement of the construct relative to the bioreactor which, in turn, is affected by the hydrodynamical and gravitational forces the construct experiences. The construct motion is thus coupled to the flow within the bioreactor. Over the timescale of a few hours, the construct appears to move in a periodic orbit but, over tens of hours, the construct drifts from periodicity. In the biological literature, this effect is often attributed to the change in density of the construct that occurs via tissue growth. In this paper, we show that weak inertia can cause the construct to drift from its periodic orbit over the same timescale as tissue growth. We consider the coupled flow and construct motion problem within a rotating high-aspect- ratio vessel bioreactor. Using an asymptotic analysis, we investigate the case where the Reynolds number is large but the geometry of the bioreactor yields a small reduced Reynolds number, resulting in a weak inertial effect. In particular, to accurately couple the bioreactor and porous flow regions, we extend the nested boundary layer analysis of Dalwadi et al. (J. Fluid Mech. vol. 798, pp. 88–139, 2016) to include moving walls and the thin region between the porous construct and the bioreactor wall. This allows us to derive a closed system of nonlinear ordinary differential equations for the construct trajectory, from which we show that neglecting inertia results in periodic orbits; we solve the inertia-free problem analytically, calculating the periodic orbits in terms of the system parameters. Using a multiple-scale analysis, we then systematically derive a simpler system of nonlinear ordinary differential equations that describe the long-time drift of the construct due to the effect of weak inertia. We investigate the bifurcations of the construct trajectory behaviour, and the limit cycles that appear when the construct is less dense than the surrounding fluid and the rotation rate is large enough. Thus, we are able to predict when the tissue construct will drift towards a stable limit cycle within the bioreactor and when it will drift out until it hits the bioreactor edg

SNP Discovery and Genomic Architecture of Highly Inbred Leghorn and Fayoumi Chicken Breeds Using Whole Genome Resequencing

Advances in the use of next generation sequencing (NGS) and ability to pool individuals into groups that represent distinct livestock populations has made it possible to examine trait differences between breeds of chicken. The breeds examined are very divergent when compared on their history of laying ability and immune response. The long-term objective is to understand the genetic differences between the Leghorn and Fayoumi breeds for use in developing more productive and disease resistant chickens. Statistical testing of the sequence of the two breeds along with Gene set enrichment analysis (GSEA) to make connections between the genetic variation seen in the NGS data and the breed specific traits of egg laying and heightened immune response can be used to characterize these two breeds. Genetic terms having the highest level of differentiation between the lines appear to group into metabolic processes, with terms over-enriched for immune system process, sexual reproduction, and growth for variants examined between lines. Terms for functions within the Fayoumi and Leghorn populations aligned to immune function and reproductive function, respectively. These results are consistent with known breed phenotypes and provide a means to focus on specific DNA variations and the birds’ genetic diversity that are potentially of more commercial importance

On the boundary layer structure near a highly permeable porous interface

The method of matched asymptotic expansions is used to study the canonical problem of steady laminar flow through a narrow two-dimensional channel blocked by a tight-fitting finite-length highly permeable porous obstacle. We investigate the behaviour of the local flow close to the interface between the single-phase and porous regions (governed by the incompressible Navier--Stokes and Darcy flow equations, respectively). We solve for the flow in these inner regions in the limits of low and high Reynolds number, facilitating an understanding of the nature of the transition from Poiseuille to plug to Poiseuille flow in each of these limits. Significant analytical progress is made in the high-Reynolds-number limit, and we explore in detail the rich boundary layer structure that occurs. We derive general results for the interfacial stress and for the conditions that couple the flow in the outer regions away from the interface. We consider the three-dimensional generalization to unsteady laminar flow through and around a tight-fitting highly permeable cylindrical porous obstacle within a Hele-Shaw cell. For the high-Reynolds-number limit, we give the coupling conditions and interfacial stress in terms of the outer flow variables, allowing information from a nonlinear three-dimensional problem to be obtained by solving a linear two-dimensional problem. Finally, we illustrate the utility of our analysis by considering the specific example of time-dependent forced far-field flow in a Hele-Shaw cell containing a porous cylinder with a circular cross-section. We determine the internal stress within the porous obstacle, which is key for tissue engineering applications, and the interfacial stress on the boundary of the porous obstacle, which has applications to biofilm erosion. In the high-Reynolds-number limit, we demonstrate that the fluid inertia can result in the cylinder experiencing a time-independent net force, even when the far-field forcing is periodic with zero mean

Letters, Lumbees, and Lists

Book 12 of Readings in Bulloch County History is divided into three sections. The first is devoted primarily to correspondence and includes letters from Confederate soldier James Waters, Samuel W. Hodges, and a letter addressed to Rhoda Quinn in Wilkes County. These are followed by notes on the Hodges family by Smith Callaway Banks. The second section of this book is composed of two articles on the Lumbee Indians in Bulloch County, and the third section contains a history of Statesboro High School by Mattie Lively and an early roster of the school’s students and faculty.https://digitalcommons.georgiasouthern.edu/bchs-pubs/1019/thumbnail.jp

Spitzer 24 micron Survey of Debris Disks in the Pleiades

We performed a 24 micron 2 Deg X 1 Deg survey of the Pleiades cluster, using the MIPS instrument on Spitzer. Fifty four members ranging in spectral type from B8 to K6 show 24 micron fluxes consistent with bare photospheres. All Be stars show excesses attributed to free-free emission in their gaseous envelopes. Five early-type stars and four solar-type stars show excesses indicative of debris disks. We find a debris disk fraction of 25 % for B-A members and 10 % for F-K3 ones. These fractions appear intermediate between those for younger clusters and for the older field stars. They indicate a decay with age of the frequency of the dust-production events inside the planetary zone, with similar time scales for solar-mass stars as have been found previously for A-stars.Comment: accepted to Ap

A clinical prediction model for long-term functional outcome after traumatic spinal cord injury based on acute clinical and imaging factors.

To improve clinicians\u27 ability to predict outcome after spinal cord injury (SCI) and to help classify patients within clinical trials, we have created a novel prediction model relating acute clinical and imaging information to functional outcome at 1 year. Data were obtained from two large prospective SCI datasets. Functional independence measure (FIM) motor score at 1 year follow-up was the primary outcome, and functional independence (score ≥ 6 for each FIM motor item) was the secondary outcome. A linear regression model was created with the primary outcome modeled relative to clinical and imaging predictors obtained within 3 days of injury. A logistic model was then created using the dichotomized secondary outcome and the same predictor variables. Model validation was performed using a bootstrap resampling procedure. Of 729 patients, 376 met the inclusion criteria. The mean FIM motor score at 1 year was 62.9 (±28.6). Better functional status was predicted by less severe initial American Spinal Injury Association (ASIA) Impairment Scale grade, and by an ASIA motor score \u3e50 at admission. In contrast, older age and magnetic resonance imaging (MRI) signal characteristics consistent with spinal cord edema or hemorrhage predicted worse functional outcome. The linear model predicting FIM motor score demonstrated an R-square of 0.52 in the original dataset, and 0.52 (95% CI 0.52,0.53) across the 200 bootstraps. Functional independence was achieved by 148 patients (39.4%). For the logistic model, the area under the curve was 0.93 in the original dataset, and 0.92 (95% CI 0.92,0.93) across the bootstraps, indicating excellent predictive discrimination. These models will have important clinical impact to guide decision making and to counsel patients and families

Absence of neuronal autoantibodies in neuropsychiatric systemic lupus erythematosus

International audienceThis study aimed to characterise both neuronal autoantibodies and levels of interferon α, two proposed causative agents in neuropsychiatric systemic lupus erythematosus (NPSLE). Cerebrospinal fluid (CSF) and plasma from 35 patients with systemic lupus erythematosus (SLE; 15 with NPSLE) showed no antibodies against natively expressed N-methyl-D-aspartate receptors (NMDARs), or the surface of live hippocampal neurons. By comparison to controls (n = 104), patients with SLE had antibodies that bound to a peptide representing the extracellular domain of NMDARs (p < 0.0001), however, binding was retained against both rearranged peptides and no peptide (r = 0.85 and r = 0.79, respectively, p < 0.0001). In summary, neuronal-surface reactive antibodies were not detected in NPSLE. Further, while interferon α levels were higher in SLE (p < 0.0001), they lacked specificity for NPSLE. Our findings mandate a search for novel biomarkers in this condition. ANN NEUROL 2020