Genetic Diversity of Asclepias Tuberosa in Iowa Prairies

Reduced population size can result in the loss of genetic diversity, which in turn can make organisms more susceptible to environmental challenges. In Iowa less than one percent of the original tallgrass prairie remains, isolated in a few remnant prairies. We are undertaking a long term project to assess the genetic variability in native prairie plants on remnant prairies in Northwest Iowa. We are testing six microsatellite sequences for butterfly milkweed (Asclepias tuberosa) from the Steele Prairie State Preserve, Broken Kettle Grasslands, a private prairie near Cherokee IA, a prairie restoration project on the Dordt College campus and populations from suppliers in Oklahoma and Pennsylvania. We hope to answer the following questions: A) Do nearby remnant prairies share alleles and have similar allelic diversity? B) Is there evidence for inbreeding in remnant populations? C) Is there evidence that plant populations found in local native prairies are genetically distinct from restored prairies and from those originating outside the state of Iowa? Preliminary results suggest that A) Essentially all of the alleles are found in at least 2 of the populations analyzed B) the degree of homozygosity is not higher than expected values and C) the four remnant prairie populations of butterfly milkweed that were tested show little genetic differentiation from each other but show moderate differentiation from commercial seed. The answers to these questions will help inform strategies for prairie conservation and restoration in Iowa and across the Midwest

Blood-Based Immune Profiling Combined with Machine Learning Discriminates Psoriatic Arthritis from Psoriasis Patients

Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions of differentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RA-CD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso

Plasmodium falciparum adapts its investment into replication versus transmission according to the host environment

The malaria parasite life cycle includes asexual replication in human blood, with a proportion of parasites differentiating to gametocytes required for transmission to mosquitoes. Commitment to differentiate into gametocytes, which is marked by activation of the parasite transcription factor ap2-g, is known to be influenced by host factors but a comprehensive model remains uncertain. Here we analyze data from 828 children in Kilifi, Kenya with severe, uncomplicated, and asymptomatic malaria infection over 18 years of falling malaria transmission. We examine markers of host immunity and metabolism, and markers of parasite growth and transmission investment. We find that inflammatory responses associated with reduced plasma lysophosphatidylcholine levels are associated with markers of increased investment in parasite sexual reproduction (i.e., transmission investment) and reduced growth (i.e., asexual replication). This association becomes stronger with falling transmission and suggests that parasites can rapidly respond to the within-host environment, which in turn is subject to changing transmission

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

What increase in modern contraceptive use is needed in FP2020 countries to reach 75% demand satisfied by 2030? An assessment using the Accelerated Transition Method and Family Planning Estimation Model

Background: Sustainable Development Goal 3.7 aims to ensure universal access to sexual and reproductive health services. One suggested benchmark is to have at least 75% of the demand for contraception satisfied with modern methods (DS) in all countries by 2030. The translation of DS-based targets into targets for the modern contraceptive prevalence rate (mCPR) is needed to make targets actionable. Methods: We propose the Accelerated Transition (AT) method for determining the mCPR needed to reach demand-satisfied targets by 2030. The starting point for this method is the projection of DS under “business as usual” using the one-country implementation of the Family Planning Estimation Model (FPEMcountry). For countries in which the DS target is projected to be later than 2030, the AT method assumes that meeting the DS target by 2030 requires an acceleration of the contraceptive use transition such that the DS target, and its associated mCPR, will be reached in 2030 as opposed to the later year. The DS-target-associated mCPR becomes the mCPR target for the year 2030. Results: We apply the AT method to assess progress needed for attaining the 75% DS target for married or in-union women in the world’s poorest countries. For 50 out of 68 countries, we estimate that accelerations are needed, with required mCPR increases ranging from 4.3 to 50.8 percentage points. Conclusions: The AT method quantifies the acceleration needed – as compared to business as usual projections – for a country to meet a family planning target. The method can be used to determine the mCPR needed to reach demand-satisfied targets

Modern contraceptive use, unmet need, and demand satisfied among women of reproductive age who are married or in a union in the focus countries of the Family Planning 2020 initiative: a systematic analysis using the Family Planning Estimation Tool

Background The London Summit on Family Planning in 2012 inspired the Family Planning 2020 (FP2020) initiative and the 120×20 goal of having an additional 120 million women and adolescent girls become users of modern contraceptives in 69 of the world’s poorest countries by the year 2020. Working towards achieving 120×20 is crucial for ultimately achieving the Sustainable Development Goals of universal access and satisfying demand for reproductive health. Thus, a performance assessment is required to determine countries’ progress. Methods An updated version of the Family Planning Estimation Tool (FPET) was used to construct estimates and projections of the modern contraceptive prevalence rate (mCPR), unmet need for, and demand satisfied with modern methods of contraception among women of reproductive age who are married or in a union in the focus countries of the FP2020 initiative. We assessed current levels of family planning indicators and changes between 2012 and 2017. A counterfactual analysis was used to assess if recent levels of mCPR exceeded pre-FP2020 expectations. Findings In 2017, the mCPR among women of reproductive age who are married or in a union in the FP2020 focus countries was 45·7% (95% uncertainty interval [UI] 42·4–49·1), unmet need for modern methods was 21·6% (19·7–23·9), and the demand satisfied with modern methods was 67·9% (64·4–71·1). Between 2012 and 2017 the number of women of reproductive age who are married or in a union who use modern methods increased by 28·8 million (95% UI 5·8–52·5). At the regional level, Asia has seen the mCPR among women of reproductive age who are married or in a union grow from 51·0% (95% UI 48·5–53·4) to 51·8% (47·3–56·5) between 2012 and 2017, which is slow growth, particularly when compared with a change from 23·9% (22·9–25·0) to 28·5% (26·8–30·2) across Africa. At the country level, based on a counterfactual analysis, we found that 61% of the countries that have made a commitment to FP2020 exceeded pre-FP2020 expectations for modern contraceptive use. Country success stories include rapid increases in Kenya, Mozambique, Malawi, Lesotho, Sierra Leone, Liberia, and Chad relative to what was expected in 2012. Interpretation Whereas the estimate of additional users up to 2017 for women of reproductive age who are married or in a union would suggest that the 120×20 goal for all women is overly ambitious, the aggregate outcomes mask the diversity in progress at the country level. We identified countries with accelerated progress, that provide inspiration and guidance on how to increase the use of family planning and inform future efforts, especially in countries where progress has been poor. Funding The Bill & Melinda Gates Foundation, through grant support to the University of Massachusetts Amherst and Avenir Health

The NCA sodium leak channel is required for persistent motor circuit activity that sustains locomotion

Persistent neural activity, a sustained circuit output that outlasts the stimuli, underlies short-term or working memory, as well as various mental representations. Molecular mechanisms that underlie persistent activity are not well understood. Combining in situ whole-cell patch clamping and quantitative locomotion analyses, we show here that the Caenorhabditis elegans neuromuscular system exhibits persistent rhythmic activity, and such an activity contributes to the sustainability of basal locomotion, and the maintenance of acceleration after stimulation. The NALCN family sodium leak channel regulates the resting membrane potential and excitability of invertebrate and vertebrate neurons. Our molecular genetics and electrophysiology analyses show that the C. elegans NALCN, NCA, activates a premotor interneuron network to potentiate persistent motor circuit activity and to sustain C. elegans locomotion. Collectively, these results reveal a mechanism for, and physiological function of, persistent neural activity using a simple animal model, providing potential mechanistic clues for working memory in other systems

Blood-Based Immune Profiling Combined with Machine Learning Discriminates Psoriatic Arthritis from Psoriasis Patients

Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions of differentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RACD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso