A multi-pronged scoping review approach to understanding the evolving implementation of the Smallpox and Polio eradication programs: what can other Global Health initiatives learn?

Background: Previous initiatives have aimed to document the history and legacy of the Smallpox Eradication Program (SEP) and the Global Polio Eradication Initiative (GPEI). In this multi-pronged scoping review, we explored the evolution and learning from SEP and GPEI implementation over time at global and country levels to inform other global health programs. // Methods: Three related reviews of literature were conducted; we searched for documents on 1) the SEP and 2) GPEI via online database searches and also conducted global and national-level grey literature searches for documents related to the GPEI in seven purposively selected countries under the Synthesis and Translation of Research and Innovations from Polio Eradication (STRIPE) project. We included documents relevant to GPEI implementation. We conducted full text data analysis and captured data on Expert Recommendations for Implementing Change (ERIC) implementation strategies and principles, tools, outcomes, target audiences, and relevance to global health knowledge areas. // Results: 200 articles were included in the SEP scoping review, 1885 articles in the GPEI scoping review, and 963 documents in the grey literature review. M&E and engagement strategies were consistently translated from the SEP to GPEI; these evolved into newer approaches under the GPEI. Management strategies including setting up robust record systems also carried forward from SEP to GPEI; however, lessons around the need for operational flexibility in applying these strategies at national and sub-national levels did not. Similarly, strategies and lessons around conducting health systems readiness assessments prior to implementation were not carried forward from SEP to GPEI. Differences in the planning and communication strategies between the two programs included fidelity to implementation blueprints appeared to be higher under SEP, and independent monitoring boards and communication and media strategies were more prominent under GPEI. // Conclusions: Linear learning did not always occur between SEP and GPEI; several lessons were lost and had to be re-learned. Implementation and adaptation of strategies in global health programs should be well codified, including information on the contextual, time and stakeholders’ issues that elicit adaptations. Such description can improve the systematic translation of knowledge, and gains in efficiency and effectiveness of future global health programs

Lessons from polio eradication: a synthesis of implementation strategies for global health services delivery from a scoping review

IntroductionThere is limited guidance on strategies for delivering complex global health programs. We synthesized available evidence on implementation strategies and outcomes utilized in the global polio eradication initiative (GPEI) across low and middle-income country (LMIC) settings.MethodsWe nested our scoping review into a literature review conducted as part of a parent study, STRIPE. This review systematically searched PubMed for articles between 1 January 1988 and 25 April 2018 using polio search terms. Strategies from included studies were organized according to the Expert Recommendations for Implementing Change (ERIC) framework, specified using Proctor's framework, and linked to various outcomes (implementation, services delivery, impact).Results152 unique articles fulfilled our inclusion criteria (from 1,885 articles included in the parent study). Only 43 out of the 152 articles described a suitable quantitative study design for evaluating outcomes. We extracted 66 outcomes from the 43 unique studies. Study publication dates ranged from 1989 to 2018 and represented diverse country settings. The most common implementation strategies were developing mechanisms for feedback, monitoring, and evaluation (n = 69); increasing awareness among the population (n = 58); involving stakeholders, workers, and consumers in the implementation efforts (n = 46); conducting workshops (n = 33); using mass media (n = 31); and building robust record systems to capture outcomes (n = 31). Coverage (n = 13) and morbidity (n = 12) were the most frequently identified outcomes, followed by effectiveness (n = 9) and fidelity (n = 6). Feasibility and sustainability were rarely evaluated.ConclusionsThis review provides a catalogue of implementation strategies and outcomes relevant for advancing global health services delivery in LMICs drawing from the GPEI. Implementation strategies reviewed were poorly described and not adequately linked to outcomes. It calls for additional implementation research to unravel the mechanisms of implementation strategies and their effectiveness, and adaptation of the ERIC framework in LMICs

Perineuronal Net Formation and the Critical Period for Neuronal Maturation in the Hypothalamic Arcuate Nucleus

In leptin-deficient ob/ob mice, obesity and diabetes are associated with abnormal development of neurocircuits in the hypothalamic arcuate nucleus (ARC)1, a critical brain area for energy and glucose homoeostasis2,3. Because this developmental defect can be remedied by systemic leptin administration, but only if given before postnatal day 28, a critical period for leptin-dependent development of ARC neurocircuits has been proposed4. In other brain areas, critical-period closure coincides with the appearance of perineuronal nets (PNNs), extracellular matrix specializations that restrict the plasticity of neurons that they enmesh5. Here we report that in humans and rodents, subsets of neurons in the mediobasal aspect of the ARC are enmeshed in PNN-like structures. In mice, these neurons are densely packed into a continuous ring that encircles the junction of the ARC and median eminence, which facilitates exposure of ARC neurons to the circulation. Most of the enmeshed neurons are both γ-aminobutyric acid-ergic and leptin-receptor positive, including a majority of Agouti-related-peptide neurons. Postnatal formation of the PNN-like structures coincides precisely with closure of the critical period for maturation of Agouti-related-peptide neurons and is dependent on input from circulating leptin, because postnatal ob/ob mice have reduced ARC PNN-like material that is restored by leptin administration during the critical period. We conclude that neurons crucial to metabolic homoeostasis are enmeshed in PNN-like structures and organized into a densely packed cluster situated circumferentially at the ARC–median eminence junction, where metabolically relevant humoral signals are sensed

The bracteatus pineapple genome and domestication of clonally propagated crops

Domestication of clonally propagated crops such as pineapple from South America was hypothesized to be a 'one-step operation'. We sequenced the genome of Ananas comosus var. bracteatus CB5 and assembled 513 Mb into 25 chromosomes with 29,412 genes. Comparison of the genomes of CB5, F153 and MD2 elucidated the genomic basis of fiber production, color formation, sugar accumulation and fruit maturation. We also resequenced 89 Ananas genomes. Cultivars 'Smooth Cayenne' and 'Queen' exhibited ancient and recent admixture, while 'Singapore Spanish' supported a one-step operation of domestication. We identified 25 selective sweeps, including a strong sweep containing a pair of tandemly duplicated bromelain inhibitors. Four candidate genes for self-incompatibility were linked in F153, but were not functional in self-compatible CB5. Our findings support the coexistence of sexual recombination and a one-step operation in the domestication of clonally propagated crops. This work guides the exploration of sexual and asexual domestication trajectories in other clonally propagated crops

Automated assembly scaffolding using RagTag elevates a new tomato system for high-throughput genome editing

Advancing crop genomics requires efficient genetic systems enabled by high-quality personalized genome assemblies. Here, we introduce RagTag, a toolset for automating assembly scaffolding and patching, and we establish chromosome-scale reference genomes for the widely used tomato genotype M82 along with Sweet-100, a new rapid-cycling genotype that we developed to accelerate functional genomics and genome editing in tomato. This work outlines strategies to rapidly expand genetic systems and genomic resources in other plant species

Establishing Physalis as a Solanaceae model system enables genetic reevaluation of the inflated calyx syndrome

The highly diverse Solanaceae family contains several widely studied model and crop species. Fully exploring, appreciating, and exploiting this diversity requires additional model systems. Particularly promising are orphan fruit crops in the genus Physalis, which occupy a key evolutionary position in the Solanaceae and capture understudied variation in traits such as inflorescence complexity, fruit ripening and metabolites, disease and insect resistance, self-compatibility, and most notable, the striking inflated calyx syndrome (ICS), an evolutionary novelty found across angiosperms where sepals grow exceptionally large to encapsulate fruits in a protective husk. We recently developed transformation and genome editing in Physalis grisea (groundcherry). However, to systematically explore and unlock the potential of this and related Physalis as genetic systems, high-quality genome assemblies are needed. Here, we present chromosome-scale references for P. grisea and its close relative P. pruinosa and use these resources to study natural and engineered variation in floral traits. We first rapidly identified a natural structural variant in a bHLH gene that causes petal color variation. Further, and against expectations, we found that CRISPR-Cas9 targeted mutagenesis of 11 MADS-box genes, including purported essential regulators of ICS, had no effect on inflation. In a forward genetics screen, we identified huskless, which lacks ICS due to mutation of an AP2-like gene that causes sepals and petals to merge into a single whorl of mixed identity. These resources and findings elevate Physalis to a new Solanaceae model system, and establish a paradigm in the search for factors driving ICS

The genetic and epigenetic landscape of the Arabidopsis centromeres.

Centromeres attach chromosomes to spindle microtubules during cell division and, despite this conserved role, show paradoxically rapid evolution and are typified by complex repeats. We used longread sequencing to generate the Col-CEN Arabidopsis thaliana genome assembly that resolves all five centromeres. The centromeres consist of megabase-scale tandemly repeated satellite arrays, which support CENH3 occupancy and are densely DNA methylated, with satellite variants private to each chromosome. CENH3 preferentially occupies satellites that show least divergence and occur in higherorder repeats. The centromeres are invaded by ATHILA retrotransposons, which disrupt genetic and epigenetic organization. Centromeric crossover recombination is suppressed, yet low levels of meiotic DSBs occur that are regulated by DNA methylation. We propose that Arabidopsis centromeres are evolving via cycles of satellite homogenization and retrotransposon-driven diversification.BBSRC grants BB/S006842/1, BB/S020012/1 and BB/V003984/1

The genome sequence and transcriptome of Potentilla micrantha and their comparison to Fragaria vesca (the woodland strawberry)

Background The genus Potentilla is closely related to that of Fragaria, the economically important strawberry genus. Potentilla micrantha is a species that does not develop berries, but shares numerous morphological and ecological characteristics with F. vesca. These similarities make P. micrantha an attractive choice for comparative genomics studies with F. vesca Findings In this study, the Potentilla micrantha genome was sequenced and annotated, and RNA-Seq data from the different developmental stages of flowering and fruiting were used to develop a set of gene predictions. A 327 Mbp sequence and annotation of the genome of P. micrantha, spanning 2,674 sequence contigs, with an N50 size of 335,712, estimated to cover 80% of the total genome size of the species was developed. The genus Potentilla has a characteristically larger genome size than Fragaria, but the recovered sequence scaffolds were remarkably collinear at the micro-syntenic level with the genome of F. vesca, its closest sequenced relative. A total of 33,602 genes were predicted, and 95.1% of BUSCO genes were complete within the presented sequence. Thus, we argue that the majority of the gene-rich regions of the genome have been sequenced Conclusions Comparisons of RNA-Seq data from the stages of floral and fruit development revealed genes differentially expressed between P. micrantha and F. vesca. The data presented are a valuable resource for future studies of berry development in Fragaria and the Rosaceae and they also shed light on the evolution of genome size and organization in this family

Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission

n rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling