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The planarian Schmidtea mediterranea is an important model for stem cell research and regeneration, but adequate genome resources for this species have been lacking. Here we report a highly contiguous genome assembly of S. mediterranea , using long-read sequencing and a de novo assembler (MARVEL) enhanced for low-complexity reads. The S. mediterranea genome is highly polymorphic and repetitive, and harbours a novel class of giant retroelements. Furthermore, the genome assembly lacks a number of highly conserved genes, including critical components of the mitotic spindle assembly checkpoint, but planarians maintain checkpoint function. Our genome assembly provides a key model system resource that will be useful for studying regeneration and the evolutionary plasticity of core cell biological mechanisms. An improved genome assembly for Schmidtea mediterranea shows that the genome is highly polymorphic and repetitive, and lacks multiple genes encoding core components of cell biological mechanisms. Genome of a regenerating worm The flatworm Schmidtea mediterranea is an important model for regeneration. Jochen Rink, Eugene Myers and colleagues report an improved genome assembly for the planarian S. mediterranea using long-read sequencing and a new genome assembler called MARVEL. They find that the S. mediterranea genome is highly polymorphic and repetitive, and includes a novel class of giant retroelements. This improved genome assembly provides a useful resource for studying regeneration and the evolution of cell plasticity.

The planarian Schmidtea mediterranea is an important model for stem cell research and regeneration. We report the first highly contiguous genome assembly of Schmidtea mediterranea, using long-read sequencing and a de novo assembler (MARVEL) enhanced for low complexity reads. The S. mediterranea genome is highly polymorphic and repetitive genome, and harbors a novel class of giant Gypsy retroelements. Further, the genome assembly lacks a number of highly conserved genes, including critical components of the mitotic spindle assembly checkpoint, yet planarians maintain checkpoint function. Our genome assembly provides a key model system resource that will be useful for studying regeneration and the evolutionary plasticity of cell biological core mechanisms.

Planarian flatworms undergo continuous internal turnover, wherein old cells are replaced by the division progeny of adult pluripotent stem cells known as neoblasts. How dynamic cell turnover is executed at the organismal scale remains an intriguing question in planarians and biological systems in general. While previous studies have predominantly focused on neoblast proliferation, little is known about the processes that mediate cell loss during tissue homeostasis. Here, we use the planarian epidermis as a model to study the mechanisms of cell removal in Schmidtea mediterranea. We established a covalent dye-labeling assay and image analysis pipeline to quantify the cell turnover rate in the planarian epidermis. Our findings indicate that the ventral epidermis is highly dynamic, with a half-life of the constituent cells of approximately 4.5 days. Using live-imaging and pulse-chase assays, we find that epidermal cells undergo internalization via basal extrusion, followed by a migration towards the intestine and ultimately digestion by intestinal phagocytes. Overall, our studies reveal an intricate homeostatic cell clearance process that may reduce the metabolic costs of high turnover tissues in planarians.Competing Interest StatementThe authors have declared no competing interest.

Polarity is a universal design principle of biological systems that manifests at all organizational scales. Although well understood at the cellular level, the mechanisms that coordinate polarity at the tissue or organismal scale remain poorly understood. Here, we make use of the extreme body plan plasticity of planarian flatworms to probe the multi-scale coordination of polarity. Quantitative analysis of ciliary rootlet orientation in the epidermis reveals a global polarization field with head and tail as independent mediators of anteroposterior (A/P) polarization and the body margin influencing mediolateral (M/L) polarization. Mathematical modeling demonstrates that superposition of separate A/P- and M/L-fields can explain the global polarity field and we identify the core planar cell polarity (PCP) and Ft/Ds pathways as their specific mediators. Overall, our study establishes a mechanistic framework for the multi-scale coordination of planar polarity in planarians and establishes the core PCP and Ft/Ds pathways as evolutionarily conserved 2D-polarization module.

Luminescent reporters are due to their intrinsically high signal-to-noise ratio a powerful labelling tool for microscopy and macroscopic in vivo imaging in biomedical research. However, luminescence signal detection requires longer exposure times than fluorescence imaging and is consequently less suited for applications requiring high temporal resolution or throughput. Here we demonstrate that content aware image restoration can drastically reduce the exposure time requirements in luminescence imaging, thus overcoming one of the major limitations of the technique. Summary Content-aware image restoration (CARE) is extended to luminescence imaging allowing shorter exposure times thus improving temporal resolution and throughput.

IntroductionPeople in need of care or support are severely affected by the COVID-19 pandemic. We lack valid data of long-term assessments. We present a register study to detect the physical and psychosocial impact of the COVID-19 pandemic on people in need of care or support in Bavaria, Germany. To describe the persons’ life conditions comprehensively, we assess the perspectives and needs of the respective care teams too. Results will serve as evidence-based source to manage the pandemic and long-term prevention strategies.Methods and analysisThe ‘Bavarian ambulatory COVID-19 Monitor’ is a multicentre registry including a purposive sample of up to 1000 patient–participants across three study sites in Bavaria. The study group consists of 600 people in need of care with a positive SARS-CoV-2 PCR test. Control group 1 comprises 200 people in need of care with a negative SARS-CoV-2 PCR test, while control group 2 comprises 200 people with a positive SARS-CoV-2 PCR test but are not in need of care. We assess the clinical course of infection, psychosocial aspects and care needs using validated measures. Follow-up is every 6 months for up to 3 years. Additionally, we assess up to 400 people linked to these patient–participants (caregivers, general practitioners (GPs)) for their health and needs. Main analyses are stratified by level of care I–V (I=minor/V=most severe impairment of independence), inpatient/outpatient care setting, sex and age. We use descriptive and inferential statistics to analyse cross-sectional data and changes over time. In qualitative interviews with 60 stakeholders (people in need of care, caregivers, GPs, politicians), we explore interface problems of different functional logics, of everyday and professional perspectives.Ethics and disseminationThe Institutional Review Board of the University Hospital LMU Munich (#20-860) and the study sites (Universities of Wurzburg and Erlangen) approved the protocol. We disseminate the results by peer-reviewed publications, international conferences, governmental reports, etc.

Abstract BACKGROUND: We recently demonstrated that 86% of the patients treated with peripheral nerve stimulation (PNS) for therapy-refractory sacroiliac joint (SIJ) pain were satisfied with the result after 1 year of treatment. OBJECTIVE: To investigate the long-term (up to 4 years) response rate of this novel treatment. METHODS: Sixteen consecutive patients with therapy-refractory SIJ pain were treated with PNS and followed for 4 years in 3 patients, 3 years in 6 patients, and 2 years in 1 patient. Quality of life, pain, and patient satisfaction were assessed using the Oswestry Disability Index 2.0, Visual Analog Scale (VAS), and International Patient Satisfaction Index. RESULTS: Patients reported a pain reduction from 8.8 to 1.6 (VAS) at 1 year (P < .001), and 13 of 14 patients (92.9%) rated the therapy as effective (International Patient Satisfaction Index score ≤ 2). At 2 years, average pain score was 1.9 (P < .001), and 9 of 10 patients (90.0%) considered the treatment a success. At 3 years, 8 of 9 patients (88.9%) were satisfied with the treatment results, reporting an average VAS of 2.0 (P < .005). At 4 years, 2 of 3 patients were satisfied with the treatment results. CONCLUSION: We have shown for the first time that PNS is a successful long-term therapy for SIJ pain.