Population genomics and epigenomics of Spirodela polyrhiza provide insights into the evolution of facultative asexuality.

Many plants are facultatively asexual, balancing short-term benefits with long-term costs of asexuality. During range expansion, natural selection likely influences the genetic controls of asexuality in these organisms. However, evidence of natural selection driving asexuality is limited, and the evolutionary consequences of asexuality on the genomic and epigenomic diversity remain controversial. We analyzed population genomes and epigenomes of Spirodela polyrhiza, (L.) Schleid., a facultatively asexual plant that flowers rarely, revealing remarkably low genomic diversity and DNA methylation levels. Within species, demographic history and the frequency of asexual reproduction jointly determined intra-specific variations of genomic diversity and DNA methylation levels. Genome-wide scans revealed that genes associated with stress adaptations, flowering and embryogenesis were under positive selection. These data are consistent with the hypothesize that natural selection can shape the evolution of asexuality during habitat expansions, which alters genomic and epigenomic diversity levels.

Latex - a potential plant defense against microbes.

Laticifers - among the most common defensive reservoirs in plants - are hypothesized to benefit plant fitness by preventing microbes from entering wounds. I argue that while latex seals wounds, and can suppress microbial growth, direct evidence that these processes benefit plant fitness is scarce. I outline a roadmap for filling this knowledge gap.

Induced responses contribute to rapid adaptation of Spirodela polyrhiza to herbivory by Lymnaea stagnalis.

Herbivory-induced responses in plants are typical examples of phenotypic plasticity, and their evolution is thought to be driven by herbivory. However, direct evidence of the role of induced responses in plant adaptive evolution to herbivores is scarce. Here, we experimentally evolve populations of an aquatic plant (Spirodela polyrhiza, giant duckweed) and its native herbivore (Lymnaea stagnalis, freshwater snail), testing whether herbivory drives rapid adaptive evolution in plant populations using a combination of bioassays, pool-sequencing, metabolite analyses, and amplicon metagenomics. We show that snail herbivory drove rapid phenotypic changes, increased herbivory resistance, and altered genotype frequencies in the plant populations. Additional bioassays suggest that evolutionary changes of induced responses contributed to the rapid increase of plant resistance to herbivory. This study provides direct evidence that herbivory-induced responses in plants can be subjected to selection and have an adaptive role by increasing resistance to herbivores.

Natural rubber reduces herbivory and alters the microbiome below ground.

Laticifers are hypothesized to mediate both plant-herbivore and plant-microbe interactions. However, there is little evidence for this dual function. We investigated whether the major constituent of natural rubber, cis-1,4-polyisoprene, a phylogenetically widespread and economically important latex polymer, alters plant resistance and the root microbiome of the Russian dandelion (Taraxacum koksaghyz) under attack of a root herbivore, the larva of the May cockchafer (Melolontha melolontha). Rubber-depleted transgenic plants lost more shoot and root biomass upon herbivory than normal rubber content near-isogenic lines. Melolontha melolontha preferred to feed on artificial diet supplemented with rubber-depleted rather than normal rubber content latex. Likewise, adding purified cis-1,4-polyisoprene in ecologically relevant concentrations to diet deterred larval feeding and reduced larval weight gain. Metagenomics and metabarcoding revealed that abolishing biosynthesis of natural rubber alters the structure but not the diversity of the rhizosphere and root microbiota (ecto- and endophytes) and that these changes depended on M. melolontha damage. However, the assumption that rubber reduces microbial colonization or pathogen load is contradicted by four lines of evidence. Taken together, our data demonstrate that natural rubber biosynthesis reduces herbivory and alters the plant microbiota, which highlights the role of plant-specialized metabolites and secretory structures in shaping multitrophic interactions.

Advancement of door-to-needle times in acute stroke treatment after repetitive process analysis: never give up!

Background: In acute ischemic stroke, timely treatment is of utmost relevance. Identification of delaying factors and knowledge about challenges concerning hospital structures are crucial for continuous improvement of process times in stroke care. Objective: In this study, we report on our experience in optimizing the door-to-needle time (DNT) at our tertiary care center by continuous quality improvement. Methods: Five hundred forty patients with acute ischemic stroke receiving intravenous thrombolysis (IVT) at Hannover Medical School were consecutively analyzed in two phases. In study phase I, including 292 patients, process times and delaying factors were collected prospectively from May 2015 until September 2017. In study phase II, process times of 248 patients were obtained from January 2019 until February 2021. In each study phase, a new clinical standard operation procedure (SOP) was implemented, considering previously identified delaying factors. Pre- and post-SOP treatment times and delaying factors were analyzed to evaluate the new protocols. Results: In study phase I, SOP I reduced the median DNT by 15 min. The probability to receive treatment within 30 min after admission increased by factor 5.35 [95% confidence interval (CI): 2.46-11.66]. Further development of the SOP with implementation of a mobile thrombolysis kit led to a further decrease of DNT by 5 min in median in study phase II. The median DNT was 29 (25th-75th percentiles: 18-44) min, and the probability to undergo IVT within 15 min after admission increased by factor 4.2 (95% CI: 1.63-10.83) compared with study phase I. Conclusion: Continuous process analysis and subsequent development of targeted workflow adjustments led to a substantial improvement of DNT. These results illustrate that with appropriate vigilance, there is constantly an opportunity for improvement in stroke care.

Can SARS-CoV-2 Infection Lead to Neurodegeneration and Parkinson's Disease?

The SARS-CoV-2 pandemic has affected the daily life of the worldwide population since 2020. Links between the newly discovered viral infection and the pathogenesis of neurodegenerative diseases have been investigated in different studies. This review aims to summarize the literature concerning COVID-19 and Parkinson's disease (PD) to give an overview on the interface between viral infection and neurodegeneration with regard to this current topic. We will highlight SARS-CoV-2 neurotropism, neuropathology and the suspected pathophysiological links between the infection and neurodegeneration as well as the psychosocial impact of the pandemic on patients with PD. Some evidence discussed in this review suggests that the SARS-CoV-2 pandemic might be followed by a higher incidence of neurodegenerative diseases in the future. However, the data generated so far are not sufficient to confirm that COVID-19 can trigger or accelerate neurodegenerative diseases.

[Neuroprotective treatment of tauopathies]. / Neuroprotektive Therapien bei Tauopathien.

Tau pathology is now considered to be the main cause of a wide spectrum of neurodegenerative diseases, which are collectively referred to as tauopathies. These include primary tauopathies, in which tau plays the main role in the pathogenesis as well as secondary tauopathies, such as Alzheimer's disease, in which amyloid beta also plays a substantial role in the disease process in addition to the tau pathology. Primary tauopathies include progressive supranuclear palsy, corticobasal degeneration, Pick's disease and rare hereditary tauopathies, which are referred to as frontotemporal lobar degeneration with microtubule-associated protein tau (MAPT) mutation. Tauopathies differ from each other pathologically by the affected brain regions and cell types as well as by the biochemical characteristics of the aggregated tau protein. Various tau-centered neuroprotective treatment approaches are currently in preclinical and clinical development. They target different mechanisms, including the reduction of tau expression, inhibition of tau aggregation, dissolution of tau aggregates, improvement of cellular mechanisms to eliminate toxic tau species, stabilization of microtubules and prevention of intercellular tau spreading. This review article gives an overview of tauopathies and the current concepts for the development of disease-modifying treatment.

A beta-glucosidase of an insect herbivore determines both toxicity and deterrence of a dandelion defense metabolite.

Gut enzymes can metabolize plant defense compounds and thereby affect the growth and fitness of insect herbivores. Whether these enzymes also influence feeding preference is largely unknown. We studied the metabolization of taraxinic acid ß-D-glucopyranosyl ester (TA-G), a sesquiterpene lactone of the common dandelion (Taraxacum officinale) that deters its major root herbivore, the common cockchafer larva (Melolontha melolontha). We have demonstrated that TA-G is rapidly deglucosylated and conjugated to glutathione in the insect gut. A broad-spectrum M. melolontha ß-glucosidase, Mm_bGlc17, is sufficient and necessary for TA-G deglucosylation. Using cross-species RNA interference, we have shown that Mm_bGlc17 reduces TA-G toxicity. Furthermore, Mm_bGlc17 is required for the preference of M. melolontha larvae for TA-G-deficient plants. Thus, herbivore metabolism modulates both the toxicity and deterrence of a plant defense compound. Our work illustrates the multifaceted roles of insect digestive enzymes as mediators of plant-herbivore interactions.

Plants produce certain substances to fend off attackers like plant-feeding insects. To stop these compounds from damaging their own cells, plants often attach sugar molecules to them. When an insect tries to eat the plant, the plant removes the stabilizing sugar, 'activating' the compounds and making them toxic or foul-tasting. Curiously, some insects remove the sugar themselves, but it is unclear what consequences this has, especially for insect behavior. Dandelions, Taraxacum officinale, make high concentrations of a sugar-containing defense compound in their roots called taraxinic acid ß-D-glucopyranosyl ester, or TA-G for short. TA-G deters the larvae of the Maybug ­ a pest also known as the common cockchafer or the doodlebug ­ from eating dandelion roots. When Maybug larvae do eat TA-G, it is found in their systems without its sugar. However, it is unclear whether it is the plant or the larva that removes the sugar. A second open question is how the sugar removal process affects the behavior of the Maybug larvae. Using chemical analysis and genetic manipulation, Huber et al. investigated what happens when Maybug larvae eat TA-G. This revealed that the acidity levels in the larvae's digestive system deactivate the proteins from the dandelion that would normally remove the sugar from TA-G. However, rather than leaving the compound intact, larvae remove the sugar from TA-G themselves. They do this using a digestive enzyme, known as a beta-glucosidase, that cuts through sugar. Removing the sugar from TA-G made the compound less toxic, allowing the larvae to grow bigger, but it also increased TA-G's deterrent effects, making the larvae less likely to eat the roots. Any organism that eats plants, including humans, must deal with chemicals like TA-G in their food. Once inside the body, enzymes can change these chemicals, altering their effects. This happens with many medicines, too. In the future, it might be possible to design compounds that activate only in certain species, or under certain conditions. Further studies in different systems may aid the development of new methods of pest control, or new drug treatments.

Transgenerational non-genetic inheritance has fitness costs and benefits under recurring stress in the clonal duckweed Spirodela polyrhiza.

Although non-genetic inheritance is thought to play an important role in plant ecology and evolution, evidence for adaptive transgenerational plasticity is scarce. Here, we investigated the consequences of copper excess on offspring defences and fitness under recurring stress in the duckweed Spirodela polyrhiza across multiple asexual generations. Growing large monoclonal populations (greater than 10 000 individuals) for 30 generations under copper excess had negative fitness effects after short and no fitness effect after prolonged growth under recurring stress. These time-dependent growth rates were likely influenced by environment-induced transgenerational responses, as propagating plants as single descendants for 2 to 10 generations under copper excess had positive, negative or neutral effects on offspring fitness depending on the interval between initial and recurring stress (5 to 15 generations). Fitness benefits under recurring stress were independent of flavonoid accumulations, which in turn were associated with altered plant copper concentrations. Copper excess modified offspring fitness under recurring stress in a genotype-specific manner, and increasing the interval between initial and recurring stress reversed these genotype-specific fitness effects. Taken together, these data demonstrate time- and genotype-dependent adaptive and non-adaptive transgenerational responses under recurring stress, which suggests that non-genetic inheritance alters the evolutionary trajectory of clonal plant lineages in fluctuating environments.

Validation of the Parkinson's Disease Caregiver Burden Questionnaire in Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is an atypical Parkinson syndrome with axial akinetic-rigid symptoms, early postural instability, and ocular motor impairments. Patients experience a rapid loss of autonomy and care dependency; thus, caregivers must assist in the activities of daily living early in the course of the disease. Caregiver burden is an extremely important factor in disease management. However, there are no specific questionnaires for assessment of caregiver burden in PSP. This study aims to validate the Parkinson's disease caregiver burden questionnaire (PDCB) as a specific measure of caregiver burden in PSP. PSP patients were assessed by the PSP rating scale, PSP quality-of-life questionnaire (PSP-QoL), Montreal cognitive assessment test (MoCA), and geriatric depression scale (GDS-15). Caregivers filled out the short form 36-health survey, GDS-15, PDCB, and the caregiver burden inventory (CBI). 22 patient caregiver pairs completed the study. PDCB showed a highly significant correlation with the CBI (r 0.911; p < 0.001). Internal reliability of the PDCB measured by Cronbach's alpha was favourable at 0.803. These data support the specificity of the PDCB in PSP caregivers. Future studies with larger sample sizes of PSP patients and caregivers and a multicentric longitudinal design should be performed to gain further insight of caregiver burden in PSP.

A Modified Progressive Supranuclear Palsy Rating Scale.

BACKGROUND: The Progressive Supranuclear Palsy Rating Scale is a prospectively validated physician-rated measure of disease severity for progressive supranuclear palsy. We hypothesized that, according to experts' opinion, individual scores of items would differ in relevance for patients' quality of life, functionality in daily living, and mortality. Thus, changes in the score may not equate to clinically meaningful changes in the patient's status. OBJECTIVE: The aim of this work was to establish a condensed modified version of the scale focusing on meaningful disease milestones. METHODS: Sixteen movement disorders experts evaluated each scale item for its capacity to capture disease milestones (0 = no, 1 = moderate, 2 = severe milestone). Items not capturing severe milestones were eliminated. Remaining items were recalibrated in proportion to milestone severity by collapsing across response categories that yielded identical milestone severity grades. Items with low sensitivity to change were eliminated, based on power calculations using longitudinal 12-month follow-up data from 86 patients with possible or probable progressive supranuclear palsy. RESULTS: The modified scale retained 14 items (yielding 0-2 points each). The items were rated as functionally relevant to disease milestones with comparable severity. The modified scale was sensitive to change over 6 and 12 months and of similar power for clinical trials of disease-modifying therapy as the original scale (achieving 80% power for two-sample t test to detect a 50% slowing with n = 41 and 25% slowing with n = 159 at 12 months). CONCLUSIONS: The modified Progressive Supranuclear Palsy Rating Scale may serve as a clinimetrically sound scale to monitor disease progression in clinical trials and routine. © 2021 International Parkinson and Movement Disorder Society.

Differential localization of flavonoid glucosides in an aquatic plant implicates different functions under abiotic stress.

Flavonoids may mediate UV protection in plants either by screening of harmful radiation or by minimizing the resulting oxidative stress. To help distinguish between these alternatives, more precise knowledge of flavonoid distribution is needed. We used confocal laser scanning microscopy (cLSM) with the "emission fingerprinting" feature to study the cellular and subcellular distribution of flavonoid glucosides in the giant duckweed (Spirodela polyrhiza), and investigated the fitness effects of these compounds under natural UV radiation and copper sulphate addition (oxidative stress) using common garden experiments indoors and outdoors. cLSM "emission fingerprinting" allowed us to individually visualize the major dihydroxylated B-ring-substituted flavonoids, luteolin 7-O-glucoside and luteolin 8-C-glucoside, in cross-sections of the photosynthetic organs. While luteolin 8-C-glucoside accumulated mostly in the vacuoles and chloroplasts of mesophyll cells, luteolin 7-O-glucoside was predominantly found in the vacuoles of epidermal cells. In congruence with its cellular distribution, the mesophyll-associated luteolin 8-C-glucoside increased plant fitness under copper sulphate addition but not under natural UV light treatment, whereas the epidermis-associated luteolin 7-O-glucoside tended to increase fitness under both stresses across chemically diverse genotypes. Taken together, we demonstrate that individual flavonoid glucosides have distinct cellular and subcellular locations and promote duckweed fitness under different abiotic stresses.

Postinfectious Onset of Myasthenia Gravis in a COVID-19 Patient.

Objective: We report the case of a young woman with postinfectious onset of myasthenia gravis after COVID-19 with mild respiratory symptoms and anosmia/ageusia 1 month before admission to our neurological department. Methods: Patient data were derived from medical records of Hannover Medical School, Germany. Written informed consent was obtained from the patient. Results: The 21-year-old female patient presented with subacute, vertically shifted double vision evoked by right sided partial oculomotor paresis and ptosis. About 4 weeks earlier she had suffered from mild respiratory symptoms, aching limbs and head without fever, accompanied by anosmia/ageusia. During the persistence of the latter symptoms for around 10 days the patient had already noticed "tired eyes" and fluctuating double vision. Clinical assessment including a positive test with edrophonium chloride and increased acetylcholine receptor antibodies related the ocular manifestation etiologically to myasthenia gravis. Antibodies (IgA/IgG) against SARS-CoV-2 using three different serological tests (Abbott, DiaSorin, Euroimmun) were detected in serum suggesting this specific coronavirus as previously infectious agent in our patient. The myasthenic syndrome was treated successfully with intravenous immunoglobulins and oral pyridostigmine. Conclusion: This is the first case presentation of postinfectious myasthenia gravis as neurological complication in a COVID-19 patient.

Alexithymia Is Associated with Reduced Quality of Life and Increased Caregiver Burden in Parkinson's Disease.

Parkinson's disease (PD) is the second most frequent neurodegenerative disease of people who are beyond 50 years of age. People with PD (PwP) suffer from a large variety of motor and non-motor symptoms resulting in reduced health-related quality of life (HR-QoL). In the last two decades, alexithymia was identified as an additional non-motor symptom in PD. Alexithymia is defined as a cognitive affective disturbance resulting in difficulty to identify and distinguish feelings from bodily sensations of emotional arousal. In PD, the frequency of patients suffering of alexithymia is increased compared to healthy controls. The aim of the present study was to determine the relationship of alexithymia to HR-QoL of the PwP and caregiver burden of the corresponding caregiver. This cross-sectional questionnaire-based study used disease specific questionnaires for HR-QoL and caregiver burden. In total 119 PwP and their corresponding caregivers were included in the study. HR-QoL of the PwP correlated significantly with alexithymia (p < 0.001), especially the sub-components "identifying feelings" (p < 0.001) and "difficulties describing feelings" (p = 0.001). Caregiver burden also correlated significantly with PwP alexithymia (p < 0.001). However, caregiver burden was associated with sub-components "identifying feelings" (p < 0.008) and "external oriented thinking" (p < 0.004). These data support the importance of alexithymia as a non-motor symptom in PD.

Adapted dandelions trade dispersal for germination upon root herbivore attack.

A plant's offspring may escape unfavourable local conditions through seed dispersal. Whether plants use this strategy to escape insect herbivores is not well understood. Here, we explore how different dandelion (Taraxacum officinale agg.) populations, including diploid outcrossers and triploid apomicts, modify seed dispersal in response to root herbivore attack by their main root-feeding natural enemy, the larvae of the common cockchafer Melolontha melolontha. In a manipulative field experiment, root herbivore attack increased seed dispersal potential through a reduction in seed weight in populations that evolved under high root herbivore pressure, but not in populations that evolved under low pressure. This increase in dispersal potential was independent of plant cytotype, but associated with a reduction in germination rate, suggesting that adapted dandelions trade dispersal for establishment upon attack by root herbivores. Analysis of vegetative growth parameters suggested that the increased dispersal capacity was not the result of stress flowering. In summary, these results suggest that root herbivory selects for an induced increase in dispersal ability in response to herbivore attack. Induced seed dispersal may be a strategy that allows adapted plants to escape from herbivores.

Publisher Correction: Low genetic variation is associated with low mutation rate in the giant duckweed.

The original HTML version of this Article had an incorrect Published online date of 20 March 2019; it should have been 18 March 2019. This has been corrected in the HTML version of the Article. The PDF version was correct from the time of publication.

Low genetic variation is associated with low mutation rate in the giant duckweed.

Mutation rate and effective population size (Ne) jointly determine intraspecific genetic diversity, but the role of mutation rate is often ignored. Here we investigate genetic diversity, spontaneous mutation rate and Ne in the giant duckweed (Spirodela polyrhiza). Despite its large census population size, whole-genome sequencing of 68 globally sampled individuals reveals extremely low intraspecific genetic diversity. Assessed under natural conditions, the genome-wide spontaneous mutation rate is at least seven times lower than estimates made for other multicellular eukaryotes, whereas Ne is large. These results demonstrate that low genetic diversity can be associated with large-Ne species, where selection can reduce mutation rates to very low levels. This study also highlights that accurate estimates of mutation rate can help to explain seemingly unexpected patterns of genome-wide variation.

Separate Pathways Contribute to the Herbivore-Induced Formation of 2-Phenylethanol in Poplar.

Upon herbivory, the tree species western balsam poplar (Populus trichocarpa) produces a variety of Phe-derived metabolites, including 2-phenylethylamine, 2-phenylethanol, and 2-phenylethyl-ß-d-glucopyranoside. To investigate the formation of these potential defense compounds, we functionally characterized aromatic l-amino acid decarboxylases (AADCs) and aromatic aldehyde synthases (AASs), which play important roles in the biosynthesis of specialized aromatic metabolites in other plants. Heterologous expression in Escherichia coli and Nicotiana benthamiana showed that all five AADC/AAS genes identified in the P trichocarpa genome encode active enzymes. However, only two genes, PtAADC1 and PtAAS1, were significantly upregulated after leaf herbivory. Despite a sequence similarity of ∼96%, PtAADC1 and PtAAS1 showed different enzymatic functions and converted Phe into 2-phenylethylamine and 2-phenylacetaldehyde, respectively. The activities of both enzymes were interconvertible by switching a single amino acid residue in their active sites. A survey of putative AADC/AAS gene pairs in the genomes of other plants suggests an independent evolution of this function-determining residue in different plant families. RNA interference -mediated-downregulation of AADC1 in gray poplar (Populus × canescens) resulted in decreased accumulation of 2-phenylethylamine and 2-phenylethyl-ß-d-glucopyranoside, whereas the emission of 2-phenylethanol was not influenced. To investigate the last step of 2-phenylethanol formation, we identified and characterized two P trichocarpa short-chain dehydrogenases, PtPAR1 and PtPAR2, which were able to reduce 2-phenylacetaldehyde to 2-phenylethanol in vitro. In summary, 2-phenylethanol and its glucoside may be formed in multiple ways in poplar. Our data indicate that PtAADC1 controls the herbivore-induced formation of 2-phenylethylamine and 2-phenylethyl-ß-d-glucopyranoside in planta, whereas PtAAS1 likely contributes to the herbivore-induced emission of 2-phenylethanol.