Recent Submissions

  • Journal Article

    Changes in shunt, ventilation/perfusion mismatch, and lung aeration with PEEP in patients with ARDS: a prospective single-arm interventional study 

    Karbing, Dan S; Panigada, Mauro; Bottino, Nicola; Spinelli, Elena; Protti, Alessandro; Rees, Stephen E; Gattinoni, Luciano
    Critical Care. 2020 Mar 23;24(1):111
    Abstract Background Several studies have found only a weak to moderate correlation between oxygenation and lung aeration in response to changes in PEEP. This study aimed to investigate the association between changes in shunt, low and high ventilation/perfusion (V/Q) mismatch, and computed tomography-measured lung aeration following an increase in PEEP in patients with ARDS. Methods In this preliminary study, 12 ARDS patients were subjected to recruitment maneuvers followed by setting PEEP at 5 and then either 15 or 20 cmH2O. Lung aeration was measured by computed tomography. Values of pulmonary shunt and low and high V/Q mismatch were calculated by a model-based method from measurements of oxygenation, ventilation, and metabolism taken at different inspired oxygen levels and an arterial blood gas sample. Results Increasing PEEP resulted in reduced values of pulmonary shunt and the percentage of non-aerated tissue, and an increased percentage of normally aerated tissue (p < 0.05). Changes in shunt and normally aerated tissue were significantly correlated (r = − 0.665, p = 0.018). Three distinct responses to increase in PEEP were observed in values of shunt and V/Q mismatch: a beneficial response in seven patients, where shunt decreased without increasing high V/Q; a detrimental response in four patients where both shunt and high V/Q increased; and a detrimental response in a patient with reduced shunt but increased high V/Q mismatch. Non-aerated tissue decreased with increased PEEP in all patients, and hyperinflated tissue increased only in patients with a detrimental response in shunt and V/Q mismatch. Conclusions The results show that improved lung aeration following an increase in PEEP is not always consistent with reduced shunt and V/Q mismatch. Poorly matched redistribution of ventilation and perfusion, between dependent and non-dependent regions of the lung, may explain why patients showed detrimental changes in shunt and V/Q mismatch on increase in PEEP, despite improved aeration. Trial registration ClinicalTrails.gov, NCT04067154. Retrospectively registered on August 26, 2019.
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  • Journal Article

    Comparison of estimators of variance for forest inventories with systematic sampling - results from artificial populations 

    Magnussen, Steen; McRoberts, Ronald E; Breidenbach, Johannes; Nord-Larsen, Thomas; Ståhl, Göran; Fehrmann, Lutz; Schnell, Sebastian
    Forest Ecosystems. 2020 Mar 23;7(1):17
    Abstract Background Large area forest inventories often use regular grids (with a single random start) of sample locations to ensure a uniform sampling intensity across the space of the surveyed populations. A design-unbiased estimator of variance does not exist for this design. Oftentimes, a quasi-default estimator applicable to simple random sampling (SRS) is used, even if it carries with it the likely risk of overestimating the variance by a practically important margin. To better exploit the precision of systematic sampling we assess the performance of five estimators of variance, including the quasi default. In this study, simulated systematic sampling was applied to artificial populations with contrasting covariance structures and with or without linear trends. We compared the results obtained with the SRS, Matérn’s, successive difference replication, Ripley’s, and D’Orazio’s variance estimators. Results The variances obtained with the four alternatives to the SRS estimator of variance were strongly correlated, and in all study settings consistently closer to the target design variance than the estimator for SRS. The latter always produced the greatest overestimation. In populations with a near zero spatial autocorrelation, all estimators, performed equally, and delivered estimates close to the actual design variance. Conclusion Without a linear trend, the SDR and DOR estimators were best with variance estimates more narrowly distributed around the benchmark; yet in terms of the least average absolute deviation, Matérn’s estimator held a narrow lead. With a strong or moderate linear trend, Matérn’s estimator is choice. In large populations, and a low sampling intensity, the performance of the investigated estimators becomes more similar.
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  • Journal Article

    Flare or foe? - Mycobacterium marinum infection mimicking rheumatoid arthritis tenosynovitis: case report and literature review 

    Schubert, Nils; Schill, Tillmann; Plüß, Marlene; Korsten, Peter
    BMC Rheumatology. 2020 Mar 16;4(1):11
    Abstract Background Rheumatoid arthritis is the most common type of inflammatory arthritis affecting about 1% of the population. With the advent of disease-modifying anti-rheumatic drugs the disease can be well controlled in many cases. Patients, however, are prone to developing infectious complications. In rare cases, these can mimic a flare of the underlying itself. Case presentation We report the case of a 45-year-old female patient with a history of seronegative rheumatoid arthritis (RA) who presented with swelling and tenderness of the third metacarpophalangeal joint of the right hand. A flare of her RA was suspected based on clinical and ultrasound findings which showed a tenosynovitis with intense power doppler activity. Her steroid dose was increased but the clinical response to glucocorticoid therapy was very limited. Subsequently, she developed skin manifestations of ‘swimmer’s granuloma’ over the next 2 weeks after first presentation. Finally, a diagnosis of a Mycobacterium marinum infection was established with the help of tissue biopsy and culture, and the patient received appropriate antibiotic treatment with the desired effect. Conclusions This case highlights the difficulty of distinction between infection and inflammation in patients with joint swelling and pain, especially in the age of disease-modifying drugs (DMARDs) and the concomitant risk of atypical infections. A review of the literature identified eight additional published cases, which suggests that Mycobacterium marinum infection is a rare but recognized complication of DMARD therapy. It can mimic a flare of the underlying arthritis potentially leading to diagnostic delays, and requires differential diagnostic methods to identify the pathogen and pave the way for appropriate treatment.
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  • Journal Article

    Overcoming language barriers in paramedic care: a study protocol of the interventional trial ‘DICTUM rescue’ evaluating an app designed to improve communication between paramedics and foreign-language patients 

    Noack, Eva M; Kleinert, Evelyn; Müller, Frank
    BMC Health Services Research. 2020 Mar 18;20(1):223
    Abstract Background It is essential for medical treatment that patients and medical staff can communicate about acute complaints, pre-existing conditions, and the treatment procedure. Misunderstandings can have far-reaching consequences, particularly in time-critical emergencies, which require rapid assessments and decision-making and in which interpreters are rarely available. In this study, we aim to develop a digital communication tool that is to help paramedics communicate with patients who speak hardly any or no German, to monitor its implementation, and to investigate its effect on communication between foreign-language patients and staff. Furthermore, a large amount of data on patients that are cared for in emergency medical services in Germany are collected for the first time. Methods To consider the complex situations of paramedic care and to meet paramedics’ demands, we use an action-oriented research approach to develop the tool. We include the staff of the participating emergency medical service stations and software designers in our approach. The tool is then used and evaluated within an open interventional, non-randomised study with two control groups. Control group 1 (German-speaking patients) and control group 2 (non-German-speaking patients treated without the tool) are recruited starting from the first study phase. In the second study phase, an intervention group is additionally recruited, i.e. non-German-speaking patients with whom the tool is used. The primary outcome of the clinical trial is improved communication with non-German-speaking patients in emergencies by means of the communication tool. The secondary outcome is an improved quality and quantity of the collected information. We exploratively observe on-scene times, demands for emergency physicians, and the usage of the intervention. By recording patients’ clinical parameters, we consider the severity of the health restrictions. Discussion Our study is an innovative research project in paramedic healthcare comprising the development of a digital communication tool to overcome language barriers in emergency medical services and investigating its usability, acceptance, and effect on communication, in short, its usefulness and value for paramedic care. Additonally, we expect to gain comprehensive information on rescue operations. Trial registration German Clinical Trials Register, DRKS00016719, registered 08 February 2019, World Health Organization Trial Registration Data Set, http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00016719
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  • Journal Article

    The complete mitochondrial genome of a parasite at the animal-fungal boundary 

    Sana, Salma; Hardouin, Emilie A; Paley, Richard; Zhang, Tiantian; Andreou, Demetra
    Parasites & Vectors. 2020 Feb 17;13(1):81
    Abstract Background Sphaerothecum destruens is an obligate intracellular fish parasite which has been identified as a serious threat to freshwater fishes. Taxonomically, S. destruens belongs to the order Dermocystida within the class Ichthyosporea (formerly referred to as Mesomycetozoea), which sits at the animal-fungal boundary. Mitochondrial DNA (mtDNA) sequences can be valuable genetic markers for species detection and are increasingly used in environmental DNA (eDNA) based species detection. Furthermore, mtDNA sequences can be used in epidemiological studies by informing detection, strain identification and geographical spread. Methods We amplified the entire mitochondrial (mt) genome of S. destruens in two overlapping long fragments using primers designed based on the cox1, cob and nad5 partial sequences. The mt-genome architecture of S. destruens was then compared to close relatives to gain insights into its evolution. Results The complete mt-genome of Sphaerothecum destruens is 23,939 bp in length and consists of 47 genes including 21 protein-coding genes, 2 rRNA, 22 tRNA and two unidentified open reading frames. The mitochondrial genome of S. destruens is intronless and compact with a few intergenic regions and includes genes that are often missing from animal and fungal mt-genomes, such as, the four ribosomal proteins (small subunit rps13 and 14; large subunit rpl2 and 16), tatC (twin-arginine translocase component C), and ccmC and ccmF (cytochrome c maturation protein ccmC and heme lyase). Conclusions We present the first mt-genome of S. destruens which also represents the first mt-genome for the order Dermocystida. The availability of the mt-genome can assist the detection of S. destruens and closely related parasites in eukaryotic diversity surveys using eDNA and assist epidemiological studies by improving molecular detection and tracking the parasite’s spread. Furthermore, as the only representative of the order Dermocystida, its mt-genome can be used in the study of mitochondrial evolution of the unicellular relatives of animals.
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  • Journal Article

    Unravelling the effects of tropical land use conversion on the soil microbiome 

    Berkelmann, Dirk; Schneider, Dominik; Meryandini, Anja; Daniel, Rolf
    Environmental Microbiome. 2020 Feb 03;15(1):5
    Abstract Background The consequences of deforestation and agricultural treatments are complex and affect all trophic levels. Changes of microbial community structure and composition associated with rainforest conversion to managed systems such as rubber and oil palm plantations have been shown by 16S rRNA gene analysis previously, but functional profile shifts have been rarely addressed. In this study, we analysed the effects of rainforest conversion to different converted land use systems, including agroforestry (“jungle rubber”) and monoculture plantations comprising rubber and oil palm, on soilborne microbial communities by metagenomic shotgun sequencing in Sumatra, Indonesia. Results The diversity of bacteria and archaea decreased whereas diversity of fungi increased in the converted land use systems. The soil microbiome was dominated by bacteria followed by fungi. We detected negative effects of land use conversion on the abundance of Proteobacteria (especially on Rhizobiales and Burkholderiales) and positive effects on the abundance of Acidobacteria and Actinobacteria. These abundance changes were mainly driven by pH, C:N ratio, and Fe, C and N content. With increasing land use intensity, the functional diversity decreased for bacteria, archaea and fungi. Gene abundances of specific metabolisms such as nitrogen metabolism and carbon fixation were affected by land use management practices. The abundance of genes related to denitrification and nitrogen fixation increased in plantations while abundance of genes involved in nitrification and methane oxidation showed no significant difference. Linking taxonomic and functional assignment per read indicated that nitrogen metabolism-related genes were mostly assigned to members of the Rhizobiales and Burkholderiales. Abundances of carbon fixation genes increased also with increasing land use intensity. Motility- and interaction-related genes, especially genes involved in flagellar assembly and chemotaxis genes, decreased towards managed land use systems. This indicated a shift in mobility and interspecific interactions in bacterial communities within these soils. Conclusions Rainforest conversion to managed land use systems drastically affects structure and functional potential of soil microbial communities. The decrease in motility- and interaction-related functions from rainforest to converted land use systems indicated not only a shift in nutrient cycling but also in community dynamics. Fertilizer application and correspondingly higher availability of nutrients in intensively managed plantations lead to an environment in which interspecific interactions are not favoured compared to rainforest soils. We could directly link effects of land management, microbial community structure and functional potential for several metabolic processes. As our study is the first study of this size and detail on soil microbial communities in tropical systems, we provide a basis for further analyses.
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  • Journal Article

    Are scurs in heterozygous polled (Pp) cattle a complex quantitative trait? 

    Gehrke, Lilian J; Capitan, Aurélien; Scheper, Carsten; König, Sven; Upadhyay, Maulik; Heidrich, Kristin; Russ, Ingolf; Seichter, Doris; Tetens, Jens; Medugorac, Ivica; et al.
    Thaller, Georg
    Genetics Selection Evolution. 2020 Feb 07;52(1):6
    Abstract Background Breeding genetically hornless, i.e. polled, cattle provides an animal welfare-friendly and non-invasive alternative to the dehorning of calves. However, the molecular regulation of the development of horns in cattle is still poorly understood. Studying genetic characters such as polledness and scurs, can provide valuable insights into this process. Scurs are hornlike formations that occur occasionally in a wide variety of sizes and forms as an unexpected phenotype when breeding polled cattle. Methods We present a unique dataset of 885 Holstein–Friesian cattle with polled parentage. The horn phenotype was carefully examined, and the phenotypic heterogeneity of the trait is described. Using a direct gene test for polledness, the polled genotype of the animals was determined. Subsequently, the existence of a putative scurs locus was investigated using high-density genotype data of a selected subset of 232 animals and two mapping approaches: mixed linear model-based association analyses and combined linkage disequilibrium and linkage analysis. Results The results of an exploratory data analysis indicated that the expression of scurs depends on age at phenotyping, sex and polled genotype. Scurs were more prevalent in males than in females. Moreover, homozygous polled animals did not express any pronounced scurs and we found that the Friesian polled allele suppresses the development of scurs more efficiently than the Celtic polled allele. Combined linkage and linkage disequilibrium mapping revealed four genome-wide significant loci that affect the development of scurs, one on BTA5 and three on BTA12. Moreover, suggestive associations were detected on BTA16, 18 and 23. The mixed linear model-based association analysis supports the results of the combined linkage and linkage disequilibrium analysis. None of the mapping approaches provided convincing evidence for a monogenic inheritance of scurs. Conclusions Our results contradict the initial and still broadly accepted model for the inheritance of horns and scurs. We hypothesise an oligogenetic model to explain the development of scurs and polledness.
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  • Journal Article

    Motor, cognitive and mobility deficits in 1000 geriatric patients: protocol of a quantitative observational study before and after routine clinical geriatric treatment – the ComOn-study 

    Geritz, Johanna; Maetzold, Sara; Steffen, Maren; Pilotto, Andrea; Corrà, Marta F; Moscovich, Mariana; Rizzetti, Maria C; Borroni, Barbara; Padovani, Alessandro; Alpes, Annekathrin; et al.
    Bang, CorinnaBarcellos, IgorBaron, RalfBartsch, ThorstenBecktepe, Jos SBerg, DanielaBergeest, Lu MBergmann, PhilippBouça-Machado, RaquelDrey, MichaelElshehabi, MoradFarahmandi, SusanFerreira, Joaquim JFranke, AndreFriederich, AnjaGeisler, CorinnaHüllemann, PhilippGierthmühlen, JanneGranert, OliverHeinzel, SebastianHeller, Maren KHobert, Markus AHofmann, MarcJemlich, BjörnKerkmann, LauraKnüpfer, StephanieKrause, KatharinaKress, MaximilianKrupp, SonjaKudelka, JenniferKuhlenbäumer, GregorKurth, RolandLeypoldt, FrankMaetzler, CorinaMaia, Luis FMoewius, AndreasNeumann, PatriciaNiemann, KatharinaOrtlieb, Christian TPaschen, SteffenPham, Minh HPuehler, ThomasRadloff, FranziskaRiedel, ChristianRogalski, MartenSablowsky, SimoneSchanz, Elena MSchebesta, LindaSchicketmüller, AndreasStudt, SimoneThieves, MartinaTönges, LarsUllrich, SebastianUrban, Peter PVila-Chã, NunoWiegard, AnnaWarmerdam, ElkeWarnecke, TobiasWeiss, MichaelWelzel, JuliusHansen, ClintMaetzler, Walter
    BMC Geriatrics. 2020 Feb 06;20(1):45
    Abstract Background Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). Methods This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week’s inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. Discussion This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.
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  • Journal Article

    SMART coils for intracranial aneurysm repair – a single center experience 

    Daniel, Behme; Henrik, Sack; Ioannis, Tsogkas; Veit, Rohde; Marios-Nikos, Psychogios
    BMC Neurology. 2020 Jan 29;20(1):38
    Abstract Background Due to uniform stiffness of standard platinum coils, dense packing of intracranial aneurysms can be difficult to achieve, since stiffer coils can cause microcatheter prolapse or coil migration. SMART coils have a varying softness along the length of the coils to improve deliverability. We report our initial 2 year experience with the SMART coil system, including direct and follow-up results. Methods We performed a retrospective study of all patients who underwent coil embolization of an intracranial aneurysm with SMART coils between July 2016 and August 2018 at our institution. We analyzed clinical and angiographic data before and directly after treatment as well as at 6 months follow-up. Results A total of 49 patients harboring 49 aneurysms were treated; 23 (47%) were ruptured aneurysms. Most aneurysms (57%) were located in the anterior circulation. Median patient age was 55 (31–88), 63% were female. Mean aneurysm size was: neck 3.4 (±1.5), height 6.3 (±2.9) and width 5.2 (±2.3) mm. SMART coils were solely used in 96% of cases. Initial favorable angiographic results were achieved in 45 (92%) of 49 cases, which were stable at 6 months in 26/29 (90%). Thromboembolic complications occurred in 4 (8%) cases without clinical sequelae; microcatheter prolapse occurred in 1 case. No aneurysm rupture or device malfunction was observed. Conclusion The treatment of ruptured and unruptured intracranial aneurysms with SMART Coils was safe and efficacious in our cohort.
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  • Journal Article

    Gene content evolution in the arthropods 

    Thomas, Gregg W C; Dohmen, Elias; Hughes, Daniel S T; Murali, Shwetha C; Poelchau, Monica; Glastad, Karl; Anstead, Clare A; Ayoub, Nadia A; Batterham, Phillip; Bellair, Michelle; et al.
    Binford, Greta JChao, HsuChen, Yolanda HChilders, ChristopherDinh, HuyenDoddapaneni, Harsha VDuan, Jian JDugan, ShannonEsposito, Lauren AFriedrich, MarkusGarb, JessicaGasser, Robin BGoodisman, Michael A DGundersen-Rindal, Dawn EHan, YiHandler, Alfred MHatakeyama, MasatsuguHering, LarsHunter, Wayne BIoannidis, PanagiotisJayaseelan, Joy CKalra, DivyaKhila, AbderrahmanKorhonen, Pasi KLee, Carol ELee, Sandra LLi, YiyuanLindsey, Amelia R IMayer, GeorgMcGregor, Alistair PMcKenna, Duane DMisof, BernhardMunidasa, MalaMunoz-Torres, MonicaMuzny, Donna MNiehuis, OliverOsuji-Lacy, NkechinyerePalli, Subba RPanfilio, Kristen APechmann, MatthiasPerry, TrentPeters, Ralph SPoynton, Helen CPrpic, Nikola-MichaelQu, JiaxinRotenberg, DorithSchal, CobySchoville, Sean DScully, Erin DSkinner, EvetteSloan, Daniel BStouthamer, RichardStrand, Michael RSzucsich, Nikolaus UWijeratne, AselaYoung, Neil DZattara, Eduardo EBenoit, Joshua BZdobnov, Evgeny MPfrender, Michael EHackett, Kevin JWerren, John HWorley, Kim CGibbs, Richard AChipman, Ariel DWaterhouse, Robert MBornberg-Bauer, ErichHahn, Matthew WRichards, Stephen
    Genome Biology. 2020 Jan 23;21(1):15
    Abstract Background Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Results Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. Conclusions These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity.
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  • Journal Article

    Profiling of the muscle-specific dystroglycan interactome reveals the role of Hippo signaling in muscular dystrophy and age-dependent muscle atrophy 

    Yatsenko, Andriy S; Kucherenko, Mariya M; Xie, Yuanbin; Aweida, Dina; Urlaub, Henning; Scheibe, Renate J; Cohen, Shenhav; Shcherbata, Halyna R
    BMC Medicine. 2020 Jan 21;18(1):8
    Abstract Background Dystroglycanopathies are a group of inherited disorders characterized by vast clinical and genetic heterogeneity and caused by abnormal functioning of the ECM receptor dystroglycan (Dg). Remarkably, among many cases of diagnosed dystroglycanopathies, only a small fraction can be linked directly to mutations in Dg or its regulatory enzymes, implying the involvement of other, not-yet-characterized, Dg-regulating factors. To advance disease diagnostics and develop new treatment strategies, new approaches to find dystroglycanopathy-related factors should be considered. The Dg complex is highly evolutionarily conserved; therefore, model genetic organisms provide excellent systems to address this challenge. In particular, Drosophila is amenable to experiments not feasible in any other system, allowing original insights about the functional interactors of the Dg complex. Methods To identify new players contributing to dystroglycanopathies, we used Drosophila as a genetic muscular dystrophy model. Using mass spectrometry, we searched for muscle-specific Dg interactors. Next, in silico analyses allowed us to determine their association with diseases and pathological conditions in humans. Using immunohistochemical, biochemical, and genetic interaction approaches followed by the detailed analysis of the muscle tissue architecture, we verified Dg interaction with some of the discovered factors. Analyses of mouse muscles and myocytes were used to test if interactions are conserved in vertebrates. Results The muscle-specific Dg complexome revealed novel components that influence the efficiency of Dg function in the muscles. We identified the closest human homologs for Dg-interacting partners, determined their significant enrichment in disease-associations, and verified some of the newly identified Dg interactions. We found that Dg associates with two components of the mechanosignaling Hippo pathway: the WW domain-containing proteins Kibra and Yorkie. Importantly, this conserved interaction manages adult muscle size and integrity. Conclusions The results presented in this study provide a new list of muscle-specific Dg interactors, further analysis of which could aid not only in the diagnosis of muscular dystrophies, but also in the development of new therapeutics. To regulate muscle fitness during aging and disease, Dg associates with Kibra and Yorkie and acts as a transmembrane Hippo signaling receptor that transmits extracellular information to intracellular signaling cascades, regulating muscle gene expression.
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  • Journal Article

    Effect of the micro-environment on α-synuclein conversion and implication in seeded conversion assays 

    Candelise, Niccolo; Schmitz, Matthias; Thüne, Katrin; Cramm, Maria; Rabano, Alberto; Zafar, Saima; Stoops, Erik; Vanderstichele, Hugo; Villar-Pique, Anna; Llorens, Franc; et al.
    Zerr, Inga
    Translational Neurodegeneration. 2020 Jan 17;9(1):5
    Abstract Background α-Synuclein is a small soluble protein, whose physiological function in the healthy brain is poorly understood. Intracellular inclusions of α-synuclein, referred to as Lewy bodies (LBs), are pathological hallmarks of α-synucleinopathies, such as Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). Main body Understanding of the molecular basis as well as the factors or conditions promoting α-synuclein misfolding and aggregation is an important step towards the comprehension of pathological mechanism of α-synucleinopathies and for the development of efficient therapeutic strategies. Based on the conversion and aggregation mechanism of α-synuclein, novel diagnostic tests, such as protein misfolding seeded conversion assays, e.g. the real-time quaking-induced conversion (RT-QuIC), had been developed. In diagnostics, α-synuclein RT-QuIC exhibits a specificity between 82 and 100% while the sensitivity varies between 70 and 100% among different laboratories. In addition, the α-synuclein RT-QuIC can be used to study the α-synuclein-seeding-characteristics of different α-synucleinopathies and to differentiate between DLB and PD. Conclusion The variable diagnostic accuracy of current α-synuclein RT-QuIC occurs due to different protocols, cohorts and material etc.. An impact of micro-environmental factors on the α-synuclein aggregation and conversion process and the occurrence and detection of differential misfolded α-synuclein types or strains might underpin the clinical heterogeneity of α-synucleinopathies.
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  • Journal Article

    Transcriptome of pleuropodia from locust embryos supports that these organs produce enzymes enabling the larva to hatch 

    Konopová, Barbora; Buchberger, Elisa; Crisp, Alastair
    Frontiers in Zoology. 2020 Jan 16;17(1):4
    Abstract Background Pleuropodia are limb-derived glandular organs that transiently appear on the first abdominal segment in embryos of insects from majority of “orders”. They are missing in the genetic model Drosophila and little is known about them. Experiments carried out on orthopteran insects 80 years ago indicated that the pleuropodia secrete a “hatching enzyme” that digests the serosal cuticle to enable the larva to hatch, but evidence by state-of-the-art molecular methods is missing. Results We used high-throughput RNA-sequencing to identify the genes expressed in the pleuropodia of the locust Schistocerca gregaria (Orthoptera). First, using transmission electron microscopy we studied the development of the pleuropodia during 11 stages of the locust embryogenesis. We show that the glandular cells differentiate and start secreting just before the definitive dorsal closure of the embryo and the secretion granules outside the cells become more abundant prior to hatching. Next, we generated a comprehensive embryonic reference transcriptome for the locust and used it to study genome wide gene expression across ten morphologicaly defined stages of the pleuropodia. We show that when the pleuropodia have morphological markers of functional organs and produce secretion, they are primarily enriched in transcripts associated with transport functions. They express genes encoding enzymes capable of digesting cuticular protein and chitin. These include the potent cuticulo-lytic Chitinase 5, whose transcript rises just before hatching. Unexpected finding was the enrichment in transcripts for immunity-related enzymes. This indicates that the pleuropodia are equipped with epithelial immunity similarly as barrier epithelia in postembryonic stages. Conclusions These data provide transcriptomic support for the historic hypothesis that pleuropodia produce cuticle-degrading enzymes and function in hatching. They may also have other functions, such as facilitation of embryonic immune defense. By the genes that they express the pleuropodia are specialized embryonic organs and apparently an important though neglected part of insect physiology.
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  • Journal Article

    Pre-treatment with the viral Toll-like receptor 3 agonist poly(I:C) modulates innate immunity and protects neutropenic mice infected intracerebrally with Escherichia coli 

    Ribes, Sandra; Arcilla, Christa; Ott, Martina; Schütze, Sandra; Hanisch, Uwe-Karsten; Nessler, Stefan; Nau, Roland
    Journal of Neuroinflammation. 2020 Jan 17;17(1):24
    Abstract Background Individuals with impaired immunity are more susceptible to infections than immunocompetent subjects. No vaccines are currently available to induce protection against E. coli meningoencephalitis. This study evaluated the potential of poly(I:C) pre-treatment to induce trained immunity. Poly(I:C) was administered as a non-specific stimulus of innate immune responses to protect immunocompetent and neutropenic wild-type mice from a subsequent challenge by the intracranial injection of E. coli K1. Methods Three days prior to infection, mice received an intraperitoneal injection of poly(I:C) or vehicle. Kaplan-Meier survival curves were analyzed. In short-term experiments, bacterial titers and the inflammatory response were characterized in the blood, cerebellum, and spleen homogenates. NK cell subpopulations in the brain and spleen were analyzed by flow cytometry. Numbers of microglia and activation scores were evaluated by histopathology. Results Pre-treatment with 200 μg poly(I:C) increased survival time, reduced mortality, and enhanced bacterial clearance in the blood, cerebellum, and spleen at early infection in neutropenic mice. Poly(I:C)-mediated protection correlated with an augmented number of NK cells (CD45+NK1.1+CD3−) and Iba-1+ microglial cells and a higher production of IFN-γ in the brain. In the spleen, levels of CCL5/RANTES and IFN-γ were increased and sustained in surviving poly(I:C)-treated animals for 14 days after infection. In immunocompetent animals, survival time was not significantly prolonged in poly(I:C)-treated animals although poly(I:C) priming reduced brain bacterial concentrations compared with vehicle-injected animals at early infection. Conclusions Pre-treatment with the viral TLR3 agonist poly(I:C) modulated innate immune responses and strengthened the resistance of neutropenic mice against E. coli K1 meningoencephalitis.
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  • Journal Article

    Evaluation of sex differences in dietary behaviours and their relationship with cardiovascular risk factors: a cross-sectional study of nationally representative surveys in seven low- and middle-income countries 

    McKenzie, Briar L; Santos, Joseph A; Geldsetzer, Pascal; Davies, Justine; Manne-Goehler, Jennifer; Gurung, Mongal S; Sturua, Lela; Gathecha, Gladwell; Aryal, Krishna K; Tsabedze, Lindiwe; et al.
    Andall-Brereton, GlennisBärnighausen, TillAtun, RifatVollmer, SebastianWoodward, MarkJaacks, Lindsay MWebster, Jacqui
    Nutrition Journal. 2020 Jan 13;19(1):3
    Abstract Background Cardiovascular diseases (CVD) are the leading causes of death for men and women in low-and-middle income countries (LMIC). The nutrition transition to diets high in salt, fat and sugar and low in fruit and vegetables, in parallel with increasing prevalence of diet-related CVD risk factors in LMICs, identifies the need for urgent action to reverse this trend. To aid identification of the most effective interventions it is crucial to understand whether there are sex differences in dietary behaviours related to CVD risk. Methods From a dataset of 46 nationally representative surveys, we included data from seven countries that had recorded the same dietary behaviour measurements in adults; Bhutan, Eswatini, Georgia, Guyana, Kenya, Nepal and St Vincent and the Grenadines (2013–2017). Three dietary behaviours were investigated: positive salt use behaviour (SUB), meeting fruit and vegetable (F&V) recommendations and use of vegetable oil rather than animal fats in cooking. Generalized linear models were used to investigate the association between dietary behaviours and waist circumference (WC) and undiagnosed and diagnosed hypertension and diabetes. Interaction terms between sex and dietary behaviour were added to test for sex differences. Results Twenty-four thousand three hundred thirty-two participants were included. More females than males reported positive SUB (31.3 vs. 27.2% p-value < 0.001), yet less met F&V recommendations (13.2 vs. 14.8%, p-value< 0.05). The prevalence of reporting all three dietary behaviours in a positive manner was 2.7%, varying by country, but not sex. Poor SUB was associated with a higher prevalence of undiagnosed hypertension for females (13.1% vs. 9.9%, p-value = 0.04), and a higher prevalence of undiagnosed diabetes for males (2.4% vs. 1.5%, p-value = 0.02). Meeting F&V recommendations was associated with a higher prevalence of high WC (24.4% vs 22.6%, p-value = 0.01), but was not associated with undiagnosed or diagnosed hypertension or diabetes. Conclusion Interventions to increase F&V intake and positive SUBs in the included countries are urgently needed. Dietary behaviours were not notably different between sexes. However, our findings were limited by the small proportion of the population reporting positive dietary behaviours, and further research is required to understand whether associations with CVD risk factors and interactions by sex would change as the prevalence of positive behaviours increases.
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  • Journal Article

    Enhanced genome assembly and a new official gene set for Tribolium castaneum 

    Herndon, Nicolae; Shelton, Jennifer; Gerischer, Lizzy; Ioannidis, Panos; Ninova, Maria; Dönitz, Jürgen; Waterhouse, Robert M; Liang, Chun; Damm, Carsten; Siemanowski, Janna; et al.
    Kitzmann, PeterUlrich, JuliaDippel, StefanOberhofer, GeorgHu, YonggangSchwirz, JonasSchacht, MagdalenaLehmann, SabrinaMontino, AlicePosnien, NicoGurska, DanielaHorn, ThorstenSeibert, JanVargas Jentzsch, Iris MPanfilio, Kristen ALi, JianweiWimmer, Ernst AStappert, DominikRoth, SiegfriedSchröder, ReinhardPark, YoonseongSchoppmeier, MichaelChung, Ho-RyunKlingler, MartinKittelmann, SebastianFriedrich, MarkusChen, RuiAltincicek, BoranVilcinskas, AndreasZdobnov, EvgenyGriffiths-Jones, SamRonshaugen, MatthewStanke, MarioBrown, Sue JBucher, Gregor
    BMC Genomics. 2020 Jan 14;21(1):47
    Abstract Background The red flour beetle Tribolium castaneum has emerged as an important model organism for the study of gene function in development and physiology, for ecological and evolutionary genomics, for pest control and a plethora of other topics. RNA interference (RNAi), transgenesis and genome editing are well established and the resources for genome-wide RNAi screening have become available in this model. All these techniques depend on a high quality genome assembly and precise gene models. However, the first version of the genome assembly was generated by Sanger sequencing, and with a small set of RNA sequence data limiting annotation quality. Results Here, we present an improved genome assembly (Tcas5.2) and an enhanced genome annotation resulting in a new official gene set (OGS3) for Tribolium castaneum, which significantly increase the quality of the genomic resources. By adding large-distance jumping library DNA sequencing to join scaffolds and fill small gaps, the gaps in the genome assembly were reduced and the N50 increased to 4753kbp. The precision of the gene models was enhanced by the use of a large body of RNA-Seq reads of different life history stages and tissue types, leading to the discovery of 1452 novel gene sequences. We also added new features such as alternative splicing, well defined UTRs and microRNA target predictions. For quality control, 399 gene models were evaluated by manual inspection. The current gene set was submitted to Genbank and accepted as a RefSeq genome by NCBI. Conclusions The new genome assembly (Tcas5.2) and the official gene set (OGS3) provide enhanced genomic resources for genetic work in Tribolium castaneum. The much improved information on transcription start sites supports transgenic and gene editing approaches. Further, novel types of information such as splice variants and microRNA target genes open additional possibilities for analysis.
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  • Journal Article

    Global exponential stability and existence of periodic solutions of fuzzy wave equations 

    Liu, Wei; Lou, Yimin
    Advances in Difference Equations. 2020 Jan 07;2020(1):13
    Abstract In this paper, the global exponential stability and the existence of periodic solutions of fuzzy wave equations are investigated. By variable substitution the system of partial differential equations (PDEs) is transformed from second order to first order. Some sufficient conditions that ensure the global exponential stability and the existence of periodic solution of the system are obtained by an analysis that uses a suitable Lyapunov functional. In addition, a concrete example is given to show the effectiveness of the results.
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  • Journal Article

    Towards the restoration of the Mesoamerican Biological Corridor for large mammals in Panama: comparing multi-species occupancy to movement models 

    Meyer, Ninon F V; Moreno, Ricardo; Reyna-Hurtado, Rafael; Signer, Johannes; Balkenhol, Niko
    Movement Ecology. 2020 Jan 09;8(1):3
    Abstract Background Habitat fragmentation is a primary driver of wildlife loss, and the establishment of biological corridors is a conservation strategy to mitigate this problem. Identifying areas with high potential functional connectivity typically relies on the assessment of landscape resistance to movement. Many modeling approaches exist to estimate resistance surfaces but to date only a handful of studies compared the outputs resulting from different methods. Moreover, as many species are threatened by fragmentation, effective biodiversity conservation requires that corridors simultaneously meet the needs of multiple species. While many corridor planning initiatives focus on single species, we here used a combination of data types and analytical approaches to identify and compare corridors for several large mammal species within the Panama portion of the Mesoamerican Biological Corridor. Methods We divided a large mammal assemblage into two groups depending on the species sensitivity to habitat disturbance. We subsequently used cost-distance methods to produce multi-species corridors which were modeled on the basis of (i) occupancy of nine species derived from camera trapping data collected across Panama, and (ii) step selection functions based on GPS telemetry data from white-lipped peccary Tayassu pecari, puma Puma concolor, and ocelot Leopardus pardalis. In addition to different data sources and species groups, we also used different transformation curves to convert occupancy and step-selection results into landscape resistance values. Results Corridors modeled differed between sensitive and tolerant species, between the data sets, and between the transformation curves. There were more corridors identified for tolerant species than for sensitive species. For tolerant species, several corridors developed with occupancy data overlapped with corridors produced with step selection functions, but this was not the case for sensitive species. Conclusion Our study represents the first comparison of multispecies corridors parametrized with step selection functions versus occupancy models. Given the wide variability in output corridors, our findings underscore the need to consider the ecological requirements of several species. Our results also suggest that occupancy models can be used for estimating connectivity of generalist species. Finally, this effort allowed to identify important corridors within the MBC (i) at a country scale and (ii) for several species simultaneously to accurately inform the local authorities in conservation planning. The approach we present is reproducible in other sites and/or for other species.
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  • Journal Article

    Eumelanin and pheomelanin pigmentation in mollusc shells may be less common than expected: insights from mass spectrometry 

    Affenzeller, Susanne; Wolkenstein, Klaus; Frauendorf, Holm; Jackson, Daniel J.
    Frontiers in Zoology. 2019 Dec 23;16(1):47
    Abstract Background The geometric patterns that adorn the shells of many phylogenetically disparate molluscan species are comprised of pigments that span the visible spectrum. Although early chemical studies implicated melanin as a commonly employed pigment, surprisingly little evidence generated with more recent and sensitive techniques exists to support these observations. Results Here we present the first mass spectrometric investigations for the presence of eumelanin and pheomelanin in 13 different molluscan species from three conchiferan classes: Bivalvia, Cephalopoda and Gastropoda. In the bivalve Mytilus edulis we demonstrate that eumelanin mainly occurs in the outermost, non-mineralised and highly pigmented layer of the shell (often referred to as the periostracum). We also identified eumelanin in the shells of the cephalopod Nautilus pompilius and the marine gastropods Clanculus pharaonius and Steromphala adriatica. In the terrestrial gastropod Cepaea nemoralis we verify the presence of pheomelanin in a mollusc shell for the first time. Surprisingly, in a large number of brown/black coloured shells we did not find any evidence for either type of melanin. Conclusions We recommend methods such as high-performance liquid chromatography with mass spectrometric detection for the analysis of complex biological samples to avoid potential false-positive identification of melanin. Our results imply that many molluscan species employ as yet unidentified pigments to pattern their shells. This has implications for our understanding of how molluscs evolved the ability to pigment and pattern their shells, and for the identification of the molecular mechanisms that regulate these processes.
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  • Journal Article

    TRITEX: chromosome-scale sequence assembly of Triticeae genomes with open-source tools 

    Monat, Cécile; Padmarasu, Sudharsan; Lux, Thomas; Wicker, Thomas; Gundlach, Heidrun; Himmelbach, Axel; Ens, Jennifer; Li, Chengdao; Muehlbauer, Gary J; Schulman, Alan H; et al.
    Waugh, RobbieBraumann, IlkaPozniak, CurtisScholz, UweMayer, Klaus F XSpannagl, ManuelStein, NilsMascher, Martin
    Genome Biology. 2019 Dec 18;20(1):284
    Abstract Chromosome-scale genome sequence assemblies underpin pan-genomic studies. Recent genome assembly efforts in the large-genome Triticeae crops wheat and barley have relied on the commercial closed-source assembly algorithm DeNovoMagic. We present TRITEX, an open-source computational workflow that combines paired-end, mate-pair, 10X Genomics linked-read with chromosome conformation capture sequencing data to construct sequence scaffolds with megabase-scale contiguity ordered into chromosomal pseudomolecules. We evaluate the performance of TRITEX on publicly available sequence data of tetraploid wild emmer and hexaploid bread wheat, and construct an improved annotated reference genome sequence assembly of the barley cultivar Morex as a community resource.
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