Items 1-20 of 550

    • 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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      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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      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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      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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      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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    • Journal Article

      The prognostic capacities of CBP and p300 in locally advanced rectal cancer 

      Rühlmann, Felix; Windhof-Jaidhauser, Indra M; Menze, Cornelius; Beißbarth, Tim; Bohnenberger, Hanibal; Ghadimi, Michael; Dango, Sebastian
      World Journal of Surgical Oncology. 2019 Dec 19;17(1):224
      Abstract Background CREB-binding protein (CBP) and p300 represent histone acetyltransferases (HATs) and transcriptional coactivators that play essential roles in tumour initiation and progression. Both proteins are generally thought to function as tumour suppressors, although their distinct roles in colorectal cancer (CRC) remain inconsistent and ambiguous. Thus, we analysed the expression of these two HATs in human tissue samples from patients with locally advanced rectal cancer via immunohistochemistry and evaluated their potential impacts on future CRC diagnosis and treatment. Methods In our analysis, we included ninety-three (n = 93) patients diagnosed with adenocarcinoma in the upper third of the rectum. None of the patients received preoperative chemoradiotherapy, but the patients did undergo primary resection of the tumour within the phase II GAST-05 trial. By using H-scores, the expression of both proteins was visualised via immunohistochemistry in resected specimens from the patients. CBP and p300 expression were correlated with clinical and follow-up data. Results Our analysis showed that high expression of CBP was significantly associated with prolonged cancer-specific survival (CSS; p = 0.002). In univariate analysis, CBP was an independent prognostic parameter for CSS (p = 0.042). High nuclear CBP expression was observed in two-thirds of patients. In contrast, we could not find any significant correlation between the expression of p300 and cancer-specific survival in this cohort of patients (p = 0.09). We did not observe any cooperation between CBP and p300 in our analysis. Conclusions High expression of CBP was significantly associated with improved oncological outcomes. This finding could help to stratify patients in the future for CRC treatment. Histone deacetylase (HDAC) inhibitors are increasingly playing a role in oncological treatment and could additionally become therapeutic options in CRC. Our findings need to be further evaluated and verified in future clinical analyses.
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    • Journal Article

      Read-SpaM: assembly-free and alignment-free comparison of bacterial genomes with low sequencing coverage 

      Lau, Anna-Katharina; Dörrer, Svenja; Leimeister, Chris-André; Bleidorn, Christoph; Morgenstern, Burkhard
      BMC Bioinformatics. 2019 Dec 17;20(Suppl 20):638
      Abstract Background In many fields of biomedical research, it is important to estimate phylogenetic distances between taxa based on low-coverage sequencing reads. Major applications are, for example, phylogeny reconstruction, species identification from small sequencing samples, or bacterial strain typing in medical diagnostics. Results We adapted our previously developed software program Filtered Spaced-Word Matches (FSWM) for alignment-free phylogeny reconstruction to take unassembled reads as input; we call this implementation Read-SpaM. Conclusions Test runs on simulated reads from semi-artificial and real-world bacterial genomes show that our approach can estimate phylogenetic distances with high accuracy, even for large evolutionary distances and for very low sequencing coverage.
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    • Journal Article

      PedCAPNETZ – prospective observational study on community acquired pneumonia in children and adolescents 

      Wetzke, Martin; Kopp, Matthias V; Seidenberg, Jürgen; Vogelberg, Christian; Ankermann, Tobias; Happle, Christine; Voigt, Gesche; Köster, Holger; Illig, Thomas; Lex, Christiane; et al.
      Schuster, AntjePanning, MarcusBarten, GritRohde, GernotWelte, TobiasHansen, Gesine
      BMC Pulmonary Medicine. 2019 Dec 09;19(1):238
      Abstract Background Pediatric community acquired pneumonia (pedCAP) is one of the leading causes for childhood morbidity accounting for up to 20% of pediatric hospital admissions in high income countries. In spite of its high morbidity, updated epidemiological and pathogen data after introduction of preventive vaccination and novel pathogen screening strategies are limited. Moreover, there is a need for validated recommendations on diagnostic and treatment regimens in pedCAP. Through collection of patient data and analysis of pathogen and host factors in a large sample of unselected pedCAP patients in Germany, we aim to address and substantially improve this situation. Methods pedCAPNETZ is an observational, multi-center study on pedCAP. Thus far, nine study centers in hospitals, outpatient clinics and practices have been initiated and more than 400 patients with radiologically confirmed pneumonia have been enrolled, aiming at a total of 1000 study participants. Employing an online data base, information on disease course, treatment as well as demographical and socioeconomical data is recorded. Patients are followed up until day 90 after enrollment; Comprehensive biosample collection and a central pedCAPNETZ biobank allow for in-depth analyses of pathogen and host factors. Standardized workflows to assure sample logistics and data management in more than fifteen future study centers have been established. Discussion Through comprehensive epidemiological, clinical and biological analyses, pedCAPNETZ fills an important gap in pediatric and infection research. To secure dissemination of the registry, we will raise clinical and scientific awareness at all levels. We aim at participating in decision making processes for guidelines and prevention strategies. Ultimately, we hope the results of the pedCAPNETZ registry will help to improve care and quality of life in pedCAP patients in the future.
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    • Journal Article

      Pharmacotherapy of borderline personality disorder: what has changed over two decades? A retrospective evaluation of clinical practice 

      Timäus, Charles; Meiser, Miriam; Bandelow, Borwin; Engel, Kirsten R; Paschke, Anne M; Wiltfang, Jens; Wedekind, Dirk
      BMC Psychiatry. 2019 Dec 12;19(1):393
      Abstract Background The purpose of this study was to assess the pharmacological treatment strategies of inpatients with borderline personality disorder between 2008 and 2012. Additionally, we compared pharmacotherapy during this period to a previous one (1996 to 2004). Methods Charts of 87 patients with the main diagnosis of borderline personality disorder receiving inpatient treatment in the University Medical Center of Goettingen, Germany, between 2008 and 2012 were evaluated retrospectively. For each inpatient treatment, psychotropic drug therapy including admission and discharge medication was documented. We compared the prescription rates of the interval 2008–2012 with the interval 1996–2004. Results 94% of all inpatients of the interval 2008–2012 were treated with at least one psychotropic drug at time of discharge. All classes of psychotropic drugs were applied. We found high prescription rates of naltrexone (35.6%), quetiapine (19.5%), mirtazapine (18.4%), sertraline (12.6%), and escitalopram (11.5%). Compared to 1996–2004, rates of low-potency antipsychotics, tri−/tetracyclic antidepressants and mood stabilizers significantly decreased while usage of naltrexone significantly increased. Conclusions In inpatient settings, pharmacotherapy is still highly prevalent in the management of BPD. Prescription strategies changed between 1996 and 2012. Quetiapine was preferred, older antidepressants and low-potency antipsychotics were avoided. Opioid antagonists are increasingly used and should be considered for further investigation.
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    • Journal Article

      Mothers’ experiences of quality of care and potential benefits of implementing the WHO safe childbirth checklist: a case study of Aceh Indonesia 

      Doria, Siobhan; Diba, Farah; Susanti, Suryane S; Vollmer, Sebastian; Monfared, Ida G
      BMC Pregnancy and Childbirth. 2019 Dec 03;19(1):461
      Abstract Background In an effort to mitigate missed opportunities to provide high-quality care, the World Health Organization (WHO) has developed the Safe Childbirth Checklist (SCC) to support health providers perform essential tasks. Our qualitative study is a baseline assessment of quality of care (QoC) perceived by mothers who gave birth at health facilities aiming to highlight areas where implementing the SCC can potentially improve the QoC as well as areas that are not part of the SCC yet require improvement. Methods Assessing the overall experience of care, our qualitative study focuses on 8 out of 29 items in the checklist that are related to the personal interactions between healthcare provider and mothers. Using a set of semi-structured questions, we interviewed 26 new mothers who gave institutional births in Aceh province in Indonesia. Results Our findings revealed some gaps where implementing the SCC can potentially improve safety and QoC. They include communicating danger signs at critical points during birth and after discharge, encouraging breastfeeding, and providing mothers with information on family planning. Moreover, taking a qualitative approach allowed us to identify additional aspects such as need for clarity at the point of admission, maintaining dignity, and protecting mothers’ rights in the decision-making process to be also essential for better QoC. Conclusions Our study highlights the need to actively listen to and engage with the experiences of women in the adaptation and implementation of the checklist. While our findings indicate that implementing the SCC has the potential to improve the quality of maternal care and overall birth experience, a more holistic understanding of the lived experiences of women and the dynamics of their interactions with health facilities, care providers, and their birth companions can complement the implementation of the checklist.
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