TY - JOUR
A1 - Buyinza, Daniel
A1 - Derese, Solomon
A1 - Ndakala, Albert
A1 - Heydenreich, Matthias
A1 - Yenesew, Abiy
A1 - Koch, Andreas
A1 - Oriko, Richard
T1 - A coumestan and a coumaronochromone from Millettia lasiantha
JF - Biochemical systematics and ecology
N2 - The manuscript describes the phytochemical investigation of the roots, leaves and stem bark of Millettia lasiantha resulting in the isolation of twelve compounds including two new isomeric isoflavones lascoumestan and las-coumaronochromone. The structures of the new compounds were determined using different spectroscopic techniques.
KW - Millettia lasiantha
KW - Leguminosae
KW - Coumestan
KW - Coumaronochromone
Y1 - 2021
U6 - https://doi.org/10.1016/j.bse.2021.104277
SN - 0305-1978
SN - 1873-2925
VL - 97
PB - Elsevier
CY - Oxford
ER -
TY - JOUR
A1 - Luetkecosmann, Steffi
A1 - Faupel, Thomas
A1 - Porstmann, Silvia
A1 - Porstmann, Tomas
A1 - Micheel, Burkhard
A1 - Hanack, Katja
T1 - A cross-reactive monoclonal antibody as universal detection antibody in autoantibody diagnostic assays
JF - Clinica chimica acta
N2 - Diagnostics of Autoimmune Diseases involve screening of patient samples for containing autoantibodies against various antigens. To ensure quality of diagnostic assays a calibrator is needed in each assay system. Different calibrators as recombinant human monoclonal antibodies as well as chimeric antibodies against the autoantigens of interest are described. A less cost-intensive and also more representative possibility covering different targets on the antigens is the utilization of polyclonal sera from other species. Nevertheless, the detection of human autoantibodies as well as the calibration reagent containing antibodies from other species in one assay constitutes a challenge in terms of assay calibration. We therefore developed a cross-reactive monoclonal antibody which binds human as well as rabbit sera with similar affinities in the nanomolar range. We tested our monoclonal antibody S38CD11B12 successfully in the commercial Serazym (R) Anti-Cardiolipin-beta 2-GPI IgG/IgM assay and could thereby prove the eligibility of S38CD11B12 as detection antibody in autoimmune diagnostic assays using rabbit derived sera as reference material.
KW - Monoclonal antibody
KW - Detection
KW - Autoimmune diagnostics
KW - Cross reactivity
KW - Assay calibration
Y1 - 2019
U6 - https://doi.org/10.1016/j.cca.2019.09.003
SN - 0009-8981
SN - 1873-3492
VL - 499
SP - 87
EP - 92
PB - Elsevier
CY - Amsterdam
ER -
TY - JOUR
A1 - Demal, Till Joscha
A1 - Heise, Melina
A1 - Reiz, Benedikt
A1 - Dogra, Deepika
A1 - Braenne, Ingrid
A1 - Reichenspurner, Hermann
A1 - Männer, Jörg
A1 - Aherrahrou, Zouhair
A1 - Schunkert, Heribert
A1 - Erdmann, Jeanette
A1 - Abdelilah-Seyfried, Salim
T1 - A familial congenital heart disease with a possible multigenic origin involving a mutation in BMPR1A
JF - Scientific reports
N2 - The genetics of many congenital heart diseases (CHDs) can only unsatisfactorily be explained by known chromosomal or Mendelian syndromes. Here, we present sequencing data of a family with a potentially multigenic origin of CHD. Twelve of nineteen family members carry a familial mutation [NM_004329.2:c.1328 G > A (p.R443H)] which encodes a predicted deleterious variant of BMPR1A. This mutation co-segregates with a linkage region on chromosome 1 that associates with the emergence of severe CHDs including Ebstein’s anomaly, atrioventricular septal defect, and others. We show that the continuous overexpression of the zebrafish homologous mutation bmpr1aap.R438H within endocardium causes a reduced AV valve area, a downregulation of Wnt/ß-catenin signalling at the AV canal, and growth of additional tissue mass in adult zebrafish hearts. This finding opens the possibility of testing genetic interactions between BMPR1A and other candidate genes within linkage region 1 which may provide a first step towards unravelling more complex genetic patterns in cardiovascular disease aetiology.
Y1 - 2019
U6 - https://doi.org/10.1038/s41598-019-39648-7
SN - 2045-2322
VL - 9
PB - Nature Publ. Group
CY - London
ER -
TY - JOUR
A1 - Xiao, Shangbin
A1 - Liu, Liu
A1 - Wang, Wei
A1 - Lorke, Andreas
A1 - Woodhouse, Jason Nicholas
A1 - Grossart, Hans-Peter
T1 - A Fast-Response Automated Gas Equilibrator (FaRAGE) for continuous in situ measurement of CH4 and CO2 dissolved in water
JF - Hydrology and earth system sciences : HESS
N2 - Biogenic greenhouse gas emissions, e.g., of methane (CH4) and carbon dioxide (CO2) from inland waters, contribute substantially to global warming. In aquatic systems, dissolved greenhouse gases are highly heterogeneous in both space and time. To better understand the biological and physical processes that affect sources and sinks of both CH4 and CO2, their dissolved concentrations need to be measured with high spatial and temporal resolution. To achieve this goal, we developed the Fast-Response Automated Gas Equilibrator (FaRAGE) for real-time in situ measurement of dissolved CH4 and CO2 concentrations at the water surface and in the water column. FaRAGE can achieve an exceptionally short response time (t(95%) = 12 s when including the response time of the gas analyzer) while retaining an equilibration ratio of 62.6% and a measurement accuracy of 0.5% for CH4. A similar performance was observed for dissolved CO2 (t(95%) = 10 s, equilibration ratio 67.1 %). An equilibration ratio as high as 91.8% can be reached at the cost of a slightly increased response time (16 s). The FaRAGE is capable of continuously measuring dissolved CO2 and CH4 concentrations in the nM-to-submM (10(-9)-10(-3) mol L-1) range with a detection limit of subnM (10(-10) mol L-1), when coupling with a cavity ring-down greenhouse gas analyzer (Picarro GasScouter). FaRAGE allows for the possibility of mapping dissolved concentration in a "quasi" three-dimensional manner in lakes and provides an inexpensive alternative to other commercial gas equilibrators. It is simple to operate and suitable for continuous monitoring with a strong tolerance for suspended particles. While the FaRAGE is developed for inland waters, it can be also applied to ocean waters by tuning the gas-water mixing ratio. The FaRAGE is easily adapted to suit other gas analyzers expanding the range of potential applications, including nitrous oxide and isotopic composition of the gases.
Y1 - 2020
U6 - https://doi.org/10.5194/hess-24-3871-2020
SN - 1027-5606
SN - 1607-7938
VL - 24
IS - 7
SP - 3871
EP - 3880
PB - European Geosciences Union (EGU) ; Copernicus
CY - Munich
ER -
TY - JOUR
A1 - Sharma, Neha
A1 - Ruelens, Philip
A1 - Maggen, Thomas
A1 - Dochy, Niklas
A1 - Torfs, Sanne
A1 - Kaufmann, Kerstin
A1 - Rohde, Antje
A1 - Geuten, Koen
T1 - A Flowering Locus C Homolog Is a Vernalization-Regulated Repressor in Brachypodium and Is Cold Regulated in Wheat
JF - Plant physiology : an international journal devoted to physiology, biochemistry, cellular and molecular biology, biophysics and environmental biology of plants
N2 - Winter cereals require prolonged cold to transition from vegetative to reproductive development. This process, referred to as vernalization, has been extensively studied in Arabidopsis (Arabidopsis thaliana). In Arabidopsis, a key flowering repressor called FLOWERING LOCUS C (FLC) quantitatively controls the vernalization requirement. By contrast, in cereals, the vernalization response is mainly regulated by the VERNALIZATION genes, VRN1 and VRN2. Here, we characterize ODDSOC2, a recently identified FLC ortholog in monocots, knowing that it belongs to the FLC lineage. By studying its expression in a diverse set of Brachypodium accessions, we find that it is a good predictor of the vernalization requirement. Analyses of transgenics demonstrated that BdODDSOC2 functions as a vernalization-regulated flowering repressor. In most Brachypodium accessions BdODDSOC2 is down-regulated by cold, and in one of the winter accessions in which this down-regulation was evident, BdODDSOC2 responded to cold before BdVRN1. When stably down-regulated, the mechanism is associated with spreading H3K27me3 modifications at the BdODDSOC2 chromatin. Finally, homoeolog-specific gene expression analyses identify TaAGL33 and its splice variant TaAGL22 as the FLC orthologs in wheat (Triticum aestivum) behaving most similar to Brachypodium ODDSOC2. Overall, our study suggests that ODDSOC2 is not only phylogenetically related to FLC in eudicots but also functions as a flowering repressor in the vernalization pathway of Brachypodium and likely other temperate grasses. These insights could prove useful in breeding efforts to refine the vernalization requirement of temperate cereals and adapt varieties to changing climates.
Y1 - 2016
U6 - https://doi.org/10.1104/pp.16.01161
SN - 0032-0889
SN - 1532-2548
VL - 173
IS - 2
SP - 1301
EP - 1315
PB - American Society of Plant Physiologists
CY - Rockville
ER -
TY - JOUR
A1 - Lah, Ljerka
A1 - Löber, Ulrike
A1 - Hsiang, Tom
A1 - Hartmann, Stefanie
T1 - A genomic comparison of putative pathogenicity-related gene families in five members of the Ophiostomatales with different lifestyles
JF - Fungal biology
N2 - Ophiostomatoid fungi are vectored by their bark-beetle associates and colonize different host tree species. To survive and proliferate in the host, they have evolved mechanisms for detoxification and elimination of host defence compounds, efficient nutrient sequestration, and, in pathogenic species, virulence towards plants. Here, we assembled a draft genome of the spruce pathogen Ophiostoma bicolor. For our comparative and phylogenetic analyses, we mined the genomes of closely related species (Ophiostoma piceae, Ophiostoma ulmi, Ophiostoma novo-ulmi, and Grosmannia clavigera). Our aim was to acquire a genomic and evolutionary perspective of gene families important in host colonization. Genome comparisons showed that both the nuclear and mitochondrial genomes in our assembly were largely complete. Our O. bicolor 25.3 Mbp draft genome had 10 018 predicted genes, 6041 proteins with gene ontology (GO) annotation, 269 carbohydrate-active enzymes (CAZymes), 559 peptidases and inhibitors, and 1373 genes likely involved in pathogen-host interactions. Phylogenetic analyses of selected protein families revealed core sets of cytochrome P450 genes, ABC transporters and backbone genes involved in secondary metabolite (SM) biosynthesis (polyketide synthases (PKS) and non-ribosomal synthases), and species-specific gene losses and duplications. Phylogenetic analyses of protein families of interest provided insight into evolutionary adaptations to host biochemistry in ophiostomatoid fungi.
KW - Bark beetle
KW - Bluestain fungi
KW - Ips typographus
Y1 - 2016
U6 - https://doi.org/10.1016/j.funbio.2016.12.002
SN - 1878-6146
SN - 1878-6162
VL - 121
SP - 234
EP - 252
PB - Elsevier
CY - Oxford
ER -
TY - JOUR
A1 - Zhang, Youjun
A1 - Chen, Moxian
A1 - Siemiatkowska, Beata
A1 - Toleco, Mitchell Rey
A1 - Jing, Yue
A1 - Strotmann, Vivien
A1 - Zhang, Jianghua
A1 - Stahl, Yvonne
A1 - Fernie, Alisdair R.
T1 - A highly efficient agrobacterium-mediated method for transient gene expression and functional studies in multiple plant species
JF - Plant Communications
N2 - Although the use of stable transformation technology has led to great insight into gene function, its application in high-throughput studies remains arduous. Agro-infiltration have been widely used in species such as Nicotiana benthamiana for the rapid detection of gene expression and protein interaction analysis, but this technique does not work efficiently in other plant species, including Arabidopsis thaliana. As an efficient high-throughput transient expression system is currently lacking in the model plant species A. thaliana, we developed a method that is characterized by high efficiency, reproducibility, and suitability for transient expression of a variety of functional proteins in A. thaliana and 7 other plant species, including Brassica oleracea, Capsella rubella, Thellungiella salsuginea, Thellungiella halophila, Solanum tuberosum, Capsicum annuum, and N. benthamiana. Efficiency of this method was independently verified in three independent research facilities, pointing to the robustness of this technique. Furthermore, in addition to demonstrating the utility of this technique in a range of species, we also present a case study employing this method to assess protein-protein interactions in the sucrose biosynthesis pathway in Arabidopsis.
KW - transient expression
KW - agro-infiltration
KW - subcellular localization
KW - protein-protein interaction
Y1 - 2019
SN - 2590-3462
VL - 1
IS - 5
PB - Science Direct
CY - New York
ER -
TY - JOUR
A1 - Jantzen, Friederike
A1 - Wozniak, Natalia Joanna
A1 - Kappel, Christian
A1 - Sicard, Adrien
A1 - Lenhard, Michael
T1 - A high‑throughput amplicon‑based method for estimating outcrossing rates
JF - Plant Methods
N2 - Background: The outcrossing rate is a key determinant of the population-genetic structure of species and their long-term evolutionary trajectories. However, determining the outcrossing rate using current methods based on PCRgenotyping individual offspring of focal plants for multiple polymorphic markers is laborious and time-consuming.
Results: We have developed an amplicon-based, high-throughput enabled method for estimating the outcrossing rate and have applied this to an example of scented versus non-scented Capsella (Shepherd’s Purse) genotypes. Our results show that the method is able to robustly capture differences in outcrossing rates. They also highlight potential biases in the estimates resulting from differential haplotype sharing of the focal plants with the pollen-donor population at individual amplicons.
Conclusions: This novel method for estimating outcrossing rates will allow determining this key population-genetic parameter with high-throughput across many genotypes in a population, enabling studies into the genetic determinants of successful pollinator attraction and outcrossing.
KW - Outcrossing
KW - Mixed mating
KW - Outcrossing rate
KW - Capsella
KW - Amplicon sequencing
Y1 - 2019
U6 - https://doi.org/10.1186/s13007-019-0433-9
SN - 1746-4811
VL - 15
IS - 47
PB - BioMed Central
CY - London
ER -
TY - JOUR
A1 - Wandt, Viktoria Klara Veronika
A1 - Winkelbeiner, Nicola Lisa
A1 - Bornhorst, Julia
A1 - Witt, Barbara
A1 - Raschke, Stefanie
A1 - Simon, Luise
A1 - Ebert, Franziska
A1 - Kipp, Anna Patricia
A1 - Schwerdtle, Tanja
T1 - A matter of concern
BT - trace element dyshomeostasis and genomic stability in neurons
JF - Redox Biology
N2 - Neurons are post-mitotic cells in the brain and their integrity is of central importance to avoid neurodegeneration. Yet, the inability of self-replenishment of post-mitotic cells results in the need to withstand challenges from numerous stressors during life. Neurons are exposed to oxidative stress due to high oxygen consumption during metabolic activity in the brain. Accordingly, DNA damage can occur and accumulate, resulting in genome instability. In this context, imbalances in brain trace element homeostasis are a matter of concern, especially regarding iron, copper, manganese, zinc, and selenium. Although trace elements are essential for brain physiology, excess and deficient conditions are considered to impair neuronal maintenance. Besides increasing oxidative stress, DNA damage response and repair of oxidative DNA damage are affected by trace elements. Hence, a balanced trace element homeostasis is of particular importance to safeguard neuronal genome integrity and prevent neuronal loss. This review summarises the current state of knowledge on the impact of deficient, as well as excessive iron, copper, manganese, zinc, and selenium levels on neuronal genome stability
Y1 - 2021
U6 - https://doi.org/10.1016/j.redox.2021.101877
VL - 41
PB - Elsevier
CY - Amsterdam
ER -
TY - JOUR
A1 - Hartung, Niklas
A1 - Borghardt, Jens Markus
T1 - A mechanistic framework for a priori pharmacokinetic predictions of orally inhaled drugs
JF - PLoS Computational Biology : a new community journal
N2 - Author summary
The use of orally inhaled drugs for treating lung diseases is appealing since they have the potential for lung selectivity, i.e. high exposure at the site of action -the lung- without excessive side effects. However, the degree of lung selectivity depends on a large number of factors, including physiochemical properties of drug molecules, patient disease state, and inhalation devices. To predict the impact of these factors on drug exposure and thereby to understand the characteristics of an optimal drug for inhalation, we develop a predictive mathematical framework (a "pharmacokinetic model"). In contrast to previous approaches, our model allows combining knowledge from different sources appropriately and its predictions were able to adequately predict different sets of clinical data. Finally, we compare the impact of different factors and find that the most important factors are the size of the inhaled particles, the affinity of the drug to the lung tissue, as well as the rate of drug dissolution in the lung. In contrast to the common belief, the solubility of a drug in the lining fluids is not found to be relevant. These findings are important to understand how inhaled drugs should be designed to achieve best treatment results in patients.
The fate of orally inhaled drugs is determined by pulmonary pharmacokinetic processes such as particle deposition, pulmonary drug dissolution, and mucociliary clearance. Even though each single process has been systematically investigated, a quantitative understanding on the interaction of processes remains limited and therefore identifying optimal drug and formulation characteristics for orally inhaled drugs is still challenging. To investigate this complex interplay, the pulmonary processes can be integrated into mathematical models. However, existing modeling attempts considerably simplify these processes or are not systematically evaluated against (clinical) data. In this work, we developed a mathematical framework based on physiologically-structured population equations to integrate all relevant pulmonary processes mechanistically. A tailored numerical resolution strategy was chosen and the mechanistic model was evaluated systematically against data from different clinical studies. Without adapting the mechanistic model or estimating kinetic parameters based on individual study data, the developed model was able to predict simultaneously (i) lung retention profiles of inhaled insoluble particles, (ii) particle size-dependent pharmacokinetics of inhaled monodisperse particles, (iii) pharmacokinetic differences between inhaled fluticasone propionate and budesonide, as well as (iv) pharmacokinetic differences between healthy volunteers and asthmatic patients. Finally, to identify the most impactful optimization criteria for orally inhaled drugs, the developed mechanistic model was applied to investigate the impact of input parameters on both the pulmonary and systemic exposure. Interestingly, the solubility of the inhaled drug did not have any relevant impact on the local and systemic pharmacokinetics. Instead, the pulmonary dissolution rate, the particle size, the tissue affinity, and the systemic clearance were the most impactful potential optimization parameters. In the future, the developed prediction framework should be considered a powerful tool for identifying optimal drug and formulation characteristics.
Y1 - 2020
U6 - https://doi.org/10.1371/journal.pcbi.1008466
SN - 1553-734X
SN - 1553-7358
VL - 16
IS - 12
PB - PLoS
CY - San Fransisco
ER -