TY  - JOUR
A1  - Wiesner-Reinhold, Melanie
A1  - Barknowitz, Gitte
A1  - Florian, Simone
A1  - Mewis, Inga
A1  - Schumacher, Fabian
A1  - Schreiner, Monika
A1  - Glatt, Hansruedi
T1  - 1-Methoxy-3-indolylmethyl DNA adducts in six tissues, and blood protein adducts, in mice under pak choi diet: time course and persistence
JF  - Archives of toxicology : official journal of EUROTOX
N2  - We previously showed that purified 1-methoxy-3-indolylmethyl (1-MIM) glucosinolate, a secondary plant metabolite in Brassica species, is mutagenic in various in vitro systems and forms DNA and protein adducts in mouse models. In the present study, we administered 1-MIM glucosinolate in a natural matrix to mice, by feeding a diet containing pak choi powder and extract. Groups of animals were killed after 1, 2, 4 and 8 days of pak choi diet, directly or, in the case of the 8-day treatment, after 0, 8 and 16 days of recovery with pak choi-free diet. DNA adducts [N-2-(1-MIM)-dG, N-6-(1-MIM)-dA] in six tissues, as well as protein adducts [tau N-(1-MIM)-His] in serum albumin (SA) and hemoglobin (Hb) were determined using UPLC-MS/MS with isotopically labeled internal standards. None of the samples from the 12 control animals under standard diet contained any 1-MIM adducts. All groups receiving pak choi diet showed DNA adducts in all six tissues (exception: lung of mice treated for a single day) as well as SA and Hb adducts. During the feeding period, all adduct levels continuously increased until day 8 (in the jejunum until day 4). During the 14-day recovery period, N-2-(1-MIM)-dG in liver, kidney, lung, jejunum, cecum and colon decreased to 52, 41, 59, 11, 7 and 2%, respectively, of the peak level. The time course of N-6-(1-MIM)-dA was similar. Immunohistochemical analyses indicated that cell turnover is a major mechanism of DNA adduct elimination in the intestine. In the same recovery period, protein adducts decreased more rapidly in SA than in Hb, to 0.7 and 37%, respectively, of the peak level, consistent with the differential turnover of these proteins. In conclusion, the pak choi diet lead to the formation of high levels of adducts in mice. Cell and protein turnover was a major mechanism of adduct elimination, at least in gut and blood.
KW  - 1-Methoxy-3-indolylmethyl glucosinolate
KW  - Neoglucobrassicin
KW  - DNA adducts
KW  - Blood protein adducts
KW  - Pak choi
Y1  - 2019
U6  - https://doi.org/10.1007/s00204-019-02452-3
SN  - 0340-5761
SN  - 1432-0738
VL  - 93
IS  - 6
SP  - 1515
EP  - 1527
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Klauschies, Toni
A1  - Coutinho, Renato Mendes
A1  - Gaedke, Ursula
T1  - A beta distribution-based moment closure enhances the reliability of trait-based aggregate models for natural populations and communities
JF  - Ecological modelling : international journal on ecological modelling and engineering and systems ecolog
N2  - Ecological communities are complex adaptive systems that exhibit remarkable feedbacks between their biomass and trait dynamics. Trait-based aggregate models cope with this complexity by focusing on the temporal development of the community’s aggregate properties such as its total biomass, mean trait and trait variance. They are based on particular assumptions about the shape of the underlying trait distribution, which is commonly assumed to be normal. However, ecologically important traits are usually restricted to a finite range, and empirical trait distributions are often skewed or multimodal. As a result, normal distribution-based aggregate models may fail to adequately represent the biomass and trait dynamics of natural communities. We resolve this mismatch by developing a new moment closure approach assuming the trait values to be beta-distributed. We show that the beta distribution captures important shape properties of both observed and simulated trait distributions, which cannot be captured by a Gaussian. We further demonstrate that a beta distribution-based moment closure can strongly enhance the reliability of trait-based aggregate models. We compare the biomass, mean trait and variance dynamics of a full trait distribution (FD) model to the ones of beta (BA) and normal (NA) distribution-based aggregate models, under different selection regimes. This way, we demonstrate under which general conditions (stabilizing, fluctuating or disruptive selection) different aggregate models are reliable tools. All three models predicted very similar biomass and trait dynamics under stabilizing selection yielding unimodal trait distributions with small standing trait variation. We also obtained an almost perfect match between the results of the FD and BA models under fluctuating selection, promoting skewed trait distributions and ongoing oscillations in the biomass and trait dynamics. In contrast, the NA model showed unrealistic trait dynamics and exhibited different alternative stable states, and thus a high sensitivity to initial conditions under fluctuating selection. Under disruptive selection, both aggregate models failed to reproduce the results of the FD model with the mean trait values remaining within their ecologically feasible ranges in the BA model but not in the NA model. Overall, a beta distribution-based moment closure strongly improved the realism of trait-based aggregate models.
KW  - Moment closure
KW  - Normal and beta distribution
KW  - Skewed and peaked trait distributions
KW  - Fitness landscape and frequency-dependent selection
KW  - Eco-evolutionary dynamics
KW  - Modelling functional diversity
Y1  - 2018
U6  - https://doi.org/10.1016/j.ecolmodel.2018.02.001
SN  - 0304-3800
SN  - 1872-7026
VL  - 381
SP  - 46
EP  - 77
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Omidbakhshfard, Mohammad Amin
A1  - Neerakkal, Sujeeth
A1  - Gupta, Saurabh
A1  - Omranian, Nooshin
A1  - Guinan, Kieran J.
A1  - Brotman, Yariv
A1  - Nikoloski, Zoran
A1  - Fernie, Alisdair R.
A1  - Mueller-Roeber, Bernd
A1  - Gechev, Tsanko S.
T1  - A Biostimulant Obtained from the Seaweed Ascophyllum nodosum Protects Arabidopsis thaliana from Severe Oxidative Stress
JF  - International Journal of Molecular Sciences
N2  - Abiotic stresses cause oxidative damage in plants. Here, we demonstrate that foliar application of an extract from the seaweed Ascophyllum nodosum, SuperFifty (SF), largely prevents paraquat (PQ)-induced oxidative stress in Arabidopsis thaliana. While PQ-stressed plants develop necrotic lesions, plants pre-treated with SF (i.e., primed plants) were unaffected by PQ. Transcriptome analysis revealed induction of reactive oxygen species (ROS) marker genes, genes involved in ROS-induced programmed cell death, and autophagy-related genes after PQ treatment. These changes did not occur in PQ-stressed plants primed with SF. In contrast, upregulation of several carbohydrate metabolism genes, growth, and hormone signaling as well as antioxidant-related genes were specific to SF-primed plants. Metabolomic analyses revealed accumulation of the stress-protective metabolite maltose and the tricarboxylic acid cycle intermediates fumarate and malate in SF-primed plants. Lipidome analysis indicated that those lipids associated with oxidative stress-induced cell death and chloroplast degradation, such as triacylglycerols (TAGs), declined upon SF priming. Our study demonstrated that SF confers tolerance to PQ-induced oxidative stress in A. thaliana, an effect achieved by modulating a range of processes at the transcriptomic, metabolic, and lipid levels.
KW  - Ascophyllum nodosum
KW  - Arabidopsis thaliana
KW  - biostimulant
KW  - paraquat
KW  - priming
KW  - oxidative stress tolerance
KW  - reactive oxygen species
Y1  - 2019
U6  - https://doi.org/10.3390/ijms21020474
SN  - 1422-0067
VL  - 21
IS  - 2
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - JOUR
A1  - Christakoudi, Sofa
A1  - Tsilidis, Konstantinos K.
A1  - Muller, David C.
A1  - Freisling, Heinz
A1  - Weiderpass, Elisabete
A1  - Overvad, Kim
A1  - Söderberg, Stefan
A1  - Häggström, Christel
A1  - Pischon, Tobias
A1  - Dahm, Christina C.
A1  - Zhang, Jie
A1  - Tjønneland, Anne
A1  - Schulze, Matthias Bernd
T1  - A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort
JF  - Scientific Reports
N2  - Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
KW  - all-cause mortality
KW  - anthropometric measures
KW  - mass index
KW  - overweight
KW  - cancer
KW  - prediction
KW  - adiposity
KW  - size
Y1  - 2020
VL  - 10
IS  - 1
PB  - Springer Nature
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Haueis, Lisa
A1  - Stech, Marlitt
A1  - Kubick, Stefan
T1  - A Cell-free Expression Pipeline for the Generation and Functional Characterization of Nanobodies
JF  - Frontiers in Bioengineering and Biotechnology
N2  - Cell-free systems are well-established platforms for the rapid synthesis, screening, engineering and modification of all kinds of recombinant proteins ranging from membrane proteins to soluble proteins, enzymes and even toxins. Also within the antibody field the cell-free technology has gained considerable attention with respect to the clinical research pipeline including antibody discovery and production. Besides the classical full-length monoclonal antibodies (mAbs), so-called "nanobodies" (Nbs) have come into focus. A Nb is the smallest naturally-derived functional antibody fragment known and represents the variable domain (VHH, similar to 15 kDa) of a camelid heavy-chain-only antibody (HCAb). Based on their nanoscale and their special structure, Nbs display striking advantages concerning their production, but also their characteristics as binders, such as high stability, diversity, improved tissue penetration and reaching of cavity-like epitopes. The classical way to produce Nbs depends on the use of living cells as production host. Though cell-based production is well-established, it is still time-consuming, laborious and hardly amenable for high-throughput applications. Here, we present for the first time to our knowledge the synthesis of functional Nbs in a standardized mammalian cell-free system based on Chinese hamster ovary (CHO) cell lysates. Cell-free reactions were shown to be time-efficient and easy-to-handle allowing for the "on demand" synthesis of Nbs. Taken together, we complement available methods and demonstrate a promising new system for Nb selection and validation.
KW  - cell-free protein synthesis
KW  - In vitro transcription
KW  - translation
KW  - nanobody
KW  - VHH
KW  - camelid
KW  - CHO cell lysate
Y1  - 2022
U6  - https://doi.org/10.3389/fbioe.2022.896763
SN  - 2296-4185
VL  - 10
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Çabuk, Uğur
A1  - Ünlü, Ercan Selçuk
T1  - A combined de novo assembly approach increases the quality of prokaryotic draft genomes
JF  - Folia microbiologica : international journal for general, environmental and applied microbiology, and immunology
N2  - Next-generation sequencing methods provide comprehensive data for the analysis of structural and functional analysis of the genome. The draft genomes with low contig number and high N50 value can give insight into the structure of the genome as well as provide information on the annotation of the genome. In this study, we designed a pipeline that can be used to assemble prokaryotic draft genomes with low number of contigs and high N50 value. We aimed to use combination of two de novo assembly tools (SPAdes and IDBA-Hybrid) and evaluate the impact of this approach on the quality metrics of the assemblies. The followed pipeline was tested with the raw sequence data with short reads (< 300) for a total of 10 species from four different genera. To obtain the final draft genomes, we firstly assembled the sequences using SPAdes to find closely related organism using the extracted 16 s rRNA from it. IDBA-Hybrid assembler was used to obtain the second assembly data using the closely related organism genome. SPAdes assembler tool was implemented using the second assembly, produced by IDBA-hybrid as a hint. The results were evaluated using QUAST and BUSCO. The pipeline was successful for the reduction of the contig numbers and increasing the N50 statistical values in the draft genome assemblies while preserving the coverage of the draft genomes.
KW  - De novo assembly
KW  - Prokaryotes
KW  - Bacteria
KW  - NGS
KW  - Short reads
KW  - Draft genome
Y1  - 2022
U6  - https://doi.org/10.1007/s12223-022-00980-7
SN  - 0015-5632
SN  - 1874-9356
VL  - 67
SP  - 801
EP  - 810
PB  - Springer
CY  - Dordrecht
ER  - 
TY  - JOUR
A1  - Noonan, Michael J.
A1  - Tucker, Marlee A.
A1  - Fleming, Christen H.
A1  - Akre, Thomas S.
A1  - Alberts, Susan C.
A1  - Ali, Abdullahi H.
A1  - Altmann, Jeanne
A1  - Antunes, Pamela Castro
A1  - Belant, Jerrold L.
A1  - Beyer, Dean
A1  - Blaum, Niels
A1  - Boehning-Gaese, Katrin
A1  - Cullen Jr, Laury
A1  - de Paula, Rogerio Cunha
A1  - Dekker, Jasja
A1  - Drescher-Lehman, Jonathan
A1  - Farwig, Nina
A1  - Fichtel, Claudia
A1  - Fischer, Christina
A1  - Ford, Adam T.
A1  - Goheen, Jacob R.
A1  - Janssen, Rene
A1  - Jeltsch, Florian
A1  - Kauffman, Matthew
A1  - Kappeler, Peter M.
A1  - Koch, Flavia
A1  - LaPoint, Scott
A1  - Markham, A. Catherine
A1  - Medici, Emilia Patricia
A1  - Morato, Ronaldo G.
A1  - Nathan, Ran
A1  - Oliveira-Santos, Luiz Gustavo R.
A1  - Olson, Kirk A.
A1  - Patterson, Bruce D.
A1  - Paviolo, Agustin
A1  - Ramalho, Emiliano Estero
A1  - Rosner, Sascha
A1  - Schabo, Dana G.
A1  - Selva, Nuria
A1  - Sergiel, Agnieszka
A1  - da Silva, Marina Xavier
A1  - Spiegel, Orr
A1  - Thompson, Peter
A1  - Ullmann, Wiebke
A1  - Zieba, Filip
A1  - Zwijacz-Kozica, Tomasz
A1  - Fagan, William F.
A1  - Mueller, Thomas
A1  - Calabrese, Justin M.
T1  - A comprehensive analysis of autocorrelation and bias in home range estimation
JF  - Ecological monographs : a publication of the Ecological Society of America.
N2  - Home range estimation is routine practice in ecological research. While advances in animal tracking technology have increased our capacity to collect data to support home range analysis, these same advances have also resulted in increasingly autocorrelated data. Consequently, the question of which home range estimator to use on modern, highly autocorrelated tracking data remains open. This question is particularly relevant given that most estimators assume independently sampled data. Here, we provide a comprehensive evaluation of the effects of autocorrelation on home range estimation. We base our study on an extensive data set of GPS locations from 369 individuals representing 27 species distributed across five continents. We first assemble a broad array of home range estimators, including Kernel Density Estimation (KDE) with four bandwidth optimizers (Gaussian reference function, autocorrelated‐Gaussian reference function [AKDE], Silverman's rule of thumb, and least squares cross‐validation), Minimum Convex Polygon, and Local Convex Hull methods. Notably, all of these estimators except AKDE assume independent and identically distributed (IID) data. We then employ half‐sample cross‐validation to objectively quantify estimator performance, and the recently introduced effective sample size for home range area estimation ( N̂ area
) to quantify the information content of each data set. We found that AKDE 95% area estimates were larger than conventional IID‐based estimates by a mean factor of 2. The median number of cross‐validated locations included in the hold‐out sets by AKDE 95% (or 50%) estimates was 95.3% (or 50.1%), confirming the larger AKDE ranges were appropriately selective at the specified quantile. Conversely, conventional estimates exhibited negative bias that increased with decreasing N̂ area. To contextualize our empirical results, we performed a detailed simulation study to tease apart how sampling frequency, sampling duration, and the focal animal's movement conspire to affect range estimates. Paralleling our empirical results, the simulation study demonstrated that AKDE was generally more accurate than conventional methods, particularly for small N̂ area. While 72% of the 369 empirical data sets had >1,000 total observations, only 4% had an N̂ area >1,000, where 30% had an N̂ area <30. In this frequently encountered scenario of small N̂ area, AKDE was the only estimator capable of producing an accurate home range estimate on autocorrelated data.
KW  - animal movement
KW  - kernel density estimation
KW  - local convex hull
KW  - minimum convex polygon
KW  - range distribution
KW  - space use
KW  - telemetry
KW  - tracking data
Y1  - 2018
U6  - https://doi.org/10.1002/ecm.1344
SN  - 0012-9615
SN  - 1557-7015
VL  - 89
IS  - 2
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Palkopoulou, Eleftheria
A1  - Lipson, Mark
A1  - Mallick, Swapan
A1  - Nielsen, Svend
A1  - Rohland, Nadin
A1  - Baleka, Sina Isabelle
A1  - Karpinski, Emil
A1  - Ivancevici, Atma M.
A1  - Thu-Hien To, 
A1  - Kortschak, Daniel
A1  - Raison, Joy M.
A1  - Qu, Zhipeng
A1  - Chin, Tat-Jun
A1  - Alt, Kurt W.
A1  - Claesson, Stefan
A1  - Dalen, Love
A1  - MacPhee, Ross D. E.
A1  - Meller, Harald
A1  - Rocar, Alfred L.
A1  - Ryder, Oliver A.
A1  - Heiman, David
A1  - Young, Sarah
A1  - Breen, Matthew
A1  - Williams, Christina
A1  - Aken, Bronwen L.
A1  - Ruffier, Magali
A1  - Karlsson, Elinor
A1  - Johnson, Jeremy
A1  - Di Palma, Federica
A1  - Alfoldi, Jessica
A1  - Adelsoni, David L.
A1  - Mailund, Thomas
A1  - Munch, Kasper
A1  - Lindblad-Toh, Kerstin
A1  - Hofreiter, Michael
A1  - Poinar, Hendrik
A1  - Reich, David
T1  - A comprehensive genomic history of extinct and living elephants
JF  - Proceedings of the National Academy of Sciences of the United States of America
KW  - paleogenomics
KW  - elephantid evolution
KW  - mammoth
KW  - admixture
KW  - species divergence
Y1  - 2018
U6  - https://doi.org/10.1073/pnas.1720554115
SN  - 0027-8424
VL  - 115
IS  - 11
SP  - E2566
EP  - E2574
PB  - National Acad. of Sciences
CY  - Washington
ER  - 
TY  - JOUR
A1  - Chapman, Eric M.
A1  - Lant, Benjamin
A1  - Ohashi, Yota
A1  - Yu, Bin
A1  - Schertzberg, Michael
A1  - Go, Christopher
A1  - Dogra, Deepika
A1  - Koskimaki, Janne
A1  - Girard, Romuald
A1  - Li, Yan
A1  - Fraser, Andrew G.
A1  - Awad, Issam A.
A1  - Abdelilah-Seyfried, Salim
A1  - Gingras, Anne-Claude
A1  - Derry, William Brent
T1  - A conserved CCM complex promotes apoptosis non-autonomously by regulating zinc homeostasis
JF  - Nature Communications
N2  - Apoptotic death of cells damaged by genotoxic stress requires regulatory input from surrounding tissues. The C. elegans scaffold protein KRI-1, ortholog of mammalian KRIT1/CCM1, permits DNA damage-induced apoptosis of cells in the germline by an unknown cell non-autonomous mechanism. We reveal that KRI-1 exists in a complex with CCM-2 in the intestine to negatively regulate the ERK-5/MAPK pathway. This allows the KLF-3 transcription factor to facilitate expression of the SLC39 zinc transporter gene zipt-2.3, which functions to sequester zinc in the intestine. Ablation of KRI-1 results in reduced zinc sequestration in the intestine, inhibition of IR-induced MPK-1/ERK1 activation, and apoptosis in the germline. Zinc localization is also perturbed in the vasculature of krit1(-/-) zebrafish, and SLC39 zinc transporters are mis-expressed in Cerebral Cavernous Malformations (CCM) patient tissues. This study provides new insights into the regulation of apoptosis by cross-tissue communication, and suggests a link between zinc localization and CCM disease.
Y1  - 2019
U6  - https://doi.org/10.1038/s41467-019-09829-z
SN  - 2041-1723
VL  - 10
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Wolff, Martin
A1  - Gast, Klaus
A1  - Evers, Andreas
A1  - Kurz, Michael
A1  - Pfeiffer-Marek, Stefania
A1  - Schüler, Anja
A1  - Seckler, Robert
A1  - Thalhammer, Anja
T1  - A Conserved Hydrophobic Moiety and Helix-Helix Interactions Drive the Self-Assembly of the Incretin Analog Exendin-4
JF  - Biomolecules
N2  - Exendin-4 is a pharmaceutical peptide used in the control of insulin secretion. Structural information on exendin-4 and related peptides especially on the level of quaternary structure is scarce. We present the first published association equilibria of exendin-4 directly measured by static and dynamic light scattering. We show that exendin-4 oligomerization is pH dependent and that these oligomers are of low compactness. We relate our experimental results to a structural hypothesis to describe molecular details of exendin-4 oligomers. Discussion of the validity of this hypothesis is based on NMR, circular dichroism and fluorescence spectroscopy, and light scattering data on exendin-4 and a set of exendin-4 derived peptides. The essential forces driving oligomerization of exendin-4 are helix–helix interactions and interactions of a conserved hydrophobic moiety. Our structural hypothesis suggests that key interactions of exendin-4 monomers in the experimentally supported trimer take place between a defined helical segment and a hydrophobic triangle constituted by the Phe22 residues of the three monomeric subunits. Our data rationalize that Val19 might function as an anchor in the N-terminus of the interacting helix-region and that Trp25 is partially shielded in the oligomer by C-terminal amino acids of the same monomer. Our structural hypothesis suggests that the Trp25 residues do not interact with each other, but with C-terminal Pro residues of their own monomers.
KW  - biophysics
KW  - diabetes
KW  - peptides
KW  - oligomerization
KW  - conformational change
KW  - molecular modeling
KW  - static and dynamic light scattering
KW  - spectroscopy
Y1  - 2021
U6  - https://doi.org/10.3390/biom11091305
SN  - 2218-273X
VL  - 11
IS  - 9
PB  - MDPI
CY  - Basel
ER  - 
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 <br /> 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. <br /> 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  - 
TY  - JOUR
A1  - Schiro, Gabriele
A1  - Colangeli, Pierluigi
A1  - Müller, Marina E. H.
T1  - A Metabarcoding Analysis of the Mycobiome of Wheat Ears Across a Topographically Heterogeneous Field
JF  - Frontiers in microbiology
KW  - Fusarium
KW  - microclimate
KW  - canopy
KW  - fungal community
KW  - Alternaria
KW  - spatially induced variance
Y1  - 2019
U6  - https://doi.org/10.3389/fmicb.2019.02095
SN  - 1664-302X
VL  - 10
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Winkelbeiner, Nicola Lisa
A1  - Wandt, Viktoria Klara Veronika
A1  - Ebert, Franziska
A1  - Lossow, Kristina
A1  - Bankoglu, Ezgi E.
A1  - Martin, Maximilian
A1  - Mangerich, Aswin
A1  - Stopper, Helga
A1  - Bornhorst, Julia
A1  - Kipp, Anna Patricia
A1  - Schwerdtle, Tanja
T1  - A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice
BT  - Impact of Sex and Age
JF  - International Journal of Molecular Sciences
N2  - Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.
KW  - maintenance of genomic integrity
KW  - ageing
KW  - sex
KW  - DNA damage
KW  - base excision repair (incision activity)
KW  - DNA damage response
KW  - poly(ADP-ribosyl)ation
KW  - liver
Y1  - 2020
U6  - https://doi.org/10.3390/ijms21186600
SN  - 1422-0067
VL  - 21
IS  - 18
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - JOUR
A1  - Obbard, Darren J.
A1  - Shi, Mang
A1  - Roberts, Katherine E.
A1  - Longdon, Ben
A1  - Dennis, Alice B.
T1  - A new lineage of segmented RNA viruses infecting animals
JF  - Virus Evolution
N2  - Metagenomic sequencing has revolutionised our knowledge of virus diversity, with new virus sequences being reported faster than ever before. However, virus discovery from metagenomic sequencing usually depends on detectable homology: without a sufficiently close relative, so-called ‘dark’ virus sequences remain unrecognisable. An alternative approach is to use virus-identification methods that do not depend on detecting homology, such as virus recognition by host antiviral immunity. For example, virus-derived small RNAs have previously been used to propose ‘dark’ virus sequences associated with the Drosophilidae (Diptera). Here, we combine published Drosophila data with a comprehensive search of transcriptomic sequences and selected meta-transcriptomic datasets to identify a completely new lineage of segmented positive-sense single-stranded RNA viruses that we provisionally refer to as the Quenyaviruses. Each of the five segments contains a single open reading frame, with most encoding proteins showing no detectable similarity to characterised viruses, and one sharing a small number of residues with the RNA-dependent RNA polymerases of single- and double-stranded RNA viruses. Using these sequences, we identify close relatives in approximately 20 arthropods, including insects, crustaceans, spiders, and a myriapod. Using a more conserved sequence from the putative polymerase, we further identify relatives in meta-transcriptomic datasets from gut, gill, and lung tissues of vertebrates, reflecting infections of vertebrates or of their associated parasites. Our data illustrate the utility of small RNAs to detect viruses with limited sequence conservation, and provide robust evidence for a new deeply divergent and phylogenetically distinct RNA virus lineage.
KW  - metagenome
KW  - RNA virus
KW  - dark virus
KW  - arthropod
KW  - RNA interference
Y1  - 2020
U6  - https://doi.org/10.1093/ve/vez061
SN  - 2057-1577
VL  - 6
IS  - 1
SP  - 1
EP  - 10
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Van den Wyngaert, Silke
A1  - Seto, Kensuke
A1  - Rojas-Jimenez, Keilor
A1  - Kagami, Maiko
A1  - Grossart, Hans-Peter
T1  - A New Parasitic Chytrid, Staurastromyces oculus (Rhizophydiales, Staurastromy-cetaceae fam. nov.), Infecting the Freshwater Desmid Staurastrum sp.
JF  - Protist
N2  - Chytrids are a diverse group of ubiquitous true zoosporic fungi. The recent molecular discovery of a large diversity of undescribed chytrids has raised awareness on their important, but so far understudied ecological role in aquatic ecosystems. In the pelagic zone, of both freshwater and marine ecosystems, many chytrid species have been morphologically described as parasites on almost all major groups of phytoplankton. However, the majority of these parasitic chytrids has rarely been isolated and lack DNA sequence data, resulting in a large proportion of "dark taxa" in databases. Here, we report on the isolation and in-depth morphological, molecular and host range characterization of a chytrid infecting the common freshwater desmid Staurastrum sp. We provide first insights on the metabolic activity of the different chytrid development stages by using the vital dye FUN (R)-1 (2-chloro-4-[2,3-dihydro-3-methyl-[benzo-1,3-thiazol-2-yl]-methylidene]-1-phenylquinolinium iodide). Cross infection experiments suggest that this chytrid is an obligate parasite and specific for the genus Staurastrum sp. Phylogenetic analysis, based on ITS1-5.8S-ITS2 and 28S rDNA sequences, placed it in the order Rhizophydiales. Based on the unique zoospore ultrastructure, combined with thallus morphology, and molecular phylogenetic placement, we describe this parasitic chytrid as a new genus and species Staurastromyces oculus, within a new family Staurastromycetaceae. (C) 2017 Elsevier GmbH. All rights reserved.
KW  - Chytrids
KW  - parasite
KW  - phytoplankton
KW  - Staurastromyces oculus
KW  - Staurastrum sp.
Y1  - 2017
U6  - https://doi.org/10.1016/j.protis.2017.05.001
SN  - 1434-4610
VL  - 168
SP  - 392
EP  - 407
PB  - Elsevier
CY  - Jena
ER  - 
TY  - JOUR
A1  - Göthel, Markus
A1  - Listek, Martin
A1  - Messerschmidt, Katrin
A1  - Schlör, Anja
A1  - Hönow, Anja
A1  - Hanack, Katja
T1  - A New Workflow to Generate Monoclonal Antibodies against Microorganisms
JF  - Applied Sciences
N2  - Monoclonal antibodies are used worldwide as highly potent and efficient detection reagents for research and diagnostic applications. Nevertheless, the specific targeting of complex antigens such as whole microorganisms remains a challenge. To provide a comprehensive workflow, we combined bioinformatic analyses with novel immunization and selection tools to design monoclonal antibodies for the detection of whole microorganisms. In our initial study, we used the human pathogenic strain E. coli O157:H7 as a model target and identified 53 potential protein candidates by using reverse vaccinology methodology. Five different peptide epitopes were selected for immunization using epitope-engineered viral proteins. The identification of antibody-producing hybridomas was performed by using a novel screening technology based on transgenic fusion cell lines. Using an artificial cell surface receptor expressed by all hybridomas, the desired antigen-specific cells can be sorted fast and efficiently out of the fusion cell pool. Selected antibody candidates were characterized and showed strong binding to the target strain E. coli O157:H7 with minor or no cross-reactivity to other relevant microorganisms such as Legionella pneumophila and Bacillus ssp. This approach could be useful as a highly efficient workflow for the generation of antibodies against microorganisms.
KW  - monoclonal antibody
KW  - antibody producing cell selection
KW  - hybridoma
KW  - epitope prediction
Y1  - 2021
U6  - https://doi.org/10.3390/app11209359
SN  - 1454-5101
VL  - 11
IS  - 20
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Hahnewald, Rita
A1  - Leimkühler, Silke
A1  - Vilaseca, Antonia
A1  - Acquaviva-Bourdain, Cecile
A1  - Lenz, Ulrike
A1  - Reiss, Jochen
T1  - A novel MOCS2 mutation reveals coordinated expression of the small and large subunit of molybdopterin synthase
JF  - Molecular genetics and metabolism
N2  - The small and large subunits of molybdopterin (MPT) synthase (MOCS2A and MOCS2B), are both encoded by the MOCS2 gene in overlapping and shifted open reading frames (ORFs), which is a highly unusual structure for eukaryotes. Theoretical analysis of genomic sequences suggested that the expression of these overlapping ORFs is facilitated by the use of alternate first exons leading to alternative transcripts. Here, we confirm the existence of these overlapping transcripts experimentally. Further, we identified a deletion in a molybdenum cofactor deficient patient, which removes the start codon for the small subunit (MOCS2A). We observed undisturbed production of both transcripts, while Western blot analysis demonstrated that MOCS2B, the large subunit, is unstable in the absence of MOCS2A. This reveals new insights into the expression of this evolutionary ancient anabolic system.
KW  - molybdenum cofactor deficiency
KW  - MOCS2
KW  - overlapping reading frames
Y1  - 2006
U6  - https://doi.org/10.1016/j.ymgme.2006.04.008
SN  - 1096-7192
VL  - 89
IS  - 3
SP  - 210
EP  - 213
PB  - Elsevier
CY  - San Diego
ER  - 
TY  - JOUR
A1  - Lütkecosmann, Steffi
A1  - Warsinke, Axel
A1  - Tschöpe, Winfried
A1  - Eichler, Rüdiger
A1  - Hanack, Katja
T1  - A novel monoclonal antibody suitable for the detection of leukotriene B4
JF  - Biochemical and biophysical research communications
N2  - Leukotriene B4 as an inflammatory mediator is an important biomarker for different respiratory diseases like asthma, chronic obstructive pulmonary disease or cystic lung fibrosis. Therefore the detection of LTB4 is helpful in the diagnosis of these pulmonary diseases. However, until now its determination in exhaled breath condensates suffers from problems of accuracy. Reasons for that could be improper sample collection and preparation methods of condensates and the lack of consistently assay specificity and reproducibility of the used immunoassay detection system. In this study we describe the development and the characterization of a specific monoclonal antibody (S27BC6) against LTB4, its use as molecular recognition element for the development of an enzyme-linked immunoassay to detect LTB4 and discuss possible future diagnostic applications.
KW  - Leukotriene B4
KW  - Monoclonal antibody
KW  - Immunosensor
KW  - Chronic obstructive pulmonary disease (COPD)
KW  - Hapten
Y1  - 2017
U6  - https://doi.org/10.1016/j.bbrc.2016.11.157
SN  - 0006-291X
SN  - 1090-2104
VL  - 482
IS  - 4
SP  - 1054
EP  - 1059
PB  - Elsevier
CY  - San Diego
ER  - 
TY  - JOUR
A1  - Kagel, Heike
A1  - Bier, Frank Fabian
A1  - Frohme, Marcus
A1  - Glökler, Jörn F.
T1  - A Novel Optical Method To Reversibly Control Enzymatic Activity Based On Photoacids
JF  - Scientific reports
N2  - Most biochemical reactions depend on the pH value of the aqueous environment and some are strongly favoured to occur in an acidic environment. A non-invasive control of pH to tightly regulate such reactions with defined start and end points is a highly desirable feature in certain applications, but has proven difficult to achieve so far. We report a novel optical approach to reversibly control a typical biochemical reaction by changing the pH and using acid phosphatase as a model enzyme. The reversible photoacid G-acid functions as a proton donor, changing the pH rapidly and reversibly by using high power UV LEDs as an illumination source in our experimental setup. The reaction can be tightly controlled by simply switching the light on and off and should be applicable to a wide range of other enzymatic reactions, thus enabling miniaturization and parallelization through non-invasive optical means.
Y1  - 2019
U6  - https://doi.org/10.1038/s41598-019-50867-w
SN  - 2045-2322
VL  - 9
PB  - Nature Publishing Group
CY  - London
ER  - 
TY  - JOUR
A1  - Spikes, Montrai
A1  - Rodríguez-Silva, Rodet
A1  - Bennett, Kerri-Ann
A1  - Bräger, Stefan
A1  - Josaphat, James
A1  - Torres-Pineda, Patricia
A1  - Ernst, Anja
A1  - Havenstein, Katja
A1  - Schlupp, Ingo
A1  - Tiedemann, Ralph
T1  - A phylogeny of the genus Limia (Teleostei: Poeciliidae) suggests a single-lake radiation nested in a Caribbean-wide allopatric speciation scenario
JF  - BMC Research Notes
N2  - Objective
The Caribbean is an important global biodiversity hotspot. Adaptive radiations there lead to many speciation events within a limited period and hence are particularly prominent biodiversity generators. A prime example are freshwater fish of the genus Limia, endemic to the Greater Antilles. Within Hispaniola, nine species have been described from a single isolated site, Lake Miragoâne, pointing towards extraordinary sympatric speciation. This study examines the evolutionary history of the Limia species in Lake Miragoâne, relative to their congeners throughout the Caribbean.

Results
For 12 Limia species, we obtained almost complete sequences of the mitochondrial cytochrome b gene, a well-established marker for lower-level taxonomic relationships. We included sequences of six further Limia species from GenBank (total N  = 18 species). Our phylogenies are in concordance with other published phylogenies of Limia. There is strong support that the species found in Lake Miragoâne in Haiti are monophyletic, confirming a recent local radiation. Within Lake Miragoâne, speciation is likely extremely recent, leading to incomplete lineage sorting in the mtDNA. Future studies using multiple unlinked genetic markers are needed to disentangle the relationships within the Lake Miragoâne clade.
KW  - Cytochrome b
KW  - Island biogeography
KW  - Fresh water fish
KW  - Phylogeny
Y1  - 2021
U6  - https://doi.org/10.1186/s13104-021-05843-x
SN  - 1756-0500
VL  - 14
SP  - 1
EP  - 8
PB  - BMC Research Notes / Biomed Central
CY  - London
ER  - 
TY  - JOUR
A1  - Kopp, Johannes Florian
A1  - Müller, Sandra Marie
A1  - Pohl, Gabriele
A1  - Lossow, Kristina
A1  - Kipp, Anna Patricia
A1  - Schwerdtle, Tanja
T1  - A quick and simple method for the determination of six trace elements in mammalian serum samples using ICP-MS/MS
JF  - Journal of trace elements in medicine and biology
N2  - In order to assess the individual trace element status of humans for either medical or scientific purposes, amongst others, blood serum levels are determined. Furthermore, animal models are used to study interactions of trace elements. Most published methods require larger amounts (500-1000 mu L) of serum to achieve a reliable determination of multiple trace elements. However, oftentimes, these amounts of serum cannot be dedicated to a single analysis and the amount available for TE-determination is much lower. Therefore, a published ICP-MS/MS method for trace element determination in serum was miniaturized, optimized and validated for the measurement of Mn, Fe, Cu Zn, I and Se in as little as 50 mu L of human and murine serum and is presented in this work. For validation, recoveries of multiple LOTs and levels from commercially available human reference serum samples were determined, infra- and inter-day variations were assessed and limits of detection and quantification determined. It is shown, that the method is capable of giving accurate and reproducible results for all six elements within the relevant concentration ranges for samples from humans living in central Europe as well as from laboratory mice. As a highlight, the achieved limits of detection and quantification for Mn were found to be at 0.02 mu g/L serum and 0.05 mu g/L serum, respectively, while using an alkaline diluent for the parallel determination of iodine.
Y1  - 2019
U6  - https://doi.org/10.1016/j.jtemb.2019.04.015
SN  - 0946-672X
VL  - 54
SP  - 221
EP  - 225
PB  - Elsevier
CY  - München
ER  - 
TY  - JOUR
A1  - Petrović, Saša
A1  - Wendler, Petra
T1  - A RADD approach to probing AAA plus protein function
JF  - Nature structural & molecular biology
N2  - AAA+ proteins (ATPases associated with various cellular activities) catalyze the energy-dependent movement or rearrangement of macromolecules. A new study addresses the important question of how to design a selective chemical inhibitor for specific proteins in this diverse superfamily. The powerful chemical genetics approach adds to a growing toolbox of applications that allow dissection of the functions of distinct AAA+ proteins in vivo, facilitating the first steps toward effective drug development.
Y1  - 2021
U6  - https://doi.org/10.1038/s41594-021-00579-5
SN  - 1545-9993
SN  - 1545-9985
VL  - 28
IS  - 4
SP  - 329
EP  - 330
PB  - Nature Publishing Group
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Fiorini, Vanina D.
A1  - Domínguez, Marisol
A1  - Reboreda, Juan C.
A1  - Swaddle, John P.
T1  - A recent invasive population of the European starling sturnus vulgaris has lower genetic diversity and higher fluctuating asymmetry than primary invasive and native populations
JF  - Biological invasions : unique international journal uniting scientists in the broad field of biological invasions
N2  - Fluctuating asymmetries (FA) are small stress-induced random deviations from perfect symmetry that arise during the development of bilaterally symmetrical traits. One of the factors that can reduce developmental stability of the individuals and cause FA at a population level is the loss of genetic variation. Populations of founding colonists frequently have lower genetic variation than their ancestral populations that could be reflected in a higher level of FA. The European starling (Sturnus vulgaris) is native to Eurasia and was introduced successfully in the USA in 1890 and Argentina in 1983. In this study, we documented the genetic diversity and FA of starlings from England (ancestral population), USA (primary introduction) and Argentina (secondary introduction). We predicted the Argentinean starlings would have the highest level of FA and lowest genetic diversity of the three populations. We captured wild adult European starlings in England, USA, and Argentina, measured their mtDNA diversity and allowed them to molt under standardized conditions to evaluate their FA of primary feathers. For genetic analyses, we extracted DNA from blood samples of individuals from Argentina and USA and from feather samples from individuals from England and sequenced the mitochondrial control region. Starlings in Argentina showed the highest composite FA and exhibited the lowest haplotype and nucleotide diversity. The USA population showed a level of FA and genetic diversity similar to the native population. Therefore, the level of asymmetry and genetic diversity found among these populations was consistent with our predictions based on their invasion history.
KW  - Exotic bird species
KW  - Fluctuating asymmetry
KW  - Genetic variability
KW  - Sturnus
KW  - vulgaris
Y1  - 2022
U6  - https://doi.org/10.1007/s10530-021-02653-x
SN  - 1387-3547
SN  - 1573-1464
VL  - 24
IS  - 2
SP  - 437
EP  - 448
PB  - Springer
CY  - Dordrecht
ER  - 
TY  - JOUR
A1  - Kersting, Sebastian
A1  - Rausch, Valentina
A1  - Bier, Frank Fabian
A1  - von Nickisch-Rosenegk, Markus
T1  - A recombinase polymerase amplification assay for the diagnosis of atypical pneumonia
JF  - Analytical biochemistry : methods in the biological sciences
N2  - Pneumonia is one of the most common and potentially lethal infectious conditions worldwide. Streptococcus pneumoniae is the pathogen most frequently associated with bacterial community-acquired pneumonia, while Legionella pneumophila is the major cause for local outbreaks of legionellosis. Both pathogens can be difficult to diagnose since signs and symptoms are nonspecific and do not differ from other causes of pneumonia. Therefore, a rapid diagnosis within a clinically relevant time is essential for a fast onset of the proper treatment. Although methods based on polymerase chain reaction significantly improved the identification of pathogens, they are difficult to conduct and need specialized equipment. We describe a rapid and sensitive test using isothermal recombinase polymerase amplification and detection on a disposable test strip. This method does not require any special instrumentation and can be performed in less than 20 min. The analytical sensitivity in the multiplex assay amplifying specific regions of S. pneumoniae and L. pneumophila simultaneously was 10 CFUs of genomic DNA per reaction. In cross detection studies with closely related strains and other bacterial agents the specificity of the RPA was confirmed. The presented method is applicable for near patient and field testing with a rather simple routine and the possibility for a read out with the naked eye.
Y1  - 2018
U6  - https://doi.org/10.1016/j.ab.2018.04.014
SN  - 0003-2697
SN  - 1096-0309
VL  - 550
SP  - 54
EP  - 60
PB  - Elsevier
CY  - San Diego
ER  - 
TY  - JOUR
A1  - Sedaghatmehr, Mastoureh
A1  - Thirumalaikumar, Venkatesh P.
A1  - Kamranfar, Iman
A1  - Marmagne, Anne
A1  - Masclaux-Daubresse, Celine
A1  - Balazadeh, Salma
T1  - A regulatory role of autophagy for resetting the memory of heat stress in plants
JF  - Plant, cell & environment : cell physiology, whole-plant physiology, community physiology
N2  - As sessile life forms, plants are repeatedly confronted with adverse environmental conditions, which can impair development, growth, and reproduction. During evolution, plants have established mechanisms to orchestrate the delicate balance between growth and stress tolerance, to reset cellular biochemistry once stress vanishes, or to keep a molecular memory, which enables survival of a harsher stress that may arise later. Although there are several examples of memory in diverse plants species, the molecular machinery underlying the formation, duration, and resetting of stress memories is largely unknown so far. We report here that autophagy, a central self-degradative process, assists in resetting cellular memory of heat stress (HS) in Arabidopsis thaliana. Autophagy is induced by thermopriming (moderate HS) and, intriguingly, remains high long after stress termination. We demonstrate that autophagy mediates the specific degradation of heat shock proteins at later stages of the thermorecovery phase leading to the accumulation of protein aggregates after the second HS and a compromised heat tolerance. Autophagy mutants retain heat shock proteins longer than wild type and concomitantly display improved thermomemory. Our findings reveal a novel regulatory mechanism for HS memory in plants.
KW  - Arabidopsis
KW  - heat shock proteins
KW  - priming
KW  - resetting
Y1  - 2019
U6  - https://doi.org/10.1111/pce.13426
SN  - 0140-7791
SN  - 1365-3040
VL  - 42
IS  - 3
SP  - 1054
EP  - 1064
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Albers, Philip
A1  - Üstün, Suayib
A1  - Witzel, Katja
A1  - Kraner, Max Erdmund
A1  - Börnke, Frederik
T1  - A Remorin from Nicotiana benthamiana Interacts with the Pseudomonas Type-III Effector Protein HopZ1a and is Phosphorylated by the Immune-Related Kinase PBS1
JF  - Molecular Plant-Microbe Interactions
N2  - The plasma membrane (PM) is at the interface of plant-pathogen interactions and, thus, many bacterial type-III effector (T3E) proteins target membrane-associated processes to interfere with immunity. The Pseudomonas syringae T3E HopZ1a is a host cell PM-localized effector protein that has several immunity-associated host targets but also activates effector-triggered immunity in resistant backgrounds. Although HopZ1a has been shown to interfere with early defense signaling at the PM, no dedicated PM-associated HopZ1a target protein has been identified until now. Here, we show that HopZ1a interacts with the PM-associated remorin protein NbREM4 from Nicotiana benthamiana in several independent assays. NbREM4 relocalizes to membrane nanodomains after treatment with the bacterial elicitor flg22 and transient overexpression of NbREM4 in N. benthamiana induces the expression of a subset of defense-related genes. We can further show that NbREM4 interacts with the immune-related receptor-like cytoplasmic kinase avrPphB-susceptible 1 (PBS1) and is phosphorylated by PBS1 on several residues in vitro. Thus, we conclude that NbREM4 is associated with early defense signaling at the PM. The possible relevance of the HopZ1a-NbREM4 interaction for HopZ1a virulence and avirulence functions is discussed.
KW  - bacterial pathogenesis
KW  - defense signaling pathways
KW  - effectors
KW  - elicitors
KW  - HopZ1a
KW  - MAMPs
KW  - PAMPs
KW  - PBS1
KW  - Pseudomonas syringae
KW  - remorin
KW  - type-3 secretion
Y1  - 2019
U6  - https://doi.org/10.1094/MPMI-04-19-0105-R
SN  - 0894-0282
SN  - 1943-7706
VL  - 32
IS  - 9
SP  - 1229
EP  - 1242
PB  - Amer phytopathological  SOC
CY  - ST Paul
ER  - 
TY  - JOUR
A1  - Rojas-Jimenez, Keilor
A1  - Rieck, Angelika
A1  - Wurzbacher, Christian
A1  - Jürgens, Klaus
A1  - Labrenz, Matthias
A1  - Grossart, Hans-Peter
T1  - A Salinity Threshold Separating Fungal Communities in the Baltic Sea
JF  - Frontiers in Microbiology
N2  - Salinity is a significant factor for structuring microbial communities, but little is known for aquatic fungi, particularly in the pelagic zone of brackish ecosystems. In this study, we explored the diversity and composition of fungal communities following a progressive salinity decline (from 34 to 3 PSU) along three transects of ca. 2000 km in the Baltic Sea, the world’s largest estuary. Based on 18S rRNA gene sequence analysis, we detected clear changes in fungal community composition along the salinity gradient and found significant differences in composition of fungal communities established above and below a critical value of 8 PSU. At salinities below this threshold, fungal communities resembled those from freshwater environments, with a greater abundance of Chytridiomycota, particularly of the orders Rhizophydiales, Lobulomycetales, and
Gromochytriales. At salinities above 8 PSU, communities were more similar to those from marine environments and, depending on the season, were dominated by a strain of the LKM11 group (Cryptomycota) or by members of Ascomycota and Basidiomycota. Our results highlight salinity as an important environmental driver also for pelagic fungi, and thus should be taken into account to better understand fungal diversity and ecological function in the aquatic realm.
KW  - fungal diversity
KW  - baltic sea
KW  - salinity gradient
KW  - brackish waters
KW  - chytridiomycota
KW  - cryptomycota
Y1  - 2019
U6  - https://doi.org/10.3389/fmicb.2019.00680
SN  - 1664-302X
VL  - 10
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Trindade, Ines
T1  - A shelter for the future
BT  - how WUSCHEL protects the shoot apical meristem from viral infection
JF  - Molecular plant
N2  - Plant development in its majority occurs post-embryonically
through the activity of local meristems that provide daughter cells
for the development of new organs. It has long been acknowledged
that the shoot apical meristem (SAM), which holds the stem cells
that will form above-ground organs, is recalcitrant to infection by
multiple pathogens, a crucial strategy to safeguard normal devel-
opment and subsequent generations. However, the molecular
mechanisms underlying SAM immunity remain largely unknown.
Y1  - 2020
U6  - https://doi.org/10.1016/j.molp.2020.11.009
SN  - 1674-2052
SN  - 1752-9867
VL  - 13
IS  - 12
SP  - 1675
EP  - 1675
PB  - Cell Press
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Grimm, Volker
A1  - Berger, Uta
A1  - Bastiansen, Finn
A1  - Eliassen, Sigrunn
A1  - Ginot, Vincent
A1  - Giske, Jarl
A1  - Goss-Custard, John
A1  - Grand, Tamara
A1  - Heinz, Simone K.
A1  - Huse, Geir
A1  - Huth, Andreas
A1  - Jepsen, Jane U.
A1  - Jorgensen, Christian
A1  - Mooij, Wolf M.
A1  - Mueller, Birgit
A1  - Piou, Cyril
A1  - Railsback, Steven Floyd
A1  - Robbins, Andrew M.
A1  - Robbins, Martha M.
A1  - Rossmanith, Eva
A1  - Rueger, Nadja
A1  - Strand, Espen
A1  - Souissi, Sami
A1  - Stillman, Richard A.
A1  - Vabo, Rune
A1  - Visser, Ute
A1  - DeAngelis, Donald L.
T1  - A standard protocol for describing individual-based and agent-based models
JF  - Ecological modelling : international journal on ecological modelling and engineering and systems ecolog
N2  - Simulation models that describe autonomous individual organisms (individual based models, IBM) or agents (agent-based models, ABM) have become a widely used tool, not only in ecology, but also in many other disciplines dealing with complex systems made up of autonomous entities. However, there is no standard protocol for describing such simulation models, which can make them difficult to understand and to duplicate. This paper presents a proposed standard protocol, ODD, for describing IBMs and ABMs, developed and tested by 28 modellers who cover a wide range of fields within ecology. This protocol consists of three blocks (Overview, Design concepts, and Details), which are subdivided into seven elements: Purpose, State variables and scales, Process overview and scheduling, Design concepts, Initialization, Input, and Submodels. We explain which aspects of a model should be described in each element, and we present an example to illustrate the protocol in use. In addition, 19 examples are available in an Online Appendix. We consider ODD as a first step for establishing a more detailed common format of the description of IBMs and ABMs. Once initiated, the protocol will hopefully evolve as it becomes used by a sufficiently large proportion of modellers. (c) 2006 Elsevier B.V. All rights reserved.
KW  - individual-based model
KW  - agent-based model
KW  - model description
KW  - scientific communication
KW  - standardization
Y1  - 2006
U6  - https://doi.org/10.1016/j.ecolmodel.2006.04.023
SN  - 0304-3800
VL  - 198
SP  - 115
EP  - 126
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Cao, Xianyong
A1  - Tian, Fang
A1  - Andreev, Andrei
A1  - Anderson, Patricia M.
A1  - Lozhkin, Anatoly V.
A1  - Bezrukova, Elena
A1  - Ni, Jian
A1  - Rudaya, Natalia
A1  - Stobbe, Astrid
A1  - Wieczorek, Mareike
A1  - Herzschuh, Ulrike
T1  - A taxonomically harmonized and temporally standardized fossil pollen dataset from Siberia covering the last 40 kyr
JF  - Earth System Science Data
N2  - Pollen records from Siberia are mostly absent in global or Northern Hemisphere synthesis works. Here we present a taxonomically harmonized and temporally standardized pollen dataset that was synthesized using 173 palynological records from Siberia and adjacent areas (northeastern Asia, 42-75 degrees N, 50-180 degrees E). Pollen data were taxonomically harmonized, i.e. the original 437 taxa were assigned to 106 combined pollen taxa. Age-depth models for all records were revised by applying a constant Bayesian age-depth modelling routine. The pollen dataset is available as count data and percentage data in a table format (taxa vs. samples), with age information for each sample. The dataset has relatively few sites covering the last glacial period between 40 and 11.5 ka (calibrated thousands of years before 1950 CE) particularly from the central and western part of the study area. In the Holocene period, the dataset has many sites from most of the area, with the exception of the central part of Siberia. Of the 173 pollen records, 81 % of pollen counts were downloaded from open databases (GPD, EPD, PANGAEA) and 10 % were contributions by the original data gatherers, while a few were digitized from publications. Most of the pollen records originate from peatlands (48 %) and lake sediments (33 %). Most of the records (83 %) have >= 3 dates, allowing the establishment of reliable chronologies. The dataset can be used for various purposes, including pollen data mapping (example maps for Larix at selected time slices are shown) as well as quantitative climate and vegetation reconstructions. The datasets for pollen counts and pollen percentages are available at https://doi.org/10.1594/PANGAEA.898616 (Cao et al., 2019a), also including the site information, data source, original publication, dating data, and the plant functional type for each pollen taxa.
KW  - Late Quaternary vegetation
KW  - Holocene environmental history
KW  - eastern continental Asia
KW  - plant macrofossil data
KW  - late pleistocene
KW  - paleoenvironmental records
KW  - Verkhoyansk mountains
KW  - climate dynamics
KW  - glacial maximum
KW  - Northern Asia
Y1  - 2020
U6  - https://doi.org/10.5194/essd-12-119-2020
SN  - 1866-3508
SN  - 1866-3516
VL  - 12
IS  - 1
SP  - 119
EP  - 135
PB  - Copernics Publications
CY  - Katlenburg-Lindau
ER  - 
TY  - JOUR
A1  - Scheller, Frieder W.
A1  - Schmid, Rolf
T1  - A tribute to Isao Karube (1942-2020) and his influence on sensor science
JF  - Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica
KW  - Karube
KW  - Japan
KW  - biosensors
KW  - lifetime achievements
Y1  - 2020
U6  - https://doi.org/10.1007/s00216-020-02946-5
SN  - 1618-2642
SN  - 1618-2650
VL  - 412
IS  - 28
SP  - 7709
EP  - 7711
PB  - Springer
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Gonzalez-Fortes, Gloria M.
A1  - Tassi, F.
A1  - Trucchi, E.
A1  - Henneberger, K.
A1  - Paijmans, Johanna L. A.
A1  - Diez-del-Molino, D.
A1  - Schroeder, H.
A1  - Susca, R. R.
A1  - Barroso-Ruiz, C.
A1  - Bermudez, F. J.
A1  - Barroso-Medina, C.
A1  - Bettencourt, A. M. S.
A1  - Sampaio, H. A.
A1  - Salas, A.
A1  - de Lombera-Hermida, A.
A1  - Fabregas Valcarce, Ramón
A1  - Vaquero, M.
A1  - Alonso, S.
A1  - Lozano, Marina
A1  - Rodriguez-Alvarez, Xose Pedro
A1  - Fernandez-Rodriguez, C.
A1  - Manica, Andrea
A1  - Hofreiter, Michael
A1  - Barbujani, Guido
T1  - A western route of prehistoric human migration from Africa into the Iberian Peninsula
JF  - Proceedings of the Royal Society of London : B, Biological sciences
N2  - Being at the western fringe of Europe, Iberia had a peculiar prehistory and a complex pattern of Neolithization. A few studies, all based on modern populations, reported the presence of DNA of likely African origin in this region, generally concluding it was the result of recent gene flow, probably during the Islamic period. Here, we provide evidence of much older gene flow from Africa to Iberia by sequencing whole genomes from four human remains from northern Portugal and southern Spain dated around 4000 years BP (from the Middle Neolithic to the Bronze Age). We found one of them to carry an unequivocal sub-Saharan mitogenome of most probably West or West-Central African origin, to our knowledge never reported before in prehistoric remains outside Africa. Our analyses of ancient nuclear genomes show small but significant levels of sub-Saharan African affinity in several ancient Iberian samples, which indicates that what we detected was not an occasional individual phenomenon, but an admixture event recognizable at the population level. We interpret this result as evidence of an early migration process from Africa into the Iberian Peninsula through a western route, possibly across the Strait of Gibraltar.
KW  - palaeogenome
KW  - Africa
KW  - Iberia
KW  - mitochondrial DNA
KW  - gene flow
KW  - admixture
Y1  - 2019
U6  - https://doi.org/10.1098/rspb.2018.2288
SN  - 0962-8452
SN  - 1471-2954
VL  - 286
IS  - 1895
PB  - Royal Society
CY  - London
ER  - 
TY  - JOUR
A1  - Alker, Wiebke
A1  - Schwerdtle, Tanja
A1  - Schomburg, Lutz
A1  - Haase, Hajo
T1  - A Zinpyr-1-based Fluorimetric Microassay for Free Zinc in Human Serum
JF  - International journal of molecular sciences
N2  - Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual’s zinc status. The total serum zinc concentration, which is presently the most commonly used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body’s zinc status, and its suitability as a future biomarker for an individual’s zinc status.
KW  - zinc
KW  - free zinc
KW  - serum
KW  - biomarker
KW  - fluorescent probe
KW  - Zinypr-1
Y1  - 2019
U6  - https://doi.org/10.3390/ijms20164006
SN  - 1661-6596
SN  - 1422-0067
VL  - 20
IS  - 16
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Hasnat, Muhammad Abrar
A1  - Zupok, Arkadiusz
A1  - Olas-Apelt, Justyna Jadwiga
A1  - Müller-Röber, Bernd
A1  - Leimkühler, Silke
T1  - A-type carrier proteins are involved in [4Fe-4S] cluster insertion into the radical S-adenosylmethionine protein MoaA for the synthesis of active molybdoenzymes
JF  - Journal of bacteriology
N2  - Iron sulfur (Fe-S) clusters are important biological cofactors present in proteins with crucial biological functions, from photosynthesis to DNA repair, gene expression, and bioenergetic processes. For the insertion of Fe-S clusters into proteins, A-type carrier proteins have been identified. So far, three of them have been characterized in detail in Escherichia coli, namely, IscA, SufA, and ErpA, which were shown to partially replace each other in their roles in [4Fe-4S] cluster insertion into specific target proteins. To further expand the knowledge of [4Fe-4S] cluster insertion into proteins, we analyzed the complex Fe-S cluster-dependent network for the synthesis of the molybdenum cofactor (Moco) and the expression of genes encoding nitrate reductase in E. coli. Our studies include the identification of the A-type carrier proteins ErpA and IscA, involved in [4Fe-4S] cluster insertion into the radical Sadenosyl-methionine (SAM) enzyme MoaA. We show that ErpA and IscA can partially replace each other in their role to provide [4Fe-4S] clusters for MoaA. Since most genes expressing molybdoenzymes are regulated by the transcriptional regulator for fumarate and nitrate reduction (FNR) under anaerobic conditions, we also identified the proteins that are crucial to obtain an active FNR under conditions of nitrate respiration. We show that ErpA is essential for the FNR-dependent expression of the narGHJI operon, a role that cannot be compensated by IscA under the growth conditions tested. SufA does not appear to have a role in Fe-S cluster insertion into MoaA or FNR under anaerobic growth employing nitrate respiration, based on the low level of gene expression. <br /> IMPORTANCE Understanding the assembly of iron-sulfur (Fe-S) proteins is relevant to many fields, including nitrogen fixation, photosynthesis, bioenergetics, and gene regulation. Remaining critical gaps in our knowledge include how Fe-S clusters are transferred to their target proteins and how the specificity in this process is achieved, since different forms of Fe-S clusters need to be delivered to structurally highly diverse target proteins. Numerous Fe-S carrier proteins have been identified in prokaryotes like Escherichia coli, including ErpA, IscA, SufA, and NfuA. In addition, the diverse Fe-S cluster delivery proteins and their target proteins underlie a complex regulatory network of expression, to ensure that both proteins are synthesized under particular growth conditions.
KW  - iron-sulfur clusters
KW  - Moco biosynthesis
KW  - MoaA
KW  - A-type carrier protein
KW  - FNR
KW  - nitrate reductase
KW  - molybdenum cofactor
Y1  - 2021
U6  - https://doi.org/10.1128/JB.00086-21
SN  - 1098-5530
VL  - 203
IS  - 12
PB  - American Society for Microbiology
CY  - Washington
ER  - 
TY  - JOUR
A1  - Boekstegers, Felix
A1  - Marcelain, Katherine
A1  - Barahona Ponce, Carol
A1  - Baez Benavides, Pablo F.
A1  - Müller, Bettina
A1  - de Toro, Gonzalo
A1  - Retamales, Javier
A1  - Barajas, Olga
A1  - Ahumada, Monica
A1  - Aleksandrova, Krasimira
A1  - Bermejo, Justo Lorenzo
T1  - ABCB1/4 gallbladder cancer risk variants identified in India also show strong effects in Chileans
JF  - Cancer Epidemiology
N2  - Background: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence.
Methods: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication.
Results: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low.
Conclusion: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.
KW  - cancer epidemiology
KW  - gallbladder cancer
KW  - native American ancestry
KW  - population-specific risk marker
Y1  - 2020
VL  - 65
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Laux, Eva-Maria
A1  - Wenger, Christian
A1  - Bier, Frank Fabian
A1  - Hoelzel, Ralph
T1  - AC electrokinetic immobilization of organic dye molecules
JF  - Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry and Analusis
N2  - The application of inhomogeneous AC electric fields for molecular immobilization is a very fast and simple method that does not require any adaptions to the molecule's functional groups or charges. Here, the method is applied to a completely new category of molecules: small organic fluorescence dyes, whose dimensions amount to only 1 nm or even less. The presented setup and the electric field parameters used allow immobilization of dye molecules on the whole electrode surface as opposed to pure dielectrophoretic applications, where molecules are attracted only to regions of high electric field gradients, i.e., to the electrode tips and edges. In addition to dielectrophoresis and AC electrokinetic flow, molecular scale interactions and electrophoresis at short time scales are discussed as further mechanisms leading to migration and immobilization of the molecules.
KW  - AC electrokinetics
KW  - AC electrophoresis
KW  - Molecular dielectrophoresis
KW  - Interdigitated electrodes
KW  - Organic dyes
Y1  - 2020
U6  - https://doi.org/10.1007/s00216-020-02480-4
SN  - 1618-2642
SN  - 1618-2650
VL  - 412
IS  - 16
SP  - 3859
EP  - 3870
PB  - Springer
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Lang, Judith
A1  - Bohn, Patrick
A1  - Bhat, Hilal
A1  - Jastrow, Holger
A1  - Walkenfort, Bernd
A1  - Cansiz, Feyza
A1  - Fink, Julian
A1  - Bauer, Michael
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Lang, Karl S.
T1  - Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease
JF  - Nature Communications
N2  - Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1(-/-) mice results in replication of HSV-1 and Asah1(-/-) mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol.
KW  - immunology
KW  - infection
KW  - membrane fusion
KW  - phagocytosis
KW  - sphingolipids
Y1  - 2020
U6  - https://doi.org/10.1038/s41467-020-15072-8
SN  - 2041-1723
VL  - 11
IS  - 1
SP  - 1
EP  - 15
PB  - Nature Publishing Group UK
CY  - London
ER  - 
TY  - JOUR
A1  - Zeitler, Stefanie
A1  - Ye, Lian
A1  - Andreyeva, Aksana
A1  - Schumacher, Fabian
A1  - Monti, Juliana
A1  - Nürnberg, Bernd
A1  - Nowak, Gabriel
A1  - Kleuser, Burkhard
A1  - Reichel, Martin
A1  - Fejtova, Anna
A1  - Kornhuber, Johannes
A1  - Rhein, Cosima
A1  - Friedland, Kristina
T1  - Acid sphingomyelinase - a regulator of canonical transient receptor potential channel 6 (TRPC6) activity
JF  - Journal of neurochemistry
N2  - Recent investigations propose the acid sphingomyelinase (ASM)/ceramide system as a novel target for antidepressant action. ASM catalyzes the breakdown of the abundant membrane lipid sphingomyelin to the lipid messenger ceramide. This ASM‐induced lipid modification induces a local shift in membrane properties, which influences receptor clustering and downstream signaling. Canonical transient receptor potential channels 6 (TRPC6) are non‐selective cation channels located in the cell membrane that play an important role in dendritic growth, synaptic plasticity and cognition in the brain. They can be activated by hyperforin, an ingredient of the herbal remedy St. John’s wort for treatment of depression disorders. Because of their role in the context of major depression, we investigated the crosstalk between the ASM/ceramide system and TRPC6 ion channels in a pheochromocytoma cell line 12 neuronal cell model (PC12 rat pheochromocytoma cell line). Ca2+ imaging experiments indicated that hyperforin‐induced Ca2+ influx through TRPC6 channels is modulated by ASM activity. While antidepressants, known as functional inhibitors of ASM activity, reduced TRPC6‐mediated Ca2+ influx, extracellular application of bacterial sphingomyelinase rebalanced TRPC6 activity in a concentration‐related way. This effect was confirmed in whole‐cell patch clamp electrophysiology recordings. Lipidomic analyses revealed a decrease in very long chain ceramide/sphingomyelin molar ratio after ASM inhibition, which was connected with changes in the abundance of TRPC6 channels in flotillin‐1–positive lipid rafts as visualized by western blotting. Our data provide evidence that the ASM/ceramide system regulates TRPC6 channels likely by controlling their recruitment to specific lipid subdomains and thereby fine‐tuning their physical properties.
KW  - acid sphingomyelinase
KW  - antidepressants
KW  - ceramide
KW  - hyperforin
KW  - lipid rafts
KW  - TRPC6
Y1  - 2019
U6  - https://doi.org/10.1111/jnc.14823
SN  - 0022-3042
SN  - 1471-4159
VL  - 150
IS  - 6
SP  - 678
EP  - 690
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Beckmann, Nadine
A1  - Becker, Katrin Anne
A1  - Kadow, Stephanie
A1  - Schumacher, Fabian
A1  - Kramer, Melanie
A1  - Kuehn, Claudine
A1  - Schulz-Schaeffer, Walter J.
A1  - Edwards, Michael J.
A1  - Kleuser, Burkhard
A1  - Gulbins, Erich
A1  - Carpinteiro, Alexander
T1  - Acid Sphingomyelinase Deficiency Ameliorates Farber Disease
JF  - International journal of molecular sciences
N2  - Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients.
KW  - Farber disease
KW  - lysosomal storage disorders
KW  - acid ceramidase
KW  - acid sphingomyelinase
KW  - amitriptyline
Y1  - 2019
U6  - https://doi.org/10.3390/ijms20246253
SN  - 1422-0067
VL  - 20
IS  - 24
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Hoehn, Richard S.
A1  - Jernigan, Peter L.
A1  - Japtok, Lukasz
A1  - Chang, Alex L.
A1  - Midura, Emily F.
A1  - Caldwell, Charles C.
A1  - Kleuser, Burkhard
A1  - Lentsch, Alex B.
A1  - Edwards, Michael J.
A1  - Gulbins, Erich
A1  - Pritts, Timothy A.
T1  - Acid sphingomyelinase inhibition in stored erythrocytes reduces transfusion-associated lung inflammation
JF  - Annals of surgery : a monthly review of surgical science and practice
N2  - Objective: We aimed to identify the role of the enzyme acid sphingomyelinase in the aging of stored units of packed red blood cells (pRBCs) and subsequent lung inflammation after transfusion.
Summary Background Data: Large volume pRBC transfusions are associated with multiple adverse clinical sequelae, including lung inflammation. Microparticles are formed in stored pRBCs over time and have been shown to contribute to lung inflammation after transfusion.
Methods: Human and murine pRBCs were stored with or without amitriptyline, a functional inhibitor of acid sphingomyelinase, or obtained from acid sphingomyelinase-deficient mice, and lung inflammation was studied in mice receiving transfusions of pRBCs and microparticles isolated from these units.
Results: Acid sphingomyelinase activity in pRBCs was associated with the formation of ceramide and the release of microparticles. Treatment of pRBCs with amitriptyline inhibited acid sphingomyelinase activity, ceramide accumulation, and microparticle production during pRBC storage. Transfusion of aged pRBCs or microparticles isolated from aged blood into mice caused lung inflammation. This was attenuated after transfusion of pRBCs treated with amitriptyline or from acid sphingomyelinase-deficient mice.
Conclusions: Acid sphingomyelinase inhibition in stored pRBCs offers a novel mechanism for improving the quality of stored blood.
KW  - acid sphingomyelinase
KW  - blood banking
KW  - ceramide
KW  - lung inflammation
KW  - microparticle
Y1  - 2017
U6  - https://doi.org/10.1097/SLA.0000000000001648
SN  - 0003-4932
SN  - 1528-1140
VL  - 265
IS  - 1
SP  - 218
EP  - 226
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  - 
TY  - JOUR
A1  - McVey, Mark J.
A1  - Kim, Michael
A1  - Tabuchi, Arata
A1  - Srbely, Victoria
A1  - Japtok, Lukasz
A1  - Arenz, Christoph
A1  - Rotstein, Ori
A1  - Kleuser, Burkhard
A1  - Semple, John W.
A1  - Kuebler, Wolfgang M.
T1  - Acid sphingomyelinase mediates murine acute lung injury following transfusion of aged platelets
JF  - American journal of physiology : Lung cellular and molecular physiology
N2  - Pulmonary complications from stored blood products are the leading cause of mortality related to transfusion. Transfusion-related acute lung injury is mediated by antibodies or bioactive mediators, yet underlying mechanisms are incompletely understood. Sphingolipids such as ceramide regulate lung injury, and their composition changes as a function of time in stored blood. Here, we tested the hypothesis that aged platelets may induce lung injury via a sphingolipid-mediated mechanism. To assess this hypothesis, a two-hit mouse model was devised. Recipient mice were treated with 2 mg/kg intraperitoneal lipopolysaccharide (priming) 2 h before transfusion of 10 ml/kg stored (1-5 days) platelets treated with or without addition of acid sphingomyelinase inhibitor ARC39 or platelets from acid sphingomyelinase-deficient mice, which both reduce ceramide formation. Transfused mice were examined for signs of pulmonary neutrophil accumulation, endothelial barrier dysfunction, and histological evidence of lung injury. Sphingolipid profiles in stored platelets were analyzed by mass spectrophotometry. Transfusion of aged platelets into primed mice induced characteristic features of lung injury, which increased in severity as a function of storage time. Ceramide accumulated in platelets during storage, but this was attenuated by ARC39 or in acid sphingomyelinase-deficient platelets. Compared with wild-type platelets, transfusion of ARC39-treated or acid sphingomyelinase-deficient aged platelets alleviated lung injury. Aged platelets elicit lung injury in primed recipient mice, which can be alleviated by pharmacological inhibition or genetic deletion of acid sphingomyelinase. Interventions targeting sphingolipid formation represent a promising strategy to increase the safety and longevity of stored blood products.
KW  - transfusion-related acute lung injury
KW  - ceramide
KW  - acid sphingomyelinase
KW  - platelets
KW  - storage
Y1  - 2017
U6  - https://doi.org/10.1152/ajplung.00317.2016
SN  - 1040-0605
SN  - 1522-1504
VL  - 312
IS  - 5
SP  - 625
EP  - 637
PB  - American Physiological Society
CY  - Bethesda
ER  -