49108
2019
2019
eng
1515
1527
13
6
93
article
Springer
Heidelberg
1
2019-04-15
2019-04-15
--
1-Methoxy-3-indolylmethyl DNA adducts in six tissues, and blood protein adducts, in mice under pak choi diet: time course and persistence
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.
Archives of toxicology : official journal of EUROTOX
10.1007/s00204-019-02452-3
30993378
0340-5761
1432-0738
wos:2019
WOS:000475702100006
Glatt, H (reprint author), Inst Human Nutr Potsdam Rehbrucke, Dept Nutr Toxicol, Arthur Scheunert Allee 114-116, D-14558 Nuthetal, Germany.; Glatt, H (reprint author), Fed Inst Risk Assessment, Dept Food Safety, Max Dohrn Str 8-10, D-10589 Berlin, Germany., wiesner@igzev.de; glatt@dife.de
German Federal Ministry of Education and ResearchFederal Ministry of Education & Research (BMBF) [0315370D]
2021-01-27T08:56:34+00:00
sword
importub
filename=package.tar
21a68ea5eada776ca59841d973d50434
Glatt, Hansruedi
false
true
Melanie Wiesner-Reinhold
Gitte Barknowitz
Simone Florian
Inga Mewis
Fabian Schumacher
Monika Schreiner
Hansruedi Glatt
eng
uncontrolled
1-Methoxy-3-indolylmethyl glucosinolate
eng
uncontrolled
Neoglucobrassicin
eng
uncontrolled
DNA adducts
eng
uncontrolled
Blood protein adducts
eng
uncontrolled
Pak choi
Biowissenschaften; Biologie
Institut für Ernährungswissenschaft
Referiert
Import
52262
2018
2018
eng
46
77
32
381
article
Elsevier
Amsterdam
1
2018-05-08
--
--
A beta distribution-based moment closure enhances the reliability of trait-based aggregate models for natural populations and communities
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.
Ecological modelling : international journal on ecological modelling and engineering and systems ecolog
10.1016/j.ecolmodel.2018.02.001
0304-3800
1872-7026
wos:2018
WOS:000435052000005
Klauschies, T (reprint author), Univ Potsdam, Inst Biochem & Biol, Dept Ecol & Ecosyst Modeling, Neuen Palais 10, D-14469 Potsdam, Germany., tklausch@uni-potsdam.de; renato.coutinho@ufabc.edu.br; gaedke@uni-potsdam.de
German Research Foundation (DFG)German Research Foundation (DFG) [GA 401/26-1]; Sao Paulo Research Foundation (FAPESP), BrazilFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2014/23497-0]
2021-10-18T07:33:32+00:00
sword
importub
filename=package.tar
33a3a1a83ece3eae53ebb11d1fcc9435
Klauschies, Toni
false
true
Toni Klauschies
Renato Mendes Coutinho
Ursula Gaedke
eng
uncontrolled
Moment closure
eng
uncontrolled
Normal and beta distribution
eng
uncontrolled
Skewed and peaked trait distributions
eng
uncontrolled
Fitness landscape and frequency-dependent selection
eng
uncontrolled
Eco-evolutionary dynamics
eng
uncontrolled
Modelling functional diversity
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Import
44508
2020
2019
eng
26
2
21
article
Molecular Diversity Preservation International
Basel
1
2020-01-09
2019-12-05
--
A Biostimulant Obtained from the Seaweed Ascophyllum nodosum Protects Arabidopsis thaliana from Severe Oxidative Stress
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.
International Journal of Molecular Sciences
10.3390/ijms21020474
1422-0067
Universität Potsdam
PA 2020_009
1243.0
<a href="https://doi.org/10.25932/publishup-44509">Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 823</a>
474
CC-BY - Namensnennung 4.0 International
Mohammad Amin Omidbakhshfard
Sujeeth Neerakkal
Saurabh Gupta
Nooshin Omranian
Kieran J. Guinan
Yariv Brotman
Zoran Nikoloski
Alisdair R. Fernie
Bernd Mueller-Roeber
Tsanko S. Gechev
eng
uncontrolled
Ascophyllum nodosum
eng
uncontrolled
Arabidopsis thaliana
eng
uncontrolled
biostimulant
eng
uncontrolled
paraquat
eng
uncontrolled
priming
eng
uncontrolled
oxidative stress tolerance
eng
uncontrolled
reactive oxygen species
Chemie und zugeordnete Wissenschaften
Biowissenschaften; Biologie
Mathematisch-Naturwissenschaftliche Fakultät
Referiert
Publikationsfonds der Universität Potsdam
Open Access
52584
2020
eng
15
1
10
article
Springer Nature
Berlin
1
2020-09-03
--
--
A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort
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.
Scientific Reports
Universität Potsdam
<a href="https://doi.org/10.25932/publishup-52582">Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 1200</a>
14541
false
false
CC-BY - Namensnennung 4.0 International
Sofa Christakoudi
Konstantinos K. Tsilidis
David C. Muller
Heinz Freisling
Elisabete Weiderpass
Kim Overvad
Stefan Söderberg
Christel Häggström
Tobias Pischon
Christina C. Dahm
Jie Zhang
Anne Tjønneland
Matthias Bernd Schulze
eng
uncontrolled
all-cause mortality
eng
uncontrolled
anthropometric measures
eng
uncontrolled
mass index
eng
uncontrolled
overweight
eng
uncontrolled
cancer
eng
uncontrolled
prediction
eng
uncontrolled
adiposity
eng
uncontrolled
size
Biowissenschaften; Biologie
Institut für Ernährungswissenschaft
Referiert
Gold Open-Access
62883
2022
2022
eng
11
10
article
Frontiers Media
Lausanne
1
2022-04-28
2022-04-28
--
A Cell-free Expression Pipeline for the Generation and Functional Characterization of Nanobodies
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.
Frontiers in Bioengineering and Biotechnology
10.3389/fbioe.2022.896763
35573250
2296-4185
outputup:dataSource:WoS:2022
896763
WOS:000794317900001
Kubick, S (corresponding author), Fraunhofer Inst Cell Therapy & Immunol IZI, Branch Bioanalyt & Bioproc IZI BB, Potsdam, Germany.; Kubick, S (corresponding author), Free Univ Berlin, Inst Chem & Biochem, Berlin, Germany.; Kubick, S (corresponding author), Brandenburg Univ Technol Cottbus Senftenberg, Joint Fac, Fac Hlth Sci, Brandenburg Med Sch Theodor Fontane, Potsdam, Germany.; Kubick, S (corresponding author), Univ Potsdam, Potsdam, Germany., Stefan.Kubick@izi-bb.fraunhofer.de
Kubick, Stefan
2024-03-06T14:01:39+00:00
sword
importub
filename=package.tar
820ff070ee5b8e830b15a8dfdae44968
false
true
CC-BY - Namensnennung 4.0 International
Lisa Haueis
Marlitt Stech
Stefan Kubick
eng
uncontrolled
cell-free protein synthesis
eng
uncontrolled
In vitro transcription
eng
uncontrolled
translation
eng
uncontrolled
nanobody
eng
uncontrolled
VHH
eng
uncontrolled
camelid
eng
uncontrolled
CHO cell lysate
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Import
Gold Open-Access
DOAJ gelistet
62780
2022
2022
eng
801
810
10
67
article
Springer
Dordrecht
1
2022-06-06
2022-06-06
--
A combined de novo assembly approach increases the quality of prokaryotic draft genomes
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.
Folia microbiologica : international journal for general, environmental and applied microbiology, and immunology
10.1007/s12223-022-00980-7
35668290
0015-5632
1874-9356
outputup:dataSource:WoS:2022
WOS:000806656300001
Unlu, ES (corresponding author), Abant Izzet Baysal Univ, Fac Arts & Sci, Dept Chem, Bolu, Turkey., esunlu06@gmail.com
Ünlü, Ercan Selçuk
2024-02-26T11:10:58+00:00
sword
importub
filename=package.tar
a3a0b5924182143a84839127a84cd43b
false
true
Uğur Çabuk
Ercan Selçuk Ünlü
eng
uncontrolled
De novo assembly
eng
uncontrolled
Prokaryotes
eng
uncontrolled
Bacteria
eng
uncontrolled
NGS
eng
uncontrolled
Short reads
eng
uncontrolled
Draft genome
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Import
49489
2018
2018
eng
21
2
89
article
Wiley
Hoboken
1
2018-11-29
2018-11-29
--
A comprehensive analysis of autocorrelation and bias in home range estimation
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.
Ecological monographs : a publication of the Ecological Society of America.
10.1002/ecm.1344
0012-9615
1557-7015
wos:2019
UNSP e01344
WOS:000477640700002
Calabrese, JM (reprint author), Natl Zool Pk, Smithsonian Conservat Biol Inst, 1500 Remt Rd, Front Royal, VA 22630 USA.; Calabrese, JM (reprint author), Univ Maryland, Dept Biol, College Pk, MD 20742 USA., calabresej@si.edu
US NSF Advances in Biological Informatics program [ABI-1458748]; Smithsonian Institution CGPS grant; Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [DFG-GRK 2118/1]; Robert Bosch Foundation; NASANational Aeronautics & Space Administration (NASA) [NNX15AV92A]
2021-02-16T08:59:57+00:00
sword
importub
filename=package.tar
26aac959a856d5efd8e020306b631bdd
Calabrese, Justin M.
false
true
Michael J. Noonan
Marlee A. Tucker
Christen H. Fleming
Thomas S. Akre
Susan C. Alberts
Abdullahi H. Ali
Jeanne Altmann
Pamela Castro Antunes
Jerrold L. Belant
Dean Beyer
Niels Blaum
Katrin Boehning-Gaese
Laury Cullen Jr
Rogerio Cunha de Paula
Jasja Dekker
Jonathan Drescher-Lehman
Nina Farwig
Claudia Fichtel
Christina Fischer
Adam T. Ford
Jacob R. Goheen
Rene Janssen
Florian Jeltsch
Matthew Kauffman
Peter M. Kappeler
Flavia Koch
Scott LaPoint
A. Catherine Markham
Emilia Patricia Medici
Ronaldo G. Morato
Ran Nathan
Luiz Gustavo R. Oliveira-Santos
Kirk A. Olson
Bruce D. Patterson
Agustin Paviolo
Emiliano Estero Ramalho
Sascha Rosner
Dana G. Schabo
Nuria Selva
Agnieszka Sergiel
Marina Xavier da Silva
Orr Spiegel
Peter Thompson
Wiebke Ullmann
Filip Zieba
Tomasz Zwijacz-Kozica
William F. Fagan
Thomas Mueller
Justin M. Calabrese
eng
uncontrolled
animal movement
eng
uncontrolled
kernel density estimation
eng
uncontrolled
local convex hull
eng
uncontrolled
minimum convex polygon
eng
uncontrolled
range distribution
eng
uncontrolled
space use
eng
uncontrolled
telemetry
eng
uncontrolled
tracking data
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Import
Bronze Open-Access
53320
2018
2018
eng
E2566
E2574
9
11
115
article
National Acad. of Sciences
Washington
1
2018-02-26
2018-02-26
--
A comprehensive genomic history of extinct and living elephants
Proceedings of the National Academy of Sciences of the United States of America
10.1073/pnas.1720554115
29483247
0027-8424
wos:2018
WOS:000427245400014
Palkopoulou, E; Reich, D (reprint author), Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.; Palkopoulou, E; Reich, D (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA., elle.palkopoulou@gmail.com; reich@genetics.med.harvard.edu
National Human Genome Research InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [U54 HG003067-08]; US Fish and Wildlife Service African Elephant Conservation FundUS Fish & Wildlife Service; Wellcome TrustWellcome Trust [WT098051, WT108749/Z/15/Z]; European Molecular Biology Laboratory; European Research CouncilEuropean Research Council (ERC) [310763 GeneFlow]; Natural Sciences and Engineering Research Council of CanadaNatural Sciences and Engineering Research Council of Canada [RFMAC-10539150]; Canada Research Chairs programCanada Research Chairs; NSF (HOMINID) Grant [BCS-1032255]; NIH (National Institute of General Medical Sciences) Grant [GM100233]
2022-01-06T12:48:51+00:00
sword
importub
filename=package.tar
012c9c2018c402e1455926599b6541d5
Palkopoulou, Eleftheria
Reich, David
false
true
Eleftheria Palkopoulou
Mark Lipson
Swapan Mallick
Svend Nielsen
Nadin Rohland
Sina Isabelle Baleka
Emil Karpinski
Atma M. Ivancevici
Thu-Hien To
Daniel Kortschak
Joy M. Raison
Zhipeng Qu
Tat-Jun Chin
Kurt W. Alt
Stefan Claesson
Love Dalen
Ross D. E. MacPhee
Harald Meller
Alfred L. Rocar
Oliver A. Ryder
David Heiman
Sarah Young
Matthew Breen
Christina Williams
Bronwen L. Aken
Magali Ruffier
Elinor Karlsson
Jeremy Johnson
Federica Di Palma
Jessica Alfoldi
David L. Adelsoni
Thomas Mailund
Kasper Munch
Kerstin Lindblad-Toh
Michael Hofreiter
Hendrik Poinar
David Reich
eng
uncontrolled
paleogenomics
eng
uncontrolled
elephantid evolution
eng
uncontrolled
mammoth
eng
uncontrolled
admixture
eng
uncontrolled
species divergence
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Import
Bronze Open-Access
49703
2019
2019
eng
15
10
article
Nature Publ. Group
London
1
2019-04-17
2019-04-17
--
A conserved CCM complex promotes apoptosis non-autonomously by regulating zinc homeostasis
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.
Nature Communications
10.1038/s41467-019-09829-z
30996251
2041-1723
wos:2019
1791
WOS:000464976200004
Derry, WB (reprint author), Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.; Derry, WB (reprint author), Hosp Sick Children, Dev & Stem Cell Biol Program, Peter Gilgan Ctr Res & Learning, Toronto, ON M5G 0A4, Canada., brent.derry@sickkids.ca
Canadian Institutes of Health Research (CIHR)Canadian Institutes of Health Research (CIHR) [MOP 137089]; CIHR FoundationCanadian Institutes of Health Research (CIHR) [FDN 143301]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 NS092521]; Excellence cluster REBIRTH by Deutsche Forschungsgemeinschaft (DFG) [SFB958, SE2016/7-2, SE2016/10-1]; DZHK; Alexander Graham Bell Canada Graduate Scholarship from the Natural Sciences and Engineering Council of Canada; Terry Fox Foundation Strategic Training in Transdisciplinary Radiation Science Scholarship; Safadi Translational Fellowship; Sigrid Juselius FoundationSigrid Juselius Foundation
2021-03-02T10:20:43+00:00
sword
importub
filename=package.tar
710287a9f9a587d809ef923a9770f9a3
Derry, W. Brent
false
true
CC-BY - Namensnennung 4.0 International
Eric M. Chapman
Benjamin Lant
Yota Ohashi
Bin Yu
Michael Schertzberg
Christopher Go
Deepika Dogra
Janne Koskimaki
Romuald Girard
Yan Li
Andrew G. Fraser
Issam A. Awad
Salim Abdelilah-Seyfried
Anne-Claude Gingras
William Brent Derry
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Import
Gold Open-Access
DOAJ gelistet
52207
2021
2021
eng
20
9
11
article
MDPI
Basel
1
2021-09-03
2021-07-14
--
A Conserved Hydrophobic Moiety and Helix-Helix Interactions Drive the Self-Assembly of the Incretin Analog Exendin-4
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.
Biomolecules
2218-273X
10.3390/biom11091305
Universität Potsdam
PA 2021_108
1931.47
<a href="https://doi.org/10.25932/publishup-52208">Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 1161</a>
1305
Thalhammer, Anja
CC-BY - Namensnennung 4.0 International
Martin Wolff
Klaus Gast
Andreas Evers
Michael Kurz
Stefania Pfeiffer-Marek
Anja Schüler
Robert Seckler
Anja Thalhammer
eng
uncontrolled
biophysics
eng
uncontrolled
diabetes
eng
uncontrolled
peptides
eng
uncontrolled
oligomerization
eng
uncontrolled
conformational change
eng
uncontrolled
molecular modeling
eng
uncontrolled
static and dynamic light scattering
eng
uncontrolled
spectroscopy
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Publikationsfonds der Universität Potsdam
Gold Open-Access
62229
2021
2021
eng
5
97
article
Elsevier
Oxford
1
2021-05-25
2021-05-25
--
A coumestan and a coumaronochromone from Millettia lasiantha
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.
Biochemical systematics and ecology
10.1016/j.bse.2021.104277
0305-1978
1873-2925
outputup:dataSource:WoS:2021
104277
WOS:000677436100016
Buyinza, Daniel (corresponding author), Kabale Univ, Dept Chem, POB 317, Kabale, Uganda., buyinza.daniel2015@gmail.com
International Science Program (ISP) [KEN 02]
Buyinza, Daniel
2024-01-22T08:20:28+00:00
sword
importub
filename=package.tar
9111f13831e78314a0981739fecab63c
1499902-X
187551-6
false
true
Daniel Buyinza
Solomon Derese
Albert Ndakala
Matthias Heydenreich
Abiy Yenesew
Andreas Koch
Richard Oriko
eng
uncontrolled
Millettia lasiantha
eng
uncontrolled
Leguminosae
eng
uncontrolled
Coumestan
eng
uncontrolled
Coumaronochromone
Biowissenschaften; Biologie
Institut für Chemie
Referiert
Import
47820
2019
2019
eng
87
92
6
499
article
Elsevier
Amsterdam
1
2019-09-04
--
--
A cross-reactive monoclonal antibody as universal detection antibody in autoantibody diagnostic assays
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.
Clinica chimica acta
10.1016/j.cca.2019.09.003
31493374
0009-8981
1873-3492
wos:2019
WOS:000500383600013
Hanack, K (reprint author), Univ Potsdam, Inst Biochem & Biol, Dept Biotechnol, Karl Liebknecht Str 24-25, D-14476 Potsdam, Germany., katja.hanack@uni-potsdam.de
Federal Ministry for Economic Affairs and Energy (BMWi)Federal Ministry for Economic Affairs and Energy (BMWi) [KF2144007CS4]
importub
2020-10-02T09:16:15+00:00
filename=package.tar
1a3baa48757530b96e18fda4573b374c
false
true
Steffi Luetkecosmann
Thomas Faupel
Silvia Porstmann
Tomas Porstmann
Burkhard Micheel
Katja Hanack
eng
uncontrolled
Monoclonal antibody
eng
uncontrolled
Detection
eng
uncontrolled
Autoimmune diagnostics
eng
uncontrolled
Cross reactivity
eng
uncontrolled
Assay calibration
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Import
50175
2019
2019
eng
12
9
article
Nature Publ. Group
London
1
--
2019-02-27
--
A familial congenital heart disease with a possible multigenic origin involving a mutation in BMPR1A
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.
Scientific reports
10.1038/s41598-019-39648-7
30814609
2045-2322
wos:2019
2959
WOS:000459799800108
Erdmann, J (reprint author), Univ Lubeck, DZHK German Res Ctr Cardiovasc Res, Univ Heart Ctr Lubeck, Inst Cardiogenet, Partner Site Hamburg Lubeck Kiel, D-23562 Lubeck, Germany.; Abdelilah-Seyfried, S (reprint author), Hannover Med Sch, Inst Mol Biol, D-30625 Hannover, Germany.; Abdelilah-Seyfried, S (reprint author), Potsdam Univ, Inst Biochem & Biol, D-14476 Potsdam, Germany., jeanette.erdmann@uni-luebeck.de; salim.seyfried@uni-potsdam.de
Excellence cluster REBIRTH [SFB958]; DZHK (Deutsches Zentrum fur Herz-Kreislauf-Forschung e.V.); Kaltenbach grant of the Deutsche Herzstiftung e.V.; scholarship "Lubecker Exzellenzmedizin" of the University of Lubeck; DZHK; Joachim Herz foundation; Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [SE2016/7-2, SE2016/10-1]
2021-04-06T09:01:57+00:00
sword
importub
filename=package.tar
ab11d0e51d7203cb37e7d8f6f1a9be27
Erdmann, Jeanette
Abdelilah-Seyfried, Salim
false
true
CC-BY - Namensnennung 4.0 International
Till Joscha Demal
Melina Heise
Benedikt Reiz
Deepika Dogra
Ingrid Braenne
Hermann Reichenspurner
Jörg Männer
Zouhair Aherrahrou
Heribert Schunkert
Jeanette Erdmann
Salim Abdelilah-Seyfried
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Import
Gold Open-Access
DOAJ gelistet
61211
2020
2020
eng
3871
3880
10
7
24
article
European Geosciences Union (EGU) ; Copernicus
Munich
1
2020-07-30
2020-07-30
--
A Fast-Response Automated Gas Equilibrator (FaRAGE) for continuous in situ measurement of CH4 and CO2 dissolved in water
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.
Hydrology and earth system sciences : HESS
10.5194/hess-24-3871-2020
1027-5606
1607-7938
outputup:dataSource:WoS:2020
WOS:000557883500002
Liu, L; Grossart, HP (corresponding author), Leibniz Inst Freshwater Ecol & Inland Fisheries, Dept Expt Limnol, D-16775 Stechlin, Germany.; Grossart, HP (corresponding author), Potsdam Univ, Inst Biochem & Biol, D-14669 Potsdam, Germany., liu.liu@igb-berlin.de; hgrossart@igb-berlin.de
National Natural Science Foundation of ChinaNational Natural Science; Foundation of China (NSFC) [51979148, 91647207]; German Research; FoundationGerman Research Foundation (DFG) [DFG GR1540/21-1]
Liu, Liu
Grossart, Hans-Peter
2023-11-03T08:58:15+00:00
sword
importub
filename=package.tar
8b7096ecb0fd858abc3eedd77a4d5dc8
2100610-6
2020249-0
false
true
CC-BY - Namensnennung 4.0 International
Shangbin Xiao
Liu Liu
Wei Wang
Andreas Lorke
Jason Nicholas Woodhouse
Hans-Peter Grossart
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Import
Gold Open-Access
DOAJ gelistet
55415
2017
2016
eng
1301
1315
15
2
173
article
American Society of Plant Physiologists
Rockville
1
2016-12-29
2016-12-29
--
A Flowering Locus C Homolog Is a Vernalization-Regulated Repressor in Brachypodium and Is Cold Regulated in Wheat
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.
Plant physiology : an international journal devoted to physiology, biochemistry, cellular and molecular biology, biophysics and environmental biology of plants
10.1104/pp.16.01161
28034954
0032-0889
1532-2548
wos:2017
WOS:000394140800029
Geuten, K (reprint author), Katholieke Univ Leuven, Dept Biol, B-3001 Leuven, Belgium., koen.geuten@kuleuven.be
2022-06-30T09:24:36+00:00
sword
importub
filename=package.tar
306a846ad1ae0748f9c4ef27b011d278
Geuten, Koen
false
true
CC-BY - Namensnennung 4.0 International
Neha Sharma
Philip Ruelens
Thomas Maggen
Niklas Dochy
Sanne Torfs
Kerstin Kaufmann
Antje Rohde
Koen Geuten
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Import
55274
2017
2017
eng
234
252
19
121
article
Elsevier
Oxford
1
2016-12-27
2016-12-27
--
A genomic comparison of putative pathogenicity-related gene families in five members of the Ophiostomatales with different lifestyles
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.
Fungal biology
10.1016/j.funbio.2016.12.002
28215351
1878-6146
1878-6162
wos:2017
WOS:000395614700004
Lah, L (reprint author), Univ Potsdam, Evolutionary Biol, Karl Liebknecht Str 24-25, D-14476 Potsdam, Germany., ljerka.lah@uni-potsdam.de
2022-06-22T08:21:29+00:00
sword
importub
filename=package.tar
99aadf52a4bc2c8714fff8d7b4ee1cb8
Lah, Ljerka
false
true
Ljerka Lah
Ulrike Löber
Tom Hsiang
Stefanie Hartmann
eng
uncontrolled
Bark beetle
eng
uncontrolled
Bluestain fungi
eng
uncontrolled
Ips typographus
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Import
52502
2020
2019
eng
12
5
1
article
Science Direct
New York
1
2020-02-05
2019-09-04
--
A highly efficient agrobacterium-mediated method for transient gene expression and functional studies in multiple plant species
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.
Plant Communications
2590-3462
Universität Potsdam
<a href="https://doi.org/10.25932/publishup-52425">Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 1189</a>
100028
false
false
CC-BY-NC-ND - Namensnennung, nicht kommerziell, keine Bearbeitungen 4.0 International
Youjun Zhang
Moxian Chen
Beata Siemiatkowska
Mitchell Rey Toleco
Yue Jing
Vivien Strotmann
Jianghua Zhang
Yvonne Stahl
Alisdair R. Fernie
eng
uncontrolled
transient expression
eng
uncontrolled
agro-infiltration
eng
uncontrolled
subcellular localization
eng
uncontrolled
protein-protein interaction
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Gold Open-Access
43564
2019
2019
eng
14
47
15
article
BioMed Central
London
1
2019-05-18
2019-05-18
--
A high‑throughput amplicon‑based method for estimating outcrossing rates
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.
Plant Methods
10.1186/s13007-019-0433-9
1746-4811
Universität Potsdam
PA 2019_44
1894.48
<a href="http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-435657">Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 745</a>
false
false
CC-BY - Namensnennung 4.0 International
Friederike Jantzen
Natalia Joanna Wozniak
Christian Kappel
Adrien Sicard
Michael Lenhard
eng
uncontrolled
Outcrossing
eng
uncontrolled
Mixed mating
eng
uncontrolled
Outcrossing rate
eng
uncontrolled
Capsella
eng
uncontrolled
Amplicon sequencing
Biowissenschaften; Biologie
Pflanzen (Botanik)
open_access
Institut für Biochemie und Biologie
Referiert
Publikationsfonds der Universität Potsdam
Open Access
52585
2021
2021
eng
13
41
article
Elsevier
Amsterdam
1
--
--
--
A matter of concern
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
Redox Biology
trace element dyshomeostasis and genomic stability in neurons
10.1016/j.redox.2021.101877
false
false
CC-BY - Namensnennung 4.0 International
Viktoria Klara Veronika Wandt
Nicola Lisa Winkelbeiner
Julia Bornhorst
Barbara Witt
Stefanie Raschke
Luise Simon
Franziska Ebert
Anna Patricia Kipp
Tanja Schwerdtle
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
58566
2020
2020
eng
24
12
16
article
PLoS
San Fransisco
1
2020-12-15
2020-12-15
--
A mechanistic framework for a priori pharmacokinetic predictions of orally inhaled drugs
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.
PLoS Computational Biology : a new community journal
10.1371/journal.pcbi.1008466
33320846
1553-734X
1553-7358
outputup:dataSource:WoS:2020
e1008466
WOS:000600141200001
Hartung, N (corresponding author), Univ Potsdam, Inst Math, Potsdam, Germany., niklas.hartung@uni-potsdam.de
Hartung, Niklas
2023-03-28T06:24:37+00:00
sword
importub
filename=package.tar
6ece40e24350762f6dff35cd9cf2d97e
2193340-6
2740066-9
false
true
CC-BY - Namensnennung 4.0 International
Niklas Hartung
Jens Markus Borghardt
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
Medizin und Gesundheit
Institut für Mathematik
Referiert
Import
Gold Open-Access