TY  - THES
A1  - Aga-Barfknecht, Heja
T1  - Investigation of the phenotype and genetic variant(s) of the diabetes locus Nidd/DBA
N2  - Diabetes is a major public health problem with increasing global prevalence. Type 2 diabetes (T2D), which accounts for 90% of all diagnosed cases, is a complex polygenic disease also modulated by epigenetics and lifestyle factors. For the identification of T2D-associated genes, linkage analyses combined with mouse breeding strategies and bioinformatic tools were useful in the past. In a previous study in which a backcross population of the lean and diabetes-prone dilute brown non-agouti (DBA) mouse and the obese and diabetes-susceptible New Zealand obese (NZO) mouse was characterized, a major diabetes quantitative trait locus (QTL) was identified on chromosome 4. The locus was designated non-insulin dependent diabetes from DBA (Nidd/DBA). The aim of this thesis was (i) to perform a detailed phenotypic characterization of the Nidd/DBA mice, (ii) to further narrow the critical region and (iii) to identify the responsible genetic variant(s) of the Nidd/DBA locus. The phenotypic characterization of recombinant congenic mice carrying a 13.6 Mbp Nidd/DBA fragment with 284 genes presented a gradually worsening metabolic phenotype. Nidd/DBA allele carriers exhibited severe hyperglycemia (~19.9 mM) and impaired glucose clearance at 12 weeks of age. Ex vivo perifusion experiments with islets of 13-week-old congenic mice revealed a tendency towards reduced insulin secretion in homozygous DBA mice. In addition, 16-week-old mice showed a severe loss of β-cells and reduced pancreatic insulin content. Pathway analysis of transcriptome data from islets of congenic mice pointed towards a downregulation of cell survival genes. Morphological analysis of pancreatic sections displayed a reduced number of bi-hormonal cells co-expressing glucagon and insulin in homozygous DBA mice, which could indicate a reduced plasticity of endocrine cells in response to hyperglycemic stress. Further generation and phenotyping of recombinant congenic mice enabled the isolation of a 3.3 Mbp fragment that was still able to induce hyperglycemia and contained 61 genes. Bioinformatic analyses including haplotype mapping, sequence and transcriptome analysis were integrated in order to further reduce the number of candidate genes and to identify the presumable causative gene variant. Four putative candidate genes (Ttc39a, Kti12, Osbpl9, Calr4) were defined, which were either differentially expressed or carried a sequence variant. In addition, in silico ChIP-Seq analyses of the 3.3 Mbp region indicated a high number of SNPs located in active regions of binding sites of β-cell transcription factors. This points towards potentially altered cis-regulatory elements that could be responsible for the phenotype conferred by the Nidd/DBA locus. In summary, the Nidd/DBA locus mediates impaired glucose homeostasis and reduced insulin secretion capacity which finally leads to β-cell death. The downregulation of cell survival genes and reduced plasticity of endocrine cells could further contribute to the β-cell loss. The critical region was narrowed down to a 3.3 Mbp fragment containing 61 genes, of which four might be involved in the development of the diabetogenic Nidd/DBA phenotype.
N2  - Die Diabetesprävalenz nimmt seit Jahren weltweit zu, wobei etwa 90% der diagnostizierten Diabeteserkrankungen einem Typ-2-Diabetes (T2D) zuzuordnen sind. T2D ist eine komplexe polygene Stoffwechselerkrankung, die auch durch epigenetische Faktoren und den Lebensstil beeinflusst wird. Die Identifizierung und Untersuchung von Diabetes-assoziierten Genen wird unter anderem durch Kopplungsanalysen und darauf aufbauende zuchtstrategische und bioinformatische Analysen ermöglicht. In einer vorangegangenen Studie wurde der schlanke, Diabetes-anfällige dilute brown non-agouti (DBA)-Mausstamm mit der adipösen und ebenfalls Diabetes-suszeptiblen New Zealand obese (NZO)-Maus verpaart und die erste Rückkreuzungsgeneration einer Kopplungsanalyse unterzogen. Hierbei wurde ein hoch signifikanter quantitative trait locus (QTL) für Diabetes auf Chromosom 4 nachgewiesen. Dieser Locus ist mit erhöhten Blutzuckerwerten, reduzierten Plasmainsulinkonzentrationen und einem niedrigen pankreatischen Insulingehalt assoziiert und wurde als Nidd/DBA (engl. für nicht insulinabhängiger Diabetes von DBA-Allelen) bezeichnet. Das Ziel der vorliegenden Arbeit war es, (i) das kritische Fragment des Nidd/DBA-Locus‘ zu verkleinern, (ii) die phänotypische Ausprägung des Nidd/DBA-Locus‘ zu untersuchen sowie (iii) die ursächliche(n) genetische(n) Variante(n) zu identifizieren. Die phänotypische Charakterisierung von kongenen Mäusen mit einem kritischen Fragment von 13.6 Mbp, welches 284 Gene enthält, zeigte bereits im Alter von 12 Wochen eine starke Hyperglykämie (~19.9 mM) und eine unzureichende Glucose-Clearance bei Nidd/DBA-Allelträgern. Ex-vivo Perifusionsversuche mit isolierten Inseln von 13 Wochen alten kongenen Mäusen zeigten eine tendenziell reduzierte Insulinsekretion in homozygoten DBA-Allelträgern. Im Alter von 16 Wochen wiesen die Tiere einen erheblichen Verlust der β-Zellen, sowie eine Abnahme der pankreatischen Insulinkonzentration auf. Transkriptomdaten der Langerhans-Inseln mit anschließender Signalweganalyse deuteten darauf hin, dass Nidd/DBA-Allelträger eine verminderte Expression von Genen aufzeigen, die für das Überleben von Zellen essentiell sind. In homozygoten DBA-Allelträgern wurde eine reduzierte Anzahl von Glucagon/Insulin-bi-hormonellen Zellen nachgewiesen, was auf eine verminderte Plastizität der endokrinen Zellen hinweisen könnte. Die Zucht weiterer kongener Mäuse und ihre Phänotypisierung ermöglichten die Isolierung eines 3.3 Mbp großen Fragments, das 61 Gene enthielt und eine Hyperglykämie auslöste. Bioinformatische Analysen, wie die Kartierung von Haplotypen und Datenbank-, Sequenz- sowie Transkriptomanalysen, wurden integriert, um die Anzahl der Kandidatengene weiter zu reduzieren und die Hyperglykämie auslösende(n) Genvariante(n) zu identifizieren. Es konnten vier potentielle Kandidatengene (Ttc39a, Osbpl9, Kti12, Calr4) definiert werden, die entweder eine differenzielle Expression oder eine Sequenzvariante aufwiesen. Mit Hilfe von in-silico-Analysen von ChIP-Seq-Daten wurden SNPs in aktiven Bindungsstellen von β-Zell-Transkriptionsfaktoren identifiziert. Diese könnten cis-regulatorische Elemente darstellen, die Gene außerhalb dieses 3.3 Mbp großen Fragments beeinflussen und möglichweise für den Phänotyp verantwortlich sind. Zusammenfassend konnte gezeigt werden, dass der Nidd/DBA-Locus für eine beeinträchtigte Glucosehomöostase und eine Verschlechterung der Insulinsekretion verantwortlich ist, welche langfristig zum Verlust von β-Zellen führen. Die bisherigen Ergebnisse deuten darauf hin, dass sowohl die verringerte Expression der für das Zellüberleben essentiellen Gene als auch eine verringerte Plastizität der endokrinen Zellen zum Untergang von Langerhans-Inseln beitragen. Das kritische Fragment wurde auf eine Größe von 3.3 Mbp mit 61 Genen reduziert, von denen vier Gene als verantwortliche Kandidaten für den beschriebenen Nidd/DBA-Phänotyp bedeutsam sein können
KW  - Diabetes
KW  - Genetics
KW  - Glucose intolerance
KW  - Insulin secretion
KW  - Susceptibility-genes
KW  - Diabetes
KW  - Genetik
KW  - Glukoseintoleranz
KW  - Insulinsekretion
KW  - Suszeptibilitätsgene
Y1  - 2021
ER  - 
TY  - JOUR
A1  - Bakanidze, George
A1  - Brandl, Eva J.
A1  - Hutzler, Christine
A1  - Aurass, Friederike
A1  - Onken, Silke
A1  - Rapp, Michael Armin
A1  - Puls, Imke
T1  - Association of Dystrobrevin-Binding Protein 1 Polymorphisms with Sustained Attention and Set-Shifting in Schizophrenia Patients
JF  - Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography
N2  - Background: Despite extensive research in the past decades, the influence of genetics on cognitive functions in schizophrenia remains unclear. Dystrobrevin-binding protein 1 (DTNBP1) is one of the most promising candidate genes in schizophrenia. An association of DTNBP1 with cognitive dysfunction, particularly memory impairment, has been reported in a number of studies. However, the results remain inconsistent. The aim of this study was to measure the association between DTNBP1 polymorphisms and cognitive domains in a well-characterized sample. Methods: Ninety-one clinically stable schizophrenia outpatients underwent a battery of cognitive tests. Six single nucleotide polymorphisms (SNPs) of DTNBP1 were genotyped in all participants. Statistical and multivariate analyses were performed. Results: Factor analysis revealed 4 factors corresponding to distinct cognitive domains, namely sustained attention, set-shifting, executive functioning, and memory. We found a significant association of the rs909706 polymorphism with attention (p = 0.030) and a nonsignificant trend for set-shifting (p = 0.060). The other SNPs and haplotypes were not associated with cognitive function. Discussion: Replication of this finding in a larger sample is needed in order to confirm the importance of this particular polymorphism in the genetics of schizophrenia, particularly the distinct cognitive domains. In conclusion, the present study supports the involvement of DTNBP1 in the regulation of cognitive processes and demonstrates association in particular with sustained attention and set-shifting in schizophrenia patients. (C) 2016 S. Karger AG, Basel
KW  - DTNBP1
KW  - Genetics
KW  - Cognitive dysfunction
KW  - Factor analysis
Y1  - 2016
U6  - https://doi.org/10.1159/000450550
SN  - 0302-282X
SN  - 1423-0224
VL  - 74
SP  - 41
EP  - 47
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Huber, Matthias
A1  - Treszl, Andras
A1  - Reibis, Rona Katharina
A1  - Teichmann, Christopher
A1  - Zergibel, Irina
A1  - Bolbrinker, Juliane
A1  - Scholze, Juergen
A1  - Wegscheider, Karl
A1  - Völler, Heinz
A1  - Kreutz, Reinhold
T1  - Genetics of melatonin receptor type 2 is associated with left ventricular function in hypertensive patients treated according to guidelines
JF  - European journal of internal medicine : official journal of the European Federation of Internal Medicine
N2  - Background: Melatonin exerts multiple biological effects with potential impact on human diseases. This is underscored by genetic studies that demonstrated associations between melatonin receptor type 2 gene (MTNR1B) polymorphisms and characteristics of type 2 diabetes. We set out to test the hypothesis whether genetic variants at MTNR1B are also relevant for other disease phenotypes within the cardiovascular continuum. We thus investigated single nucleotide polymorphisms (SNPs) of MTNR1B in relation to blood pressure (BP) and cardiac parameters in hypertensive patients.
 Methods: Patients (n = 605, mean age 56.2 +/- 9.4 years, 82.3% male) with arterial hypertension and cardiac ejection fraction (EF) >= 40% were studied. Cardiac parameters were assessed by echocardiography.
 Results: The cohort comprised subjects with coronary heart disease (73.1%) and myocardial infarction (48.1%) with a mean EF of 63.7 +/- 8.9%. Analysis of SNPs rs10830962, rs4753426, rs12804291, rs10830963, and rs3781638 revealed two haplotypes 1 and 2 with frequencies of 0.402 and 0.277, respectively. Carriers with haplotype 1 (CTCCC) showed compared to non-carriers a higher mean 24-hour systolic BP (difference BP: 2.4 mm Hg, 95% confidence interval (CI): 0.3 to 4.5 mm Hg, p = 0.023). Haplotype 2 (GCCGA) was significantly related to EF with an absolute increase of 1.8% (CI: 0.45 to 3.14%) in carriers versus non-carriers (p = 0.009).
 Conclusion: Genetics of MTNR1B point to impact of the melatonin signalling pathway for BP and left ventricular function. This may support the importance of the melatonin system as a potential therapeutic target.
KW  - Clinical study
KW  - Genetics
KW  - Heart
KW  - Hypertension
KW  - Melatonin receptor type 2
Y1  - 2013
U6  - https://doi.org/10.1016/j.ejim.2013.03.015
SN  - 0953-6205
VL  - 24
IS  - 7
SP  - 650
EP  - 655
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - McLoughlin, Grainne
A1  - Palmer, Jason
A1  - Makeig, Scott
A1  - Bigdely-Shamlo, Nima
A1  - Banaschewski, Tobias
A1  - Laucht, Manfred
A1  - Brandeis, D.
T1  - EEG Source Imaging Indices of Cognitive Control Show Associations with Dopamine System Genes
JF  - Brain Topography
N2  - Cognitive or executive control is a critical mental ability, an important marker of mental illness, and among the most heritable of neurocognitive traits. Two candidate genes, catechol-O-methyltransferase (COMT) and DRD4, which both have a roles in the regulation of cortical dopamine, have been consistently associated with cognitive control. Here, we predicted that individuals with the COMT Met/Met allele would show improved response execution and inhibition as indexed by event-related potentials in a Go/NoGo task, while individuals with the DRD4 7-repeat allele would show impaired brain activity. We used independent component analysis (ICA) to separate brain source processes contributing to high-density EEG scalp signals recorded during the task. As expected, individuals with the DRD4 7-repeat polymorphism had reduced parietal P3 source and scalp responses to response (Go) compared to those without the 7-repeat. Contrary to our expectation, the COMT homozygous Met allele was associated with a smaller frontal P3 source and scalp response to response-inhibition (NoGo) stimuli, suggesting that while more dopamine in frontal cortical areas has advantages in some tasks, it may also compromise response inhibition function. An interaction effect emerged for P3 source responses to Go stimuli. These were reduced in those with both the 7-repeat DRD4 allele and either the COMT Val/Val or the Met/Met homozygous polymorphisms but not in those with the heterozygous Val/Met polymorphism. This epistatic interaction between DRD4 and COMT replicates findings that too little or too much dopamine impairs cognitive control. The anatomic and functional separated maximally independent cortical EEG sources proved more informative than scalp channel measures for genetic studies of brain function and thus better elucidate the complex mechanisms in psychiatric illness.
KW  - EEG
KW  - Genetics
KW  - DRD4
KW  - COMT
KW  - ICA
KW  - Measure projection
Y1  - 2017
U6  - https://doi.org/10.1007/s10548-017-0601-z
SN  - 0896-0267
SN  - 1573-6792
VL  - 31
IS  - 3
SP  - 392
EP  - 406
PB  - Springer
CY  - Dordrecht
ER  - 
TY  - JOUR
A1  - Middeldorp, Christel M.
A1  - Mahajan, Anubha
A1  - Horikoshi, Momoko
A1  - Robertson, Neil R.
A1  - Beaumont, Robin N.
A1  - Bradfield, Jonathan P.
A1  - Bustamante, Mariona
A1  - Cousminer, Diana L.
A1  - Day, Felix R.
A1  - De Silva, N. Maneka
A1  - Guxens, Monica
A1  - Mook-Kanamori, Dennis O.
A1  - St Pourcain, Beate
A1  - Warrington, Nicole M.
A1  - Adair, Linda S.
A1  - Ahlqvist, Emma
A1  - Ahluwalia, Tarunveer Singh
A1  - Almgren, Peter
A1  - Ang, Wei
A1  - Atalay, Mustafa
A1  - Auvinen, Juha
A1  - Bartels, Meike
A1  - Beckmann, Jacques S.
A1  - Bilbao, Jose Ramon
A1  - Bond, Tom
A1  - Borja, Judith B.
A1  - Cavadino, Alana
A1  - Charoen, Pimphen
A1  - Chen, Zhanghua
A1  - Coin, Lachlan
A1  - Cooper, Cyrus
A1  - Curtin, John A.
A1  - Custovic, Adnan
A1  - Das, Shikta
A1  - Davies, Gareth E.
A1  - Dedoussis, George V.
A1  - Duijts, Liesbeth
A1  - Eastwood, Peter R.
A1  - Eliasen, Anders U.
A1  - Elliott, Paul
A1  - Eriksson, Johan G.
A1  - Estivill, Xavier
A1  - Fadista, Joao
A1  - Fedko, Iryna O.
A1  - Frayling, Timothy M.
A1  - Gaillard, Romy
A1  - Gauderman, W. James
A1  - Geller, Frank
A1  - Gilliland, Frank
A1  - Gilsanz, Vincente
A1  - Granell, Raquel
A1  - Grarup, Niels
A1  - Groop, Leif
A1  - Hadley, Dexter
A1  - Hakonarson, Hakon
A1  - Hansen, Torben
A1  - Hartman, Catharina A.
A1  - Hattersley, Andrew T.
A1  - Hayes, M. Geoffrey
A1  - Hebebrand, Johannes
A1  - Heinrich, Joachim
A1  - Helgeland, Oyvind
A1  - Henders, Anjali K.
A1  - Henderson, John
A1  - Henriksen, Tine B.
A1  - Hirschhorn, Joel N.
A1  - Hivert, Marie-France
A1  - Hocher, Berthold
A1  - Holloway, John W.
A1  - Holt, Patrick
A1  - Hottenga, Jouke-Jan
A1  - Hypponen, Elina
A1  - Iniguez, Carmen
A1  - Johansson, Stefan
A1  - Jugessur, Astanand
A1  - Kahonen, Mika
A1  - Kalkwarf, Heidi J.
A1  - Kaprio, Jaakko
A1  - Karhunen, Ville
A1  - Kemp, John P.
A1  - Kerkhof, Marjan
A1  - Koppelman, Gerard H.
A1  - Korner, Antje
A1  - Kotecha, Sailesh
A1  - Kreiner-Moller, Eskil
A1  - Kulohoma, Benard
A1  - Kumar, Ashish
A1  - Kutalik, Zoltan
A1  - Lahti, Jari
A1  - Lappe, Joan M.
A1  - Larsson, Henrik
A1  - Lehtimaki, Terho
A1  - Lewin, Alexandra M.
A1  - Li, Jin
A1  - Lichtenstein, Paul
A1  - Lindgren, Cecilia M.
A1  - Lindi, Virpi
A1  - Linneberg, Allan
A1  - Liu, Xueping
A1  - Liu, Jun
A1  - Lowe, William L.
A1  - Lundstrom, Sebastian
A1  - Lyytikainen, Leo-Pekka
A1  - Ma, Ronald C. W.
A1  - Mace, Aurelien
A1  - Magi, Reedik
A1  - Magnus, Per
A1  - Mamun, Abdullah A.
A1  - Mannikko, Minna
A1  - Martin, Nicholas G.
A1  - Mbarek, Hamdi
A1  - McCarthy, Nina S.
A1  - Medland, Sarah E.
A1  - Melbye, Mads
A1  - Melen, Erik
A1  - Mohlke, Karen L.
A1  - Monnereau, Claire
A1  - Morgen, Camilla S.
A1  - Morris, Andrew P.
A1  - Murray, Jeffrey C.
A1  - Myhre, Ronny
A1  - Najman, Jackob M.
A1  - Nivard, Michel G.
A1  - Nohr, Ellen A.
A1  - Nolte, Ilja M.
A1  - Ntalla, Ioanna
A1  - Oberfield, Sharon E.
A1  - Oken, Emily
A1  - Oldehinkel, Albertine J.
A1  - Pahkala, Katja
A1  - Palviainen, Teemu
A1  - Panoutsopoulou, Kalliope
A1  - Pedersen, Oluf
A1  - Pennell, Craig E.
A1  - Pershagen, Goran
A1  - Pitkanen, Niina
A1  - Plomin, Robert
A1  - Power, Christine
A1  - Prasad, Rashmi B.
A1  - Prokopenko, Inga
A1  - Pulkkinen, Lea
A1  - Raikkonen, Katri
A1  - Raitakari, Olli T.
A1  - Reynolds, Rebecca M.
A1  - Richmond, Rebecca C.
A1  - Rivadeneira, Fernando
A1  - Rodriguez, Alina
A1  - Rose, Richard J.
A1  - Salem, Rany
A1  - Santa-Marina, Loreto
A1  - Saw, Seang-Mei
A1  - Schnurr, Theresia M.
A1  - Scott, James G.
A1  - Selzam, Saskia
A1  - Shepherd, John A.
A1  - Simpson, Angela
A1  - Skotte, Line
A1  - Sleiman, Patrick M. A.
A1  - Snieder, Harold
A1  - Sorensen, Thorkild I. A.
A1  - Standl, Marie
A1  - Steegers, Eric A. P.
A1  - Strachan, David P.
A1  - Straker, Leon
A1  - Strandberg, Timo
A1  - Taylor, Michelle
A1  - Teo, Yik-Ying
A1  - Thiering, Elisabeth
A1  - Torrent, Maties
A1  - Tyrrell, Jessica
A1  - Uitterlinden, Andre G.
A1  - van Beijsterveldt, Toos
A1  - van der Most, Peter J.
A1  - van Duijn, Cornelia M.
A1  - Viikari, Jorma
A1  - Vilor-Tejedor, Natalia
A1  - Vogelezang, Suzanne
A1  - Vonk, Judith M.
A1  - Vrijkotte, Tanja G. M.
A1  - Vuoksimaa, Eero
A1  - Wang, Carol A.
A1  - Watkins, William J.
A1  - Wichmann, H-Erich
A1  - Willemsen, Gonneke
A1  - Williams, Gail M.
A1  - Wilson, James F.
A1  - Wray, Naomi R.
A1  - Xu, Shujing
A1  - Xu, Cheng-Jian
A1  - Yaghootkar, Hanieh
A1  - Yi, Lu
A1  - Zafarmand, Mohammad Hadi
A1  - Zeggini, Eleftheria
A1  - Zemel, Babette S.
A1  - Hinney, Anke
A1  - Lakka, Timo A.
A1  - Whitehouse, Andrew J. O.
A1  - Sunyer, Jordi
A1  - Widen, Elisabeth E.
A1  - Feenstra, Bjarke
A1  - Sebert, Sylvain
A1  - Jacobsson, Bo
A1  - Njolstad, Pal R.
A1  - Stoltenberg, Camilla
A1  - Smith, George Davey
A1  - Lawlor, Debbie A.
A1  - Paternoster, Lavinia
A1  - Timpson, Nicholas J.
A1  - Ong, Ken K.
A1  - Bisgaard, Hans
A1  - Bonnelykke, Klaus
A1  - Jaddoe, Vincent W. V.
A1  - Tiemeier, Henning
A1  - Jarvelin, Marjo-Riitta
A1  - Evans, David M.
A1  - Perry, John R. B.
A1  - Grant, Struan F. A.
A1  - Boomsma, Dorret I.
A1  - Freathy, Rachel M.
A1  - McCarthy, Mark I.
A1  - Felix, Janine F.
T1  - The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
BT  - design, results and future prospects
JF  - European journal of epidemiology
N2  - The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
KW  - Genetics
KW  - Consortium
KW  - Childhood traits and disorders
KW  - Longitudinal
Y1  - 2019
U6  - https://doi.org/10.1007/s10654-019-00502-9
SN  - 0393-2990
SN  - 1573-7284
VL  - 34
IS  - 3
SP  - 279
EP  - 300
PB  - Springer
CY  - Dordrecht
ER  - 
TY  - JOUR
A1  - Pearson, Leanne A.
A1  - Dittmann, Elke
A1  - Mazmouz, Rabia
A1  - Ongley, Sarah E.
A1  - Neilan, Brett A.
T1  - The genetics, biosynthesis and regulation of toxic specialized metabolites of cyanobacteria
JF  - Harmful algae
N2  - The production of toxic metabolites by cyanobacterial blooms represents a significant threat to the health of humans and ecosystems worldwide. Here we summarize the current state of the knowledge regarding the genetics, biosynthesis and regulation of well-characterized cyanotoxins, including the microcystins, nodularin, cylindrospermopsin, saxitoxins and antitoxins, as well as the lesser-known marine toxins (e.g. lyngbyatoxin, aplysiatoxin, jamaicamides, barbamide, curacin, hectochlorin and apratoxins). (C) 2015 Elsevier B.V. All rights reserved.
KW  - Cyanobacteria
KW  - Cyanotoxins
KW  - Specialized metabolites
KW  - Genetics
KW  - Biosynthesis
KW  - Regulation
Y1  - 2016
U6  - https://doi.org/10.1016/j.hal.2015.11.002
SN  - 1568-9883
SN  - 1878-1470
VL  - 54
SP  - 98
EP  - 111
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - GEN
A1  - Ziege, Madlen
A1  - Theodorou, Panagiotis
A1  - Jüngling, Hannah
A1  - Merker, Stefan
A1  - Plath, Martin
A1  - Streit, Bruno
A1  - Lerp, Hannes
T1  - Population genetics of the European rabbit along a rural-to-urban gradient
T2  - Postprints der Universität Potsdam : Mathematisch Naturwissenschaftliche Reihe
N2  - The European rabbit (Oryctolagus cuniculus) is declining in large parts of Europe but populations in some German cities remained so far unaffected by this decline. The question arises of how urbanization affects patterns of population genetic variation and differentiation in German rabbit populations, as urban habitat fragmentation may result in altered meta-population dynamics. To address this question, we used microsatellite markers to genotype rabbit populations occurring along a rural-to-urban gradient in and around the city of Frankfurt, Germany. We found no effect of urbanization on allelic richness. However, the observed heterozygosity was significantly higher in urban than rural populations and also the inbreeding coefficients were lower, most likely reflecting the small population sizes and possibly on-going loss of genetic diversity in structurally impoverished rural areas. Global FST and G'ST-values suggest moderate but significant differentiation between populations. Multiple matrix regression with randomization ascribed this differentiation to isolation-by-environment rather than isolation-by-distance. Analyses of migration rates revealed asymmetrical gene flow, which was higher from rural into urban populations than vice versa and may again reflect intensified agricultural land-use practices in rural areas. We discuss that populations inhabiting urban areas will likely play an important role in the future distribution of European rabbits.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 880 
KW  - Conservation biology
KW  - Genetics
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-460354
SN  - 1866-8372
IS  - 880
ER  - 
TY  - JOUR
A1  - Ziege, Madlen
A1  - Theodorou, Panagiotis
A1  - Jüngling, Hannah
A1  - Merker, Stefan
A1  - Plath, Martin
A1  - Streit, Bruno
A1  - Lerp, Hannes
T1  - Population genetics of the European rabbit along a rural-to-urban gradient
JF  - Scientific Reports
N2  - The European rabbit (Oryctolagus cuniculus) is declining in large parts of Europe but populations in some German cities remained so far unaffected by this decline. The question arises of how urbanization affects patterns of population genetic variation and differentiation in German rabbit populations, as urban habitat fragmentation may result in altered meta-population dynamics. To address this question, we used microsatellite markers to genotype rabbit populations occurring along a rural-to-urban gradient in and around the city of Frankfurt, Germany. We found no effect of urbanization on allelic richness. However, the observed heterozygosity was significantly higher in urban than rural populations and also the inbreeding coefficients were lower, most likely reflecting the small population sizes and possibly on-going loss of genetic diversity in structurally impoverished rural areas. Global FST and G'ST-values suggest moderate but significant differentiation between populations. Multiple matrix regression with randomization ascribed this differentiation to isolation-by-environment rather than isolation-by-distance. Analyses of migration rates revealed asymmetrical gene flow, which was higher from rural into urban populations than vice versa and may again reflect intensified agricultural land-use practices in rural areas. We discuss that populations inhabiting urban areas will likely play an important role in the future distribution of European rabbits.
KW  - Conservation biology
KW  - Genetics
Y1  - 2018
U6  - https://doi.org/10.1038/s41598-020-57962-3
SN  - 2045-2322
VL  - 10
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Zühlke, Martin
A1  - Meiling, Till Thomas
A1  - Roder, Phillip
A1  - Riebe, Daniel
A1  - Beitz, Toralf
A1  - Bald, Ilko
A1  - Löhmannsröben, Hans-Gerd
A1  - Janßen, Traute
A1  - Erhard, Marcel
A1  - Repp, Alexander
T1  - Photodynamic inactivation of E. coli bacteria via carbon nanodots
JF  - ACS omega / American Chemical Society
N2  - The increasing development of antibiotic resistance in bacteria has been a major problem for years, both in human and veterinary medicine. Prophylactic measures, such as the use of vaccines, are of great importance in reducing the use of antibiotics in livestock. These vaccines are mainly produced based on formaldehyde inactivation. However, the latter damages the recognition elements of the bacterial proteins and thus could reduce the immune response in the animal. An alternative inactivation method developed in this work is based on gentle photodynamic inactivation using carbon nanodots (CNDs) at excitation wavelengths λex > 290 nm. The photodynamic inactivation was characterized on the nonvirulent laboratory strain Escherichia coli K12 using synthesized CNDs. For a gentle inactivation, the CNDs must be absorbed into the cytoplasm of the E. coli cell. Thus, the inactivation through photoinduced formation of reactive oxygen species only takes place inside the bacterium, which means that the outer membrane is neither damaged nor altered. The loading of the CNDs into E. coli was examined using fluorescence microscopy. Complete loading of the bacterial cells could be achieved in less than 10 min. These studies revealed a reversible uptake process allowing the recovery and reuse of the CNDs after irradiation and before the administration of the vaccine. The success of photodynamic inactivation was verified by viability assays on agar. In a homemade flow photoreactor, the fastest successful irradiation of the bacteria could be carried out in 34 s. Therefore, the photodynamic inactivation based on CNDs is very effective. The membrane integrity of the bacteria after irradiation was verified by slide agglutination and atomic force microscopy. The method developed for the laboratory strain E. coli K12 could then be successfully applied to the important avian pathogens Bordetella avium and Ornithobacterium rhinotracheale to aid the development of novel vaccines.
KW  - Bacteria
KW  - Genetics
KW  - Fluorescence
KW  - Photodynamics
KW  - Irradiation
Y1  - 2021
U6  - https://doi.org/10.1021/acsomega.1c01700
SN  - 2470-1343
VL  - 6
IS  - 37
SP  - 23742
EP  - 23749
PB  - ACS Publications
CY  - Washington, DC
ER  - 
TY  - GEN
A1  - Zühlke, Martin
A1  - Meiling, Till Thomas
A1  - Roder, Phillip
A1  - Riebe, Daniel
A1  - Beitz, Toralf
A1  - Bald, Ilko
A1  - Löhmannsröben, Hans-Gerd
A1  - Janßen, Traute
A1  - Erhard, Marcel
A1  - Repp, Alexander
T1  - Photodynamic Inactivation of E. coli Bacteria via Carbon Nanodots
T2  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - The increasing development of antibiotic resistance in bacteria has been a major problem for years, both in human and veterinary medicine. Prophylactic measures, such as the use of vaccines, are of great importance in reducing the use of antibiotics in livestock. These vaccines are mainly produced based on formaldehyde inactivation. However, the latter damages the recognition elements of the bacterial proteins and thus could reduce the immune response in the animal. An alternative inactivation method developed in this work is based on gentle photodynamic inactivation using carbon nanodots (CNDs) at excitation wavelengths λex > 290 nm. The photodynamic inactivation was characterized on the nonvirulent laboratory strain Escherichia coli K12 using synthesized CNDs. For a gentle inactivation, the CNDs must be absorbed into the cytoplasm of the E. coli cell. Thus, the inactivation through photoinduced formation of reactive oxygen species only takes place inside the bacterium, which means that the outer membrane is neither damaged nor altered. The loading of the CNDs into E. coli was examined using fluorescence microscopy. Complete loading of the bacterial cells could be achieved in less than 10 min. These studies revealed a reversible uptake process allowing the recovery and reuse of the CNDs after irradiation and before the administration of the vaccine. The success of photodynamic inactivation was verified by viability assays on agar. In a homemade flow photoreactor, the fastest successful irradiation of the bacteria could be carried out in 34 s. Therefore, the photodynamic inactivation based on CNDs is very effective. The membrane integrity of the bacteria after irradiation was verified by slide agglutination and atomic force microscopy. The method developed for the laboratory strain E. coli K12 could then be successfully applied to the important avian pathogens Bordetella avium and Ornithobacterium rhinotracheale to aid the development of novel vaccines.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1220 
KW  - Bacteria
KW  - Genetics
KW  - Fluorescence
KW  - Photodynamics
KW  - Irradiation
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-538425
SN  - 1866-8372
SP  - 23742
EP  - 23749
PB  - Universität Potsdam
CY  - Potsdam
ER  -