882 research outputs found
Visual capabilities and cortical maps in BALB/c mice.
No full textBy combining behavioural analyses with intrinsic signal optical imaging, we analysed visual performance and visual cortical activity in the albino mouse strain BALB/c, which is increasingly being used as an animal model of neuropsychological disorders. Visual acuity, as measured by a virtual-reality optomotor system, was 0.12 cycles per degree (cyc/deg) in BALB/c mice and 0.39 cyc/deg in pigmented C57BL/6 mice. Surprisingly, BALB/c mice showed reflexive head movements against the direction of the rotating stimulus. Contrast sensitivity was significantly lower in BALB/c mice (45% contrast at 0.064 cyc/deg) than in C57BL/6 mice (6% contrast). In the visual water task, visual acuity was 0.3 cyc/deg in BALB/c mice and 0.59 cyc/deg in C57BL/6 mice. Thus, the visual performance of BALB/c mice was significantly impaired in both behavioural tests - visual acuity was ∼ 0.3 cyc/deg lower than in C57BL/6 mice, and contrast sensitivity was reduced by a factor of ∼ 8. In BALB/c mice, visual cortical maps induced by stimulation of the contralateral eye were normal in both activation strength and retinotopic map quality. In contrast, maps induced by ipsilateral eye stimulation differed significantly between the strains - activity in a region representing 15° to 19° elevation in the visual field was significantly weaker in BALB/c mice than in C57BL/6 mice. Taken together, our observations show that BALB/c mice, like the albino animals of other species, have a significantly lower visual performance than C57BL/6 mice and a modified cortical representation of the ipsilateral eye that may impair stereopsis. Thus, our results caution against disregarding vision as a confounding factor in behavioural tests of neuropsychological disorders
Gene loss and lineage specific restriction-modification systems associated with niche differentiation in the Campylobacter jejuni Sequence Type 403 clonal complex
No full textCampylobacter jejuni is a highly diverse species of bacteria commonly associated with infectious intestinal disease of humans and zoonotic carriage in poultry, cattle, pigs, and other animals. The species contains a large number of distinct clonal complexes that vary from host generalist lineages commonly found in poultry, livestock, and human disease cases to host-adapted specialized lineages primarily associated with livestock or poultry. Here, we present novel data on the ST403 clonal complex of C. jejuni, a lineage that has not been reported in avian hosts. Our data show that the lineage exhibits a distinctive pattern of intralineage recombination that is accompanied by the presence of lineage-specific restriction-modification systems. Furthermore, we show that the ST403 complex has undergone gene decay at a number of loci. Our data provide a putative link between the lack of association with avian hosts of C. jejuni ST403 and both gene gain and gene loss through nonsense mutations in coding sequences of genes, resulting in pseudogene formation
Mutation analysis in a German family identified a new cataract-causing allele in the CRYBB2 gene
No full textPURPOSE: The study demonstrates the functional candidate gene analysis in a cataract family of German descent. METHODS: We screened a German family, clinically documented to have congenital cataracts, for mutation in the candidate genes CRYG (A to D) and CRYBB2 through polymerase chain reaction analyses and sequencing. RESULTS: Congenital cataract was first observed in a daughter of healthy parents. Her two children (a boy and a girl) also suffer from congenital cataracts and have been operated within the first weeks of birth. Morphologically, the cataract is characterized as nuclear with an additional ring-shaped cortical opacity. Molecular analysis revealed no causative mutation in any of the CRYG genes. However, sequencing of the exons of the CRYBB2 gene identified a sequence variation in exon 5 (383 A > T) with a substitution of Asp to Val at position 128. All three affected family members revealed this change but it was not observed in any of the unaffected persons of the family. The putative mutation creates a restriction site for the enzyme TaiI. This mutation was checked for in controls of randomly selected DNA samples from ophthalmologically normal individuals from the population-based KORA S4 study (n=96) and no mutation was observed. Moreover, the Asp at position 128 is within a stretch of 12 amino acids, which are highly conserved throughout the animal kingdom. For the mutant protein, the isoelectric point is raised from pH 6.50 to 6.75. Additionally, the random coil structure of the protein between the amino acids 126-139 is interrupted by a short extended strand structure. In addition, this region becomes hydrophobic (from neutral to +1) and the electrostatic potential in the region surrounding the exchanged amino acid alters from a mainly negative potential to an enlarged positive potential. CONCLUSIONS: The D128V mutation segregates only in affected family members and is not seen in representative controls. It represents the first mutation outside exon 6 of the human CRYBB2 gene
Mutation analysis in a German family identified a new cataract-causing allele in the CRYBB2 gene
No full textPURPOSE: The study demonstrates the functional candidate gene analysis in a cataract family of German descent. METHODS: We screened a German family, clinically documented to have congenital cataracts, for mutation in the candidate genes CRYG (A to D) and CRYBB2 through polymerase chain reaction analyses and sequencing. RESULTS: Congenital cataract was first observed in a daughter of healthy parents. Her two children (a boy and a girl) also suffer from congenital cataracts and have been operated within the first weeks of birth. Morphologically, the cataract is characterized as nuclear with an additional ring-shaped cortical opacity. Molecular analysis revealed no causative mutation in any of the CRYG genes. However, sequencing of the exons of the CRYBB2 gene identified a sequence variation in exon 5 (383 A > T) with a substitution of Asp to Val at position 128. All three affected family members revealed this change but it was not observed in any of the unaffected persons of the family. The putative mutation creates a restriction site for the enzyme TaiI. This mutation was checked for in controls of randomly selected DNA samples from ophthalmologically normal individuals from the population-based KORA S4 study (n=96) and no mutation was observed. Moreover, the Asp at position 128 is within a stretch of 12 amino acids, which are highly conserved throughout the animal kingdom. For the mutant protein, the isoelectric point is raised from pH 6.50 to 6.75. Additionally, the random coil structure of the protein between the amino acids 126-139 is interrupted by a short extended strand structure. In addition, this region becomes hydrophobic (from neutral to +1) and the electrostatic potential in the region surrounding the exchanged amino acid alters from a mainly negative potential to an enlarged positive potential. CONCLUSIONS: The D128V mutation segregates only in affected family members and is not seen in representative controls. It represents the first mutation outside exon 6 of the human CRYBB2 gene
Die Römische Republik /
No full textWer sich für antike Geschichte interessiert, greift zu dieser knappen und gut lesbaren Geschichte der Römischen Republik, geschrieben von einem der bekanntesten Althistoriker Deutschlands. Jochen Bleicken (1926-2005) führt den Leser von der Zeit der Etrusker bis zum Ende der Republik, das die Herrschaft Caesars besiegelte. Alle wichtigen Phasen der republikanischen Geschichte entfalten sich: die Ständekämpfe, Aufstieg Roms zur Weltherrschaft - und die zugehörigen ungeheuren kriegerischen Auseinandersetzungen -, Ursachen und Beginn der inneren Krise seit den Gracchen, die Restauration unter Sulla und schließlich: die Auflösung der Republik und die Begründung der Monarchie. Aloys Winterling Jochen Bleicken, 1926-2005, war Professor für Alte Geschichte an der Universität Göttingen und u.a. Mitherausgeber von "Oldenbourg Grundriss der Geschichte" und der HISTORISCHEN ZEITSCHRIFT.Wer sich für antike Geschichte interessiert, greift zu dieser knappen und gut lesbaren Geschichte der Römischen Republik, geschrieben von einem der bekanntesten Althistoriker Deutschlands. Jochen Bleicken (1926-2005) führt den Leser von der Zeit der Etrusker bis zum Ende der Republik, das die Herrschaft Caesars besiegelte. Alle wichtigen Phasen der republikanischen Geschichte entfalten sich: die Ständekämpfe, Aufstieg Roms zur Weltherrschaft - und die zugehörigen ungeheuren kriegerischen Auseinandersetzungen -, Ursachen und Beginn der inneren Krise seit den Gracchen, die Restauration unter Sulla und schließlich: die Auflösung der Republik und die Begründung der Monarchie. Aloys Winterling Jochen Bleicken, 1926-2005, war Professor für Alte Geschichte an der Universität Göttingen und u.a. Mitherausgeber von "Oldenbourg Grundriss der Geschichte" und der HISTORISCHEN ZEITSCHRIFT.Mode of access: Internet via World Wide Web.Description based on online resource; title from PDF title page (publisher's Web site, viewed 08. Jul 2019
Essentials of services marketing / Jochen Wirtz, Christopher Lovelock.
No full textIncludes bibliographical references and indexes.(xxxii, 670 pages) :Essentials of Services Marketing, 3e, is meant for courses directed at undergraduate and polytechnic students, especially those heading for a career in the service sector, whether at the executive or management level. It delivers streamlined coverage of services marketing topics with an exciting global outlook with visual learning aids and clear language. It has been designed so that instructors can make selective use of chapters and cases to teach courses of different lengths and formats in either services marketing or services management
<em>Crybb2</em>, ein neues Kandidatengen für Schizophrenie?
No full textIn my study, I demonstrate that in Crybb2 mutant mice, O377, the hippocampus volume is reduced compared with wild type. In addition, the cell density of parvalbumin positive GABAergic interneuron is reduced in an age-dependent manner, specifically in ventral hippocampus. Furthermore, loss of dendritic complexity in hippocampal neurons and less astrogensis in adult O377 mutants are also observed. Up-regulation of Capn3 and Tmsb4x caused by increase of calcium concentration in hippocampal neurons is associated with these observed changes in O377 mutants. All results suggest that Crybb2 is a new candidate gene for psychiatric disorders, especially for schizophrenia.Untersuchungen der Mauslinie O377 (Mutation im Crybb2 – Gen) ergaben eine veränderte Struktur sowie ein verringertes Volumen des Hippokampus. Im ventralen Hippokampus zeigte sich eine altersabhängige Verringerung der Zelldichte von Parvalbumin positiven GABA-ergen Interneuronen. Genauere Analysen ergaben außerdem eine verringerte Verzweigung der Denriten der hippokampaler Neurone und eine verringerte Astrogenese. Des Weiteren zeigte sich eine erhöhte Expression von Capn3 und Tmsb4x die aufgrund einer erhöhten Calciumkonzentration in hippokampalen Neuronen verursacht werden könnte. Die Ergebnisse dieser Arbeit deuten auf eine neue Funktion von Crybb2 als Kandidatengen für psychiatrische Studien wie Schizophrenieerkrankungen hin
Untersuchung der Diversifikation von Humanisierten Antikörper aus Kaninchen und Mäuse mittels transgene Immunglobulin Schwere kette (IgH) mini-loci
No full textSomatic mutation of rearranged immunoglobulin genes (IgH and IgL) is a key
process because it leads to the diversification of the antibody chains, a vital
progression in the affinity maturation process whereby antibody-antigen binding is
enhanced.
Two different mechanisms of somatic mutation have been described and attributed
to different species: somatic hypermutaion (in man and mouse) occurs by fixation
of individual non-templated nucleotide substitutions, whereas gene conversion (in
rabbits, sheep, birds and cattle) occurs by templated substitutions with sequences
donated by upstream pseudogenes to the rearranged IgV gene segment. These two
processes have been described to be alternative methods employed in revamping a
lesion caused by the protein Activation Induced Deanimase (AID) in the
rearranged IgV gene segment. The decision which method is thereby used depends
on interplay of cis (Ig promoter and enhancer) and trans (genes involved in
homologous recombination) elements.
In this work a transgenic vector is created using a novel approach, whereby the
coding sequences of a rabbit IgH locus are substituted with their human
counterparts.
In the first part of the study, this transgenic vector is used to generated transgenic
mice, and somatic diversification of the humanized antibodies investigated; the
question posed being what would be the result of the interaction between rabbit ( a
gene converting animal) cis regulatory elements (on the transgenic vector) and the
trans elements of the mouse host ( a hypermutating animal)? The results advocate a
species specific activity of the Ig cis and trans elements as no somatic hypermutation
was observed, albeit successful rearrangement and employment of the translocus.
In the second part of the work, a second humanized rabbit transgenic vector was
used to generate transgenic rabbits and mice and the somatic diversification of the
humanized antibodies investigated. Mice and rabbits transgenic for the same locus
proffer a much comprehensible comparison of somatic hypermutation in these
animals. The question to be answered in this second part was would the humanized
antibodies undergo somatic hypermutation in the transgenic mice and gene
conversion in the transgenic rabbits? The results give credit to the hypothesis from
the first part: the humanized antibodies from the transgenic mice showed no
somatic hypermutation, while those from the transgenic rabbits did undergo
effective gene conversion.
In total these results argue for a species specific interaction of Ig cis and trans
regulatory elements in determining the method of somatic mutation employed.Unter der somatischen Mutation versteht man das Einfügen von Mutationen in die V-Region von Antikörpergenen einer reifenden B-Zelle. Die Hypermutation kommt bei Mensch und Maus vor und die Genkonversion wird Kaninchen, Schaf, Vogel und Rind zugeordnet. In der vorliegenden Arbeit wurde einen IgH-Mini-Lokus mit humanisierten Genen hergestellt, die noch die Regulationselemente des Kaninchens enthalten. B-Zellen aus transgenen Mäusen und Kaninchen wurden analysiert. In den transgenen Mäusen konnte keine somatische Hypermutation nachgewiesen werden. Die transgenen Kaninchen wiesen Genkonversion auf, was vermutlich auf die kaninchenspezifischen Regulationselemente zurückzuführen ist
Funktionale und regulatorische Netzwerk-Analyse von Pitx3 in der <em>aphakia</em> Mutante - ein Mausmodell für Mikrophthalmie und der Parkinson-Krankheit
No full textPitx3 is a paired homeodomain transcription factor that plays an important role in the development of dopaminergic neurons and ocular lens. Its role in the regulatory cascade of lens development is investigated using Pitx3-deficient aphakia mice. Expression analysis of various transcription factors critical in lens development revealed the reduced expression of Ap-2α, diminished Foxe3 and Prox1 even do not express, causing reduced proliferation and inappropriate differentiation in these mutants. By using luciferase reporter assay, I have shown that these factors are directly regulated by Pitx3. Additionally, Tube1 is identified as a novel target of Pitx3. These finding helped to develop a lens regulatory cascade and can further be extrapolated in other expression domains of Pitx3.Pitx3 ist ein paired-like-Transkriptionsfaktor, der für die Entwicklung von dopaminergen Neuronen und der Augenlinse notwendig ist. In dieser Arbeit wurde die Rolle von Pitx3 während der Entwicklung der Linse mittels Pitx3-defizienten aphakia Mäusen untersucht. Dabei konnte gezeigt werden, dass der Verlust von Pitx3 zu einer reduzierten Zellproliferation und fehlerhafter Differenzierung der Linsenfaserzellen führte. Expressionsanalysen von verschiedenen, für die Linsenentwicklung wichtigen Transkriptionsfaktoren ergaben eine verringerte Expression von Ap-2α, eine leicht verminderte von Foxe3 und den Verlust von Prox1. Des Weiteren konnte anhand von Luciferase Reporter Assays gezeigt werden, dass diese Faktoren direkt von Pitx3 reguliert werden können. Zusätzlich dazu würde Tube1 als ein neuer von Pitx3 reguliertes Gen nachgewiesen.
Diese Arbeit hilft nicht nur bei der Entwicklung eines molekularen Signalweges in der Linse, sondern kann zum besseren Verständnis von der Funktion von Pitx3 in dessen anderen Expressionsdomänen, wie das Mittelhirn oder Skelettmuskulatur, übertragen werden
Studies on functional characterization of Eya3 in vertebrates
No full textWährend die Funktion des Gens Eya3 in Vertebraten nur unzureichend verstanden ist, führen Mutationen im orthologen Gen eyes absent in Drosophila zu schweren Defekten in der Augenentwicklung. Untersuchungen in der Maus konnten anhand von detaillierten Expressionsstudien die Möglichkeit pleiotroper Effekte aufzeigen. Interessanterweise ergab die Charakterisierung einer Eya3-defizienten Mauslinie keine Hinweise auf Augen-erkrankungen. Sie zeigte jedoch einen Einfluss von Eya3 auf das Größenwachstum, auf die Herz- und Muskelfunktion sowie auf das lokomotorische Verhalten. Vergleichende Untersuchungen im Zebrafisch durch eine Genexpressionsanalyse und einen Morpholino-induzierten Knockdown kamen zu ähnlichen Ergebnissen wie in der Maus und konnten, anders als im Xenopus, keine Beeinträchtigung der frühen Neurogenese zeigen.While the function of the gene Eya3 in vertebrates is only partially understood, mutations in the Drosophila ortholog eyes absent lead to severe defects in eye development. A detailed gene expression analysis in mice suggested pleiotropic effects. Surprisingly, the characterization of Eya3-deficient mice did not show ocular defects. But, phenotypical characterization demonstrated an impact of Eya3 on growth, cardiac and muscle function as well as locomotor activity. Comparative studies in zebrafish by expression analysis and a morpholino knockdown of eya3 displayed similar results as in mice and, different from Xenopus, no affection of neurogenesis was detectable during early developmental stages
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