8 research outputs found
SIRA- Hühneraugen-Hobel, unerreicht, F.M. Lenzner, Stettin.
No full textSIRA- HÜHNERAUGEN-HOBEL, UNERREICHT, F.M. LENZNER, STETTIN.
SIRA- Hühneraugen-Hobel, unerreicht, F.M. Lenzner, Stettin. ( -
Sira Rasier Apparat, allenvoran.
No full textSIRA RASIER APPARAT, ALLENVORAN.
Sira Rasier Apparat, allenvoran. ( -
Retinitis Pigmentosa GTPase Regulator (RPGR) protein isoforms in mammalian retina:insights into X-linked Retinitis Pigmentosa and associated ciliopathies
No full textMutations in the cilia-centrosomal protein Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of retinal degeneration. The RPGR gene undergoes complex alternative splicing and encodes multiple protein isoforms. To elucidate the function of major RPGR isoforms (RPGR 1-19 and RPGR ORF15), we have generated isoform-specific antibodies and examined their expression and localization in the retina. Using sucrose-gradient centrifugation, immunofluorescence and co-immunoprecipitation methods, we show that RPGR isoforms localize to distinct sub-cellular compartments in mammalian photoreceptors and associate with a number of cilia-centrosomal proteins. The RCC1-like domain of RPGR, which is present in all major RPGR isoforms, is sufficient to target it to the cilia and centrosomes in cultured cells. Our findings indicate that multiple isotypes of RPGR may perform overlapping yet somewhat distinct transport-related functions in photoreceptors
Chromatin and oxygen sensing in the context of JmjC histone demethylases
No full textResponding appropriately to changes in oxygen availability is essential for multicellular organism survival. Molecularly, cells have evolved intricate gene expression programmes to handle this stressful condition. Although it is appreciated that gene expression is co-ordinated by changes in transcription and translation in hypoxia, much less is known about how chromatin changes allow for transcription to take place. The missing link between co-ordinating chromatin structure and the hypoxiainduced transcriptional programme could be in the form of a class of dioxygenases called JmjC (Jumonji C) enzymes, the majority of which are histone demethylases. In the present review, we will focus on the function of JmjC histone demethylases, and howthese could act as oxygen sensors for chromatin in hypoxia. The current knowledge concerning the role of JmjC histone demethylases in the process of organism development and human disease will also be reviewed. © 2014 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC-BY).</p
No saturation in the accumulation of alien species worldwide
No full textAlthough research on human-mediated exchanges of species has substantially intensified during the last centuries, we know surprisingly little about temporal dynamics of alien species accumulations across regions and taxa. Using a novel database of 45,813 first records of 16,926 established alien species, we show that the annual rate of first records worldwide has increased during the last 200 years, with 37% of all first records reported most recently (1970-2014). Inter-continental and inter-taxonomic variation can be largely attributed to the diaspora of European settlers in the nineteenth century and to the acceleration in trade in the twentieth century. For all taxonomic groups, the increase in numbers of alien species does not show any sign of saturation and most taxa even show increases in the rate of first records over time. This highlights that past efforts to mitigate invasions have not been effective enough to keep up with increasing globalization. © The Author(s) 2017
No saturation in the accumulation of alien species worldwide
No full textAlthough research on human-mediated exchanges of species has substantially intensified during the last centuries, we know surprisingly little about temporal dynamics of alien species accumulations across regions and taxa. Using a novel database of 45,813 first records of 16,926 established alien species, we show that the annual rate of first records worldwide has increased during the last 200 years, with 37% of all first records reported most recently (1970–2014). Inter-continental and inter-taxonomic variation can be largely attributed to the diaspora of European settlers in the nineteenth century and to the acceleration in trade in the twentieth century. For all taxonomic groups, the increase in numbers of alien species does not show any sign of saturation and most taxa even show increases in the rate of first records over time. This highlights that past efforts to mitigate invasions have not been effective enough to keep up with increasing globalization.© The Author(s) 201
Role of metal ions dyshomeostasis in neurodegeneration
No full textIn the present study metal ions role in neurodegenerative processes has been investigated. Two major pathways have been developed: 1) metal ions role in β-amyloid (Aβ folding and deposition from in vitro to in vivo; 2) calcium dyshomeostasis in an in vitro model of neurodegeneration.
Firstly, metal ions role (aluminum, copper, iron, zinc) in Aβ folding and deposition was assessed. Aβ misfolding is, in fact, believed to play a critical role in Alzheimer’s disease pathogenesis. Our data confirm that Aβ folding is closely related to the conjugated metal ion, thereby following peculiar metal ion-dependent conformational changes. Strikingly, we report that aluminum, a non physiological metal ion, is the most efficient in “freezing” Aβ in its oligomeric and most toxic state.
Within this framework we investigated the mechanisms underlying Aβ and Aβ-metal conjugates toxicity. To that aim we employed two natural compounds (resveratrol and cholesterol) acting on two different Aβ mechanisms of toxicity: oxidative stress and membrane damage, respectively.
In both cases, in vitro analysis revealed that resveratrol and cholesterol do not influence Aβ and Aβ-metal conjugates folding processes, but are still effective in protecting a neuronal-like cell line against Aβ toxicity. We reported that resveratrol was able to significantly reduce the Aβ-triggered generation of reactive oxygen species, meanwhile physiological concentrations of cholesterol were effective in protecting cellular membrane structure against Aβ (especially Aβ-Al) lipid disrupting activity.
To further assess that differently shaped Aβ-metal conjugates result in different biological responses, we investigated Aβ-Cu and Aβ-Zn role in influencing/altering gene expression profile in a neuronal-like cell line. We found that these two conjugates are effective in modulating expression of transcripts involved in inflammatory processes, oxidative stress, and in apoptotic cell death.
Following these in vitro studies we decided to investigate whether expression of transcripts involved in metal ions homeostasis resulted affected in an in vivo model of the disease, represented by the 3xTg-AD mice. Our data highlight a significant overlapping between the expression profiles of young 3xTg-AD mice compared with aged wild type mice; this finding support the notion that Alzheimer’s disease can be interpreted as a boosted variant of otherwise naturally occurring age-driven changes. In our dataset we found several differentially expressed transcripts involved in calcium homeostasis, a key metal ion for the physiology of the cell.
Secondly, calcium dyshomeostasis in striatal neurons following excitotoxic challenge was assessed. Striatal neurons degeneration is involved in several pathologies showing motor and behavioral sequelae, such as Huntington’s disease (HD). We tried to determine why a subpopulation of striatal neurons results spared in HD striata, showing a peculiar resistance towards excitotoxic challenges. Our data demonstrate that the striking resistance of these cells may be due to boosted scavenging capabilities embedded in such neuronal subpopulation, resulting in lack of ROS generation upon excitotoxic insults.
Collectively, these findings highlight the pivotal role played by metal ions in the development of neurodegenerative disorders. Noteworthy, not only endogenous and biologically relevant metal ions (iron, copper, zinc and calcium) seem involved in the pathogenesis of neurodegenerative disorders, but also exogenous metals (i.e.: aluminum) could have a key and subtle, although less investigated, role in neuronal degeneratio
Conditional mutagenesis in the immune system: targeting the expression of the iCre2 recombinase to neutrophils and macrophages
No full textConditional mutagenesis allows the introduction of tissue specific mutations in the mouse and is
of crucial importance in converting genome sequence information into functional data for
biomedical research. Mice expressing the Cre recombinase in a spatially controlled manner are
essential in creating such conditional knock-outs. A wide variety of Cre mice have been
generated, but there is a distinct lack of models expressing the recombinase faithfully and at
high levels in cells of the innate immune system. To address this need, three target genes,
Itgb2l, Marco and Msr1, were chosen to create novel neutrophil and macrophage specific
knock-in models harbouring iCre2, a recombinase engineered for increased expression levels.
Two strategies were employed. Initially gene specific bacterial artificial chromosomes in which
the iCre2 fragment replaced the endogenous translation start codon were created by Red/ET
recombineering. Utilization of these BAC vectors for embryonic stem cell targeting successfully
created knock-ins but the identification of homologous recombinants was complicated by the
vectors’ large size. As the discovery of mutations impeding iCre2 functionality in the knock-in
lines necessitated repeating the vector creation process, novel shorter vectors were designed.
These vectors achieved targeting frequencies of around 10% and facilitated the isolation and
verification of 9 Itgb2l and Marco specific iCre2 knock-in murine embryonic stem cell lines on
the 129 genetic background. To determine tissue specific iCre2 expression before generating
mouse models, an in vitro haematopoietic differentiation system, utilising three-dimensional
embryoid body formation and selective expansion of progenitors in the presence of IL-3 and
MCSF, was adapted. Embryonic stem cells were successfully differentiated into macrophages
as assessed by CD11b and F4/80 marker expression. Collectively, this work has established the
foundations for obtaining viable myeloid specific Cre producer mouse strains and discusses the
potential of their future application in elucidating the role of macrophages and neutrophils in
innate immune function
