Fernerkundungsgestützte Prozessanalyse im Küstenraum Benins = Analyse de processus par télédétection dans la zone côtière du Bénin

Die Arbeit präsentiert einen methodischen Ansatz zur Analyse raumverändernder Prozesse mit heterogenen Fernerkundungsdaten - eine für Entwicklungsländer typische Situation. Dazu werden beispielhaft Teilräume der Küstenzone Benins untersucht, die einem extremen Nutzungsdruck und -wandel ausgesetzt sind. Als besonders bedeutsame Prozesse werden Siedlungsentwicklungen, Veränderungen landwirtschaftlicher Nutzflächen und Küstenerosion herausgegriffen und vorgestellt

DNA damage-induced translocation of S100A11 into the nucleus regulates cell proliferation

<p>Abstract</p> <p>Background</p> <p>Proteins are able to react in response to distinct stress stimuli by alteration of their subcellular distribution. The stress-responsive protein S100A11 belongs to the family of multifunctional S100 proteins which have been implicated in several key biological processes. Previously, we have shown that S100A11 is directly involved in DNA repair processes at damaged chromatin in the nucleus. To gain further insight into the underlying mechanism subcellular trafficking of S100A11 in response to DNA damage was analyzed.</p> <p>Results</p> <p>We show that DNA damage induces a nucleolin-mediated translocation of S100A11 from the cytoplasm into the nucleus. This translocation is impeded by inhibition of the phosphorylation activity of PKCα. Translocation of S100A11 into the nucleus correlates with an increased cellular p21 protein level. Depletion of nucleolin by siRNA severely impairs translocation of S100A11 into the nucleus resulting in a decreased p21 protein level. Additionally, cells lacking nucleolin showed a reduced colony forming capacity.</p> <p>Conclusions</p> <p>These observations suggest that regulation of the subcellular distribution of S100A11 plays an important role in the DNA damage response and p21-mediated cell cycle control.</p

Performative arts and pedagogy: A German perspective

This report resulted from a number of meetings in the context of The Performative Arts and Pedagogy Project – Towards the Development of an International Glossary (for further details click here). Representatives from five different countries (Austria, Germany, Great Britain, Ireland, Switzerland) have contributed to the project, engaging in an interdisciplinary and intercultural exchange that aims at an increased awareness of (culture-)specific concepts and associated terminologies that are applied in Performative Arts and Pedagogy contexts

On giant shoulders: How a seamount affects the microbial community composition of seawater and sponges

Seamounts represent ideal systems to study the influence and interdependency of environmental gradients at a single geographic location. These topographic features represent a prominent habitat for various forms of life, including microbiota and macrobiota, spanning benthic as well as pelagic organisms. While it is known that seamounts are globally abundant structures, it still remains unclear how and to which extent the complexity of the sea floor is intertwined with the local oceanographic mosaic, biogeochemistry, and microbiology of a seamount ecosystem. Along these lines, the present study aimed to explore whether and to what extent seamounts can have an imprint on the microbial community composition of seawater and of sessile benthic invertebrates, sponges. For our high-resolution sampling approach of microbial diversity (16S rRNA gene amplicon sequencing) along with measurements of inorganic nutrients and other biogeochemical parameters, we focused on the Schulz Bank seamount ecosystem, a sponge ground ecosystem which is located on the Arctic Mid-Ocean Ridge. Seawater samples were collected at two sampling depths (mid-water, MW, and near-bed water, BW) from a total of 19 sampling sites. With a clustering approach we defined microbial microhabitats within the pelagic realm at Schulz Bank, which were mapped onto the seamount's topography and related to various environmental parameters (such as suspended particulate matter, SPM; dissolved inorganic carbon, DIC; silicate, SiO−4; phosphate, PO3−4; ammonia, NH+4; nitrate, NO2−3; nitrite, NO−2; depth; and dissolved oxygen, O2). The results of our study reveal a “seamount effect” (sensu stricto) on the microbial mid-water pelagic community at least 200 m above the sea floor. Further, we observed a strong spatial heterogeneity in the pelagic microbial landscape across the seamount, with planktonic microbial communities reflecting oscillatory and circulatory water movements, as well as processes of bentho-pelagic coupling. Depth, NO2−3, SiO−4, and O2 concentrations differed significantly between the determined pelagic microbial clusters close to the sea floor (BW), suggesting that these parameters were presumably linked to changes in microbial community structures. Secondly, we assessed the associated microbial community compositions of three sponge species along a depth gradient of the seamount. While sponge-associated microbial communities were found to be mainly species-specific, we also detected significant intra-specific differences between individuals, depending on the pelagic near-bed cluster they originated from. The variable microbial phyla (i.e. phyla which showed significant differences across varying depth, NO2−3, SiO−4, O2 concentrations, and different from local seawater communities) were distinct for every sponge species when considering average abundances per species. Variable microbial phyla included representatives of both those taxa traditionally counted for the variable community fraction and taxa counted traditionally for the core community fraction. Microbial co-occurrence patterns for the three examined sponge species Geodia hentscheli, Lissodendoryx complicata, and Schaudinnia rosea were distinct from each other. Over all, this study shows that topographic structures such as the Schulz Bank seamount can have an imprint (seamount effect sensu lato) on both the microbial community composition of seawater and sessile benthic invertebrates such as sponges by an interplay between the geology, physical oceanography, biogeochemistry, and microbiology of seamounts

On giant shoulders: How a seamount affects the microbial community composition of seawater and sponges

Seamounts represent ideal systems to study the influence and interdependency of environmental gradients at a single geographic location. These topographic features represent a prominent habitat for various forms of life, including microbiota and macrobiota, spanning benthic as well as pelagic organisms. While it is known that seamounts are globally abundant structures, it still remains unclear how and to which extent the complexity of the sea floor is intertwined with the local oceanographic mosaic, biogeochemistry, and microbiology of a seamount ecosystem. Along these lines, the present study aimed to explore whether and to what extent seamounts can have an imprint on the microbial community composition of seawater and of sessile benthic invertebrates, sponges. For our high-resolution sampling approach of microbial diversity (16S rRNA gene amplicon sequencing) along with measurements of inorganic nutrients and other biogeochemical parameters, we focused on the Schulz Bank seamount ecosystem, a sponge ground ecosystem which is located on the Arctic Mid-Ocean Ridge. Seawater samples were collected at two sampling depths (mid-water, MW, and near-bed water, BW) from a total of 19 sampling sites. With a clustering approach we defined microbial microhabitats within the pelagic realm at Schulz Bank, which were mapped onto the seamount's topography and related to various environmental parameters (such as suspended particulate matter, SPM; dissolved inorganic carbon, DIC; silicate, SiO−4; phosphate, PO3−4; ammonia, NH+4; nitrate, NO2−3; nitrite, NO−2; depth; and dissolved oxygen, O2). The results of our study reveal a “seamount effect” (sensu stricto) on the microbial mid-water pelagic community at least 200 m above the sea floor. Further, we observed a strong spatial heterogeneity in the pelagic microbial landscape across the seamount, with planktonic microbial communities reflecting oscillatory and circulatory water movements, as well as processes of bentho-pelagic coupling. Depth, NO2−3, SiO−4, and O2 concentrations differed significantly between the determined pelagic microbial clusters close to the sea floor (BW), suggesting that these parameters were presumably linked to changes in microbial community structures. Secondly, we assessed the associated microbial community compositions of three sponge species along a depth gradient of the seamount. While sponge-associated microbial communities were found to be mainly species-specific, we also detected significant intra-specific differences between individuals, depending on the pelagic near-bed cluster they originated from. The variable microbial phyla (i.e. phyla which showed significant differences across varying depth, NO2−3, SiO−4, O2 concentrations, and different from local seawater communities) were distinct for every sponge species when considering average abundances per species. Variable microbial phyla included representatives of both those taxa traditionally counted for the variable community fraction and taxa counted traditionally for the core community fraction. Microbial co-occurrence patterns for the three examined sponge species Geodia hentscheli, Lissodendoryx complicata, and Schaudinnia rosea were distinct from each other. Over all, this study shows that topographic structures such as the Schulz Bank seamount can have an imprint (seamount effect sensu lato) on both the microbial community composition of seawater and sessile benthic invertebrates such as sponges by an interplay between the geology, physical oceanography, biogeochemistry, and microbiology of seamounts

A New Bioactive Compound From the Marine Sponge-Derived Streptomyces sp. SBT348 Inhibits Staphylococcal Growth and Biofilm Formation

Staphylococcus epidermidis, the common inhabitant of human skin and mucosal surfaces has emerged as an important pathogen in patients carrying surgical implants and medical devices. Entering the body via surgical sites and colonizing the medical devices through formation of multi-layered biofilms leads to refractory and persistent device-related infections (DRIs). Staphylococci organized in biofilms are more tolerant to antibiotics and immune responses, and thus are difficult-to-treat. The consequent morbidity and mortality, and economic losses in health care systems has strongly necessitated the need for development of new anti-bacterial and anti-biofilm-based therapeutics. In this study, we describe the biological activity of a marine sponge-derived Streptomyces sp. SBT348 extract in restraining staphylococcal growth and biofilm formation on polystyrene, glass, medically relevant titan metal, and silicone surfaces. A bioassay-guided fractionation was performed to isolate the active compound (SKC3) from the crude SBT348 extract. Our results demonstrated that SKC3 effectively inhibits the growth (MIC: 31.25 μg/ml) and biofilm formation (sub-MIC range: 1.95–<31.25 μg/ml) of S. epidermidis RP62A in vitro. Chemical characterization of SKC3 by heat and enzyme treatments, and mass spectrometry (HRMS) revealed its heat-stable and non-proteinaceous nature, and high molecular weight (1258.3 Da). Cytotoxicity profiling of SKC3 in vitro on mouse fibroblast (NIH/3T3) and macrophage (J774.1) cell lines, and in vivo on the greater wax moth larvae Galleria mellonella revealed its non-toxic nature at the effective dose. Transcriptome analysis of SKC3 treated S. epidermidis RP62A has further unmasked its negative effect on central metabolism such as carbon flux as well as, amino acid, lipid, and energy metabolism. Taken together, these findings suggest a potential of SKC3 as a putative drug to prevent staphylococcal DRIs

Novel insights into PORCN mutations, associated phenotypes and pathophysiological aspects.

BACKGROUND: Goltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants. RESULTS: We report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes. CONCLUSIONS: Our combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS

Novel insights into PORCN mutations, associated phenotypes and pathophysiological aspects.

BACKGROUND: Goltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants. RESULTS: We report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes. CONCLUSIONS: Our combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS

A Homozygous PPP1R21 Splice Variant Associated with Severe Developmental Delay, Absence of Speech, and Muscle Weakness Leads to Activated Proteasome Function

PPP1R21 acts as a co-factor for protein phosphatase 1 (PP1), an important serine/threonine phosphatase known to be essential for cell division, control of glycogen metabolism, protein synthesis, and muscle contractility. Bi-allelic pathogenic variants in PPP1R21 were linked to a neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities (NEDHFBA) with pediatric onset. Functional studies unraveled impaired vesicular transport as being part of PPP1R21-related pathomechanism. To decipher further the pathophysiological processes leading to the clinical manifestation of NEDHFBA, we investigated the proteomic signature of fibroblasts derived from the first NEDHFBA patient harboring a splice-site mutation in PPP1R21 and presenting with a milder phenotype. Proteomic findings and further functional studies demonstrate a profound activation of the ubiquitin–proteasome system with presence of protein aggregates and impact on cellular fitness and moreover suggest a cross-link between activation of the proteolytic system and cytoskeletal architecture (including filopodia) as exemplified on paradigmatic proteins including actin, thus extending the pathophysiological spectrum of the disease. In addition, the proteomic signature of PPP1R21-mutant fibroblasts displayed a dysregulation of a variety of proteins of neurological relevance. This includes increase proteins which might act toward antagonization of cellular stress burden in terms of pro-survival, a molecular finding which might accord with the presentation of a milder phenotype of our NEDHFBA patient

Changes of Proteases, Antiproteases, and Pathogens in Cystic Fibrosis Patients&apos; Upper and Lower Airways after IV-Antibiotic Therapy

Background. In cystic fibrosis (CF) the upper (UAW) and lower airways (LAW) are reservoirs for pathogens like Pseudomonas aeruginosa. The consecutive hosts&apos; release of proteolytic enzymes contributes to inflammation and progressive pulmonary destruction. Objectives were to assess dynamics of protease : antiprotease ratios and pathogens in CF-UAW and LAW sampled by nasal lavage (NL) and sputum before and after intravenous-(IV-) antibiotic therapy. Methods. From 19 IV-antibiotic courses of 17 CF patients NL (10 mL/nostril) and sputum were collected before and after treatment. Microbiological colonization and concentrations of NE/SLPI/CTSS (ELISA) and MMP-9/TIMP-1 (multiplex bead array) were determined. Additionally, changes of sinonasal symptoms were assessed (SNOT-20). Results. IV-antibiotic treatment had more pronounced effects on inflammatory markers in LAW, whereas trends to decrease were also found in UAW. Ratios of MMP-9/TIMP-1 were higher in sputum, and ratios of NE/SLPI were higher in NL. Remarkably, NE/SLPI ratio was 10-fold higher in NL compared to healthy controls. SNOT-20 scores decreased significantly during therapy ( = 0.001). Conclusion. For the first time, changes in microbiological patterns in UAW and LAW after IV-antibiotic treatments were assessed, together with changes of protease/antiprotease imbalances. Delayed responses of proteases and antiproteases to IV-antibiotic therapy were found in UAW compared to LAW