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Cat's claw creeper (Dolichandra unguis-cati), native to tropical South America, is a major invasive species and a target for biological control in Australia, South Africa and some South Pacific Island countries. Native range surveys in Argentina, Brazil, Paraguay and Venezuela have identified eight insects and four fungal pathogens as potential agents. Five leaf-feeding insects a tortoise beetle Charidotis auroguttata, two tingids Carvalhotingis visenda and C. hollandi, a leaf-tying moth Hypocosmia pyrochroma and a leaf-mining beetle Hedwigiella jureceki, have been tested and all were released in South Africa. Four of these have become established but are not widespread and cause only limited damage. In Australia, only three of these, C. visenda, H. pyrochroma and H. jureceki were released, while C. auroguttata was not approved due to perceived non-target risks. All agents have become widely established, except for H. pyrochroma which is restricted to riparian corridors in southeast Queensland. In South Africa, an accidentally introduced leaf-spot pathogen, Neoramulariopsis unguis-cati, causes necrotic lesions and premature abscission of leaves in cat's claw creeper infestations, resulting in widespread defoliation. Based on its impact and field-host specificity in its native range and in South Africa, the pathogen has been prioritised for evaluation as a potential additional agent in Australia. The current priority is to seek approval for the introduction of this leaf-spot pathogen into Australia. Future research should focus on the gall-inducing rust Uropyxis rickiana and the seed-feeding weevil Apteromechus notatus as prospective agents.

Cat's claw creeper (Dolichandra unguis-cati), native to tropical South America, is a major invasive species and a target for biological control in Australia, South Africa and some South Pacific Island countries. Native range surveys in Argentina, Brazil, Paraguay and Venezuela have identified eight insects and four fungal pathogens as potential agents. Five leaf-feeding insects a tortoise beetle Charidotis auroguttata, two tingids Carvalhotingis visenda and C. hollandi, a leaf-tying moth Hypocosmia pyrochroma and a leaf-mining beetle Hedwigiella jureceki, have been tested and all were released in South Africa. Four of these have become established but are not widespread and cause only limited damage. In Australia, only three of these, C. visenda, H. pyrochroma and H. jureceki were released, while C. auroguttata was not approved due to perceived non-target risks. All agents have become widely established, except for H. pyrochroma which is restricted to riparian corridors in southeast Queensland. In South Africa, an accidentally introduced leaf-spot pathogen, Neoramulariopsis unguis-cati, causes necrotic lesions and premature abscission of leaves in cat's claw creeper infestations, resulting in widespread defoliation. Based on its impact and field-host specificity in its native range and in South Africa, the pathogen has been prioritised for evaluation as a potential additional agent in Australia. The current priority is to seek approval for the introduction of this leaf-spot pathogen into Australia. Future research should focus on the gall-inducing rust Uropyxis rickiana and the seed-feeding weevil Apteromechus notatus as prospective agents.

Background The aim of this study was to investigate the effect of prolonged endurance exercise on adipose tissue inflammation markers and mitochondrial respiration in younger and older men. Methods “Young” (aged 30 years, n = 7) and “old” (aged 65 years, n = 7) trained men were exposed to an exercise intervention of 15 consecutive days biking 7 to 9 hours/day at 63% and 65% of maximal heart rate (young and old, respectively), going from Copenhagen, Denmark to Palermo, Italy. Adipose tissue was sampled from both the gluteal and abdominal depot before and after the intervention. Mitochondrial respiration was measured by high-resolution respirometry, and adipose inflammation was assessed by immunohistochemical staining of paraffin embedded sections. Results An increased number of CD163+ macrophages was observed in both the gluteal and abdominal depot (P < .01). In addition, an increased mitochondrial respiration was observed in the abdominal adipose tissue from men in the young group with complex I (CIp) stimulated respiration, complex I + II (CI+IIp) stimulated respiration and the capacity of the electron transport system (ETS) (P < .05), and in the older group an increase in CIp and CI+IIp stimulated respiration (P < .05) was found. Conclusion Overall, we found a positive effect of prolonged endurance exercise on adipose tissue inflammation markers and mitochondrial respiration in both young and old trained men, and no sign of attenuated function in adipose tissue with age., BACKGROUND: The aim of this study was to investigate the effect of prolonged endurance exercise on adipose tissue inflammation markers and mitochondrial respiration in younger and older men. METHODS: "Young" (aged 30 years, n = 7) and "old" (aged 65 years, n = 7) trained men were exposed to an exercise intervention of 15 consecutive days biking 7 to 9 hours/day at 63% and 65% of maximal heart rate (young and old, respectively), going from Copenhagen, Denmark to Palermo, Italy. Adipose tissue was sampled from both the gluteal and abdominal depot before and after the intervention. Mitochondrial respiration was measured by high-resolution respirometry, and adipose inflammation was assessed by immunohistochemical staining of paraffin embedded sections. RESULTS: An increased number of CD163+ macrophages was observed in both the gluteal and abdominal depot (P < .01). In addition, an increased mitochondrial respiration was observed in the abdominal adipose tissue from men in the young group with complex I (CIp) stimulated respiration, complex I + II (CI+IIp) stimulated respiration and the capacity of the electron transport system (ETS) (P < .05), and in the older group an increase in CIp and CI+IIp stimulated respiration (P < .05) was found. CONCLUSION: Overall, we found a positive effect of prolonged endurance exercise on adipose tissue inflammation markers and mitochondrial respiration in both young and old trained men, and no sign of attenuated function in adipose tissue with age.

Purpose: The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy. Patients and Methods: In this single-institution retrospective analysis, patients with biopsy-proven IHC treated with either curative-intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver-limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver-limited recurrence was analyzed in the resection cohort. Results: From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34–0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50–0.65 vs. HR 0.63, 95% CI 0.57–0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver-only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29–0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression-free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46–0.91; p = 0.01), which correlated with improved

BACKGROUND: The pro-adaptive effects of glucagon-like peptide-2 (GLP-2) include stimulation of intestinal mucosal growth as well as intestinal blood flow and angiogenesis. We have recently reported that daily subcutaneous injections of glepaglutide, a long-acting GLP-2 analog, improved intestinal absorptive function in patients with short bowel syndrome (SBS). As secondary and exploratory endpoints, the effects of glepaglutide on intestinal morphology and perfusion are reported.METHODS: The following assessments were done in 18 patients with SBS in a randomized, cross-over, dose-finding phase 2 trial before and after three weeks of treatment with glepaglutide: Plasma citrulline; Mucosa biopsies to assess changes in 1) intestinal morphology by immunohistochemistry, and 2) gene expressions associated with absorption, proliferation, and markers of tight junction integrity by quantitative polymerase chain reaction. Intestinal perfusion was assessed in stoma nipples by laser speckle contrast imaging and quantitative fluorescence angiography with indocyanine green.RESULTS: In the 1 mg and 10 mg dose groups, glepaglutide significantly increased plasma citrulline by 15.3 µmol/L (p=0.001) and 15.6 µmol/L (p=0.001), respectively. Trends towards increase in villus height, crypt depth, and epithelium height were seen in the same groups. No significant changes were seen in gene expressions or intestinal perfusion.CONCLUSION: The increase in plasma citrulline and the morphological improvements may partly account for improvement in the intestinal absorptive function. However, the finding of a stability in perfusion after three weeks of treatment with glepaglutide may have been preceded by a more profound acute-phase increase in intestinal perfusion at treatment initiation.CLINICAL RELEVANCY STATEMENT: Our findings in the present article showed that three weeks of treatment with glepaglutide, a novel long-acting glucagon-like peptide-2 analog, was ass

Navua sedge (Cyperus aromaticus) is an aggressive perennial sedge in pastures and crops in the wet tropical regions of Australia and numerous Pacific Island countries and territories. A biological control program was started in Australia to look for biological control agents for C. aromaticus in its native range in equatorial Africa. Surveys in Kenya, Tanzania, and Nigeria identified Cintractia kyllingae, Uredo kyllingae-erectae, and Curvularia tanzanica, as potential biological control agents. Cintractia kyllingae is currently under study at CABI, UK for its host specificity to C. aromaticus as a prerequisite for any future release in Australia.

Navua sedge (Cyperus aromaticus) is an aggressive perennial sedge in pastures and crops in the wet tropical regions of Australia and numerous Pacific Island countries and territories. A biological control program was started in Australia to look for biological control agents for C. aromaticus in its native range in equatorial Africa. Surveys in Kenya, Tanzania, and Nigeria identified Cintractia kyllingae, Uredo kyllingae-erectae, and Curvularia tanzanica, as potential biological control agents. Cintractia kyllingae is currently under study at CABI, UK for its host specificity to C. aromaticus as a prerequisite for any future release in Australia.

Navua sedge (Cyperus aromaticus) is an aggressive perennial sedge in pastures and crops in the wet tropical regions of Australia and numerous Pacific Island countries and territories. A biological control program was started in Australia to look for biological control agents for C. aromaticus in its native range in equatorial Africa. Surveys in Kenya, Tanzania, and Nigeria identified Cintractia kyllingae, Uredo kyllingae-erectae, and Curvularia tanzanica, as potential biological control agents. Cintractia kyllingae is currently under study at CABI, UK for its host specificity to C. aromaticus as a prerequisite for any future release in Australia.

Navua sedge (Cyperus aromaticus), a native of equatorial Africa, is an extremely aggressive perennial sedge, affecting beef, dairy, and sugarcane industries in the wet tropical regions of northern Queensland, Australia. Navua sedge is also a major weed of crops and pastures in Fiji and other South Pacific Islands. Navua sedge is unpalatable and forms dense stands that can replace palatable tropical pasture species. Current management options are mechanical and chemical, which are expensive and offer only short-term relief. Biological control is considered the most cost-effective and long-term management option. Navua sedge has been approved as a target for biological control in Australia, where a biological control program was initiated in 2017.Native range surveys in Kenya, Nigeria andTanzania found three promising biological control fungi; specifically, a smut fungus (Cintractia kyllingae) that infects flower heads and seeds; a rust fungus (Uredo kyllingae-erectae) that attacks leaves and stems; and an inflorescence-colonising ascomycete (Curvularia tanzanica). Field surveys have only recorded these fungi in association with Navua sedge. For effective biological control of Navua sedge, multiple agents that target different parts of the sedge maybe needed to reduce seed production and minimise its impact and spread. These three fungal pathogens have been exported to CABI-UK, where host-specificity testing for C.kyllingaeis in progress; and testing for U. kyllingae-erectaewill commence soon. If proven to be host specific, the pathogens will be released in Australia. Current research in Australia has focused on the search for local pathogens on Navua sedge that may have potential as mycoherbicides. Several fungi of interest have been found in Australia, including species of Curvularia, Epicoccum, Fusarium, Neopestalotiopsis, Nigrospora, and Phaeosphaeria, as well as other fungal pathogens yet to be identified.

Navua sedge (Cyperus aromaticus), a native of equatorial Africa, is an extremely aggressive perennial sedge, affecting beef, dairy, and sugarcane industries in the wet tropical regions of northern Queensland, Australia. Navua sedge is also a major weed of crops and pastures in Fiji and other South Pacific Islands. Navua sedge is unpalatable and forms dense stands that can replace palatable tropical pasture species. Current management options are mechanical and chemical, which are expensive and offer only short-term relief. Biological control is considered the most cost-effective and long-term management option. Navua sedge has been approved as a target for biological control in Australia, where a biological control program was initiated in 2017.Native range surveys in Kenya, Nigeria andTanzania found three promising biological control fungi; specifically, a smut fungus (Cintractia kyllingae) that infects flower heads and seeds; a rust fungus (Uredo kyllingae-erectae) that attacks leaves and stems; and an inflorescence-colonising ascomycete (Curvularia tanzanica). Field surveys have only recorded these fungi in association with Navua sedge. For effective biological control of Navua sedge, multiple agents that target different parts of the sedge maybe needed to reduce seed production and minimise its impact and spread. These three fungal pathogens have been exported to CABI-UK, where host-specificity testing for C.kyllingaeis in progress; and testing for U. kyllingae-erectaewill commence soon. If proven to be host specific, the pathogens will be released in Australia. Current research in Australia has focused on the search for local pathogens on Navua sedge that may have potential as mycoherbicides. Several fungi of interest have been found in Australia, including species of Curvularia, Epicoccum, Fusarium, Neopestalotiopsis, Nigrospora, and Phaeosphaeria, as well as other fungal pathogens yet to be identified.

Navua sedge (Cyperus aromaticus), a native of equatorial Africa, is an extremely aggressive perennial sedge, affecting beef, dairy, and sugarcane industries in the wet tropical regions of northern Queensland, Australia. Navua sedge is also a major weed of crops and pastures in Fiji and other South Pacific Islands. Navua sedge is unpalatable and forms dense stands that can replace palatable tropical pasture species. Current management options are mechanical and chemical, which are expensive and offer only short-term relief. Biological control is considered the most cost-effective and long-term management option. Navua sedge has been approved as a target for biological control in Australia, where a biological control program was initiated in 2017.Native range surveys in Kenya, Nigeria andTanzania found three promising biological control fungi; specifically, a smut fungus (Cintractia kyllingae) that infects flower heads and seeds; a rust fungus (Uredo kyllingae-erectae) that attacks leaves and stems; and an inflorescence-colonising ascomycete (Curvularia tanzanica). Field surveys have only recorded these fungi in association with Navua sedge. For effective biological control of Navua sedge, multiple agents that target different parts of the sedge maybe needed to reduce seed production and minimise its impact and spread. These three fungal pathogens have been exported to CABI-UK, where host-specificity testing for C.kyllingaeis in progress; and testing for U. kyllingae-erectaewill commence soon. If proven to be host specific, the pathogens will be released in Australia. Current research in Australia has focused on the search for local pathogens on Navua sedge that may have potential as mycoherbicides. Several fungi of interest have been found in Australia, including species of Curvularia, Epicoccum, Fusarium, Neopestalotiopsis, Nigrospora, and Phaeosphaeria, as well as other fungal pathogens yet to be identified.

Navua sedge (Cyperus aromaticus) is an aggressive perennial sedge in pastures and crops in the wet tropical regions of Australia and numerous Pacific Island countries and territories. A biological control program was started in Australia to look for biological control agents for C. aromaticus in its native range in equatorial Africa. Surveys in Kenya, Tanzania, and Nigeria identified Cintractia kyllingae, Uredo kyllingae-erectae, and Curvularia tanzanica, as potential biological control agents. Cintractia kyllingae is currently under study at CABI, UK for its host specificity to C. aromaticus as a prerequisite for any future release in Australia.

Navua sedge (Cyperus aromaticus) is an aggressive perennial sedge in pastures and crops in the wet tropical regions of Australia and numerous Pacific Island countries and territories. A biological control program was started in Australia to look for biological control agents for C. aromaticus in its native range in equatorial Africa. Surveys in Kenya, Tanzania, and Nigeria identified Cintractia kyllingae, Uredo kyllingae-erectae, and Curvularia tanzanica, as potential biological control agents. Cintractia kyllingae is currently under study at CABI, UK for its host specificity to C. aromaticus as a prerequisite for any future release in Australia.

Navua sedge (Cyperus aromaticus), a native of equatorial Africa, is an extremely aggressive perennial sedge, affecting beef, dairy, and sugarcane industries in the wet tropical regions of northern Queensland, Australia. Navua sedge is also a major weed of crops and pastures in Fiji and other South Pacific Islands. Navua sedge is unpalatable and forms dense stands that can replace palatable tropical pasture species. Current management options are mechanical and chemical, which are expensive and offer only short-term relief. Biological control is considered the most cost-effective and long-term management option. Navua sedge has been approved as a target for biological control in Australia, where a biological control program was initiated in 2017.Native range surveys in Kenya, Nigeria andTanzania found three promising biological control fungi; specifically, a smut fungus (Cintractia kyllingae) that infects flower heads and seeds; a rust fungus (Uredo kyllingae-erectae) that attacks leaves and stems; and an inflorescence-colonising ascomycete (Curvularia tanzanica). Field surveys have only recorded these fungi in association with Navua sedge. For effective biological control of Navua sedge, multiple agents that target different parts of the sedge maybe needed to reduce seed production and minimise its impact and spread. These three fungal pathogens have been exported to CABI-UK, where host-specificity testing for C.kyllingaeis in progress; and testing for U. kyllingae-erectaewill commence soon. If proven to be host specific, the pathogens will be released in Australia. Current research in Australia has focused on the search for local pathogens on Navua sedge that may have potential as mycoherbicides. Several fungi of interest have been found in Australia, including species of Curvularia, Epicoccum, Fusarium, Neopestalotiopsis, Nigrospora, and Phaeosphaeria, as well as other fungal pathogens yet to be identified.

Navua sedge (Cyperus aromaticus), a native of equatorial Africa, is an extremely aggressive perennial sedge, affecting beef, dairy, and sugarcane industries in the wet tropical regions of northern Queensland, Australia. Navua sedge is also a major weed of crops and pastures in Fiji and other South Pacific Islands. Navua sedge is unpalatable and forms dense stands that can replace palatable tropical pasture species. Current management options are mechanical and chemical, which are expensive and offer only short-term relief. Biological control is considered the most cost-effective and long-term management option. Navua sedge has been approved as a target for biological control in Australia, where a biological control program was initiated in 2017.Native range surveys in Kenya, Nigeria andTanzania found three promising biological control fungi; specifically, a smut fungus (Cintractia kyllingae) that infects flower heads and seeds; a rust fungus (Uredo kyllingae-erectae) that attacks leaves and stems; and an inflorescence-colonising ascomycete (Curvularia tanzanica). Field surveys have only recorded these fungi in association with Navua sedge. For effective biological control of Navua sedge, multiple agents that target different parts of the sedge maybe needed to reduce seed production and minimise its impact and spread. These three fungal pathogens have been exported to CABI-UK, where host-specificity testing for C.kyllingaeis in progress; and testing for U. kyllingae-erectaewill commence soon. If proven to be host specific, the pathogens will be released in Australia. Current research in Australia has focused on the search for local pathogens on Navua sedge that may have potential as mycoherbicides. Several fungi of interest have been found in Australia, including species of Curvularia, Epicoccum, Fusarium, Neopestalotiopsis, Nigrospora, and Phaeosphaeria, as well as other fungal pathogens yet to be identified.

Navua sedge (Cyperus aromaticus) is an aggressive perennial sedge in pastures and crops in the wet tropical regions of Australia and numerous Pacific Island countries and territories. A biological control program was started in Australia to look for biological control agents for C. aromaticus in its native range in equatorial Africa. Surveys in Kenya, Tanzania, and Nigeria identified Cintractia kyllingae, Uredo kyllingae-erectae, and Curvularia tanzanica, as potential biological control agents. Cintractia kyllingae is currently under study at CABI, UK for its host specificity to C. aromaticus as a prerequisite for any future release in Australia.

Navua sedge (Cyperus aromaticus), a native of equatorial Africa, is an extremely aggressive perennial sedge, affecting beef, dairy, and sugarcane industries in the wet tropical regions of northern Queensland, Australia. Navua sedge is also a major weed of crops and pastures in Fiji and other South Pacific Islands. Navua sedge is unpalatable and forms dense stands that can replace palatable tropical pasture species. Current management options are mechanical and chemical, which are expensive and offer only short-term relief. Biological control is considered the most cost-effective and long-term management option. Navua sedge has been approved as a target for biological control in Australia, where a biological control program was initiated in 2017.Native range surveys in Kenya, Nigeria andTanzania found three promising biological control fungi; specifically, a smut fungus (Cintractia kyllingae) that infects flower heads and seeds; a rust fungus (Uredo kyllingae-erectae) that attacks leaves and stems; and an inflorescence-colonising ascomycete (Curvularia tanzanica). Field surveys have only recorded these fungi in association with Navua sedge. For effective biological control of Navua sedge, multiple agents that target different parts of the sedge maybe needed to reduce seed production and minimise its impact and spread. These three fungal pathogens have been exported to CABI-UK, where host-specificity testing for C.kyllingaeis in progress; and testing for U. kyllingae-erectaewill commence soon. If proven to be host specific, the pathogens will be released in Australia. Current research in Australia has focused on the search for local pathogens on Navua sedge that may have potential as mycoherbicides. Several fungi of interest have been found in Australia, including species of Curvularia, Epicoccum, Fusarium, Neopestalotiopsis, Nigrospora, and Phaeosphaeria, as well as other fungal pathogens yet to be identified.

Navua sedge (Cyperus aromaticus) is an aggressive perennial sedge in pastures and crops in the wet tropical regions of Australia and numerous Pacific Island countries and territories. A biological control program was started in Australia to look for biological control agents for C. aromaticus in its native range in equatorial Africa. Surveys in Kenya, Tanzania, and Nigeria identified Cintractia kyllingae, Uredo kyllingae-erectae, and Curvularia tanzanica, as potential biological control agents. Cintractia kyllingae is currently under study at CABI, UK for its host specificity to C. aromaticus as a prerequisite for any future release in Australia.

Since the arrival of DNA nanotechnology nearly 40 years ago, the field has progressed from its beginnings of envisioning rather simple DNA structures having a branched, multi-strand architecture into creating beautifully complex structures comprising hundreds or even thousands of unique strands, with the possibility to exactly control the positions down to the molecular level. While the earliest construction methodologies, such as simple Holliday junctions or tiles, could reasonably be designed on pen and paper in a short amount of time, the advent of complex techniques, such as DNA origami or DNA bricks, require software to reduce the time required and propensity for human error within the design process. Where available, readily accessible design software catalyzes our ability to bring techniques to researchers in diverse fields and it has helped to speed the penetration of methods, such as DNA origami, into a wide range of applications from biomedicine to photonics. Here, we review the historical and current state of CAD software to enable a variety of methods that are fundamental to using structural DNA technology. Beginning with the first tools for predicting sequence-based secondary structure of nucleotides, we trace the development and significance of different software packages to the current state-of-the-art, with a particular focus on programs that are open source.

Der Beitrag setzt sich mit der Ambivalenz des dokumentarischen Blicks zwischen Sichtbarmachung und Othering auseinander. Im Zentrum steht der 2016 in Wien entstandene Dokumentarfilm Brüder der Nacht von Patric Chiha, der sich mit bulgarischen Arbeitsmigranten befasst, die in Wien als Stricher arbeiten. Das Porträt der jungen Männer dehnt die Grenzen des Dokumentarischen maximal aus und begegnet dem Problem ihrer Viktimisierung auf besondere Weise. Anhand des aktuellen Beispiels werden historische Kontinuitäten und Diskontinuitäten des dokumentarischen Blicks auf prekäres Leben und soziale Armut aufgezeigt., Andrea Seier, ‘Rotlicht im/als Filmlicht: Zur performativen Ästhetik des dokumentarischen Blicks’, in Queeres Kino / Queere Ästhetiken als Dokumentationen des Prekären, ed. by Astrid Deuber-Mankowsky and Philipp Hanke, Cultural Inquiry, 22 (Berlin: ICI Berlin Press, 2021), pp. 179-97

Background Amplification of the MYCN oncogene is a molecular hallmark of aggressive neuroblastoma (NB), a childhood cancer of the sympathetic nervous system. There is evidence that MYCN promotes a non-inflamed and T-cell infiltration-poor ('cold') tumor microenvironment (TME) by suppressing interferon signaling. This may explain, at least in part, why patients with NB seem to have little benefit from single-agent immune checkpoint blockade (ICB) therapy. Targeting MYCN or its effectors could be a strategy to convert a cold TME into a 'hot' (inflamed) TME and improve the efficacy of ICB therapy. Methods NB transcriptome analyses were used to identify epigenetic drivers of a T-cell infiltration-poor TME. Biological and molecular responses of NB cells to epigenetic drugs and interferon (IFN)-gamma exposure were assessed by proliferation assays, immunoblotting, ELISA, qRT-PCR, RNA-seq and ChIP-qPCR as well as co-culture assays with T cells. Results We identified H3K9 euchromatic histone-lysine methyltransferases EHMT2 and EHMT1, also known as G9a and GLP, as epigenetic effectors of the MYCN-driven malignant phenotype and repressors of IFN-gamma transcriptional responses in NB cells. EHMT inhibitors enhanced IFN-gamma-induced expression of the Th1-type chemokines CXCL9 and CXCL10, key factors of T-cell recruitment into the TME. In MYCN-amplified NB cells, co-inhibition of EZH2 (enhancer of zeste homologue 2), a H3K27 histone methyltransferase cooperating with EHMTs, was needed for strong transcriptional responses to IFN-gamma, in line with histone mark changes at CXCL9 and CXCL10 chemokine gene loci. EHMT and EZH2 inhibitor response gene signatures from NB cells were established as surrogate measures and revealed high EHMT and EZH2 activity in MYCN-amplified high-risk NBs with a cold immune phenotype. Conclusion Our results delineate a strategy for targeted epigenetic immunomodulation of high-risk NBs, whereby EHMT inhibitors alone or in combination with EZH2 inhibitors

Anhand von zwei Spiel- und einem Dokumentarfilm setzt sich der Beitrag mit der filmischen Inszenierung sozialer Im/Mobilität auseinander. Den Ausgangspunkt bildet die These, dass das meritokratische Versprechen eines sozialen Aufstiegs durch Leistung im Kino der Gegenwart irritiert und auf unterschiedliche Weise hinterfragt und problematisiert wird. Nicht nur die Inhalte der Filme, sondern auch die formale Gestaltung weisen ein Spannungsverhältnis zwischen linearen, narrativen Verläufen und szenischen Gefügen auf, das wir anhand der Filme Parasite (Südkorea 2019, Regie: Bong Joon-ho,), Hillbilly Elegy (USA 2020, Regie: Ron Howard) und Jetzt oder Morgen? (Österreich 2020, Regie: Lisa Weber) untersuchen. Methodisch lässt sich der Beitrag von den affekttheoretischen Thesen der Kultur- und Literaturwissenschaftlerin Lauren Berlants anleiten, die sie in ihrem 2011 erschienenen Buch Cruel Optimism entwickelt hat., Based on two feature films and a documentary, Parasite (South Korea 2019, Bong Joon-ho), Hillbilly Elegy (USA 2020, Ron Howard), and Jetzt oder Morgen? (Austria 2020, Lisa Weber), this article examines the cinematic staging of social im/mobility. The underlying thesis is that the meritocratic promise of social advancement through achievement is disrupted, called into question and problematized in contemporary cinema in different ways. Not only the content of these films but also their formal design points to a tension between linear, narrative progressions and scenic structures. The article applies the affect-theoretical approach which the cultural and literary scholar Lauren Berlant developed in her book Cruel Optimism from 2011.

Since the arrival of DNA nanotechnology nearly 40 years ago, the field has progressed from its beginnings of envisioning rather simple DNA structures having a branched, multi-strand architecture into creating beautifully complex structures comprising hundreds or even thousands of unique strands, with the possibility to exactly control the positions down to the molecular level. While the earliest construction methodologies, such as simple Holliday junctions or tiles, could reasonably be designed on pen and paper in a short amount of time, the advent of complex techniques, such as DNA origami or DNA bricks, require software to reduce the time required and propensity for human error within the design process. Where available, readily accessible design software catalyzes our ability to bring techniques to researchers in diverse fields and it has helped to speed the penetration of methods, such as DNA origami, into a wide range of applications from biomedicine to photonics. Here, we review the historical and current state of CAD software to enable a variety of methods that are fundamental to using structural DNA technology. Beginning with the first tools for predicting sequence-based secondary structure of nucleotides, we trace the development and significance of different software packages to the current state-of-the-art, with a particular focus on programs that are open source.

Der Beitrag setzt sich mit der Ambivalenz des dokumentarischen Blicks zwischen Sichtbarmachung und Othering auseinander. Im Zentrum steht der 2016 in Wien entstandene Dokumentarfilm Brüder der Nacht von Patric Chiha, der sich mit bulgarischen Arbeitsmigranten befasst, die in Wien als Stricher arbeiten. Das Porträt der jungen Männer dehnt die Grenzen des Dokumentarischen maximal aus und begegnet dem Problem ihrer Viktimisierung auf besondere Weise. Anhand des aktuellen Beispiels werden historische Kontinuitäten und Diskontinuitäten des dokumentarischen Blicks auf prekäres Leben und soziale Armut aufgezeigt., Andrea Seier, ‘Rotlicht im/als Filmlicht: Zur performativen Ästhetik des dokumentarischen Blicks’, in Queeres Kino / Queere Ästhetiken als Dokumentationen des Prekären, ed. by Astrid Deuber-Mankowsky and Philipp Hanke, Cultural Inquiry, 22 (Berlin: ICI Berlin Press, 2021), pp. 179-97

Since the arrival of DNA nanotechnology nearly 40 years ago, the field has progressed from its beginnings of envisioning rather simple DNA structures having a branched, multi-strand architecture into creating beautifully complex structures comprising hundreds or even thousands of unique strands, with the possibility to exactly control the positions down to the molecular level. While the earliest construction methodologies, such as simple Holliday junctions or tiles, could reasonably be designed on pen and paper in a short amount of time, the advent of complex techniques, such as DNA origami or DNA bricks, require software to reduce the time required and propensity for human error within the design process. Where available, readily accessible design software catalyzes our ability to bring techniques to researchers in diverse fields and it has helped to speed the penetration of methods, such as DNA origami, into a wide range of applications from biomedicine to photonics. Here, we review the historical and current state of CAD software to enable a variety of methods that are fundamental to using structural DNA technology. Beginning with the first tools for predicting sequence-based secondary structure of nucleotides, we trace the development and significance of different software packages to the current state-of-the-art, with a particular focus on programs that are open source.

Der Beitrag setzt sich mit der Ambivalenz des dokumentarischen Blicks zwischen Sichtbarmachung und Othering auseinander. Im Zentrum steht der 2016 in Wien entstandene Dokumentarfilm Brüder der Nacht von Patric Chiha, der sich mit bulgarischen Arbeitsmigranten befasst, die in Wien als Stricher arbeiten. Das Porträt der jungen Männer dehnt die Grenzen des Dokumentarischen maximal aus und begegnet dem Problem ihrer Viktimisierung auf besondere Weise. Anhand des aktuellen Beispiels werden historische Kontinuitäten und Diskontinuitäten des dokumentarischen Blicks auf prekäres Leben und soziale Armut aufgezeigt., Andrea Seier, ‘Rotlicht im/als Filmlicht: Zur performativen Ästhetik des dokumentarischen Blicks’, in Queeres Kino / Queere Ästhetiken als Dokumentationen des Prekären, ed. by Astrid Deuber-Mankowsky and Philipp Hanke, Cultural Inquiry, 22 (Berlin: ICI Berlin Press, 2021), pp. 179-97

Since the arrival of DNA nanotechnology nearly 40 years ago, the field has progressed from its beginnings of envisioning rather simple DNA structures having a branched, multi-strand architecture into creating beautifully complex structures comprising hundreds or even thousands of unique strands, with the possibility to exactly control the positions down to the molecular level. While the earliest construction methodologies, such as simple Holliday junctions or tiles, could reasonably be designed on pen and paper in a short amount of time, the advent of complex techniques, such as DNA origami or DNA bricks, require software to reduce the time required and propensity for human error within the design process. Where available, readily accessible design software catalyzes our ability to bring techniques to researchers in diverse fields and it has helped to speed the penetration of methods, such as DNA origami, into a wide range of applications from biomedicine to photonics. Here, we review the historical and current state of CAD software to enable a variety of methods that are fundamental to using structural DNA technology. Beginning with the first tools for predicting sequence-based secondary structure of nucleotides, we trace the development and significance of different software packages to the current state-of-the-art, with a particular focus on programs that are open source.

Background Amplification of the MYCN oncogene is a molecular hallmark of aggressive neuroblastoma (NB), a childhood cancer of the sympathetic nervous system. There is evidence that MYCN promotes a non-inflamed and T-cell infiltration-poor ('cold') tumor microenvironment (TME) by suppressing interferon signaling. This may explain, at least in part, why patients with NB seem to have little benefit from single-agent immune checkpoint blockade (ICB) therapy. Targeting MYCN or its effectors could be a strategy to convert a cold TME into a 'hot' (inflamed) TME and improve the efficacy of ICB therapy. Methods NB transcriptome analyses were used to identify epigenetic drivers of a T-cell infiltration-poor TME. Biological and molecular responses of NB cells to epigenetic drugs and interferon (IFN)-gamma exposure were assessed by proliferation assays, immunoblotting, ELISA, qRT-PCR, RNA-seq and ChIP-qPCR as well as co-culture assays with T cells. Results We identified H3K9 euchromatic histone-lysine methyltransferases EHMT2 and EHMT1, also known as G9a and GLP, as epigenetic effectors of the MYCN-driven malignant phenotype and repressors of IFN-gamma transcriptional responses in NB cells. EHMT inhibitors enhanced IFN-gamma-induced expression of the Th1-type chemokines CXCL9 and CXCL10, key factors of T-cell recruitment into the TME. In MYCN-amplified NB cells, co-inhibition of EZH2 (enhancer of zeste homologue 2), a H3K27 histone methyltransferase cooperating with EHMTs, was needed for strong transcriptional responses to IFN-gamma, in line with histone mark changes at CXCL9 and CXCL10 chemokine gene loci. EHMT and EZH2 inhibitor response gene signatures from NB cells were established as surrogate measures and revealed high EHMT and EZH2 activity in MYCN-amplified high-risk NBs with a cold immune phenotype. Conclusion Our results delineate a strategy for targeted epigenetic immunomodulation of high-risk NBs, whereby EHMT inhibitors alone or in combination with EZH2 inhibitors

Der Beitrag setzt sich mit der Ambivalenz des dokumentarischen Blicks zwischen Sichtbarmachung und Othering auseinander. Im Zentrum steht der 2016 in Wien entstandene Dokumentarfilm "Brüder der Nacht" von Patric Chiha, der sich mit bulgarischen Arbeitsmigranten befasst, die in Wien als Stricher arbeiten. Das Porträt der jungen Männer dehnt die Grenzen des Dokumentarischen maximal aus und begegnet dem Problem ihrer Viktimisierung auf besondere Weise. Anhand des aktuellen Beispiels werden historische Kontinuitäten und Diskontinuitäten des dokumentarischen Blicks auf prekäres Leben und soziale Armut aufgezeigt.

Background: The aim of this study was to examine feasibility of trial processes and group-based, structured exercise training in patients with first-episode psychosis.Methods: Twenty-five patients with first-episode psychosis took part in a two-arm randomised feasibility trial. They were individually randomised (1:1) via a computer-generated randomisation sequence and allocated to either an exercise intervention group (INT) or a control group (CON). Patients allocated to INT completed a physical exercise training programme at moderate-to-vigorous intensity, 1 h three times weekly for 8 weeks. CON patients were encouraged to continue their usual level of activity and were offered the training programme after 8 weeks. Primary outcomes included screening rate, recruitment rate, retention rate, attendance and adverse events. Secondary outcomes included heart rate response during training, cardiovascular health (VO2max, resting heart rate, blood pressure), body composition (muscle mass, fat percentage), muscle strength (sit-to-stand, grip strength, jump height) and balance.Results: Recruitment lasted 6 weeks and 86 out of 324 patients (27%) were screened, 71 of whom (83%) were deemed eligible. Twenty-five (35%) accepted inclusion (mean age 25.5; mean body mass index 25.1) and were subsequently randomised (INT = 13, CON = 12). Retention of patients was 76% and 52% at the 8-week and 16-week follow-up, respectively. Attendance was 43% (min. 9%, max. 96%). No significant changes were observed between groups in secondary physiological outcome measures.Conclusions: Feasibility was challenged by limited recruitment and retention rates, suggesting that modifications are required if a large-scale randomised controlled trial is to be conducted. Recommendations for modifications are presented and discussed.TRIAL REGISTRATION: Clinicaltrials.gov, NCT03409393 . Retrospectively registered.

Background: The aim of this study was to examine feasibility of trial processes and group-based, structured exercise training in patients with first-episode psychosis.Methods: Twenty-five patients with first-episode psychosis took part in a two-arm randomised feasibility trial. They were individually randomised (1:1) via a computer-generated randomisation sequence and allocated to either an exercise intervention group (INT) or a control group (CON). Patients allocated to INT completed a physical exercise training programme at moderate-to-vigorous intensity, 1 h three times weekly for 8 weeks. CON patients were encouraged to continue their usual level of activity and were offered the training programme after 8 weeks. Primary outcomes included screening rate, recruitment rate, retention rate, attendance and adverse events. Secondary outcomes included heart rate response during training, cardiovascular health (VO2max, resting heart rate, blood pressure), body composition (muscle mass, fat percentage), muscle strength (sit-to-stand, grip strength, jump height) and balance.Results: Recruitment lasted 6 weeks and 86 out of 324 patients (27%) were screened, 71 of whom (83%) were deemed eligible. Twenty-five (35%) accepted inclusion (mean age 25.5; mean body mass index 25.1) and were subsequently randomised (INT = 13, CON = 12). Retention of patients was 76% and 52% at the 8-week and 16-week follow-up, respectively. Attendance was 43% (min. 9%, max. 96%). No significant changes were observed between groups in secondary physiological outcome measures.Conclusions: Feasibility was challenged by limited recruitment and retention rates, suggesting that modifications are required if a large-scale randomised controlled trial is to be conducted. Recommendations for modifications are presented and discussed.TRIAL REGISTRATION: Clinicaltrials.gov, NCT03409393 . Retrospectively registered.

Nicht erst seit dem Klimaabkommen von Paris, welches im Kern eine Begrenzung der menschengemachten globalen Erwärmung auf deutlich unter 2 °C gegenüber vorindustriellen Werten vorsieht, ist offensichtlich, dass eine umfassende Transformation der meisten Wirtschaftssektoren erforderlich ist, um die gesteckten Ziele zu erreichen. Die Transformation erfolgt dabei zum einen durch Steigerung der Energieeffizienz und zum anderen durch eine Dekarbonisierung der bestehenden Prozesse, bei denen heute noch ein hoher Anteil fossiler Energien eingesetzt wird - dies kann gelingen durch eine weitreichende Sektorkopplung, Flexibilisierung und Elektrifizierung bei vollständiger Nutzung Erneuerbarer Energien. Letzteres stellt auch die Energieversorgung in Rheinland-Pfalz vor einen Paradigmenwechsel: Die schrittweise Transformation eines von konventionellen Energieträgern geprägten Versorgungsystems zu einem durch Erneuerbare Energien dominierten System. Als eines der ersten Bundesländer hat sich Rheinland-Pfalz bereits im Jahr 2014 ein eigenes Klimaschutzgesetz gegeben sowie erstmals im Jahr 2015 ein Landesklimaschutzkonzept (LKSK) erarbeitet, welches energiepolitische Leitplanken für den angestoßenen Transformationsprozess setzt. Die vorliegende Studie im Auftrag des Ministeriums für Umwelt, Energie, Ernährung und Forsten Rheinland-Pfalz beleuchtet die Auswirkungen eines weiteren Ausbaus der Erneuerbaren Energien in Rheinland-Pfalz und der damit verbundenen Flexibilisierung und Dekarbonisierung unterschiedlicher Anwendungsfelder, insbesondere in der Industrie aber auch im ÖPNV und zentraler Wärmeversorgung.

Objective: Parathyroid hormone (PTH) is a key hormone in regulation of calcium homeostasis and its secretion is regulated by calcium. Secretion of PTH is attenuated during intake of nutrients, but the underlying mechanism(s) are unknown. We hypothesized that insulin acts as an acute regulator of PTH secretion.Methods: Intact PTH was measured in plasma from patients with T1D and matched healthy individuals during 4-h oral glucose tolerance tests (OGTT) and isoglycemic i.v. glucose infusions on 2 separate days. In addition, expression of insulin receptors on surgical specimens of parathyroid glands was assessed by immunochemistry (IHC) and quantitative PCR (qPCR).Results: The inhibition of PTH secretion was more pronounced in healthy individuals compared to patients with T1D during an OGTT (decremental AUC(0-240min): -5256 +/- 3954 min x ng/L and -2408 +/- 1435 min x ng/L, P = 0.030). Insulin levels correlated significantly and inversely with PTH levels, also after adjusting for levels of several gut hormones and BMI (P = 0.002). Expression of insulin receptors in human parathyroid glands was detected by both IHC and qPCR.Conclusion: Our study suggests that insulin may act as an acute regulator of PTH secretion in humans.

Objective: Parathyroid hormone (PTH) is a key hormone in regulation of calcium homeostasis and its secretion is regulated by calcium. Secretion of PTH is attenuated during intake of nutrients, but the underlying mechanism(s) are unknown. We hypothesized that insulin acts as an acute regulator of PTH secretion.Methods: Intact PTH was measured in plasma from patients with T1D and matched healthy individuals during 4-h oral glucose tolerance tests (OGTT) and isoglycemic i.v. glucose infusions on 2 separate days. In addition, expression of insulin receptors on surgical specimens of parathyroid glands was assessed by immunochemistry (IHC) and quantitative PCR (qPCR).Results: The inhibition of PTH secretion was more pronounced in healthy individuals compared to patients with T1D during an OGTT (decremental AUC(0-240min): -5256 +/- 3954 min x ng/L and -2408 +/- 1435 min x ng/L, P = 0.030). Insulin levels correlated significantly and inversely with PTH levels, also after adjusting for levels of several gut hormones and BMI (P = 0.002). Expression of insulin receptors in human parathyroid glands was detected by both IHC and qPCR.Conclusion: Our study suggests that insulin may act as an acute regulator of PTH secretion in humans.

Glacier-related applications of unmanned aircraft systems (UAS) in high mountain regions with steep topography are relatively rare. This study makes a contribution to the lack of UAS applications in studying alpine glaciers in the European Alps. We transferred an established workflow of UAS-based change detection procedures to Austria’s largest glacier, the Pasterze Glacier. We focused on a selected part of the glacier tongue and its proglacial vicinity to obtain detailed knowledge of (i) the behavior of a lateral crevasse field, (ii) the evolution of glacier surface structures and velocity fields, (iii) glacier ablation behavior and the current glacier margin, and (iv) proglacial dead ice conditions and dead ice ablation. Based on two UAS flight campaigns, accomplished in 2016 (51 days apart), we produced digital elevation models (DEMs) and orthophotos with a ground sampling distance (GSD) of 0.15 m using Structure-from-Motion (SfM) photogrammetry. Electrical resistivity tomography (ERT) profiling was additionally conducted in the proglacial area. Results indicate distinct changes in the crevasse field with massive ice collapses, rapid glacier recession, surface lowering (mean of −0.9 m), and ice disintegration at the margins, calculated degree day factors on the order of −7 to −11 mm d−1·°C−1 for clean ice parts, and minimal changes of the debris-covered dead ice in the proglacial area. With this contribution we highlight the benefit of UAS in comparison to commonly used terrestrial methods and satellite-related approaches, Version of record

Glacier-related applications of unmanned aircraft systems (UAS) in high mountain regions with steep topography are relatively rare. This study makes a contribution to the lack of UAS applications in studying alpine glaciers in the European Alps. We transferred an established workflow of UAS-based change detection procedures to Austria’s largest glacier, the Pasterze Glacier. We focused on a selected part of the glacier tongue and its proglacial vicinity to obtain detailed knowledge of (i) the behavior of a lateral crevasse field, (ii) the evolution of glacier surface structures and velocity fields, (iii) glacier ablation behavior and the current glacier margin, and (iv) proglacial dead ice conditions and dead ice ablation. Based on two UAS flight campaigns, accomplished in 2016 (51 days apart), we produced digital elevation models (DEMs) and orthophotos with a ground sampling distance (GSD) of 0.15 m using Structure-from-Motion (SfM) photogrammetry. Electrical resistivity tomography (ERT) profiling was additionally conducted in the proglacial area. Results indicate distinct changes in the crevasse field with massive ice collapses, rapid glacier recession, surface lowering (mean of −0.9 m), and ice disintegration at the margins, calculated degree day factors on the order of −7 to −11 mm d−1·°C−1 for clean ice parts, and minimal changes of the debris-covered dead ice in the proglacial area. With this contribution we highlight the benefit of UAS in comparison to commonly used terrestrial methods and satellite-related approaches, Version of record

BACKGROUND: We aimed to directly compare the diagnostic and prognostic performance of a dual maker strategy (DMS) with combined testing of copeptin and high-sensitivity (hs) cardiac troponin T (cTnT) at time of presentation with other algorithms for rapid rule-out of acute myocardial infarction (AMI). METHODS: 922 patients presenting to the emergency department with suspected AMI and available baseline copeptin measurements qualified for the present TRAPID-AMI substudy. Diagnostic measures using the DMS (copeptin <10, <14 or < 20 pmol/L and hs-cTnT≤14 ng/L), the 1 h-algorithm (hs-cTnT<12 ng/L and change <3 ng/L at 1 h), as well as the hs-cTnT limit-of-blank (LoB, <3 ng/L) and -detection (LoD, <5 ng/L) were compared. Outcomes were assessed as combined end-points of death and myocardial re-infarction. RESULTS: True-negative rule-out using the DMS could be achieved in 50.9%-62.3% of all patients compared to 35.0%, 45.3% and 64.5% using LoB, LoD or the 1 h-algorithm, respectively. The DMS showed NPVs of 98.1%-98.3% compared to 99.2% for the 1 h-algorithm, 99.4% for the LoB and 99.3% for the LoD. Sensitivities were 93.5%-94.8%, as well as 96.8%, 98.7% and 98.1%, respectively. Addition of clinical low-risk criteria such as a HEART-score ≤ 3 to the DMS resulted in NPVs and sensitivities of 100% with a true-negative rule-out to 33.8%-41.6%. Rates of the combined end-point of death/MI within 30 days ranged between 0.2% and 0.3% for all fast-rule-out protocols. CONCLUSION: Depending on the applied copeptin cut-off and addition of clinical low-risk criteria, the DMS might be an alternative to the hs-cTn-only-based algorithms for rapid AMI rule-out with comparable diagnostic measures and outcomes.

Aims. Posttranslational modifications of histones and transcription factors regulate gene expression and are implicated in beta-cell failure and diabetes. We have recently shown that preserving H3K27 and H3K4 methylation using the lysine demethylase inhibitor GSK-J4 reduces cytokine-induced destruction of beta-cells and improves beta-cell function. Here, we investigate the therapeutic potential of GSK-J4 to prevent diabetes development and examine the importance of H3K4 methylation for islet function. Materials and Methods. We used two mouse models of diabetes to investigate the therapeutic potential of GSK-J4. To clarify the importance of H3K4 methylation, we characterized a mouse strain with knockout (KO) of the H3K4 demethylase KDM5B. Results. GSK-J4 administration failed to prevent the development of experimental diabetes induced by multiple low-dose streptozotocin or adoptive transfer of splenocytes from acutely diabetic NOD to NODscid mice. KDM5B-KO mice were growth retarded with altered body composition, had low IGF-1 levels, and exhibited reduced insulin secretion. Interestingly, despite secreting less insulin, KDM5B-KO mice were able to maintain normoglycemia following oral glucose tolerance test, likely via improved insulin sensitivity, as suggested by insulin tolerance testing and phosphorylation of proteins belonging to the insulin signaling pathway. When challenged with high-fat diet, KDM5B-deficient mice displayed similar weight gain and insulin sensitivity as wild-type mice. Conclusion. Our results show a novel role of KDM5B in metabolism, as KDM5B-KO mice display growth retardation and improved insulin sensitivity.

U radu se prikazuje rekonstrukcija kinematike kamenog glečera Tschadinhorn upotrebom viševremenskih konvencionalnih (mjernih) fotografija snimljenih iz zraka (1954–2015) i dodatnih nemjernih fotografija snimljenih iz zraka (2016, 2017) bespilotnim letjelicama (unmanned aerial vehicles – UAV). Letjelica s rotirajućim krilima (hexacopter twinHEX v.3.0) upotrebljena je 2016. godine, a letjelica s nepokretnim krilima (QuestUAV) upotrebljena je 2017. Povijesni slikovni podaci dobiveni su od Austri­jskog federalnog ureda za metrologiju i izmjeru (Bundesamt für Eich- und Vermessungswesen – BEV). Za svako su razdoblje izračunani digitalni ortofoto (DOP) i digitalni model reljefa (digital relief model – DTM). Precizno geo­re­­­­­­ferenciranje slikovnih podataka provedeno je u austrijskom koordinatnom su­­stavu Gauss- Krüger M31 upotrebom aerotriangulacija (AT) do­bi­venih od BEV-a i dodatnim kontrolnim točkama na tlu (ground control point – GCP) geodetski izmje­re­nih tijekom obaju izmje­ra bespilotnim letjelicama. Analiza otkrivanja promjena rezultirala je viševremenskim dvo­di­menzi­ona­lnim poljem brzina kre­tanja. Nakon toga, podaci su sređeni kako bi se dobio jednostavniji grafički prikaz brzine koji jasno po­kazuje razvoj brzine kretanja kamenog glečera. Najveća prosječna godišnja brzina kretanja od 3,28 metra u godini dobivena je u razdoblju 2014– 2015, dok je najmanja godišnja brzina od 0,16 metra u godini opažena u razdoblju 1969–1974. Na grafičkom prikazu brzine također se vidi da je razdoblje 1954–2009 bilo karakterizirano uglavnom umjerenom aktivnošću (0,16 – 0,79 metra u godini) te da od 2009. prevladavaju mnogo veće brzine kretanja. Trenutačna vrijednost za 2016–2017 iznosi 1,92 metra u godini., In this paper we present a reconstruction of the kinematics of the Tschadinhorn rock glacier using multi-temporal conventional (metric) aerial photographs (1954–2015) and additional non-metric aerial photographs (2016, 2017) taken with in-house unmanned aerial vehicles (UAVs). A rotary-wing aircraft (hexacopter twinHEX v.3.0) was used in 2016 and a fixed-wing aircraft (QuestUAV) in 2017. The historical image data was acquired from the Austrian Federal Office of Metrology and Surveying (BEV). Both a digital orthophoto (DOP) and a digital terrain model (DTM) were computed for each given epoch. Precise georeferencing of the image data was carried out in the Austrian Gauss-Krüger M31 coordinate system using available aerotriangulations (ATs) of BEV and additional ground control points (GCPs) measured geodetically during both UAV campaigns. Change detection analysis provided multi-temporal 2D flow velocity fields. Subsequently, these data were collated to produce a simpler velocity graph showing clearly the temporal evolution of the flow velocity of Tschadinhorn rock glacier: A maximum mean annual flow velocity of 3.28 m/year was obtained for 2014–2015, while the lowest annual flow velocity of 0.16 m/year was observed for 1969–1974. The velocity graph also revealed that 1954–2009 was characterized by generally moderate activity (0.16 – 0.79 m/year) and that much higher flow velocities have prevailed since 2009. The present value for 2016–2017 is 1.92 m/year.

Aims. Posttranslational modifications of histones and transcription factors regulate gene expression and are implicated in beta-cell failure and diabetes. We have recently shown that preserving H3K27 and H3K4 methylation using the lysine demethylase inhibitor GSK-J4 reduces cytokine-induced destruction of beta-cells and improves beta-cell function. Here, we investigate the therapeutic potential of GSK-J4 to prevent diabetes development and examine the importance of H3K4 methylation for islet function. Materials and Methods. We used two mouse models of diabetes to investigate the therapeutic potential of GSK-J4. To clarify the importance of H3K4 methylation, we characterized a mouse strain with knockout (KO) of the H3K4 demethylase KDM5B. Results. GSK-J4 administration failed to prevent the development of experimental diabetes induced by multiple low-dose streptozotocin or adoptive transfer of splenocytes from acutely diabetic NOD to NODscid mice. KDM5B-KO mice were growth retarded with altered body composition, had low IGF-1 levels, and exhibited reduced insulin secretion. Interestingly, despite secreting less insulin, KDM5B-KO mice were able to maintain normoglycemia following oral glucose tolerance test, likely via improved insulin sensitivity, as suggested by insulin tolerance testing and phosphorylation of proteins belonging to the insulin signaling pathway. When challenged with high-fat diet, KDM5B-deficient mice displayed similar weight gain and insulin sensitivity as wild-type mice. Conclusion. Our results show a novel role of KDM5B in metabolism, as KDM5B-KO mice display growth retardation and improved insulin sensitivity.

U radu se prikazuje rekonstrukcija kinematike kamenog glečera Tschadinhorn upotrebom viševremenskih konvencionalnih (mjernih) fotografija snimljenih iz zraka (1954–2015) i dodatnih nemjernih fotografija snimljenih iz zraka (2016, 2017) bespilotnim letjelicama (unmanned aerial vehicles – UAV). Letjelica s rotirajućim krilima (hexacopter twinHEX v.3.0) upotrebljena je 2016. godine, a letjelica s nepokretnim krilima (QuestUAV) upotrebljena je 2017. Povijesni slikovni podaci dobiveni su od Austri­jskog federalnog ureda za metrologiju i izmjeru (Bundesamt für Eich- und Vermessungswesen – BEV). Za svako su razdoblje izračunani digitalni ortofoto (DOP) i digitalni model reljefa (digital relief model – DTM). Precizno geo­re­­­­­­ferenciranje slikovnih podataka provedeno je u austrijskom koordinatnom su­­stavu Gauss- Krüger M31 upotrebom aerotriangulacija (AT) do­bi­venih od BEV-a i dodatnim kontrolnim točkama na tlu (ground control point – GCP) geodetski izmje­re­nih tijekom obaju izmje­ra bespilotnim letjelicama. Analiza otkrivanja promjena rezultirala je viševremenskim dvo­di­menzi­ona­lnim poljem brzina kre­tanja. Nakon toga, podaci su sređeni kako bi se dobio jednostavniji grafički prikaz brzine koji jasno po­kazuje razvoj brzine kretanja kamenog glečera. Najveća prosječna godišnja brzina kretanja od 3,28 metra u godini dobivena je u razdoblju 2014– 2015, dok je najmanja godišnja brzina od 0,16 metra u godini opažena u razdoblju 1969–1974. Na grafičkom prikazu brzine također se vidi da je razdoblje 1954–2009 bilo karakterizirano uglavnom umjerenom aktivnošću (0,16 – 0,79 metra u godini) te da od 2009. prevladavaju mnogo veće brzine kretanja. Trenutačna vrijednost za 2016–2017 iznosi 1,92 metra u godini., In this paper we present a reconstruction of the kinematics of the Tschadinhorn rock glacier using multi-temporal conventional (metric) aerial photographs (1954–2015) and additional non-metric aerial photographs (2016, 2017) taken with in-house unmanned aerial vehicles (UAVs). A rotary-wing aircraft (hexacopter twinHEX v.3.0) was used in 2016 and a fixed-wing aircraft (QuestUAV) in 2017. The historical image data was acquired from the Austrian Federal Office of Metrology and Surveying (BEV). Both a digital orthophoto (DOP) and a digital terrain model (DTM) were computed for each given epoch. Precise georeferencing of the image data was carried out in the Austrian Gauss-Krüger M31 coordinate system using available aerotriangulations (ATs) of BEV and additional ground control points (GCPs) measured geodetically during both UAV campaigns. Change detection analysis provided multi-temporal 2D flow velocity fields. Subsequently, these data were collated to produce a simpler velocity graph showing clearly the temporal evolution of the flow velocity of Tschadinhorn rock glacier: A maximum mean annual flow velocity of 3.28 m/year was obtained for 2014–2015, while the lowest annual flow velocity of 0.16 m/year was observed for 1969–1974. The velocity graph also revealed that 1954–2009 was characterized by generally moderate activity (0.16 – 0.79 m/year) and that much higher flow velocities have prevailed since 2009. The present value for 2016–2017 is 1.92 m/year.

Background: Patients with short bowel syndrome might have impaired postprandial endogenous glucagon-like peptide-2 (GLP-2) secretion, which is required for optimal intestinal adaptation. We aimed to assess the therapeutic potential of glepaglutide, a novel long-acting GLP-2 analogue, for reducing faecal output and increasing intestinal absorption in patients with short bowel syndrome.Methods: In this single-centre, double-blind, crossover, randomised phase 2 trial, adults (aged ≥18 to ≤90 years) with short bowel syndrome and with a faecal wet weight output of 1500 g/day or more were randomly assigned to receive one of six dose sequences of glepaglutide (10 mg, 1 mg; 10 mg, 0·1 mg; 1 mg, 10 mg; 1 mg, 0·1 mg; 0·1 mg, 10 mg; or 0·1 mg, 1 mg). Patients received daily subcutaneous injections of the first assigned dose of glepaglutide for 3 weeks, followed by a washout period of 4-8 weeks, and then the second dose of glepaglutide for 3 weeks. An unmasked statistician generated the randomisation list, and the trial investigator enrolled patients and assigned them their patient numbers. Trial investigators, patients, and other care providers were masked throughout the trial. The primary endpoint was the absolute change from baseline in faecal wet weight output, measured separately over the two treatment periods. Metabolic balance studies were done before and after each treatment period to assess the primary endpoint. Per-protocol analysis was used to assess the efficacy. Safety analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02690025, and has completed.Findings: Of the 22 patients screened between Feb 5, 2016, and Jan 25, 2017, 18 patients were randomly assigned and treated with glepaglutide; 16 patients completed the trial. Treatment with 1 mg and 10 mg glepaglutide changed the adjusted mean faecal output by -592 g/day (95% CI -913 to -272; p=0·002) and -833 g

Aims. Posttranslational modifications of histones and transcription factors regulate gene expression and are implicated in beta-cell failure and diabetes. We have recently shown that preserving H3K27 and H3K4 methylation using the lysine demethylase inhibitor GSK-J4 reduces cytokine-induced destruction of beta-cells and improves beta-cell function. Here, we investigate the therapeutic potential of GSK-J4 to prevent diabetes development and examine the importance of H3K4 methylation for islet function. Materials and Methods. We used two mouse models of diabetes to investigate the therapeutic potential of GSK-J4. To clarify the importance of H3K4 methylation, we characterized a mouse strain with knockout (KO) of the H3K4 demethylase KDM5B. Results. GSK-J4 administration failed to prevent the development of experimental diabetes induced by multiple low-dose streptozotocin or adoptive transfer of splenocytes from acutely diabetic NOD to NODscid mice. KDM5B-KO mice were growth retarded with altered body composition, had low IGF-1 levels, and exhibited reduced insulin secretion. Interestingly, despite secreting less insulin, KDM5B-KO mice were able to maintain normoglycemia following oral glucose tolerance test, likely via improved insulin sensitivity, as suggested by insulin tolerance testing and phosphorylation of proteins belonging to the insulin signaling pathway. When challenged with high-fat diet, KDM5B-deficient mice displayed similar weight gain and insulin sensitivity as wild-type mice. Conclusion. Our results show a novel role of KDM5B in metabolism, as KDM5B-KO mice display growth retardation and improved insulin sensitivity.

Matrix-assisted laser-desorption and ionization time-of-flight mass spectrometry prepares proteins intact in the gas phase with predominantly a single positive charge. The times-of-flight of charged proteins along a tube held at high vacuum after acceleration in an electrical field are proportional to the square root of the mass-over-charge ratios for the proteins, thereby allowing a mass spectrum to be generated, which can then be used to characterize or identify a protein-containing sample. Several sample-preparation methods are currently available but not all of these are applicable to some forms of fungal biomass and few of these are well suited to the analysis of plant or insect material. We have therefore developed a simplified method that: lyses cells, selectively solubilizes basic proteins, dissolves matrix to a suitable concentration, generates spectra with good intensity and peak richness, costs no more (and generally less) than current methods, and is not constrained in terms of throughput by the availability of centrifuges. Using this method, and a reagent formulation comprising α-cyano-4-hydroxycinnamic acid matrix close to saturation in 60%–65% (v/v) acetonitrile in water containing 2.5% (v/v) trifluoroacetic acid, we have been able to differentiate between strains for a representative subset of aflatoxin-producing and aflatoxin-non-producing strains of Aspergillus fungi, to differentiate between Indian and Pakistani strains of Himalayan balsam rust, to differentiate between closely-related Crassula spp. and regional biotypes of Crassula helmsii, and to differentiate between rubbervine introduced into Australia and Brazil. We have also analyzed fall armyworm and stem-borer samples stored in 70% (v/v) ethanol and old dried insect specimens.

Matrix-assisted laser-desorption and ionization time-of-flight mass spectrometry prepares proteins intact in the gas phase with predominantly a single positive charge. The times-of-flight of charged proteins along a tube held at high vacuum after acceleration in an electrical field are proportional to the square root of the mass-over-charge ratios for the proteins, thereby allowing a mass spectrum to be generated, which can then be used to characterize or identify a protein-containing sample. Several sample-preparation methods are currently available but not all of these are applicable to some forms of fungal biomass and few of these are well suited to the analysis of plant or insect material. We have therefore developed a simplified method that: lyses cells, selectively solubilizes basic proteins, dissolves matrix to a suitable concentration, generates spectra with good intensity and peak richness, costs no more (and generally less) than current methods, and is not constrained in terms of throughput by the availability of centrifuges. Using this method, and a reagent formulation comprising α-cyano-4-hydroxycinnamic acid matrix close to saturation in 60%–65% (v/v) acetonitrile in water containing 2.5% (v/v) trifluoroacetic acid, we have been able to differentiate between strains for a representative subset of aflatoxin-producing and aflatoxin-non-producing strains of Aspergillus fungi, to differentiate between Indian and Pakistani strains of Himalayan balsam rust, to differentiate between closely-related Crassula spp. and regional biotypes of Crassula helmsii, and to differentiate between rubbervine introduced into Australia and Brazil. We have also analyzed fall armyworm and stem-borer samples stored in 70% (v/v) ethanol and old dried insect specimens.