A framework for a joint hydro-meteorological-social analysis of drought

This article presents an innovative framework for analysing environmental governance challenges by focusing on their Drivers, Responses and Impacts (DRI). It builds on and modifies the widely applied Drivers, Pressures, States, Impacts and Responses (DPSIR) model. It suggests, firstly and most importantly, that the various temporal and spatial scales at which Drivers, Responses and Impacts operate should be included in the DRI conceptual framework. Secondly, the framework focuses on Drivers, Impacts and Responses in order to provide a parsimonious account of a drought system that can be informed by a range of social science, humanities and science data. ‘Pressures’ are therefore considered as a sub-category of ‘Drivers’. ‘States’ are a sub-category of ‘Impacts’. Thirdly, and most fundamentally in order to facilitate cross-disciplinary research of droughts, the DRI framework defines each of its elements, ‘Drivers’, ‘Pressures’, ‘States’, ‘Impacts’ and ‘Responses’ as capable of being shaped by both linked natural and social factors. This is different from existing DPSIR models which often see ‘Responses’ and ‘Impacts’ as located mainly in the social world, while ‘States’ are considered to be states within the natural environment only. The article illustrates this argument through an application of the DRI framework to the 1976 and 2003–6 droughts. The article also starts to address how - in cross-disciplinary research that encompasses physical and social sciences – claims about relationships between Drivers as well as Impacts of and Responses to drought over time can be methodologically justified. While the DRI framework has been inductively developed out of research on droughts we argue that it can be applied to a range of environmental governance challenges

Zelluläre Mechanismen, Protektion und Regeneration

Das akute Nierenversagen ist charakterisiert durch eine rasche Reduktion der Nierenfunktion. Die bei weitem häufigste Ursache des akuten Nierenversagens ist der durch unzureichende Perfusion der Niere (Ischämie) hervorgerufene Sauerstoffmangel (Hypoxie). Hierbei wird der proximale Tubulus am schwersten geschädigt. Es besteht ein Zusammenhang zwischen der Dauer der Funktionseinschränkung und dem Verlauf der Erkrankung Dadurch wird die Regeneration des proximalen Tubulus beim akuten Nierenversagen zum entscheidenden Schritt zur Wiederherstellung der Nierenfunktion und damit zum Überleben des Patienten. Diese Regeneration ist von verschiedenen Faktoren abhängig: Vom Schweregrad der Hypoxie, von der Anzahl intakter Zellen nach der Hypoxie, von der Regeneration sublethal geschädigter Zellen, und der Proliferation der überlebenden Zellen um die irreversibel geschädigten oder abgelösten Zellen zu ersetzen. Alle diese Faktoren wurden in der vorliegenden Arbeit untersucht! Eine zentrale Bedeutung für die hypoxische Schädigung des proximalen Tubulus wird dem Anstieg der freien intrazellulären Calciumkonzentration zugeschrieben. Jedoch war in der Vergangenheit unklar, unter welchen Bedingungen es bei Hypoxie zu einem frühen reversiblen Anstieg der freien intrazellulären Calciumkonzentration kommt. In der vorliegenden Arbeit wurde die freien intrazelluläre Calciumkonzentration durch ein digitales Bild-verarbeitungssystem mit dem calciumsensitiven Fluoreszenzindikator Fura-2 bestimmt. Als Maß für die Hypoxie-induzierten funktionellen Änderungen wurde der Anstieg der Nicotinamiddinucleotid (NADH)-assoziierten-Autofluoreszenz bestimmt. Strukturelle Schädigungen wurden mit dem Fluoreszenfarbstoff Propidium-Jodid nachgewiesen. Dazu wurden im Vorfeld eine Reihe methodischer Entwicklungen durchgeführt: Erstens die Konstruktion einer Perfusionskammer, die eine schnelle Variation des Sauerstoffpartialdruckes bei gleichbleibender Metabolitenkonzentration erlaubte und die Integration eines Sauerstoffmeßsystems in diese Kammer. Zweitens die Konstruktion eines geeigneten digitalen Bildverarbeitungssystems, das durch Integration eines motorisierten Mikroskoptisches in der Lage ist, eine aussagefähige Anzahl proximaler Tubuli zu untersuchen. Die vorliegende Untersuchung charakterisiert in Abhängigkeit vom Sauerstoffpartialdruck zwei verschiedene Schweregrade der Hypoxie. Bei einem Sauerstoffpartialdruck zwischen 30 und 15 mmHg kommt es zu funktionellen, d.h. Anstieg der NADH-assozierten Autofluoreszenz und strukturellen Schädigungen, nicht jedoch zu einem Anstieg der freien intrazellulären Calciumkonzentration. Im Gegensatz dazu kommt es bei einem Sauerstoffpartialdruck unter 15 mmHg zusätzlich zu einem Anstieg der freien intrazellulären Calciumkonzentration. Eine möglichst große Anzahl überlebender Zellen kann durch die Verwendung protektiver Substanzen erreicht werden. Untersucht wurde der Einfluß von Adenosin-Triphosphat (ATP) und Quercetin auf frisch isolierte proximale Tubuli. Beide Substanzen wiesen in der Vergangenheit eine protektive Wirkung auf, ohne daß der Wirkmechanismus weiter aufgeklärt wurde. Hierfür wurde die Laktatdehydrogenase- (LDH) Freisetzung, der zelluläre Kalium-Gehalt und die Malondialdehd-Bildung bei Hypoxie untersucht. ATP wirkt sowohl in vivo als auch in vitro protektiv gegenüber der Hypoxie induzierten Zellschädigung. Hierfür wurde in der Vergangenheit die These aufgestellt, daß Abbauprodukte des ATP wie ADP und AMP für die protektive Wirkung verantwortlich sind. Da AMP in der vorliegenden Untersuchung keinerlei protektive Wirkung aufwies, ATP jedoch zu einem Rezeptor-typischen Anstieg der freien intrazellulären Calciumkonzentration führte kann der Schluß gezogen werden, daß die protektive Wirkung von ATP Rezeptor-vermittelt ist. Quercetin ist eine Bioflavonoid mit antioxidativen Eigenschaften, das sich in der Vergangenheit bei Ischämie und Reperfusion in der Rattenniere als protektiv erwies. Untersuchungen an kultivierten Nierenzellen wiesen auf einen Zusammenhang der protektiven Wirkung von Quercetin mit einer Hemmung der Lipidperoxydation hin. Die vorliegenden Untersuchungen belegen, daß die Wirkung von Quercetin zumindest teilweise auf einer Hemmung der bei einer Hypoxie vorkommenden Lipidperoxydation beruht. Die Regeneration proximaler Tubuluszellen im Anschluß an eine hypoxische Schädigung wurden in kultivierten proximalen Tubuluszellen (LLC-PK1-Zellen) anhand des Schlüsselenzyms der Wachstumsregulation, der Mitogen-aktivierten Kinase (MAP-Kinase) untersucht. Hypoxie wurde durch eine ATP-Depletion durch Hemmung der mitochondrialen Atmungskette und die Erholung durch Substrat-Substitution simuliert. Untersucht wurde der Einfluß des Epidermalen-Wachstums-Faktors (EGF) und ATP. Sowohl EGF als auch ATP haben in der Vergangenheit zu einer beschleunigten Regeneration im Anschluß an eine hypoxische Schädigung geführt. Dies führte zu der These, daß die regenerative Wirkung von EGF und ATP auf einer verstärkten Proliferation im Anschluß an eine Aktivierung des MAP-Kinase-Signaltransduktionsweges beruhen könnte. Diese These kann durch die vorliegenden Untersuchungen nicht bestätigt werden. Tatsächlich führt die Erholung im Anschluß an eine ATP-Depletion alleine zu einer Aktivierung des MAP-Kinase-Signaltransduktionsweges. Diese Aktivierung läßt sich weder durch EGF noch durch ATP verstärken. Die Proliferation proximaler Tubuluszellen beim akuten Nierenversagen wurde an kultivierten proximalen Tubuluszellen (OK-Zellen) anhand der MAP-Kinase, der c-AMP-Akkumulation und des [3H]-Thymidin-Einbaus untersucht. Während die Aktivierung der MAP-Kinase durch klassische Wachstumsfaktoren wie EGF gut untersucht ist, ist der Einfluß anderer Faktoren wie Katecholamine, die beim akuten Nierenversagen ausgeschüttet werden, sowie ihr Einfluß auf die Proliferation proximaler Tubuluszellen weniger gut bekannt. Die vorliegenden Untersuchungen belegen, daß Adrenalin die MAP-Kinase in OK-Zellen durch a2-Adrenoceptoren über Pertussistoxin-sensitive-G-Proteine stimuliert. Hierbei kommt es zu einem Abfall des cyklischen-Adenosin Monophosphat (cAMP) und der Proteinkinase C. Als Folge kommt es zu einer verstärkten zellulären Proliferation. Dies weist darauf hin, daß Katecholamine, die während des akuten Nierenversagens ausgeschüttet werden, an der tubuären Regeneration beteiligt sein können

Quantitative Comparison of Abundance Structures of Generalized Communities: From B-Cell Receptor Repertoires to Microbiomes

The \emph{community}, the assemblage of organisms co-existing in a given space and time, has the potential to become one of the unifying concepts of biology, especially with the advent of high-throughput sequencing experiments that reveal genetic diversity exhaustively. In this spirit we show that a tool from community ecology, the Rank Abundance Distribution (RAD), can be turned by the new MaxRank normalization method into a generic, expressive descriptor for quantitative comparison of communities in many areas of biology. To illustrate the versatility of the method, we analyze RADs from various \emph{generalized communities}, i.e.\ assemblages of genetically diverse cells or organisms, including human B cells, gut microbiomes under antibiotic treatment and of different ages and countries of origin, and other human and environmental microbial communities. We show that normalized RADs enable novel quantitative approaches that help to understand structures and dynamics of complex generalize communities

New Forms of European Union Governance in the Education Sector? A Preliminary Analysis of the Open Method of Coordination

ABSTRACT This article critically explores how a new form of European Union (EU) governance -the open method of coordination (OMC) -impinges on education policies. The first part discusses three key characteristics of the OMC, in particular its flexibility, reflexivity and reliance on the techniques of new public management. It also outlines briefly why the OMC is being applied to EU education policy. The second and main part of the article develops a critical analysis of the OMC in education by questioning to what extent it can be considered as a new form of EU governance and with what vision of Social Europe it is associated. Most importantly, the second part argues that there may be significant potential for the politicization of mutual policy learning in the context of OMC education measures

Academic Self-Efficacy and Undergraduate Research Opportunities Predict Intentions to Pursue Graduate School

Students who have undergraduate research opportunities tend to have higher identification as a scientist, also known as science identity. Furthermore, students with higher science identity are better prepared for advanced science education, compared to students with lower science identity. The current studies seek to examine predictors of undergraduate students’ intentions to pursue graduate school. In the first study, underrepresented students in science, technology, engineering, and mathematics (STEM) fields who attended the Annual Biomedical Research Conference for Minority Students (ABRCMS) filled out a survey that assessed their research confidence and intentions to pursue graduate school. Students who attended ABRCMS more often and had higher research confidence from attending were more likely to intend to pursue a research degree in graduate school. In study two, undergraduate students completed a survey with items measuring research confidence, science identity, and academic self-efficacy. All variables significantly predicted students’ intentions of pursuing graduate education, with science identity being the strongest predictor. Results suggest that students’ undergraduate research experiences and ability to view themselves as scientists prepares them for further education and increases their intentions of pursuing graduate education. Exposure to undergraduate research opportunities, like ABRCMS, is especially important in providing underrepresented groups a sense of belonging in STEM fields. Greater sense of belonging and stronger identification with science can increase the number of underrepresented students who pursue STEM fields, which can lead to more advances in science

School-based intervention study examining approaches for well-being and mental health literacy of pupils in Year 9 in England: study protocol for a multischool, parallel group cluster randomised controlled trial (AWARE) (vol 12, artne029044corr1, 20022)

The authors would like to notify that the co-authors Sara Evans-Lacko, Bettina Moltrecht, Kirsty Nisbet, Emma Thornton, Aurelie Lange, Paul Stallard, Abigail Thompson were missed including in the authorship list of the paper. The supplementary file has been also updated

Investigations of the Oligocene-Miocene opening of the Ligurian Basin using refraction seismic data

The Ligurian Basin is located north-west of Corsica at the transition from the western Alpine orogen to the Apennine system. The Back-arc basin was generated by the southeast trench retreat of the Apennines-Calabrian subduction zone. The opening took place from late Oligocene to Miocene. While the extension led to extreme continental thinning and un-roofing of mantle material little is known about the style of back-arc rifting. To shed light on the present day crustal and lithospheric architecture of the Ligurian Basin, active seismic data have been recorded on short period ocean bottom seismometers in the framework of SPP2017 4D-MB, the German component of AlpArray. An amphibious refraction seismic profile was shot across the Ligurian Basin in an E-W direction from the Gulf of Lion to Corsica. The profile extends onshore Corsica to image the necking zone of continental thinning. The majority of the refraction seismic data show mantle phases at offsets up to 70 km. The arrivals of seismic phases were picked and inverted in a travel time tomography. The results show a crust-mantle boundary in the central basin at ~12 km depth below sea surface. The mantle shows rather high velocities >7.8 km/s. The crust-mantle boundary deepens from ~12 km to ~18 km within 25 - 30 km towards Corsica. The results do not map an axial valley as expected for oceanic spreading. However, an extremely thinned continental crust indicates a long lasting rifting process that possibly does not initiated oceanic spreading before the opening of the Ligurian Basin stopped

Analysis of the FLVR motif of SHIP1 and its importance for the protein stability of SH2 containing signaling proteins

Under embargo until: 2020-08-02Binding of proteins with SH2 domains to tyrosine-phosphorylated signaling proteins is a key mechanism for transmission of biological signals within the cell. Characterization of dysregulated proteins in cell signaling pathways is important for the development of therapeutic approaches. The AKT pathway is a frequently upregulated pathway in most cancer cells and the SH2-containing inositol 5-phosphatase SHIP1 is a negative regulator of the AKT pathway. In this study we investigated different mutations of the conserved FLVR motif of the SH2 domain and putative phosphorylation sites of SHIP1 which are located in close proximity to its FLVR motif. We demonstrate that patient-derived SHIP1-FLVR motif mutations e.g. F28L, and L29F possess reduced protein expression and increased phospho-AKT-S473 levels in comparison to SHIP1 wildtype. The estimated half-life of SHIP1-F28L protein was reduced from 23.2 h to 0.89 h in TF-1 cells and from 4.7 h to 0.6 h in Jurkat cells. These data indicate that the phenylalanine residue at position 28 of SHIP1 is important for its stability. Replacement of F28 with other aromatic residues like tyrosine and tryptophan preserves protein stability while replacement with non-aromatic amino acids like leucine, isoleucine, valine or alanine severely affects the stability of SHIP1. In consequence, a SHIP1-mutant with an aromatic amino acid at position 28 i.e. F28W can rescue the inhibitory function of wild type SHIP1, whereas SHIP1-mutants with non-aromatic amino acids i.e. F28V do not inhibit cell growth anymore. A detailed structural analysis revealed that F28 forms hydrophobic surface contacts in particular with W5, I83, L97 and P100 which can be maintained by tyrosine and tryptophan residues, but not by non-aromatic residues at position 28. In line with this model of mutation-induced instability of SHIP1-F28L, treatment of cells with proteasomal inhibitor MG132 was able to rescue expression of SHIP1-F28L. In addition, mutation of putative phosphorylation sites S27 and S33 adjacent to the FLVR motif of SHIP1 have an influence on its protein stability. These results further support a functional role of SHIP1 as tumor suppressor protein and indicate a regulation of protein expression of SH2 domain containing proteins via the FLVR motif.acceptedVersio

Analysis of the FLVR motif of SHIP1 and its importance for the protein stability of SH2 containing signaling proteins

Under embargo until: 2020-08-02Binding of proteins with SH2 domains to tyrosine-phosphorylated signaling proteins is a key mechanism for transmission of biological signals within the cell. Characterization of dysregulated proteins in cell signaling pathways is important for the development of therapeutic approaches. The AKT pathway is a frequently upregulated pathway in most cancer cells and the SH2-containing inositol 5-phosphatase SHIP1 is a negative regulator of the AKT pathway. In this study we investigated different mutations of the conserved FLVR motif of the SH2 domain and putative phosphorylation sites of SHIP1 which are located in close proximity to its FLVR motif. We demonstrate that patient-derived SHIP1-FLVR motif mutations e.g. F28L, and L29F possess reduced protein expression and increased phospho-AKT-S473 levels in comparison to SHIP1 wildtype. The estimated half-life of SHIP1-F28L protein was reduced from 23.2 h to 0.89 h in TF-1 cells and from 4.7 h to 0.6 h in Jurkat cells. These data indicate that the phenylalanine residue at position 28 of SHIP1 is important for its stability. Replacement of F28 with other aromatic residues like tyrosine and tryptophan preserves protein stability while replacement with non-aromatic amino acids like leucine, isoleucine, valine or alanine severely affects the stability of SHIP1. In consequence, a SHIP1-mutant with an aromatic amino acid at position 28 i.e. F28W can rescue the inhibitory function of wild type SHIP1, whereas SHIP1-mutants with non-aromatic amino acids i.e. F28V do not inhibit cell growth anymore. A detailed structural analysis revealed that F28 forms hydrophobic surface contacts in particular with W5, I83, L97 and P100 which can be maintained by tyrosine and tryptophan residues, but not by non-aromatic residues at position 28. In line with this model of mutation-induced instability of SHIP1-F28L, treatment of cells with proteasomal inhibitor MG132 was able to rescue expression of SHIP1-F28L. In addition, mutation of putative phosphorylation sites S27 and S33 adjacent to the FLVR motif of SHIP1 have an influence on its protein stability. These results further support a functional role of SHIP1 as tumor suppressor protein and indicate a regulation of protein expression of SH2 domain containing proteins via the FLVR motif.acceptedVersio