Inner Alpine conifer response to 20th century drought swings

Tree rings from the Alpine area have been widely used to reconstruct variations in summer temperature. In contrast, estimates of changes in the hydrological cycle are rather scarce. In order to detect altitudinal and species-specific patterns of growth responses to anomalous dry and wet conditions, a large network of 53 tree-ring width site chronologies along the Rhone valley (Valais, Switzerland) covering the 1751-2005 period was compiled and analyzed. A total of 1,605 measurement series from four conifer species—pine, larch, spruce, fir—were detrended to allow inter-annual to multi-decadal scale variability to be preserved. Site chronologies were combined to four altitudinal (colline: 1,450m asl) and species-specific mean time-series. These records were compared with temperature, precipitation, and drought (scPDSI) data. Among the altitudinal records, the colline chronologies showed highest correlation with June precipitation and scPDSI (0.5 and 0.7). Altitudinal effects, via control on climatic conditions, were superimposed upon species-specific characteristics in affecting tree growth and response to moisture variations. In particular, species-specific differences affected the significance level of drought response, with decreasing drought sensitivity towards higher elevations. Growth conditions were found to be optimal at ~1,300m asl, with precipitation/drought limiting tree growth below and temperature above. Common years of extreme drought and low growth for the colline sites occurred in 1921, 1944, 1976, 1992, and 1998. Our results demonstrate the potential of lower elevation conifers for reconstructing long-term changes in Alpine hydro-climat

Nachhaltigkeit in der Kreditfinanzierung

Für den Einbezug von Nachhaltigkeitsaspekten in den Bereichen Anlegen und Finanzieren hat sich Sustainable Finance (nachhaltige Finanzen) als übergeordneter Begriff etabliert. Auch wenn Sustainable Finance immer schon nachhaltige Aktivitäten in den verschiedensten Finanzbereichen mit einbezogen hat, lag der Fokus der Finanzinstitute wie auch der akademischen Forschung bisher auf dem Anlagegeschäft (Sustainable Investing). Ein eher weniger beleuchtetes Themenfeld ist die nachhaltige Finanzierung (Sustainable Financing), speziell die nachhaltige Kreditfinanzierung (Sustainable Lending). Da die Kreditfinanzierung eine der wichtigsten Finanzierungsquellen des Privatsektors darstellt (vgl. Box 1), ist sie auch für die aktuelle und zukünftige Nachhaltigkeitsdiskussion von zentraler Bedeutung und soll im Rahmen der vorliegenden Publikation vertieft diskutiert werden. Ziel ist es, einen möglichst umfassenden Überblick zu Theorie, Praxis und zukünftigen Handlungsfeldern im Bereich der nachhaltigen Kreditfinanzierung zu schaffen. Praxisbeispiele zeigen begleitend auf, wie einzelne Teilaspekte bereits konkret umgesetzt werden. Der Fokus liegt auf den zwei wichtigsten Teilgebieten der Kreditfinanzierung, dem Hypothekargeschäft und dem Unternehmenskreditgeschäft. Als Grundlage werden in Kapitel 1.2 zunächst die relevanten Perspektiven zur Nachhaltigkeit im Kreditwesen und in Kapitel 1.3 die relevanten Handlungsfelder der nachhaltigen Kreditfinanzierung erarbeitet. Diese Grundlagen sind notwendig, um darauf aufbauend die Nachhaltigkeitsbestrebungen im Bereich der Unternehmenskredite (Kapitel 2) sowie im Hypothekarbereich (Kapitel 3) zu diskutieren und die Notwendigkeit der in Kapitel 4 besprochenen weitergehenden Finanzierungsformen im Kreditbereich zu verdeutlichen (spezifische Finanzierung von Nachhaltigkeitslösungen). Ergänzend finden sich in den verschiedenen Kapiteln zahlreiche Boxen, welche weiterführende Hintergrundinformationen, Fallstudien sowie Praxisbeispiele enthalten

Protein interference applications in cellular and developmental biology using DARPins that recognize GFP and mCherry

Protein–protein interactions are crucial for cellular homeostasis and play important roles in the dynamic execution of biological processes. While antibodies represent a well-established tool to study protein interactions of extracellular domains and secreted proteins, as well as in fixed and permeabilized cells, they usually cannot be functionally expressed in the cytoplasm of living cells. Non-immunoglobulin protein-binding scaffolds have been identified that also function intracellularly and are now being engineered for synthetic biology applications. Here we used the Designed Ankyrin Repeat Protein (DARPin) scaffold to generate binders to fluorescent proteins and used them to modify biological systems directly at the protein level. DARPins binding to GFP or mCherry were selected by ribosome display. For GFP, binders with KD as low as 160 pM were obtained, while for mCherry the best affinity was 6 nM. We then verified in cell culture their specific binding in a complex cellular environment and found an affinity cut-off in the mid-nanomolar region, above which binding is no longer detectable in the cell. Next, their binding properties were employed to change the localization of the respective fluorescent proteins within cells. Finally, we performed experiments in Drosophila melanogaster and Danio rerio and utilized these DARPins to either degrade or delocalize fluorescently tagged fusion proteins in developing organisms, and to phenocopy loss-of-function mutations. Specific protein binders can thus be selected in vitro and used to reprogram developmental systems in vivo directly at the protein level, thereby bypassing some limitations of approaches that function at the DNA or the RNA level

Infarct-remodelled hearts with limited oxidative capacity boost fatty acid oxidation after conditioning against ischaemia/reperfusion injury

Aims Infarct-remodelled hearts are less amenable to protection against ischaemia/reperfusion. Understanding preservation of energy metabolism in diseased vs. healthy hearts may help to develop anti-ischaemic strategies effective also in jeopardized myocardium. Methods and results Isolated infarct-remodelled/sham Sprague-Dawley rat hearts were perfused in the working mode and subjected to 15 min of ischaemia and 30 min of reperfusion. Protection of post-ischaemic ventricular work was achieved by pharmacological conditioning with sevoflurane. Oxidative metabolism was measured by substrate flux in fatty acid and glucose oxidation using [3H]palmitate and [14C]glucose. Mitochondrial oxygen consumption was measured in saponin-permeabilized left ventricular muscle fibres. Activity assays of citric acid synthase, hydroxyacyl-CoA dehydrogenase, and pyruvate dehydrogenase and mass spectrometry for acylcarnitine profiling were also performed. Six weeks after coronary artery ligation, the hearts exhibited macroscopic and molecular signs of hypertrophy consistent with remodelling and limited respiratory chain and citric acid cycle capacity. Unprotected remodelled hearts showed a marked decline in palmitate oxidation and acetyl-CoA energy production after ischaemia/reperfusion, which normalized in sevoflurane-protected remodelled hearts. Protected remodelled hearts also showed higher β-oxidation flux as determined by increased oxygen consumption with palmitoylcarnitine/malate in isolated fibres and a lower ratio of C16:1+C16OH/C14 carnitine species, indicative of a higher long-chain hydroxyacyl-CoA dehydrogenase activity. Remodelled hearts exhibited higher PPARα-PGC-1α but defective HIF-1α signalling, and conditioning enabled them to mobilize fatty acids from endogenous triglyceride stores, which closely correlated with improved recovery. Conclusions Protected infarct-remodelled hearts secure post-ischaemic energy production by activation of β-oxidation and mobilization of fatty acids from endogenous triglyceride store

Mal/SRF Is Dispensable for Cell Proliferation in Drosophila

The Mal/SRF transcription factor is regulated by the level of G-actin in cells and has important roles in cell migration and other actin-dependent processes in Drosophila. A recent report suggests that Mal/SRF and an upstream regulator, Pico, are required for cell proliferation and tissue growth in Drosophila. I find otherwise. Mutation of Mal or SRF does not affect cell proliferation in the fly wing. Furthermore, I cannot reproduce the reported effects of Pico RNAi or Pico overexpression on body size. Nevertheless, I can confirm that overexpression of Pico or Mal causes tissue overgrowth specifically in the fly wing - where SRF is most highly expressed. My results indicate that Mal/SRF can promote tissue growth when abnormally active, but is not normally required for tissue growth during development

Expression of Kallikrein-related peptidase 6 in primary mucosal malignant melanoma of the head and neck

Mucosal melanomas of the head and neck (MMHN) are aggressive tumors with poor prognosis, different opposed to cutaneous melanoma. In this study, we characterized primary mucosal malignant melanoma for the expression of Kallikrein-related peptidase 6 (KLK6), a member of the KLK family with relevance to the malignant phenotype in various cancer types including cutaneous melanoma. Paraffin-embedded MMHN of 22 patients were stained immunohistochemically for KLK6 and results were correlated with clinical and pathological data. In 77.3% (17/22) of MMHN cases, positive KLK6 staining was found. Staining pattern for tumor cells showed a predominant cytoplasmic staining. However, in six cases we also observed a prominent nuclear staining. MMHN with a high KLK6 expression showed significantly better outcome concerning local recurrence-free survival (p = 0.013) and nuclear KLK6 staining was significantly associated with the survival status (p = 0.027). Overexpression of KLK6 was detected in more than 70% of MMHN and approximately 40% of tumors showed a strong expression pattern. Correlation between clinical outcome of MMHN patients and overexpression of KLK6 has not been addressed so far. Our data demonstrate for the first time increased levels of KLK6 in MMHN and strengthen the hypothesis that there might be a context-specific regulation and function of KLK6 in mucosal melanoma

Comparative analysis of canine monocyte- and bone-marrow-derived dendritic cells

Dendritic cells (DC) represent a heterogeneous cell family of major importance for innate immune responses against pathogens and antigen presentation during infection, cancer, allergy and autoimmunity. The aim of the present study was to characterize canine DC generated in vitro with respect to their phenotype, responsiveness to toll-like receptor (TLR) ligands and T-cell stimulatory capacity. DC were derived from monocytes (MoDC) and from bone marrow hematopoietic cells cultured with either Flt3-ligand (FL-BMDC) or with GM-CSF (GM-BMDC). All three methods generated cells with typical DC morphology that expressed CD1c, CD11c and CD14, similar to macrophages. However, CD40 was only found on DC, CD206 on MΦ and BMDC, but not on monocytes and MoDC. CD1c was not found on monocytes but on all in vitro differentiated cells. FL-BMDC and GM-BMDC were partially positive for CD4 and CD8. CD45RA was expressed on a subset of FL-BMDC but not on MoDC and GM-BMDC. MoDC and FL-DC responded well to TLR ligands including poly-IC (TLR2), Pam3Cys (TLR3), LPS (TLR4) and imiquimod (TLR7) by up-regulating MHC II and CD86. The generated DC and MΦ showed a stimulatory capacity for lymphocytes, which increased upon maturation with LPS. Taken together, our results are the basis for further characterization of canine DC subsets with respect to their role in inflammation and immune responses