Potential source and sink locations for climate‐driven species range shifts in Europe since the Last Glacial Maximum

Aim To identify potential source and sink locations for climate‐driven species range shifts in Europe since the Last Glacial Maximum (LGM). Location Europe. Methods We developed a new approach combining past‐climate simulations with the concept of analogous climate space. Our index gives a continuous measure of the potential of a location to have acted as a source or a sink for species that have shifted their ranges since the LGM. High glacial source potential is indicated by LGM climatic conditions that are widespread now; high post‐glacial sink potential is indicated by current climatic conditions that were widespread at the LGM. The degree of isolation of source and sink areas was calculated as the median distance to areas with analogous climate conditions. Results We identified areas of high glacial source potential in the previously recognized refugial areas in the southern European peninsulas, but also in large areas in central‐western Europe. The most climatically isolated source areas were located in northern Spain, in north‐western Europe and in eastern Turkey. From here species would have had to cover substantial distances to find current climate conditions analogous to LGM conditions of these areas. Areas with high post‐glacial sink potential were mainly located in Fennoscandia and in central and south‐eastern Europe. Some of the most isolated sink areas were located in the Spanish highlands and around the Baltic Sea. Main conclusions Our species‐independent approach successfully identified previously recognized glacial refugial areas with high source potential for species range shifts in southern Europe and in addition highlighted other potential source areas in central Europe. This study offers new insights into how the distribution of past and current climatic conditions may have influenced past species range shifts and current large‐scale biodiversity patterns.     

Insulins with built-in glucose sensors for glucose responsive insulin release.

Derivatization of insulin with phenylboronic acids is described, thereby equipping insulin with novel glucose sensing ability. It is furthermore demonstrated that such insulins are useful in glucose‐responsive polymer‐based release systems. The preferred phenylboronic acids are sulfonamide derivatives, which, contrary to naïve boronic acids, ensure glucose binding at physiological pH, and simultaneously operate as handles for insulin derivatization at LysB29. The glucose affinities of the novel insulins were evaluated by glucose titration in a competitive assay with alizarin. The affinities were in the range 15–31 mM (K_d), which match physiological glucose fluctuations. The dose‐responsive glucose‐mediated release of the novel insulins was demonstrated using glucamine‐derived polyethylene glycol polyacrylamide (PEGA) as a model, and it was shown that Zn(II) hexamer formulation of the boronated insulins resulted in steeper glucose sensitivity relative to monomeric insulin formulation. Notably, two of the boronated insulins displayed enhanced insulin receptor affinity relative to native insulin (113%–122%) which is unusual for insulin LysB29 derivatives. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.     

Dimerization of endogenous MT1-MMP is a regulatory step in the activation of the 72-kDa gelatinase MMP-2 on fibroblasts and fibrosarcoma cells

The secreted gelatinase matrix metalloprotease-2 (MMP-2) and the membrane-anchored matrix metalloprotease MT1-MMP (MMP-14), are central players in pericellular proteolysis in extracellular matrix degradation. In addition to possessing a direct collagenolytic and gelatinolytic activity, these enzymes take part in a cascade pathway in which MT1-MMP activates the MMP-2 proenzyme. This reaction occurs in an interplay with the matrix metalloprotease inhibitor, TIMP-2, and the proposed mechanism involves two molecules of MT1-MMP in complex with one TIMP-2 molecule. We provide positive evidence that proMMP-2 activation is governed by dimerization of MT1-MMP on the surface of fibroblasts and fibrosarcoma cells. Even in the absence of transfection and overexpression, dimerization of MT1-MMP markedly stimulated the formation of active MMP-2 products. The effect demonstrated here was brought about by a monoclonal antibody that binds specifically to MT1-MMP as shown by immunofluorescence experiments. The antibody has no effect on the catalytic activity. The effect on proMMP-2 activation involves MT1-MMP dimerization because it requires the divalent monoclonal antibody, with no effect obtained with monovalent Fab fragments. Since only a negligible level of proMMP-2 activation was obtained with MT1-MMP-expressing cells in the absence of dimerization, our results identify the dimerization event as a critical level of proteolytic cascade regulation.     

Physiological activation of brown adipose tissue destabilizes thermogenin mRNA

The amount of mRNA coding for the brown fat specific uncoupling protein thermogenin was followed in the brown adipose tissue of adult mice. As expected, cold exposure or norepinephrine injection caused an increase in the amount of thermogenin mRNA. However, contrary to expectation, the half-life of thermogenin mRNA was dramatically reduced, from about 18 h to about 3 h, when the mice were cold exposed. This destabilization of thermogenin mRNA was not related to the activity of protein synthesis. It was concluded that in brown adipose tissue an unusual mechanism operates which leads to a destabilization of thermogenin mRNA under the same physiological conditions which increase thermogenin gene expression.     

Phylogenetic taxonomy of Hymenochaete and related genera (Hymenochaetales)

Species delimitation in Hymenochaete sensu lato was evaluated based on partial nucLSU rDNA sequences, isoenzyme analyses and morphological data. Analyses of LSU data revealed Hymenochaete sensu stricto and Pseudochaete as distinct monophyletic genera. Transfer of Hydnochaete olivacea into genus Pseudochaete and Dichochaete setosa into genus Hymenochaete (as H. resupinata) was supported by the results of molecular analyses. A new species Hymenochaete koeljalgii from Tanzania was described. The species of genus Hymenochaete sensu stricto were divided into four well-supported clades possessing no distinctive morphological characters.     

Forecasting shifts in habitat suitability of three marine predators suggests a rapid decline in inter‐specific overlap under future climate change

Understanding how environmental and climate change can alter habitat overlap of marine predators has great value for the management and conservation of marine ecosystems. Here, we estimated spatiotemporal changes in habitat suitability and inter‐specific overlap among three marine predators: Baltic gray seals (Halichoerus grypus), harbor seals (Phoca vitulina), and harbor porpoises (Phocoena phocoena) under contemporary and future conditions. Location data (>200 tagged individuals) were collected in the southwestern region of the Baltic Sea; one of the fastest‐warming semi‐enclosed seas in the world. We used the maximum entropy (MaxEnt) algorithm to estimate changes in total area size and overlap of species‐specific habitat suitability between 1997–2020 and 2091–2100. Predictor variables included environmental and climate‐sensitive oceanographic conditions in the area. Sea‐level rise, sea surface temperature, and salinity data were taken from representative concentration pathways [RCPs] scenarios 6.0 and 8.5 to forecast potential climate change effects. Model output suggested that habitat suitability of Baltic gray seals will decline over space and time, driven by changes in sea surface salinity and a loss of currently available haulout sites following sea‐level rise in the future. A similar, although weaker, effect was observed for harbor seals, while suitability of habitat for harbor porpoises was predicted to increase slightly over space and time. Inter‐specific overlap in highly suitable habitats was also predicted to increase slightly under RCP scenario 6.0 when compared to contemporary conditions, but to disappear under RCP scenario 8.5. Our study suggests that marine predators in the southwestern Baltic Sea may respond differently to future climatic conditions, leading to divergent shifts in habitat suitability that are likely to decrease inter‐specific overlap over time and space. We conclude that climate change can lead to a marked redistribution of area use by marine predators in the region, which may influence local food‐web dynamics and ecosystem functioning.     

Synthesis and biological evaluation of Esaprazole analogues showing σ1 binding and neuroprotective properties in vitro

Esaprazole, a molecule previously acknowledged to protect against stomach and intestinal ulcers was surprisingly discovered to have neuroprotective activities and σ₁ binding in vitro. A highly diverse set of Esaprazole analogues 2–5 was prepared in order to increase blood–brain barrier penetration. The analogues showed a structure–activity relationship at the σ₁ receptor closely matching already published pharmacophores. Many of the analogues were shown to have neuroprotective properties in two assays using primary cultures of cortical neurons exposed to glutamate and hydrogen peroxide. However, no apparent SAR for these two assays could be developed. Metabolic stability of the analogues were also investigated and the structure of R¹ had a significant bearing on the ADME properties of the compound resulting in two series of compounds. Compounds in which R¹ was a H or acyl group had good metabolic stability in RLM but poor BBB penetration, whereas compounds where R¹ was a cyclo- or bicyclo-alkyl group had poor metabolic stability but good BBB penetration.     

The relationship between extramitochondrial Ca2+ concentration, respiratory rate, and membrane potential in mitochondria from brown adipose tissue of the rat

The ability of isolated mitochondria from rat brown-adipose tissue to regulate extramitochondrial Ca2+ (measured by arsenazo) was studied in relation to their ability to produce heat (measured polarographically). The energetic state of the mitochondria was expressed as a membrane potential, delta psi (estimated with safranine), and was varied semi-physiologically by the use of different GDP concentrations. In these mitochondria GDP binds to the 32-kDa polypeptide, thermogenin, which regulates coupling. Ca2+ uptake (at 5 microM extramitochondrial Ca2+) was maximal at delta psi greater than 150 mV. Basal Ca2+ release increased from 1 to 2 nmol x min-1 x mg-1 below 150 mV. Na+ -stimulated rate of Ca2+ release was stable within the investigated delta psi span (100-160 mV). Initial Ca2+ levels were maintained below 0.2 microM for 100 mV less than delta psi less than 160 mV. Ca2+ levels maintained after Ca2+ challenge (20 nmol Ca2+ x mg-1) were below 0.4 microM for delta psi greater than 135 mM. Respiration was unstimulated for delta psi greater than 150 mV and was maximal at delta psi less than or equal to 135 mV. In the presence of well-oxidised substrates, the respiration at maximally activated thermogenin was markedly below fully uncoupled respiration and was probably limited by thermogenin activity--i.e. by a limited H+ reentry (OH- exit) and therefore by a membrane potential maintained at about 135 mV. It is concluded that at membrane potentials of 135 mV and above the mitochondria exhibit full Ca2+ control and are able to regulate thermogenic output up to maximum without interfering with this Ca2+ control. Membrane potential probably does not decrease below 135 mV in vivo. Therefore, Ca2+ homeostasis and thermogenesis are non-interfering and can be hormonally independently regulated, e.g. by alpha-adrenergic and beta-adrenergic stimuli, respectively.