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21.
Lars Lønsmann Iversen Riinu Rannap Philip Francis Thomsen Jos Kielgast Kaj Sand‐Jensen 《Ecography》2013,36(7):770-777
Species’ dispersal abilities have been considered a major driving force in establishment and maintenance of large range sizes. However, recent studies question the general validity of this relationship because the relationship between dispersal ability and range size might in some cases be less important than species phylogeny or local spatial attributes. In this study we used the water beetle Graphoderus bilineatus a philopatric species of conservation concern in Europe as a model to explain large range size and to support effective conservation measures for such species that also have limited dispersal. We recorded the presence/absence of G. bilineatus and measured 14 habitat and 20 landscape variables at 228 localities in Estonia, Poland and Sweden within the core range of the species. Using information theory and average multivariate logistic regression models we determined that presence of G. bilineatus depended on landscape connectivity, distance to a possible source habitat, and stability of the site; however, specificity of habitat characteristics was not vital for the species. We reason that the large range of G. bilineatus is best explained by the historical combination of lakes, river systems and wetlands which used to be highly connected throughout the central plains of Europe. Our data suggest that a broad habitat niche can prevent landscape elements from becoming barriers for species like G. bilineatus. Therefore, we question the usefulness of site protection as conservation measures for G. bilineatus and similar philopatric species. Instead, conservation actions should be focused at the landscape level to ensure a long‐term viability of such species across their range. 相似文献
22.
23.
Alyssa A. Carrell Max Kolton Jennifer B. Glass Dale A. Pelletier Melissa J. Warren Joel E. Kostka Colleen M. Iversen Paul J. Hanson David J. Weston 《Global Change Biology》2019,25(9):2993-3004
Sphagnum‐dominated peatlands comprise a globally important pool of soil carbon (C) and are vulnerable to climate change. While peat mosses of the genus Sphagnum are known to harbor diverse microbial communities that mediate C and nitrogen (N) cycling in peatlands, the effects of climate change on Sphagnum microbiome composition and functioning are largely unknown. We investigated the impacts of experimental whole‐ecosystem warming on the Sphagnum moss microbiome, focusing on N2 fixing microorganisms (diazotrophs). To characterize the microbiome response to warming, we performed next‐generation sequencing of small subunit (SSU) rRNA and nitrogenase (nifH) gene amplicons and quantified rates of N2 fixation activity in Sphagnum fallax individuals sampled from experimental enclosures over 2 years in a northern Minnesota, USA bog. The taxonomic diversity of overall microbial communities and diazotroph communities, as well as N2 fixation rates, decreased with warming (p < 0.05). Following warming, diazotrophs shifted from a mixed community of Nostocales (Cyanobacteria) and Rhizobiales (Alphaproteobacteria) to predominance of Nostocales. Microbiome community composition differed between years, with some diazotroph populations persisting while others declined in relative abundance in warmed plots in the second year. Our results demonstrate that warming substantially alters the community composition, diversity, and N2 fixation activity of peat moss microbiomes, which may ultimately impact host fitness, ecosystem productivity, and C storage potential in peatlands. 相似文献
24.
Mark R. Hickman David L. Saunders Catherine A. Bigger Christopher D. Kane Patrick L. Iversen 《PLoS neglected tropical diseases》2022,16(3)
The Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEO-CBRND) began development of a broad-spectrum antiviral countermeasure against deliberate use of high-consequence viral hemorrhagic fevers (VHFs) in 2016. The effort featured comprehensive preclinical research, including laboratory testing and rapid advancement of lead molecules into nonhuman primate (NHP) models of Ebola virus disease (EVD). Remdesivir (GS-5734, Veklury, Gilead Sciences) was the first small molecule therapeutic to successfully emerge from this effort. Remdesivir is an inhibitor of RNA-dependent RNA polymerase, a viral enzyme that is essential for viral replication. Its robust potency and broad-spectrum antiviral activity against certain RNA viruses including Ebola virus and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) led to its clinical evaluation in randomized, controlled trials (RCTs) in human patients during the 2018 EVD outbreak in the Democratic Republic of the Congo (DRC) and the ongoing Coronavirus Disease 2019 (COVID-19) pandemic today. Remdesivir was recently approved by the US Food and Drug Administration (FDA) for the treatment of COVID-19 requiring hospitalization. Substantial gaps remain in improving the outcomes of acute viral infections for patients afflicted with both EVD and COVID-19, including how to increase therapeutic breadth and strategies for the prevention and treatment of severe disease. Combination therapy that joins therapeutics with complimentary mechanisms of action appear promising, both preclinically and in RCTs. Importantly, significant programmatic challenges endure pertaining to a clear drug and biological product development pathway for therapeutics targeting biodefense and emerging pathogens when human efficacy studies are not ethical or feasible. For example, remdesivir’s clinical development was facilitated by outbreaks of Ebola and SARS-CoV-2; as such, the development pathway employed for remdesivir is likely to be the exception rather than the rule.The current regulatory licensure pathway for therapeutics targeting rare, weaponizable VHF agents is likely to require use of FDA’s established Animal Rule (21 CFR 314.600–650 for drugs; 21 CFR 601.90–95 for biologics). The FDA may grant marketing approval based on adequate and well-controlled animal efficacy studies when the results of those studies establish that the drug is safe and likely to produce clinical benefit in humans. In practical terms, this is anticipated to include a series of rigorous, well-documented, animal challenge studies, to include aerosol challenge, combined with human safety data. While small clinical studies against naturally occurring, high-consequence pathogens are typically performed where possible, approval for the therapeutics currently under development against biodefense pathogens will likely require the Animal Rule pathway utilizing studies in NHPs. We review the development of remdesivir as illustrative of the effort that will be needed to field future therapeutics against highly lethal, infectious agents. 相似文献
25.
AIMS: To study the growth, thermotolerance and biofilm formation of the emergent pathogen Enterobacter sakazakii in infant formula milk (IFM). METHODS AND RESULTS: The temperature range, death kinetics and biofilm formation of E. sakazakii were determined using impedance microbiology and conventional methods. In IFM the organism grew as low as 6 degrees C and optimally at 37-43 degrees C. In faecal coliform tests, 23% of strains (n = 70) produced gas from lauryl sulphate broth (LSB) at 44 degrees C after 48 h incubation. Three strains failed to grow in LSB at any of the temperatures. The D-value of cells suspended in IFM was determined between 54 and 62 degrees C. The resultant z-value was 5.7 degrees C. The organism was able to adhere and grow on latex, polycarbonate, silicon and to a lesser extent stainless steel. CONCLUSIONS: Enterobacter sakazakii was able to grow at refrigeration temperatures and on infant-feeding equipment. The thermotolerance of the organism was similar to other Enterobacteriaceae and should be killed during standard pasteurization treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Enterobacter sakazakii has been associated with infant meningitis through consumption of contaminated IFM. Enterobacter sakazakii is able to grow in IFM during storage at refrigeration temperatures and attach to infant-feeding equipment, which may become reservoirs of infection. 相似文献
26.
Boysen S Fogh-Schultz B Andersen I Højrup P Iversen JJ Wittenhagen P Nielsen EH Svehag SE 《Protein expression and purification》2004,35(2):284-292
Human serum amyloid P component (SAP) was expressed in the methylotrophic yeast Pichia pastoris. SAP cDNA was placed under control of regulatory sequences derived from the alcohol oxidase gene (AOX1), and its protein product was secreted using the Saccharomyces cerevisiae alpha-mating factor signal sequence. Recombinant SAP (r-SAP) was produced in a bioreactor with computer controlled fed-batch mode and purified by use of a C-terminal histidine tag. The yield of purified r-SAP was 3-4mg from 1L supernatant and 5-6mg from 1L cell paste, indicating that the majority of the produced SAP was not secreted. Treatment of the cell paste with EDTA increased the yield further by about 30%. The N-terminal of r-SAP purified from the supernatant showed non-complete cleavage of the alpha-mating factor signal sequence. Purified r-SAP, analyzed under native conditions, was shown to be a decamer, like purified human SAP (h-SAP), with monomers of 27kDa. Each monomer had one N-glycosylation site, positioned at the same site as for h-SAP. r-SAP bound to antibodies produced against h-SAP. Furthermore, r-SAP bound to ds DNA and influenza A virus subunits in a Ca(2+)-dependent manner and inhibited influenza A virus hemagglutination. These results indicate that r-SAP produced in P. pastoris has the same biological activity as purified h-SAP. 相似文献
27.
Hirstein W Iversen P Ramachandran VS 《Proceedings. Biological sciences / The Royal Society》2001,268(1479):1883-1888
Several recent lines of inquiry have pointed to the amygdala as a potential lesion site in autism. Because one function of the amygdala may be to produce autonomic arousal at the sight of a significant face, we compared the responses of autistic children to their mothers' face and to a plain paper cup. Unlike normals, the autistic children as a whole did not show a larger response to the person than to the cup. We also monitored sympathetic activity in autistic children as they engaged in a wide range of everyday behaviours. The children tended to use self-stimulation activities in order to calm hyper-responsive activity of the sympathetic ('fight or flight') branch of the autonomic nervous system. A small percentage of our autistic subjects had hyporesponsive sympathetic activity, with essentially no electrodermal responses except to self-injurious behaviour. We sketch a hypothesis about autism according to which autistic children use overt behaviour in order to control a malfunctioning autonomic nervous system and suggest that they have learned to avoid using certain processing areas in the temporal lobes. 相似文献
28.
Kastrup JS Linde V Pedersen AK Stoffer B Iversen LF Larsen IK Rasmussen PB Flodgaard HJ Bjørn SE 《Proteins》2001,42(4):442-451
Heparin binding protein (HBP) is an inactive serine protease homologue with important implications in host defense during infections and inflammations. Two mutants of human HBP, [R23S,F25E]HBP and [G175Q]HBP, have been produced to investigate structure-function relationships of residues in the putative lipid A/lipopolysaccharide (LPS) binding site and BPTI (bovine pancreatic trypsin inhibitor) binding site. The X-ray structures have been determined at 1.9 A resolution for [G175Q]HBP and at 2.5 A resolution for the [R23S,F25E]HBP mutant, and the structures have been fully refined to R-factors of 18.2 % and 20.7 %, respectively. The G175Q mutation does not alter the overall structure of the protein, but the ability to bind BPTI has been eliminated, and the mutant mediates only a limited stimulation of the LPS-induced cytokine release from human monocytes. The lipid A/LPS binding property of [G175Q]HBP is comparable with that of native HBP. The R23S,F25E mutations do not affect the binding of lipid A/LPS and BPTI or the LPS-induced cytokine release from human monocytes. This shows that two diverse ligands, lipid A/LPS and BPTI, do not share binding sites. Previously, there was convincing evidence for the proposed lipid A/LPS binding site of HBP. Unexpectedly, the extensive structural changes introduced by mutation of Arg23 and Phe25 do not affect the binding of lipid A/LPS, indicating that another not yet identified site on HBP is involved in the binding of lipid A/LPS. 相似文献
29.
Structure determination of T cell protein-tyrosine phosphatase 总被引:2,自引:0,他引:2
Iversen LF Moller KB Pedersen AK Peters GH Petersen AS Andersen HS Branner S Mortensen SB Moller NP 《The Journal of biological chemistry》2002,277(22):19982-19990
Protein-tyrosine phosphatase 1B (PTP1B) has recently received much attention as a potential drug target in type 2 diabetes. This has in particular been spurred by the finding that PTP1B knockout mice show increased insulin sensitivity and resistance to diet-induced obesity. Surprisingly, the highly homologous T cell protein-tyrosine phosphatase (TC-PTP) has received much less attention, and no x-ray structure has been provided. We have previously co-crystallized PTP1B with a number of low molecular weight inhibitors that inhibit TC-PTP with similar efficiency. Unexpectedly, we were not able to co-crystallize TC-PTP with the same set of inhibitors. This seems to be due to a multimerization process where residues 130-132, the DDQ loop, from one molecule is inserted into the active site of the neighboring molecule, resulting in a continuous string of interacting TC-PTP molecules. Importantly, despite the high degree of functional and structural similarity between TC-PTP and PTP1B, we have been able to identify areas close to the active site that might be addressed to develop selective inhibitors of each enzyme. 相似文献
30.
Pathways followed by ricin and Shiga toxin into cells 总被引:21,自引:5,他引:16
Sandvig K Grimmer S Lauvrak SU Torgersen ML Skretting G van Deurs B Iversen TG 《Histochemistry and cell biology》2002,117(2):131-141
The plant toxin ricin and the bacterial toxin Shiga toxin belong to a group of protein toxins that inhibit protein synthesis in cells enzymatically after entry into the cytosol. Ricin and Shiga toxin, which both have an enzymatically active moiety that inactivates ribosomes and a moiety that binds to cell surface receptors, enter the cytosol after binding to the cell surface, endocytosis by different mechanisms, and retrograde transport to the Golgi apparatus and the endoplasmic reticulum (ER). The toxins can be used to investigate the various transport steps involved, both the endocytic mechanisms as well as pathways for retrograde transport to the ER. Recent studies show that not only do several endocytic mechanisms exist in the same cell, but they are not equally sensitive to removal of cholesterol. New data have revealed that there is also more than one pathway leading from endosomes to the Golgi apparatus and retrogradely from the Golgi to the ER. Trafficking of protein toxins along these pathways will be discussed in the present article. 相似文献