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991.
Synthesis and evaluation of novel lipidated neuromedin U analogs with increased stability and effects on food intake 下载免费PDF全文
Louise S. Dalbøge Søren L. Pedersen Søren B. van Witteloostuijn Jakob E. Rasmussen Kristoffer T. G. Rigbolt Knud J. Jensen Birgitte Holst Niels Vrang Jacob Jelsing 《Journal of peptide science》2015,21(2):85-94
Neuromedin U (NMU) is a 25 amino acid peptide expressed and secreted in the brain and gastrointestinal tract. Data have shown that peripheral administration of human NMU decreases food intake and body weight and improves glucose tolerance in mice, suggesting that NMU receptors constitute a possible anti‐diabetic and anti‐obesity drug target. However, the clinical use of native NMU is hampered by a poor pharmacokinetic profile. In the current study, we report in vitro and in vivo data from a series of novel lipidated NMU analogs. In vitro plasma stability studies of native NMU were performed to investigate the proteolytic stability and cleavage sites using LC–MS. Native NMU was found to be rapidly cleaved at the C‐terminus between Arg24 and Asn25, followed by cleavage between Arg16 and Gly17. Lipidated NMU analogs were generated using solid‐phase peptide synthesis, and in vitro potency was investigated using a human embryonic kidney 293‐based inositol phosphate accumulation assay. All lipidated analogs had preserved in vitro activity on both NMU receptors with potency improving as the lipidation site was moved away from the receptor‐interacting C‐terminal octapeptide segment. In vivo efficacy was assessed in lean mice as reduction in food intake after acute subcutaneous administration of 1, 0.3, 0.1, and 0.03 µmol/kg. These lipidated NMU analogs prolonged the anorectic effect of NMU in a dose‐dependent manner. This was likely an effect of improved pharmacokinetic properties because of improved vitro plasma stability. Accordingly, the data demonstrate that lipidated NMU analogs may represent drug candidates for the treatment of obesity. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
992.
Svetlana Friedel Andreas Börner Harald Todt Peter M. Jakob Ljudmilla Borisjuk 《Plant biotechnology journal》2015,13(2):188-199
The large numbers of samples processed in breeding and biodiversity programmes require the development of efficient methods for the nondestructive evaluation of basic seed properties. Near‐infrared spectroscopy is the state‐of‐the‐art solution for this analytical demand, but it also has some limitations. Here, we present a novel, rapid, accurate procedure based on time domain‐nuclear magnetic resonance (TD‐NMR), designed to simultaneously quantify a number of basic seed traits without any seed destruction. Using a low‐field, benchtop 1H‐NMR instrument, the procedure gives a high‐accuracy measurement of oil content (R2 = 0.98), carbohydrate content (R2 = 0.99), water content (R2 = 0.98) and both fresh and dry weight of seeds/grains (R2 = 0.99). The method requires a minimum of ~20 mg biomass per sample and thus enables to screen individual, intact seeds. When combined with an automated sample delivery system, a throughput of ~1400 samples per day is achievable. The procedure has been trialled as a proof of concept on cereal grains (collection of ~3000 accessions of Avena spp. curated at the IPK genebank). A mathematical multitrait selection approach has been designed to simplify the selection of outlying (most contrasting) accessions. To provide deeper insights into storage oil topology, some oat accessions were further analysed by three‐dimensional seed modelling and lipid imaging. We conclude that the novel TD‐NMR‐based screening tool opens perspectives for breeding and plant biology in general. 相似文献
993.
Rasmus Liedigk Jakob Kolleck Kai O B?ker Erik Meijaard Badrul Munir Md-Zain Muhammad Abu Bakar Abdul-Latiff Ahmad Ampeng Maklarin Lakim Pazil Abdul-Patah Anthony J Tosi Markus Brameier Dietmar Zinner Christian Roos 《BMC genomics》2015,16(1)
Background
Long-tailed macaques (Macaca fascicularis) are an important model species in biomedical research and reliable knowledge about their evolutionary history is essential for biomedical inferences. Ten subspecies have been recognized, of which most are restricted to small islands of Southeast Asia. In contrast, the common long-tailed macaque (M. f. fascicularis) is distributed over large parts of the Southeast Asian mainland and the Sundaland region. To shed more light on the phylogeny of M. f. fascicularis, we sequenced complete mitochondrial (mtDNA) genomes of 40 individuals from all over the taxon’s range, either by classical PCR-amplification and Sanger sequencing or by DNA-capture and high-throughput sequencing.Results
Both laboratory approaches yielded complete mtDNA genomes from M. f. fascicularis with high accuracy and/or coverage. According to our phylogenetic reconstructions, M. f. fascicularis initially diverged into two clades 1.70 million years ago (Ma), with one including haplotypes from mainland Southeast Asia, the Malay Peninsula and North Sumatra (Clade A) and the other, haplotypes from the islands of Bangka, Java, Borneo, Timor, and the Philippines (Clade B). The three geographical populations of Clade A appear as paraphyletic groups, while local populations of Clade B form monophyletic clades with the exception of a Philippine individual which is nested within the Borneo clade. Further, in Clade B the branching pattern among main clades/lineages remains largely unresolved, most likely due to their relatively rapid diversification 0.93-0.84 Ma.Conclusions
Both laboratory methods have proven to be powerful to generate complete mtDNA genome data with similarly high accuracy, with the DNA-capture and high-throughput sequencing approach as the most promising and only practical option to obtain such data from highly degraded DNA, in time and with relatively low costs. The application of complete mtDNA genomes yields new insights into the evolutionary history of M. f. fascicularis by providing a more robust phylogeny and more reliable divergence age estimations than earlier studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1437-0) contains supplementary material, which is available to authorized users. 相似文献994.
Karin Tubbert Clausen Jakob Tougaard Jacob Carstensen Matthieu Delefosse 《Bioacoustics.》2019,28(5):443-458
Automatic click detectors and full-bandwidth sound recorders are widely used in passive acoustic monitoring of small cetaceans. Detection of these signals depends on a variety of factors, including signal to noise ratio. Passive acoustic monitoring is often used to study impact of underwater noise on small cetaceans, but as detection probability is affected by changes in signal to noise ratio, variable noise levels may affect conclusions drawn from these experiments. Therefore, we examine how different detectors and filters perform in varying ocean noise conditions. C-PODs and full-bandwidth recorders (Wildlife Acoustics, SM2M+) were deployed at two stations in an environment with fluctuating ambient noise for 42 days. Noise level and harbour porpoise (Phocoena phocoena) click trains simultaneously recorded on both loggers were compared. Overall, we found that porpoise click detections by the algorithm used to analyse full-band recorder data (Pamguard) paralleled detections by the C-POD. However, Pamguard detected significantly more clicks than the C-POD. A decrease in detections was seen for both loggers with increasing noise in the band 20 –160 kHz, in particular for levels above 100 dB re 1μPa rms. We also found that the Pamguard detection function changed the least over varying noise conditions when compared to the C-POD detectors. This study sheds light on the fact that inference of animal presence/absence or density that are based on echolocation cues (here, Porpoise Positive Minutes) shall account for the acoustic environments where probability of detecting signals may be affected by variability in ambient noise levels. 相似文献
995.
To improve process economics of the lignocellulose to ethanol process a reactor system for enzymatic liquefaction and saccharification at high-solids concentrations was developed. The technology is based on free fall mixing employing a horizontally placed drum with a horizontal rotating shaft mounted with paddlers for mixing. Enzymatic liquefaction and saccharification of pretreated wheat straw was tested with up to 40% (w/w) initial DM. In less than 10 h, the structure of the material was changed from intact straw particles (length 1-5 cm) into a paste/liquid that could be pumped. Tests revealed no significant effect of mixing speed in the range 3.3-11.5 rpm on the glucose conversion after 24 h and ethanol yield after subsequent fermentation for 48 h. Low-power inputs for mixing are therefore possible. Liquefaction and saccharification for 96 h using an enzyme loading of 7 FPU/g.DM and 40% DM resulted in a glucose concentration of 86 g/kg. Experiments conducted at 2%-40% (w/w) initial DM revealed that cellulose and hemicellulose conversion decreased almost linearly with increasing DM. Performing the experiments as simultaneous saccharification and fermentation also revealed a decrease in ethanol yield at increasing initial DM. Saccharomyces cerevisiae was capable of fermenting hydrolysates up to 40% DM. The highest ethanol concentration, 48 g/kg, was obtained using 35% (w/w) DM. Liquefaction of biomass with this reactor system unlocks the possibility of 10% (w/w) ethanol in the fermentation broth in future lignocellulose to ethanol plants. 相似文献
996.
Genetic variability of Athyrium filix-femina populations was evaluated with regard to phenotypic, allozyme, and RAPD variation in 20 Swiss populations along five altitudinal gradients at four different elevations in the northern Swiss Alps. Additionally, allozyme and phenotypic variations in one Italian and two Spanish populations were compared with the variation in the Swiss populations. We hypothesized that there will be statistically significant genetic differences among populations of different altitudes and sites. The results showed no substantial correlation between genetic variation and phenotypic variation among Swiss populations. These results imply that outbreeding and effective gene exchange (long-distance spore dispersal) are the keys to population structure in this fern species, and as a consequence, phenotypic plasticity is assumed to be favored. This contrasts with results found in similar studies of herbaceous flowering plants where genetic adaptation to gradients like altitude is common. However, when data from the more distant Italian and Spanish populations of A. filix-femina were included, significant variation was detected. 相似文献
997.
The NADH dehydrogenase I from Escherichia coli is a bacterial homolog of the mitochondrial complex I which translocates Na+ rather than H+. To elucidate the mechanism of Na+ transport, the C-terminally truncated NuoL subunit (NuoLN) which is related to Na+/H+ antiporters was expressed as a protein A fusion protein (ProtA–NuoLN) in the yeast Saccharomyces cerevisiae which lacks an endogenous complex I. The fusion protein inserted into membranes from the endoplasmatic reticulum (ER), as
confirmed by differential centrifugation and Western analysis. Membrane vesicles containing ProtA–NuoLN catalyzed the uptake of Na+ and K+ at rates which were significantly higher than uptake by the control vesicles under identical conditions, demonstrating that
ProtA–NuoLN translocated Na+ and K+ independently from other complex I subunits. Na+ transport by ProtA–NuoLN was inhibited by EIPA (5-(N-ethyl-N-isopropyl)-amiloride) which specifically reacts with Na+/H+ antiporters. The cation selectivity and function of the NuoL subunit as a transporter module of the NADH dehydrogenase complex
is discussed.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
998.
Calpain-10 variants and haplotypes are associated with polycystic ovary syndrome in Caucasians 总被引:1,自引:0,他引:1
Vollmert C Hahn S Lamina C Huth C Kolz M Schöpfer-Wendels A Mann K Bongardt F Mueller JC Kronenberg F Wichmann HE Herder C Holle R Löwel H Illig T Janssen OE;KORA group 《American journal of physiology. Endocrinology and metabolism》2007,292(3):E836-E844
PCOS is known to be associated with an increased risk of T2DM and has been proposed to share a common genetic background with T2DM. Recent studies suggest that the Calpain-10 gene (CAPN10) is an interesting candidate gene for PCOS susceptibility. However, contradictory results were reported concerning the contribution of certain CAPN10 variants, especially of UCSNP-44, to genetic predisposition to T2DM, hirsutism, and PCOS. By means of MALDI-TOF MS technique, we genotyped an expanded single nucleotide polymorphism panel, including the CAPN10 UCSNP-44, -43, -56, ins/del-19, -110, -58, -63, and -22 in a sample of 146 German PCOS women and 606 population-based controls. Statistical analysis revealed an association between UCSNP-56 and susceptibility to PCOS with an odds ratio (OR) of 2.91 (95% CI=1.51-5.61) for women carrying an AA genotype compared with GG. As expected, the 22-genotype of the ins/del-19 variant, which is in high linkage disequilibrium (r2=0.98) with UCSNP-56, was also significantly associated (OR=2.98, 95% CI=1.55-5.73). None of the additionally tested variants alone showed any significant association with PCOS. A meta-analysis including our study (altogether 623 PCOS cases and 1,224 controls) also showed significant association only with ins/del-19. The most common haplotype TGG3AGCA was significantly associated with a lower risk for PCOS (OR=0.487, P=0.0057). In contrast, the TGA2AGCA haplotype was associated with an increased risk for PCOS (OR=3.557, P=0.0011). By investigating a broad panel of CAPN10 variants, our results pointed to an allele dose-dependent association of UCSNP-56 and ins/del-19 with PCOS. 相似文献
999.
1000.
Veríssimo AF Pereira MM Melo AM Hreggvidsson GO Kristjansson JK Teixeira M 《FEMS microbiology letters》2007,269(1):41-47
The aerobic respiratory chain of the thermohalophilic bacterium Rhodothermus marinus has been extensively studied. In this study the isolation and characterization of a third oxygen reductase expressed in this organism are described. This newly isolated enzyme is a typical member of the type B family of haem-copper oxygen reductases, showing 43% amino acid sequence identity and 63% similarity with the ba3 oxygen reductase from Thermus thermophilus. It constitutes two subunits with apparent molecular masses of 42 and 38 kDa. It contains a low-spin B-type haem and a high-spin A-type haem. A stoichiometry of 1B: 1A haem per protein was obtained by spectral integration of UV-visible spectra. Metal analysis showed the presence of two iron and three copper ions, which is in agreement with the existence of a CuA centre. Taking advantage of having two spectroscopically distinct haems, the redox behaviour of the ba3 oxygen reductase was analysed and discussed in the framework of a model with interacting centres. Both haems, B and A, present two transitions, have unusually low reduction potentials of -65 mV and an interaction potential of -52.5 mV. 相似文献