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1.
Susanne Berglund Bryan J. Egner Henrik Gradén Joakim Gradén David G.A. Morgan Tord Inghardt Fabrizio Giordanetto 《Bioorganic & medicinal chemistry letters》2009,19(15):4268-4273
Herein, we disclose the discovery and optimization of 2-piperidin-4-yl-acetamide derivatives as MCH-R1 antagonists. Structural investigation of piperidin-4-yl-amide and piperidin-4-yl-ureas identified 2-piperidin-4-yl-acetamide-based MCH-R1 antagonists with outstanding in vivo efficacy but flawed with high affinity towards the hERG potassium channel. While existing hERG SAR information was employed to discover highly potent MCH-R1 antagonists with minimized hERG inhibition, additional hurdles prevented their subsequent clinical exploration. 相似文献
2.
Gene expression in autumn leaves 总被引:36,自引:0,他引:36
Bhalerao R Keskitalo J Sterky F Erlandsson R Björkbacka H Birve SJ Karlsson J Gardeström P Gustafsson P Lundeberg J Jansson S 《Plant physiology》2003,131(2):430-442
Two cDNA libraries were prepared, one from leaves of a field-grown aspen (Populus tremula) tree, harvested just before any visible sign of leaf senescence in the autumn, and one from young but fully expanded leaves of greenhouse-grown aspen (Populus tremula x tremuloides). Expressed sequence tags (ESTs; 5,128 and 4,841, respectively) were obtained from the two libraries. A semiautomatic method of annotation and functional classification of the ESTs, according to a modified Munich Institute of Protein Sequences classification scheme, was developed, utilizing information from three different databases. The patterns of gene expression in the two libraries were strikingly different. In the autumn leaf library, ESTs encoding metallothionein, early light-inducible proteins, and cysteine proteases were most abundant. Clones encoding other proteases and proteins involved in respiration and breakdown of lipids and pigments, as well as stress-related genes, were also well represented. We identified homologs to many known senescence-associated genes, as well as seven different genes encoding cysteine proteases, two encoding aspartic proteases, five encoding metallothioneins, and 35 additional genes that were up-regulated in autumn leaves. We also indirectly estimated the rate of plastid protein synthesis in the autumn leaves to be less that 10% of that in young leaves. 相似文献
3.
Inside Back Cover: Development of a 3‐dimensional tissue lung phantom of a preterm infant for optical measurements of oxygen—Laser‐detector position considerations (J. Biophotonics 3/2018) 下载免费PDF全文
Jim Larsson Peilang Liao Patrik Lundin Emilie Krite Svanberg Johannes Swartling Märta Lewander Xu Joakim Bood Stefan Andersson‐Engels 《Journal of biophotonics》2018,11(3)
The picture depicts the different 3d‐printed organs, thorax, lungs, heart and bone. Assembled it is used as an optical phantom of a preterm infant for performing percutaneous optical measurements of the gas content in the lungs. In order to simulate the optical properties of the tissue, the heart and thorax can be filled with liquid phantoms, a mixture of Intralipid and Indian Ink. Further details can be found in the article by Jim Larsson et al. ( e201700097 ).
4.
Huber J Fürnkranz A Bochkov VN Patricia MK Lee H Hedrick CC Berliner JA Binder BR Leitinger N 《Journal of lipid research》2006,47(5):1054-1062
Oxidized phospholipids stimulate endothelial cells to bind monocytes, but not neutrophils, an initiating event in atherogenesis. Here, we investigate intracellular signaling events induced by oxidized phospholipids in human umbilical vein endothelial cells (HUVECs) that lead to specific monocyte adhesion. In a static adhesion assay, oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine and one of its components, 1-palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphorylcholine, stimulated HUVECs to bind U937 cells and human peripheral blood monocytes but not HL-60 cells or blood neutrophils. Monocyte adhesion was dependent on protein kinases A and C, extracellular signal-regulated kinase 1/2, p38 mitogen activated protein kinases (MAPKs), and cytosolic phospholipase A(2) (cPLA(2)). Inhibition of 12-lipoxygenase (12-LOX), but not cyclooxygenases, blocked monocyte adhesion, and addition of 12-hydroxyeicosatetraenoic acid (12-HETE) mimicked the effects of oxidized phospholipids. Peroxisome proliferator-activated receptor alpha (PPARalpha) was excluded as a possible target for 12-HETE, because monocyte adhesion was still induced in endothelial cells from PPARalpha null mice. Together, our results suggest that oxidized phospholipids stimulate HUVECs to specifically bind monocytes involving MAPK pathways, which lead to the activation of cPLA(2) and 12-LOX. Further analysis of signaling pathways induced by oxidized phospholipids that lead to specific monocyte adhesion should ultimately lead to the development of novel therapeutic approaches against chronic inflammatory diseases. 相似文献
5.
Tom Thorvaldsen Harald Osnes Joakim Sundnes 《Computer methods in biomechanics and biomedical engineering》2013,16(6):369-379
In this paper we present a mixed finite element method for modeling the passive properties of the myocardium. The passive properties are described by a non-linear, transversely isotropic, hyperelastic material model, and the myocardium is assumed to be almost incompressible. Single-field, pure displacement-based formulations are known to cause numerical difficulties when applied to incompressible or slightly compressible material cases. This paper presents an alternative approach in the form of a mixed formulation, where a separately interpolated pressure field is introduced as a primary unknown in addition to the displacement field. Moreover, a constraint term is included in the formulation to enforce (almost) incompressibility. Numerical results presented in the paper demonstrate the difficulties related to employing a pure displacement-based method, applying a set of physically relevant material parameter values for the cardiac tissue. The same problems are not experienced for the proposed mixed method. We show that the mixed formulation provides reasonable numerical results for compressible as well as nearly incompressible cases, also in situations of large fiber stretches. There is good agreement between the numerical results and the underlying analytical models. 相似文献
6.
7.
Salvatore Vaccarella Anna S?derlund-Strand Silvia Franceschi Martyn Plummer Joakim Dillner 《PloS one》2013,8(8)
Background
To evaluate the pattern of co-infection of human papillomavirus (HPV) types in both sexes in Sweden.Methods
Cell samples from genital swabs, first-void urine, and genital swabs immersed in first-void urine were collected in the present cross-sectional High Throughput HPV Monitoring study. Overall, 31,717 samples from women and 9,949 from men (mean age 25) were tested for 16 HPV types using mass spectrometry. Multilevel logistic regression was used to estimate the expected number of multiple infections with specific HPV types, adjusted for age, type of sample, and accounting for correlations between HPV types due to unobserved risk factors using sample-level random effects. Bonferroni correction was used to allow for multiple comparisons (120).Results
Observed-to-expected ratio for any multiple infections was slightly above unity in both sexes, but, for most 2-type combinations, there was no evidence of significant departure from expected numbers. HPV6/18 was found more often and HPV51/68 and 6/68 less often than expected. However, HPV68 tended to be generally underrepresented in co-infections, suggesting a sub-optimal performance of our testing method for this HPV type.Conclusions
We found no evidence for positive or negative clustering between HPV types included in the current prophylactic vaccines and other untargeted oncogenic types, in either sex. 相似文献8.
Sam Nordfeldt Teresia ?ngarne-Lindberg Maria Nordwall Joakim Ekberg Carina Berter? 《PloS one》2013,8(6)
Background
Continued refinement of resources for patient information, education and support is needed. Considering the rapid development of new communication practices, the perspectives of young people themselves warrant more attention using a wide research focus. The purpose of this study was to understand information-seeking behaviours, Internet use and social networking online in adolescents with type 1 diabetes (T1DM). This applied to their everyday life, including the context of diabetes and their experiences and need of contact with T1DM peers.Methodology/Principal Findings
Twenty-four adolescents aged 10–17 years with T1DM were recruited from a county hospital in the south-east of Sweden. Qualitative data were obtained using eight focus groups, wherein each participant engaged in a 60–90 minute video/audio-recorded session. The focus group data were transcribed and analysed using qualitative content analysis. Some demographic and medical information was also collected. The three main categories that were identified; Aspects of Security, Updating, and Plainness and their sub-categories gave significant information about how to enhance information retrieval and peer contacts related to T1DM. Regarding the persons'' information-seeking behaviour, Internet use, and use of social media some differences could be identified depending on gender and age.Conclusions/Significance
Sensitivity and adaptation to users'' needs and expectations seem crucial in the development of future online resources for adolescents with T1DM. To start with, this could mean applying a wider range of already existing information and communication technologies. Health practitioners need to focus on the areas of security of information and communication, frequency of updating, and simplicity of design-less is more. 相似文献9.
Joakim Lundqvist Ilka Braumann Marzena Kurowska André H. Müller Mats Hansson 《The Journal of biological chemistry》2013,288(33):24012-24019
The ATP-dependent insertion of Mg2+ into protoporphyrin IX is the first committed step in the chlorophyll biosynthetic pathway. The reaction is catalyzed by magnesium chelatase, which consists of three gene products: BchI, BchD, and BchH. The BchI and BchD subunits belong to the family of AAA+ proteins (ATPases associated with various cellular activities) and form a two-ring complex with six BchI subunits in one layer and six BchD subunits in the other layer. This BchID complex is a two-layered trimer of dimers with the ATP binding site located at the interface between two neighboring BchI subunits. ATP hydrolysis by the BchID motor unit fuels the insertion of Mg2+ into the porphyrin by the BchH subunit. In the present study, we explored mutations that were originally identified in semidominant barley (Hordeum vulgare L.) mutants. The resulting recombinant BchI proteins have marginal ATPase activity and cannot contribute to magnesium chelatase activity although they apparently form structurally correct complexes with BchD. Mixing experiments with modified and wild-type BchI in various combinations showed that an exchange of BchI subunits in magnesium chelatase occurs during the catalytic cycle, which indicates that dissociation of the complex may be part of the reaction mechanism related to product release. Mixing experiments also showed that more than three functional interfaces in the BchI ring structure are required for magnesium chelatase activity. 相似文献
10.
Nachiket P. Marathe Sudarshan A. Shetty Yogesh S. Shouche D. G. Joakim Larsson 《PloS one》2016,11(11)
Biological treatment of waste water from bulk drug production, contaminated with high levels of fluoroquinolone antibiotics, can lead to massive enrichment of antibiotic resistant bacteria, resistance genes and associated mobile elements, as previously shown. Such strong selection may be boosted by the use of activated sludge (AS) technology, where microbes that are able to thrive on the chemicals within the wastewater are reintroduced at an earlier stage of the process to further enhance degradation of incoming chemicals. The microbial community structure within such a treatment plant is, however, largely unclear. In this study, Illumina-based 16S rRNA amplicon sequencing was applied to investigate the bacterial communities of different stages from an Indian treatment plant operated by Patancheru Environment Technology Limited (PETL) in Hyderabad, India. The plant receives waste water with high levels of fluoroquinolones and applies AS technology. A total of 1,019,400 sequences from samples of different stages of the treatment process were analyzed. In total 202, 303, 732, 652, 947 and 864 operational taxonomic units (OTUs) were obtained at 3% distance cutoff in the equilibrator, aeration tanks 1 and 2, settling tank, secondary sludge and old sludge samples from PETL, respectively. Proteobacteria was the most dominant phyla in all samples with Gammaproteobacteria and Betaproteobacteria being the dominant classes. Alcaligenaceae and Pseudomonadaceae, bacterial families from PETL previously reported to be highly multidrug resistant, were the dominant families in aeration tank samples. Despite regular addition of human sewage (approximately 20%) to uphold microbial activity, the bacterial diversity within aeration tanks from PETL was considerably lower than corresponding samples from seven, regular municipal waste water treatment plants. The strong selection pressure from antibiotics present may be one important factor in structuring the microbial community in PETL, which may affect not only resistance promotion but also general efficiency of the waste treatment process. 相似文献