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71.
Pesonen AK Sjöstén NM Matthews KA Heinonen K Martikainen S Kajantie E Tammelin T Eriksson JG Strandberg T Räikkönen K 《PloS one》2011,6(8):e22958
Objectives
We examined temporal associations between objectively-measured physical activity (PA) during the day and in the evening, and sleep quantity and quality.Study Design
PA and sleep were measured by actigraphs for an average of one week in an epidemiological cohort study of 275 eight-year-old children.Results
For each one standard deviation (SD) unit of increased PA during the day, sleep duration was decreased by 0.30, sleep efficiency by 0.16, and sleep fragmentation increased by 0.08 SD units that night. For each one SD unit increase in sleep duration and efficiency the preceding night, PA the following day decreased by 0.09 and 0.16 SD units, respectively. When we contrasted days with a high amount of moderate to vigorous activity during the day or in the evening to days with a more sedentary profile, the results were essentially similar. However, moderate to vigorous PA in the evening shortened sleep latency.Conclusions
The relationship between a higher level of PA and poorer sleep is bidirectional. These within-person findings challenge epidemiological findings showing that more active people report better sleep. Since only a few studies using objective measurements of both PA and sleep have been conducted in children, further studies are needed to confirm/refute these results. 相似文献72.
Merrell MA Ilvesaro JM Lehtonen N Sorsa T Gehrs B Rosenthal E Chen D Shackley B Harris KW Selander KS 《Molecular cancer research : MCR》2006,4(7):437-447
Toll-like receptor 9 (TLR9) recognizes microbial DNA. We show here that TLR9 protein is expressed in human breast cancer cells and clinical breast cancer samples. Stimulation of TLR9-expressing breast cancer cells with the TLR9 agonistic CpG oligonucleotides (1-10 mumol/L) dramatically increased their in vitro invasion in both Matrigel assays and three-dimensional collagen cultures. Similar effects on invasion were seen in TLR9-expressing astrocytoma and glioblastoma cells and in the immortalized human breast epithelial cell line MCF-10A. This effect was not, however, dependent on the CpG content of the TLR9 ligands because the non-CpG oligonucleotides induced invasion of TLR9-expressing cells. CpG or non-CpG oligonucleotide-induced invasion in MDA-MB-231 cells was blunted by chloroquine and they did not induce invasion of TLR9(-) breast cancer cells. Treatment of MDA-MB-231 cells with CpG or non-CpG oligonucleotides induced the formation of approximately 50-kDa gelatinolytic band in zymograms. This band and the increased invasion were abolished by a matrix metalloproteinase (MMP) inhibitor GM6001 but not by a serine proteinase inhibitor aprotinin. Furthermore, CpG oligonucleotide treatment decreased tissue inhibitor of metalloproteinase-3 expression and increased levels of active MMP-13 in TLR9-expressing but not TLR9(-) breast cancer cells without affecting MMP-8. Neutralizing anti-MMP-13 antibodies inhibited the CpG oligonucleotide-induced invasion. These findings suggest that infections may promote cancer progression through a novel TLR9-mediated mechanism. They also propose a new molecular target for cancer therapy, because TLR9 has not been associated with cancer invasiveness previously. 相似文献
73.
Shilpa Dutta Osbaldo Lopez Charcas Samuel Tanner Frédéric Gradek Virginie Driffort Sébastien Roger Katri Selander Sadanandan E. Velu Wayne Brouillette 《Bioorganic & medicinal chemistry》2018,26(9):2428-2436
Voltage-gated sodium channels (VGSC) are a well-established drug target for anti-epileptic, anti-arrhythmic and pain medications due to their presence and the important roles that they play in excitable cells. Recently, their presence has been recognized in non-excitable cells such as cancer cells and their overexpression has been shown to be associated with metastatic behavior in a variety of human cancers. The neonatal isoform of the VGSC subtype, Nav1.5 (nNav1.5) is overexpressed in the highly aggressive human breast cancer cell line, MDA-MB-231. The activity of nNav1.5 is known to promote the breast cancer cell invasion in vitro and metastasis in vivo, and its expression in primary mammary tumors has been associated with metastasis and patient death. Metastasis development is responsible for the high mortality of breast cancer and currently there is no treatment available to specifically prevent or inhibit breast cancer metastasis. In the present study, a 3D-QSAR model is used to assist the development of low micromolar small molecule VGSC blockers. Using this model, we have designed, synthesized and evaluated five small molecule compounds as blockers of nNav1.5-dependent inward currents in whole-cell patch-clamp experiments in MDA-MB-231 cells. The most active compound identified from these studies blocked sodium currents by 34.9?±?6.6% at 1?μM. This compound also inhibited the invasion of MDA-MB-231 cells by 30.3?±?4.5% at 1?μM concentration without affecting the cell viability. The potent small molecule compounds presented here have the potential to be developed as drugs for breast cancer metastasis treatment. 相似文献
74.
Lotta Koskinen Jihane Romanos Katri Kaukinen Kirsi Mustalahti Ilma Korponay-Szabo Donatella Barisani Maria Teresa Bardella Fabiana Ziberna Serena Vatta György Széles Zsuzsa Pocsai Kati Karell Katri Haimila Róza Ádány Tarcisio Not Alessandro Ventura Markku Mäki Jukka Partanen Cisca Wijmenga Päivi Saavalainen 《Immunogenetics》2009,61(4):247-256
Human leukocyte antigen (HLA) genes, located on chromosome 6p21.3, have a crucial role in susceptibility to various autoimmune
and inflammatory diseases, such as celiac disease and type 1 diabetes. Certain HLA heterodimers, namely DQ2 (encoded by the
DQA1*05 and DQB1*02 alleles) and DQ8 (DQA1*03 and DQB1*0302), are necessary for the development of celiac disease. Traditional
genotyping of HLA genes is laborious, time-consuming, and expensive. A novel HLA-genotyping method, using six HLA-tagging
single-nucleotide polymorphisms (SNPs) and suitable for high-throughput approaches, was described recently. Our aim was to
validate this method in the Finnish, Hungarian, and Italian populations. The six previously reported HLA-tagging SNPs were
genotyped in patients with celiac disease and in healthy individuals from Finland, Hungary, and two distinct regions of Italy.
The potential of this method was evaluated in analyzing how well the tag SNP results correlate with the HLA genotypes previously
determined using traditional HLA-typing methods. Using the tagging SNP method, it is possible to determine the celiac disease
risk haplotypes accurately in Finnish, Hungarian, and Italian populations, with specificity and sensitivity ranging from 95%
to 100%. In addition, it predicts homozygosity and heterozygosity for a risk haplotype, allowing studies on genotypic risk
effects. The method is transferable between populations and therefore suited for large-scale research studies and screening
of celiac disease among high-risk individuals or at the population level.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Lotta Koskinen and Jihane Romanos are authors with equal contribution. 相似文献
75.
Tamminen JA Myllärniemi M Hyytiäinen M Keski-Oja J Koli K 《Journal of cellular biochemistry》2012,113(7):2234-2247
The inhalation of asbestos fibers is considered to be highly harmful, and lead to fibrotic and/or malignant disease. Epithelial-to-mesenchymal transition (EMT) is a common pathogenic mechanism in asbestos associated fibrotic (asbestosis) and malignant lung diseases. The characterization of molecular pathways contributing to EMT may provide new possibilities for prognostic and therapeutic applications. The role of asbestos as an inducer of EMT has not been previously characterized. We exposed cultured human lung epithelial cells to crocidolite asbestos and analyzed alterations in the expression of epithelial and mesenchymal marker proteins and cell morphology. Asbestos was found to induce downregulation of E-cadherin protein levels in A549 lung carcinoma cells in 2-dimensional (2D) and 3D cultures. Similar findings were made in primary small airway epithelial cells cultured in 3D conditions where the cells retained alveolar type II cell phenotype. A549 cells also exhibited loss of cell-cell contacts, actin reorganization and expression of α-smooth muscle actin (α-SMA) in 2D cultures. These phenotypic changes were not associated with increased transforming growth factor (TGF)-β signaling activity. MAPK/Erk signaling pathway was found to mediate asbestos-induced downregulation of E-cadherin and alterations in cell morphology. Our results suggest that asbestos can induce epithelial plasticity, which can be interfered by blocking the MAPK/Erk kinase activity. 相似文献
76.
Thallium is an extremely toxic metal which, due to its similarities to K, is readily taken up by plants grown in Tl-contaminated
soils. Thallium is also a precious metal nearly as economically valuable as gold. Thallium is efficiently hyperaccumulated
in Iberis intermedia as aqueous Tl(I) with highest concentrations within the vascular network of leaves. In this study we examine the utility
of synchrotron X-ray differential absorption-edge computed microtomography (CMT) in determining the distribution and compartmentalization
of thallium (Tl) in Iberis intermedia. We found Tl to be distributed in solution throughout the vascular system of I. intermedia. Current laboratory experiments are examining the characteristics and potential recovery of Tl by I. intermedia with the objectives to remediate its toxic risks and to facilitate its reclamation for reuse. However, the recovery and reuse
of Tl from I. intermedia by way of phytomining requires knowledge on the speciation, distribution and compartmentalization of thallium. CMT shows
great promise for application in a wide variety of metal-related structural issues due to its high 3D resolution and being
a non-destructive analysis tool.
Electronic Supplementary Material Supplementary material is available in the online version of this article at and is accessible for authorized users.
An erratum to this article can be found at 相似文献
77.
Katri Jalava Hanna Rintala Jukka Ollgren Leena Maunula Vicente Gomez-Alvarez Joana Revez Marja Palander Jenni Antikainen Ari Kauppinen Pia R?s?nen Sallamaari Siponen Outi Nyholm Aino Kyyhkynen Sirpa Hakkarainen Juhani Merentie Martti P?rn?nen Raisa Loginov Hodon Ryu Markku Kuusi Anja Siitonen Ilkka Miettinen Jorge W. Santo Domingo Marja-Liisa H?nninen Tarja Pitk?nen 《PloS one》2014,9(8)
Failures in the drinking water distribution system cause gastrointestinal outbreaks with multiple pathogens. A water distribution pipe breakage caused a community-wide waterborne outbreak in Vuorela, Finland, July 2012. We investigated this outbreak with advanced epidemiological and microbiological methods. A total of 473/2931 inhabitants (16%) responded to a web-based questionnaire. Water and patient samples were subjected to analysis of multiple microbial targets, molecular typing and microbial community analysis. Spatial analysis on the water distribution network was done and we applied a spatial logistic regression model. The course of the illness was mild. Drinking untreated tap water from the defined outbreak area was significantly associated with illness (RR 5.6, 95% CI 1.9–16.4) increasing in a dose response manner. The closer a person lived to the water distribution breakage point, the higher the risk of becoming ill. Sapovirus, enterovirus, single Campylobacter jejuni and EHEC O157:H7 findings as well as virulence genes for EPEC, EAEC and EHEC pathogroups were detected by molecular or culture methods from the faecal samples of the patients. EPEC, EAEC and EHEC virulence genes and faecal indicator bacteria were also detected in water samples. Microbial community sequencing of contaminated tap water revealed abundance of Arcobacter species. The polyphasic approach improved the understanding of the source of the infections, and aided to define the extent and magnitude of this outbreak. 相似文献
78.
The alphaviruses induce membrane invaginations known as spherules as their RNA replication sites. Here, we show that inactivation of any function (polymerase, helicase, protease, or membrane association) essential for RNA synthesis also prevents the generation of spherule structures in a Semliki Forest virus trans-replication system. Mutants capable of negative-strand synthesis, including those defective in RNA capping, gave rise to spherules. Recruitment of RNA to membranes in the absence of spherule formation was not detected. 相似文献
79.
Eight polymorphic bovine microsatellites 总被引:1,自引:1,他引:0
80.