| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 3. |
- Anderson, Cynthia M., et al.
(författare)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 December 2009-31 January 2010
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:3, s. 576-579
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 220 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Allanblackia floribunda, Amblyraja radiata, Bactrocera cucurbitae, Brachycaudus helichrysi, Calopogonium mucunoides, Dissodactylus primitivus, Elodea canadensis, Ephydatia fluviatilis, Galapaganus howdenae howdenae, Hoplostethus atlanticus, Ischnura elegans, Larimichthys polyactis, Opheodrys vernalis, Pelteobagrus fulvidraco, Phragmidium violaceum, Pistacia vera, and Thunnus thynnus. These loci were cross-tested on the following species: Allanblackia gabonensis, Allanblackia stanerana, Neoceratitis cyanescens, Dacus ciliatus, Dacus demmerezi, Bactrocera zonata, Ceratitis capitata, Ceratitis rosa, Ceratits catoirii, Dacus punctatifrons, Ephydatia mulleri, Spongilla lacustris, Geodia cydonium, Axinella sp., Ischnura graellsii, Ischnura ramburii, Ischnura pumilio, Pistacia integerrima and Pistacia terebinthus.
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| 4. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 5. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 6. |
- Kim, J. H., et al.
(författare)
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Outer Membrane Vesicles Derived from Escherichia coli Up-Regulate Expression of Endothelial Cell Adhesion Molecules In Vitro and In Vivo
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli, as one of the gut microbiota, can evoke severe inflammatory diseases including peritonitis and sepsis. Gram-negative bacteria including E. coli constitutively release nano-sized outer membrane vesicles (OMVs). Although E. coli OMVs can induce the inflammatory responses without live bacteria, the effect of E. coli OMVs in vivo on endothelial cell function has not been previously elucidated. In this study, we show that bacteria-free OMVs increased the expression of endothelial intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1, and enhanced the leukocyte binding on human microvascular endothelial cells in vitro. Inhibition of NF-κB and TLR4 reduced the expression of cell adhesion molecules in vitro. OMVs given intraperitoneally to the mice induced ICAM-1 expression and neutrophil sequestration in the lung endothelium, and the effects were reduced in ICAM-1-/- and TLR4-/- mice. When compared to free lipopolysaccharide, OMVs were more potent in inducing both ICAM-1 expression as well as leukocyte adhesion in vitro, and ICAM-1 expression and neutrophil sequestration in the lungs in vivo. This study shows that OMVs potently up-regulate functional cell adhesion molecules via NF-κB- and TLR4-dependent pathways, and that OMVs are more potent than free lipopolysaccharide.
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| 7. |
- Kowal, Paul, et al.
(författare)
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Data resource profile : the World Health Organization Study on global AGEing and adult health (SAGE)
- 2012
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 41:6, s. 1639-1649
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Tidskriftsartikel (refereegranskat)abstract
- Population ageing is rapidly becoming a global issue and will have a major impact on health policies and programmes. The World Health Organization's Study on global AGEing and adult health (SAGE) aims to address the gap in reliable data and scientific knowledge on ageing and health in low- and middle-income countries. SAGE is a longitudinal study with nationally representative samples of persons aged 50+ years in China, Ghana, India, Mexico, Russia and South Africa, with a smaller sample of adults aged 18-49 years in each country for comparisons. Instruments are compatible with other large high-income country longitudinal ageing studies. Wave 1 was conducted during 2007-2010 and included a total of 34 124 respondents aged 50+ and 8340 aged 18-49. In four countries, a subsample consisting of 8160 respondents participated in Wave 1 and the 2002/04 World Health Survey (referred to as SAGE Wave 0). Wave 2 data collection will start in 2012/13, following up all Wave 1 respondents. Wave 3 is planned for 2014/15. SAGE is committed to the public release of study instruments, protocols and meta- and micro-data: access is provided upon completion of a Users Agreement available through WHO's SAGE website (www.who.int/healthinfo/systems/sage) and WHO's archive using the National Data Archive application (http://apps.who.int/healthinfo/systems/surveydata).
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| 8. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 9. |
- Qi, Qibin, et al.
(författare)
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FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
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Tidskriftsartikel (refereegranskat)abstract
- FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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| 10. |
- An, Junghwa, et al.
(författare)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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| 11. |
- Ballantyne, Kaye N., et al.
(författare)
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Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
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Tidskriftsartikel (refereegranskat)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
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| 12. |
- Coviello, Andrea D, et al.
(författare)
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A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
- 2012
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p=1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p=1.4×10(-11)), GCKR (rs780093, 2p23.3, p=2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p=3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p=6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p=1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p=8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p=3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p=4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p=1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p=2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p=5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p=2.5×10(-08), women p=0.66, heterogeneity p=0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
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| 13. |
- Rajaraman, Preetha, et al.
(författare)
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Genome-wide association study of glioma and meta-analysis
- 2012
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Ingår i: Human Genetics. - : SPRINGER. - 0340-6717 .- 1432-1203. ; 131:12, s. 1877-1888
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Tidskriftsartikel (refereegranskat)abstract
- Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.
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| 14. |
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| 15. |
- Bard-Chapeau, Emilie A, et al.
(författare)
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Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model.
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:1
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Tidskriftsartikel (refereegranskat)abstract
- The most common risk factor for developing hepatocellular carcinoma (HCC) is chronic infection with hepatitis B virus (HBV). To better understand the evolutionary forces driving HCC, we performed a near-saturating transposon mutagenesis screen in a mouse HBV model of HCC. This screen identified 21 candidate early stage drivers and a very large number (2,860) of candidate later stage drivers that were enriched for genes that are mutated, deregulated or functioning in signaling pathways important for human HCC, with a striking 1,199 genes being linked to cellular metabolic processes. Our study provides a comprehensive overview of the genetic landscape of HCC.
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| 16. |
- Blattner, Mirjam, et al.
(författare)
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SPOP Mutations in Prostate Cancer across Demographically Diverse Patient Cohorts
- 2014
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Ingår i: Neoplasia. - New York : Elsevier. - 1522-8002 .- 1476-5586. ; 16:1, s. 14-U34
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown.OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material.DESIGN, SETTING, AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features.RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P < .01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P < .01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes.CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.
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| 17. |
- Davis, Nichola J., et al.
(författare)
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Predictors of Sustained Reduction in Energy and Fat Intake in the Diabetes Prevention Program Outcomes Study Intensive Lifestyle Intervention
- 2013
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Ingår i: Journal of the American Dietetic Association. - : Elsevier BV. - 0002-8223. ; 113:11, s. 1455-1464
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Tidskriftsartikel (refereegranskat)abstract
- Background Few lifestyle intervention studies examine long-term sustainability of dietary changes. Objective To describe sustainability of dietary changes over 9 years in the Diabetes Prevention Program and its outcomes study, the Diabetes Prevention Program Outcomes Study, among participants receiving the intensive lifestyle intervention. Design One thousand seventy-nine participants were enrolled in the intensive lifeStyle intervention arm of the Diabetes Prevention Program; 910 continued participation in the Diabetes Prevention Program Outcomes Study. Fat and energy intake derived from food frequency questionnaires at baseline and post-randomization Years 1 and 9 were examined. Parsimonious models determined whether baseline characteristics and intensive lifestyle intervention session participation predicted sustainability. Results Self-reported energy intake was reduced from a median of 1,876 kcal/day (interquartile range [IQR]=1,452 to 2,549 kcal/day) at baseline to 1,520 kcal/day (IQR=1,192 to 1,986 kcal/day) at Year 1, and 1,560 kcal/day (IQR=1,223 to 2,026 kcal/ day) at Year 9. Dietary fat was reduced from a median of 70.4 g (IQR=49.3 to 102.5 g) to 45 g (IQR=32.2 to 63.8 g) at Year 1 and increased to 61.0 g (IQR=44.6 to 82.7 g) at Year 9. Percent energy from fat was reduced from a median of 34.4% (IQR=29.6% to 38.5%) to 27.1% (IQR=23.1% to 31.5%) at Year 1 but increased to 35.3% (IQR=29.7% to 40.2%) at Year 9. Lower baseline energy intake and Year 1 dietary reduction predicted lower energy and fat gram intake at Year 9. Higher leisure physical activity predicted lower fat gram intake but not energy intake. Conclusions Intensive lifestyle intervention can result in reductions in total energy intake for up to 9 years. Initial success in achieving reductions in fat and energy intake and success in attaining activity goals appear to predict long-term success at maintaining changes.
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| 18. |
- Hempel, Antje, et al.
(författare)
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The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces.
- 2012
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 109:35, s. 2371-2379
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Tidskriftsartikel (refereegranskat)abstract
- In cells that exhibit apical growth, mechanisms that regulate cell polarity are crucial for determination of cellular shape and for the adaptation of growth to intrinsic and extrinsic cues. Broadly conserved pathways control cell polarity in eukaryotes, but less is known about polarly growing prokaryotes. An evolutionarily ancient form of apical growth is found in the filamentous bacteria Streptomyces, and is directed by a polarisome-like complex involving the essential protein DivIVA. We report here that this bacterial polarization machinery is regulated by a eukaryotic-type Ser/Thr protein kinase, AfsK, which localizes to hyphal tips and phosphorylates DivIVA. During normal growth, AfsK regulates hyphal branching by modulating branch-site selection and some aspect of the underlying polarisome-splitting mechanism that controls branching of Streptomyces hyphae. Further, AfsK is activated by signals generated by the arrest of cell wall synthesis and directly communicates this to the polarisome by hyperphosphorylating DivIVA. Induction of high levels of DivIVA phosphorylation by using a constitutively active mutant AfsK causes disassembly of apical polarisomes, followed by establishment of multiple hyphal branches elsewhere in the cell, revealing a profound impact of this kinase on growth polarity. The function of AfsK is reminiscent of the phoshorylation of polarity proteins and polarisome components by Ser/Thr protein kinases in eukaryotes.
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| 19. |
- Jarfors, A. E. W., et al.
(författare)
-
Preface
- 2010
-
Ingår i: Materials & Design. - : Elsevier BV. - 0261-3069. ; 31:SUPPL. 1, s. S1-
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 20. |
- Kim, O. Y., et al.
(författare)
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Immunization with Escherichia coli Outer Membrane Vesicles Protects Bacteria-Induced Lethality via Th1 and Th17 Cell Responses
- 2013
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 190:8, s. 4092-4102
-
Tidskriftsartikel (refereegranskat)abstract
- Outer membrane vesicles (OMVs), secreted from Gram-negative bacteria, are spherical nanometer-sized proteolipids enriched with outer membrane proteins. OMVs, also known as extracellular vesicles, have gained interests for use as nonliving complex vaccines and have been examined for immune-stimulating effects. However, the detailed mechanism on how OMVs elicit the vaccination effect has not been studied extensively. In this study, we investigated the immunological mechanism governing the protective immune response of OMV vaccines. Immunization with Escherichia coli-derived OMVs prevented bacteria-induced lethality and OMV-induced systemic inflammatory response syndrome. As verified by adoptive transfer and gene-knockout studies, the protective effect of OMV immunization was found to be primarily by the stimulation of T cell immunity rather than B cell immunity, especially by the OMV-Ag-specific production of IFN-gamma and IL-17 from T cells. By testing the bacteria-killing ability of macrophages, we also demonstrated that IFN-gamma and IL-17 production is the main factor promoting bacterial clearances. Our findings reveal that E. coli-derived OMV immunization effectively protects bacteria-induced lethality and OMV-induced systemic inflammatory response syndrome primarily via Th1 and Th17 cell responses. This study therefore provides a new perspective on the immunological detail regarding OMV vaccination.
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| 21. |
- Li, Fay-Wei, et al.
(författare)
-
Horizontal transfer of an adaptive chimeric photoreceptor from bryophytes to ferns
- 2014
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:18, s. 6672-6677
-
Tidskriftsartikel (refereegranskat)abstract
- Ferns are well known for their shade-dwelling habits. Their ability to thrive under low-light conditions has been linked to the evolution of a novel chimeric photoreceptor-neochrome-that fuses red-sensing phytochrome and blue-sensing phototropin modules into a single gene, thereby optimizing phototropic responses. Despite being implicated in facilitating the diversification of modern ferns, the origin of neochrome has remained a mystery. We present evidence for neochrome in hornworts (a bryophyte lineage) and demonstrate that ferns acquired neochrome from hornworts via horizontal gene transfer (HGT). Fern neochromes are nested within hornwort neochromes in our large-scale phylogenetic reconstructions of phototropin and phytochrome gene families. Divergence date estimates further support the HGT hypothesis, with fern and hornwort neochromes diverging 179 Mya, long after the split between the two plant lineages (at least 400 Mya). By analyzing the draft genome of the hornwort Anthoceros punctatus, we also discovered a previously unidentified phototropin gene that likely represents the ancestral lineage of the neochrome phototropin module. Thus, a neochrome originating in hornworts was transferred horizontally to ferns, where it may have played a significant role in the diversification of modern ferns.
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| 22. |
- Ma, Li-Jun, et al.
(författare)
-
Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium.
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 464:7287, s. 367-73
-
Tidskriftsartikel (refereegranskat)abstract
- Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective.
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| 23. |
- Melendez, J., et al.
(författare)
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The solar, exoplanet and cosmological lithium problems
- 2010
-
Ingår i: Astrophysics and Space Science. - : Springer Science and Business Media LLC. - 0004-640X .- 1572-946X. ; 328:1-2, s. 193-200
-
Tidskriftsartikel (refereegranskat)abstract
- We review three Li problems. First, the Li problem in the Sun, for which some previous studies have argued that it may be Li-poor compared to other Suns. Second, we discuss the Li problem in planet hosting stars, which are claimed to be Li-poor when compared to field stars. Third, we discuss the cosmological Li problem, i.e. the discrepancy between the Li abundance in metal-poor stars (Spite plateau stars) and the predictions from standard Big Bang Nucleosynthesis. In all three cases we find that the "problems" are naturally explained by non-standard mixing in stars.
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| 24. |
- Norris, J. E., et al.
(författare)
-
The most metal-poor stars. I. Discovery, data, and atmospheric parameters
- 2013
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 762:1, s. 25-
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of 34 stars in the Hamburg/ESO Survey for metal-poor stars and the Sloan Digital Sky Survey that have [Fe/H] ≲ -3.0. Their median and minimum abundances are [Fe/H] = -3.1 and -4.1, respectively, while 10 stars have [Fe/H] < -3.5. High-resolution, high signal-to-noise spectroscopic data - equivalent widths and radial velocities - are presented for these stars, together with an additional four objects previously reported or currently being investigated elsewhere. We have determined the atmospheric parameters, effective temperature (T eff), and surface gravity (log g), which are critical in the determination of the chemical abundances and the evolutionary status of these stars. Three techniques were used to derive these parameters. Spectrophotometric fits to model atmosphere fluxes were used to derive T eff, log g, and an estimate of E(B - V); Hα, Hβ, and Hγ profile fitting to model atmosphere results provided the second determination of T eff and log g; and finally, we used an empirical T eff-calibrated Hδ index, for the third, independent T eff determination. The three values of T eff are in good agreement, although the profile fitting may yield systematically cooler T eff values, by ∼100 K. This collective data set will be analyzed in future papers in the present series to utilize the most metal-poor stars as probes of conditions in the early universe.
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| 25. |
- Weinhold, Niels, et al.
(författare)
-
Inherited genetic susceptibility to monoclonal gammopathy of unknown significance
- 2014
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 123:16, s. 2513-2517
-
Tidskriftsartikel (refereegranskat)abstract
- Monoclonal gammopathy of undetermined significance (MGUS) is present in similar to 2% of individuals age >50 years. The increased risk of multiple myeloma (MM) in relatives of individuals with MGUS is consistent with MGUS being a marker of inherited genetic susceptibility to MM. Common single-nucleotide polymorphisms (SNPs) at 2p23.3 (rs6746082), 3p22.1 (rs1052501), 3q26.2 (rs10936599), 6p21.33 (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077), and 22q13.1 (rs877529) have recently been shown to influence MM risk. To examine the impact of these 7 SNPs on MGUS, we analyzed two case-control series totaling 492 cases and 7306 controls. Each SNP independently influenced MGUS risk with statistically significant associations (P < .02) for rs1052501, rs2285803, rs4487645, and rs4273077. SNP associations were independent, with risk increasing with a larger number of risk alleles carried (per allele odds ratio, 1.18; P < 10(-7)). Collectively these data are consistent with a polygenic model of disease susceptibility to MGUS.
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| 26. |
- Zhang, Guojie, et al.
(författare)
-
Comparative genomics reveals insights into avian genome evolution and adaptation
- 2014
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1311-1320
-
Tidskriftsartikel (refereegranskat)abstract
- Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.
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| 27. |
- Bensby, Thomas, et al.
(författare)
-
A First Constraint on the Thick Disk Scale Length: Differential Radial Abundances in K Giants at Galactocentric Radii 4, 8, and 12 kpc
- 2011
-
Ingår i: Astrophysical Journal Letters. - 2041-8213. ; 735:2
-
Tidskriftsartikel (refereegranskat)abstract
- Based on high-resolution spectra obtained with the MIKE spectrograph on the Magellan telescopes, we present detailed elemental abundances for 20 red giant stars in the outer Galactic disk, located at Galactocentric distances between 9 and 13 kpc. The outer disk sample is complemented with samples of red giants from the inner Galactic disk and the solar neighborhood, analyzed using identical methods. For Galactocentric distances beyond 10 kpc, we only find chemical patterns associated with the local thin disk, even for stars far above the Galactic plane. Our results show that the relative densities of the thick and thin disks are dramatically different from the solar neighborhood, and we therefore suggest that the radial scale length of the thick disk is much shorter than that of the thin disk. We make a first estimate of the thick disk scale length of L-thick = 2.0 kpc, assuming L-thin = 3.8 kpc for the thin disk. We suggest that radial migration may explain the lack of radial age, metallicity, and abundance gradients in the thick disk, possibly also explaining the link between the thick disk and the metal-poor bulge.
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| 28. |
- Bensby, Thomas, et al.
(författare)
-
Abundance Trends in the Inner and Outer Galactic Disk
- 2012
-
Ingår i: Galactic archeology, near-field cosmology and the formation of the Milky Way (ASP Conference Series). ; 458, s. 171-174
-
Konferensbidrag (refereegranskat)abstract
- Based on high-resolution spectra obtained with the MIKE spectrograph on the Magellan telescopes we present detailed elemental abundances for 64 red giant stars in the inner and outer Galactic disk. For the inner disk sample (4-7 kpc from the Galactic centre) we find that stars with both thin and thick disk abundance patterns are present while for Galactocentric distances beyond 10 kpc, we only find chemical patterns associated with the local thin disk, even for stars far above the Galactic plane. Our results show that the relative densities of the thick and thin disks are dramatically different from the solar neighbourhood, and we therefore suggest that the radial scale length of the thick disk is much shorter than that of the thin disk. A thick disk scale-length of L-thick = 2.0 kpc, and L-thin = 3.8 kpc for the thin disk, better match the data.
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| 29. |
- Berrill, Mark, et al.
(författare)
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Improved beam characteristics of solid-target son x-ray laser amplifiers by injection seeding with high harmonic pulses
- 2010
-
Ingår i: Optics Letters. - : Optical Society of America. - 0146-9592 .- 1539-4794. ; 35:14, s. 2317-2319
-
Tidskriftsartikel (refereegranskat)abstract
- Injection seeding of solid-target soft x-ray laser amplifiers with high harmonic pulses is shown to dramatically improve the far-field laser beam profile and reduce the beam divergence. Measurements and two-dimensional simulations for a 13.9 nm nickel-like Ag amplifier show that the amplified beam divergence depends strongly on the seed and can therefore be controlled by selecting the divergence of the seed. The near-field beam size of both the seeded and unseeded lasers is shown to be determined by the size of the gain region and the divergence of the amplified beams.
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| 30. |
- Brizuela, Fernando, et al.
(författare)
-
Extreme ultraviolet laser-based table-top aerial image metrology of lithographic masks
- 2010
-
Ingår i: Optics Express. - : Optical Society of America. - 1094-4087. ; 18:14, s. 14467-14473
-
Tidskriftsartikel (refereegranskat)abstract
- We have realized the first demonstration of a table-top aerial imaging microscope capable of characterizing pattern and defect printability in extreme ultraviolet lithography masks. The microscope combines the output of a 13.2 nm wavelength, table-top, plasma-based, EUV laser with zone plate optics to mimic the imaging conditions of an EUV lithographic stepper. We have characterized the illumination of the system and performed line-edge roughness measurements on an EUVL mask. The results open a path for the development of a compact aerial imaging microscope for high-volume manufacturing.
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| 31. |
- Brown, Solomon, et al.
(författare)
-
CO(2)QUEST : Techno-economic assessment of CO2 quality effect on its storage and transport
- 2014
-
Ingår i: 12TH INTERNATIONAL CONFERENCE ON GREENHOUSE GAS CONTROL TECHNOLOGIES, GHGT-12. - : Elsevier BV. ; , s. 2622-2629
-
Konferensbidrag (refereegranskat)abstract
- Presented is an overview of the CO(2)QUEST project that addresses fundamentally important issues regarding the impact of typical impurities in the gas or dense phase CO2 stream captured from fossil fuel power plants on its safe and economic transportation and storage. Previous studies have mainly investigated the impact of CO2 stream impurities on each part of the carbon capture and storage (CCS) chain in isolation. This is a significant drawback given the different sensitivities of pipeline, wellbore materials and storage sites to the various impurities. The project brings together leading researchers and stakeholders, to address the impact of the typical impurities upon safe and economic CO2 transportation and storage. State-of-the-art mathematical models, backed by laboratory and industrial-scale experimentation, are implemented to perform a comprehensive techno-economic assessment of the impact of impurities upon the thermo-physical phenomena governing pipeline and storage-site integrities.
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| 32. |
- Bushnell, David L., et al.
(författare)
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90Y-edotreotide for metastatic carcinoid refractory to octreotide
- 2010
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 28:10, s. 1652-1659
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Metastatic carcinoid is an incurable malignancy whose symptoms, such as diarrhea and flushing, can be debilitating and occasionally life-threatening. Although symptom relief is available with octreotide, the disease eventually becomes refractory to octreotide, leaving no proven treatment options. The goal of this study was to evaluate the clinical effect of using (90)Y-edotreotide to treat symptomatic patients with carcinoid tumors. PATIENTS AND METHODS: Patients enrolled had metastatic carcinoid, at least one sign/symptom refractory to octreotide, and at least one measurable lesion. Study treatment consisted of three cycles of 4.4 GBq (120 mCi) (90)Y-edotreotide each, once every 6 weeks. RESULTS: Ninety patients were enrolled in the study. Using Southwest Oncology Group tumor response criteria, 67 (74.%) of 90 patients (95% CI, 65.4% to 83.4%) were objectively stable or responded. A statistically significant linear trend toward improvement was demonstrated across all 12 symptoms assessed. Median progression-free survival was significantly greater (P = .03) for the 38 patients who had durable diarrhea improvement than the 18 patients who did not (18.2 v 7.9 months, respectively). Adverse events (AEs) were reported in 96.7% (87 of 90) of patients. These AEs consisted primarily of reversible GI events (76 of 90), which could be caused in part by concomitant administration of amino acid solution given to reduce radiation exposure to the kidneys. There was one case each of grade 3 oliguria and grade 4 renal failure, each lasting 6 days. CONCLUSION: (90)Y-edotreotide treatment improved symptoms associated with malignant carcinoid among subjects with no treatment alternatives. Treatment was well-tolerated and had an acceptable expected AE profile.
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| 33. |
- Howes, Louise, et al.
(författare)
-
The Gaia-ESO Survey: the most metal-poor stars in the Galactic bulge
- 2014
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 1365-2966 .- 0035-8711. ; 445:4, s. 4241-4246
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first results of the EMBLA survey (Extremely Metal-poor BuLge stars with AAOmega), aimed at finding metal-poor stars in the Milky Way bulge, where the oldest stars should now preferentially reside. EMBLA utilizes SkyMapper photometry to pre-select metal-poor candidates, which are subsequently confirmed using AAOmega spectroscopy. We describe the discovery and analysis of four bulge giants with -2.72 <= [Fe/H] <= -2.48, the lowest metallicity bulge stars studied with high-resolution spectroscopy to date. Using FLAMES/UVES spectra through the Gaia-ESO Survey we have derived abundances of twelve elements. Given the uncertainties, we find a chemical similarity between these bulge stars and halo stars of the same metallicity, although the abundance scatter may be larger, with some of the stars showing unusual [alpha/Fe] ratios.
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| 34. |
- Jarvis, Erich D., et al.
(författare)
-
Whole-genome analyses resolve early branches in the tree of life of modern birds
- 2014
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
-
Tidskriftsartikel (refereegranskat)abstract
- To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
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| 35. |
- Kalra, Hina, et al.
(författare)
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Vesiclepedia : a compendium for extracellular vesicles with continuous community annotation
- 2012
-
Ingår i: PLoS biology. - : Public library of science. - 1544-9173 .- 1545-7885. ; 10:12, s. e1001450-
-
Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs. Here, we describe Vesiclepedia, a manually curated compendium of molecular data (lipid, RNA, and protein) identified in different classes of EVs from more than 300 independent studies published over the past several years. Even though databases are indispensable resources for the scientific community, recent studies have shown that more than 50% of the databases are not regularly updated. In addition, more than 20% of the database links are inactive. To prevent such database and link decay, we have initiated a continuous community annotation project with the active involvement of EV researchers. The EV research community can set a gold standard in data sharing with Vesiclepedia, which could evolve as a primary resource for the field.
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| 36. |
- Li, Cai, et al.
(författare)
-
Two Antarctic penguin genomes reveal insights into their evolutionary history and molecular changes related to the Antarctic environment
- 2014
-
Ingår i: GigaScience. - 2047-217X. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Penguins are flightless aquatic birds widely distributed in the Southern Hemisphere. The distinctive morphological and physiological features of penguins allow them to live an aquatic life, and some of them have successfully adapted to the hostile environments in Antarctica. To study the phylogenetic and population history of penguins and the molecular basis of their adaptations to Antarctica, we sequenced the genomes of the two Antarctic dwelling penguin species, the Adelie penguin [Pygoscelis adeliae] and emperor penguin [Aptenodytes forsteri]. Results: Phylogenetic dating suggests that early penguins arose similar to 60 million years ago, coinciding with a period of global warming. Analysis of effective population sizes reveals that the two penguin species experienced population expansions from similar to 1 million years ago to similar to 100 thousand years ago, but responded differently to the climatic cooling of the last glacial period. Comparative genomic analyses with other available avian genomes identified molecular changes in genes related to epidermal structure, phototransduction, lipid metabolism, and forelimb morphology. Conclusions: Our sequencing and initial analyses of the first two penguin genomes provide insights into the timing of penguin origin, fluctuations in effective population sizes of the two penguin species over the past 10 million years, and the potential associations between these biological patterns and global climate change. The molecular changes compared with other avian genomes reflect both shared and diverse adaptations of the two penguin species to the Antarctic environment.
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| 37. |
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| 38. |
- Mandal, Goutam, et al.
(författare)
-
Modulation of Leishmania major aquaglyceroporin activity by a mitogen-activated protein kinase.
- 2012
-
Ingår i: Molecular microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 85:6, s. 1204-1218
-
Tidskriftsartikel (refereegranskat)abstract
- Leishmania major aquaglyceroporin (LmjAQP1) adventitiously facilitates the uptake of antimonite [Sb(III)], an active form of Pentostam® or Glucantime®, which are the first line of defence against all forms of leishmaniasis. The present paper shows that LmjAQP1 activity is modulated by the mitogen-activated protein kinase, LmjMPK2. Leishmania parasites coexpressing LmjAQP1 and LmjMPK2 show increased Sb(III) uptake and increased Sb(III) sensitivity. When subjected to a hypo-osmotic stress, these cells show faster volume recovery than cells expressing LmjAQP1 alone. LmjAQP1 is phosphorylated in vivo at Thr-197 and this phosphorylation requires LmjMPK2 activity. Lys-42 of LmjMPK2 is critical for its kinase activity. Cells expressing altered T197A LmjAQP1 or K42A LmjMPK2 showed decreased Sb(III) influx and a slower volume recovery than cells expressing wild-type proteins. Phosphorylation of LmjAQP1 led to a decrease in its turnover rate affecting LmjAQP1 activity. Although LmjAQP1 is localized to the flagellum of promastigotes, upon phosphorylation, it is relocalized to the entire surface of the parasite. Leishmania mexicana promastigotes with an MPK2 deletion showed reduced Sb(III) uptake and slower volume recovery than wild-type cells. This is the first report where a parasite aquaglyceroporin activity is post-translationally modulated by a mitogen-activated protein kinase.
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| 39. |
- Navarro-Alvarez, Nalu, et al.
(författare)
-
Intramuscular transplantation of engineered hepatic tissue constructs corrects acute and chronic liver failure in mice
- 2010
-
Ingår i: Journal of Hepatology. - 0168-8278 .- 1600-0641. ; 52:2, s. 211-219
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Transplantation of isolated hepatocytes holds great promise as ail alternative to whole organ liver transplantation. For treatment of liver failure, access to the portal circulation has significant risks and intrahepatic hepatocyte engraftment is poor. In advanced cirrhosis, transplantation into ail extrahepatic site is necessary and intrasplenic engraftment is short-lived. Strategies that allow repeated extrahepatic infusion of hepatocytes Could improve the efficacy and safety of hepatocyte transplantation for the treatment of liver failure. Methods: A non-immunogenic self-assembling peptide nanofiber (SAPNF) was developed as a three-dimensional scaffold and combined with growth factors derived from a conditionally immortalized human hepatocyte cell line to engineer a hepatic tissue graft that Would allow hepatocyte engraftment outside the liver. Results:The hepatic tissue Constructs maintained hepatocyte-specific gene expression and functionality in vitro. When transplanted into skeletal muscle as ail extrahepatic site for engraftment, the engineered hepatic grafts provided life-saving support in models of acute, fulminant, and chronic liver failure that recapitulates these clinical diseases. Conclusions: SAPNF-engineered hepatic Constructs engrafted and functioned as hepatic tissues within the muscle to provide life-sustaining liver Support. These engineered tissue Constructs contained no animal products that Would limit their development as a therapeutic approach.
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| 40. |
- Norris, J. E., et al.
(författare)
-
The most metal-poor stars. IV. the two populations with [Fe/H] ≲ -3.0
- 2013
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 762:1, s. 28-
-
Tidskriftsartikel (refereegranskat)abstract
- We discuss the carbon-normal and carbon-rich populations of Galactic halo stars having [Fe/H] ≲ -3.0, utilizing chemical abundances from high-resolution, high signal-to-noise model-atmosphere analyses. The C-rich population represents ∼28% of stars below [Fe/H] = -3.1, with the present C-rich sample comprising 16 CEMP-no stars, and two others with [Fe/H] ∼ -5.5 and uncertain classification. The population is O-rich ([O/Fe] ≳ +1.5); the light elements Na, Mg, and Al are enhanced relative to Fe in half the sample; and for Z > 20 (Ca) there is little evidence for enhancements relative to solar values. These results are best explained in terms of the admixing and processing of material from H-burning and He-burning regions as achieved by nucleosynthesis in zero-heavy-element models in the literature of "mixing and fallback" supernovae (SNe); of rotating, massive, and intermediate-mass stars; and of Type II SNe with relativistic jets. The available (limited) radial velocities offer little support for the C-rich stars with [Fe/H] < -3.1 being binary. More data are required before one could conclude that binarity is key to an understanding of this population. We suggest that the C-rich and C-normal populations result from two different gas cooling channels in the very early universe of material that formed the progenitors of the two populations. The first was cooling by fine-structure line transitions of C II and O I (to form the C-rich population); the second, while not well defined (perhaps dust-induced cooling?), led to the C-normal group. In this scenario, the C-rich population contains the oldest stars currently observed.
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| 41. |
- Park, K. S., et al.
(författare)
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Pulmonary Inflammation Induced by Bacteria-Free Outer Membrane Vesicles from Pseudomonas aeruginosa
- 2013
-
Ingår i: American Journal of Respiratory Cell and Molecular Biology. - 1044-1549. ; 49:4, s. 637-645
-
Tidskriftsartikel (refereegranskat)abstract
- Pseudomonas aeruginosa is often involved in lung diseases such as cystic fibrosis. These bacteria can release outer membrane vesicles (OMVs), which are bilayered proteolipids with diameters of approximately 20 to 250 nm. In vitro, these OMVs activate macrophages and airway epithelial cells. The aim of this study was to determine whether OMVs from P. aeruginosa can induce pulmonary inflammation in vivo and to elucidate the mechanisms involved. Bacteria-free OMVs were isolated from P. aeruginosa cultures. Wild-type, Toll-like receptor (TLR) 2 and TLR4 knockout mice were exposed to OMVs by the airway, and inflammation in the lung was assessed using differential counts, histology, and quantification of chemokines and cytokines. The involvement of the TLR2 and TLR4 pathways was studied in human cells using transfection. OMVs given to the mouse lung caused dose-and time-dependent pulmonary cellular inflammation. Furthermore, OMVs increased concentrations of several chemokines and cytokines in the mouse lungs and mouse alveolar macrophages. The inflammatory responses to OMVs were comparable to those of live bacteria and were only partly regulated by the TLR2 and TLR4 pathways, according to studies in knockout mice. This study shows that OMVs from P. aeruginosa cause pulmonary inflammation without live bacteria in vivo. This effect is only partly controlled by TLR2 and TLR4. The role of OMVs in clinical disease warrants further studies because targeting of OMVs in addition to live bacteria may add clinical benefit compared with treating with antibiotics alone.
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| 42. |
- Yong, D., et al.
(författare)
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The most metal-poor stars. II. Chemical abundances of 190 metal-poor stars including 10 new stars with [Fe/H] ≤ -3.5
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 762:1, s. 26-
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Tidskriftsartikel (refereegranskat)abstract
- We present a homogeneous chemical abundance analysis of 16 elements in 190 metal-poor Galactic halo stars (38 program and 152 literature objects). The sample includes 171 stars with [Fe/H] ≤ -2.5, of which 86 are extremely metal poor, [Fe/H] ≤ -3.0. Our program stars include 10 new objects with [Fe/H] ≤ -3.5. We identify a sample of "normal" metal-poor stars and measure the trends between [X/Fe] and [Fe/H], as well as the dispersion about the mean trend for this sample. Using this mean trend, we identify objects that are chemically peculiar relative to "normal" stars at the same metallicity. These chemically unusual stars include CEMP-no objects, one star with high [Si/Fe], another with high [Ba/Sr], and one with unusually low [X/Fe] for all elements heavier than Na. The Sr and Ba abundances indicate that there may be two nucleosynthetic processes at lowest metallicity that are distinct from the main r-process. Finally, for many elements, we find a significant trend between [X/Fe] versus T eff, which likely reflects non-LTE and/or three-dimensional effects. Such trends demonstrate that care must be exercised when using abundance measurements in metal-poor stars to constrain chemical evolution and/or nucleosynthesis predictions.
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| 43. |
- Yoo, Lina, et al.
(författare)
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A simple one-step assay platform based on fluorescence quenching of macroporous silicon
- 2013
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Ingår i: Biosensors & Bioelectronics. - : Elsevier BV. - 1873-4235 .- 0956-5663. ; 41, s. 477-483
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Tidskriftsartikel (refereegranskat)abstract
- We synthesized 3D macroporous silicon through a simple electrochemical dissolution process and systematically estimated its protein adsorption and effect on fluorescence emission. Compared with conventional 2D polystyrene plate, the macroporous silicon showed a superior protein adsorption capacity and significant fluorescence quenching effect. We developed a 3D macroporous silicon-based adenosine assay system through the following fabrication process: streptavidin molecules that have been immobilized on the surface of macroporous silicon are attached with biotin-linked and adenosine-specific DNA aptamer, followed by hybridization between the attached aptamer and fluorescent chemical (carboxytetramethylrhodamine/CTMR) that is conjugated with a short complementary DNA sequence. In the absence of adenosine, the aptamer-CTMR complexes remain closely attached to the surface of porous silicon, hence fluorescence being significantly quenched. Upon binding to adenosine, the DNA aptamer is subject to structure switching that leads to dissociation of CTMR from DNA aptamer, and consequently the CTMR fluorescence is restored, indicating a simple one-step assay of adenosine. Compared to the conventional 2D PS and ZnO nanorods-based assays, adenosine at much lower (sub-micromolar) concentration was successfully detected through the 3D macroporous silicon-based assay. The three-dimensionally and densely immobilized aptamer probes and effective fluorescence quenching on the surface of macroporous silicon enables adenosine to be detected at lower levels. Although the adenosine detection is reported here as a proof-of-concept, the developed macroporous silicon-based simple one-step assay platform can be applied in general to fluorescence quenching -based detection of many other biomolecules. (C) 2012 Elsevier B.V. All rights reserved.
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| 44. |
- Zhang, Yan, et al.
(författare)
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Study on the verification of IR and RTD methods applied in the thermal measurement of high power chips
- 2014
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Ingår i: 15th International Conference on Electronic Packaging Technology, ICEPT 2014; Wangjiang HotelChengdu; China; 12 August 2014 through 15 August 2014. - 9781479947072 ; , s. 1507-1511
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Konferensbidrag (refereegranskat)abstract
- In the present paper, a chip with a Pt-based RTD that functions as a heater and sensor is tested under serial power loads, and infrared (IR) thermal imaging system is adopted to obtain the thermal measurement. Comparisons of the hotspot temperatures of the chip obtained by RTD and IR methods have been made, where different surfaces of the chip were observed by the IR camera. Combing with the heat conduction law, the IR results of the test chip with surface preparation showed quite a good agreement with the RTD data, verifying the validation of the IR analysis method.
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