| 1. |
- McKay, James D., et al.
(författare)
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A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
- 2011
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
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| 2. |
- Baquero, María-Rosario, et al.
(författare)
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Polymorphic mutation frequencies in Escherichia coli : emergence of weak mutators in clinical isolates
- 2004
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Ingår i: Journal of Bacteriology. - 0021-9193 .- 1098-5530. ; 186:16, s. 5538-5542
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms in the rifampin resistance mutation frequency (f) were studied in 696 Escherichia coli strains from Spain, Sweden, and Denmark. Of the 696 strains, 23% were weakly hypermutable (4 x 10(-8) < or = f < 4 x 10(-7)), and 0.7% were strongly hypermutable (f > or = 4 x 10(-7)). Weak mutators were apparently more frequent in southern Europe and in blood isolates (38%) than in urinary tract isolates (25%) and feces of healthy volunteers (11%).
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| 3. |
- Behren, Sandra, 1990-
(författare)
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Development and Evaluation of Tools to Explore Posttranslational HexNAc-Tyrosine and Mucin-Type O-Glycosylation
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glycosylation is the most abundant form of post-translational modification (PTM). Recently, O-glycosylation attracted much attention in the glycoproteomic field due to its association with various diseases, such as pathogenic infections and cancer. However, glycoproteomic analysis of O-linked glycosylation is highly challenging due its structural diversity and complexity. New and efficient methods need to be developed to obtain a better understanding of the biological functions of O-glycans. In the presented thesis, glycopeptide microarrays were used as tools to explore the role of mucin type O-glycosylation in cancer, bacterial adhesion processes and galectin recognition on a molecular level, and to get insights into a new group of tyrosine O-glycosylation. A better understanding of these carbohydrate-protein interactions on a molecular level could facilitate the development of glycomimetic inhibitors to fight bacterial infections or block glycan binding proteins involved in cancer progression, or improve the design of novel carbohydrate-based cancer vaccines.In the first part of this work, tools were developed to elucidate the role of a novel group of PTMs, where N-acetylhexosamine (HexNAc = α-GalNAc, α- or β-GlcNAc) was found to modify the hydroxyl group of tyrosine. Synthetic glycopeptides carrying this new modification, as well as glycopeptide microarray libraries were prepared to evaluate the abilities of plant lectins (carbohydrate-binding proteins) to detect HexNAc-O-Tyr modifications. These lectins are commonly used in glycoproteomic work flows to detect and enrich glycopeptides and -proteins. Additionally, HexNAc-O-Tyr-specific rabbit antibodies were raised and immunologically analyzed by enzyme-linked immunosorbent assays, western blot and microarray binding studies.In the second part of the presented thesis, synthetic mucin glycopeptide microarray libraries were prepared and employed to explore carbohydrate-protein interactions of galectins, bacterial lectins and tumor specific antibodies. Mucin glycoproteins are part of the mucus barrier that protects the host against invading pathogens. However, bacteria and viruses have co-evolved with the human host and have developed strategies to promote virulence, for example by adhering to glycans on the host cell-surface. To combat bacterial infections, their virulence and pathogenicity must be understood on a molecular level. In this work, mucin glycopeptides were enzymatically modified with different fucose motifs and used to determine the fine binding specificities of fucose-recognizing lectins LecB from Pseudomonas aeruginosa and the Clostridium difficile toxin A. Furthermore, a synthesis strategy was developed to generate simplified mucin core glycopeptides that could be used as scaffolds to enzymatically generate LacdiNAc modified glycopeptides. They could be used in microarray binding studies to evaluate the glycan binding preferences of various proteins, including the Helicobacter pylori lectin LabA and human galectins, which play roles in cancer development and progression. Aberrant glycosylation of mucin glycoproteins has been associated with various types of cancer. Tumor specific carbohydrate antigens on mucins represent attractive antigenic targets for the development of effective anti-cancer vaccines. In this work, antibodies induced by tumor-associated MUC1 glycopeptide-bacteriophage Qβ vaccine conjugates were immunologically analyzed using MUC1 glycopeptide microarray libraries.
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| 4. |
- Dahl, Åslög, 1955, et al.
(författare)
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The onset, course and intensity of the pollen season
- 2013
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Ingår i: Sofiev, M, Bergman, KC (eds.) 2013: Allergenic Pollen. A review of the production, release, distribution and health impacts. Springer, Dordrecht etc.. - Dordrecht Heidelberg New York London : Springer Science + Business Media. - 9789400748804 ; , s. 29-70
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Bokkapitel (refereegranskat)abstract
- The onset, duration and intensity of the period when pollen is present in the air varies from year to year. Amongst other things, there is an effect upon the quality of life of allergy sufferers. The production and emission of pollens are governed by interacting environmental factors. Any change in these factors may affect the phenology and intensity of the season. Readiness to flower in a plant, and the amount of pollen produced, is the result of conditions during an often long period foregoing flowering. When a plant is ready to flower, temporary ambient circumstances e.g., irradiation and humidity, determine the timing of the actual pollen release. In order to understand variation between years and to be able to safely predict future situations, not least due to the ongoing climate change, it is necessary to know the determinants of all related processes and differences between and within species, here reviewed.
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| 5. |
- de Weger, Letty, et al.
(författare)
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Impact of pollen.
- 2013
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Ingår i: Sofiev, M. and Bergmann, KC: Allergenic Pollen. A review of the production, release, distribution and health impacts.. - Dordrecht Heidelberg New York London : Springer. - 9789400748804 ; , s. 161-215
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Bokkapitel (refereegranskat)abstract
- The impact of pollen on human health is primarily evident in allergic diseases. Sensitized patients can respond to pollen by symptoms of nose, eyes and bronchi. Pollen threshold levels for symptom development vary among the different studies. Factors that influence the threshold level of a pollen species for symptom development are discussed. (i) Differences in response are observed among individual patients, but also among (ii) ethnic populations, (iii) changes in response to pollen concentrations during the pollen season occur, (iv) the amount of allergens carried by the pollen grains can differ in per region, from day to day and from year to year, and finally (v) threshold levels are affected by environmental factors, like weather conditions (temperature, pressure, and storms), and air pollutants. The diversity of factors that influence the health impact of pollen has hampered the definition of a straight forward relationship between pollen and the severity of symptoms. However, within the public, the policymakers and the pharmaceutical industry there is a need for a definition of threshold pollen levels. A first approach to meet this need could be to define preliminary threshold values for different regions, followed by a validation of these preliminary threshold levels with patient symptom scores that can be collected by using new information and communication technology (ICT). Finally, the possible role of pollen in non-allergic diseases is discussed, especially non-allergic respiratory diseases, cardio- and cerebrovascular diseases, and psychiatric diseases, including suicide and suicide attempt.
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| 6. |
- Eguiluz-Gracia, Ibon, et al.
(författare)
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The need for clean air : The way air pollution and climate change affect allergic rhinitis and asthma
- 2020
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 75:9, s. 2170-2184
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Forskningsöversikt (refereegranskat)abstract
- Air pollution and climate change have a significant impact on human health and well-being and contribute to the onset and aggravation of allergic rhinitis and asthma among other chronic respiratory diseases. In Westernized countries, households have experienced a process of increasing insulation and individuals tend to spend most of their time indoors. These sequelae implicate a high exposure to indoor allergens (house dust mites, pets, molds, etc), tobacco smoke, and other pollutants, which have an impact on respiratory health. Outdoor air pollution derived from traffic and other human activities not only has a direct negative effect on human health but also enhances the allergenicity of some plants and contributes to global warming. Climate change modifies the availability and distribution of plant- and fungal-derived allergens and increases the frequency of extreme climate events. This review summarizes the effects of indoor air pollution, outdoor air pollution, and subsequent climate change on asthma and allergic rhinitis in children and adults and addresses the policy adjustments and lifestyle changes required to mitigate their deleterious effects.
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| 7. |
- Galán, Iñaki, et al.
(författare)
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Individual and Contextual Factors Associated With Hazardous Drinking in Spain : Evidence From a National Population-Based Study
- 2020
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Ingår i: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 44:11, s. 2247-2256
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Heavy drinking (HD) and binge drinking (BD) exhibit marked differences in their relationships with contextual-level factors imbedded in geographical areas of residence. The objective is to identify sociodemographic factors, both at the individual and at the contextual level, associated with these 2 main hazardous consumption patterns.METHODS: Cross-sectional study using data from the 2011 to 2012 National Health Survey in Spain. The sample included 21,007 individuals ≥15 years of age. HD was defined as an alcohol intake of ≥40 g/d in men and ≥24 g/d in women. BD was defined as the consumption in the previous month of ≥6 alcoholic drinks (men) or ≥5 drinks (women) within 4 to 6 hours. Individual-level variables included sociodemographic factors, urban/rural residence, smoking, and perceived social support. Contextual-level variables covered percentage of population with no schooling, unemployment rate, and hospitality industry-related economic activity, all at the census tract level. We analyzed data using multilevel logistic regression and calculated areas under the curve (AUC).RESULTS: Being male, smoking, high-income, and low perceived social support were associated with both hazardous drinking patterns. Younger individuals were at higher risk for BD but at lower risk for HD. BD was more common among rural than urban dwellers (odds ratios [OR] = 1.35; 95% CI: 1.05 to 1.72), whereas HD was less likely in participants residing in areas with high unemployment rates (OR = 0.62; 95% CI: 0.41 to 0.93). HD was more likely in census tracts with higher levels of hospitality industry activity (OR = 1.74; 95% CI: 1.20 to 2.54). The AUC increased substantially for both HD and BD when the census tract variable was entered in the respective models (reaching 89.5 and 93.3%, respectively).CONCLUSIONS: Except for age, both drinking patterns have similar associations with individual-level variables but disparate links to contextual-level indicators. In both cases, accounting for area of residence substantially increased the ability to discriminate between high-risk drinkers from nonhazardous alcohol consumers.
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| 8. |
- Galán, Iñaki, et al.
(författare)
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Small area influences on the individual unhealthy lifestyle behaviors : A multilevel analysis of discriminatory accuracy
- 2021
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Ingår i: Health and Place. - : Elsevier BV. - 1353-8292. ; 67
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Tidskriftsartikel (refereegranskat)abstract
- We estimated the discriminatory power of area of residence (census tract) on the prevalence of main risk factors for chronic diseases. Results, based on a sample of 21,007 participants from the 2011–2012 National Health Survey of Spain, show a differential influence of the geosocial environment on the four health risk factors. Accounting for census tracts substantially increases the discriminatory power regarding at-risk alcohol consumption, unbalanced diet, and leisure-time sedentarism but not tobacco consumption. However, the socioeconomic characteristics of the tracts played a minor role. Further research on the specific geosocial contextual variables explaining variability in these risk factors is necessary.
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| 9. |
- Hartley, Philippa, et al.
(författare)
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SKA Science Data Challenge 2: analysis and results
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:2, s. 1967-1993
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Tidskriftsartikel (refereegranskat)abstract
- The Square Kilometre Array Observatory (SKAO) will explore the radio sky to new depths in order to conduct transformational science. SKAO data products made available to astronomers will be correspondingly large and complex, requiring the application of advanced analysis techniques to extract key science findings. To this end, SKAO is conducting a series of Science Data Challenges, each designed to familiarize the scientific community with SKAO data and to drive the development of new analysis techniques. We present the results from Science Data Challenge 2 (SDC2), which invited participants to find and characterize 233 245 neutral hydrogen (H i) sources in a simulated data product representing a 2000 h SKA-Mid spectral line observation from redshifts 0.25-0.5. Through the generous support of eight international supercomputing facilities, participants were able to undertake the Challenge using dedicated computational resources. Alongside the main challenge, 'reproducibility awards' were made in recognition of those pipelines which demonstrated Open Science best practice. The Challenge saw over 100 participants develop a range of new and existing techniques, with results that highlight the strengths of multidisciplinary and collaborative effort. The winning strategy - which combined predictions from two independent machine learning techniques to yield a 20 per cent improvement in overall performance - underscores one of the main Challenge outcomes: that of method complementarity. It is likely that the combination of methods in a so-called ensemble approach will be key to exploiting very large astronomical data sets.
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| 10. |
- Lopez-Vilchez, Irene, et al.
(författare)
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Redistribution and Hemostatic Action of Recombinant Activated Factor VII Associated with Platelets
- 2011
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 178:6, s. 2938-2948
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Tidskriftsartikel (refereegranskat)abstract
- Clinical evidence accumulated from hemophilic patients during prophylaxis with recombinant activated factor VII (rFVIIa) suggests that the duration of the hemostatic action of rFVIIa exceeds its predicted plasma half-life. Mechanisms involved in this outcome have not been elucidated. We have investigated in vitro the redistribution of rFVIIa in platelets from healthy donors, patients with FVII deficiency, and one patient with Bernard-Soulier syndrome. Platelet-rich plasma was exposed to rFVIla (3 to 60 mu g/mL). Flow cytometry, inununocytochemistry, and coagulation tests were applied to detect and quantify rFVila. The hemostatic effect of rFV1Ia associated to platelets was evaluated using perfusion models. Our studies revealed a dose-dependent association of rFVIla to the platelet cytoplasm with redistribution into the open canalicular system, and a granules. Mechanisms implicated in the internalization are multiple, involve GPIb and GPIV, and require phospholipids and cytoskeletal assembly. After platelet activation with thrombin, platelets exposed rFVIla on their membrane. Perfusion studies revealed that the presence of 30% of platelets containing FVIIa improved platelet aggregate formation and enhanced fibrin generation (P < 0.01 versus control). Our results indicate that, at therapeutic concentrations, rFVIIa can be internalized into platelets, where it is protected from physiological clearance mechanisms and can still promote hemostatic activity. Redistribution of rFVIIa into platelets may explain the prolonged prophylactic effectiveness of rFYlla in hemophilia. (AmJ Pathol 2011, 178:2938-294% DOI: 10.1016/j.ajpath.2011.02.026)
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