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| 6. |
- Weiner, D. J., et al.
(author)
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Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
- 2017
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:7
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Journal article (peer-reviewed)abstract
- Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
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| 7. |
- Anney, R. J. L., et al.
(author)
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Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia
- 2017
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In: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
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Journal article (peer-reviewed)abstract
- Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) < 1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P= 9 x10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental- related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
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| 9. |
- Das, A., et al.
(author)
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Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency
- 2022
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28:1, s. 125-135
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Journal article (peer-reviewed)abstract
- Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion–deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10–100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in ‘immunologically cold’ tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy. © 2022, The Author(s).
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| 10. |
- Anderson, Cynthia M., et al.
(author)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 December 2009-31 January 2010
- 2010
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:3, s. 576-579
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Journal article (peer-reviewed)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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| 11. |
- Lukasik, J., et al.
(author)
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Discriminant analysis and secondary-beam charge recognition
- 2008
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 587:2-3, s. 413-419
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Journal article (peer-reviewed)abstract
- The discriminant-analysis method has been applied to optimize the exotic-beam charge recognition in a projectile fragmentation experiment. The experiment was carried out at the GSI using the fragment separator (FRS) to produce and select the relativistic secondary beams, and the ALADIN setup to measure their fragmentation products following collisions with Sn target nuclei. The beams of neutron poor isotopes around La-124 and Sn-107 were selected to study the isospin dependence of the limiting temperature of heavy nuclei by comparing with results for stable Sn-124 projectiles. A dedicated detector to measure the projectile charge upstream of the reaction target was not used, and alternative methods had to be developed. The presented method, based on the multivariate discriminant analysis, allowed to increase the efficacy of charge recognition up to about 90%, which was about 20% more than achieved with the simple scalar methods.
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| 12. |
- Pawlowski, P., et al.
(author)
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Neutron recognition in the LAND detector for large neutron multiplicity
- 2012
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 694, s. 47-54
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Journal article (peer-reviewed)abstract
- The performance of the LAND neutron detector is studied. Using an event-mixing technique based on one-neutron data obtained in the S107 experiment at the GSI laboratory, we test the efficiency of various analytic tools used to determine the multiplicity and kinematic properties of detected neutrons. A new algorithm developed recently for recognizing neutron showers from spectator decays in the ALADIN experiment S254 is described in detail. Its performance is assessed in comparison with other methods. The properties of the observed neutron events are used to estimate the detection efficiency of LAND in this experiment. (C) 2012 Elsevier B.V. All rights reserved.
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| 13. |
- Trautmann, W., et al.
(author)
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Isotopic dependence of the caloric curve
- 2009
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In: Progress in Particle and Nuclear Physics. - : Elsevier BV. - 0146-6410. ; 62:2, s. 407-412
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Journal article (peer-reviewed)abstract
- Isotopic effects in projectile fragmentation at relativistic energies have been studied with the ALADIN forward spectrometer at SIS. Stable and radioactive Sn and La beams with an incident energy of 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. Chemical freeze-out temperatures are found to be nearly invariant with respect to the A/Z ratio of the produced spectator sources, consistent with predictions for expanded systems. Consequences for the proposed interpretation of chemical breakup temperatures as representing the limiting temperatures predicted by microscopic models are discussed. (C) 2009 Elsevier B.V. All rights reserved.
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| 14. |
- Fung, X. C. C., et al.
(author)
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Psychosocial Variables Related to Weight-Related Self-Stigma in Physical Activity among Young Adults across Weight Status
- 2020
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:1
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Journal article (peer-reviewed)abstract
- A healthy lifestyle with sufficient physical activity (PA) can contribute to weight management. Yet, many people do not maintain a healthy lifestyle. To explain PA, we propose a model that incorporates the Theory of Planned Behavior (TPB) with weight-related self-stigma. We recruited 325 young adults to complete questionnaires regarding their physical activities, weight-related self-stigma, and TPB factors. We used structural equation modeling to examine the model fit and the path invariance across weight groups. The model showed excellent model fit, but path invariance was not supported. Weight-related self-stigma significantly explained the perceived behavioral control, behavioral intention, and engagement of PA. People without overweight and people with overweight have different considerations for PA. Weight-related self-stigma is important for PA as well. To promote a healthy lifestyle, healthcare providers should provide different suggestions or interventions that suit their patients' weight-related concerns.
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| 15. |
- Retherford, K. D., et al.
(author)
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Io's Atmosphere Silhouetted by Jupiter Ly alpha
- 2019
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In: Astronomical Journal. - : IOP PUBLISHING LTD. - 0004-6256 .- 1538-3881. ; 158:4
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Journal article (peer-reviewed)abstract
- We report results from a new technique for mapping Io's SO2 vapor distribution. The Space Telescope Imaging Spectrograph (STIS) instrument on the Hubble Space Telescope observed Io during four Jupiter transit events to obtain medium resolution far-UV spectral images near the Ly alpha wavelength of 121.6 nm. Jupiter's bright Ly alpha dayglow provides a bright, mostly uniform background light source for opacity measurements, much like during a stellar occultation or transiting exoplanet event. Peaks in the photoabsorption cross-sections for sulfur dioxide occur near 122 nm, with resulting absorptions raising the altitude where a tangential line-of-sight opacity of similar to 1 occurs. This method of measuring column densities along lines of sight above the limb uses detailed image simulations and complements Ly alpha reflectance imaging and other methods for measuring Io's SO2 gas on the disk. Our reported near-terminator limb observations with STIS confirm the findings from previous Ly alpha disk reflectance imaging that Io's polar SO2 density is an order of magnitude lower than found at the equator. We provide constraints for additional attenuation by atmospheric hydrogen atoms produced by charge exchange reactions between magnetospheric protons and Io's atmosphere. Searches for plume-related features provided no definitive enhancements within the signal quality, ruling out unusually high levels of activity for Pele and Tvashtar.
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| 16. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 18. |
- Andersen, M. R., et al.
(author)
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Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88
- 2011
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In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 21:6, s. 885-897
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Journal article (peer-reviewed)abstract
- The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook wholegenome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi
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| 19. |
- Bolan, Nanthi, et al.
(author)
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Remediation of poly- and perfluoroalkyl substances (PFAS) contaminated soils : To mobilize or to immobilize or to degrade?
- 2021
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In: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 401
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Journal article (peer-reviewed)abstract
- Poly- and perfluoroalkyl substances (PFASs) are synthetic chemicals, which are introduced to the environment through anthropogenic activities. Aqueous film forming foam used in firefighting, wastewater effluent, landfill leachate, and biosolids are major sources of PFAS input to soil and groundwater. Remediation of PFAS contaminated solid and aqueous media is challenging, which is attributed to the chemical and thermal stability of PFAS and the complexity of PFAS mixtures. In this review, remediation of PFAS contaminated soils through manipulation of their bioavailability and destruction is presented. While the mobilizing amendments (e.g., surfactants) enhance the mobility and bioavailability of PFAS, the immobilizing amendments (e.g., activated carbon) decrease their bioavailability and mobility. Mobilizing amendments can be applied to facilitate the removal of PFAS though soil washing, phytoremediation, and complete destruction through thermal and chemical redox reactions. Immobilizing amendments are likely to reduce the transfer of PFAS to food chain through plant and biota (e.g., earthworm) uptake, and leaching to potable water sources. Future studies should focus on quantifying the potential leaching of the mobilized PFAS in the absence of removal by plant and biota uptake or soil washing, and regular monitoring of the long-term stability of the immobilized PFAS.
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| 21. |
- Klug, Stefanie J, et al.
(author)
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TP53 codon 72 polymorphism and cervical cancer : a pooled analysis of individual data from 49 studies
- 2009
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In: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 10:8, s. 772-784
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Journal article (peer-reviewed)abstract
- BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes). INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies.
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| 22. |
- Pakpour, Amir H., et al.
(author)
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Psychometric properties and measurement invariance of the Weight Self-Stigma Questionnaire and Weight Bias Internalization Scale in children and adolescents
- 2019
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In: International Journal of Clinical and Health Psychology. - : Elsevier. - 1697-2600 .- 2174-0852. ; 19:2, s. 150-159
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Journal article (peer-reviewed)abstract
- Background/Objective: Given the negative consequences of weight bias, including internalized weight stigma, on health outcomes, two instruments—the Weight Self-Stigma Questionnaire (WSSQ) and Weight Bias Internalization Scale (WBIS)—have been developed. However, their psychometric properties are yet to be tested for Asian pediatric populations.Method: Participants aged 8 to 12 years (N = 287; 153 boys) completed the WSSQ and the WBIS, and they were classified into either a group with overweight or a group without overweight based on self-reported weight and height.Results: Both WSSQ and WBIS had their factor structures supported by confirmatory factor analyses (CFAs). The measurement invariance of two-factor structure was further supported for WSSQ across gender and weight status. The measurement invariance of single-factor structure was supported for WBIS across gender but not across weight status.Conclusions: WSSQ and WBIS were both valid to assess the internalization of weight bias. However, the two instruments demonstrated different properties and should be applied in different situations.
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| 25. |
- Alimoradi, Z., et al.
(author)
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Is alexithymia associated with sleep problems? : A systematic review and meta-analysis
- 2022
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In: Neuroscience and Biobehavioral Reviews. - : Elsevier. - 0149-7634 .- 1873-7528. ; 133
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Journal article (peer-reviewed)abstract
- Alexithymia, a difficulty identifying and expressing emotions experienced by oneself or others, measurably harms quality of sleep. Research has observed the association between alexithymia and sleep problems; however, the cumulative effect of this association is still unknown. Therefore, this systematic review and meta-analysis was conducted to present scientific evidence regarding the relationship between alexithymia and sleep quality. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, and using relevant keywords, we searched six databases: Scopus, PubMed Central, ProQuest, ISI Web of Knowledge, EMBASE, and Science Direct. We selected observational studies on the association between alexithymia and sleep. We conducted meta-analysis using a random-effect model to calculate the effect size (ES) with Fisher's z transformation. Eligible studies (N = 26) in 24 papers included 7546 participants from 12 countries. The entire ES for the association between alexithymia and sleep was 0.44 (95 % CI: 0.31, 0.56). Additionally, patient populations had a larger ES (ES = 0.55; 95 % CI: 0.30, 0.79) than healthy populations (ES = 0.30; 95 % CI: 0.20, 0.41). The results of the present systematic review and meta-analysis revealed a significant association between alexithymia and sleep problems, especially among people with any medical condition.
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