| 1. |
- Aktaş, Vezir, et al.
(författare)
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Saldırgan Olan ve Olmayan Çocuklarda Düşmanca Niyet Yükleme Yanlılığının Cinsiyete Bağlı Olarak İncelenmesi (Hostile attributional bias in aggressive and nonaggressive children)
- 2005
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Ingår i: Türk Psikoloji Dergisi (Turkish Journal of Psychology). - 1300-4433. ; 20:55, s. 43-59
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Tidskriftsartikel (refereegranskat)abstract
- Bu çalışmada olumsuz niyet yükleme eğiliminin çocukların sosyal ilişkilerinde saldırgan olup olmamalarına ve cinsiyetlerine göre değişip değişmediği incelenmiştir. Ayrıca, bu çalışmada fiziksel, pasif ve sözel saldırganlık türlerinde düşmanca yüklemede bulunma açısından saldırganlık düzeyi ve cinsiyete göre bir farklılık gözlenip gözlenmeyeceği de araştırılmıştır. Bu amaçla, ilköğretim 5. sınıfta okuyan 236 kız ve 293 erkek öğrenciye sosyometrik bir saldırganlık ölçeği ve 11 resimden oluşan bir resim anketi uygulanmıştır. Verilere 2 (saldırganlık düzeyi: saldırgan-saldırgan değil) x 2 (cinsiyet: kız-erkek) faktörlü araştırma desenine uygun varyans analizleri uygulanmıştır. Bulgular, sosyal ilişkileri açısından saldırgan olarak tanınan çocukların olumsuz tepkileri içeren davranış seçeneklerini (kişisel nedenlere ve olumsuz niyete yapılan yüklemeler) saldırgan olmayan çocuklara kıyasla daha fazla seçtiklerini göstermiştir. Bu bulgu daha önce yapılan çalışmalardan elde edilen bulgularla da uyuşmaktadır. Saldırganlığın alt boyutları açısından bakıldığında ise sadece fiziksel saldırganlık gösteren çocuklar, fiziksel saldırganlık göstermeyen çocuklara kıyasla daha fazla olumsuz yüklemelerde bulunmuşlardır. Dolayısıyla bu çalışmada aktif yönelimli saldırganlığın da tepkisel saldırganlık gibi düşmanca yükleme yanlılığıyla ilişkili olabileceği yönünde bir bulgu elde edilmiştir. Araştırmada düşmanca niyet yükleme eğiliminde cinsiyet temel etkisi de gözlenmiştir. Sosyal ilişkileri açısından genel olarak saldırgan tanınan erkekler, saldırgan tanınan kızlardan daha fazla düşmanca niyet yüklemesinde bulunma eğilimi göstermişlerdir.
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| 2. |
- Brautigam, Lars, et al.
(författare)
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Glutaredoxin regulates vascular development by reversible glutathionylation of sirtuin 1
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:50, s. 20057-20062
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Tidskriftsartikel (refereegranskat)abstract
- Embryonic development depends on complex and precisely orchestrated signaling pathways including specific reduction/oxidation cascades. Oxidoreductases of the thioredoxin family are key players conveying redox signals through reversible posttranslational modifications of protein thiols. The importance of this protein family during embryogenesis has recently been exemplified for glutaredoxin 2, a vertebrate-specific glutathione-disulfide oxidoreductase with a critical role for embryonic brain development. Here, we discovered an essential function of glutaredoxin 2 during vascular development. Confocal microscopy and time-lapse studies based on two-photon microscopy revealed that morpholino-based knockdown of glutaredoxin 2 in zebrafish, a model organism to study vertebrate embryogenesis, resulted in a delayed and disordered blood vessel network. We were able to show that formation of a functional vascular system requires glutaredoxin 2-dependent reversible S-glutathionylation of the NAD(+)-dependent protein deacetylase sirtuin 1. Using mass spectrometry, we identified a cysteine residue in the conserved catalytic region of sirtuin 1 as target for glutaredoxin 2-specific deglutathionylation. Thereby, glutaredoxin 2-mediated redox regulation controls enzymatic activity of sirtuin 1, a mechanism we found to be conserved between zebrafish and humans. These results link S-glutathionylation to vertebrate development and successful embryonic angiogenesis.
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| 3. |
- Gómez-Fernández, Paloma, et al.
(författare)
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The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis
- 2020
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The IL22RA2 locus is associated with risk for multiple sclerosis (MS) but causative variants are yet to be determined. In a single nucleotide polymorphism (SNP) screen of this locus in a Basque population, rs28385692, a rare coding variant substituting Leu for Pro at position 16 emerged significantly (p = 0.02). This variant is located in the signal peptide (SP) shared by the three secreted protein isoforms produced by IL22RA2 (IL-22 binding protein-1(IL-22BPi1), IL-22BPi2 and IL-22BPi3). Genotyping was extended to a Europe-wide case-control dataset and yielded high significance in the full dataset (p = 3.17 × 10-4). Importantly, logistic regression analyses conditioning on the main known MS-associated SNP at this locus, rs17066096, revealed that this association was independent from the primary association signal in the full case-control dataset. In silico analysis predicted both disruption of the alpha helix of the H-region of the SP and decreased hydrophobicity of this region, ultimately affecting the SP cleavage site. We tested the effect of the p.Leu16Pro variant on the secretion of IL-22BPi1, IL-22BPi2 and IL-22BPi3 and observed that the Pro16 risk allele significantly lowers secretion levels of each of the isoforms to around 50%-60% in comparison to the Leu16 reference allele. Thus, our study suggests that genetically coded decreased levels of IL-22BP isoforms are associated with augmented risk for MS.
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| 4. |
- Jensen, Poul Erik H., et al.
(författare)
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Detection and kinetics of persistent neutralizing anti-interferon-beta antibodies in patients with multiple sclerosis : Results from the ABIRISK prospective cohort study
- 2019
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Ingår i: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 326, s. 19-27
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Tidskriftsartikel (refereegranskat)abstract
- Two validated assays, a bridging ELISA and a luciferase-based bioassay, were compared for detection of anti-drug antibodies (ADA) against interferon-beta (IFN-β) in patients with multiple sclerosis. Serum samples were tested from patients enrolled in a prospective study of 18 months. In contrast to the ELISA, when IFN-β-specific rabbit polyclonal and human monoclonal antibodies were tested, the bioassay was the more sensitive to detect IFN-β ADA in patients' sera. For clinical samples, selection of method of ELISA should be evaluated prior to the use of a multi-tiered approach. A titer threshold value is reported that may be used as a predictor for persistently positive neutralizing ADA.
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| 5. |
- Lill, Christina M., et al.
(författare)
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Closing the case of APOE in multiple sclerosis : no association with disease risk in over 29 000 subjects
- 2012
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 49:9, s. 558-562
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Tidskriftsartikel (refereegranskat)abstract
- Background Single nucleotide polymorphisms (SNPs) rs429358 (ε4) and rs7412 (ε2), both invoking changes in the amino-acid sequence of the apolipoprotein E (APOE) gene, have previously been tested for association with multiple sclerosis (MS) risk. However, none of these studies was sufficiently powered to detect modest effect sizes at acceptable type-I error rates. As both SNPs are only imperfectly captured on commonly used microarray genotyping platforms, their evaluation in the context of genome-wide association studies has been hindered until recently.Methods We genotyped 12 740 subjects hitherto not studied for their APOE status, imputed raw genotype data from 8739 subjects from five independent genome-wide association studies datasets using the most recent high-resolution reference panels, and extracted genotype data for 8265 subjects from previous candidate gene assessments.Results Despite sufficient power to detect associations at genome-wide significance thresholds across a range of ORs, our analyses did not support a role of rs429358 or rs7412 on MS susceptibility. This included meta-analyses of the combined data across 13 913 MS cases and 15 831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412, respectively).Conclusion Given the large sample size of our analyses, it is unlikely that the two APOE missense SNPs studied here exert any relevant effects on MS susceptibility.
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