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  • 1
    Online Resource
    Online Resource
    Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 36 ( 2023-09-05)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 36 ( 2023-09-05)
    Abstract: Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2302720120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 1 ( 2021-01-05)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 1 ( 2021-01-05)
    Abstract: Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies ( n NationMS = 946, n BIONAT = 990). Additionally, effect-modification by medication and photosensitivity-associated MC1R variants was assessed. High serum vitD was associated with a reduced MS severity score (MSSS), reduced risk for relapses, and lower disability accumulation over time. Low latitude was associated with higher vitD, lower MSSS, fewer gadolinium-enhancing lesions, and lower disability accumulation. The association of latitude with disability was lacking in IFN-β–treated patients. In carriers of MC1R :rs1805008(T), who reported increased sensitivity toward sunlight, lower latitude was associated with higher MRI activity, whereas for noncarriers there was less MRI activity at lower latitudes. In a further exploratory approach, the effect of ultraviolet (UV)-phototherapy on the transcriptome of immune cells of MS patients was assessed using samples from an earlier study. Phototherapy induced a vitD and type I IFN signature that was most apparent in monocytes but that could also be detected in B and T cells. In summary, our study suggests beneficial effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD, and disease severity. However, sun exposure might be detrimental for photosensitive patients. Furthermore, a direct induction of type I IFNs through sun exposure could be another mechanism of UV-mediated immune-modulation in MS.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2018457118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
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  • 3
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    Online Resource
    The Bicultural Phenomenon : The Interplay of Group Prototypicality and Cultural Identity Switching
    Hogrefe Publishing Group ; 2016
    In:  Social Psychology Vol. 47, No. 5 ( 2016-09), p. 233-243
    Details
    In: Social Psychology, Hogrefe Publishing Group, Vol. 47, No. 5 ( 2016-09), p. 233-243
    Abstract: Abstract. Cross-cultural research has indicated that bicultural individuals switch their behavioral patterns according to situational cultural frames. Based on self-categorization theory and evidence that being prototypical for an ingroup can increase ingroup identification, we investigated the idea that when being prototypical for a specific culture, bicultural individuals switch their cultural identification toward the culture for which they are prototypical. According to previous findings, we additionally investigated the moderating role of perceived cultural compatibility. In this study, we manipulated cultural group prototypicality by giving immigrant Polish-German participants test performance feedback. As hypothesized, participants either showed increased identification with the German culture when the feedback rendered them prototypically German, or with the Polish culture when the feedback rendered them prototypically Polish. This effect was moderated by perceived cultural compatibility. Implications for a self-enhancement motive are discussed.
    Type of Medium: Online Resource
    ISSN: 1864-9335 , 2151-2590
    URL: Article
    DOI: 10.1027/1864-9335/a000276
    Language: English
    Publisher: Hogrefe Publishing Group
    Publication Date: 2016
    detail.hit.zdb_id: 2404430-1
    detail.hit.zdb_id: 2404438-6
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    SSG: 5,2
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  • 4
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    A mechanistic classification of clinical phenotypes in neuroblastoma
    American Association for the Advancement of Science (AAAS) ; 2018
    In:  Science Vol. 362, No. 6419 ( 2018-12-07), p. 1165-1170
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 362, No. 6419 ( 2018-12-07), p. 1165-1170
    Abstract: Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Its clinical course ranges from spontaneous tumor regression to fatal progression. To investigate the molecular features of the divergent tumor subtypes, we performed genome sequencing on 416 pretreatment neuroblastomas and assessed telomere maintenance mechanisms in 208 of these tumors. We found that patients whose tumors lacked telomere maintenance mechanisms had an excellent prognosis, whereas the prognosis of patients whose tumors harbored telomere maintenance mechanisms was substantially worse. Survival rates were lowest for neuroblastoma patients whose tumors harbored telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations. Spontaneous tumor regression occurred both in the presence and absence of these mutations in patients with telomere maintenance–negative tumors. On the basis of these data, we propose a mechanistic classification of neuroblastoma that may benefit the clinical management of patients.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aat6768
    RVK:
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2018
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  • 5
    Online Resource
    Online Resource
    “I Don’t Know Anything About Soccer” : How Personal Weaknesses and Strengths Guide Inferences About Women’s Qualification in Sex-Typed Jobs
    Hogrefe Publishing Group ; 2011
    In:  Swiss Journal of Psychology Vol. 70, No. 3 ( 2011-01), p. 149-154
    Details
    In: Swiss Journal of Psychology, Hogrefe Publishing Group, Vol. 70, No. 3 ( 2011-01), p. 149-154
    Abstract: A great deal of research has been dedicated to the difficulties women face in business management domains because they lack the required “masculinity” in terms of masculine skills and traits. Previous work has shown that when males are judged, failures in typical feminine tasks can signal high masculinity and can therefore become an asset in terms of attributed occupational success in a typical masculine job (i.e., manager position). However, jobs at lower levels of organizational hierarchies differ in their trait requirements, with some jobs requiring mostly typical feminine traits and others mostly typical masculine traits. The present study therefore tested and found support for the hypothesis that personal weaknesses and strengths in a feminine or masculine domain guide recruiters’ inferences about a candidate’s gender prototypicality. These inferences, in turn, predict job-suitability ratings for sex-typed jobs. It is shown that for women, too, stating weaknesses can sometimes be more advantageous than stating strengths.
    Type of Medium: Online Resource
    ISSN: 1421-0185 , 1662-0879
    URL: Article
    DOI: 10.1024/1421-0185/a000050
    RVK:
    CL 1000
    Language: English
    Publisher: Hogrefe Publishing Group
    Publication Date: 2011
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    SSG: 5,2
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  • 6
    Online Resource
    Online Resource
    Prediction of flow induced noise in rotating devices using nonmatching grids
    Acoustical Society of America (ASA) ; 2008
    In:  The Journal of the Acoustical Society of America Vol. 123, No. 5_Supplement ( 2008-05-01), p. 3538-3538
    Details
    In: The Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 123, No. 5_Supplement ( 2008-05-01), p. 3538-3538
    Abstract: With increasing number of electrical devices, e.g. air conditioning systems, used in homes and offices, noise pollution is becoming a more and more relevant topic. A large amount of this noise is generated by turbulent flows and laminar flows at leading and trailing edges, where mainly tonal noise is generated. The objective of our contribution is to investigate shape optimizations of rotating devices in order to reduce their noise levels. For this purpose, we conduct a simulation of the turbulent flow in a ventilator. The acoustic source terms are obtained from the fluid dynamics solution by using Lighthill's acoustic analogy. The acoustic domain is decomposed into a rotating part and a fixed part. The coupling between these two parts is enforced at their interface by a mortar finite element method, which uses Lagrange multipliers in order to ''glue'' the geometrically independent parts together. The mortar method takes into account the movement of the rotating part through a moving nonmatching grid, that is recomputed at each time step.
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
    URL: Article
    DOI: 10.1121/1.2934515
    RVK:
    EQ 1000
    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 2008
    detail.hit.zdb_id: 1461063-2
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  • 7
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    Online Resource
    Chiroptera-inspired robotic cephaloid (CIRCE): A next generation biomimetic sonar head
    Acoustical Society of America (ASA) ; 2002
    In:  The Journal of the Acoustical Society of America Vol. 112, No. 5_Supplement ( 2002-11-01), p. 2335-2335
    Details
    In: The Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 112, No. 5_Supplement ( 2002-11-01), p. 2335-2335
    Abstract: The dynamic interplay between signal processing in the acoustic and neural domain renders the biosonar system of bats, a prime example of intelligent, integrated systems in biology. Previous attempts at technical reproductions of this system have studied a few functional aspects but did not produce convincing replicas of the integrated system. In particular, none of them could provide for beamforming pinnae, ear mobility, signal bandwidth and an adequate number of elements in the primary signal representation at the scale of the biological paragon. The CIRCE (http://www.circe-project.org) project brings together a multidisciplinary consortium with all competences necessary for addressing these aspects in conjunction. Well-integrated solutions to the following technological key challenges are therefore sought: (a) Evolution of pinna shapes to optimize performance in natural biosonar tasks. (b) Adaptation of state-of-the-art ultrasonic transducer technology for matching bats in terms of bandwidth and sound pressure level/sensitivity. (c) Actuation of mobile pinnae (including the possibility of nonrigid transformations) within the scale constraints of a bat’s head. (d) Custom-designed DSP hardware providing a qualitative and quantitative reproduction of the neural signal representation at the level of the auditory nerve. [Work supported by the European Commission, LPS Initiative.]
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
    URL: Article
    DOI: 10.1121/1.4779429
    RVK:
    EQ 1000
    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 2002
    detail.hit.zdb_id: 1461063-2
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  • 8
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    Online Resource
    Despite high objective numeracy, lower numeric confidence relates to worse financial and medical outcomes
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 39 ( 2019-09-24), p. 19386-19391
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 39 ( 2019-09-24), p. 19386-19391
    Abstract: People often laugh about being “no good at math.” Unrecognized, however, is that about one-third of American adults are likely too innumerate to operate effectively in financial and health environments. Two numeric competencies conceivably matter—objective numeracy (ability to “run the numbers” correctly; like literacy but with numbers) and numeric self-efficacy (confidence that provides engagement and persistence in numeric tasks). We reasoned, however, that attaining objective numeracy’s benefits should depend on numeric confidence. Specifically, among the more objectively numerate, having more numeric confidence (vs. less) should lead to better outcomes because they persist in numeric tasks and have the skills to support numeric success. Among the less objectively numerate, however, having more (vs. less) numeric confidence should hurt outcomes, as they also persist, but make unrecognized mistakes. Two studies were designed to test the generalizability of this hypothesized interaction. We report secondary analysis of financial outcomes in a diverse US dataset and primary analysis of disease activity among systemic lupus erythematosus patients. In both domains, best outcomes appeared to require numeric calculation skills and the persistence of numeric confidence. “Mismatched” individuals (high ability/low confidence or low ability/high confidence) experienced the worst outcomes. For example, among the most numerate patients, only 7% of the more numerically confident had predicted disease activity indicative of needing further treatment compared with 31% of high-numeracy/low-confidence patients and 44% of low-numeracy/high-confidence patients. Our work underscores that having 1 of these competencies (objective numeracy or numeric self-efficacy) does not guarantee superior outcomes.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1903126116
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
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  • 9
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    A Household Study of Self-Regulation in Children : Intergenerational Links and Maternal Antecedents
    Hogrefe Publishing Group ; 2012
    In:  Swiss Journal of Psychology Vol. 71, No. 4 ( 2012-10), p. 215-226
    Details
    In: Swiss Journal of Psychology, Hogrefe Publishing Group, Vol. 71, No. 4 ( 2012-10), p. 215-226
    Abstract: Delay of gratification (DoG) and delay discounting (DD) are behavioral measures of self-regulation and impulsivity. Whereas DoG refers to the postponement of gratification, DD involves the devaluation of a reward over time. Previous studies have demonstrated associations between paternal self-control, paternal personality traits, parenting styles, maternal intelligence, and children’s self-regulation. The present study explored intergenerational links between mothers’ and child’s self-regulation and maternal antecedents of children’s DoG. We analyzed 267 mother-child dyads in the German Socio-Economic Panel (SOEP) Children’s Study. Measures included an experiment using gummy bears as rewards to assess DoG in children and monetary choice procedures to assess DD in mothers. Additionally, cognitive abilities and personality traits of mothers and children were assessed. The main result was that the children’s age and breastfeeding were significant predictors of DoG in children, even when we controlled for other influences such as maternal cognitive abilities and personality traits. We explain the result in the context of previous findings concerning attachment security, bonding, maternal sensitivity, children’s self-regulation of energy intake, neuroscientific evidence, and breastfeeding. Further studies should use equivalent measures of DoG in children and parents to further explore this link between breastfeeding and DoG in a genetically sensitive design.
    Type of Medium: Online Resource
    ISSN: 1421-0185 , 1662-0879
    URL: Article
    DOI: 10.1024/1421-0185/a000090
    RVK:
    CL 1000
    Language: German
    Publisher: Hogrefe Publishing Group
    Publication Date: 2012
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    SSG: 2,1
    SSG: 5,2
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  • 10
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    HSPC117 Is the Essential Subunit of a Human tRNA Splicing Ligase Complex
    American Association for the Advancement of Science (AAAS) ; 2011
    In:  Science Vol. 331, No. 6018 ( 2011-02-11), p. 760-764
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 331, No. 6018 ( 2011-02-11), p. 760-764
    Abstract: Splicing of mammalian precursor transfer RNA (tRNA) molecules involves two enzymatic steps. First, intron removal by the tRNA splicing endonuclease generates separate 5′ and 3′ exons. In animals, the second step predominantly entails direct exon ligation by an elusive RNA ligase. Using activity-guided purification of tRNA ligase from HeLa cell extracts, we identified HSPC117, a member of the UPF0027 (RtcB) family, as the essential subunit of a tRNA ligase complex. RNA interference–mediated depletion of HSPC117 inhibited maturation of intron-containing pre-tRNA both in vitro and in living cells. The high sequence conservation of HSPC117/RtcB proteins is suggestive of RNA ligase roles of this protein family in various organisms.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1197847
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2011
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    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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