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41.
Katja Apelt Susan M. White Hyun Suk Kim Jung-Eun Yeo Angela Kragten Annelotte P. Wondergem Martin A. Rooimans Romn Gonzlez-Prieto Wouter W. Wiegant Sebastian Lunke Daniel Flanagan Sarah Pantaleo Catherine Quinlan Winita Hardikar Haico van Attikum Alfred C.O. Vertegaal Brian T. Wilson Rob M.F. Wolthuis Orlando D. Schrer Martijn S. Luijsterburg 《The Journal of experimental medicine》2021,218(3)
ERCC1-XPF is a multifunctional endonuclease involved in nucleotide excision repair (NER), interstrand cross-link (ICL) repair, and DNA double-strand break (DSB) repair. Only two patients with bi-allelic ERCC1 mutations have been reported, both of whom had features of Cockayne syndrome and died in infancy. Here, we describe two siblings with bi-allelic ERCC1 mutations in their teenage years. Genomic sequencing identified a deletion and a missense variant (R156W) within ERCC1 that disrupts a salt bridge below the XPA-binding pocket. Patient-derived fibroblasts and knock-in epithelial cells carrying the R156W substitution show dramatically reduced protein levels of ERCC1 and XPF. Moreover, mutant ERCC1 weakly interacts with NER and ICL repair proteins, resulting in diminished recruitment to DNA damage. Consequently, patient cells show strongly reduced NER activity and increased chromosome breakage induced by DNA cross-linkers, while DSB repair was relatively normal. We report a new case of ERCC1 deficiency that severely affects NER and considerably impacts ICL repair, which together result in a unique phenotype combining short stature, photosensitivity, and progressive liver and kidney dysfunction. 相似文献
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Katja Pavšič Andrej Fabjan Vid Zgonc Katarina Šurlan Popović Janja Pretnar Oblak Fajko F. Bajrović 《Journal of stroke and cerebrovascular diseases》2021,30(9):105947
BackgroundThe prognosis for unilateral lateral medullary infarction (ULMI) is generally good but may be aggravated by respiratory failure with fatal outcome. Respiratory failure has been reported in patients with severe bulbar dysfunction and large rostral medullary lesions, but its associated factors have not been systematically studied. We aimed to assess clinical and radiological characteristics associated with respiratory failure in patients with pure acute ULMI.Materials and MethodsSeventy-one patients (median age 55 years, 59 males) with MRI-confirmed acute pure ULMI were studied retrospectively. Clinical characteristics were assessed and bulbar symptoms were scored using a scale developed for this study. MRI lesions were classified into 4 groups based on their vertical extent (localized/extensive) and the involvement of the open and/or closed medulla. Clinical characteristics, bulbar scores and MRI lesion characteristics were compared between patients with and without respiratory failure.ResultsRespiratory failure occurred in 8(11%) patients. All patients with respiratory failure were male (p = 0.336), had extensive lesions involving the open medulla (p = 0.061), progression of bulbar symptoms (p=0.002) and aspiration pneumonia (p < 0.001). Peak bulbar score (OR, 7.9 [95% CI, 2.3–160.0]; p < 0.001) and older age (OR, 1.2 [95%CI, 1.0-1.6]; p=0.006) were independently associated with respiratory failure.ConclusionsExtensive damage involving the open/rostral medulla, clinically presenting with severe bulbar dysfunction, in conjunction with factors such as aspiration pneumonia and older age appears to be crucial for the development of respiratory failure in pure ULMI. Further prospective studies are needed to identify other potential risk factors, pathophysiology, and effective preventive measures for respiratory failure in these patients. 相似文献
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Linking Penetrance and Transcription in DYT-THAP1: Insights From a Human iPSC-Derived Cortical Model
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ABSTRACTBackground: Attachment Theory has become one of the leading theories in human development. Nonetheless, empirical studies focusing on how attachment unfolds during adolescence are still scarce particularly in Spain, due to the lack of adequate measures. Objective: This study aims to validate the Important People Interview (IPI) in a shorter questionnaire version (Important People- Questionnaire; IP-Q); to analyse the changes in different affiliative bonds to multiple figures -family, peers, romantic partners – over the course of adolescence; and to identify boys’ and girls’ hierarchical ordering of their specific attachment bonds. Method: 1025 Spanish adolescents, aged 12–17 years old completed the IP-Q. Results: The results showed that the IP-Q has convergent and divergent validity. Moreover, this measure indicated that peers overtake some family members in proximity-seeking and support-seeking, but not in the overall hierarchical ordering of the attachment bond during adolescence. Conclusions: The bond with the romantic partner increases in terms of scoring on the affiliative subscales as adolescence progresses. There are significant gender differences among the hierarchy patterns of attachment for boys and girls. Developmental changes in adolescent attachment are discussed. 相似文献
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Evaluating Nonverbal Behavior of Individuals with Dementia During Feeding: A Survey of the Nursing Staff in Residential Care Homes for Elderly Adults 下载免费PDF全文
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Koschollek Carmen Kajikhina Katja Bug Marleen Santos-Hövener Claudia 《Der Diabetologe》2020,16(8):698-704
Die Diabetologie - Deutschland ist ein Einwanderungsland und 2019 hatte mehr als jede vierte hier lebende Person einen sog. Migrationshintergrund. Bei dieser statistisch definierten Gruppe handelt... 相似文献