cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5121508.v1
title: Supplementary Material for: Overexpression of Dyrk1A Causes the Defects in Synaptic Vesicle Endocytosis

description: Trisomy 21-linked Dyrk1A (dual-specificity tyrosine phosphorylation-regulated kinase 1A) overexpression is implicated in pathogenic mechanisms underlying mental retardation in Down syndrome (DS). It is known to phosphorylate multiple substrates including endocytic proteins in vitro, but the functional consequence of Dyrk1A-mediated phosphorylation on endocytosis has never been investigated. Here, we show that overexpression of Dyrk1A causes defects in clathrin-mediated endocytosis and specifically, in the recruitment of endocytic proteins to clathrin-coated pits in fibroblasts. Synaptic vesicle endocytosis also significantly slowed down as a result of Dyrk1A overexpression in cultured hippocampal neurons. These effects are dependent on Dyrk1A kinase activity. The inhibitory effect of Dyrk1A on synaptic vesicle endocytosis was confirmed in neuronal cultures derived from transgenic mice overexpressing Dyrk1A at levels found in DS. Pharmacological blockade of Dyrk1A with epigallocatechin gallate rescued the endocytic phenotypes found in transgenic neurons. Together, our results suggest that aberrant Dyrk1A-mediated phosphorylation of the endocytic machinery perturbs synaptic vesicle endocytosis, which may contribute to synaptic dysfunctions and cognitive deficits associated with DS.
DOI: 10.6084/m9.figshare.5121493
title: Supplementary Material for: The Impact of Single Gene and Chromosomal Disorders on Hospital Admissions of Children and Adolescents: A Population-Based Study

description: <i>Background:</i> It is well recognized that genetic disease makes a significant contribution to childhood illness. Here, we present recent population data describing the impact of single gene and chromosomal disorders on hospital admissions of children and adolescents. <i>Methods:</i> Hospital admissions for patients aged 0–19 years between 2000 and 2006, with a single gene or chromosomal disorder, were extracted from the Western Australian Hospital Morbidity Data System using 296 diagnosis codes identified from the International Statistical Classification of Diseases, Tenth Revision, Australian Modification. Data extracted for each patient included the number, length and cost of all admissions. <i>Results:</i> Between 2000 and 2006, 14,197 admissions were identified for 3,271 patients aged 0–19 years with single gene and chromosomal disorders, representing 2.6% of admissions and 4.3% of total hospital costs in this age group. Patients with genetic disorders had more admissions and stayed longer in hospital than patients admitted for any reason. Specific disorders associated with a high demand on hospital services included cystic fibrosis, Down syndrome, osteogenesis imperfecta, thalassemia, and von Willebrand’s disease. <i>Conclusions:</i> Children and adolescents with single gene and chromosomal disorders placed higher demands on hospital services than other patients in their age group, but were responsible for a relatively small proportion of hospital admissions and costs. These data will enable informed planning of health care services for patients with single gene and chromosomal disorders in Western Australia.
DOI: 10.6084/m9.figshare.5121496
title: Supplementary Material for: Detection of Merkel Cell Polyomavirus in Epidermodysplasia-Verruciformis-Associated Skin Neoplasms

description: <i>Background:</i> Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias. <i>Objective:</i> To examine whether EV is associated with cutaneous MCPyV infection. <i>Methods:</i> We used MCPyV-specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient with acquired EV. <i>Results:</i> In all congenital EV patients, MCPyV DNA was found in carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In 4 of these patients, the MCPyV-positive skin lesions were from different anatomic locations. In addition, 1 immunosuppressed patient suffering from acquired EV harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of 30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV DNA. <i>Conclusions:</i> The strong association of EV-associated skin neoplasms with MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV. Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the development of EV-associated skin neoplasms.
DOI: 10.6084/m9.figshare.5121499.v1
title: Supplementary Material for: Microinflammation in Hemodialysis Patients Is Associated with Increased CD14<sup>+</sup>CD16<sup>+</sup> Pro-Inflammatory Monocytes: Possible Modification by On-Line Hemodiafiltration

description: <i>Background:</i> An increased percentage of pro-inflammatory CD14<sup>+</sup>CD16<sup>+</sup> monocytes might contribute to inflammation in hemodialysis (HD) patients. The purpose of the study was to evaluate the possible contribution of pro-inflammatory monocytes to inflammation in HD patients and also to evaluate the effect of on-line hemodiafiltration (HDF). <i>Methods:</i> Flow cytometric detection of monocytes in patients undergoing HD, on-line HDF and healthy controls as well as plasma cytokines and cytokine mRNA measurement were performed. <i>Results:</i> Percent pro-inflammatory monocytes, plasma cytokines and cytokine mRNA significantly increased in HD patients. Intracellular cytokine staining showed pro-inflammatory monocytes were the predominant source of tumor necrosis factor-α. Percent pro-inflammatory monocytes positively correlated with plasma inflammatory cytokines. Percent pro-inflammatory monocytes, plasma cytokines and cytokine mRNA significantly decreased in on-line HDF patients. <i>Conclusion:</i> Increased pro-inflammatory monocytes are likely to contribute to inflammation in HD patients, and beneficial effect of on-line HDF might be partially mediated by modulating the inflammatory response.
DOI: 10.6084/m9.figshare.5121502.v1
title: Supplementary Material for: Prävention sozialer Angststörungen im Kindes- und Jugendalter: Notwendig oder überflüssig?

description: In dem vorliegenden Überblicksbeitrag wird zunächst anhand der Symptomatik und des Verlaufs sozialer Ängste und sozialer Phobien vom Kindes- und Jugendalter bis hin zum Erwachsenenalter deutlich gemacht, dass es notwendig ist, wirksame Präventionsprogramme zu entwickeln, um soziale Ängste von Kindern und Jugendlichen bereits frühzeitig zu reduzieren bzw. einer Chronifizierung und Verschlimmerung entgegenzuwirken. Darauf aufbauend wird der Stand der Forschung zur Prävention sozialer Ängste bzw. sozialer Phobien im Kindes- und Jugendalter vorgestellt und bewertet.
DOI: 10.6084/m9.figshare.5121484
title: Supplementary Material for: Analysis of <i>IL2/IL21</i> Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

description: <i>Background/Aims:</i> The chromosome 4q27 region harboring <i>IL2</i> and <i>IL21</i> is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the <i>IL2/IL21</i> region may also modulate the susceptibility to these two rare cholestatic liver diseases. <i>Methods:</i> Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the <i>KIAA1109/TENR/IL2/IL21</i> linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. <i>Results:</i> The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). <i>Conclusion:</i> The <i>IL2/IL21</i> region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC.
DOI: 10.6084/m9.figshare.5121487
title: Supplementary Material for: Duplication 5q and Deletion 9p due to a t(5;9)(q34;p23) in 2 Cousins with Features of Hunter-McAlpine Syndrome and Hypothyroidism

description: We report on 2 similarly affected cousins with a compound imbalance resulting from a familial t(5;9)(q34;p23) and entailing both an ∼17-Mb 5q terminal duplication and an ∼12-Mb 9p terminal deletion as determined by G-banding, subtelomere FISH, and aCGH. The proband’s karyotype was 46,XX,der(9)t(5;9)(q34;p23)mat.ish der(9)t(5;9)(q34;p23)(9pter–,5qter+).arr 5q34q35(163,328,000–180,629,000)×3, 9p24p23(194,000–12,664,000)×1. Her cousin had the same unbalanced karyotype inherited from his father. The clinical phenotype mainly consists of a distinct craniofacial dysmorphism featuring microcephaly, flat facies, down slanting palpebral fissures, small flat nose, long philtrum, and small mouth with thin upper lip. Additional remarkable findings were craniosynostosis of several sutures, craniolacunia and preaxial polydactyly in the proband and hypothyroidism in both subjects. The observed clinical constellation generally fits the phenotypic spectrum of the 5q distal duplication syndrome (known also as Hunter-McAlpine syndrome), except for the thyroid insufficiency which can likely be ascribed to the concurrent 9p deletion, as at least 4 other 9pter monosomic patients without chromosome 5 involvement had this hormonal disorder. The present observation further confirms the etiology of the HMS phenotype from gain of the 5q35→qter region, expands the clinical pictures of partial trisomy 5q and monosomy 9p, and provides a comprehensive list of 160 patients with 5q distal duplication.
DOI: 10.6084/m9.figshare.5121490
title: Supplementary Material for: Development of Gold Standard Ion-Selective Electrode-Based Methods for Fluoride Analysis

description: <i>Background/Aims:</i> Currently available techniques for fluoride analysis are not standardized. Therefore, this study was designed to develop standardized methods for analyzing fluoride in biological and nonbiological samples used for dental research. <i>Methods:</i> A group of nine laboratories analyzed a set of standardized samples for fluoride concentration using their own methods. The group then reviewed existing analytical techniques for fluoride analysis, identified inconsistencies in the use of these techniques and conducted testing to resolve differences. Based on the results of the testing undertaken to define the best approaches for the analysis, the group developed recommendations for direct and microdiffusion methods using the fluoride ion-selective electrode. <i>Results:</i> Initial results demonstrated that there was no consensus regarding the choice of analytical techniques for different types of samples. Although for several types of samples, the results of the fluoride analyses were similar among some laboratories, greater differences were observed for saliva, food and beverage samples. In spite of these initial differences, precise and true values of fluoride concentration, as well as smaller differences between laboratories, were obtained once the standardized methodologies were used. Intraclass correlation coefficients ranged from 0.90 to 0.93, for the analysis of a certified reference material, using the standardized methodologies. <i>Conclusion:</i> The results of this study demonstrate that the development and use of standardized protocols for F analysis significantly decreased differences among laboratories and resulted in more precise and true values.
DOI: 10.6084/m9.figshare.5121493.v1
title: Supplementary Material for: The Impact of Single Gene and Chromosomal Disorders on Hospital Admissions of Children and Adolescents: A Population-Based Study

description: <i>Background:</i> It is well recognized that genetic disease makes a significant contribution to childhood illness. Here, we present recent population data describing the impact of single gene and chromosomal disorders on hospital admissions of children and adolescents. <i>Methods:</i> Hospital admissions for patients aged 0–19 years between 2000 and 2006, with a single gene or chromosomal disorder, were extracted from the Western Australian Hospital Morbidity Data System using 296 diagnosis codes identified from the International Statistical Classification of Diseases, Tenth Revision, Australian Modification. Data extracted for each patient included the number, length and cost of all admissions. <i>Results:</i> Between 2000 and 2006, 14,197 admissions were identified for 3,271 patients aged 0–19 years with single gene and chromosomal disorders, representing 2.6% of admissions and 4.3% of total hospital costs in this age group. Patients with genetic disorders had more admissions and stayed longer in hospital than patients admitted for any reason. Specific disorders associated with a high demand on hospital services included cystic fibrosis, Down syndrome, osteogenesis imperfecta, thalassemia, and von Willebrand’s disease. <i>Conclusions:</i> Children and adolescents with single gene and chromosomal disorders placed higher demands on hospital services than other patients in their age group, but were responsible for a relatively small proportion of hospital admissions and costs. These data will enable informed planning of health care services for patients with single gene and chromosomal disorders in Western Australia.
DOI: 10.6084/m9.figshare.5121487.v1
title: Supplementary Material for: Duplication 5q and Deletion 9p due to a t(5;9)(q34;p23) in 2 Cousins with Features of Hunter-McAlpine Syndrome and Hypothyroidism

description: We report on 2 similarly affected cousins with a compound imbalance resulting from a familial t(5;9)(q34;p23) and entailing both an ∼17-Mb 5q terminal duplication and an ∼12-Mb 9p terminal deletion as determined by G-banding, subtelomere FISH, and aCGH. The proband’s karyotype was 46,XX,der(9)t(5;9)(q34;p23)mat.ish der(9)t(5;9)(q34;p23)(9pter–,5qter+).arr 5q34q35(163,328,000–180,629,000)×3, 9p24p23(194,000–12,664,000)×1. Her cousin had the same unbalanced karyotype inherited from his father. The clinical phenotype mainly consists of a distinct craniofacial dysmorphism featuring microcephaly, flat facies, down slanting palpebral fissures, small flat nose, long philtrum, and small mouth with thin upper lip. Additional remarkable findings were craniosynostosis of several sutures, craniolacunia and preaxial polydactyly in the proband and hypothyroidism in both subjects. The observed clinical constellation generally fits the phenotypic spectrum of the 5q distal duplication syndrome (known also as Hunter-McAlpine syndrome), except for the thyroid insufficiency which can likely be ascribed to the concurrent 9p deletion, as at least 4 other 9pter monosomic patients without chromosome 5 involvement had this hormonal disorder. The present observation further confirms the etiology of the HMS phenotype from gain of the 5q35→qter region, expands the clinical pictures of partial trisomy 5q and monosomy 9p, and provides a comprehensive list of 160 patients with 5q distal duplication.
DOI: 10.6084/m9.figshare.5121490.v1
title: Supplementary Material for: Development of Gold Standard Ion-Selective Electrode-Based Methods for Fluoride Analysis

description: <i>Background/Aims:</i> Currently available techniques for fluoride analysis are not standardized. Therefore, this study was designed to develop standardized methods for analyzing fluoride in biological and nonbiological samples used for dental research. <i>Methods:</i> A group of nine laboratories analyzed a set of standardized samples for fluoride concentration using their own methods. The group then reviewed existing analytical techniques for fluoride analysis, identified inconsistencies in the use of these techniques and conducted testing to resolve differences. Based on the results of the testing undertaken to define the best approaches for the analysis, the group developed recommendations for direct and microdiffusion methods using the fluoride ion-selective electrode. <i>Results:</i> Initial results demonstrated that there was no consensus regarding the choice of analytical techniques for different types of samples. Although for several types of samples, the results of the fluoride analyses were similar among some laboratories, greater differences were observed for saliva, food and beverage samples. In spite of these initial differences, precise and true values of fluoride concentration, as well as smaller differences between laboratories, were obtained once the standardized methodologies were used. Intraclass correlation coefficients ranged from 0.90 to 0.93, for the analysis of a certified reference material, using the standardized methodologies. <i>Conclusion:</i> The results of this study demonstrate that the development and use of standardized protocols for F analysis significantly decreased differences among laboratories and resulted in more precise and true values.
DOI: 10.6084/m9.figshare.5121496.v1
title: Supplementary Material for: Detection of Merkel Cell Polyomavirus in Epidermodysplasia-Verruciformis-Associated Skin Neoplasms

description: <i>Background:</i> Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias. <i>Objective:</i> To examine whether EV is associated with cutaneous MCPyV infection. <i>Methods:</i> We used MCPyV-specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient with acquired EV. <i>Results:</i> In all congenital EV patients, MCPyV DNA was found in carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In 4 of these patients, the MCPyV-positive skin lesions were from different anatomic locations. In addition, 1 immunosuppressed patient suffering from acquired EV harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of 30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV DNA. <i>Conclusions:</i> The strong association of EV-associated skin neoplasms with MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV. Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the development of EV-associated skin neoplasms.
DOI: 10.6084/m9.figshare.5121475
title: Supplementary Material for: Analysis of Thioester-Containing Proteins during the Innate Immune Response of Drosophila melanogaster

description: Thioester-containing proteins (TEPs) are conserved proteins among insects that are thought to be involved in innate immunity. In <i>Drosophila</i>, the <i>Tep</i> family is composed of 6 genes named <i>Tep1–Tep6</i>. In this study, we investigated the phylogeny, expression pattern and roles of these genes in the host defense of <i>Drosophila</i>. Protostomian<i> Tep </i>genes are clustered in 3 distinct branches, 1 of which is specific to mosquitoes. Most <i>D. melanogaster Tep</i> genes are expressed in hemocytes, can be induced in the fat body, and are expressed in specific regions of the hypodermis. This expression pattern is consistent with a role in innate immunity. However, we find that TEP1, TEP2, and TEP4 are not strictly required in the body cavity to fight several bacterial and fungal infections. One possibility is that <i>Drosophila</i> TEPs act redundantly or that their absence can be compensated by other components of the immune response. TEPs may thus provide a subtle selective advantage during evolution. Alternatively, they may be required in host defense against specific as yet unidentified natural pathogens of <i>Drosophila</i>.
DOI: 10.6084/m9.figshare.5121481
title: Supplementary Material for: A Balanced Translocation t(6;14)(q25.3;q13.2) Leading to Reciprocal Fusion Transcripts in a Patient with Intellectual Disability and Agenesis of Corpus Callosum

description: We identified a male patient presenting with intellectual disability and agenesis of the corpus callosum, carrying an apparently balanced, reciprocal, de novo translocation t(6;14)(q25.3;q13.2). Breakpoint mapping, using array painting, identified 2 interesting candidate genes, <i>ARID1B</i> and <i>MRPP3</i>, disrupted in the patient. Unexpectedly, the rearrangement produced 3 in-frame reciprocal fusion transcripts that were further characterized. Formation of fusion transcripts is mainly reported in acquired malignancies and is very rarely observed in patients with intellectual disability (ID) and/or multiple congenital malformations (MCA). Additional experimental results suggest that <i>ARID1B</i>, a gene involved in chromatin remodeling, constitutes a good candidate for the central nervous system phenotype present in the patient.
DOI: 10.6084/m9.figshare.5121469
title: Supplementary Material for: High Efficiency of a Sequential Recombinase-Mediated Cassette Exchange Reaction in <i>Escherichia coli</i>

description: A comparison between the efficiency of recombinase-mediated cassette exchange (RMCE) reactions catalyzed in <i>Escherichia coli</i> by the site-specific recombinases Flp of yeast and Int of coliphage HK022 has revealed that an Flp-catalyzed RMCE reaction is more efficient than an Int-HK022 catalyzed reaction. In contrast, an RMCE reaction with 1 pair of <i>frt</i> sites and 1 pair of <i>att</i> sites catalyzed in the presence of both recombinases is very inefficient. However, the same reaction catalyzed by each recombinase individually supplied in a sequential order is very efficient, regardless of the order. Atomic force microscopy images of Flp with its DNA substrates show that only 1 pair of recombination sites forms a synaptic complex with the recombinase. The results suggest that the RMCE reaction is sequential.