cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123173.v1
title: Supplementary Material for: Lack of Any Cardiac Involvement in a Patient with Andersen-Tawil Syndrome Associated with the c.574A→G Mutation in <i>KCNJ2</i>

description: The Andersen-Tawil syndrome (ATS) is characterized by hypo-normokaliemic muscle periodic paralysis, dysmorphic features and ventricular arrhythmias. Most cases are caused by mutations in <i>KCNJ2,</i> encoding for the potassium inwardly rectifying channel, Kir2.1 (ATS1). Although <i>KCNJ2</i> mutations show no obvious genotype-phenotype correlations and incomplete penetrance, signs of cardiac involvement are usually present in most ATS1 cases. In contrast, here we describe an Italian ATS1 patient, carrying a c.574A→G mutation in <i>KCNJ2,</i> who had both facial dysmorphisms and muscle periodic paralysis but who did not manifest any cardiac involvement, although the same mutation was originally described in a Japanese kindred, in which all affected individuals manifested a severe cardiac phenotype.
DOI: 10.6084/m9.figshare.5123164
title: Supplementary Material for: MIP-3α Expression in Macrophages Is NOD Dependent

description: <i>Background:</i> The first identified susceptibility gene for Crohn’s disease, <i>NOD2</i>, acts as a sensor for the bacterial-wall peptidoglycan fragment muramyl dipeptide (MDP) and activates the transcription factor nuclear factor-ĸB (NF-ĸB). Upon NF-ĸB activation, intestinal macrophages (IMACs) induce expression of macrophage inflammatory protein (MIP)-3α to attract memory T lymphocytes. We therefore investigated the influence of NOD2 ligation of IMAC differentiation and functional MIP-3α induction. <i>Methods:</i> Human embryonal kidney HEK293 cells were transfected with NOD2 wild-type (NOD2<sup>WT</sup>) and the NOD2 SNP13 variant (NOD2<sup>L1007fsinsC</sup>) and stimulated with MDP. Recruitment of CD45R0<sup>+</sup> and Th17 cells was determined by immunohistochemistry. <i>Results:</i> Endogenous NOD2 stimulation was followed by a dose-dependent increase in MIP-3α secretion in MONO-MAC-6 (MM6) cells. MIP-3α mRNA was also significantly (* p &lt; 0.05) induced in HEK293 transfected with NOD2<sup>WT</sup> via MDP ligation. In vivo cell-cell contacts between IMACs and CD45R0<sup>+</sup> memory T cells as well as recruitment of Th17 cells in patients of NOD2 variants were unchanged as compared to wild-type patients. <i>Conclusion:</i> Our data demonstrate a dose-dependent increase in MIP-3α secretion in the human myeloid cell line MM6 upon MDP. However, MIP-3α-driven recruitment of Th17 cells or CD45R0<sup>+</sup> memory T lymphocytes is not affected in patients carrying heterozygous NOD2 variants.
DOI: 10.6084/m9.figshare.5123167.v1
title: Supplementary Material for: Comparative Analysis of a Putative Tuberculosis-Susceptibility Gene, <i>MC3R</i>, and Pseudogene Sequences in Cattle, African Buffalo, Hyena, Rhinoceros and Other African Bovids and Ruminants

description: Studies in humans have suggested the possible involvement of melanocortin-3-receptor (MC3R) and other components of the central melanocortin system in host defense against mycobacteria. We report a genomic DNA nucleotide sequence highly homologous to human <i>MC3R</i> in several bovids and non-bovid African wildlife species. Nucleotide sequence analysis indicates that the orthologous genes of cattle and buffalo are highly homologous (89.4 and 90%, respectively) to the human <i>MC3R</i> gene. Sequence results also identified a typical non-functional, duplicated pseudogene, <i>MC3RP</i>, in 7 species from the family Bovidae. No pseudogene was found in animals outside Bovidae. The presence of the pseudogene in tuberculosis-susceptible species could have possible immunomodulatory effects on susceptibility to bovine tuberculosis infection, as well as a considerable influence on energy metabolism and food conversion efficiency.
DOI: 10.6084/m9.figshare.5123176.v1
title: Supplementary Material for: First Report of a Single Exon Deletion in TCOF1 Causing Treacher Collins Syndrome

description: Treacher Collins syndrome (TCS) is a rare craniofacial disorder characterized by facial anomalies and ear defects. TCS is caused by mutations in the <i>TCOF1</i> gene and follows autosomal dominant inheritance. Recently, mutations in the <i>POLR1D </i>and<i> POLR1C</i> genes have also been identified to cause TCS. However, in a subset of patients no causative mutation could be found yet. Inter- and intrafamilial phenotypic variability is high as is the variety of mainly family-specific mutations identified throughout <i>TCOF1</i>. No obvious correlation between pheno- and genotype could be observed. The majority of described point mutations, small insertions and deletions comprising only a few nucleotides within <i>TCOF1</i> lead to a premature termination codon. We investigated a cohort of 112 patients with a tentative clinical diagnosis of TCS by multiplex ligation-dependent probe amplification (MLPA) to search for larger deletions not detectable with other methods used. All patients were selected after negative screening for mutations in <i>TCOF1</i>, <i>POLR1D</i> and <i>POLR1C</i>. In 1 patient with an unequivocal clinical diagnosis of TCS, we identified a 3.367 kb deletion. This deletion abolishes exon 3 and is the first described single exon deletion within <i>TCOF1</i>. On RNA level we observed loss of this exon which supposedly leads to haploinsufficiency of TREACLE, the nucleolar phosphoprotein encoded by <i>TCOF1.</i>
DOI: 10.6084/m9.figshare.5123179.v1
title: Supplementary Material for: From Genotypes of Immunoglobulin Constant Heavy G Chains (Fcγ) (GM) Genes <b><i>(IGHG)</i></b> to Phenotypes in Childhood Asthma

description: <b><i>Background:</i></b> IgE-mediated allergy is associated with immunoglobulin heavy constant G chain (Fcγ) (GM) genes <i>(IGHG)</i> on chromosome 14q32.3. Investigation of the alternative GM allotypes of γ3, γ1 and γ2 chains has disclosed new structural and functional IgG subclasses and B-cell variants, with possible effects on childhood asthma. <b><i>Objective:</i></b> To investigate different <i>IGHG</i> (GM) gene complexes in a childhood asthma population for allergy parameters. <b><i>Methods:</i></b><i>IGHG</i> alleles and correlated allotypic (allelic) IgG subclass levels were analyzed with a sensitive indirect competitive ELISA in 10-year-old children with bronchial asthma. Individual <i>IGHG</i> diplotype-, genotype- and haplotype-related B cells were compared for allelic IgG subclass levels, IgE sensitization, IgE, IgA and IgM levels, and numbers of peripheral blood eosinophils and lymphocytes. <b><i>Results:</i></b> The group with homozygous <i>IGHG</i>*<i>bfn/</i>*<i>bfn</i> (B1/B1 cells) demonstrated low IgG1*f levels (p &lt; 0.001) but increased IgG2*n levels (p &lt; 0.001) together with increasd IgE and <i>IGHG2</i>*<i>n </i>gene dose-dependent IgE sensitization (atopic phenotype). The <i>IGHG</i>*<i>bf–n</i>/*<i>bf–n</i> (B2/B2 cells) demonstrated low IgG1*f (p &lt; 0.05) and IgG2*–n (p &lt; 0.001) and the <i>IGHG</i>*<i>ga–n/</i>*<i>ga–n</i> (B4/B4 cells) low IgG1*a (p &lt; 0.001) and IgG2*–n (p &lt; 0.02) together with low IgE sensitization (non-atopic phenotype). B*<sup>bfn</sup> (B1) and B*<sup>bf–n</sup> (B2) demonstrated increased numbers of peripheral blood eosinophils, compared to B*<sup>gan</sup> (B4) cells, which demonstrated increased peripheral blood CD8 lymphocytes instead. <b><i>Conclusion:</i></b><i>IGHG</i> diplotypes present different phenotypes in childhood asthma. The <i>IGHG2</i>*n dose relationship to IgE sensitization and increased IgG2*n levels in IgE sensitized are risk markers for IgE-mediated asthma. The opposite <i>IGHG2</i>*<i>–n</i> presents non-IgE-mediated asthma and IgG subclass deficiencies.
DOI: 10.6084/m9.figshare.5123158
title: Supplementary Material for: Computerised Cognitive Behavioural Therapy for Insomnia: A Systematic Review and Meta-Analysis

description: <b><i>Background:</i></b> Computerised cognitive behavioural therapy (CCBT) is an innovative mode of delivering services to patients with psychological disorders. The present paper uses a meta-analysis to systematically review and evaluate the effectiveness of CCBT for insomnia (CCBT-I). <b><i>Method:</i></b> A comprehensive search was conducted on 7 databases including MEDLINE, PsycINFO, EMBASE, CINAHL, Cochrane Library, Social Sciences Citation Index and PubMed (up to March 2011). Search terms covered 3 concepts: (1) [<i>internet, web, online, computer-aided, computer-assisted, computer-guided, computerized</i> OR<i> computerised</i>] AND (2) [<i>CBT, cognitive therapy, behavio(u)ral therapy</i> OR <i>behavio(u)r therapy</i>] AND (3) [<i>insomnia, sleep disorders </i>OR<i> sleeping problem</i>]. <b><i>Results:</i></b> 533 potentially relevant papers were identified, and 6 randomised controlled trials (RCTs) that met the selection criteria were included in the review and analysis. Two RCTs were done by the same group of investigators (Ritterband and colleagues) using the same internet programmes. Post-treatment mean differences between groups showed that the effects of CCBT-I on sleep quality, sleep efficiency, the number of awakenings, sleep onset latency and the Insomnia Severity Index were significant, ranging from small to large effect sizes. However, effects on wake time after sleep onset, total sleep time and time in bed were non-significant. On average, the number needed to treat was 3.59. The treatment adherence rate for CCBT-I was high (78%). <b><i>Conclusion:</i></b> The results lend support to CCBT as a mildly to moderately effective self-help therapy in the short run for insomnia. CCBT-I can be an acceptable form of low-intensity treatment in the stepped care model for insomnia.
DOI: 10.6084/m9.figshare.5123161.v1
title: Supplementary Material for: Körperbeschwerden nach politischer Inhaftierung und deren Zusammenhang mit Ängstlichkeit und Depressivität

description: <i>Hintergrund:</i> Über 200.000 Menschen waren in der DDR aus politischen Gründen inhaftiert. Mehrere Studien existieren zu den psychischen (Langzeit-)Folgen dieser biografischen Erfahrung. Weniger untersucht wurden bisher die körperlichen Folgen. Ziel dieser Studie ist (1) die Ausprägungen körperlicher Beschwerden von ehemals politisch Inhaftierten in der DDR mit Daten aus der Allgemeinbevölkerung zu vergleichen, (2) die körperlichen Beschwerden mit soziodemografischen und Inhaftierungsmerkmalen in Beziehung zu setzen und (3) den Zusammenhang zwischen körperlichen Beschwerden und Ängstlichkeit sowie Depressivität innerhalb der Gruppe der ehemals Inhaftierten zu untersuchen. <i>Methoden:</i> In dieser Querschnittstudie beantworteten 149 Personen, die aus politischen Gründen in der DDR inhaftiert waren, einen Fragebogen über körperliche Beschwerden (Gießener Beschwerdebogen, Kurzform), Ängstlichkeit und Depressivität (Hospital Anxiety and Depression Scale). Für den Vergleich mit der Allgemeinbevölkerung wurde eine hinsichtlich Alter und Geschlecht vergleichbare Stichprobe aus einer deutschen Repräsentativbefragung verwendet (n = 473). <i>Ergebnisse:</i> Ehemalige politisch Inhaftierte berichten im Vergleich zur Allgemeinbevölkerung auch viele Jahre nach der politischen Inhaftierung deutlich mehr körperliche Beschwerden (p &lt; 0,001). Soziodemografische Merkmale und Merkmale der Inhaftierung stehen nur punktuell mit den angegebenen Körperbeschwerden im Zusammenhang. Zur Vorhersage von Ängstlichkeit in der Gruppe der politisch Inhaftierten leisten insbesondere Herzbeschwerden einen substantiellen Beitrag, zur Vorhersage von Depressivität Erschöpfung. Die Haftdauer ist für Ängstlichkeit und Depressivität kein signifikanter Prädiktor. <i>Schlussfolgerungen:</i> Personen, die aus politischen Gründen in der DDR inhaftiert waren, stellen eine Risikogruppe in der medizinischen Versorgung dar. Sie berichten über deutlich mehr Körperbeschwerden als die Allgemeinbevölkerung und weisen stark erhöhte Werte für Depression und Ängstlichkeit auf.
DOI: 10.6084/m9.figshare.5123152
title: Supplementary Material for: Coincidence Signaling of Dopamine D<sub>1</sub>-Like and M<sub>1</sub> Muscarinic Receptors in the Regulation of Cyclic AMP Formation and CREB Phosphorylation in Mouse Prefrontal Cortex

description: In the prefrontal cortex, dopamine D<sub>1</sub>-like and M<sub>1</sub> muscarinic receptors are both involved in the regulation of attentional, cognitive and emotional processes but so far no information has been provided on their functional interaction. In the present study we show that in mouse medial prefrontal cortex, concomitant activation of M<sub>1</sub> muscarinic receptors potentiated D<sub>1</sub>-like receptor-induced cyclic AMP formation through a mechanism involving activation of G<sub>q/11</sub> and the release of G protein βγ subunits. Immunohistochemical studies indicated that the adenylyl cyclase isoforms AC2 and AC4 are expressed in mouse prefrontal cortex and that they colocalize with D<sub>1</sub>-like receptors with a greater association for AC4. In primary cultures of frontal cortex neurons, D<sub>1</sub>-like receptor-induced Ser133 phosphorylation of the transcription factor cyclic AMP-responsive element binding protein (CREB) was potentiated by concurrent stimulation of M<sub>1</sub> receptors. Suppression of AC4 expression with small interfering RNA transfection reduced D<sub>1</sub> stimulation of cyclic AMP formation and CREB phosphorylation and abolished the M<sub>1</sub> potentiation, whereas knockdown of AC2 had no significant effects. These data indicate that in mouse prefrontal cortex G<sub>q/11</sub>-coupled M<sub>1</sub> receptor and G<sub>s</sub>-coupled D<sub>1</sub>-like receptor inputs converge on AC4 with a consequent enhancement of cyclic AMP formation and signaling to the nucleus.
DOI: 10.6084/m9.figshare.5123155
title: Supplementary Material for: Differences in Copy Number Variation between Discordant Monozygotic Twins as a Model for Exploring Chromosomal Mosaicism in Congenital Heart Defects

description: Studies addressing the role of somatic copy number variation (CNV) in the genesis of congenital heart defects (CHDs) are scarce, as cardiac tissue is difficult to obtain, especially in non-affected individuals. We explored the occurrence of copy number differences in monozygotic (MZ) twins discordant for the presence of a CHD, as an illustrative model for chromosomal mosaicism in CHDs. Array comparative genomic hybridization was performed on peripheral blood-derived DNA obtained from 6 discordant MZ twin pairs and on sex-matched reference samples. To identify CNV differences between both twin members as well as potential CNVs in both twins contributing to the phenotype, DNA from each twin was hybridized against its co-twin, and against a normal control. Three copy number differences in 1 out of 6 MZ twin pairs were detected, confirming the occurrence of somatic CNV events in MZ twins. Further investigation by copy number and (epi)genome sequencing analyses in MZ twins, discordant for the presence of CHDs, is required to improve our knowledge on how postzygotic genetic, environmental and stochastic factors can affect human heart development.
DOI: 10.6084/m9.figshare.5123149
title: Supplementary Material for: Deficient Expression of Genes Involved in the Endogenous Defense System against Transposons in Cryptorchid Boys with Impaired Mini-Puberty

description: Mini-puberty is the period between 30 and 80 days after birth when testosterone and gonadotropin surges occur in male infants to induce the transformation of gonocytes into adult/dark spermatogonia. Cryptorchid boys with impaired mini-puberty develop infertility despite timely and successful surgical treatment. The decreased germ cell count found in this group of boys could be the result of uncontrolled transposon activity inducing genomic instability and germ cell death. A genome-wide analysis of 18 cryptorchid and 4 control testes was performed with Affymetrix chips. We found that 5 of 8 genes that are important for transposon silencing were not expressed in the high azoospermia risk group of cryptorchid boys but were expressed in the low azoospermia risk and control groups. Two genes, <i>CBX3</i> and <i>DNMT1</i>, were equally expressed in all 3 groups. Impaired expression of the <i>DDX4, MAEL,</i><i>MOV10L1, PIWIL2, PIWIL4,</i> and<i> TDRD9</i> genes in the group of cryptorchid boys at high risk of infertility indicates that gene instability induced by impaired expression of transposon silencing genes contribute to the development of azoospermia. Intact mini-puberty appears to be essential for the development of the endogenous defense system mediated by transposon silencing.
DOI: 10.6084/m9.figshare.5123152.v1
title: Supplementary Material for: Coincidence Signaling of Dopamine D<sub>1</sub>-Like and M<sub>1</sub> Muscarinic Receptors in the Regulation of Cyclic AMP Formation and CREB Phosphorylation in Mouse Prefrontal Cortex

description: In the prefrontal cortex, dopamine D<sub>1</sub>-like and M<sub>1</sub> muscarinic receptors are both involved in the regulation of attentional, cognitive and emotional processes but so far no information has been provided on their functional interaction. In the present study we show that in mouse medial prefrontal cortex, concomitant activation of M<sub>1</sub> muscarinic receptors potentiated D<sub>1</sub>-like receptor-induced cyclic AMP formation through a mechanism involving activation of G<sub>q/11</sub> and the release of G protein βγ subunits. Immunohistochemical studies indicated that the adenylyl cyclase isoforms AC2 and AC4 are expressed in mouse prefrontal cortex and that they colocalize with D<sub>1</sub>-like receptors with a greater association for AC4. In primary cultures of frontal cortex neurons, D<sub>1</sub>-like receptor-induced Ser133 phosphorylation of the transcription factor cyclic AMP-responsive element binding protein (CREB) was potentiated by concurrent stimulation of M<sub>1</sub> receptors. Suppression of AC4 expression with small interfering RNA transfection reduced D<sub>1</sub> stimulation of cyclic AMP formation and CREB phosphorylation and abolished the M<sub>1</sub> potentiation, whereas knockdown of AC2 had no significant effects. These data indicate that in mouse prefrontal cortex G<sub>q/11</sub>-coupled M<sub>1</sub> receptor and G<sub>s</sub>-coupled D<sub>1</sub>-like receptor inputs converge on AC4 with a consequent enhancement of cyclic AMP formation and signaling to the nucleus.
DOI: 10.6084/m9.figshare.5123143
title: Supplementary Material for: Loss-of-Function <i>CNKSR2</i> Mutation Is a Likely Cause of Non-Syndromic X-Linked Intellectual Disability

description: In a non-dysmorphic 5-year-old boy with developmental delay, well-controlled epilepsy, and microcephaly, a 234-kb deletion of Xp22.12 was detected by copy number analysis. The maternally inherited deletion removed the initial 15 of the 21 exons of the connector enhancer of KSR-2 gene called <i>CNKSR2 </i>or <i>CNK2</i>. Our finding suggests that loss of <i>CNKSR2</i> is a novel cause of non-syndromic X-linked mental retardation, an assumption supported by high gene expression in the brain, localization to the post-synaptic density, and a role in RAS/MAPK-dependent signal transduction.
DOI: 10.6084/m9.figshare.5123146
title: Supplementary Material for: Pathobiological Implications of MUC16/CA125 Expression in Intrahepatic Cholangiocarcinoma-Mass Forming Type

description: <i>Objectives:</i> MUC16 carries the peptide epitope CA125, which is well known as a marker of ovarian cancer. High serum levels of MUC16 (CA125) have been reported not only in patients with ovarian cancer but also in patients with liver diseases. We evaluated the expression of MUC16 in intrahepatic cholangiocarcinoma-mass forming type (ICC-MF) tissues. <i>Methods:</i> We examined the expression of MUC16 by immunohistochemical analyses using the monoclonal antibody M11 in ICC-MF tissues from 63 patients. To compare the prevalence of each mucin expression by clinicopathological features, appropriate statistical analysis was performed. <i>Results:</i> MUC16 was detected in 48% of samples (30/63). After adjusting for the effects of other prognostic factors, multivariate survival analysis revealed that MUC16 expression is a significant independent factor of poor prognosis (p = 0.005). <i>Conclusion:</i> The current results indicate that MUC16 expression is a prognostic factor of poor survival in ICC-MF.
DOI: 10.6084/m9.figshare.5123155.v1
title: Supplementary Material for: Differences in Copy Number Variation between Discordant Monozygotic Twins as a Model for Exploring Chromosomal Mosaicism in Congenital Heart Defects

description: Studies addressing the role of somatic copy number variation (CNV) in the genesis of congenital heart defects (CHDs) are scarce, as cardiac tissue is difficult to obtain, especially in non-affected individuals. We explored the occurrence of copy number differences in monozygotic (MZ) twins discordant for the presence of a CHD, as an illustrative model for chromosomal mosaicism in CHDs. Array comparative genomic hybridization was performed on peripheral blood-derived DNA obtained from 6 discordant MZ twin pairs and on sex-matched reference samples. To identify CNV differences between both twin members as well as potential CNVs in both twins contributing to the phenotype, DNA from each twin was hybridized against its co-twin, and against a normal control. Three copy number differences in 1 out of 6 MZ twin pairs were detected, confirming the occurrence of somatic CNV events in MZ twins. Further investigation by copy number and (epi)genome sequencing analyses in MZ twins, discordant for the presence of CHDs, is required to improve our knowledge on how postzygotic genetic, environmental and stochastic factors can affect human heart development.
DOI: 10.6084/m9.figshare.5123137
title: Supplementary Material for: The Expression of Preaxial Polydactyly Is Influenced by Modifying Genetic Elements and Is Not Maintained by Chromosomal Inversion in an Avian Biomedical Model

description: Polydactyly (Po) is a common mutation found in many vertebrates. The UCD-Po.003 congenic chicken line was previously characterized for Po inheritance (autosomal dominant) and the mutation was mapped to chromosome 2p. Here, we describe for the first time the range and variability of the phenotype in this congenic line. Further, we studied the hypothesis that a chromosomal inversion was responsible for the maintenance of a large (6.3 Mb) candidate gene region. Fluorescence in situ hybridization employing BACs encompassing a 10.7-Mb region of GGA2p showed that the Po chromosome was normal, i.e. exhibits the wild-type BAC order. Continued fine-mapping along with a change in breeding strategy reduced the size of the causative region to 1.43 Mb. Recent research indicates that the cause of preaxial Po resides within a 794-bp highly conserved zone of polarizing activity regulatory sequence (ZRS) element located in intron 5 of the <i>LMBR1</i> gene; however, the ZRS polymorphism of interest is found in some but not all breeds of polydactylous chicken. Therefore, we sequenced the ZRS in 101 heterozygous and 30 unaffected (wild-type) individuals to establish the relevance of this region to the Po condition in the UCD-Po.003 congenic line. A single point mutation (C/A at coordinate GGA2p: 8,414,121) within the ZRS segregated with carrier status. The polydactylous UCD-Silkie line also maintains this SNP in addition to a single base deletion. An inheritance analysis of the phenotypic variation in UCD-Po.003 suggests recessive epistasis as the mode of inheritance for the additional modifying genetic elements, residing outside the ZRS, to impact the preaxial polydactyl phenotype. These results contribute to our understanding of the cause of Po in an important vertebrate model.