cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5122768
title: Supplementary Material for: De novo Interstitial Triplication of <i>MECP2</i> in a Girl with Neurodevelopmental Disorder and Random X Chromosome Inactivation

description: Loss-of-function mutations of the <i>MECP2</i> gene are the cause of most cases of Rett syndrome in females, a progressive neurodevelopmental disorder characterized by severe mental retardation, global regression, hand stereotypies, and microcephaly. On the other hand, gain of dosage of this gene causes the <i>MECP2</i> duplication syndrome in males characterized by severe mental retardation, absence of speech development, infantile hypotonia, progressive spasticity, recurrent infections, and facial dysmorphism. Female carriers of a heterozygous duplication show a skewed X-inactivation pattern which is the most probable cause of the lack of clinical symptoms. In this paper, we describe a girl with a complex de novo copy number gain at Xq28 and non-skewed X-inactivation pattern that causes mental retardation and motor and language delay. This rearrangement implies triplication of the <i>MECP2</i> and <i>IRAK1</i> genes, but it does not span other proximal genes located in the common minimal region of patients affected by the <i>MECP2 </i>duplication syndrome. We conclude that the triplication leads to a severe phenotype due to random X-inactivation, while the preferential X chromosome inactivation in healthy carriers may be caused by a negative selection effect of the duplication on some proximal genes like <i>ARD1A</i> or <i>HCFC1</i>.
DOI: 10.6084/m9.figshare.5122771.v1
title: Supplementary Material for: Hypospadias in a Male (78,XY; <i>SRY</i>-Positive) Dog and Sex Reversal Female (78,XX; <i>SRY</i>-Negative) Dogs: Clinical, Histological and Genetic Studies

description: Hypospadias is rarely reported in dogs. In this study we pre-sent 2 novel cases of this disorder of sexual development and, in addition, a case of hereditary sex reversal in a female with an enlarged clitoris. The first case was a male Moscow watchdog with a normal karyotype (78,XY) and the presence of the <i>SRY</i> gene. In this dog, perineal hypospadias, bilateral inguinal cryptorchidism and testes were observed. The second case, representing the Cocker spaniel breed, had a small penis with a hypospadic orifice of the urethra, bilateral cryptorchidism, testis and a rudimentary gonad inside an ovarian bursa, a normal female karyotype (78,XX) and a lack of the <i>SRY</i> gene. This animal was classified as a compound sex reversal (78,XX, <i>SRY</i>-negative) with the hypospadias syndrome. The third case was a Cocker spaniel female with an enlarged clitoris and internally located ovotestes. Cytogenetic and molecular analyses revealed a normal female karyotype (78,XX) and a lack of the <i>SRY</i> gene, while histology of the gonads showed an ovotesticular structure. This case was classified as a typical hereditary sex reversal syndrome (78,XX, <i>SRY</i>-negative). Molecular studies were focused on coding sequences of the <i>SRY</i> gene (case 1) and 2 candidates for monogenic hypospadias, namely <i>MAMLD1</i> (mastermind-like domain containing 1) and <i>SRD5A2</i> (steroid-5-alpha-reductase, alpha polypeptide 2). Sequencing of the entire<i> SRY</i> gene, including 5′- and 3′-flanking regions, did not reveal any mutation. The entire coding sequence of <i>MAMLD1</i> and <i>SRD5A2</i> was analyzed in all the intersexes, as well as in 4 phenotypically normal control dogs (3 females and 1 male). In <i>MAMLD1</i> 2 SNPs, including 1 missense substitution in exon 1 (c.128A&gt;G, Asp43Ser), were identified, whereas in <i>SRD5A2</i> 7 polymorphisms, including 1 missense SNP (c.358G&gt;A, Ala120Thr), were found. None of the identified polymorphisms cosegregated with the intersexual phenotype, thus, we cannot confirm that hypospadias may be associated with polymorphism in the coding sequence of the studied genes.
DOI: 10.6084/m9.figshare.5122759
title: Supplementary Material for: Abnormal MicroRNA Expression in Ts65Dn Hippocampus and Whole Blood: Contributions to Down Syndrome Phenotypes

description: Down syndrome (DS; trisomy 21) is one of the most common genetic causes of intellectual disability, which is attributed to triplication of genes located on chromosome 21. Elevated levels of several microRNAs (miRNAs) located on chromosome 21 have been reported in human DS heart and brain tissues. The Ts65Dn mouse model is the most investigated DS model with a triplicated segment of mouse chromosome 16 harboring genes orthologous to those on human chromosome 21. Using ABI TaqMan miRNA arrays, we found a set of miRNAs that were significantly up- or downregulated in the Ts65Dn hippocampus compared to euploid controls. Furthermore, miR-155 and miR-802 showed significant overexpression in the Ts65Dn hippocampus, thereby confirming results of previous studies. Interestingly, miR-155 and miR-802 were also overexpressed in the Ts65Dn whole blood but not in lung tissue. We also found overexpression of the miR-155 precursors, pri- and pre-miR-155 derived from the miR-155 host gene, known as B cell integration cluster, suggesting enhanced biogenesis of miR-155. Bioinformatic analysis revealed that neurodevelopment, differentiation of neuroglia, apoptosis, cell cycle, and signaling pathways including ERK/MAPK, protein kinase C, phosphatidylinositol 3-kinase, m-TOR and calcium signaling are likely targets of these miRNAs. We selected some of these potential gene targets and found downregulation of mRNA encoding Ship1, Mecp2 and Ezh2 in Ts65Dn hippocampus. Interestingly, the miR-155 target gene Ship1 (inositol phosphatase) was also downregulated in Ts65Dn whole blood but not in lung tissue. Our findings provide insights into miRNA-mediated gene regulation in Ts65Dn mice and their potential contribution to impaired hippocampal synaptic plasticity and neurogenesis, as well as hemopoietic abnormalities observed in DS.
DOI: 10.6084/m9.figshare.5122762
title: Supplementary Material for: Quality of Life after Traumatic Injury: A Latent Trajectory Modeling Approach

description: <b><i>Background:</i></b> It is largely unknown how quality of life (QoL) changes following accidental injuries. Equally, the mechanisms underlying such changes have not yet been identified in detail. This study of injured accident survivors aimed to: (1) detect a model of change which best explains the observed course of QoL, and (2) identify potential predictor variables. <b><i>Methods:</i></b> 323 injured accident survivors were interviewed within 2 weeks of the trauma, and followed up at 6 and 12 months. Latent trajectory modeling was used to analyze the fit of three potential trajectories regarding the observed course of general QoL as measured by the Questions on Life Satisfaction questionnaire. <b><i>Results:</i></b> The trajectory model adopting a negative square-root change fitted the observed data best, meaning that shortly after the accident, general QoL decreased strongly with diminishing negative changes occurring later on. Early and prolonged QoL impairment was largely attributable to the initial level of posttraumatic stress as measured by the Clinician-Administered PTSD Scale. To a lesser extent, depressive symptoms also predicted change in subjective QoL, while injury severity showed no direct effect; rather, its impact on QoL was mediated by initial posttraumatic stress. By contrast, reduced occupational functioning was attributable to injury severity rather than psychopathology. <b><i>Conclusions:</i></b> When treating injured accident survivors, clinicians should consider symptoms of posttraumatic stress and comorbid depression in order to prevent or mitigate negative changes in QoL.
DOI: 10.6084/m9.figshare.5122765.v1
title: Supplementary Material for: Alexithymia in Cancer Patients: Review of the Literature

description: <i>Objective:</i> To summarize the literature on alexithymia in cancer patients. <i>Methods:</i> The empirical literature published between 1972 and January 2010 was searched through MEDLINE, PSYINFO, EMBASE and the Cochrane Library. Key words were: alexithymia, affective symptoms, cancer, neoplasms. <i>Results:</i> The search identified 16 relevant studies which are methodologically problematic and show conflicting results. However, several interesting hypotheses emerge such as a possible link between alexithymia and the immune system, between alexithymia and quality of life, or between alexithymia, anxiety and depression. The question to what degree alexithymia in cancer patients is a trait or a state cannot be answered by these studies. <i>Conclusions:</i> A lack of methodologically sound studies and the large variations of results among studies suggest that the role of alexithymia in patients with cancer deserves more systematic research. Consequently, studies are needed which investigate the nature (state or trait) of alexithymia, its impact on cancer development and progression, as well as its influence on compliance and on the underestimation of psychological distress and psychiatric outcome in cancer patients.
DOI: 10.6084/m9.figshare.5122768.v1
title: Supplementary Material for: De novo Interstitial Triplication of <i>MECP2</i> in a Girl with Neurodevelopmental Disorder and Random X Chromosome Inactivation

description: Loss-of-function mutations of the <i>MECP2</i> gene are the cause of most cases of Rett syndrome in females, a progressive neurodevelopmental disorder characterized by severe mental retardation, global regression, hand stereotypies, and microcephaly. On the other hand, gain of dosage of this gene causes the <i>MECP2</i> duplication syndrome in males characterized by severe mental retardation, absence of speech development, infantile hypotonia, progressive spasticity, recurrent infections, and facial dysmorphism. Female carriers of a heterozygous duplication show a skewed X-inactivation pattern which is the most probable cause of the lack of clinical symptoms. In this paper, we describe a girl with a complex de novo copy number gain at Xq28 and non-skewed X-inactivation pattern that causes mental retardation and motor and language delay. This rearrangement implies triplication of the <i>MECP2</i> and <i>IRAK1</i> genes, but it does not span other proximal genes located in the common minimal region of patients affected by the <i>MECP2 </i>duplication syndrome. We conclude that the triplication leads to a severe phenotype due to random X-inactivation, while the preferential X chromosome inactivation in healthy carriers may be caused by a negative selection effect of the duplication on some proximal genes like <i>ARD1A</i> or <i>HCFC1</i>.
DOI: 10.6084/m9.figshare.5122756
title: Supplementary Material for: Topoisomerase Mutations That Are Associated with High-Level Resistance to Earlier Fluoroquinolones in <i>Staphylococcus aureus</i> Have Less Effect on the Antibacterial Activity of Besifloxacin

description: <i>Background:</i> The impact of mutations in DNA gyrase and topoisomerase IV on minimum inhibitory concentrations (MICs) was investigated to better understand why besifloxacin has a higher potency against <i>Staphylococcus aureus</i> when compared to other fluoroquinolones, which was especially pronounced against ciprofloxacin-resistant isolates. <i>Methods:</i> MICs were determined for 52 clinical isolates against besifloxacin, moxifloxacin, gatifloxacin, ciprofloxacin, and levofloxacin. The genes encoding GyrA, GyrB, ParC, and ParE were sequenced and the potential impact of mutations assessed in light of recent structural data. <i>Results:</i> For all fluoroquinolones tested, the MICs increased with the number of mutations in the quinolone resistance-determining regions. However, this increase was the smallest for besifloxacin and the largest for ciprofloxacin and levofloxacin. In addition to the commonly observed mutations in ParC and GyrA, more unusual mutations in ParE, such as Asp-432→His or Pro-585→Ser, were also detected. <i>Conclusions:</i> Compared to earlier fluoroquinolones, the higher potency of besifloxacin suggests that the drug’s unique combination of a 7-azepinyl ring and an 8-chloro-substituent results in unique interactions with DNA gyrase and topoisomerase IV.
DOI: 10.6084/m9.figshare.5122750
title: Supplementary Material for: Sensitivity and Specificity of Urinary Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 for the Diagnosis of Renal Cell Carcinoma

description: <i>Background/Aims:</i> Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are urinary biomarkers of diagnostic relevance in a wide variety of acute and chronic kidney diseases. Their diagnostic sensitivity and specificity for kidney cancer are largely unknown and therefore the subject of this investigation. <i>Methods:</i> A prospective cohort study was performed to evaluate urine biomarkers for clear-cell and papillary subtypes of renal cancer (67 patients undergoing nephrectomy) and 55 control patients undergoing non-kidney surgery. Urinary KIM-1 and NGAL concentrations were determined by sensitive and specific ELISAs. <i>Results:</i> In renal cancer patients, median NGAL excretion was 0.52 (1st to 3rd quartiles: 0.28–0.82) ng/mg urinary creatinine (U<sub>Cr</sub>) before nephrectomy compared to 0.15 (0.04–0.31) ng/mg U<sub>Cr</sub> in controls (p &lt; 0.001), and there was a modest decrease of 30% after nephrectomy (p &lt; 0.008). NGAL was not correlated to tumor size (r = 0.19, p = 0.27) or stage. Before nephrectomy, KIM-1 excretion was 0.68 (0.40–1.12) ng/mg U<sub>Cr</sub> compared to 0.03 (0.01–0.06) in controls (p &lt; 0.001). There was a linear correlation between KIM-1 excretion before nephrectomy and tumor size (Spearman’s r = 0.66, p &lt; 0.001), tumor stage, and a 50% decrease in median KIM-1 concentration 1 month following tumor excision (p &lt; 0.01). Biomarker concentration ranges for renal cancer patients and controls overlapped substantially for NGAL but not KIM-1. <i>Conclusion:</i> NGAL is not a sensitive or specific urinary biomarker of kidney cancer. Although KIM-1 had diagnostic sensitivity for kidney cancer, it is well known to reflect many types of kidney injuries, thus limiting its specificity as a diagnostic biomarker for renal cancer.
DOI: 10.6084/m9.figshare.5122753
title: Supplementary Material for: Protective Therapy with Novel Chromone Derivative against <i>Leishmania donovani</i> Infection Induces Th1 Response in vivo

description: <i>Background:</i> Visceral leishmaniasis is a chronic protozoan disease caused by <i>Leishmania donovani,</i> an obligatory intracellular parasite that resides and multiplies within macrophages of the reticuloendothelial system. The aim of this study was to evaluate the efficacy of nine novel synthetic chromone derivatives as antileishmanial molecules in experimental murine visceral leishmaniasis. <i>Methods:</i> In vitro activity of the molecules (2, 5 and 10 µg/ml) was assessed against promastigotes of both pentavalent antimonial-responsive strain AG83 and pentavalent antimonial-resistant strain GE1F8R at days 2 (48 h), 4 (96 h) and 6 (144 h). The efficacy of the most efficient chromone derivative [C-(6-Methyl-4-oxo-4<i>H</i>-1-benzopyran-3-yl)-N-(<i>p</i>-tolyl) nitrone], designated here as NP1, was also tested against intracellular amastigotes in vitro and in vivo. <i>Results:</i> NP1, 5 µg/ml, inhibited the growth of AG83 and GE1F8R promastigotes by 98.57% (day 4) and 75.75% (day 6), respectively, and also inhibited the growth of intracellular amastigotes by 85% (day 3), compared to DMSO control. Treatment of <i>L. donovani-</i>infected mice with NP1 resulted in a 70% significant decrease in parasite load in the spleen in the 7th week after infection (5 mice in each group), with associated induction of interferon-γ synthesis by dose 2 (37.5 mg/kg body weight) compared to DMSO control. Dose 2 was found efficient over dose 1 (25 mg/kg body weight). <i>Conclusions:</i> The novel synthetic chromone derivative is effective in the treatment of visceral leishmaniasis and induces the synthesis of interferon-γ in rodent models.
DOI: 10.6084/m9.figshare.5122762.v1
title: Supplementary Material for: Quality of Life after Traumatic Injury: A Latent Trajectory Modeling Approach

description: <b><i>Background:</i></b> It is largely unknown how quality of life (QoL) changes following accidental injuries. Equally, the mechanisms underlying such changes have not yet been identified in detail. This study of injured accident survivors aimed to: (1) detect a model of change which best explains the observed course of QoL, and (2) identify potential predictor variables. <b><i>Methods:</i></b> 323 injured accident survivors were interviewed within 2 weeks of the trauma, and followed up at 6 and 12 months. Latent trajectory modeling was used to analyze the fit of three potential trajectories regarding the observed course of general QoL as measured by the Questions on Life Satisfaction questionnaire. <b><i>Results:</i></b> The trajectory model adopting a negative square-root change fitted the observed data best, meaning that shortly after the accident, general QoL decreased strongly with diminishing negative changes occurring later on. Early and prolonged QoL impairment was largely attributable to the initial level of posttraumatic stress as measured by the Clinician-Administered PTSD Scale. To a lesser extent, depressive symptoms also predicted change in subjective QoL, while injury severity showed no direct effect; rather, its impact on QoL was mediated by initial posttraumatic stress. By contrast, reduced occupational functioning was attributable to injury severity rather than psychopathology. <b><i>Conclusions:</i></b> When treating injured accident survivors, clinicians should consider symptoms of posttraumatic stress and comorbid depression in order to prevent or mitigate negative changes in QoL.
DOI: 10.6084/m9.figshare.5122747
title: Supplementary Material for: Updated Neuronal Scaling Rules for the Brains of Glires (Rodents/Lagomorphs)

description: Brain size scales as different functions of its number of neurons across mammalian orders such as rodents, primates, and insectivores. In rodents, we have previously shown that, across a sample of 6 species, from mouse to capybara, the cerebral cortex, cerebellum and the remaining brain structures increase in size faster than they gain neurons, with an accompanying decrease in neuronal density in these structures [Herculano-Houzel et al.: Proc Natl Acad Sci USA 2006;103:12138–12143]. Important remaining questions are whether such neuronal scaling rules within an order apply equally to all pertaining species, and whether they extend to closely related taxa. Here, we examine whether 4 other species of Rodentia, as well as the closely related rabbit (Lagomorpha), conform to the scaling rules identified previously for rodents. We report the updated neuronal scaling rules obtained for the average values of each species in a way that is directly comparable to the scaling rules that apply to primates [Gabi et al.: Brain Behav Evol 2010;76:32–44], and examine whether the scaling relationships are affected when phylogenetic relatedness in the dataset is accounted for. We have found that the brains of the spiny rat, squirrel, prairie dog and rabbit conform to the neuronal scaling rules that apply to the previous sample of rodents. The conformity to the previous rules of the new set of species, which includes the rabbit, suggests that the cellular scaling rules we have identified apply to rodents in general, and probably to Glires as a whole (rodents/lagomorphs), with one notable exception: the naked mole-rat brain is apparently an outlier, with only about half of the neurons expected from its brain size in its cerebral cortex and cerebellum.
DOI: 10.6084/m9.figshare.5122759.v1
title: Supplementary Material for: Abnormal MicroRNA Expression in Ts65Dn Hippocampus and Whole Blood: Contributions to Down Syndrome Phenotypes

description: Down syndrome (DS; trisomy 21) is one of the most common genetic causes of intellectual disability, which is attributed to triplication of genes located on chromosome 21. Elevated levels of several microRNAs (miRNAs) located on chromosome 21 have been reported in human DS heart and brain tissues. The Ts65Dn mouse model is the most investigated DS model with a triplicated segment of mouse chromosome 16 harboring genes orthologous to those on human chromosome 21. Using ABI TaqMan miRNA arrays, we found a set of miRNAs that were significantly up- or downregulated in the Ts65Dn hippocampus compared to euploid controls. Furthermore, miR-155 and miR-802 showed significant overexpression in the Ts65Dn hippocampus, thereby confirming results of previous studies. Interestingly, miR-155 and miR-802 were also overexpressed in the Ts65Dn whole blood but not in lung tissue. We also found overexpression of the miR-155 precursors, pri- and pre-miR-155 derived from the miR-155 host gene, known as B cell integration cluster, suggesting enhanced biogenesis of miR-155. Bioinformatic analysis revealed that neurodevelopment, differentiation of neuroglia, apoptosis, cell cycle, and signaling pathways including ERK/MAPK, protein kinase C, phosphatidylinositol 3-kinase, m-TOR and calcium signaling are likely targets of these miRNAs. We selected some of these potential gene targets and found downregulation of mRNA encoding Ship1, Mecp2 and Ezh2 in Ts65Dn hippocampus. Interestingly, the miR-155 target gene Ship1 (inositol phosphatase) was also downregulated in Ts65Dn whole blood but not in lung tissue. Our findings provide insights into miRNA-mediated gene regulation in Ts65Dn mice and their potential contribution to impaired hippocampal synaptic plasticity and neurogenesis, as well as hemopoietic abnormalities observed in DS.
DOI: 10.6084/m9.figshare.5122744
title: Supplementary Material for: Prevalence of Atopy and Allergic Diseases in Korean Children: Associations with a Farming Environment and Rural Lifestyle

description: <i>Background:</i> The results of recent studies suggest that factors in rural environments may protect against the development of allergic diseases, but the underlying mechanisms are not well understood. The aim of this study was to investigate the prevalence of allergic diseases, to establish if this prevalence is influenced by migration from rural to urban areas and to identify environmental risk factors associated with these diseases. <i>Methods:</i> A cross-sectional study of children aged 9–12 years from a rural village, a rural town and an urban city in Korea was conducted. Demographic and disease-related information was obtained via a detailed questionnaire, and skin prick tests were performed. <i>Results:</i> There were significant differences in lifestyle and environmental factors between children from the rural village, the rural town and the urban children. The prevalence of allergic diseases and atopy was higher in urban children. A lower prevalence of allergic diseases and atopy was associated with farming parents, contact with farm animals during pregnancy, owning pets or a stable, breast-feeding and having older siblings. A comparison of rural village and rural town children revealed no evidence of an association of allergic diseases and atopy with farming parents, contact with farm animals during pregnancy or owning a stable. On the other hand, having older siblings and antibiotic use during infancy were significantly associated with allergic diseases and atopy in these children. <i>Conclusions:</i> Protective factors associated with a farming environment and/or rural lifestyle may influence the prevalence of allergic diseases and atopy in Korean children.