cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5122441
title: Supplementary Material for: Transcranial Sonography Reveals Cerebellar, Nigral, and Forebrain Abnormalities in Friedreich’s Ataxia

description: <i>Background:</i> Friedreich’s ataxia (FA) is essentially characterized by degeneration of the dorsal root ganglia, the dorsal nuclei of Clarke, and the long spinal fiber tracts, yet there is accumulating evidence that neurodegeneration extends beyond these predilection sites. Transcranial sonography (TCS) has evolved as a valuable complementary neuroimaging tool in the assessment of neurodegenerative diseases due to its capacity to well depict structural changes and the accumulation of heavy metals. Its use for assessing cerebellar neurodegeneration, however, has not yet been investigated.Here we investigated whether TCS allows to assess particular features of cerebellar as well as midbrain and forebrain abnormalities in FA. <i>Methods:</i> Comprehensive TCS imaging of 34 FA patients and 34 age-matched healthy controls. <i>Results:</i> Hyperechogenicity of the dentate nucleus was very frequent in FA patients (85%) and could even be observed in patients with short disease duration, suggesting that dentate alterations are a common and probably early feature of FA. Substantia nigra was significantly hypoechogenic, possibly indicating regional changes in subcellular brain iron regulation. FA patients showed significantly enlarged 4th, 3rd, and lateral ventricles, thus corroborating earlier MRI and postmortem findings of substantial cerebellar and forebrain atrophy in FA. <i>Conclusions:</i> TCS provides a quick-to-apply and inexpensive in vivo assessment of both cerebellar and noncerebellar abnormalities in FA, in particular highlighting dentate hyperechogenicity as a core feature. It might serve as a promising tool for imaging aspects of cerebellar neurodegeneration also in other neurodegenerative disorders.
DOI: 10.6084/m9.figshare.5122447.v1
title: Supplementary Material for: Variation in Missegregation Rates among Human Chromosomes in Hybrid Cells

description: Chinese hamster ovary-human hybrid cells containing chromosomes 16, 18, X, or 21 have been used to test the ability of human kinetochores to successfully bind to spindle microtubules and to be distributed to daughter cells. The intrinsic rates of non-disjunction among these human chromosomes have been determined and compared to non-disjunction rates in cells presented with taxol as a mitotic challenge. Cells grown on culture slides were fixed and processed for immunofluorescence and fluorescence in situ hybridization. Daughter cell pairs were identified by staining with anti-α-tubulin to identify midbodies. DNA probes specific for human centromeres were used to test for the successful passage of human chromosomes to daughter cells. Our data indicate that different human kinetochores vary in their ability to properly engage the spindle and to be successfully distributed. In addition, our data indicate that the 4 human chromosomes studied can be divided into 2 groups, based on their overall intrinsic rate of non-disjunction and their response to microtubule perturbation. The mechanism of this effect is not yet known.
DOI: 10.6084/m9.figshare.5122435
title: Supplementary Material for: On the Uses and Applications of the Most Commonly Used Measures of Linkage Disequilibrium from the Comparative Analysis of Their Statistical Properties

description: <i>Background/Objective:</i> The analysis of linkage disequilibrium is relevant for the exploration of the structure and evolution of genomes and for the gene mapping of quantitative characters and human diseases. The strength of linkage disequilibrium between diallelic loci is commonly measured by the coefficients <i>D</i>′ and <i>r</i>. Recent studies suggest that <i>r</i> is more useful than <i>D</i>′ as a general measure of the strength of disequilibrium because it provides much more precise (lower sampling variance) and accurate (lower bias) estimates of disequilibrium. We compared for the first time the statistical properties of <i>D</i>′ and <i>r</i> taking into account their differences in range. <i>Methods:</i> The sampling properties of <i>D</i>′ and <i>r</i> were evaluated by simulation under a variety of realistic population conditions and varying sample sizes using standardised statistics that allow for comparisons of the precision, accuracy and efficiency of estimates with different ranges. <i>Results:</i> Simulations revealed that estimates of <i>r</i> do not tend to be significantly more precise, accurate or efficient than those of <i>D</i>′ when compared by means of standardised statistics. <i>Conclusion:</i> The supposed advantage of <i>r</i> over <i>D</i>′ based on direct comparisons of their sampling distributions is more apparent than real. The obtained results are useful to assess the uses and applications of these widely used disequilibrium measures.
DOI: 10.6084/m9.figshare.5122450.v1
title: Supplementary Material for: Dendrin Location in Podocytes Is Associated with Disease Progression in Animal and Human Glomerulopathy

description: <i>Background:</i> Adriamycin (ADR) nephrosis in mice has been extensively studied and has enabled a greater understanding of the processes underlying the progression of renal injury. Dendrin is a novel component of the slit diaphragm with proapoptotic signaling properties, and it accumulates in the podocyte nucleus in response to glomerular injury in mice. The present study re-evaluated chronic progressive nephropathy in ADR mice and the localization of dendrin in mice and in human glomerulopathy. <i>Methods:</i> To investigate the localization of dendrin, a mouse model of nephrosis and glomerulosclerosis was used, in which ADR was injected once. WT-1-positive cells and apoptotic cells were counted in vivo and in vitro. To check the expression of dendrin in ADR mice, immunostaining and Western blot were performed. A survey of dendrin staining was performed on human kidney biopsy specimens. <i>Results:</i> The injection of ADR induced proteinuria, podocyte loss and glomerulosclerosis. It also caused the relocation of dendrin from the slit diaphragm to the podocyte nucleus. We demonstrated the location of dendrin to podocyte nuclei in several cases of human glomerulopathy. The mean occurrence of dendrin-positive nucleus per glomerulus increased in several cases of human glomerulopathy. <i>Conclusions:</i> These findings suggest that the relocation of dendrin to the podocyte nuclei is useful as a novel marker of podocyte injury in human glomerulopathy.
DOI: 10.6084/m9.figshare.5122441.v1
title: Supplementary Material for: Transcranial Sonography Reveals Cerebellar, Nigral, and Forebrain Abnormalities in Friedreich’s Ataxia

description: <i>Background:</i> Friedreich’s ataxia (FA) is essentially characterized by degeneration of the dorsal root ganglia, the dorsal nuclei of Clarke, and the long spinal fiber tracts, yet there is accumulating evidence that neurodegeneration extends beyond these predilection sites. Transcranial sonography (TCS) has evolved as a valuable complementary neuroimaging tool in the assessment of neurodegenerative diseases due to its capacity to well depict structural changes and the accumulation of heavy metals. Its use for assessing cerebellar neurodegeneration, however, has not yet been investigated.Here we investigated whether TCS allows to assess particular features of cerebellar as well as midbrain and forebrain abnormalities in FA. <i>Methods:</i> Comprehensive TCS imaging of 34 FA patients and 34 age-matched healthy controls. <i>Results:</i> Hyperechogenicity of the dentate nucleus was very frequent in FA patients (85%) and could even be observed in patients with short disease duration, suggesting that dentate alterations are a common and probably early feature of FA. Substantia nigra was significantly hypoechogenic, possibly indicating regional changes in subcellular brain iron regulation. FA patients showed significantly enlarged 4th, 3rd, and lateral ventricles, thus corroborating earlier MRI and postmortem findings of substantial cerebellar and forebrain atrophy in FA. <i>Conclusions:</i> TCS provides a quick-to-apply and inexpensive in vivo assessment of both cerebellar and noncerebellar abnormalities in FA, in particular highlighting dentate hyperechogenicity as a core feature. It might serve as a promising tool for imaging aspects of cerebellar neurodegeneration also in other neurodegenerative disorders.
DOI: 10.6084/m9.figshare.5122426
title: Supplementary Material for: Expression and Functional Analysis of Dkk1 during Early Gonadal Development

description: WNT signalling plays a central role in mammalian sex determination by promoting ovarian development and repressing aspects of testis development in the early gonad. Dickkopf homolog 1 (DKK1) is a WNT signalling antagonist that plays critical roles in multiple developmental systems by modulating WNT activity. Here, we examined the role of DKK1 in mouse sex determination and early gonadal development. <i>Dkk1</i> mRNA was upregulated sex-specifically during testis differentiation, suggesting that DKK1 could repress WNT signalling in the developing testis. However, we observed overtly normal testis development in <i>Dkk1</i>-null XY gonads, and found no significant upregulation of <i>Axin2</i> or <i>Sp5</i> that would indicate increased canonical WNT signalling. Nor did we find significant differences in expression of key markers of testis and ovarian development. We propose that DKK1 may play a protective role that is not unmasked by loss-of-function in the absence of other stressors.
DOI: 10.6084/m9.figshare.5122429
title: Supplementary Material for: Holocentric Chromosomes of <i>Luzula elegans</i> Are Characterized by a Longitudinal Centromere Groove, Chromosome Bending, and a Terminal Nucleolus Organizer Region

description: The structure of holocentric chromosomes was analyzed in mitotic cells of <i>Luzula elegans</i>. Light and scanning electron microscopy observations provided evidence for the existence of a longitudinal groove along each sister chromatid. The centromere-specific histone H3 variant, CENH3, colocalized with this groove and with microtubule attachment sites. The terminal chromosomal regions were CENH3-negative. During metaphase to anaphase transition, <i>L. elegans</i> chromosomes typically curved to a sickle-like shape, a process that is likely to be influenced by the pulling forces of microtubules along the holocentric axis towards the corresponding microtubule organizing regions. A single pair of 45S rDNA sites, situated distal to <i>Arabidopsis</i>-telomere repeats, was observed at the terminal region of one chromosome pair. We suggest that the 45S rDNA position in distal centromere-free regions could be required to ensure chromosome stability.
DOI: 10.6084/m9.figshare.5122432
title: Supplementary Material for: Neurotrophin-3 Gene-Modified Schwann Cells Promote TrkC Gene-Modified Mesenchymal Stem Cells to Differentiate into Neuron-Like Cells in Poly(Lactic-Acid-Co-Glycolic Acid) Multiple-Channel Conduit

description: Rapid progress in the field of nerve tissue engineering has opened up the way for new therapeutic strategies for spinal cord injury (SCI). Bone marrow-derived mesenchymal stem cells (MSCs) could be differentiated into neural lineages, which can be used as a potential cell source for nerve repair. Schwann cells (SCs) have been reported to support structural and functional recovery of SCI. In this study, we co-cultured neurotrophin-3 (NT-3) gene-modified SCs and NT-3 receptor tyrosine protein kinase C (TrkC) gene-modified MSCs in a three-dimensional porous poly(lactic-acid-co-glycolic acid) (PLGA) conduit with multiple channels in vitro for 14 days. Our results showed that more than 50% of the grafted MSCs were MAP2- and β-III-tubulin-positive cells, and the MSCs expressed a high level of β-III-tubulin detected by Western blotting, indicating a high rate of neuronal differentiation. Furthermore, immunostaining of PSD95 revealed the formation of a synapse-like structure, which was confirmed under electron microscopy. In conclusion, co-culture of NT-3 gene-modified SCs and TrkC gene-modified MSCs in the PLGA multiple-channeled conduit can promote MSCs’ differentiation into neuron-like cells with synaptogenesis potential. Our study provides a biological basis for future application of this artificial MSCs/SCs/PLGA complex in the SCI treatment.
DOI: 10.6084/m9.figshare.5122435.v1
title: Supplementary Material for: On the Uses and Applications of the Most Commonly Used Measures of Linkage Disequilibrium from the Comparative Analysis of Their Statistical Properties

description: <i>Background/Objective:</i> The analysis of linkage disequilibrium is relevant for the exploration of the structure and evolution of genomes and for the gene mapping of quantitative characters and human diseases. The strength of linkage disequilibrium between diallelic loci is commonly measured by the coefficients <i>D</i>′ and <i>r</i>. Recent studies suggest that <i>r</i> is more useful than <i>D</i>′ as a general measure of the strength of disequilibrium because it provides much more precise (lower sampling variance) and accurate (lower bias) estimates of disequilibrium. We compared for the first time the statistical properties of <i>D</i>′ and <i>r</i> taking into account their differences in range. <i>Methods:</i> The sampling properties of <i>D</i>′ and <i>r</i> were evaluated by simulation under a variety of realistic population conditions and varying sample sizes using standardised statistics that allow for comparisons of the precision, accuracy and efficiency of estimates with different ranges. <i>Results:</i> Simulations revealed that estimates of <i>r</i> do not tend to be significantly more precise, accurate or efficient than those of <i>D</i>′ when compared by means of standardised statistics. <i>Conclusion:</i> The supposed advantage of <i>r</i> over <i>D</i>′ based on direct comparisons of their sampling distributions is more apparent than real. The obtained results are useful to assess the uses and applications of these widely used disequilibrium measures.
DOI: 10.6084/m9.figshare.5122426.v1
title: Supplementary Material for: Expression and Functional Analysis of Dkk1 during Early Gonadal Development

description: WNT signalling plays a central role in mammalian sex determination by promoting ovarian development and repressing aspects of testis development in the early gonad. Dickkopf homolog 1 (DKK1) is a WNT signalling antagonist that plays critical roles in multiple developmental systems by modulating WNT activity. Here, we examined the role of DKK1 in mouse sex determination and early gonadal development. <i>Dkk1</i> mRNA was upregulated sex-specifically during testis differentiation, suggesting that DKK1 could repress WNT signalling in the developing testis. However, we observed overtly normal testis development in <i>Dkk1</i>-null XY gonads, and found no significant upregulation of <i>Axin2</i> or <i>Sp5</i> that would indicate increased canonical WNT signalling. Nor did we find significant differences in expression of key markers of testis and ovarian development. We propose that DKK1 may play a protective role that is not unmasked by loss-of-function in the absence of other stressors.
DOI: 10.6084/m9.figshare.5122423
title: Supplementary Material for: <i>FOXD1</i> Duplication Causes Branchial Defects and Interacts with the <i>TFAP2A</i> Gene Implicated in the Branchio-Oculo-Facial Syndrome in Causing Eye Effects in Zebrafish

description: Branchio-oculo-facial syndrome (BOFS) is a rare disorder characterized by maldevelopment of the first and second branchial arches, skin defects, facial dysmorphism, auricular, ophthalmological and oral abnormalities. A high clinical variability has been reported. Recently, mutations in <i>TFAP2A</i> were found to underlie this condition. A small duplication on 5q13 was detected in 2 family members with mild BOFS features. Molecular cytogenetic delineation of the duplication demonstrated that only 7 genes are affected: <i>LOC100289045, RGNEF, UTP15, ANKRA2, FUNDC2P1, BTF3</i> and <i>FOXD1</i>. The latter is expressed in the developing branchial arches and involved in cranio-facial development. Zebrafish embryos with combined inhibition of the expression of <i>foxd1l</i> and <i>tfap2a</i> show optic axis defects. We identified a novel locus associated with a mild BOFS-like phenotype. The functional in vivo experiments suggest an interaction between <i>FOXD1</i> and <i>TFAP2A</i>.
DOI: 10.6084/m9.figshare.5122417
title: Supplementary Material for: Cerebral Hemodynamic Failure Presenting as Limb-Shaking Transient Ischemic Attacks

description: Limb-shaking transient ischemic attacks (TIA) may occur in patients with insufficient brain perfusion due to an underlying occlusive disease. We present the case of a 64-year-old patient who suffered from repetitive TIA presenting with shaking movements of the right-sided extremities and accompanying speech arrest. Symptoms are documented in the online supplementary video (www.karger.com/doi/10.1159/000327683). These episodes were frequently triggered in orthostatic situations. The diagnosis of limb-shaking TIA was established. The diagnostic workup revealed pseudo-occlusion of the left internal carotid artery, a poor intracranial collateral status and, as a consequence, an exhausted vasomotor reserve capacity. At ultrasound examination, symptoms were provoked by a change of the patient’s position from supine to sitting. During evolvement of symptoms, a dramatic decrease of flow velocities in the left middle cerebral artery was observed. This case thus documents the magnitude and dynamics of perfusion failure in a rare manifestation of cerebral ischemic disease.
DOI: 10.6084/m9.figshare.5122420
title: Supplementary Material for: Advantages and Pitfalls of Three-Dimensional Ultrasound Imaging of Carotid Bifurcation

description: <i>Objectives:</i> Several specialists use three-dimensional (3D) ultrasound as adjuvant imaging technique in their clinical practice. It has been applied to study carotid plaque morphology, surface and volume during atherosclerosis progression. Nonetheless, no papers have so far described the use of this technique in conditions different than carotid stenosis, such as bifurcation anatomy changes of the caliber and vessel course modifications. <i>Methods:</i> Patients admitted to our ultrasound laboratory for vascular screening were submitted to standard carotid duplex and to 3D ultrasound reconstruction of the carotid bifurcation. <i>Results:</i> Forty normal subjects, 7 patients with caliber alterations (4 carotid bulb ectasia and 3 internal carotid lumen narrowing), 45 patients with course variations (tortuosities and kinking) and 35 patients with internal carotid artery stenosis of various degrees have been investigated. <i>Conclusions:</i> 3D ultrasound is a feasible technique. It can improve carotid axis imaging through a better presentation of caliber variations and vessel course ‘at a glance’. 3D ultrasound from the inward flow can provide imaging of the stenosis, but stenosis quantification should always take into account the assessment of plaque morphology and vessel wall.
DOI: 10.6084/m9.figshare.5122429.v1
title: Supplementary Material for: Holocentric Chromosomes of <i>Luzula elegans</i> Are Characterized by a Longitudinal Centromere Groove, Chromosome Bending, and a Terminal Nucleolus Organizer Region

description: The structure of holocentric chromosomes was analyzed in mitotic cells of <i>Luzula elegans</i>. Light and scanning electron microscopy observations provided evidence for the existence of a longitudinal groove along each sister chromatid. The centromere-specific histone H3 variant, CENH3, colocalized with this groove and with microtubule attachment sites. The terminal chromosomal regions were CENH3-negative. During metaphase to anaphase transition, <i>L. elegans</i> chromosomes typically curved to a sickle-like shape, a process that is likely to be influenced by the pulling forces of microtubules along the holocentric axis towards the corresponding microtubule organizing regions. A single pair of 45S rDNA sites, situated distal to <i>Arabidopsis</i>-telomere repeats, was observed at the terminal region of one chromosome pair. We suggest that the 45S rDNA position in distal centromere-free regions could be required to ensure chromosome stability.
DOI: 10.6084/m9.figshare.5122420.v1
title: Supplementary Material for: Advantages and Pitfalls of Three-Dimensional Ultrasound Imaging of Carotid Bifurcation

description: <i>Objectives:</i> Several specialists use three-dimensional (3D) ultrasound as adjuvant imaging technique in their clinical practice. It has been applied to study carotid plaque morphology, surface and volume during atherosclerosis progression. Nonetheless, no papers have so far described the use of this technique in conditions different than carotid stenosis, such as bifurcation anatomy changes of the caliber and vessel course modifications. <i>Methods:</i> Patients admitted to our ultrasound laboratory for vascular screening were submitted to standard carotid duplex and to 3D ultrasound reconstruction of the carotid bifurcation. <i>Results:</i> Forty normal subjects, 7 patients with caliber alterations (4 carotid bulb ectasia and 3 internal carotid lumen narrowing), 45 patients with course variations (tortuosities and kinking) and 35 patients with internal carotid artery stenosis of various degrees have been investigated. <i>Conclusions:</i> 3D ultrasound is a feasible technique. It can improve carotid axis imaging through a better presentation of caliber variations and vessel course ‘at a glance’. 3D ultrasound from the inward flow can provide imaging of the stenosis, but stenosis quantification should always take into account the assessment of plaque morphology and vessel wall.
DOI: 10.6084/m9.figshare.5122408
title: Google Trends time series

description: Google Trends time series on which analyses in Tran et al. (2017), published in PLOS ONE, were based on.<br>
DOI: 10.6084/m9.figshare.5122417.v1
title: Supplementary Material for: Cerebral Hemodynamic Failure Presenting as Limb-Shaking Transient Ischemic Attacks

description: Limb-shaking transient ischemic attacks (TIA) may occur in patients with insufficient brain perfusion due to an underlying occlusive disease. We present the case of a 64-year-old patient who suffered from repetitive TIA presenting with shaking movements of the right-sided extremities and accompanying speech arrest. Symptoms are documented in the online supplementary video (www.karger.com/doi/10.1159/000327683). These episodes were frequently triggered in orthostatic situations. The diagnosis of limb-shaking TIA was established. The diagnostic workup revealed pseudo-occlusion of the left internal carotid artery, a poor intracranial collateral status and, as a consequence, an exhausted vasomotor reserve capacity. At ultrasound examination, symptoms were provoked by a change of the patient’s position from supine to sitting. During evolvement of symptoms, a dramatic decrease of flow velocities in the left middle cerebral artery was observed. This case thus documents the magnitude and dynamics of perfusion failure in a rare manifestation of cerebral ischemic disease.
DOI: 10.6084/m9.figshare.5122393
title: poster-delft_fig-7

description: Figure 7 of poster for Cumulus Parameterization workshop in Deflt<br>
DOI: 10.6084/m9.figshare.5122408.v1
title: Google Trends time series

description: Google Trends time series on which analyses in Tran et al. (2017), published in PLOS ONE, were based on.<br>
DOI: 10.6084/m9.figshare.5122387
title: poster-delft_fig4

description: Figure 3 of Poster for Cumulus Parameterization workshop in Delft<br>
DOI: 10.6084/m9.figshare.5122390
title: poster-delft_fig-5

description: Figure 5 of poster fo Cumulus Parameterization workshop in Delft<br>
DOI: 10.6084/m9.figshare.5122393.v1
title: poster-delft_fig-7

description: Figure 7 of poster for Cumulus Parameterization workshop in Deflt<br>
DOI: 10.6084/m9.figshare.5122381
title: poster-delft_fig-3

description: Figure 2 for Poster at Cumulus Parameterization workshop in Delft