cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5121766.v1
title: Supplementary Material for: Direct Interaction of α-Synuclein and AKT Regulates IGF-1 Signaling: Implication of Parkinson Disease

description: Genetic mutation of α-synuclein (α-SYN) is clearly verified as the causal factor of human and mouse Parkinson’s disease. However, biological function of α-SYN has not been clearly demonstrated until now. In this investigation, we reveal that α-SYN is a co-regulator of growth factor-induced AKT activation. Elimination of SYN reduces the IGF-1-mediated AKT activation. Similarly, mutant SYN suppresses the IGF-1-induced AKT activation. Wild-type SYN can interact with AKT and enhance the solubility and plasma localization of AKT in response to IGF-1, whereas mutant α-SYNs do not interact with AKT. In addition, elevated expression of SYN blocks the AKT activation. We also find that si-RNA against α-SYN abolished the protective effect of IGF-1 against DNA damage-induced apoptosis. Our result strongly indicates that Parkinson’s disease, induced by α-SYN mutation, is evoked by deregulation of the AKT-signaling cascade.
DOI: 10.6084/m9.figshare.5121757
title: Supplementary Material for: Comparison of Area 17 Cellular Composition in Laboratory and Wild-Caught Rats Including Diurnal and Nocturnal Species

description: In this study we examine the size of primary sensory areas in the neocortex and the cellular composition of area 17/V1 in three rodent groups: laboratory nocturnal Norway rats (Long-Evans; <i>Rattus norvegicus</i>), wild-caught nocturnal Norway rats (<i>R. norvegicus), </i>and laboratory diurnal Nile grass rats <i>(Arvicanthis niloticus). </i>Specifically, we used areal measures of myeloarchitecture of the primary sensory areas to compare area size and the isotropic fractionator method to estimate the number of neurons and nonneurons in area 17 in each species. Our results demonstrate that the percentage of cortex devoted to area 17 is significantly greater and the percentage of cortex devoted to S1 is significantly smaller in the diurnal Nile grass rat compared with the nocturnal Norway rat groups. Further, the laboratory rodent groups have a greater percentage of cortex devoted to auditory cortex compared with the wild-caught group. We also demonstrate that wild-caught rats have a greater density of neurons in area 17 compared to laboratory-reared animals. However, there were no other clear cellular composition differences in area 17 or differences in the percentage of brain weight devoted to area 17 between nocturnal and diurnal rats. Thus, there are differences in primary sensory area size between diurnal versus nocturnal and laboratory versus wild-caught rat groups and cellular density between wild-caught and laboratory rat groups. Our results demonstrate that the differences in the size and cellular composition of cortical areas do not fit with what would be expected based on brain scaling differences alone, and have a consistent relationship with lifestyle and sensory morphology.
DOI: 10.6084/m9.figshare.5121751
title: Supplementary Material for: Impact of Acquired Enamel Pellicle Modification on Initial Dental Erosion

description: The acquired enamel pellicle that forms on the tooth surface serves as a natural protective barrier against dental erosion. Numerous proteins composing the pellicle serve different functions within this thin layer. Our study examined the effect of incorporated mucin and casein on the erosion-inhibiting potential of the acquired enamel pellicle. Cyclic acidic conditions were applied to mimic the erosive environment present at the human enamel interface during the consumption of soft drinks. One hundred enamel specimens were prepared for microhardness tests and distributed randomly into 5 groups (n = 20) that received the following treatment: deionized water, humidity chamber, mucin, casein, or a combination of mucin and casein. Each group was exposed to 3 cycles of a 2-hour incubation in human saliva, followed by a 2-hour treatment in the testing solution and a 1-min exposure to citric acid. The microhardness analysis demonstrated that the mixture of casein and mucin significantly improved the erosion-inhibiting properties of the human pellicle layer. The addition of individual proteins did not statistically impact the function of the pellicle. These data suggest that protein-protein interactions may play an important role in the effectiveness of the pellicle to prevent erosion.
DOI: 10.6084/m9.figshare.5121754
title: Supplementary Material for: Genome-Wide Linkage Analysis to Identify Genetic Modifiers of <i>ALK</i> Mutation Penetrance in Familial Neuroblastoma

description: <i>Background:</i> Neuroblastoma (NB) is an important childhood cancer with a strong genetic component related to disease susceptibility. Approximately 1% of NB cases have a positive family history. Following a genome-wide linkage analysis and sequencing of candidate genes in the critical region, we identified <i>ALK</i> as the major familial NB gene. Dominant mutations in <i>ALK</i> are found in more than 50% of familial NB cases. However, in the families used for the linkage study, only about 50% of carriers of <i>ALK</i> mutations are affected by NB. <i>Methods:</i> To test whether genetic variation may explain the reduced penetrance of the disease phenotype, we analyzed genome-wide genotype data in <i>ALK</i> mutation-positive families using a model-based linkage approach with different liability classes for carriers and non-carriers of <i>ALK</i> mutations. <i>Results:</i> The region with the highest LOD score was located at chromosome 2p23–p24 and included the <i>ALK</i> locus under models of dominant and recessive inheritance. <i>Conclusions:</i> This finding suggests that variants in the non-mutated <i>ALK</i> gene or another gene linked to it may affect penetrance of the <i>ALK</i> mutations and risk of developing NB in familial cases.
DOI: 10.6084/m9.figshare.5121757.v1
title: Supplementary Material for: Comparison of Area 17 Cellular Composition in Laboratory and Wild-Caught Rats Including Diurnal and Nocturnal Species

description: In this study we examine the size of primary sensory areas in the neocortex and the cellular composition of area 17/V1 in three rodent groups: laboratory nocturnal Norway rats (Long-Evans; <i>Rattus norvegicus</i>), wild-caught nocturnal Norway rats (<i>R. norvegicus), </i>and laboratory diurnal Nile grass rats <i>(Arvicanthis niloticus). </i>Specifically, we used areal measures of myeloarchitecture of the primary sensory areas to compare area size and the isotropic fractionator method to estimate the number of neurons and nonneurons in area 17 in each species. Our results demonstrate that the percentage of cortex devoted to area 17 is significantly greater and the percentage of cortex devoted to S1 is significantly smaller in the diurnal Nile grass rat compared with the nocturnal Norway rat groups. Further, the laboratory rodent groups have a greater percentage of cortex devoted to auditory cortex compared with the wild-caught group. We also demonstrate that wild-caught rats have a greater density of neurons in area 17 compared to laboratory-reared animals. However, there were no other clear cellular composition differences in area 17 or differences in the percentage of brain weight devoted to area 17 between nocturnal and diurnal rats. Thus, there are differences in primary sensory area size between diurnal versus nocturnal and laboratory versus wild-caught rat groups and cellular density between wild-caught and laboratory rat groups. Our results demonstrate that the differences in the size and cellular composition of cortical areas do not fit with what would be expected based on brain scaling differences alone, and have a consistent relationship with lifestyle and sensory morphology.
DOI: 10.6084/m9.figshare.5121763.v1
title: Supplementary Material for: Dimebon Does Not Ameliorate Pathological Changes Caused by Expression of Truncated (1–120) Human Alpha-Synuclein in Dopaminergic Neurons of Transgenic Mice

description: <i>Background:</i> Recent clinical studies have demonstrated that dimebon, a drug originally designed and used as a non-selective antihistamine, ameliorates symptoms and delays progress of mild to moderate forms of Alzheimer’s and Huntington’s diseases. Although the mechanism of dimebon action on pathological processes in degenerating brain is elusive, results of studies carried out in cell cultures and animal models suggested that this drug might affect the process of pathological accumulation and aggregation of various proteins involved in the pathogenesis of proteinopathies. However, the effect of this drug on the pathology caused by overexpression and aggregation of alpha-synuclein, including Parkinson’s disease (PD), has not been assessed. <i>Objective:</i>To test if dimebon affected alpha-synuclein-induced pathology using a transgenic animal model. <i>Methods:</i> We studied the effects of chronic dimebon treatment on transgenic mice expressing the C-terminally truncated (1–120) form of human alpha-synuclein in dopaminergic neurons, a mouse model that recapitulates several biochemical, histopathological and behavioral characteristics of the early stage of PD. <i>Results:</i> Dimebon did not improve balance and coordination of aging transgenic animals or increase the level of striatal dopamine, nor did it prevent accumulation of alpha-synuclein in cell bodies of dopaminergic neurons. <i>Conclusion:</i> Our observations suggest that in the studied model of alpha-synucleinopathy dimebon has very limited effect on certain pathological alterations typical of PD and related diseases.
DOI: 10.6084/m9.figshare.5121748
title: Supplementary Material for: Integrated Cytogenetic and High-Resolution Array CGH Analysis of Genomic Alterations Associated with <i>MYCN</i> Amplification

description: Amplification of oncogenes and closely linked flanking genes is common in some types of cancer and can be associated with complex chromosome rearrangements and/or co-amplification of non-syntenic chromosomal regions. To better understand the etiology and structural complexity of focal <i>MYCN</i> amplicons in human neuronal cancer, we investigated the precise chromosomal locations of high copy number genomic regions in <i>MYCN</i> amplified cell lines. An integrated cytogenetic map of the <i>MYCN</i> amplicon was created using high-resolution array CGH, spectral karyotyping (SKY), multi-color banding (mBAND), and fluorescence in situ hybridization (FISH) in 4 human neuronal tumor cell lines. The evidence of complex intra- and inter-chromosomal events, providing clues concerning the nature of the genomic mechanisms that contributed to the process of <i>MYCN</i> amplification, was observed. The presence of multiple co-amplified syntenic or non-syntenic sequences in the <i>MYCN</i> amplicon is quite intriguing. <i>MYCN</i> is usually centrally located in the amplicon; however, the structure and complexity of the amplicons were highly variable. It is noteworthy that clusters of unstable repetitive regions characterized by CNV sequences were present throughout the regions encompassed by <i>MYCN</i> gene amplification, and these sequences could provide a mechanism to destabilize this region of the genome. Complex structural rearrangements involving genomic losses and gains in the 2p24 region lead to <i>MYCN</i> amplification and that these rearrangements can trigger amplification events.
DOI: 10.6084/m9.figshare.5121751.v1
title: Supplementary Material for: Impact of Acquired Enamel Pellicle Modification on Initial Dental Erosion

description: The acquired enamel pellicle that forms on the tooth surface serves as a natural protective barrier against dental erosion. Numerous proteins composing the pellicle serve different functions within this thin layer. Our study examined the effect of incorporated mucin and casein on the erosion-inhibiting potential of the acquired enamel pellicle. Cyclic acidic conditions were applied to mimic the erosive environment present at the human enamel interface during the consumption of soft drinks. One hundred enamel specimens were prepared for microhardness tests and distributed randomly into 5 groups (n = 20) that received the following treatment: deionized water, humidity chamber, mucin, casein, or a combination of mucin and casein. Each group was exposed to 3 cycles of a 2-hour incubation in human saliva, followed by a 2-hour treatment in the testing solution and a 1-min exposure to citric acid. The microhardness analysis demonstrated that the mixture of casein and mucin significantly improved the erosion-inhibiting properties of the human pellicle layer. The addition of individual proteins did not statistically impact the function of the pellicle. These data suggest that protein-protein interactions may play an important role in the effectiveness of the pellicle to prevent erosion.
DOI: 10.6084/m9.figshare.5121742
title: Supplementary Material for: Copy Number Variation Accuracy in Genome-Wide Association Studies

description: <i>Background/Aim:</i> Copy number variations (CNVs) are a major source of alterations among individuals and are a potential risk factor in many diseases. Numerous diseases have been linked to deletions and duplications of these chromosomal segments. Data from genome-wide association studies and other microarrays may be used to identify CNVs by several different computer programs, but the reliability of the results has been questioned. <i>Methods:</i> To help researchers reduce the number of false-positive CNVs that need to be followed up with laboratory testing, we evaluated the relative performance of CNVPartition, PennCNV and QuantiSNP, and developed a statistical method for estimating sensitivity and positive predictive values of CNV calls and tested it on 96 duplicate samples in our dataset. <i>Results:</i> We found that the positive predictive rate increases with the number of probes in the CNV and the size of the CNV, with the highest positive predicted rates in CNVs of at least 500 kb and at least 100 probes. Our analysis also indicates that identifying CNVs reported by multiple programs can greatly improve the reproducibility rate and the positive predicted rate. <i>Conclusion:</i> Our methods can be used by investigators to identify CNVs in genome-wide data with greater reliability.
DOI: 10.6084/m9.figshare.5121748.v1
title: Supplementary Material for: Integrated Cytogenetic and High-Resolution Array CGH Analysis of Genomic Alterations Associated with <i>MYCN</i> Amplification

description: Amplification of oncogenes and closely linked flanking genes is common in some types of cancer and can be associated with complex chromosome rearrangements and/or co-amplification of non-syntenic chromosomal regions. To better understand the etiology and structural complexity of focal <i>MYCN</i> amplicons in human neuronal cancer, we investigated the precise chromosomal locations of high copy number genomic regions in <i>MYCN</i> amplified cell lines. An integrated cytogenetic map of the <i>MYCN</i> amplicon was created using high-resolution array CGH, spectral karyotyping (SKY), multi-color banding (mBAND), and fluorescence in situ hybridization (FISH) in 4 human neuronal tumor cell lines. The evidence of complex intra- and inter-chromosomal events, providing clues concerning the nature of the genomic mechanisms that contributed to the process of <i>MYCN</i> amplification, was observed. The presence of multiple co-amplified syntenic or non-syntenic sequences in the <i>MYCN</i> amplicon is quite intriguing. <i>MYCN</i> is usually centrally located in the amplicon; however, the structure and complexity of the amplicons were highly variable. It is noteworthy that clusters of unstable repetitive regions characterized by CNV sequences were present throughout the regions encompassed by <i>MYCN</i> gene amplification, and these sequences could provide a mechanism to destabilize this region of the genome. Complex structural rearrangements involving genomic losses and gains in the 2p24 region lead to <i>MYCN</i> amplification and that these rearrangements can trigger amplification events.
DOI: 10.6084/m9.figshare.5121754.v1
title: Supplementary Material for: Genome-Wide Linkage Analysis to Identify Genetic Modifiers of <i>ALK</i> Mutation Penetrance in Familial Neuroblastoma

description: <i>Background:</i> Neuroblastoma (NB) is an important childhood cancer with a strong genetic component related to disease susceptibility. Approximately 1% of NB cases have a positive family history. Following a genome-wide linkage analysis and sequencing of candidate genes in the critical region, we identified <i>ALK</i> as the major familial NB gene. Dominant mutations in <i>ALK</i> are found in more than 50% of familial NB cases. However, in the families used for the linkage study, only about 50% of carriers of <i>ALK</i> mutations are affected by NB. <i>Methods:</i> To test whether genetic variation may explain the reduced penetrance of the disease phenotype, we analyzed genome-wide genotype data in <i>ALK</i> mutation-positive families using a model-based linkage approach with different liability classes for carriers and non-carriers of <i>ALK</i> mutations. <i>Results:</i> The region with the highest LOD score was located at chromosome 2p23–p24 and included the <i>ALK</i> locus under models of dominant and recessive inheritance. <i>Conclusions:</i> This finding suggests that variants in the non-mutated <i>ALK</i> gene or another gene linked to it may affect penetrance of the <i>ALK</i> mutations and risk of developing NB in familial cases.
DOI: 10.6084/m9.figshare.5121739
title: Supplementary Material for: Differential Kidney Proteome Profiling in a Murine Model of Renal Fibrosis under Treatment with Mycophenolate Mofetil

description: <i>Aim:</i> The aim of this study was to investigate the effect of mycophenolate mofetil (MMF) using differential kidney proteome profiling of COL4A3-deficient mice as a model of progressive renal disease. <i>Methods:</i> Histological evaluation of kidney sections was performed. Total protein lysate from kidneys of placebo- and MMF-treated COL4A3-deficient mice was studied for significant differences in protein abundance using 2-dimensional electrophoresis and mass spectrometry. <i>Results:</i> While tubulointerstitial fibrosis in COL4A3-deficient mice was inhibited by MMF, 19 proteins in the kidneys were regulated: 12 with lower (ATPO, TAGL2, CAH1, TPD52, VA0D1, SERPH, GNAL, PSB6, EF1D, OTUB1, NDUS8, and NAPSA) and 7 with higher (ACADM, ACY3, CK054, ACTB/G, ACTB, UBP5, and ACY1) spot intensity. Nine differentially expressed proteins showed interaction potential (ATPO, TPD52, PSB6, EF1D, OTUB1, NAPSA, ACTB, ACTG, and UBP5). <i>Conclusions:</i> The identified proteins take part in different signaling pathways. With the highest probability, the VEGF signaling pathway (TAGL2, EF1D, and ACTB) and hypoxia (CAH1, PSB6, and ACTG) were influenced by MMF in fibrotic conditions. Moreover, MMF may modulate antifibrotic and apoptotic pathways as well as epithelial-mesenchymal transition (EMT). Different signaling pathways may be influenced by MMF therapy. These results suggest an inhibitory effect of MMF on renal EMT in COL4A3-deficient mice. Further studies are necessary to validate these findings.
DOI: 10.6084/m9.figshare.5121742.v1
title: Supplementary Material for: Copy Number Variation Accuracy in Genome-Wide Association Studies

description: <i>Background/Aim:</i> Copy number variations (CNVs) are a major source of alterations among individuals and are a potential risk factor in many diseases. Numerous diseases have been linked to deletions and duplications of these chromosomal segments. Data from genome-wide association studies and other microarrays may be used to identify CNVs by several different computer programs, but the reliability of the results has been questioned. <i>Methods:</i> To help researchers reduce the number of false-positive CNVs that need to be followed up with laboratory testing, we evaluated the relative performance of CNVPartition, PennCNV and QuantiSNP, and developed a statistical method for estimating sensitivity and positive predictive values of CNV calls and tested it on 96 duplicate samples in our dataset. <i>Results:</i> We found that the positive predictive rate increases with the number of probes in the CNV and the size of the CNV, with the highest positive predicted rates in CNVs of at least 500 kb and at least 100 probes. Our analysis also indicates that identifying CNVs reported by multiple programs can greatly improve the reproducibility rate and the positive predicted rate. <i>Conclusion:</i> Our methods can be used by investigators to identify CNVs in genome-wide data with greater reliability.
DOI: 10.6084/m9.figshare.5121745
title: Supplementary Material for: Conserved although Very Different Karyotypes in Gliridae and Sciuridae and Their Contribution to Chromosomal Signatures in Glires

description: Rodents represent the largest order of living mammals. It comprises 5 sub-orders, among which Sciuromorpha (Sciuridae, Gliridae and Aplodontiidae) are assumed to occupy a basal position in rodent evolution. Banded karyotypes of some representatives of the Sciuridae family have been compared to each other, and comparisons with man were performed using chromosome paintings. Sciuridae karyotypes have conserved several eutherian ancestral syntenies. Like Sciuridae, Gliridae possess some chromosomes easily comparable with those of Primates. Comparisons of Gliridae and Sciuridae chromosomes with those of the presumed eutherian ancestor provide information about their chromosomal evolution and their position among Rodentia. Although both Sciuridae and Gliridae karyotypes are relatively conserved, they display many differences, indicating their early divergence. The reconstruction of their chromosomal evolution allowed us to propose the composition of their presumed ancestral karyotypes, with 2n = 48 and 2n = 38 for Gliridae and Sciuridae, respectively. Since rodent emergence, a single rearrangement is common to these 2 families. It formed a chromosome with fragments homologous to human chromosomes 4-8p-4-12-22, not detected in other rodents, and thus characteristic for the Sciuromorpha. This allowed us to reassess the chromosomal signatures of Rodentia. Finally, we show that the speed of chromosomal evolution in Gliridae is intermediate between that of Sciuridae (low) and Muridae (high).
DOI: 10.6084/m9.figshare.5121733
title: Supplementary Material for: The Type I Inositol 1,4,5-Trisphosphate Receptor Interacts with Protein 4.1N to Mediate Neurite Formation through Intracellular Ca<sup>2+</sup> Waves

description: Ca<sup>2+</sup> waves are an important mechanism for encoding Ca<sup>2+</sup> signaling information, but the molecular basis for wave formation and how this regulates neuronal function is not entirely understood. Using nerve growth factor-differentiated PC12 cells as a model system, we investigated the interaction between the type I inositol 1,4,5-trisphosphate receptor (IP3R1) and the cytoskeletal linker, protein 4.1N, to examine the relationship between Ca<sup>2+</sup> wave formation and neurite development. This was examined using RNAi and overexpressed dominant negative binding regions of each protein. Confocal microscopy was used to monitor neurite formation and Ca<sup>2+</sup> waves. Knockdown of IP3R1 or 4.1N attenuated neurite formation, as did binding regions of IP3R1 and 4.1N, which colocalized with endogenous 4.1N and IP3R1, respectively. Upon stimulation with the IP3-producing agonist carbachol, both RNAi and dominant negative molecules shifted signaling events from waves to homogeneous patterns of Ca<sup>2+</sup> release. These findings provide evidence that IP3R1 localization, via protein 4.1N, is necessary for Ca<sup>2+</sup> wave formation, which in turn mediates neurite formation.