cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1568144.v3
title: Synthesis, crystal structure, redox behavior and DNA-binding properties of a series of copper(II) complexes with two new carboxamide derivatives

description: Four mononuclear copper(II) complexes of two new carboxamide derivatives formulated as [Cu(L<sup>1</sup>)<sub>2</sub>](ClO<sub>4</sub>)<sub>2</sub> (<b>1a</b>), [Cu(L<sup>1</sup>)<sub>2</sub>](NO<sub>3</sub>)<sub>2</sub> (<b>1b</b>), [Cu(L<sup>2</sup>)<sub>2</sub>(H<sub>2</sub>O)<sub>2</sub>](ClO<sub>4</sub>)<sub>2</sub> (<b>2a</b>) and [Cu(L<sup>2</sup>)<sub>2</sub>(H<sub>2</sub>O)](NO<sub>3</sub>)<sub>2</sub> (<b>2b</b>) have been isolated in pure form from the reaction of <b>L</b><sup><b>1</b></sup> and <b>L</b><sup><b>2</b></sup> [where <b>L</b><sup><b>1</b></sup> = <i>N</i>-(furan-2-ylmethyl)-2-pyridinecarboxamide and <b>L</b><sup><b>2</b></sup> = <i>N</i>-(thiophen-2-ylmethyl)-2-pyridinecarboxamide] with copper(II) salts of perchlorate and nitrate. All the complexes were characterized by physico-chemical and spectroscopic tools along with single crystal X–ray diffraction studies. The structural analyses showed that <b>1</b> is monomeric of square planar geometry with copper(II) chelated by two <b>L</b><sup><b>1</b></sup> ligands. Complexes <b>2</b> differs in coordination geometry, being octahedral and distorted square pyramidal. Two <b>L</b><sup><b>2</b></sup> ligands occupy the equatorial positions of the octahedral <b>2a</b> and the basal sites of the pyramidal <b>2b</b>, with water molecules that complete the coordination sphere in each case. Electrochemical studies using cyclic voltammetry showed a reversible redox behavior of the copper(II) in <b>1</b> and <b>2</b>. The electronic spectroscopic behavior and the trend of one electron equivalent redox potential corresponding to a Cu<sup>II</sup>/Cu<sup>I</sup> couple have also been confirmed by DFT calculations. The spectroscopic and viscosity measurement study in tris-HCl buffer suggested an intercalative interaction of <b>1a</b> and <b>2</b> with calf thymus-DNA (CT-DNA) likely due to the stacking between the non-coordinated furan or thiophene chromophore with the base pairs of DNA.
DOI: 10.6084/m9.figshare.1568139
title: Epigenetic markers for newborn congenital heart defect (CHD)

description: <i>Objective</i>: Our objective was to determine whether there were significant differences in genome-wide DNA methylation in newborns with major congenital heart defect (CHD) compared to controls. We also evaluated methylation of cytosines in CpG motifs for the detection of these CHDs. <i>Methods</i>: Genome-wide DNA methylation analysis was performed on DNA from 60 newborns with various CHDs, including hypoplastic left heart syndrome, ventricular septal deficit, atrial septal defect, pulmonary stenosis, coarctation of the aorta and Tetralogy of Fallot, and 32 controls. <i>Results</i>: Highly significant differences in cytosine methylation were seen in a large number of genes throughout the genome for all CHD categories. Gene ontology analysis of CHD overall indicated over-represented biological processes involving cell development and differentiation, and anatomical structure morphogenesis. Methylation of individual cytosines in CpG motifs had high diagnostic accuracy for the detection of CHD. For example, for coarctation one predictive model based on levels of particular cytosine nucleotides achieved a sensitivity of 100% and specificity of 93.8% (AUC = 0.974, <i>p</i> <i>Conclusion</i>: Profound differences in cytosine methylation were observed in hundreds of genes in newborns with different types of CHD. There appears to be the potential for development of accurate genetic biomarkers for CHD detection in newborns.
DOI: 10.6084/m9.figshare.1568139.v1
title: Epigenetic markers for newborn congenital heart defect (CHD)

description: <i>Objective</i>: Our objective was to determine whether there were significant differences in genome-wide DNA methylation in newborns with major congenital heart defect (CHD) compared to controls. We also evaluated methylation of cytosines in CpG motifs for the detection of these CHDs. <i>Methods</i>: Genome-wide DNA methylation analysis was performed on DNA from 60 newborns with various CHDs, including hypoplastic left heart syndrome, ventricular septal deficit, atrial septal defect, pulmonary stenosis, coarctation of the aorta and Tetralogy of Fallot, and 32 controls. <i>Results</i>: Highly significant differences in cytosine methylation were seen in a large number of genes throughout the genome for all CHD categories. Gene ontology analysis of CHD overall indicated over-represented biological processes involving cell development and differentiation, and anatomical structure morphogenesis. Methylation of individual cytosines in CpG motifs had high diagnostic accuracy for the detection of CHD. For example, for coarctation one predictive model based on levels of particular cytosine nucleotides achieved a sensitivity of 100% and specificity of 93.8% (AUC = 0.974, <i>p</i> <i>Conclusion</i>: Profound differences in cytosine methylation were observed in hundreds of genes in newborns with different types of CHD. There appears to be the potential for development of accurate genetic biomarkers for CHD detection in newborns.
DOI: 10.6084/m9.figshare.1568133
title: Dissection of autophagy in tobacco BY-2 cells under sucrose starvation conditions using the vacuolar H<sup>+</sup>-ATPase inhibitor concanamycin A and the autophagy-related protein Atg8

description: Tobacco BY-2 cells undergo autophagy in sucrose-free culture medium, which is the process mostly responsible for intracellular protein degradation under these conditions. Autophagy was inhibited by the vacuolar H<sup>+</sup>-ATPase inhibitors concanamycin A and bafilomycin A<sub>1</sub>, which caused the accumulation of autophagic bodies in the central vacuoles. Such accumulation did not occur in the presence of the autophagy inhibitor 3-methyladenine, and concanamycin in turn inhibited the accumulation of autolysosomes in the presence of the cysteine protease inhibitor E-64c. Electron microscopy revealed not only that the autophagic bodies were accumulated in the central vacuole, but also that autophagosome-like structures were more frequently observed in the cytoplasm in treatments with concanamycin, suggesting that concanamycin affects the morphology of autophagosomes in addition to raising the pH of the central vacuole. Using BY-2 cells that constitutively express a fusion protein of autophagosome marker protein Atg8 and green fluorescent protein (GFP), we observed the appearance of autophagosomes by fluorescence microscopy, which is a reliable morphological marker of autophagy, and the processing of the fusion protein to GFP, which is a biochemical marker of autophagy. Together, these results suggest the involvement of vacuole type H<sup>+</sup>-ATPase in the maturation step of autophagosomes to autolysosomes in the autophagic process of BY-2 cells. The accumulation of autophagic bodies in the central vacuole by concanamycin is a marker of the occurrence of autophagy; however, it does not necessarily mean that the central vacuole is the site of cytoplasm degradation.
DOI: 10.6084/m9.figshare.1568133.v1
title: Dissection of autophagy in tobacco BY-2 cells under sucrose starvation conditions using the vacuolar H<sup>+</sup>-ATPase inhibitor concanamycin A and the autophagy-related protein Atg8

description: Tobacco BY-2 cells undergo autophagy in sucrose-free culture medium, which is the process mostly responsible for intracellular protein degradation under these conditions. Autophagy was inhibited by the vacuolar H<sup>+</sup>-ATPase inhibitors concanamycin A and bafilomycin A<sub>1</sub>, which caused the accumulation of autophagic bodies in the central vacuoles. Such accumulation did not occur in the presence of the autophagy inhibitor 3-methyladenine, and concanamycin in turn inhibited the accumulation of autolysosomes in the presence of the cysteine protease inhibitor E-64c. Electron microscopy revealed not only that the autophagic bodies were accumulated in the central vacuole, but also that autophagosome-like structures were more frequently observed in the cytoplasm in treatments with concanamycin, suggesting that concanamycin affects the morphology of autophagosomes in addition to raising the pH of the central vacuole. Using BY-2 cells that constitutively express a fusion protein of autophagosome marker protein Atg8 and green fluorescent protein (GFP), we observed the appearance of autophagosomes by fluorescence microscopy, which is a reliable morphological marker of autophagy, and the processing of the fusion protein to GFP, which is a biochemical marker of autophagy. Together, these results suggest the involvement of vacuole type H<sup>+</sup>-ATPase in the maturation step of autophagosomes to autolysosomes in the autophagic process of BY-2 cells. The accumulation of autophagic bodies in the central vacuole by concanamycin is a marker of the occurrence of autophagy; however, it does not necessarily mean that the central vacuole is the site of cytoplasm degradation.
DOI: 10.6084/m9.figshare.1568129
title: Developmental Dyslexia With and Without Language Impairment: ERPs Reveal Qualitative Differences in Morphosyntactic Processing

description: This study aimed to characterize neuropsychological and linguistic skills in children with Developmental Dyslexia (DD) with and without Language Impairment (LI). Behavioral tests of short-term memory, phonemic awareness, and morphosyntactic processing and electrophysiological responses to agreement violations were administered to 32 DD children (16 with additional LI) and 16 controls. Behavioral data revealed quantitative differences among groups: DD+LI children showed the worst performance, followed by DD-only children and controls. Event-related potential results confirmed atypical morphosyntactic processing in the DD-only group, highlighting qualitative differences between groups. These results support multifactor models of learning disabilities, where different patterns of deficits characterize different subgroups.
DOI: 10.6084/m9.figshare.1568129.v2
title: Developmental Dyslexia With and Without Language Impairment: ERPs Reveal Qualitative Differences in Morphosyntactic Processing

description: This study aimed to characterize neuropsychological and linguistic skills in children with Developmental Dyslexia (DD) with and without Language Impairment (LI). Behavioral tests of short-term memory, phonemic awareness, and morphosyntactic processing and electrophysiological responses to agreement violations were administered to 32 DD children (16 with additional LI) and 16 controls. Behavioral data revealed quantitative differences among groups: DD+LI children showed the worst performance, followed by DD-only children and controls. Event-related potential results confirmed atypical morphosyntactic processing in the DD-only group, highlighting qualitative differences between groups. These results support multifactor models of learning disabilities, where different patterns of deficits characterize different subgroups.
DOI: 10.6084/m9.figshare.1568129.v1
title: Developmental Dyslexia With and Without Language Impairment: ERPs Reveal Qualitative Differences in Morphosyntactic Processing

description: This study aimed to characterize neuropsychological and linguistic skills in children with Developmental Dyslexia (DD) with and without Language Impairment (LI). Behavioral tests of short-term memory, phonemic awareness, and morphosyntactic processing and electrophysiological responses to agreement violations were administered to 32 DD children (16 with additional LI) and 16 controls. Behavioral data revealed quantitative differences among groups: DD+LI children showed the worst performance, followed by DD-only children and controls. Event-related potential results confirmed atypical morphosyntactic processing in the DD-only group, highlighting qualitative differences between groups. These results support multifactor models of learning disabilities, where different patterns of deficits characterize different subgroups.
DOI: 10.6084/m9.figshare.1568122
title: Nd–Sr isotopic constraint to the formation of metatexite and diatexite migmatites, Higo metamorphic terrane, central Kyushu, Japan

description: ABSTRACTMetatexite and diatexite migmatites are widely distributed within the upper amphibolite and granulite-facies zones of the Higo low-<i>P</i>/high-<i>T</i> metamorphic terrane. Here we report Nd–Sr isotopic and whole rock composition data from an outcrop in the highest-grade part of the granulite-facies zone, in which diatexite occurs as a 3 m-thick layer between 2 m-thick layers of stromatic-structured metatexite within pelitic gneiss. The metatexite has Nd–Sr isotopes and whole rock compositions similar to those of the gneiss, but the diatexite shows the reverse. The diatexite has a higher ε<sub>Nd</sub>(t) and <sup>147</sup>Sm/<sup>144</sup>Nd ratio (ε<sub>Nd</sub>(t) = −0.5; <sup>147</sup>Sm/<sup>144</sup>Nd = 0.1636) than the gneiss (ε<sub>Nd</sub>(t) = −2.1; <sup>147</sup>Sm/<sup>144</sup>Nd = 0.1287) and metatexite (ε<sub>Nd</sub>(t) = −3.1; <sup>147</sup>Sm/<sup>144</sup>Nd = 0.1188). The (<sup>87</sup>Sr/<sup>86</sup>Sr)<sub>initial</sub> and <sup>87</sup>Rb/<sup>86</sup>Sr of the diatexite ((<sup>87</sup>Sr/<sup>86</sup>Sr)<sub>initial</sub> = 0.70568; <sup>87</sup>Rb/<sup>86</sup>Sr = 0.416) are lower than those of the gneiss ((<sup>87</sup>Sr/<sup>86</sup>Sr)<sub>initial</sub> = 0.70857; <sup>87</sup>Rb/<sup>86</sup>Sr = 1.13) and metatexite ((<sup>87</sup>Sr/<sup>86</sup>Sr)<sub>initial</sub> = 0.70792; <sup>87</sup>Rb/<sup>86</sup>Sr = 1.11). The metatexite and gneiss show enrichment of Th and depletion of P and Eu and have a similar chondrite-normalized REE pattern, which shows steep LREE–MREE-enriched and gently declining HREE patterns and negative Eu anomalies, whereas the diatexite shows enrichment of Sr and depletion of Th and Y, and exhibits gently declining LREE and steeply declining HREE pattern and weak Eu depletion. The metatexite migmatite is interpreted to have formed by <i>in situ</i> partial melting in which the melt did not migrate from the source, whereas the diatexite migmatite included an externally derived melt with a juvenile component. The Cretaceous high-temperature metamorphism of the Higo metamorphic terrane is interpreted to reflect emplacement of mantle-derived basalts under a volcanic arc along the eastern margin of the Eurasian continent, and mass transfer and advection of heat <i>via</i> hybrid silicic melts from the lower crust.
DOI: 10.6084/m9.figshare.1568122.v1
title: Nd–Sr isotopic constraint to the formation of metatexite and diatexite migmatites, Higo metamorphic terrane, central Kyushu, Japan

description: ABSTRACTMetatexite and diatexite migmatites are widely distributed within the upper amphibolite and granulite-facies zones of the Higo low-<i>P</i>/high-<i>T</i> metamorphic terrane. Here we report Nd–Sr isotopic and whole rock composition data from an outcrop in the highest-grade part of the granulite-facies zone, in which diatexite occurs as a 3 m-thick layer between 2 m-thick layers of stromatic-structured metatexite within pelitic gneiss. The metatexite has Nd–Sr isotopes and whole rock compositions similar to those of the gneiss, but the diatexite shows the reverse. The diatexite has a higher ε<sub>Nd</sub>(t) and <sup>147</sup>Sm/<sup>144</sup>Nd ratio (ε<sub>Nd</sub>(t) = −0.5; <sup>147</sup>Sm/<sup>144</sup>Nd = 0.1636) than the gneiss (ε<sub>Nd</sub>(t) = −2.1; <sup>147</sup>Sm/<sup>144</sup>Nd = 0.1287) and metatexite (ε<sub>Nd</sub>(t) = −3.1; <sup>147</sup>Sm/<sup>144</sup>Nd = 0.1188). The (<sup>87</sup>Sr/<sup>86</sup>Sr)<sub>initial</sub> and <sup>87</sup>Rb/<sup>86</sup>Sr of the diatexite ((<sup>87</sup>Sr/<sup>86</sup>Sr)<sub>initial</sub> = 0.70568; <sup>87</sup>Rb/<sup>86</sup>Sr = 0.416) are lower than those of the gneiss ((<sup>87</sup>Sr/<sup>86</sup>Sr)<sub>initial</sub> = 0.70857; <sup>87</sup>Rb/<sup>86</sup>Sr = 1.13) and metatexite ((<sup>87</sup>Sr/<sup>86</sup>Sr)<sub>initial</sub> = 0.70792; <sup>87</sup>Rb/<sup>86</sup>Sr = 1.11). The metatexite and gneiss show enrichment of Th and depletion of P and Eu and have a similar chondrite-normalized REE pattern, which shows steep LREE–MREE-enriched and gently declining HREE patterns and negative Eu anomalies, whereas the diatexite shows enrichment of Sr and depletion of Th and Y, and exhibits gently declining LREE and steeply declining HREE pattern and weak Eu depletion. The metatexite migmatite is interpreted to have formed by <i>in situ</i> partial melting in which the melt did not migrate from the source, whereas the diatexite migmatite included an externally derived melt with a juvenile component. The Cretaceous high-temperature metamorphism of the Higo metamorphic terrane is interpreted to reflect emplacement of mantle-derived basalts under a volcanic arc along the eastern margin of the Eurasian continent, and mass transfer and advection of heat <i>via</i> hybrid silicic melts from the lower crust.
DOI: 10.6084/m9.figshare.1568113
title: Multimodal approach to explore the pathogenicity of BARD1, ARG 658 CYS, and ILE 738 VAL mutants

description: BARD1–BRCA1 complex plays an important role in DNA damage repair, apoptosis, chromatin remodeling, and other important processes required for cell survival. BRCA1 and BARD1 heterodimer possess E3 ligase activity and is involved in genome maintenance, by functioning in surveillance for DNA damage, thereby regulating multiple pathways including tumor suppression. BRCT domains are evolutionary conserved domains present in different proteins such as BRCA1, BARD1, XRCC, and MDC1 regulating damage response and cell-cycle control through protein–protein interactions. Nonetheless, the role of BARD1BRCT in the recruitment of DNA repair mechanism and structural integrity with BRCA1 complex is still implicit. To explicate the role of BARD1BRCT in the DNA repair mechanism, in silico, <i>in vitro</i>, and biophysical approach were applied to characterize BARD1 BRCT <i>wild</i>-<i>type</i> and Arg658Cys and Ile738Val mutants. However, no drastic secondary and tertiary structural changes in the mutant proteins were observed. Thermal and chemical denaturation studies revealed that mutants Arg658Cys and Ile738Val have a decrease in <i>T</i><sub>m</sub> and ∆<i>G</i> than the <i>wild type</i>. <i>In silico</i> studies of BARD1 BRCT (568-777) and mutant protein indicate loss in structural compactness on the Ile738Val mutant. Comparative studies of <i>wild</i>-<i>type</i> and mutants will thus be helpful in understanding the basic role of BARD1BRCT in DNA damage repair.
DOI: 10.6084/m9.figshare.1568113.v2
title: Multimodal approach to explore the pathogenicity of BARD1, ARG 658 CYS, and ILE 738 VAL mutants

description: BARD1–BRCA1 complex plays an important role in DNA damage repair, apoptosis, chromatin remodeling, and other important processes required for cell survival. BRCA1 and BARD1 heterodimer possess E3 ligase activity and is involved in genome maintenance, by functioning in surveillance for DNA damage, thereby regulating multiple pathways including tumor suppression. BRCT domains are evolutionary conserved domains present in different proteins such as BRCA1, BARD1, XRCC, and MDC1 regulating damage response and cell-cycle control through protein–protein interactions. Nonetheless, the role of BARD1BRCT in the recruitment of DNA repair mechanism and structural integrity with BRCA1 complex is still implicit. To explicate the role of BARD1BRCT in the DNA repair mechanism, in silico, <i>in vitro</i>, and biophysical approach were applied to characterize BARD1 BRCT <i>wild</i>-<i>type</i> and Arg658Cys and Ile738Val mutants. However, no drastic secondary and tertiary structural changes in the mutant proteins were observed. Thermal and chemical denaturation studies revealed that mutants Arg658Cys and Ile738Val have a decrease in <i>T</i><sub>m</sub> and ∆<i>G</i> than the <i>wild type</i>. <i>In silico</i> studies of BARD1 BRCT (568-777) and mutant protein indicate loss in structural compactness on the Ile738Val mutant. Comparative studies of <i>wild</i>-<i>type</i> and mutants will thus be helpful in understanding the basic role of BARD1BRCT in DNA damage repair.
DOI: 10.6084/m9.figshare.1568111
title: Integrated methylome and transcriptome analysis reveals novel regulatory elements in pediatric acute lymphoblastic leukemia

description: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children under the age of 15. In addition to genetic aberrations, epigenetic modifications such as DNA methylation are altered in cancer and impact gene expression. To identify epigenetic alterations in ALL, genome-wide methylation profiles were generated using the methylated CpG island recovery assay followed by next-generation sequencing. More than 25,000 differentially methylated regions (DMR) were observed in ALL patients with ∼90% present within intronic or intergenic regions. To determine the regulatory potential of the DMR, whole-transcriptome analysis was performed and integrated with methylation data. Aberrant promoter methylation was associated with the altered expression of genes involved in transcriptional regulation, apoptosis, and proliferation. Novel enhancer-like sequences were identified within intronic and intergenic DMR. Aberrant methylation in these regions was associated with the altered expression of neighboring genes involved in cell cycle processes, lymphocyte activation and apoptosis. These genes include potential epi-driver genes, such as <i>SYNE1, PTPRS, PAWR, HDAC9, RGCC, MCOLN2, LYN, TRAF3, FLT1</i>, and <i>MELK</i>, which may provide a selective advantage to leukemic cells. In addition, the differential expression of epigenetic modifier genes, pseudogenes, and non-coding RNAs was also observed accentuating the role of erroneous epigenetic gene regulation in ALL.
DOI: 10.6084/m9.figshare.1568111.v2
title: Integrated methylome and transcriptome analysis reveals novel regulatory elements in pediatric acute lymphoblastic leukemia

description: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children under the age of 15. In addition to genetic aberrations, epigenetic modifications such as DNA methylation are altered in cancer and impact gene expression. To identify epigenetic alterations in ALL, genome-wide methylation profiles were generated using the methylated CpG island recovery assay followed by next-generation sequencing. More than 25,000 differentially methylated regions (DMR) were observed in ALL patients with ∼90% present within intronic or intergenic regions. To determine the regulatory potential of the DMR, whole-transcriptome analysis was performed and integrated with methylation data. Aberrant promoter methylation was associated with the altered expression of genes involved in transcriptional regulation, apoptosis, and proliferation. Novel enhancer-like sequences were identified within intronic and intergenic DMR. Aberrant methylation in these regions was associated with the altered expression of neighboring genes involved in cell cycle processes, lymphocyte activation and apoptosis. These genes include potential epi-driver genes, such as <i>SYNE1, PTPRS, PAWR, HDAC9, RGCC, MCOLN2, LYN, TRAF3, FLT1</i>, and <i>MELK</i>, which may provide a selective advantage to leukemic cells. In addition, the differential expression of epigenetic modifier genes, pseudogenes, and non-coding RNAs was also observed accentuating the role of erroneous epigenetic gene regulation in ALL.