cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1568111.v1
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.1568113.v1
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. BRCTs 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 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<i>-silico</i>, <i>in-vitro</i> and biophysical approach were applied to characterize BARD1BRCT <i>wild -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 mutant Arg658Cys and Ile738Val has a decrease T<sub>m</sub> and ∆G than the <i>wild- type</i>. <i>In-silico</i> studies of BARD1BRCT (568-777) and mutant protein indicates loss in structural compactness on the Ile738Val mutant. Comparative studies of <i>wild- type</i> and mutants will thus be helpful in understanding the basic role of BARD1BRCT in DNA damage repair.
DOI: 10.6084/m9.figshare.1568112.v1
title: Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

description: Several studies have described phenotypic changes in the offspring of mice exposed to a variety of environmental factors, including diet, toxins, and stress; however, the molecular pathways involved in these changes remain unclear. Using a high fat diet (HFD)-induced obesity mouse model, we examined liver gene expression in male offspring and analyzed chromatin of paternal spermatozoa. We found that the hepatic mRNA level of 7 genes (out of 20 evaluated) was significantly altered in HFD male offspring compared to control mice, suggesting that phenotypic changes in the offspring depend on parental diet. We examined 7 imprinted loci in spermatozoa DNA from HFD-treated and control fathers by bisulfite sequencing, but did not detect changes in DNA methylation associated with HFD. Using chromatin immunoprecipitation followed by high-throughput sequencing, we found differential histone H3-occupancy at genes involved in the regulation of embryogenesis and differential H3K4me1-enrichment at transcription regulatory genes in HFD fathers vs. control mice. These results suggest that dietary exposure can modulate histone composition at regulatory genes implicated in developmental processes.
DOI: 10.6084/m9.figshare.1568112
title: Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

description: Several studies have described phenotypic changes in the offspring of mice exposed to a variety of environmental factors, including diet, toxins, and stress; however, the molecular pathways involved in these changes remain unclear. Using a high fat diet (HFD)-induced obesity mouse model, we examined liver gene expression in male offspring and analyzed chromatin of paternal spermatozoa. We found that the hepatic mRNA level of 7 genes (out of 20 evaluated) was significantly altered in HFD male offspring compared to control mice, suggesting that phenotypic changes in the offspring depend on parental diet. We examined 7 imprinted loci in spermatozoa DNA from HFD-treated and control fathers by bisulfite sequencing, but did not detect changes in DNA methylation associated with HFD. Using chromatin immunoprecipitation followed by high-throughput sequencing, we found differential histone H3-occupancy at genes involved in the regulation of embryogenesis and differential H3K4me1-enrichment at transcription regulatory genes in HFD fathers vs. control mice. These results suggest that dietary exposure can modulate histone composition at regulatory genes implicated in developmental processes.
DOI: 10.6084/m9.figshare.1568112.v3
title: Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

description: Several studies have described phenotypic changes in the offspring of mice exposed to a variety of environmental factors, including diet, toxins, and stress; however, the molecular pathways involved in these changes remain unclear. Using a high fat diet (HFD)-induced obesity mouse model, we examined liver gene expression in male offspring and analyzed chromatin of paternal spermatozoa. We found that the hepatic mRNA level of 7 genes (out of 20 evaluated) was significantly altered in HFD male offspring compared to control mice, suggesting that phenotypic changes in the offspring depend on parental diet. We examined 7 imprinted loci in spermatozoa DNA from HFD-treated and control fathers by bisulfite sequencing, but did not detect changes in DNA methylation associated with HFD. Using chromatin immunoprecipitation followed by high-throughput sequencing, we found differential histone H3-occupancy at genes involved in the regulation of embryogenesis and differential H3K4me1-enrichment at transcription regulatory genes in HFD fathers vs. control mice. These results suggest that dietary exposure can modulate histone composition at regulatory genes implicated in developmental processes.
DOI: 10.6084/m9.figshare.1568112.v2
title: Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

description: Several studies have described phenotypic changes in the offspring of mice exposed to a variety of environmental factors, including diet, toxins, and stress; however, the molecular pathways involved in these changes remain unclear. Using a high fat diet (HFD)-induced obesity mouse model, we examined liver gene expression in male offspring and analyzed chromatin of paternal spermatozoa. We found that the hepatic mRNA level of 7 genes (out of 20 evaluated) was significantly altered in HFD male offspring compared to control mice, suggesting that phenotypic changes in the offspring depend on parental diet. We examined seven imprinted loci in spermatozoa DNA from HFD-treated and control fathers by bisulfite sequencing, but did not detect changes in DNA methylation associated with HFD. Using chromatin immunoprecipitation followed by high-throughput sequencing, we found differential histone H3-occupancy at genes involved in the regulation of embryogenesis and differential H3K4me1-enrichment at transcription regulatory genes in HFD fathers versus control mice. These results suggest that dietary exposure can modulate histone composition at regulatory genes implicated in developmental processes.
DOI: 10.6084/m9.figshare.1568104
title: A gustatory second-order neuron that connects sucrose-sensitive primary neurons and a distinct region of the gnathal ganglion in the <i>Drosophila</i> brain

description: Although the gustatory system provides animals with sensory cues important for food choice and other critical behaviors, little is known about neural circuitry immediately following gustatory sensory neurons (GSNs). Here, we identify and characterize a bilateral pair of gustatory second-order neurons (G2Ns) in <i>Drosophila</i>. Previous studies identified GSNs that relay taste information to distinct subregions of the primary gustatory center (PGC) in the gnathal ganglia (GNG). To identify candidate G2Ns, we screened ∼5,000 GAL4 driver strains for lines that label neural fibers innervating the PGC. We then combined GRASP (GFP reconstitution across synaptic partners) with presynaptic labeling to visualize potential synaptic contacts between the dendrites of the candidate G2Ns and the axonal terminals of <i>Gr5a</i>-expressing GSNs, which are known to respond to sucrose. Results of the GRASP analysis, followed by a single-cell analysis by FLP-out recombination, revealed a pair of neurons that contact <i>Gr5a</i> axon terminals in both brain hemispheres and send axonal arborizations to a distinct region outside the PGC but within the GNG. To characterize the input and output branches, respectively, we expressed fluorescence-tagged acetylcholine receptor subunit (Dα7) and active-zone marker (Brp) in the G2Ns. We found that G2N input sites overlaid GRASP-labeled synaptic contacts to <i>Gr5a</i> neurons, while presynaptic sites were broadly distributed throughout the neurons’ arborizations. GRASP analysis and further tests with the Syb–GRASP method suggested that the identified G2Ns receive synaptic inputs from <i>Gr5a</i>-expressing GSNs, but not <i>Gr66a</i>-expressing GSNs, which respond to caffeine. The identified G2Ns relay information from <i>Gr5a</i>-expressing GSNs to distinct regions in the GNG, and are distinct from other, recently identified gustatory projection neurons, which relay information about sugars to a brain region called the antennal mechanosensory and motor center (AMMC). Our findings suggest unexpected complexity for taste information processing in the first relay of the gustatory system.
DOI: 10.6084/m9.figshare.1568104.v2
title: A gustatory second-order neuron that connects sucrose-sensitive primary neurons and a distinct region of the gnathal ganglion in the <i>Drosophila</i> brain

description: Although the gustatory system provides animals with sensory cues important for food choice and other critical behaviors, little is known about neural circuitry immediately following gustatory sensory neurons (GSNs). Here, we identify and characterize a bilateral pair of gustatory second-order neurons (G2Ns) in <i>Drosophila</i>. Previous studies identified GSNs that relay taste information to distinct subregions of the primary gustatory center (PGC) in the gnathal ganglia (GNG). To identify candidate G2Ns, we screened ∼5,000 GAL4 driver strains for lines that label neural fibers innervating the PGC. We then combined GRASP (GFP reconstitution across synaptic partners) with presynaptic labeling to visualize potential synaptic contacts between the dendrites of the candidate G2Ns and the axonal terminals of <i>Gr5a</i>-expressing GSNs, which are known to respond to sucrose. Results of the GRASP analysis, followed by a single-cell analysis by FLP-out recombination, revealed a pair of neurons that contact <i>Gr5a</i> axon terminals in both brain hemispheres and send axonal arborizations to a distinct region outside the PGC but within the GNG. To characterize the input and output branches, respectively, we expressed fluorescence-tagged acetylcholine receptor subunit (Dα7) and active-zone marker (Brp) in the G2Ns. We found that G2N input sites overlaid GRASP-labeled synaptic contacts to <i>Gr5a</i> neurons, while presynaptic sites were broadly distributed throughout the neurons’ arborizations. GRASP analysis and further tests with the Syb–GRASP method suggested that the identified G2Ns receive synaptic inputs from <i>Gr5a</i>-expressing GSNs, but not <i>Gr66a</i>-expressing GSNs, which respond to caffeine. The identified G2Ns relay information from <i>Gr5a</i>-expressing GSNs to distinct regions in the GNG, and are distinct from other, recently identified gustatory projection neurons, which relay information about sugars to a brain region called the antennal mechanosensory and motor center (AMMC). Our findings suggest unexpected complexity for taste information processing in the first relay of the gustatory system.
DOI: 10.6084/m9.figshare.1568104.v1
title: A gustatory second-order neuron that connects sucrose-sensitive primary neurons and a distinct region of the gnathal ganglion in the <i>Drosophila</i> brain

description: Although the gustatory system provides animals with sensory cues important for food choice and other critical behaviors, little is known about neural circuitry immediately following gustatory sensory neurons (GSNs). Here, we identify and characterize a bilateral pair of gustatory second-order neurons (G2Ns) in <i>Drosophila</i>. Previous studies identified GSNs that relay taste information to distinct subregions of the primary gustatory center (PGC) in the gnathal ganglia (GNG). To identify candidate G2Ns, we screened ∼5,000 GAL4 driver strains for lines that label neural fibers innervating the PGC. We then combined GRASP (GFP reconstitution across synaptic partners) with presynaptic labeling to visualize potential synaptic contacts between the dendrites of the candidate G2Ns and the axonal terminals of <i>Gr5a</i>-expressing GSNs, which are known to respond to sucrose. Results of the GRASP analysis, followed by a single-cell analysis by FLP-out recombination, revealed a pair of neurons that contact <i>Gr5a</i> axon terminals in both brain hemispheres and send axonal arborizations to a distinct region outside the PGC but within the GNG. To characterize the input and output branches, respectively, we expressed fluorescence-tagged acetylcholine receptor subunit (Dα7) and active-zone marker (Brp) in the G2Ns. We found that G2N input sites overlaid GRASP-labeled synaptic contacts to <i>Gr5a</i> neurons, while presynaptic sites were broadly distributed throughout the neurons’ arborizations. GRASP analysis and further tests with the Syb–GRASP method suggested that the identified G2Ns receive synaptic inputs from <i>Gr5a</i>-expressing GSNs, but not <i>Gr66a</i>-expressing GSNs, which respond to caffeine. The identified G2Ns relay information from <i>Gr5a</i>-expressing GSNs to distinct regions in the GNG, and are distinct from other, recently identified gustatory projection neurons, which relay information about sugars to a brain region called the antennal mechanosensory and motor center (AMMC). Our findings suggest unexpected complexity for taste information processing in the first relay of the gustatory system.
DOI: 10.6084/m9.figshare.1568099
title: Palaeomagnetic assessment of plutons from the southern Peninsular Ranges batholith and the Jurassic Vizcaíno igneous suites, Baja California, México

description: ABSTRACTWe report geological and palaeomagnetic data from five discrete plutons in the southern part of the Peninsular Ranges batholith (PRB) and one pluton that is part of the Jurassic plutonic suite in the Vizcaíno peninsula. The PRB plutons are Cretaceous and belong to the Alisitos island arc. The Jurassic pluton intrudes a Triassic-Jurassic ophiolite.Our study was designed to evaluate the palaeomagnetic homogeneity of the batholith from the Sierra San Pedro Mártir, at ~31°N, to about ~28.3°N. The Punta Prieta, Nuevo Rosarito, San Jerónimo, and La Rinconada plutons in the western zone of the PRB are characterized by magnetizations residing in magnetite. The Compostela pluton is emplaced in a transition zone and has a magnetization that resides in haematite. The five Cretaceous plutons yield a combined palaeopole at 80.3°N, 162.1°E, <i>A</i><sub>95</sub> = 9.8°, <i>N</i> = 5 that after correcting for the opening of the Gulf of California rotates to 77.6°N, 173.6°E, the rotated pole being in angular distance of only 4.4° from the North America reference pole. The Jurassic San Roque pluton yields a mean 0.6°N, 306.1°E, <i>A</i><sub>95</sub> = 9.2°, <i>N</i> = 10, which is discordant, showing a clockwise rotation of about 131° ± 16° and flattening of 9.5° ± 12.9° with respect to the 150 Ma cratonic reference palaeopole. The results suggest that the intrusion of the undeformed Cretaceous Punta Prieta to Compostela plutons (128.1 ± 1.4 and 100.5 ± 2.7 Ma, respectively) restricts tectonic accretion of the Jurassic-Early Cretaceous sequences to the North America margin to the time before mid-Cretaceous magmatism (~100 Ma) in the PRB near present latitude 28°N. Mesozoic and Cenozoic strike-slip faulting along the Vizcaíno margin can account for the 131° clockwise rotation of the San Roque pluton. Our results do not support significant latitudinal movement between Vizcaíno, the PRB, and mainland Mexico with the exception of the Neogene San Andreas Fault-related right lateral movement.
DOI: 10.6084/m9.figshare.1568099.v1
title: Palaeomagnetic assessment of plutons from the southern Peninsular Ranges batholith and the Jurassic Vizcaíno igneous suites, Baja California, México

description: ABSTRACTWe report geological and palaeomagnetic data from five discrete plutons in the southern part of the Peninsular Ranges batholith (PRB) and one pluton that is part of the Jurassic plutonic suite in the Vizcaíno peninsula. The PRB plutons are Cretaceous and belong to the Alisitos island arc. The Jurassic pluton intrudes a Triassic-Jurassic ophiolite.Our study was designed to evaluate the palaeomagnetic homogeneity of the batholith from the Sierra San Pedro Mártir, at ~31°N, to about ~28.3°N. The Punta Prieta, Nuevo Rosarito, San Jerónimo, and La Rinconada plutons in the western zone of the PRB are characterized by magnetizations residing in magnetite. The Compostela pluton is emplaced in a transition zone and has a magnetization that resides in haematite. The five Cretaceous plutons yield a combined palaeopole at 80.3°N, 162.1°E, <i>A</i><sub>95</sub> = 9.8°, <i>N</i> = 5 that after correcting for the opening of the Gulf of California rotates to 77.6°N, 173.6°E, the rotated pole being in angular distance of only 4.4° from the North America reference pole. The Jurassic San Roque pluton yields a mean 0.6°N, 306.1°E, <i>A</i><sub>95</sub> = 9.2°, <i>N</i> = 10, which is discordant, showing a clockwise rotation of about 131° ± 16° and flattening of 9.5° ± 12.9° with respect to the 150 Ma cratonic reference palaeopole. The results suggest that the intrusion of the undeformed Cretaceous Punta Prieta to Compostela plutons (128.1 ± 1.4 and 100.5 ± 2.7 Ma, respectively) restricts tectonic accretion of the Jurassic-Early Cretaceous sequences to the North America margin to the time before mid-Cretaceous magmatism (~100 Ma) in the PRB near present latitude 28°N. Mesozoic and Cenozoic strike-slip faulting along the Vizcaíno margin can account for the 131° clockwise rotation of the San Roque pluton. Our results do not support significant latitudinal movement between Vizcaíno, the PRB, and mainland Mexico with the exception of the Neogene San Andreas Fault-related right lateral movement.
DOI: 10.6084/m9.figshare.1568094
title: Embryonic development and maternal regulation of murine circadian clock function

description: The importance of circadian clocks in the regulation of adult physiology in mammals is well established. In contrast, the ontogenesis of the circadian system and its role in embryonic development are still poorly understood. Although there is experimental evidence that the clock machinery is present prior to birth, data on gestational clock functionality are inconsistent. Moreover, little is known about the dependence of embryonic rhythms on maternal and environmental time cues and the role of circadian oscillations for embryonic development. The aim of this study was to test if fetal mouse tissues from early embryonic stages are capable of expressing endogenous, self-sustained circadian rhythms and their contribution to embryogenesis. Starting on embryonic day 13, we collected precursor tissues for suprachiasmatic nucleus (SCN), liver and kidney from embryos carrying the circadian reporter gene <i>Per2::Luc</i> and investigated rhythmicity and circadian traits of these tissues <i>ex vivo</i>. We found that even before the respective organs were fully developed, embryonic tissues were capable of expressing circadian rhythms. Period and amplitude of which were determined very early during development and phases of liver and kidney explants are not influenced by tissue preparation, whereas SCN explants phasing is strongly dependent on preparation time. Embryonic circadian rhythms also developed in the absence of maternal and environmental time signals. Morphological and histological comparison of offspring from matings of <i>Clock-Δ19</i> mutant and wild-type mice revealed that both fetal and maternal clocks have distinct roles in embryogenesis. While genetic disruptions of maternal and embryonic clock function leads to increased fetal fat depots, abnormal ossification and organ development, <i>Clock</i> gene mutant newborns from mothers with a functional clock showed a larger body size compared to wild-type littermates. These data may contribute to the understanding of the ontogenesis of circadian clocks and the risk of disturbed maternal or embryonic circadian rhythms for embryonic development.