cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1399208.v1
title: Destabilization of pluripotency in the absence of Mad2l2

description: The induction and maintenance of pluripotency requires the expression of several core factors at appropriate levels (Oct4, Sox2, Klf4, Prdm14). A subset of these proteins (Oct4, Sox2, Prdm14) also plays crucial roles for the establishment of primordial germ cells (PGCs). Here we demonstrate that the Mad2l2 (MAD2B, Rev7) gene product is not only required by PGCs, but also by pluripotent embryonic stem cells (ESCs), depending on the growth conditions. Mad2l2<sup>−/−</sup> ESCs were unstable in LIF/serum medium, and differentiated into primitive endoderm. However, they could be stably propagated using small molecule inhibitors of MAPK signaling. Several components of the MAPK cascade were up- or downregulated even in undifferentiated Mad2l2<sup>−/−</sup> ESCs. Global levels of repressive histone H3 variants were increased in mutant ESCs, and the epigenetic signatures on pluripotency-, primitive endoderm-, and MAPK-related loci differed. Thus, H3K9me2 repressed the Nanog promoter, while the promoter of Gata4 lost H3K27me3 and became de-repressed in LIF/serum condition. Promoters associated with genes involved in MAPK signaling also showed misregulation of these histone marks. Such epigenetic modifications could be indirect consequences of mutating Mad2l2. However, our previous observations suggested the histone methyltransferases as direct (G9a) or indirect (Ezh2) targets of Mad2l2. In effect, the intricate balance necessary for pluripotency becomes perturbed in the absence of Mad2l2.
DOI: 10.6084/m9.figshare.1399206.v1
title: BRCA1 deficiency in ovarian cancer is associated with alteration in expression of several key regulators of cell motility – A proteomics study

description: Functional loss of expression of breast cancer susceptibility gene 1(<i>BRCA1</i>) has been implicated in genomic instability and cancer progression. There is emerging evidence that <i>BRCA1</i> gene product (BRCA1) also plays a role in cancer cell migration. We performed a quantitative proteomics study of EOC patient tumor tissues and identified changes in expression of several key regulators of actin cytoskeleton/cell adhesion and cell migration (CAPN1, 14–3–3, CAPG, PFN1, SPTBN1, CFN1) associated with loss of BRCA1 function. Gene expression analyses demonstrate that several of these proteomic hits are differentially expressed between early and advanced stage EOC thus suggesting clinical relevance of these proteins to disease progression. By immunohistochemistry of ovarian tumors with BRCA1<sup>+/+</sup> and BRCA1<sup>null</sup> status, we further verified our proteomic-based finding of elevated PFN1 expression associated with BRCA1 deficiency. Finally, we established a causal link between PFN1 and BRCA1-induced changes in cell migration thus uncovering a novel mechanistic basis for BRCA1-dependent regulation of ovarian cancer cell migration. Overall, findings of this study open up multiple avenues by which BRCA1 can potentially regulate migration and metastatic phenotype of EOC cells.
DOI: 10.6084/m9.figshare.1399208.v2
title: Destabilization of pluripotency in the absence of Mad2l2

description: The induction and maintenance of pluripotency requires the expression of several core factors at appropriate levels (Oct4, Sox2, Klf4, Prdm14). A subset of these proteins (Oct4, Sox2, Prdm14) also plays crucial roles for the establishment of primordial germ cells (PGCs). Here we demonstrate that the Mad2l2 (MAD2B, Rev7) gene product is not only required by PGCs, but also by pluripotent embryonic stem cells (ESCs), depending on the growth conditions. Mad2l2<sup>−/−</sup> ESCs were unstable in LIF/serum medium, and differentiated into primitive endoderm. However, they could be stably propagated using small molecule inhibitors of MAPK signaling. Several components of the MAPK cascade were up- or downregulated even in undifferentiated Mad2l2<sup>−/−</sup> ESCs. Global levels of repressive histone H3 variants were increased in mutant ESCs, and the epigenetic signatures on pluripotency-, primitive endoderm-, and MAPK-related loci differed. Thus, H3K9me2 repressed the Nanog promoter, while the promoter of Gata4 lost H3K27me3 and became de-repressed in LIF/serum condition. Promoters associated with genes involved in MAPK signaling also showed misregulation of these histone marks. Such epigenetic modifications could be indirect consequences of mutating Mad2l2. However, our previous observations suggested the histone methyltransferases as direct (G9a) or indirect (Ezh2) targets of Mad2l2. In effect, the intricate balance necessary for pluripotency becomes perturbed in the absence of Mad2l2.
DOI: 10.6084/m9.figshare.1399206.v2
title: BRCA1 deficiency in ovarian cancer is associated with alteration in expression of several key regulators of cell motility – A proteomics study

description: Functional loss of expression of breast cancer susceptibility gene 1(<i>BRCA1</i>) has been implicated in genomic instability and cancer progression. There is emerging evidence that <i>BRCA1</i> gene product (BRCA1) also plays a role in cancer cell migration. We performed a quantitative proteomics study of EOC patient tumor tissues and identified changes in expression of several key regulators of actin cytoskeleton/cell adhesion and cell migration (CAPN1, 14-3-3, CAPG, PFN1, SPTBN1, CFN1) associated with loss of BRCA1 function. Gene expression analyses demonstrate that several of these proteomic hits are differentially expressed between early and advanced stage EOC thus suggesting clinical relevance of these proteins to disease progression. By immunohistochemistry of ovarian tumors with BRCA1<sup>+/+</sup> and BRCA1<sup>null</sup> status, we further verified our proteomic-based finding of elevated PFN1 expression associated with BRCA1 deficiency. Finally, we established a causal link between PFN1 and BRCA1-induced changes in cell migration thus uncovering a novel mechanistic basis for BRCA1-dependent regulation of ovarian cancer cell migration. Overall, findings of this study open up multiple avenues by which BRCA1 can potentially regulate migration and metastatic phenotype of EOC cells.
DOI: 10.6084/m9.figshare.1399208.v3
title: Destabilization of pluripotency in the absence of Mad2l2

description: The induction and maintenance of pluripotency requires the expression of several core factors at appropriate levels (Oct4, Sox2, Klf4, Prdm14). A subset of these proteins (Oct4, Sox2, Prdm14) also plays crucial roles for the establishment of primordial germ cells (PGCs). Here we demonstrate that the Mad2l2 (MAD2B, Rev7) gene product is not only required by PGCs, but also by pluripotent embryonic stem cells (ESCs), depending on the growth conditions. Mad2l2<sup>−/−</sup> ESCs were unstable in LIF/serum medium, and differentiated into primitive endoderm. However, they could be stably propagated using small molecule inhibitors of MAPK signaling. Several components of the MAPK cascade were up- or downregulated even in undifferentiated Mad2l2<sup>−/−</sup> ESCs. Global levels of repressive histone H3 variants were increased in mutant ESCs, and the epigenetic signatures on pluripotency-, primitive endoderm-, and MAPK-related loci differed. Thus, H3K9me2 repressed the Nanog promoter, while the promoter of Gata4 lost H3K27me3 and became de-repressed in LIF/serum condition. Promoters associated with genes involved in MAPK signaling also showed misregulation of these histone marks. Such epigenetic modifications could be indirect consequences of mutating Mad2l2. However, our previous observations suggested the histone methyltransferases as direct (G9a) or indirect (Ezh2) targets of Mad2l2. In effect, the intricate balance necessary for pluripotency becomes perturbed in the absence of Mad2l2.
DOI: 10.6084/m9.figshare.1409398.v222
title: ABO phenotype protected reproduction as it is based on fucosylations.

description: The molecular biological relationship between human fertility and ABO(H) blood group phenotype formation becomes evident with the rare (Oh) or <i>Bombay</i> blood type, which based on the history of his own family, Charles Darwin would have interpreted as resulting from reduced fertility in consanguinities. In its native form, the <i>Bombay</i> type occurs in individuals with an extremely rare genotype (h/h;se/se), by which the fucosyltransferases FUT1 and FUT2 are not produced due to point mutations. These enzymes, encoded on chromosome 19, are epistatically connected with the A and B allelic glycotransferase functions encoded on chromosome 9, while the fucosyl residues provide the functional-structural basis for the formation of any ABO(H) phenotype on the cell surface or in secretions and plasma proteins. Immunoglobulins are also heavily fucosylated, and via developmental variation of the positions between the cell surfaces and the heavy chains of immunoglobulins, fucosyl residues appear to augment or reduce antibody-mediated cellular cytotoxicity involving physiological anti-self-reactivity; moreover, by regulating the assembly and intracellular signaling of precursor B cell receptors, the core fucosylation of immunoglobulin heavy chains represents a key mechanism in clonal selection. In fact, the seminal plasma of leucospermic infertile men has been reported to exert high levels of poorly core-fucosylated IgG. Consequently, in <i>Bombay </i>type individuals, the non-somatic glycosylation processes of embryogenic stem cell-to-germ cell transformation, which involve the modification and <i>O</i>-fucosylation of epidermal growth factor (EGF), are most likely exposed to metabolic competition with multiple glycosidic sites of poorly fucosylated, glycan-depleted immunoglobulins that might promote increased anti-self-reactive cytotoxicity.
DOI: 10.6084/m9.figshare.1399206.v3
title: BRCA1 deficiency in ovarian cancer is associated with alteration in expression of several key regulators of cell motility – A proteomics study

description: Functional loss of expression of breast cancer susceptibility gene 1(<i>BRCA1</i>) has been implicated in genomic instability and cancer progression. There is emerging evidence that <i>BRCA1</i> gene product (BRCA1) also plays a role in cancer cell migration. We performed a quantitative proteomics study of EOC patient tumor tissues and identified changes in expression of several key regulators of actin cytoskeleton/cell adhesion and cell migration (CAPN1, 14-3-3, CAPG, PFN1, SPTBN1, CFN1) associated with loss of BRCA1 function. Gene expression analyses demonstrate that several of these proteomic hits are differentially expressed between early and advanced stage EOC thus suggesting clinical relevance of these proteins to disease progression. By immunohistochemistry of ovarian tumors with BRCA1<sup>+/+</sup> and BRCA1<sup>null</sup> status, we further verified our proteomic-based finding of elevated PFN1 expression associated with BRCA1 deficiency. Finally, we established a causal link between PFN1 and BRCA1-induced changes in cell migration thus uncovering a novel mechanistic basis for BRCA1-dependent regulation of ovarian cancer cell migration. Overall, findings of this study open up multiple avenues by which BRCA1 can potentially regulate migration and metastatic phenotype of EOC cells.
DOI: 10.6084/m9.figshare.1399208.v4
title: Destabilization of pluripotency in the absence of Mad2l2

description: The induction and maintenance of pluripotency requires the expression of several core factors at appropriate levels (Oct4, Sox2, Klf4, Prdm14). A subset of these proteins (Oct4, Sox2, Prdm14) also plays crucial roles for the establishment of primordial germ cells (PGCs). Here we demonstrate that the Mad2l2 (MAD2B, Rev7) gene product is not only required by PGCs, but also by pluripotent embryonic stem cells (ESCs), depending on the growth conditions. Mad2l2<sup>−/−</sup> ESCs were unstable in LIF/serum medium, and differentiated into primitive endoderm. However, they could be stably propagated using small molecule inhibitors of MAPK signaling. Several components of the MAPK cascade were up- or downregulated even in undifferentiated Mad2l2<sup>−/−</sup> ESCs. Global levels of repressive histone H3 variants were increased in mutant ESCs, and the epigenetic signatures on pluripotency-, primitive endoderm-, and MAPK-related loci differed. Thus, H3K9me2 repressed the Nanog promoter, while the promoter of Gata4 lost H3K27me3 and became de-repressed in LIF/serum condition. Promoters associated with genes involved in MAPK signaling also showed misregulation of these histone marks. Such epigenetic modifications could be indirect consequences of mutating Mad2l2. However, our previous observations suggested the histone methyltransferases as direct (G9a) or indirect (Ezh2) targets of Mad2l2. In effect, the intricate balance necessary for pluripotency becomes perturbed in the absence of Mad2l2.
DOI: 10.6084/m9.figshare.1399206
title: BRCA1 deficiency in ovarian cancer is associated with alteration in expression of several key regulators of cell motility – A proteomics study

description: Functional loss of expression of breast cancer susceptibility gene 1(<i>BRCA1</i>) has been implicated in genomic instability and cancer progression. There is emerging evidence that <i>BRCA1</i> gene product (BRCA1) also plays a role in cancer cell migration. We performed a quantitative proteomics study of EOC patient tumor tissues and identified changes in expression of several key regulators of actin cytoskeleton/cell adhesion and cell migration (CAPN1, 14-3-3, CAPG, PFN1, SPTBN1, CFN1) associated with loss of BRCA1 function. Gene expression analyses demonstrate that several of these proteomic hits are differentially expressed between early and advanced stage EOC thus suggesting clinical relevance of these proteins to disease progression. By immunohistochemistry of ovarian tumors with BRCA1<sup>+/+</sup> and BRCA1<sup>null</sup> status, we further verified our proteomic-based finding of elevated PFN1 expression associated with BRCA1 deficiency. Finally, we established a causal link between PFN1 and BRCA1-induced changes in cell migration thus uncovering a novel mechanistic basis for BRCA1-dependent regulation of ovarian cancer cell migration. Overall, findings of this study open up multiple avenues by which BRCA1 can potentially regulate migration and metastatic phenotype of EOC cells.
DOI: 10.6084/m9.figshare.1399206.v5
title: BRCA1 deficiency in ovarian cancer is associated with alteration in expression of several key regulators of cell motility – A proteomics study

description: Functional loss of expression of breast cancer susceptibility gene 1(<i>BRCA1</i>) has been implicated in genomic instability and cancer progression. There is emerging evidence that <i>BRCA1</i> gene product (BRCA1) also plays a role in cancer cell migration. We performed a quantitative proteomics study of EOC patient tumor tissues and identified changes in expression of several key regulators of actin cytoskeleton/cell adhesion and cell migration (CAPN1, 14-3-3, CAPG, PFN1, SPTBN1, CFN1) associated with loss of BRCA1 function. Gene expression analyses demonstrate that several of these proteomic hits are differentially expressed between early and advanced stage EOC thus suggesting clinical relevance of these proteins to disease progression. By immunohistochemistry of ovarian tumors with BRCA1<sup>+/+</sup> and BRCA1<sup>null</sup> status, we further verified our proteomic-based finding of elevated PFN1 expression associated with BRCA1 deficiency. Finally, we established a causal link between PFN1 and BRCA1-induced changes in cell migration thus uncovering a novel mechanistic basis for BRCA1-dependent regulation of ovarian cancer cell migration. Overall, findings of this study open up multiple avenues by which BRCA1 can potentially regulate migration and metastatic phenotype of EOC cells.
DOI: 10.6084/m9.figshare.1399201
title: Per-site per-gene estimates of selection posterior densities

description: 'site_hpds.csv' summarizes selection coefficients obtained by renaissance counting.<br>It contains 12 columns: * 'subject': Subject for the analyzed sample ('A', 'B', or 'C').<br>* 'sample': A sample identifier.<br>* 'gene': The IGHV gene and allele analyzed.<br>* 'variable': One of:<br>- 'dN' - the nonsynonymous substitution rate.<br>- 'dS' - the synonymous substitution rate.<br>- 'dNdS' - the selection coefficient, omega.<br>* 'subset': Subset of sequences represented by the row. One of:<br>- 'out-of-frame': out of frame sequences only.<br>- 'productive': in frame sequences without stop-codons identified.<br>- 'productive/out-of-frame': productive rates normalized by out-of-frame rates. See manuscript for details.<br>* 'site': The codon site within the V gene.<br>* 'imgt_site': The codon site within the V gene, using IMGT unique numbering.<br>* 'median': Median value<br>* 'hpdLower': Lower bound of the 95% HPD interval.<br>* 'hpdUpper': Upper bound of the 95% HPD interval.<br>* 'coverage': Number of sequences analyzed covering this position.<br>* 'oof_coverage': Number of out-of-frame sequences covering this position. The selection coefficients presented in the manuscript are the subset of rows for which:<br>* 'oof_coverage &gt; 100'<br>* 'subset == "productive/out-of-frame"'<br>* 'variable == "dNdS"'
DOI: 10.6084/m9.figshare.1409398.v223
title: ABO phenotype protected reproduction as it is based on fucosylations.

description: The molecular biological relationship between human fertility and ABO(H) blood group phenotype formation becomes evident with the rare (Oh) or <i>Bombay</i> blood type, which based on the history of his own family, Charles Darwin would have interpreted as resulting from reduced fertility in consanguinities. In its native form, the <i>Bombay</i> type occurs in individuals with an extremely rare genotype (h/h;se/se), by which the fucosyltransferases FUT1 and FUT2 are not produced due to point mutations. These enzymes, encoded on chromosome 19, are epistatically connected with the A and B allelic glycotransferase functions encoded on chromosome 9, while the fucosyl residues provide the functional-structural basis for the formation of any ABO(H) phenotype on the cell surface or in secretions and plasma proteins. Immunoglobulins are also heavily fucosylated, and via developmental variation of the positions between the cell surfaces and the heavy chains of immunoglobulins, fucosyl residues appear to augment or reduce antibody-mediated cellular cytotoxicity involving physiological anti-self-reactivity; moreover, by regulating the assembly and intracellular signaling of precursor B cell receptors, the core fucosylation of immunoglobulin heavy chains represents a key mechanism in clonal selection. In fact, the seminal plasma of leucospermic infertile men has been reported to exert high levels of poorly core-fucosylated IgG. Consequently, in <i>Bombay </i>type individuals, the non-somatic glycosylation processes of embryogenic stem cell-to-germ cell transformation, which involve the modification and <i>O</i>-fucosylation of epidermal growth factor (EGF), are most likely exposed to metabolic competition with multiple glycosidic sites of poorly fucosylated, glycan-depleted immunoglobulins that might promote increased anti-self-reactive cytotoxicity.
DOI: 10.6084/m9.figshare.1399201.v1
title: Per-site per-gene estimates of selection posterior densities

description: 'site_hpds.csv' summarizes selection coefficients obtained by renaissance counting.<br>It contains 12 columns: * 'subject': Subject for the analyzed sample ('A', 'B', or 'C').<br>* 'sample': A sample identifier.<br>* 'gene': The IGHV gene and allele analyzed.<br>* 'variable': One of:<br>- 'dN' - the nonsynonymous substitution rate.<br>- 'dS' - the synonymous substitution rate.<br>- 'dNdS' - the selection coefficient, omega.<br>* 'subset': Subset of sequences represented by the row. One of:<br>- 'out-of-frame': out of frame sequences only.<br>- 'productive': in frame sequences without stop-codons identified.<br>- 'productive/out-of-frame': productive rates normalized by out-of-frame rates. See manuscript for details.<br>* 'site': The codon site within the V gene.<br>* 'imgt_site': The codon site within the V gene, using IMGT unique numbering.<br>* 'median': Median value<br>* 'hpdLower': Lower bound of the 95% HPD interval.<br>* 'hpdUpper': Upper bound of the 95% HPD interval.<br>* 'coverage': Number of sequences analyzed covering this position.<br>* 'oof_coverage': Number of out-of-frame sequences covering this position. The selection coefficients presented in the manuscript are the subset of rows for which:<br>* 'oof_coverage &gt; 100'<br>* 'subset == "productive/out-of-frame"'<br>* 'variable == "dNdS"'
DOI: 10.6084/m9.figshare.1399208.v5
title: Destabilization of pluripotency in the absence of Mad2l2

description: The induction and maintenance of pluripotency requires the expression of several core factors at appropriate levels (Oct4, Sox2, Klf4, Prdm14). A subset of these proteins (Oct4, Sox2, Prdm14) also plays crucial roles for the establishment of primordial germ cells (PGCs). Here we demonstrate that the Mad2l2 (MAD2B, Rev7) gene product is not only required by PGCs, but also by pluripotent embryonic stem cells (ESCs), depending on the growth conditions. Mad2l2<sup>−/−</sup> ESCs were unstable in LIF/serum medium, and differentiated into primitive endoderm. However, they could be stably propagated using small molecule inhibitors of MAPK signaling. Several components of the MAPK cascade were up- or downregulated even in undifferentiated Mad2l2<sup>−/−</sup> ESCs. Global levels of repressive histone H3 variants were increased in mutant ESCs, and the epigenetic signatures on pluripotency-, primitive endoderm-, and MAPK-related loci differed. Thus, H3K9me2 repressed the Nanog promoter, while the promoter of Gata4 lost H3K27me3 and became de-repressed in LIF/serum condition. Promoters associated with genes involved in MAPK signaling also showed misregulation of these histone marks. Such epigenetic modifications could be indirect consequences of mutating Mad2l2. However, our previous observations suggested the histone methyltransferases as direct (G9a) or indirect (Ezh2) targets of Mad2l2. In effect, the intricate balance necessary for pluripotency becomes perturbed in the absence of Mad2l2.
DOI: 10.6084/m9.figshare.1399206.v4
title: BRCA1 deficiency in ovarian cancer is associated with alteration in expression of several key regulators of cell motility – A proteomics study

description: Functional loss of expression of breast cancer susceptibility gene 1(<i>BRCA1</i>) has been implicated in genomic instability and cancer progression. There is emerging evidence that <i>BRCA1</i> gene product (BRCA1) also plays a role in cancer cell migration. We performed a quantitative proteomics study of EOC patient tumor tissues and identified changes in expression of several key regulators of actin cytoskeleton/cell adhesion and cell migration (CAPN1, 14-3-3, CAPG, PFN1, SPTBN1, CFN1) associated with loss of BRCA1 function. Gene expression analyses demonstrate that several of these proteomic hits are differentially expressed between early and advanced stage EOC thus suggesting clinical relevance of these proteins to disease progression. By immunohistochemistry of ovarian tumors with BRCA1<sup>+/+</sup> and BRCA1<sup>null</sup> status, we further verified our proteomic-based finding of elevated PFN1 expression associated with BRCA1 deficiency. Finally, we established a causal link between PFN1 and BRCA1-induced changes in cell migration thus uncovering a novel mechanistic basis for BRCA1-dependent regulation of ovarian cancer cell migration. Overall, findings of this study open up multiple avenues by which BRCA1 can potentially regulate migration and metastatic phenotype of EOC cells.
DOI: 10.6084/m9.figshare.1399197
title: Provenance RDF Models

description: A reference data set crowdsourced from multiple data sources. Codes to generate multiple provenance RDF models are available. The sample queries for comparative analysis are also included.