cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1266490.v3
title: Inhibition of C-terminal binding protein attenuates transcription factor 4 signaling to selectively target colon cancer stem cells

description: Selective targeting of cancer stem cells (CSCs), implicated in tumor relapse, holds great promise in the treatment of colorectal cancer. Overexpression of C-terminal binding protein (CtBP), an NADH dependent transcriptional regulator, is often observed in colon cancer. Of note, TCF-4 signaling is also up-regulated in colonic CSCs. We hypothesized that CtBP, whose dehydrogenase activity is amenable to pharmacological inhibition by 4-methylthio-2-oxobutyric acid (MTOB), positively regulates TCF-4 signaling, leading to CSC growth and self-renewal. CSCs demonstrated significant upregulation of CtBP1 and CtBP2 levels (mRNA and protein) and activity partly due to increased NADH/NAD ratio, as well as increased TCF/LEF transcriptional activity, compared to respective controls. Depletion of CtBP2 inhibited, while its overexpression enhanced, CSC growth (1° spheroids) and self-renewal (2°/3° spheroids). Similarly, MTOB caused a robust inhibition of spheroid growth and self-renewal in a dose dependent manner. MTOB displayed significantly greater selectivity for growth inhibition in the spheroids, at least in part through induction of apoptosis, compared to monolayer controls. Moreover, MTOB inhibited basal as well as induced (by GSK-3β inhibitor) TCF/LEF activity while suppressing mRNA and protein levels of several β-catenin target genes (CD44, Snail, C-MYC and LGR5). Lastly, CtBP physically interacted with TCF-4, and this interaction was significantly inhibited in the presence of MTOB. The above findings point to a novel role of CtBPs in the promotion of CSC growth and self-renewal through direct regulation of TCF/LEF transcription. Moreover, small molecular inhibition of its function can selectively target CSCs, presenting a novel approach for treatment of colorectal cancer focused on targeting of CSCs.
DOI: 10.6084/m9.figshare.1266476
title: Informe de autoevaluación de actividades docentes. Jorge Hernán Ramírez. Universidad del Valle. Feb 15, 2014 a Dic 10, 2014.

description: Informe de autoevaluación Universidad del Valle. Ramirez, Jorge H (2014): Mental disease stigma and academic bullying- criminal methods to silence medical and scientific debate. fig<strong>share</strong>.
DOI: 10.6084/m9.figshare.1279394.v253
title: Early ovariectomy reveals the germline encoding of the “natural” mammalian anti-A-reactive IgM reflecting developmental malignancy.

description: The germline encoding of a non-immune immunoglobulin M (IgM) molecule in mammals was experimentally documented for the first time as a result of the specifically timed ovariectomy of C57BL/10 mice. The target of this innate antibody involves a trans-species developmental antigen that signifies malignancy when expressed in any non-developmental tissue. Although ovariectomy and castration result in uncontrolled and/or enhanced humoral and cellular immunity involving increased weights of the spleen and thymus with pronounced B and T cell production, the development of mercaptoethanol-sensitive, complement-binding, non-immune anti-A reactivity in murine plasma was not enhanced after an ovariectomy that was performed in C57BL/10 mice prior to the onset of puberty. This non-immune murine anti-A, which is complementary to the trans-species, syngeneic ovarian GalNAc-glycan-bearing glycolipids and distinct from the cross-reactive adaptive anti-A antibody, was strongly downregulated or did not appear in plasma of animals ovariectomized at the age of 20 days. In mouse and man, this molecule most likely gets its complementary footprint from the first, genetically as-yet-undefined trans-species <i>O</i>-linked glycosylation of proteins and after depletion of the volatilely expressed “immature” <i>O</i>-GalNAc transferase activities and release from the transiently appearing glycopeptides, provides the A-reactive glycosidic sites. Consequently, these volatilely expressed non-somatic <i>O</i>-GalNAc-glycosylations of proteins, involving serine/threonine residues, are either identical or metabolically related with those of the mucin-type “aberrant” monosaccharide GalNAcα1-<i>O</i>-Ser/Thr-R or Tn antigen and explain the anti-Tn cross-reactivity of anti-A specific immunoglobulins and the pronounced occurrence of anti-Tn in the plasma of the human histo (blood) group O, in which the A-allelic, phenotype-specific GalNAc glycosylation of plasma proteins does not occur and not affect the anti-Tn levels.
DOI: 10.6084/m9.figshare.1266489.v2
title: Depletion of ATR selectively sensitizes ATM-deficient human mammary epithelial cells to ionizing radiation and DNA-damaging agents

description: DNA damage response (DDR) to double strand breaks is coordinated by 3 phosphatidylinositol 3-kinase-related kinase (PIKK) family members: the ataxia-telangiectasia mutated kinase (ATM), the ATM and Rad3-related (ATR) kinase and the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs). ATM and ATR are central players in activating cell cycle checkpoints and function as an active barrier against genome instability and tumorigenesis in replicating cells. Loss of ATM function is frequently reported in various types of tumors, thus placing more reliance on ATR for checkpoint arrest and cell survival following DNA damage. To investigate the role of ATR in the G<sub>2</sub>/M checkpoint regulation in response to ionizing radiation (IR), particularly when ATM is deficient, cell lines deficient of ATM, ATR, or both were generated using a doxycycline-inducible lentiviral system. Our data suggests that while depletion of ATR or ATM alone in wild-type human mammary epithelial cell cultures (HME-CCs) has little effect on radiosensitivity or IR-induced G<sub>2</sub>/M checkpoint arrest, depletion of ATR in ATM-deficient cells causes synthetic lethality following IR, which correlates with severe G<sub>2</sub>/M checkpoint attenuation. ATR depletion also inhibits IR-induced autophagy, regardless of the ATM status, and enhances IR-induced apoptosis particularly when ATM is deficient. Collectively, our results clearly demonstrate that ATR function is required for the IR-induced G<sub>2</sub>/M checkpoint activation and subsequent survival of cells with ATM deficiency. The synthetic lethal interaction between ATM and ATR in response to IR supports ATR as a therapeutic target for improved anti-cancer regimens, especially in tumors with a dysfunctional ATM pathway.
DOI: 10.6084/m9.figshare.1266490.v2
title: Inhibition of C-terminal binding protein attenuates transcription factor 4 signaling to selectively target colon cancer stem cells

description: Selective targeting of cancer stem cells (CSCs), implicated in tumor relapse, holds great promise in the treatment of colorectal cancer. Overexpression of C-terminal binding protein (CtBP), an NADH dependent transcriptional regulator, is often observed in colon cancer. Of note, TCF-4 signaling is also up-regulated in colonic CSCs. We hypothesized that CtBP, whose dehydrogenase activity is amenable to pharmacological inhibition by 4-methylthio-2-oxobutyric acid (MTOB), positively regulates TCF-4 signaling, leading to CSC growth and self-renewal. CSCs demonstrated significant upregulation of CtBP1 and CtBP2 levels (mRNA and protein) and activity partly due to increased NADH/NAD ratio, as well as increased TCF/LEF transcriptional activity, compared to respective controls. Depletion of CtBP2 inhibited, while its overexpression enhanced, CSC growth (1° spheroids) and self-renewal (2°/3° spheroids). Similarly, MTOB caused a robust inhibition of spheroid growth and self-renewal in a dose dependent manner. MTOB displayed significantly greater selectivity for growth inhibition in the spheroids, at least in part through induction of apoptosis, compared to monolayer controls. Moreover, MTOB inhibited basal as well as induced (by GSK-3β inhibitor) TCF/LEF activity while suppressing mRNA and protein levels of several β-catenin target genes (CD44, Snail, C-MYC and LGR5). Lastly, CtBP physically interacted with TCF-4, and this interaction was significantly inhibited in the presence of MTOB. The above findings point to a novel role of CtBPs in the promotion of CSC growth and self-renewal through direct regulation of TCF/LEF transcription. Moreover, small molecular inhibition of its function can selectively target CSCs, presenting a novel approach for treatment of colorectal cancer focused on targeting of CSCs.
DOI: 10.6084/m9.figshare.1266471
title: Proyecto plantas medicinales - Universidad del Valle

description: Proyecto plantas medicinales. Jorge H. Ramírez Universidad del Valle -- Dec 10, 2014. Co-author added: Atanas Atanasov. University of Vienna.
DOI: 10.6084/m9.figshare.1266471.v1
title: Proyecto plantas medicinales - Universidad del Valle

description: Proyecto plantas medicinales. Jorge H. Ramírez Universidad del Valle -- Dec 10, 2014. Co-author added: Atanas Atanasov. University of Vienna.
DOI: 10.6084/m9.figshare.1279394.v254
title: Early ovariectomy reveals the germline encoding of the “natural” mammalian anti-A-reactive IgM reflecting developmental malignancy.

description: The germline encoding of a non-immune immunoglobulin M (IgM) molecule in mammals was experimentally documented for the first time as a result of the specifically timed ovariectomy of C57BL/10 mice. The target of this innate antibody involves a trans-species developmental antigen that signifies malignancy when expressed in any non-developmental tissue. Although ovariectomy and castration result in uncontrolled and/or enhanced humoral and cellular immunity involving increased weights of the spleen and thymus with pronounced B and T cell production, the development of mercaptoethanol-sensitive, complement-binding, non-immune anti-A reactivity in murine plasma was not enhanced after an ovariectomy that was performed in C57BL/10 mice prior to the onset of puberty. This non-immune murine anti-A, which is complementary to the GalNAc glycan of syngeneic ovarian glycolipids and distinct from the cross-reactive adaptive anti-A antibody, was strongly downregulated or did not appear in plasma of animals ovariectomized at the age of 20 days. In mouse and man, this molecule most likely gets its complementary footprint from the first, genetically as-yet-undefined trans-species <i>O</i>-linked glycosylation of proteins and after depletion of the volatilely expressed “immature” <i>O</i>-GalNAc transferase activities and release from the transiently appearing glycopeptides, provides the A-reactive glycosidic sites. Consequently, these volatilely expressed non-somatic <i>O</i>-GalNAc-glycosylations of proteins, involving serine/threonine residues, are either identical or metabolically related with those of the mucin-type “aberrant” monosaccharide GalNAcα1-<i>O</i>-Ser/Thr-R or Tn antigen and explain the anti-Tn cross-reactivity of anti-A specific immunoglobulins and the pronounced occurrence of anti-Tn in the plasma of the human histo (blood) group O, in which the A-allelic, phenotype-specific GalNAc glycosylation of plasma proteins does not occur and not affect the anti-Tn levels.
DOI: 10.6084/m9.figshare.1266468
title: Values of the distances between atoms of residues that coordinate copper ions in the models and the mold.

description: Values of the distances between atoms of residues that coordinate copper ions in the models and the mold.
DOI: 10.6084/m9.figshare.1266476.v1
title: Informe de autoevaluación de actividades docentes. Jorge Hernán Ramírez. Universidad del Valle. Feb 15, 2014 a Dic 10, 2014.

description: Informe de autoevaluación Universidad del Valle.
DOI: 10.6084/m9.figshare.1279394.v255
title: Early ovariectomy reveals the germline encoding of the “natural” mammalian anti-A-reactive IgM reflecting developmental malignancy.

description: The germline encoding of a non-immune immunoglobulin M (IgM) molecule in mammals was experimentally documented for the first time as a result of the specifically timed ovariectomy of C57BL/10 mice. The target of this innate antibody involves a trans-species developmental antigen that signifies malignancy when expressed in any non-developmental tissue. Although ovariectomy and castration result in uncontrolled and/or enhanced humoral and cellular immunity involving increased weights of the spleen and thymus with pronounced B and T cell production, the development of mercaptoethanol-sensitive, complement-binding, non-immune anti-A reactivity in murine plasma was not enhanced after an ovariectomy that was performed in C57BL/10 mice prior to the onset of puberty. This non-immune murine anti-A, which is complementary to the GalNAc glycan of syngeneic ovarian glycolipids and distinct from the cross-reactive adaptive anti-A antibody, was strongly downregulated or did not appear in plasma of animals ovariectomized at the age of 20 days. In mouse and man, this molecule most likely gets its complementary footprint from the first, genetically as-yet-undefined trans-species <i>O</i>-linked glycosylation of proteins and after depletion of the volatilely expressed “immature” <i>O</i>-GalNAc transferase activities and release from the transiently appearing glycopeptides, provides the A-reactive glycosidic sites. Consequently, these volatilely expressed non-somatic <i>O</i>-GalNAc-glycosylations of proteins, involving serine/threonine residues, are either identical or metabolically related with those of the mucin-type “aberrant” monosaccharide GalNAcα1-<i>O</i>-Ser/Thr-R or Tn antigen and explain the anti-Tn cross-reactivity of anti-A specific immunoglobulins and the pronounced occurrence of anti-Tn in the plasma of the human histo (blood) group O, in which the A-allelic, phenotype-specific GalNAc glycosylation of plasma proteins does not occur and not affect the anti-Tn levels.
DOI: 10.6084/m9.figshare.1266468.v1
title: Values of the distances between atoms of residues that coordinate copper ions in the models and the mold.

description: Values of the distances between atoms of residues that coordinate copper ions in the models and the mold.
DOI: 10.6084/m9.figshare.1266467
title: Values of rmsd between ABTS configurations of each model with the laccase of B. subtilis. The value of each configuration has a binding energy given in kcal/mol.

description: Values of rmsd between ABTS configurations of each model with the laccase of <em>B. subtilis</em>. The value of each configuration has a binding energy given in kcal/mol.
DOI: 10.6084/m9.figshare.1279394.v256
title: Early ovariectomy reveals the germline encoding of the “natural” mammalian anti-A-reactive IgM reflecting developmental malignancy.

description: s The germline encoding of a non-immune immunoglobulin M (IgM) molecule in mammals was experimentally documented for the first time as a result of the specifically timed ovariectomy of C57BL/10 mice. The target of this innate antibody involves a trans-species developmental antigen that signifies malignancy when expressed in any non-developmental tissue. Although ovariectomy and castration result in uncontrolled and/or enhanced humoral and cellular immunity involving increased weights of the spleen and thymus with pronounced B and T cell production, the development of mercaptoethanol-sensitive, complement-binding, non-immune anti-A reactivity in murine plasma was not enhanced after an ovariectomy that was performed in C57BL/10 mice prior to the onset of puberty. This non-immune murine anti-A, which is complementary to the GalNAc glycan of syngeneic ovarian glycolipids and distinct from the cross-reactive adaptive anti-A antibody, was strongly downregulated or did not appear in plasma of animals ovariectomized at the age of 20 days. In mouse and man, this molecule most likely gets its complementary footprint from the first, genetically as-yet-undefined trans-species <i>O</i>-linked glycosylation of proteins and after depletion of the volatilely expressed “immature” <i>O</i>-GalNAc transferase activities is released from the transiently appearing glycopeptides and provides the A-reactive glycosidic sites. Consequently, these volatilely expressed non-somatic <i>O</i>-GalNAc-glycosylations of proteins, involving serine/threonine residues, are either identical or metabolically related with those of the mucin-type “aberrant” monosaccharide GalNAcα1-<i>O</i>-Ser/Thr-R or Tn antigen and explain the anti-Tn cross-reactivity of anti-A specific immunoglobulins and the pronounced occurrence of anti-Tn in the plasma of the human histo (blood) group O, in which the A-allelic, phenotype-specific GalNAc glycosylation of plasma proteins does not occur and not affect the anti-Tn levels.
DOI: 10.6084/m9.figshare.1266476.v3
title: Informe de autoevaluación de actividades docentes. Jorge Hernán Ramírez. Universidad del Valle. Feb 15, 2014 a Dic 10, 2014.

description: Informe de autoevaluación Universidad del Valle.
DOI: 10.6084/m9.figshare.1266462
title: Lithic distribution data from survey of Messak, Foley RA, Lahr MM (2015) Lithic Landscapes: Early Human Impact from Stone Tool Production on the Central Saharan Environment. PLoS ONE 10(3): e0116482. doi:10.1371/journal.pone.0116482

description: Artefact density data (Oxy survey) from the Messak Settafet, Libya, as presented in Foley & Mirazon Lahr Foley RA, Lahr MM (2015) Lithic Landscapes: Early Human Impact from Stone Tool Production on the Central Saharan Environment. PLoS ONE 10(3): e0116482. doi:10.1371/journal.pone.0116482
DOI: 10.6084/m9.figshare.1266462.v1
title: Lithic distribution data from survey of Messak, Foley RA, Lahr MM (2015) Lithic Landscapes: Early Human Impact from Stone Tool Production on the Central Saharan Environment. PLoS ONE 10(3): e0116482. doi:10.1371/journal.pone.0116482

description: Artefact density data (Oxy survey) from the Messak Settafet, Libya, as presented in Foley & Mirazon Lahr Foley RA, Lahr MM (2015) Lithic Landscapes: Early Human Impact from Stone Tool Production on the Central Saharan Environment. PLoS ONE 10(3): e0116482. doi:10.1371/journal.pone.0116482
DOI: 10.6084/m9.figshare.1266476.v4
title: Informe de autoevaluación de actividades docentes. Jorge Hernán Ramírez. Universidad del Valle. Feb 15, 2014 a Dic 10, 2014.

description: Informe de autoevaluación Universidad del Valle.
DOI: 10.6084/m9.figshare.1279394.v257
title: Early ovariectomy reveals the germline encoding of the “natural” mammalian anti-A-reactive IgM reflecting developmental malignancy.

description: The germline encoding of a non-immune immunoglobulin M (IgM) molecule in mammals was experimentally documented for the first time as a result of the specifically timed ovariectomy of C57BL/10 mice. The target of this innate antibody involves a trans-species developmental antigen that signifies malignancy when expressed in any non-developmental tissue. Although ovariectomy and castration result in uncontrolled and/or enhanced humoral and cellular immunity involving increased weights of the spleen and thymus with pronounced B and T cell production, the development of mercaptoethanol-sensitive, complement-binding, non-immune anti-A reactivity in murine plasma was not enhanced after an ovariectomy that was performed in C57BL/10 mice prior to the onset of puberty. This non-immune murine anti-A, which is complementary to the GalNAc glycan of syngeneic ovarian glycolipids and distinct from the cross-reactive adaptive anti-A antibody, was strongly downregulated or did not appear in plasma of animals ovariectomized at the age of 20 days. In mouse and man, this molecule most likely gets its complementary footprint from the first, genetically as-yet-undefined trans-species <i>O</i>-linked glycosylation of proteins; after depletion of the volatilely expressed “immature” <i>O</i>-GalNAc transferase activities it is released from the transiently appearing glycopeptides and provides the A-reactive glycosidic sites. Consequently, these volatilely expressed non-somatic <i>O</i>-GalNAc-glycosylations of proteins, involving serine/threonine residues, are either identical or metabolically related with those of the mucin-type “aberrant” monosaccharide GalNAcα1-<i>O</i>-Ser/Thr-R or Tn antigen and explain the anti-Tn cross-reactivity of anti-A specific immunoglobulins and the pronounced occurrence of anti-Tn in the plasma of the human histo (blood) group O, in which the A-allelic, phenotype-specific GalNAc glycosylation of plasma proteins does not occur and not affect the anti-Tn levels.
DOI: 10.6084/m9.figshare.1266451
title: Parp1 nucleosome binding correlation study datasets

description: All RData files used in the fmdatabreastcaparp1 package and the PARP1 correlation analysis package fmcorrelationbreastcaparp1
DOI: 10.6084/m9.figshare.1266476.v5
title: Informe de autoevaluación de actividades docentes. Jorge Hernán Ramírez. Universidad del Valle. Feb 15, 2014 a Dic 10, 2014.

description: Informe de autoevaluación Universidad del Valle.
DOI: 10.6084/m9.figshare.1279394.v258
title: Early ovariectomy reveals the germline encoding of the “natural” mammalian anti-A-reactive IgM reflecting developmental malignancy.

description: The germline encoding of a non-immune immunoglobulin M (IgM) molecule in mammals was experimentally documented for the first time as a result of the specifically timed ovariectomy of C57BL/10 mice. The target of this innate antibody involves a trans-species developmental antigen that signifies malignancy when expressed in any non-developmental tissue. Although ovariectomy and castration result in uncontrolled and/or enhanced humoral and cellular immunity involving increased weights of the spleen and thymus with pronounced B and T cell production, the development of mercaptoethanol-sensitive, complement-binding, non-immune anti-A reactivity in murine plasma was not enhanced after an ovariectomy that was performed in C57BL/10 mice prior to the onset of puberty. This non-immune murine anti-A, which is complementary to the GalNAc glycan of syngeneic ovarian glycolipids and distinct from the cross-reactive adaptive anti-A antibody, was strongly downregulated or did not appear in plasma of animals ovariectomized at the age of 20 days. In mouse and man, this molecule most likely gets its complementary footprint from the early trans-species <i>O</i>-linked glycosylation of proteins and subsequent depletion of the volatilely expressed “immature” <i>O</i>-GalNAc transferase activities, which results in the release of glycan-depleted proteins that by binding sites and reactivity reflect the structure of the disappeared glycan. Consequently, these volatilely expressed non-somatic <i>O</i>-GalNAc-glycosylations of proteins, involving serine/threonine residues, are either identical or metabolically related with those of the mucin-type “aberrant” monosaccharide GalNAcα1-<i>O</i>-Ser/Thr-R or Tn antigen and explain the anti-Tn cross-reactivity of anti-A specific immunoglobulins and the pronounced occurrence of anti-Tn in the plasma of the human histo (blood) group O, in which the A-allelic, phenotype-specific GalNAc glycosylation of plasma proteins does not occur and not affect the anti-Tn levels.
DOI: 10.6084/m9.figshare.1266450
title: FIB/SEM reconstruction of identified neurons - Supplementary Movies

description: Supplementary Movies of the peer reviewed publication:<br><br>FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons. Front. Neuroanat. | doi: 10.3389/fnana2015.00060