cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1568511.v1
title: Autophagy is involved in ethanol-induced cardia bifida during chick cardiogenesis

description: Excess alcohol consumption during pregnancy has been acknowledged to increase the incidence of congenital disorders, especially the cardiovascular system. However, the mechanism involved in ethanol-induced cardiac malformation in prenatal fetus is still unknown. We demonstrated that ethanol exposure during gastrulation in the chick embryo increased the incidence of cardia bifida. Previously, we reported that autophagy was involved in heart tube formation. In this context, we demonstrated that ethanol exposure increased ATG7 and LC3 expression. mTOR was found to be inhibited by ethanol exposure. We activated autophagy using exogenous rapamycin (RAPA) and observed that it induced cardiac bifida and increased GATA5 expression. RAPA beads implantation experiments revealed that RAPA restricted ventricular myosin heavy chain (VMHC) expression. <i>In vitro</i> explant cultures of anterior primitive streak demonstrated that both ethanol and RAPA treatments could reduce cell differentiation and the spontaneous beating of cardiac precursor cells. In addition, the bead experiments showed that RAPA inhibited GATA5 expression during heart tube formation. Semiquantitative RT-PCR analysis indicated that BMP2 expression was increased while GATA4 expression was suppressed. In the embryos exposed to excess ethanol, BMP2, GATA4 and FGF8 expression was repressed. These genes are associated with cardiomyocyte differentiation, while heart tube fusion is associated with increased Wnt3a but reduced VEGF and Slit2 expression. Furthermore, the ethanol exposure also caused the production of excess ROS, which might damage the cardiac precursor cells of developing embryos. In sum, our results revealed that disrupting autophagy and excess ROS generation are responsible for inducing abnormal cardiogenesis in ethanol-treated chick embryos.
DOI: 10.6084/m9.figshare.1568511.v3
title: Autophagy is involved in ethanol-induced cardia bifida during chick cardiogenesis

description: Excess alcohol consumption during pregnancy has been acknowledged to increase the incidence of congenital disorders, especially the cardiovascular system. However, the mechanism involved in ethanol-induced cardiac malformation in prenatal fetus is still unknown. We demonstrated that ethanol exposure during gastrulation in the chick embryo increased the incidence of cardia bifida. Previously, we reported that autophagy was involved in heart tube formation. In this context, we demonstrated that ethanol exposure increased ATG7 and LC3 expression. mTOR was found to be inhibited by ethanol exposure. We activated autophagy using exogenous rapamycin (RAPA) and observed that it induced cardiac bifida and increased GATA5 expression. RAPA beads implantation experiments revealed that RAPA restricted ventricular myosin heavy chain (VMHC) expression. <i>In vitro</i> explant cultures of anterior primitive streak demonstrated that both ethanol and RAPA treatments could reduce cell differentiation and the spontaneous beating of cardiac precursor cells. In addition, the bead experiments showed that RAPA inhibited GATA5 expression during heart tube formation. Semiquantitative RT-PCR analysis indicated that BMP2 expression was increased while GATA4 expression was suppressed. In the embryos exposed to excess ethanol, BMP2, GATA4 and FGF8 expression was repressed. These genes are associated with cardiomyocyte differentiation, while heart tube fusion is associated with increased Wnt3a but reduced VEGF and Slit2 expression. Furthermore, the ethanol exposure also caused the production of excess ROS, which might damage the cardiac precursor cells of developing embryos. In sum, our results revealed that disrupting autophagy and excess ROS generation are responsible for inducing abnormal cardiogenesis in ethanol-treated chick embryos.
DOI: 10.6084/m9.figshare.1568511.v2
title: Autophagy is involved in ethanol-induced cardia bifida during chick cardiogenesis

description: Excess alcohol consumption during pregnancy has been acknowledged to increase the incidence of congenital disorders, especially the cardiovascular system. However, the mechanism involved in ethanol-induced cardiac malformation in prenatal fetus is still unknown. We demonstrated that ethanol exposure during gastrulation in the chick embryo increased the incidence of cardia bifida. Previously, we reported that autophagy was involved in heart tube formation. In this context, we demonstrated that ethanol exposure increased ATG7 and LC3 expression. mTOR was found to be inhibited by ethanol exposure. We activated autophagy using exogenous rapamycin (RAPA) and observed that it induced cardiac bifida and increased GATA5 expression. RAPA beads implantation experiments revealed that RAPA restricted ventricular myosin heavy chain (VMHC) expression. <i>In vitro</i> explant cultures of anterior primitive streak demonstrated that both ethanol and RAPA treatments could reduce cell differentiation and the spontaneous beating of cardiac precursor cells. In addition, the bead experiments showed that RAPA inhibited GATA5 expression during heart tube formation. Semiquantitative RT-PCR analysis indicated that BMP2 expression was increased while GATA4 expression was suppressed. In the embryos exposed to excess ethanol, BMP2, GATA4 and FGF8 expression was repressed. These genes are associated with cardiomyocyte differentiation, while heart tube fusion is associated with increased Wnt3a but reduced VEGF and Slit2 expression. Furthermore, the ethanol exposure also caused the production of excess ROS, which might damage the cardiac precursor cells of developing embryos. In sum, our results revealed that disrupting autophagy and excess ROS generation are responsible for inducing abnormal cardiogenesis in ethanol-treated chick embryos.
DOI: 10.6084/m9.figshare.12919004
title: Trained algorithms - Large Ensemble Testbed - XGB

description: Trained algorithms for reconstructing pCO2 of the Large Ensemble Testbed using XGB. Files stored using joblib.
DOI: 10.6084/m9.figshare.1568489
title: Structural and energetic requirements for a second binding site at the dimeric β-lactoglobulin interface

description: Through experimental and theoretical approaches, it has been shown that bovine β-lactoglobulin (βlg) uses its hydrophobic cavity or calyx as the primary binding site for hydrophobic molecules, whereas the existence of a second ligand binding site at the dimeric interface has only been structurally identified for vitamin D3 (VD3). This binding exists even in the thermally denatured state, suggesting the prevalence of this secondary site. Although crystallographic experiments have suggested that VD3 can bind to both monomeric and dimeric states without significant structural differences, theoretical and experimental reports have proposed some structural requirements. Thus, in this study, based on known experimental data, the dynamic interaction of VD3 with the monomeric or dimeric forms of βlg was investigated through a protocol combining blind docking and 2 microsecond molecular dynamics simulations coupled with binding free energy and per-residue binding free energy decomposition analyses using the Molecular Mechanics Generalized Born Surface Area approach. Binding free energy calculations allowed us to estimate the energetic differences of coupling VD3 at the calyx and the dimeric interface for the monomeric or dimeric state, revealing that the dimeric structure is required to form a stable complex with VD3 at the dimeric interface. This also has an important impact on the dimerization process, whereas although the monomeric state also forms a stable complex with VD3 at the dimeric interface, the incorporation of the entropy component contributed to producing a marginally favorable binding free energy. Finally, the per-residue decomposition analysis provided energetic information about the most relevant residues in stabilizing the different systems.
DOI: 10.6084/m9.figshare.12919004.v1
title: Trained algorithms - Large Ensemble Testbed - XGB

description: Trained algorithms for reconstructing pCO2 of the Large Ensemble Testbed using XGB. Files stored using joblib.
DOI: 10.6084/m9.figshare.1568489.v1
title: Structural and energetic requirements for a second binding site at the dimeric β-lactoglobulin interface

description: Through experimental and theoretical approaches, it has been shown that bovine β-lactoglobulin (βlg) uses its hydrophobic cavity or calyx as the primary binding site for hydrophobic molecules, whereas the existence of a second ligand binding site at the dimeric interface has only been structurally identified for vitamin D3 (VD3). This binding exists even in the thermally denatured state, suggesting the prevalence of this secondary site. Although crystallographic experiments have suggested that VD3 can bind to both monomeric and dimeric states without significant structural differences, theoretical and experimental reports have proposed some structural requirements. Thus, in this study, based on known experimental data, the dynamic interaction of VD3 with the monomeric or dimeric forms of βlg was investigated through a protocol combining blind docking and 2 microsecond molecular dynamics simulations coupled with binding free energy and per-residue binding free energy decomposition analyses using the Molecular Mechanics Generalized Born Surface Area approach. Binding free energy calculations allowed us to estimate the energetic differences of coupling VD3 at the calyx and the dimeric interface for the monomeric or dimeric state, revealing that the dimeric structure is required to form a stable complex with VD3 at the dimeric interface. This also has an important impact on the dimerization process, whereas although the monomeric state also forms a stable complex with VD3 at the dimeric interface, the incorporation of the entropy component contributed to producing a marginally favorable binding free energy. Finally, the per-residue decomposition analysis provided energetic information about the most relevant residues in stabilizing the different systems.
DOI: 10.6084/m9.figshare.1568481
title: Antagonist <i>Xist</i> and <i>Tsix</i> co-transcription during mouse oogenesis and maternal <i>Xist</i> expression during pre-implantation development calls into question the nature of the maternal imprint on the X chromosome

description: During the first divisions of the female mouse embryo, the paternal X-chromosome is coated by <i>Xist</i> non-coding RNA and gradually silenced. This imprinted X-inactivation principally results from the apposition, during oocyte growth, of an imprint on the X-inactivation master control region: the X-inactivation center (<i>Xic</i>). This maternal imprint of yet unknown nature is thought to prevent <i>Xist</i> upregulation from the maternal X (X<sup>M</sup>) during early female development. In order to provide further insight into the X<sup>M</sup> imprinting mechanism, we applied single-cell approaches to oocytes and pre-implantation embryos at different stages of development to analyze the expression of candidate genes within the <i>Xic</i>. We show that, unlike the situation pertaining in most other cellular contexts, in early-growing oocytes, <i>Xist</i> and <i>Tsix</i> sense and antisense transcription occur simultaneously from the same chromosome. Additionally, during early development, <i>Xist</i> appears to be transiently transcribed from the X<sup>M</sup> in some blastomeres of late 2-cell embryos concomitant with the general activation of the genome indicating that X<sup>M</sup> imprinting does not completely suppress maternal <i>Xist</i> transcription during embryo cleavage stages. These unexpected transcriptional regulations of the <i>Xist</i> locus call for a re-evaluation of the early functioning of the maternal imprint on the X-chromosome and suggest that <i>Xist</i>/<i>Tsix</i> antagonist transcriptional activities may participate in imprinting the maternal locus as described at other loci subject to parental imprinting.
DOI: 10.6084/m9.figshare.1568481.v1
title: Antagonist <i>Xist</i> and <i>Tsix</i> co-transcription during mouse oogenesis and maternal <i>Xist</i> expression during pre-implantation development calls into question the nature of the maternal imprint on the X chromosome

description: ABSTRACTDuring the first divisions of the female mouse embryo, the paternal X-chromosome is coated by <i>Xist</i> non-coding RNA (ncRNA) and gradually silenced. This imprinted X-inactivation principally results from the apposition, during oocyte growth, of an imprint on the X-inactivation master control region: the X-inactivation center (<i>Xic</i>). This maternal imprint of yet unknown nature is thought to prevent <i>Xist</i> upregulation from the maternal X (X<sup>M</sup>) during early female development. In order to provide further insight into the X<sup>M</sup> imprinting mechanism, we applied single-cell approaches to oocytes and pre-implantation embryos at different stages of development to analyze the expression of candidate genes within the <i>Xic</i>. We show that, unlike the situation pertaining in most other cellular contexts, in early-growing oocytes, <i>Xist</i> and <i>Tsix</i> sense and antisense transcription occur simultaneously from the same chromosome. Additionally, during early development, <i>Xist</i> appears to be transiently transcribed from the X<sup>M</sup> in some blastomeres of late 2-cell embryos concomitant with the general activation of the genome indicating that X<sup>M</sup> imprinting does not completely suppress maternal <i>Xist</i> transcription during embryo cleavage stages. These unexpected transcriptional regulations of the <i>Xist</i> locus call for a re-evaluation of the early functioning of the maternal imprint on the X-chromosome and suggest that <i>Xist/Tsix</i> antagonist transcriptional activities may participate in imprinting the maternal locus as described at other loci subject to parental imprinting.
DOI: 10.6084/m9.figshare.1568477
title: Loss of STK11 expression is an early event in prostate carcinogenesis and predicts therapeutic response to targeted therapy against MAPK/p38

description: Prostate cancer (PCa) is the second leading cause of cancer-related death in men; however, the molecular mechanisms leading to its development and progression are not yet fully elucidated. Of note, it has been recently shown that conditional <i>stk11</i> knockout mice develop atypical hyperplasia and prostate intraepithelial neoplasia (PIN). We recently reported an inverse correlation between the activity of the STK11/AMPK pathway and the MAPK/p38 cascade in HIF1A-dependent malignancies. Furthermore, MAPK/p38 overactivation was detected in benign prostate hyperplasia, PIN and PCa in mice and humans. Here we report that STK11 expression is significantly decreased in PCa compared to normal tissues. Moreover, STK11 protein levels decreased throughout prostate carcinogenesis. To gain insight into the role of STK11-MAPK/p38 activity balance in PCa, we treated PCa cell lines and primary biopsies with a well-established MAPK14-MAPK11 inhibitor (SB202190), which has been extensively used in vitro and in vivo. Our results indicate that inhibition of MAPK/p38 significantly affects PCa cell survival in an STK11-dependent manner. Indeed, we found that pharmacologic inactivation of MAPK/p38 does not affect viability of <i>STK11</i>-proficient PCa cells due to the triggering of the AMPK-dependent autophagic pathway, while it induces apoptosis in <i>STK11</i>-deficient cells irrespective of androgen receptor (AR) status. Of note, AMPK inactivation or autophagy inhibition in <i>STK11</i>-proficient cells sensitize SB202190-treated PCa cells to apoptosis. On the other end, reconstitution of functional <i>STK11</i> in <i>STK11</i>-deficient PCa cells abrogates apoptosis. Collectively, our data show that STK11 is a key factor involved in the early phases of prostate carcinogenesis, and suggest that it might be used as a predictive marker of therapeutic response to MAPK/p38 inhibitors in PCa patients.
DOI: 10.6084/m9.figshare.1568481.v3
title: Antagonist <i>Xist</i> and <i>Tsix</i> co-transcription during mouse oogenesis and maternal <i>Xist</i> expression during pre-implantation development calls into question the nature of the maternal imprint on the X chromosome

description: During the first divisions of the female mouse embryo, the paternal X-chromosome is coated by <i>Xist</i> non-coding RNA and gradually silenced. This imprinted X-inactivation principally results from the apposition, during oocyte growth, of an imprint on the X-inactivation master control region: the X-inactivation center (<i>Xic</i>). This maternal imprint of yet unknown nature is thought to prevent <i>Xist</i> upregulation from the maternal X (X<sup>M</sup>) during early female development. In order to provide further insight into the X<sup>M</sup> imprinting mechanism, we applied single-cell approaches to oocytes and pre-implantation embryos at different stages of development to analyze the expression of candidate genes within the <i>Xic</i>. We show that, unlike the situation pertaining in most other cellular contexts, in early-growing oocytes, <i>Xist</i> and <i>Tsix</i> sense and antisense transcription occur simultaneously from the same chromosome. Additionally, during early development, <i>Xist</i> appears to be transiently transcribed from the X<sup>M</sup> in some blastomeres of late 2-cell embryos concomitant with the general activation of the genome indicating that X<sup>M</sup> imprinting does not completely suppress maternal <i>Xist</i> transcription during embryo cleavage stages. These unexpected transcriptional regulations of the <i>Xist</i> locus call for a re-evaluation of the early functioning of the maternal imprint on the X-chromosome and suggest that <i>Xist</i>/<i>Tsix</i> antagonist transcriptional activities may participate in imprinting the maternal locus as described at other loci subject to parental imprinting.
DOI: 10.6084/m9.figshare.1568481.v2
title: Antagonist <i>Xist</i> and <i>Tsix</i> co-transcription during mouse oogenesis and maternal <i>Xist</i> expression during pre-implantation development calls into question the nature of the maternal imprint on the X chromosome

description: During the first divisions of the female mouse embryo, the paternal X-chromosome is coated by <i>Xist</i> non-coding RNA and gradually silenced. This imprinted X-inactivation principally results from the apposition, during oocyte growth, of an imprint on the X-inactivation master control region: the X-inactivation center (<i>Xic</i>). This maternal imprint of yet unknown nature is thought to prevent <i>Xist</i> upregulation from the maternal X (X<sup>M</sup>) during early female development. In order to provide further insight into the X<sup>M</sup> imprinting mechanism, we applied single-cell approaches to oocytes and pre-implantation embryos at different stages of development to analyze the expression of candidate genes within the <i>Xic</i>. We show that, unlike the situation pertaining in most other cellular contexts, in early-growing oocytes, <i>Xist</i> and <i>Tsix</i> sense and antisense transcription occur simultaneously from the same chromosome. Additionally, during early development, <i>Xist</i> appears to be transiently transcribed from the X<sup>M</sup> in some blastomeres of late 2-cell embryos concomitant with the general activation of the genome indicating that X<sup>M</sup> imprinting does not completely suppress maternal <i>Xist</i> transcription during embryo cleavage stages. These unexpected transcriptional regulations of the <i>Xist</i> locus call for a re-evaluation of the early functioning of the maternal imprint on the X-chromosome and suggest that <i>Xist</i>/<i>Tsix</i> antagonist transcriptional activities may participate in imprinting the maternal locus as described at other loci subject to parental imprinting.
DOI: 10.6084/m9.figshare.1568477.v2
title: Loss of STK11 expression is an early event in prostate carcinogenesis and predicts therapeutic response to targeted therapy against MAPK/p38

description: Prostate cancer (PCa) is the second leading cause of cancer-related death in men; however, the molecular mechanisms leading to its development and progression are not yet fully elucidated. Of note, it has been recently shown that conditional <i>stk11</i> knockout mice develop atypical hyperplasia and prostate intraepithelial neoplasia (PIN). We recently reported an inverse correlation between the activity of the STK11/AMPK pathway and the MAPK/p38 cascade in HIF1A-dependent malignancies. Furthermore, MAPK/p38 overactivation was detected in benign prostate hyperplasia, PIN and PCa in mice and humans. Here we report that STK11 expression is significantly decreased in PCa compared to normal tissues. Moreover, STK11 protein levels decreased throughout prostate carcinogenesis. To gain insight into the role of STK11-MAPK/p38 activity balance in PCa, we treated PCa cell lines and primary biopsies with a well-established MAPK14-MAPK11 inhibitor (SB202190), which has been extensively used in vitro and in vivo. Our results indicate that inhibition of MAPK/p38 significantly affects PCa cell survival in an STK11-dependent manner. Indeed, we found that pharmacologic inactivation of MAPK/p38 does not affect viability of <i>STK11</i>-proficient PCa cells due to the triggering of the AMPK-dependent autophagic pathway, while it induces apoptosis in <i>STK11</i>-deficient cells irrespective of androgen receptor (AR) status. Of note, AMPK inactivation or autophagy inhibition in <i>STK11</i>-proficient cells sensitize SB202190-treated PCa cells to apoptosis. On the other end, reconstitution of functional <i>STK11</i> in <i>STK11</i>-deficient PCa cells abrogates apoptosis. Collectively, our data show that STK11 is a key factor involved in the early phases of prostate carcinogenesis, and suggest that it might be used as a predictive marker of therapeutic response to MAPK/p38 inhibitors in PCa patients.
DOI: 10.6084/m9.figshare.1568477.v1
title: Loss of STK11 expression is an early event in prostate carcinogenesis and predicts therapeutic response to targeted therapy against MAPK/p38

description: Prostate cancer (PCa) is the second leading cause of cancer-related death in men; however, the molecular mechanisms leading to its development and progression are not yet fully elucidated. Of note, it has been recently shown that conditional <i>stk11</i> knockout mice develop atypical hyperplasia and prostate intraepithelial neoplasia (PIN). We recently reported an inverse correlation between the activity of the STK11/AMPK pathway and the MAPK/p38 cascade in HIF1A-dependent malignancies. Furthermore, MAPK/p38 overactivation was detected in benign prostate hyperplasia, PIN and PCa in mice and humans. Here we report that STK11 expression is significantly decreased in PCa compared to normal tissues. Moreover, STK11 protein levels decreased throughout prostate carcinogenesis. To get insight into the role of STK11-MAPK/p38 activity balance in PCa, we treated PCa cell lines and primary biopsies with a well-established MAPK14-MAPK11 inhibitor (SB202190), which has been extensively used <i>in vitro</i> and <i>in vivo</i>. Our results indicate that inhibition of MAPK/p38 significantly affects PCa cell survival in a STK11-dependent manner. Indeed, we found that pharmacologic inactivation of MAPK/p38 does not affect viability of <i>STK11</i>-proficient PCa cells due to the triggering of the AMPK-dependent autophagic pathway, while it induces apoptosis in <i>STK11</i>-deficient cells irrespective of androgen receptor (AR) status. Of note, AMPK inactivation or autophagy inhibition in <i>STK11</i>-proficient cells sensitize SB202190-treated PCa cells to apoptosis. On the other end, reconstitution of functional <i>STK11</i> in <i>STK11</i>-deficient PCa cells abrogates apoptosis. Collectively, our data show that STK11 is a key factor involved in the early phases of prostate carcinogenesis, and suggest that it might be used as a predictive marker of therapeutic response to MAPK/p38 inhibitors in PCa patients.