cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1569462.v1
title: SRSF3 and hnRNP H1 regulate a splicing hotspot of <i>HER2</i> in breast cancer cells

description: Overexpression of the oncogene HER2 occurs in 20–30% of invasive breast cancer and is associated with poor prognosis. A number of different splice variants of HER2 have been identified which produce functionally different proteins. Previously these splice variants have been investigated separately, but in the present study we collectively look at the expression and regulation of a group of HER2 splice variants produced by a splicing hotspot. Initial investigation in a cohort of tumor samples showed large variations in HER2 variant expression between patient samples. RNA interference studies identified 2 splicing factors involved in the regulation of splicing within this region, hnRNP H1 and SRSF3. siRNA targeting hnRNP H1 increases levels of X5 and the oncogenic variant Δ16HER2. Furthermore RNA chromatography assays demonstrated binding of hnRNP H1 to RNA in this region. Additionally the proto-oncogene SRSF3 was also identified as an important regulator of splicing with SRSF3 knockdown resulting in changes in all the splice variants located at the hotspot. Most notably knockdown of SRSF3 resulted in a switch from the oncogenic Δ16HER2 to p100 which inhibits cell proliferation. Binding of SRSF3 to RNA within this region was also demonstrated by RNA chromatography and more specifically 2 SRSF3 binding sites were identified within exon 15. SRSF3 and hnRNP H1 are the first splicing factors identified which regulate the production of these functionally distinct HER2 splice variants and therefore maybe important for the regulation of HER2 signaling.
DOI: 10.6084/m9.figshare.1569467.v2
title: <i>ATG5</i>-knockout mutants of <i>Physcomitrella</i> provide a platform for analyzing the involvement of autophagy in senescence processes in plant cells

description: Autophagy is a pathway in which a cell degrades part of its cytoplasm in vacuoles or lysosomes. To identify the physiological functions of autophagy in plants, we disrupted <i>ATG5</i>, an autophagy-related gene, in <i>Physcomitrella</i>, and confirmed that <i>atg5</i> mutants are deficient in the process of autophagy. On carbon or nitrogen starvation medium, <i>atg5</i> colonies turned yellow earlier than the wild-type (WT) colonies, showing that <i>Physcomitrella atg5</i> mutants, like yeast and <i>Arabidopsis</i>, are sensitive to nutrient starvation. In the dark, even under nutrient-sufficient conditions, colonies turned yellow and the net degradation of chlorophyll and Rubisco protein occurred together with the upregulation of several senescence-associated genes. Yellowing reactions were inhibited by the protein synthesis inhibitor cycloheximide, suggesting that protonemal colonies undergo dark-induced senescence like the green leaves of higher plants. Such senescence responses in the dark occurred earlier in <i>atg5</i> colonies than WT colonies. The sugar content was almost the same between WT and <i>atg5</i> colonies, indicating that the early-senescence phenotype of <i>atg5</i> is not explained by sugar deficiency. However, the levels of seven amino acids showed significantly different alteration between <i>atg5</i> and WT in the dark: six amino acids, particularly arginine and alanine, were much more deficient in the <i>atg5</i> mutants, irrespective of the early degradation of Rubisco protein. On nutrient-sufficient medium supplemented with casamino acids, the early-senescence phenotype was slightly moderated. We propose that the early-senescence phenotype in <i>atg5</i> mutants is partly explained by amino acid imbalance because of the lack of cytoplasmic degradation by autophagy in <i>Physcomitrella</i>.
DOI: 10.6084/m9.figshare.1569460.v2
title: Newly discovered eclogites from the Bangong Meso–Tethyan suture zone (Gaize, central Tibet, western China): mineralogy, geochemistry, geochronology, and tectonic implications

description: We report the occurrence, mineralogy, whole-rock geochemistry, and geochronology of two types of eclogites newly discovered in the western Bangong Meso–Tethyan suture zone (Gaize, central Tibet, western China). Type 1 eclogites contain a peak metamorphic mineral assemblage of garnet + clinopyroxene whereas Type 2 ones are characterized by a peak metamorphic mineral assemblage of garnet + clinopyroxene + rutile. Type 2 clinopyroxene and garnet are relatively more enriched in Mg contents than Type 1 ones. Type 2 eclogites are significantly more enriched in TiO<sub>2</sub>, P<sub>2</sub>O<sub>5</sub>, and light rare-earth elements, but more depleted in Al<sub>2</sub>O<sub>3</sub> contents and Mg numbers. P–T estimates for both types of eclogites are consistent with minimum pressures of 23–25 kbar at 830–920°C, with the retrograde amphibolite facies assemblage of 15.2–17.5 kbar and 500–732°C. Zircon U–Pb dating indicates that the protolith of Type 1 eclogites, with normal mid-ocean ridge basalt affinity, emplaced at ~260 Ma, whereas the protolith of Type 2 eclogites, geochemically familiar with oceanic-island basalt (OIB), erupted at ~242 Ma. <sup>40</sup>Ar/<sup>39</sup>Ar analyses of hornblende from the retrograded eclogites indicate that the Gaize eclogite-bearing high-pressure rocks were exhumed at ~194 Ma. The occurrence of these high-pressure rocks implies the subduction of oceanic crust to a depth of ~85 km along the southern margin of the Qiangtang block during the Late Triassic.
DOI: 10.6084/m9.figshare.1569460.v1
title: Newly discovered eclogites from the Bangong Meso–Tethyan suture zone (Gaize, central Tibet, western China): mineralogy, geochemistry, geochronology, and tectonic implications

description: ABSTRACTWe report the occurrence, mineralogy, whole-rock geochemistry, and geochronology of two types of eclogites newly discovered in the western Bangong Meso–Tethyan suture zone (Gaize, central Tibet, western China). Type 1 eclogites contain a peak metamorphic mineral assemblage of garnet + clinopyroxene whereas Type 2 ones are characterized by a peak metamorphic mineral assemblage of garnet + clinopyroxene + rutile. Type 2 clinopyroxene and garnet are relatively more enriched in Mg contents than Type 1 ones. Type 2 eclogites are significantly more enriched in TiO<sub>2</sub>, P<sub>2</sub>O<sub>5</sub>, and light rare-earth elements, but more depleted in Al<sub>2</sub>O<sub>3</sub> contents and Mg numbers. P–T estimates for both types of eclogites are consistent with minimum pressures of 23–25 kbar at 830–920°C, with the retrograde amphibolite facies assemblage of 15.2–17.5 kbar and 500–732°C. Zircon U–Pb dating indicates that the protolith of Type 1 eclogites, with normal mid-ocean ridge basalt affinity, emplaced at ~260 Ma, whereas the protolith of Type 2 eclogites, geochemically familiar with oceanic-island basalt (OIB), erupted at ~242 Ma. <sup>40</sup>Ar/<sup>39</sup>Ar analyses of hornblende from the retrograded eclogites indicate that the Gaize eclogite-bearing high-pressure rocks were exhumed at ~194 Ma. The occurrence of these high-pressure rocks implies the subduction of oceanic crust to a depth of ~85 km along the southern margin of the Qiangtang block during the Late Triassic.
DOI: 10.6084/m9.figshare.1569467.v3
title: <i>ATG5</i>-knockout mutants of <i>Physcomitrella</i> provide a platform for analyzing the involvement of autophagy in senescence processes in plant cells

description: Autophagy is a pathway in which a cell degrades part of its cytoplasm in vacuoles or lysosomes. To identify the physiological functions of autophagy in plants, we disrupted <i>ATG5</i>, an autophagy-related gene, in <i>Physcomitrella</i>, and confirmed that <i>atg5</i> mutants are deficient in the process of autophagy. On carbon or nitrogen starvation medium, <i>atg5</i> colonies turned yellow earlier than the wild-type (WT) colonies, showing that <i>Physcomitrella atg5</i> mutants, like yeast and <i>Arabidopsis</i>, are sensitive to nutrient starvation. In the dark, even under nutrient-sufficient conditions, colonies turned yellow and the net degradation of chlorophyll and Rubisco protein occurred together with the upregulation of several senescence-associated genes. Yellowing reactions were inhibited by the protein synthesis inhibitor cycloheximide, suggesting that protonemal colonies undergo dark-induced senescence like the green leaves of higher plants. Such senescence responses in the dark occurred earlier in <i>atg5</i> colonies than WT colonies. The sugar content was almost the same between WT and <i>atg5</i> colonies, indicating that the early-senescence phenotype of <i>atg5</i> is not explained by sugar deficiency. However, the levels of seven amino acids showed significantly different alteration between <i>atg5</i> and WT in the dark: six amino acids, particularly arginine and alanine, were much more deficient in the <i>atg5</i> mutants, irrespective of the early degradation of Rubisco protein. On nutrient-sufficient medium supplemented with casamino acids, the early-senescence phenotype was slightly moderated. We propose that the early-senescence phenotype in <i>atg5</i> mutants is partly explained by amino acid imbalance because of the lack of cytoplasmic degradation by autophagy in <i>Physcomitrella</i>.
DOI: 10.6084/m9.figshare.1569467.v5
title: ATG5-knockout mutants of Physcomitrella provide a platform for analyzing the involvement of autophagy in senescence processes in plant cells

description: Autophagy is a pathway in which a cell degrades part of its cytoplasm in vacuoles or lysosomes. To identify the physiological functions of autophagy in plants, we disrupted <i>ATG5</i>, an autophagy-related gene, in <i>Physcomitrella</i>, and confirmed that <i>atg5</i> mutants are deficient in the process of autophagy. On carbon or nitrogen starvation medium, <i>atg5</i> colonies turned yellow earlier than the wild-type (WT) colonies, showing that <i>Physcomitrella atg5</i> mutants, like yeast and <i>Arabidopsis</i>, are sensitive to nutrient starvation. In the dark, even under nutrient-sufficient conditions, colonies turned yellow and the net degradation of chlorophyll and Rubisco protein occurred together with the upregulation of several senescence-associated genes. Yellowing reactions were inhibited by the protein synthesis inhibitor cycloheximide, suggesting that protonemal colonies undergo dark-induced senescence like the green leaves of higher plants. Such senescence responses in the dark occurred earlier in <i>atg5</i> colonies than WT colonies. The sugar content was almost the same between WT and <i>atg5</i> colonies, indicating that the early-senescence phenotype of <i>atg5</i> is not explained by sugar deficiency. However, the levels of 7 amino acids showed significantly different alteration between <i>atg5</i> and WT in the dark: 6 amino acids, particularly arginine and alanine, were much more deficient in the <i>atg5</i> mutants, irrespective of the early degradation of Rubisco protein. On nutrient-sufficient medium supplemented with casamino acids, the early-senescence phenotype was slightly moderated. We propose that the early-senescence phenotype in <i>atg5</i> mutants is partly explained by amino acid imbalance because of the lack of cytoplasmic degradation by autophagy in <i>Physcomitrella</i>.
DOI: 10.6084/m9.figshare.1569452
title: Phosphorylation and dephosphorylation regulate APC/C<sup>Cdh1</sup> substrate degradation

description: The Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase activated by its G1 specific adaptor protein Cdh1 is a major regulator of the cell cycle. The APC/C<sup>Cdh1</sup> mediates degradation of dozens of proteins, however, the kinetics and requirements for their degradation are largely unknown. We demonstrate that overexpression of the constitutive active <i>CDH1</i><sup><i>m11</i></sup> mutant that is not inhibited by phosphorylation results in mitotic exit in the absence of the FEAR and MEN pathways, and DNA re-replication in the absence of Cdc7 activity. This mode of mitotic exit also reveals additional requirements for APC/C<sup>Cdh1</sup> substrate degradation, which for some substrates such as Pds1 or Clb5 is dephosphorylation, but for others such as Cdc5 is phosphorylation.
DOI: 10.6084/m9.figshare.1569467.v4
title: <i>ATG5</i>-knockout mutants of <i>Physcomitrella</i> provide a platform for analyzing the involvement of autophagy in senescence processes in plant cells

description: Autophagy is a pathway in which a cell degrades part of its cytoplasm in vacuoles or lysosomes. To identify the physiological functions of autophagy in plants, we disrupted <i>ATG5</i>, an autophagy-related gene, in <i>Physcomitrella</i>, and confirmed that <i>atg5</i> mutants are deficient in the process of autophagy. On carbon or nitrogen starvation medium, <i>atg5</i> colonies turned yellow earlier than the wild-type (WT) colonies, showing that <i>Physcomitrella atg5</i> mutants, like yeast and <i>Arabidopsis</i>, are sensitive to nutrient starvation. In the dark, even under nutrient-sufficient conditions, colonies turned yellow and the net degradation of chlorophyll and Rubisco protein occurred together with the upregulation of several senescence-associated genes. Yellowing reactions were inhibited by the protein synthesis inhibitor cycloheximide, suggesting that protonemal colonies undergo dark-induced senescence like the green leaves of higher plants. Such senescence responses in the dark occurred earlier in <i>atg5</i> colonies than WT colonies. The sugar content was almost the same between WT and <i>atg5</i> colonies, indicating that the early-senescence phenotype of <i>atg5</i> is not explained by sugar deficiency. However, the levels of seven amino acids showed significantly different alteration between <i>atg5</i> and WT in the dark: six amino acids, particularly arginine and alanine, were much more deficient in the <i>atg5</i> mutants, irrespective of the early degradation of Rubisco protein. On nutrient-sufficient medium supplemented with casamino acids, the early-senescence phenotype was slightly moderated. We propose that the early-senescence phenotype in <i>atg5</i> mutants is partly explained by amino acid imbalance because of the lack of cytoplasmic degradation by autophagy in <i>Physcomitrella</i>.
DOI: 10.6084/m9.figshare.1569452.v1
title: Phosphorylation and dephosphorylation regulate APC/C<sup>Cdh1</sup> substrate degradation

description: The Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase activated by its G1 specific adaptor protein Cdh1 is a major regulator of the cell cycle. The APC/C<sup>Cdh1</sup> mediates degradation of dozens of proteins, however, the kinetics and requirements for their degradation are largely unknown. We demonstrate that overexpression of the constitutive active <i>CDH1</i><sup><i>m11</i></sup> mutant that is not inhibited by phosphorylation results in mitotic exit in the absence of the FEAR and MEN pathways, and DNA re-replication in the absence of Cdc7 activity. This mode of mitotic exit also reveals additional requirements for APC/C<sup>Cdh1</sup> substrate degradation, which for some substrates such as Pds1 or Clb5 is dephosphorylation, but for others such as Cdc5 is phosphorylation.
DOI: 10.6084/m9.figshare.1569427
title: Prognostic effect of hENT1, dCK and HuR expression by morphological type in periampullary adenocarcinoma, including pancreatic cancer

description: <i>Background</i>: Putative biomarkers of gemcitabine response have been extensively studied in pancreatic cancer, but less so in other types of periampullary adenocarcinoma. The most studied biomarker is human equilibrative nucleoside transporter 1 (hENT1), and the activating enzyme deoxycytidine kinase (dCK) has also been linked to treatment response. The RNA-binding protein human antigen R (HuR) has been demonstrated to confer increased dCK levels in vitro and to predict gemcitabine response in vivo. Here, we investigated the prognostic impact of hENT1, dCK and HuR in pancreatobiliary (PB) and intestinal (I) type periampullary cancers, respectively. <i>Material and methods</i>: Immunohistochemical expression of hENT1, dCK and HuR was evaluated in tissue microarrays with all primary tumours and 103 paired lymph node metastases from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinomas. <i>Results</i>: In patients with PB-type tumours, neither hENT1 nor dCK expression was prognostic. A high HuR cytoplasmic/nuclear ratio was associated with a significantly reduced five-year overall survival (OS) in patients receiving adjuvant gemcitabine (HR 2.07, 95% CI 1.03–4.17) but not in untreated patients (p<sub>interaction</sub> = 0.028). In patients with I-type tumours receiving adjuvant chemotherapy, high dCK expression was significantly associated with a prolonged recurrence-free survival (RFS) (HR 0.09, 95% CI 0.01–0.73, p<sub>interaction</sub> = 0.023). Furthermore, HuR expression was associated with a prolonged OS and RFS in unadjusted but not in adjusted analysis and hENT1 expression was an independent predictor of a prolonged RFS (HR 0.24, 95% CI 0.10–0.59), regardless of adjuvant treatment. <i>Conclusion</i>: hENT1 expression is a favourable prognostic factor in I-type, but not in PB-type tumours. High dCK expression is a favourable prognostic factor in patients with I-type tumours receiving adjuvant treatment and a high cytoplasmic/nuclear HuR ratio is a negative prognostic factor in gemcitabine-treated PB-type tumours. Morphological subtype should always be considered in biomarker studies on periampullary cancer.
DOI: 10.6084/m9.figshare.1569428
title: Prognostic effect of hENT1, dCK and HuR expression by morphological type in periampullary adenocarcinoma, including pancreatic cancer

description: <i>Background</i>: Putative biomarkers of gemcitabine response have been extensively studied in pancreatic cancer, but less so in other types of periampullary adenocarcinoma. The most studied biomarker is human equilibrative nucleoside transporter 1 (hENT1), and the activating enzyme deoxycytidine kinase (dCK) has also been linked to treatment response. The RNA-binding protein human antigen R (HuR) has been demonstrated to confer increased dCK levels in vitro and to predict gemcitabine response in vivo. Here, we investigated the prognostic impact of hENT1, dCK and HuR in pancreatobiliary (PB) and intestinal (I) type periampullary cancers, respectively. <i>Material and methods</i>: Immunohistochemical expression of hENT1, dCK and HuR was evaluated in tissue microarrays with all primary tumours and 103 paired lymph node metastases from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinomas. <i>Results</i>: In patients with PB-type tumours, neither hENT1 nor dCK expression was prognostic. A high HuR cytoplasmic/nuclear ratio was associated with a significantly reduced five-year overall survival (OS) in patients receiving adjuvant gemcitabine (HR 2.07, 95% CI 1.03–4.17) but not in untreated patients (p<sub>interaction</sub> = 0.028). In patients with I-type tumours receiving adjuvant chemotherapy, high dCK expression was significantly associated with a prolonged recurrence-free survival (RFS) (HR 0.09, 95% CI 0.01–0.73, p<sub>interaction</sub> = 0.023). Furthermore, HuR expression was associated with a prolonged OS and RFS in unadjusted but not in adjusted analysis and hENT1 expression was an independent predictor of a prolonged RFS (HR 0.24, 95% CI 0.10–0.59), regardless of adjuvant treatment. <i>Conclusion</i>: hENT1 expression is a favourable prognostic factor in I-type, but not in PB-type tumours. High dCK expression is a favourable prognostic factor in patients with I-type tumours receiving adjuvant treatment and a high cytoplasmic/nuclear HuR ratio is a negative prognostic factor in gemcitabine-treated PB-type tumours. Morphological subtype should always be considered in biomarker studies on periampullary cancer.
DOI: 10.6084/m9.figshare.1569452.v2
title: Phosphorylation and dephosphorylation regulate APC/C<sup>Cdh1</sup> substrate degradation

description: The Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase activated by its G1 specific adaptor protein Cdh1 is a major regulator of the cell cycle. The APC/C<sup>Cdh1</sup> mediates degradation of dozens of proteins, however, the kinetics and requirements for their degradation are largely unknown. We demonstrate that overexpression of the constitutive active <i>CDH1</i><sup><i>m11</i></sup> mutant that is not inhibited by phosphorylation results in mitotic exit in the absence of the FEAR and MEN pathways, and DNA re-replication in the absence of Cdc7 activity. This mode of mitotic exit also reveals additional requirements for APC/C<sup>Cdh1</sup> substrate degradation, which for some substrates such as Pds1 or Clb5 is dephosphorylation, but for others such as Cdc5 is phosphorylation.
DOI: 10.6084/m9.figshare.1569427.v1
title: Prognostic effect of hENT1, dCK and HuR expression by morphological type in periampullary adenocarcinoma, including pancreatic cancer

description: <i>Background</i>: Putative biomarkers of gemcitabine response have been extensively studied in pancreatic cancer, but less so in other types of periampullary adenocarcinoma. The most studied biomarker is human equilibrative nucleoside transporter 1 (hENT1), and the activating enzyme deoxycytidine kinase (dCK) has also been linked to treatment response. The RNA-binding protein human antigen R (HuR) has been demonstrated to confer increased dCK levels in vitro and to predict gemcitabine response in vivo. Here, we investigated the prognostic impact of hENT1, dCK and HuR in pancreatobiliary (PB) and intestinal (I) type periampullary cancers, respectively. <i>Material and methods</i>: Immunohistochemical expression of hENT1, dCK and HuR was evaluated in tissue microarrays with all primary tumours and 103 paired lymph node metastases from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinomas. <i>Results</i>: In patients with PB-type tumours, neither hENT1 nor dCK expression was prognostic. A high HuR cytoplasmic/nuclear ratio was associated with a significantly reduced five-year overall survival (OS) in patients receiving adjuvant gemcitabine (HR 2.07, 95% CI 1.03–4.17) but not in untreated patients (p<sub>interaction</sub> = 0.028). In patients with I-type tumours receiving adjuvant chemotherapy, high dCK expression was significantly associated with a prolonged recurrence-free survival (RFS) (HR 0.09, 95% CI 0.01–0.73, p<sub>interaction</sub> = 0.023). Furthermore, HuR expression was associated with a prolonged OS and RFS in unadjusted but not in adjusted analysis and hENT1 expression was an independent predictor of a prolonged RFS (HR 0.24, 95% CI 0.10–0.59), regardless of adjuvant treatment. <i>Conclusion</i>: hENT1 expression is a favourable prognostic factor in I-type, but not in PB-type tumours. High dCK expression is a favourable prognostic factor in patients with I-type tumours receiving adjuvant treatment and a high cytoplasmic/nuclear HuR ratio is a negative prognostic factor in gemcitabine-treated PB-type tumours. Morphological subtype should always be considered in biomarker studies on periampullary cancer.