cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5624914
title: Supplementary Tables S1-S7 from Sex-specific adaptation and genomic responses to Y chromosome presence in female reproductive and neural tissues

description: Y chromosomes typically harbour a small number of genes and an abundance of repetitive sequences. In <i>Drosophila,</i> the Y chromosome comprises multimegabase long segments of repetitive DNA and a handful of protein-coding genes. In mammals, the Y chromosome also harbours a disproportionally high abundance of repeats. Here, we build on a <i>Drosophila melanogaster</i> model in which the Y chromosome is decoupled from sexual determination. The genotypes were genetically identical for the autosomes, X chromosome, and mitochondria, but differ by the presence or dose of the Y chromosome. Addition of an extra Y chromosome had limited impact in males. However, the presence of a Y chromosome in females induced a disproportionate response in genes expressed in the ovaries as well as genes encoded by the mitochondrial genome. Furthermore, the data revealed significant consequences of Y chromosome presence in larvae neuronal tissue. This included the repression of genes implicated in reproductive behaviour, courtship, mating and synaptic function. Our findings exhibit the Y chromosome as a hotspot for sex-specific adaptation. They suggest a role of natural selection on Y-linked genetic elements exerting impacts on sex-specific tissues as well as somatic tissues shared by males and females.
DOI: 10.6084/m9.figshare.5624914.v1
title: Supplementary Tables S1-S7 from Sex-specific adaptation and genomic responses to Y chromosome presence in female reproductive and neural tissues

description: Y chromosomes typically harbour a small number of genes and an abundance of repetitive sequences. In <i>Drosophila,</i> the Y chromosome comprises multimegabase long segments of repetitive DNA and a handful of protein-coding genes. In mammals, the Y chromosome also harbours a disproportionally high abundance of repeats. Here, we build on a <i>Drosophila melanogaster</i> model in which the Y chromosome is decoupled from sexual determination. The genotypes were genetically identical for the autosomes, X chromosome, and mitochondria, but differ by the presence or dose of the Y chromosome. Addition of an extra Y chromosome had limited impact in males. However, the presence of a Y chromosome in females induced a disproportionate response in genes expressed in the ovaries as well as genes encoded by the mitochondrial genome. Furthermore, the data revealed significant consequences of Y chromosome presence in larvae neuronal tissue. This included the repression of genes implicated in reproductive behaviour, courtship, mating and synaptic function. Our findings exhibit the Y chromosome as a hotspot for sex-specific adaptation. They suggest a role of natural selection on Y-linked genetic elements exerting impacts on sex-specific tissues as well as somatic tissues shared by males and females.
DOI: 10.6084/m9.figshare.5624878
title: Simulated dicot root systems

description: Library of simulated dicot root systems, with different architectural properties (genotypes). Each genotype was represented by 10 simulations. The different genotypes were based on a standard parameter set (mock) and had one parameter changed: growth rates (slow vs. fast), inter-lateral distances (dense vs sparse) or gravitropisms (steep vs shallow). <br>These root systems were used in web application: https://plantmodelling.shinyapps.io/archidart/
DOI: 10.6084/m9.figshare.5624863
title: Pharmacological inhibition of BCL9-β-catenin interaction to overcome resistance to immune checkpoint blockades by modulating Treg cells

description: Our study reports a promising opportunity for cancer therapy by pharmacological inhibition of the Wnt/β-cat signaling.<br>
DOI: 10.6084/m9.figshare.5624848
title: PrePex Surveillance Data 2016.xlsx

description: PrePex Surveillance Data
DOI: 10.6084/m9.figshare.5624848.v1
title: PrePex Surveillance Data 2016.xlsx

description: PrePex Surveillance Data
DOI: 10.6084/m9.figshare.5624839
title: Suppressed translation as a mechanism of initiation of CASP8 (caspase 8)-dependent apoptosis in autophagy-deficient NSCLC cells under nutrient limitation

description: Macroautophagy/autophagy inhibition under stress conditions is often associated with increased cell death. We found that under nutrient limitation, activation of CASP8/caspase-8 was significantly increased in autophagy-deficient lung cancer cells, which precedes mitochondria outer membrane permeabilization (MOMP), CYCS/cytochrome <i>c</i> release, and activation of CASP9/caspase-9, indicating that under such conditions the activation of CASP8 is a primary event in the initiation of apoptosis as well as essential to reduce clonogenic survival of autophagy-deficient cells. Starvation leads to suppression of CFLAR proteosynthesis and accumulation of CASP8 in SQSTM1 puncta. Overexpression of CFLARs reduces CASP8 activation and apoptosis during starvation, while its silencing promotes efficient activation of CASP8 and apoptosis in autophagy-deficient U1810 lung cancer cells even under nutrient-rich conditions. Similar to starvation, inhibition of protein translation leads to efficient activation of CASP8 and cell death in autophagy-deficient lung cancer cells. Thus, here for the first time we report that suppressed translation leads to activation of CASP8-dependent apoptosis in autophagy-deficient NSCLC cells under conditions of nutrient limitation. Our data suggest that targeting translational machinery can be beneficial for elimination of autophagy-deficient cells via the CASP8-dependent apoptotic pathway.
DOI: 10.6084/m9.figshare.5624842
title: Reaction paths of alane dissociation: VASP CONTCAR xyz

description: Zipped sets of 6 intermediate images output from converged VASP climbing-image calculation, in xyz format. Zip filename identifies start and end configurations which can be found in the "Alane adsorption on Si(100): VASP CONTCAR" filesets.
DOI: 10.6084/m9.figshare.5624836
title: In mammalian skeletal muscle, phosphorylation of TOMM22 by protein kinase CSNK2/CK2 controls mitophagy

description: In yeast, Tom22, the central component of the TOMM (translocase of outer mitochondrial membrane) receptor complex, is responsible for the recognition and translocation of synthesized mitochondrial precursor proteins, and its protein kinase CK2-dependent phosphorylation is mandatory for TOMM complex biogenesis and proper mitochondrial protein import. In mammals, the biological function of protein kinase CSNK2/CK2 remains vastly elusive and it is unknown whether CSNK2-dependent phosphorylation of TOMM protein subunits has a similar role as that in yeast. To address this issue, we used a skeletal muscle-specific <i>Csnk2b</i>/<i>Ck2β</i>-conditional knockout (cKO) mouse model. Phenotypically, these skeletal muscle <i>Csnk2b</i> cKO mice showed reduced muscle strength and abnormal metabolic activity of mainly oxidative muscle fibers, which point towards mitochondrial dysfunction. Enzymatically, active muscle lysates from skeletal muscle <i>Csnk2b</i> cKO mice phosphorylate murine TOMM22, the mammalian ortholog of yeast Tom22, to a lower extent than lysates prepared from controls. Mechanistically, CSNK2-mediated phosphorylation of TOMM22 changes its binding affinity for mitochondrial precursor proteins. However, in contrast to yeast, mitochondrial protein import seems not to be affected in vitro using mitochondria isolated from muscles of skeletal muscle <i>Csnk2b</i> cKO mice. PINK1, a mitochondrial health sensor that undergoes constitutive import under physiological conditions, accumulates within skeletal muscle <i>Csnk2b</i> cKO fibers and labels abnormal mitochondria for removal by mitophagy as demonstrated by the appearance of mitochondria-containing autophagosomes through electron microscopy. Mitophagy can be normalized by either introduction of a phosphomimetic TOMM22 mutant in cultured myotubes, or by in vivo electroporation of phosphomimetic <i>Tomm22</i> into muscles of mice. Importantly, transfection of the phosphomimetic <i>Tomm22</i> mutant in muscle cells with ablated <i>Csnk2b</i> restored their oxygen consumption rate comparable to wild-type levels. In sum, our data show that mammalian CSNK2-dependent phosphorylation of TOMM22 is a critical switch for mitophagy and reveal CSNK2-dependent physiological implications on metabolism, muscle integrity and behavior.
DOI: 10.6084/m9.figshare.5624842.v1
title: Reaction paths of alane dissociation: VASP CONTCAR xyz

description: Zipped sets of 6 intermediate images output from converged VASP climbing-image calculation, in xyz format. Zip filename identifies start and end configurations which can be found in the "Alane adsorption on Si(100): VASP CONTCAR" filesets.
DOI: 10.6084/m9.figshare.5624839.v1
title: Suppressed translation as a mechanism of initiation of CASP8 (caspase 8)-dependent apoptosis in autophagy-deficient NSCLC cells under nutrient limitation

description: Macroautophagy/autophagy inhibition under stress conditions is often associated with increased cell death. We found that under nutrient limitation, activation of CASP8/caspase-8 was significantly increased in autophagy-deficient lung cancer cells, which precedes mitochondria outer membrane permeabilization (MOMP), CYCS/cytochrome <i>c</i> release, and activation of CASP9/caspase-9, indicating that under such conditions the activation of CASP8 is a primary event in the initiation of apoptosis as well as essential to reduce clonogenic survival of autophagy-deficient cells. Starvation leads to suppression of CFLAR proteosynthesis and accumulation of CASP8 in SQSTM1 puncta. Overexpression of CFLARs reduces CASP8 activation and apoptosis during starvation, while its silencing promotes efficient activation of CASP8 and apoptosis in autophagy-deficient U1810 lung cancer cells even under nutrient-rich conditions. Similar to starvation, inhibition of protein translation leads to efficient activation of CASP8 and cell death in autophagy-deficient lung cancer cells. Thus, here for the first time we report that suppressed translation leads to activation of CASP8-dependent apoptosis in autophagy-deficient NSCLC cells under conditions of nutrient limitation. Our data suggest that targeting translational machinery can be beneficial for elimination of autophagy-deficient cells via the CASP8-dependent apoptotic pathway.
DOI: 10.6084/m9.figshare.5624833
title: A code for transcription elongation speed

description: The two major steps of gene expression are transcription and translation. While hundreds of studies regarding the effect of sequence features on the translation elongation process have been published, very few connect sequence features to the transcription elongation rate. We suggest, for the first time, that short transcript sub-sequences have a typical effect on RNA polymerase (RNAP) speed: we show that nucleotide 5-mers tend to have typical RNAP speed (or transcription rate), which is consistent along different parts of genes and among different groups of genes with high correlation. We also demonstrate that relative RNAP speed correlates with mRNA levels of endogenous and heterologous genes. Furthermore, we show that the estimated transcription and translation elongation rates correlate in endogenous genes. Finally, we demonstrate that our results are consistent for different high resolution experimental measurements of RNAP densities. These results suggest for the first time that transcription elongation is partly encoded in the transcript, affected by the codon-usage, and optimized by evolution with a significant effect on gene expression and organismal fitness.
DOI: 10.6084/m9.figshare.5624833.v1
title: A code for transcription elongation speed

description: The two major steps of gene expression are transcription and translation. While hundreds of studies regarding the effect of sequence features on the translation elongation process have been published, very few connect sequence features to the transcription elongation rate. We suggest, for the first time, that short transcript sub-sequences have a typical effect on RNA polymerase (RNAP) speed: we show that nucleotide 5-mers tend to have typical RNAP speed (or transcription rate), which is consistent along different parts of genes and among different groups of genes with high correlation. We also demonstrate that relative RNAP speed correlates with mRNA levels of endogenous and heterologous genes. Furthermore, we show that the estimated transcription and translation elongation rates correlate in endogenous genes. Finally, we demonstrate that our results are consistent for different high resolution experimental measurements of RNAP densities. These results suggest for the first time that transcription elongation is partly encoded in the transcript, affected by the codon-usage, and optimized by evolution with a significant effect on gene expression and organismal fitness.
DOI: 10.6084/m9.figshare.5624836.v1
title: In mammalian skeletal muscle, phosphorylation of TOMM22 by protein kinase CSNK2/CK2 controls mitophagy

description: In yeast, Tom22 the central component of the TOMM (translocase of outer mitochondrial membrane) receptor complex is responsible for the recognition and translocation of synthesized mitochondrial precursor proteins, and its protein kinase CK2-dependent phosphorylation is mandatory for TOMM complex biogenesis and proper mitochondrial protein import. In mammals, the biological function of protein kinase CSNK2/CK2 remains vastly elusive and it is unknown whether CSNK2-dependent phosphorylation of TOMM protein subunits has a similar role as that in yeast. To address this issue, we used a skeletal muscle-specific <i>Csnk2b</i>/<i>Ck2β</i>-conditional knockout (cKO) mouse model. Phenotypically, these skeletal muscle <i>Csnk2b</i> cKO mice showed reduced muscle strength and abnormal metabolic activity of mainly oxidative muscle fibers, which point towards mitochondrial dysfunction. Enzymatically, active muscle lysates from skeletal muscle <i>Csnk2b</i> cKO mice phosphorylate murine TOMM22, the mammalian ortholog of yeast Tom22, to a lower extent than lysates prepared from controls. Mechanistically, CSNK2-mediated phosphorylation of TOMM22 changes its binding affinity for mitochondrial precursor proteins. However, in contrast to yeast, mitochondrial protein import seems not to be affected <i>in vitro</i> using mitochondria isolated from muscles of skeletal muscle <i>Csnk2b</i> cKO mice. PINK1, a mitochondrial health sensor that undergoes constitutive import under physiological conditions, accumulates within skeletal muscle <i>Csnk2b</i> cKO fibers and labels abnormal mitochondria for removal by mitophagy as demonstrated by the appearance of mitochondria-containing autophagosomes through electron microscopy. Mitophagy can be normalized by either introduction of a phosphomimetic TOMM22 mutant in cultured myotubes, or by <i>in vivo</i> electroporation of phosphomimetic <i>Tomm22</i> into muscles of mice. Importantly, transfection of the phosphomimetic <i>Tomm22</i> mutant in muscle cells with ablated <i>Csnk2b</i> restored their oxygen consumption rate comparable to wild-type levels. In sum, our data show that mammalian CSNK2-dependent phosphorylation of TOMM22 is a critical switch for mitophagy and reveal CSNK2-dependent physiological implications on metabolism, muscle integrity and behavior.
DOI: 10.6084/m9.figshare.5624863.v2
title: Pharmacological inhibition of BCL9-β-catenin interaction to overcome resistance to immune checkpoint blockades by modulating Treg cells

description: Our study reports a promising opportunity for cancer therapy by pharmacological inhibition of the Wnt/β-cat signaling.<br>
DOI: 10.6084/m9.figshare.5624812
title: Dataset for: The impact of a short term high fat diet on mitochondrial respiration, reactive oxygen species production and dynamics in oxidative and glycolytic skeletal muscles of young rats

description: Background: Multiple aspects of mitochondrial function and dynamics remain poorly studied in the skeletal muscle of pediatric models in response to a short-term high fat diet (HFD). The present study investigated the impact of a short-term HFD on mitochondrial function and dynamics in the oxidative soleus (SOL) and glycolytic extensor digitorum longus (EDL) muscles in young rats. Methods: Young male Wistar rats were submitted to either HFD or normal chow (NCD) diets for 14 days. Permeabilized myofibers from SOL and EDL were prepared to assess, mitochondrial respiration and ROS production. The expression and content of protein involved in mitochondrial metabolism and dynamics (fusion/fission) were also quantified. Results: While no effects of HFD was observed on mitochondrial respiration when classical complex I and II substrates were used, both SOL and EDL of Rats submitted to a HFD displayed higher basal and ADP-stimulated respiration rates when Malate + Palmitoyl-L-carnitine were used as substrates. HFD did not alter ROS production and markers of mitochondrial content. The expression of CPT1b was significantly increased in SOL and EDL of HFD rats. Although the expression of UCP3 was increased in SOL and EDL muscles from HFD rats, uncoupling was not altered. In SOL of HFD rats, the transcript levels of Mfn2 and Fis1 were significantly upregulated. The expression and content of proteins regulating mitochondrial dynamics was not modulated by HFD in the EDL. Finally, DRP1 protein content was increased by over 4-fold in the SOL of HFD rats. Conclusions: Exposing young animals to short-term HFD results in an increase capacity of skeletal muscle mitochondria to oxidize fatty acids, without altering ROS production, coupling efficiency and mitochondrial content. Our results also highlight that the impact of HFD on mitochondrial dynamics appears to be muscle specific.
DOI: 10.6084/m9.figshare.5624812.v1
title: Dataset for: The impact of a short term high fat diet on mitochondrial respiration, reactive oxygen species production and dynamics in oxidative and glycolytic skeletal muscles of young rats

description: Background: Multiple aspects of mitochondrial function and dynamics remain poorly studied in the skeletal muscle of pediatric models in response to a short-term high fat diet (HFD). The present study investigated the impact of a short-term HFD on mitochondrial function and dynamics in the oxidative soleus (SOL) and glycolytic extensor digitorum longus (EDL) muscles in young rats. Methods: Young male Wistar rats were submitted to either HFD or normal chow (NCD) diets for 14 days. Permeabilized myofibers from SOL and EDL were prepared to assess, mitochondrial respiration and ROS production. The expression and content of protein involved in mitochondrial metabolism and dynamics (fusion/fission) were also quantified. Results: While no effects of HFD was observed on mitochondrial respiration when classical complex I and II substrates were used, both SOL and EDL of Rats submitted to a HFD displayed higher basal and ADP-stimulated respiration rates when Malate + Palmitoyl-L-carnitine were used as substrates. HFD did not alter ROS production and markers of mitochondrial content. The expression of CPT1b was significantly increased in SOL and EDL of HFD rats. Although the expression of UCP3 was increased in SOL and EDL muscles from HFD rats, uncoupling was not altered. In SOL of HFD rats, the transcript levels of Mfn2 and Fis1 were significantly upregulated. The expression and content of proteins regulating mitochondrial dynamics was not modulated by HFD in the EDL. Finally, DRP1 protein content was increased by over 4-fold in the SOL of HFD rats. Conclusions: Exposing young animals to short-term HFD results in an increase capacity of skeletal muscle mitochondria to oxidize fatty acids, without altering ROS production, coupling efficiency and mitochondrial content. Our results also highlight that the impact of HFD on mitochondrial dynamics appears to be muscle specific.
DOI: 10.6084/m9.figshare.5624821
title: Molecular subtyping of breast cancer improves identification of both high and low risk patients

description: <b>Background:</b> Transcriptome analysis enables classification of breast tumors into molecular subtypes that correlate with prognosis and effect of therapy. We evaluated the clinical benefits of molecular subtyping compared to our current diagnostic practice. <b>Materials and methods:</b> Molecular subtyping was performed on a consecutive and unselected series of 524 tumors from women with primary breast cancer (<i>n</i> = 508). Tumors were classified by the 256 gene expression signature (CIT) and compared to conventional immunohistochemistry (IHC) procedures. <b>Results:</b> More than 99% of tumors were eligible for molecular classification and final reports were available prior to the multidisciplinary conference. Using a prognostic standard mortality rate index (PSMRi) developed by the Danish Breast Cancer Group (DBCG) 39 patients were assigned with an intermediate risk and among these 16 (41%) were furthermore diagnosed by the multi-gene signature assigned with a luminal A tumor and consequently spared adjuvant chemotherapy. There was overall agreement between mRNA derived and IHC hormone receptor status, whereas IHC Ki67 protein proliferative index proved inaccurate, compared to the mRNA derived index. Forty-one patients with basal-like (basL) subtypes were screened for predisposing mutations regardless of clinical predisposition. Of those 17% carried pathogenic mutations. <b>Conclusion:</b> Transcriptome based subtyping of breast tumors evidently reduces the need for adjuvant chemotherapy and improves identification of women with predisposing mutations. The results imply that transcriptome profiling should become an integrated part of current breast cancer management.
DOI: 10.6084/m9.figshare.5624800
title: Reaction paths of alane dissociation: VASP CONTCAR

description: Zipped sets of 6 intermediate images output from converged VASP climbing-image calculation, in CONTCAR format. Zip filename identifies start and end configurations which can be found in the "Alane adsorption on Si(100): VASP CONTCAR" filesets. <br>
DOI: 10.6084/m9.figshare.5624821.v1
title: Molecular subtyping of breast cancer improves identification of both high and low risk patients

description: <b>Background:</b> Transcriptome analysis enables classification of breast tumors into molecular subtypes that correlate with prognosis and effect of therapy. We evaluated the clinical benefits of molecular subtyping compared to our current diagnostic practice. <b>Materials and methods:</b> Molecular subtyping was performed on a consecutive and unselected series of 524 tumors from women with primary breast cancer (<i>n</i> = 508). Tumors were classified by the 256 gene expression signature (CIT) and compared to conventional immunohistochemistry (IHC) procedures. <b>Results:</b> More than 99% of tumors were eligible for molecular classification and final reports were available prior to the multidisciplinary conference. Using a prognostic standard mortality rate index (PSMRi) developed by the Danish Breast Cancer Group (DBCG) 39 patients were assigned with an intermediate risk and among these 16 (41%) were furthermore diagnosed by the multi-gene signature assigned with a luminal A tumor and consequently spared adjuvant chemotherapy. There was overall agreement between mRNA derived and IHC hormone receptor status, whereas IHC Ki67 protein proliferative index proved inaccurate, compared to the mRNA derived index. Forty-one patients with basal-like (basL) subtypes were screened for predisposing mutations regardless of clinical predisposition. Of those 17% carried pathogenic mutations. <b>Conclusion:</b> Transcriptome based subtyping of breast tumors evidently reduces the need for adjuvant chemotherapy and improves identification of women with predisposing mutations. The results imply that transcriptome profiling should become an integrated part of current breast cancer management.