cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.6860387.v2
title: High throughput screening, docking, and molecular dynamics studies to identify potential inhibitors of human calcium/calmodulin-dependent protein kinase IV

description: Calcium/calmodulin-dependent protein kinase IV (CAMKIV) is associated with many diseases including cancer and neurodegenerative disorders and thus being considered as a potential drug target. Here, we have employed the knowledge of three-dimensional structure of CAMKIV to identify new inhibitors for possible therapeutic intervention. We have employed virtual high throughput screening of 12,500 natural compounds of Zinc database to screen the best possible inhibitors of CAMKIV. Subsequently, 40 compounds which showed significant docking scores (−11.6 to −10.0 kcal/mol) were selected and further filtered through Lipinski rule and drug likeness parameter to get best inhibitors of CAMKIV. Docking results are indicating that ligands are binding to the hydrophobic cavity of the kinase domain of CAMKIV and forming a significant number of non-covalent interactions. Four compounds, ZINC02098378, ZINC12866674, ZINC04293413, and ZINC13403020, showing excellent binding affinity and drug likeness were subjected to molecular dynamics simulation to evaluate their mechanism of interaction and stability of protein-ligand complex. Our observations clearly suggesting that these selected ligands may be further employed for therapeutic intervention to address CAMKIV associated diseases. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.6860387.v1
title: High throughput screening, docking and molecular dynamics studies to identify potential inhibitors of human calcium/calmodulin-dependent protein kinase IV

description: Calcium/calmodulin-dependent protein kinase IV (CAMKIV) is associated with many diseases including cancer and neurodegenerative disorders, and thus being considered as a potential drug target. Here, we have employed the knowledge of three-dimensional structure of CAMKIV to identify new inhibitors for possible therapeutic intervention. We have employed virtual high throughput screening of 12500 natural compounds of Zinc database to screen the best possible inhibitors of CAMKIV. Subsequently 40 compounds which showed significant docking scores (–11.6 to –10.0 kcal/mol) were selected and further filtered through Lipinski rule and drug likeness parameter to get best inhibitors of CAMKIV. Docking results are indicating that ligands are binding to the hydrophobic cavity of the kinase domain of CAMKIV and forming a significant number of non-covalent interactions. Four compounds, ZINC02098378, ZINC12866674, ZINC04293413 and ZINC13403020, showing excellent binding affinity and drug likeness were subjected to molecular dynamics simulation to evaluate their mechanism of interaction and stability of protein-ligand complex. Our observations clearly suggesting that these selected ligands may be further employed for therapeutic intervention to address CAMKIV associated diseases.
DOI: 10.6084/m9.figshare.6860348
title: An <i>in silico</i> study of the citrus dioxygenases CCD4 family substrates

description: The coloration of Citrus fruits is related with the concentration of carotenoids, isoprenoid pigments of 40 carbon atoms (C<sub>40</sub>). Rodrigo et al. and Ma et al. reported a CCD4-type citrus dioxygenase responsible for the generation of C<sub>30</sub> apocarotenoids providing a reddish-orange pigmentation to the peel of many mandarins and oranges. Among them, CCD4b was the first case described of a dioxygenase that cleaves carotenoids C<sub>40</sub> in the double bond 7′, 8′ or 7, 8, generating β-citraurin or 8-β-apocarotenal. Here we report the three-dimensional structures of CCD4a and CCD4b, modeled by sequence homology (2BIW) and validated by molecular dynamics (MD). Docking calculations were performed in CCD4a and CCD4b structures with thousands of rotated initial carotenoid conformations and all the possible poses in the active site were found. The interaction energy was measured by means of ASE scoring, Amber99 refinement and London Δ<i>G</i> rescoring. For the case of CCD4a model, the results showed London Δ<i>G</i> score of −19, −17 and −15 kcal/mol for zeaxanthin, β-cryptoxanthin and β-carotene, respectively. The same sequence in the estimated interaction strength for the three ligands was obtained using MD. The interaction energy of CCD4b indicated that, in agreement with experimental data, zeaxanthin and β-cryptoxanthin could be cleaved by the enzyme, β- and α-carotene have chances to be oxidized and lycopene has not good interaction energy to be predicted as substrate. These findings will be discussed considering the potential <i>in vivo</i> substrates and products, and the physiological role in Citrus fruits. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.6860348.v2
title: An <i>in silico</i> study of the citrus dioxygenases CCD4 family substrates

description: The coloration of Citrus fruits is related with the concentration of carotenoids, isoprenoid pigments of 40 carbon atoms (C<sub>40</sub>). Rodrigo et al. and Ma et al. reported a CCD4-type citrus dioxygenase responsible for the generation of C<sub>30</sub> apocarotenoids providing a reddish-orange pigmentation to the peel of many mandarins and oranges. Among them, CCD4b was the first case described of a dioxygenase that cleaves carotenoids C<sub>40</sub> in the double bond 7′, 8′ or 7, 8, generating β-citraurin or 8-β-apocarotenal. Here we report the three-dimensional structures of CCD4a and CCD4b, modeled by sequence homology (2BIW) and validated by molecular dynamics (MD). Docking calculations were performed in CCD4a and CCD4b structures with thousands of rotated initial carotenoid conformations and all the possible poses in the active site were found. The interaction energy was measured by means of ASE scoring, Amber99 refinement and London Δ<i>G</i> rescoring. For the case of CCD4a model, the results showed London Δ<i>G</i> score of −19, −17 and −15 kcal/mol for zeaxanthin, β-cryptoxanthin and β-carotene, respectively. The same sequence in the estimated interaction strength for the three ligands was obtained using MD. The interaction energy of CCD4b indicated that, in agreement with experimental data, zeaxanthin and β-cryptoxanthin could be cleaved by the enzyme, β- and α-carotene have chances to be oxidized and lycopene has not good interaction energy to be predicted as substrate. These findings will be discussed considering the potential <i>in vivo</i> substrates and products, and the physiological role in Citrus fruits. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.6860261
title: ProteomeTools - Prosit fragmentation - Data

description: ProteomeTools HCD data as training, test and holdout dataset for machine learning applications.
DOI: 10.6084/m9.figshare.6860273
title: Late Pleistocene genetic diversification and demographic expansion in the widely distributed neotropical ant <i>Neoponera villosa</i> (Ponerinae)

description: Phylogeographic studies of continent-wide distributed species are key to understand population dynamics processes that occurred at large geographical scales. Here, we examined two mitochondrial (mt) DNA sequence (COI, Cyt <i>b</i>) and eight nuclear microsatellites markers to investigate the cohesiveness, genetic diversity and demographic history of <i>Neoponera villosa</i> (Fabricius), a ponerine ant species widely distributed along most part of the Neotropics and southern Nearctic. The reconstructed phylogeny and mt variation supported the cohesiveness of the examined populations of <i>N. villosa</i>. The species probably originated in South America during the late Pliocene/middle Pleistocene and subsequently dispersed to Central America and the Transitional Nearctic-Neotropical zone during the late Pleistocene, with an increase in its population size ca. 30 thousand years ago. The limited phylogeographic structure observed in <i>N. villosa</i> supports its late Pleistocene range expansion and gene flow among distant geographic areas in central and southern Mexico and Central America.
DOI: 10.6084/m9.figshare.6860273.v1
title: Late Pleistocene genetic diversification and demographic expansion in the widely distributed neotropical ant <i>Neoponera villosa</i> (Ponerinae)

description: Phylogeographic studies of continent-wide distributed species are key to understand population dynamics processes that occurred at large geographical scales. Here, we examined two mitochondrial (mt) DNA sequence (COI, Cyt <i>b</i>) and eight nuclear microsatellites markers to investigate the cohesiveness, genetic diversity and demographic history of <i>Neoponera villosa</i> (Fabricius), a ponerine ant species widely distributed along most part of the Neotropics and southern Nearctic. The reconstructed phylogeny and mt variation supported the cohesiveness of the examined populations of <i>N. villosa</i>. The species probably originated in South America during the late Pliocene/middle Pleistocene and subsequently dispersed to Central America and the Transitional Nearctic-Neotropical zone during the late Pleistocene, with an increase in its population size ca. 30 thousand years ago. The limited phylogeographic structure observed in <i>N. villosa</i> supports its late Pleistocene range expansion and gene flow among distant geographic areas in central and southern Mexico and Central America.
DOI: 10.6084/m9.figshare.6860255
title: Supplementary Material for: Upregulation of RASSF1A in Colon Cancer by Suppression of Angiogenesis Signaling and Akt Activation

description: <b><i>Background/Aims:</i></b> Silencing of tumor suppressor genes (TSGs) and promotion of angiogenesis are associated with tumor development and metastasis. However, little is known if angiogenic molecules directly control TSGs and vice versa. <b><i>Methods:</i></b> A regulatory link between angiogenesis and down regulation of TSGs was evaluated using an anti-cancer agent, andrographolide (AGP) in cancer cells, mouse xenograft tissues and patient derived organoids through gene/protein expression, gene silencing, and immunohistochemical analyses. <b><i>Results:</i></b> AGP treatment demonstrated significant expression of RASSF1A and PTEN TSGs in colon cancer and other cancer cells, mouse tissues and organoids. Depletion of RASSF1A with siRNA limited cyclin D1 and BAX expression. SiRNA depletion of PTEN, upstream regulator of RASSF1A resulted in a 50% reduction in RASSF1A expression. Histopathological analysis of the AGP treated tumor sections showed significant reduction in vessel size, microvascular density and tumor mitotic index suggesting suppression of angiogenesis. This was corroborated by protein analysis demonstrating significant reductions in angiogenesis signaling pathway molecules VEGF<sub>165</sub>, FOXM1, and pAkt, but significant elevation of the endogenous angiogenesis inhibitor Tsp-2. Treatment of cells with exogenous VEGF prevented the suppression of angiogenesis signaling by AGP, resulting in sustained expression of pAkt, an upstream down-regulator of RASSF1A. RASSF1A expression remained low in VEGF treated cells despite the addition of AGP. <b><i>Conclusion:</i></b> Our results demonstrate for the first time that AGP induces RASSF1A expression in colon cancer cells and is dependent on angiogenesis signaling events. Therefore, our research may facilitate novel therapeutic options for advanced colon cancer therapy.
DOI: 10.6084/m9.figshare.6860255.v1
title: Supplementary Material for: Upregulation of RASSF1A in Colon Cancer by Suppression of Angiogenesis Signaling and Akt Activation

description: <b><i>Background/Aims:</i></b> Silencing of tumor suppressor genes (TSGs) and promotion of angiogenesis are associated with tumor development and metastasis. However, little is known if angiogenic molecules directly control TSGs and vice versa. <b><i>Methods:</i></b> A regulatory link between angiogenesis and down regulation of TSGs was evaluated using an anti-cancer agent, andrographolide (AGP) in cancer cells, mouse xenograft tissues and patient derived organoids through gene/protein expression, gene silencing, and immunohistochemical analyses. <b><i>Results:</i></b> AGP treatment demonstrated significant expression of RASSF1A and PTEN TSGs in colon cancer and other cancer cells, mouse tissues and organoids. Depletion of RASSF1A with siRNA limited cyclin D1 and BAX expression. SiRNA depletion of PTEN, upstream regulator of RASSF1A resulted in a 50% reduction in RASSF1A expression. Histopathological analysis of the AGP treated tumor sections showed significant reduction in vessel size, microvascular density and tumor mitotic index suggesting suppression of angiogenesis. This was corroborated by protein analysis demonstrating significant reductions in angiogenesis signaling pathway molecules VEGF<sub>165</sub>, FOXM1, and pAkt, but significant elevation of the endogenous angiogenesis inhibitor Tsp-2. Treatment of cells with exogenous VEGF prevented the suppression of angiogenesis signaling by AGP, resulting in sustained expression of pAkt, an upstream down-regulator of RASSF1A. RASSF1A expression remained low in VEGF treated cells despite the addition of AGP. <b><i>Conclusion:</i></b> Our results demonstrate for the first time that AGP induces RASSF1A expression in colon cancer cells and is dependent on angiogenesis signaling events. Therefore, our research may facilitate novel therapeutic options for advanced colon cancer therapy.
DOI: 10.6084/m9.figshare.6860216
title: Swiss Delphi Study on Iron Deficiency

description: <b>Objectives</b>Iron deficiency (ID) and iron deficiency anaemia (IDA) are important conditions affecting a large proportion of the general population, causing the patients` physical and psychosomatic symptoms, particularly fatigue, significantly affecting their quality of life. In pregnancy, ID and IDA may affect the foetus and the new-born child, and may lead to pregnancy complications. Unspecific symptoms due to ID are frequently encountered in General practice, however, little evidence is available to guide iron substitution. As a consequence, misuse of iron replacement therapy has been reported. <br><b>Design</b>We conducted a <i>Swiss Delphi Study </i><i>on Iron Deficiency </i>in order<i> </i>to generate a broad consensual Swiss expert opinion in various therapeutic areas on diagnosis and treatment of ID/IDA and their practical implications. <br><b>Setting</b>Specific statements regarding clinical relevance, practical diagnostic and therapeutic approaches, and treatment have been evaluated by Swiss experts in various therapeutic areas. <br><b>Participants </b>Expert panel.<br><b>Intervention</b>Online anonymous surveys containing overall 440 statements. <br><b>Outcome measures</b>Percentage of Consensus, Critical Consensus and Disagreement for each statement. <b>Results </b>Consensus (&gt;80% agreement) was achieved for 50% (N=218), Critical Consensus (agreement of 50-79%) for further 39% (N=173) and Disagreement for 11% (N=49) (agreement&lt;50%) of the statements. In patients without systemic inflammation, the threshold of 30 μg/L for serum ferritin provides a good accuracy for the diagnosis of ID without anaemia. Additionally, ferritin levels within the range of 30-50 μg/L with transferrin saturation (TSAT)&lt;20% can indicate ID without anaemia. Iron replacement therapy is accepted for treatment, not only of IDA, but also of symptomatic ID without anaemia. Finally, GPs play a central role in diagnosis and management of ID.<br><b>Conclusion</b> This consensus study, based on opinions of a high number of contributing specialists, provides potential therapeutic strategies for management of iron deficiency in a wide range of clinical perspectives. <br>
DOI: 10.6084/m9.figshare.6860240
title: MIRA KG

description: RDF knowledge graph with the a collection of papers associated with citation count and altmetrics.
DOI: 10.6084/m9.figshare.6860216.v1
title: Swiss Delphi Study on Iron Deficiency

description: <b>Objectives</b>Iron deficiency (ID) and iron deficiency anaemia (IDA) are important conditions affecting a large proportion of the general population, causing the patients` physical and psychosomatic symptoms, particularly fatigue, significantly affecting their quality of life. In pregnancy, ID and IDA may affect the foetus and the new-born child, and may lead to pregnancy complications. Unspecific symptoms due to ID are frequently encountered in General practice, however, little evidence is available to guide iron substitution. As a consequence, misuse of iron replacement therapy has been reported. <br><b>Design</b>We conducted a <i>Swiss Delphi Study </i><i>on Iron Deficiency </i>in order<i> </i>to generate a broad consensual Swiss expert opinion in various therapeutic areas on diagnosis and treatment of ID/IDA and their practical implications. <br><b>Setting</b>Specific statements regarding clinical relevance, practical diagnostic and therapeutic approaches, and treatment have been evaluated by Swiss experts in various therapeutic areas. <br><b>Participants </b>Expert panel.<br><b>Intervention</b>Online anonymous surveys containing overall 440 statements. <br><b>Outcome measures</b>Percentage of Consensus, Critical Consensus and Disagreement for each statement. <b>Results </b>Consensus (&gt;80% agreement) was achieved for 50% (N=218), Critical Consensus (agreement of 50-79%) for further 39% (N=173) and Disagreement for 11% (N=49) (agreement&lt;50%) of the statements. In patients without systemic inflammation, the threshold of 30 μg/L for serum ferritin provides a good accuracy for the diagnosis of ID without anaemia. Additionally, ferritin levels within the range of 30-50 μg/L with transferrin saturation (TSAT)&lt;20% can indicate ID without anaemia. Iron replacement therapy is accepted for treatment, not only of IDA, but also of symptomatic ID without anaemia. Finally, GPs play a central role in diagnosis and management of ID.<br><b>Conclusion</b> This consensus study, based on opinions of a high number of contributing specialists, provides potential therapeutic strategies for management of iron deficiency in a wide range of clinical perspectives. <br>
DOI: 10.6084/m9.figshare.6860240.v1
title: MIRA KG

description: RDF knowledge graph with the a collection of papers associated with citation count and altmetrics.
DOI: 10.6084/m9.figshare.6860138
title: B. pinnatum and E. repens hypervolume calculation

description: 1. Trait intraspecific variability determines community dynamics and species coexistence. In response to competition, plants can display intraspecific variability to enhance its competitive ability or stabilize its niche differences with their competitors. This response is multidimensional because it involves changes along different functional axes and inevitable trade-offs between traits. Here, we transposed the recent concept of the multidimensional trait space to the analysis of intraspecific plant response to competition. We specifically tested the following: (1) in the absence of competitors, the plant multidimensional trait space will be packed towards strategies promoting plant colonisation, and (2) with competitors, the plant multidimensional trait space will be directed towards competition with its size and shaping characteristics dependent on competitor species richness.<br><br>2. We studied trait intraspecific variability of two clonal species, Brachypodium pinnatum (L.) P. Beauv. and Elytrigia repens (L.) Gould, in response to competition. We analysed plant response in the absence of competitors and in competition. Competition treatments included intraspecific and interspecific experimental mixtures with increasing species richness. For each target species and each treatment, we built an hypervolume based on six traits involved in the three-dimensional competition (i.e. ramet and connection traits). We measured these hypervolumes for their size, similarity and the contribution of traits in their shaping.<br><br>3. In the absence of competitors and for both species, we demonstrated a multidimensional trait space packing towards a colonisation strategy. Under competition, the multidimensional trait spaces of the two target species were the widest at the extremes of the richness gradient, i.e., intraspecific and interspecific high richness competition treatments. High intraspecific variability either promoted niche differentiation for individuals of similar species or reflected the large range of competitive responses deployed when plants were faced with many different competitor identities. The multidimensional response process was based on fine adjustments of various traits depending on the surrounding neighbourhood composition and more specifically, on the competitor abundances and functional similarity with the target species.<br><br>4. This study emphasised the multidimensionality of species competitive response, and also underlined the so far neglected importance of competitor species richness for trait intraspecific variability and subsequently community assembly.<br><br>
DOI: 10.6084/m9.figshare.6860138.v1
title: B. pinnatum and E. repens hypervolume calculation

description: 1. Trait intraspecific variability determines community dynamics and species coexistence. In response to competition, plants can display intraspecific variability to enhance its competitive ability or stabilize its niche differences with their competitors. This response is multidimensional because it involves changes along different functional axes and inevitable trade-offs between traits. Here, we transposed the recent concept of the multidimensional trait space to the analysis of intraspecific plant response to competition. We specifically tested the following: (1) in the absence of competitors, the plant multidimensional trait space will be packed towards strategies promoting plant colonisation, and (2) with competitors, the plant multidimensional trait space will be directed towards competition with its size and shaping characteristics dependent on competitor species richness.<br><br>2. We studied trait intraspecific variability of two clonal species, Brachypodium pinnatum (L.) P. Beauv. and Elytrigia repens (L.) Gould, in response to competition. We analysed plant response in the absence of competitors and in competition. Competition treatments included intraspecific and interspecific experimental mixtures with increasing species richness. For each target species and each treatment, we built an hypervolume based on six traits involved in the three-dimensional competition (i.e. ramet and connection traits). We measured these hypervolumes for their size, similarity and the contribution of traits in their shaping.<br><br>3. In the absence of competitors and for both species, we demonstrated a multidimensional trait space packing towards a colonisation strategy. Under competition, the multidimensional trait spaces of the two target species were the widest at the extremes of the richness gradient, i.e., intraspecific and interspecific high richness competition treatments. High intraspecific variability either promoted niche differentiation for individuals of similar species or reflected the large range of competitive responses deployed when plants were faced with many different competitor identities. The multidimensional response process was based on fine adjustments of various traits depending on the surrounding neighbourhood composition and more specifically, on the competitor abundances and functional similarity with the target species.<br><br>4. This study emphasised the multidimensionality of species competitive response, and also underlined the so far neglected importance of competitor species richness for trait intraspecific variability and subsequently community assembly.<br><br>
DOI: 10.6084/m9.figshare.6860096
title: Leipzig-Helmstedt data set

description: This data set contains historical merged data from Lipsiensium and Helmstedt.
DOI: 10.6084/m9.figshare.6860096.v1
title: Leipzig-Helmstedt data set

description: This data set contains historical merged data from Lipsiensium and Helmstedt.
DOI: 10.6084/m9.figshare.6860096.v2
title: Leipzig-Helmstedt data set

description: This data set contains historical merged data from Lipsiensium and Helmstedt.