cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.4288406.v3
title: Comprehensive mapping of 5-hydroxymethylcytosine epigenetic dynamics in axon regeneration

description: In contrast to central nervous system neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated in DRG neurons, along with increased 5-hydroxymethylcytosine (5hmC). We generated genome-wide 5hmC maps in adult DRG, which revealed that peripheral and central axotomy (leading to no regenerative effect) triggered differential 5hmC changes that are associated with distinct signaling pathways. 5hmC was altered in a large set of regeneration-associated genes (RAGs), including well-known RAGs, such as <i>Atf3, Bdnf</i>, and <i>Smad1</i>, that regulate axon growth potential of DRG neurons, thus supporting its role for RAG regulation. Our analyses also predicted HIF-1, STAT, and IRF as potential transcription factors that may collaborate with Tet3 for 5hmC modifications. Intriguingly, central axotomy resulted in widespread 5hmC modifications that had little overlap with those of peripheral axotomy, thus potentially constituting a roadblock for regeneration. Our study revealed 5hmC dynamics as a previously unrecognized epigenetic mechanism underlying the divergent responses after axonal injury.
DOI: 10.6084/m9.figshare.4288406.v2
title: Comprehensive mapping of 5-hydroxymethylcytosine epigenetic dynamics in axon regeneration

description: In contrast to central nervous system neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated in DRG neurons, along with increased 5-hydroxymethylcytosine (5 hmC). We generated genome-wide 5 hmC maps in adult DRG, which revealed that peripheral and central axotomy (leading to no regenerative effect) triggered differential 5 hmC changes that are associated with distinct signaling pathways. 5 hmC was altered in a large set of regeneration-associated genes (RAGs), including well-known RAGs, such as <i>Atf3, Bdnf</i>, and <i>Smad1</i>, that regulate axon growth potential of DRG neurons, thus supporting its role for RAG regulation. Our analyses also predicted HIF-1, STAT, and IRF as potential transcription factors that may collaborate with Tet3 for 5 hmC modifications. Intriguingly, central axotomy resulted in widespread 5 hmC modifications that had little overlap with those of peripheral axotomy, thus potentially constituting a roadblock for regeneration. Our study revealed 5 hmC dynamics as a previously unrecognized epigenetic mechanism underlying the divergent responses after axonal injury.
DOI: 10.6084/m9.figshare.4288409
title: Comprehensive mapping of 5-hydroxymethylcytosine epigenetic dynamics in axon regeneration

description: In contrast to central nervous system neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated in DRG neurons, along with increased 5-hydroxymethylcytosine (5 hmC). We generated genome-wide 5 hmC maps in adult DRG, which revealed that peripheral and central axotomy (leading to no regenerative effect) triggered differential 5 hmC changes that are associated with distinct signaling pathways. 5 hmC was altered in a large set of regeneration-associated genes (RAGs), including well-known RAGs, such as <i>Atf3, Bdnf</i>, and <i>Smad1</i>, that regulate axon growth potential of DRG neurons, thus supporting its role for RAG regulation. Our analyses also predicted HIF-1, STAT, and IRF as potential transcription factors that may collaborate with Tet3 for 5 hmC modifications. Intriguingly, central axotomy resulted in widespread 5 hmC modifications that had little overlap with those of peripheral axotomy, thus potentially constituting a roadblock for regeneration. Our study revealed 5 hmC dynamics as a previously unrecognized epigenetic mechanism underlying the divergent responses after axonal injury.
DOI: 10.6084/m9.figshare.4288409.v1
title: Comprehensive mapping of 5-hydroxymethylcytosine epigenetic dynamics in axon regeneration

description: In contrast to central nervous system neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated in DRG neurons, along with increased 5-hydroxymethylcytosine (5 hmC). We generated genome-wide 5 hmC maps in adult DRG, which revealed that peripheral and central axotomy (leading to no regenerative effect) triggered differential 5 hmC changes that are associated with distinct signaling pathways. 5 hmC was altered in a large set of regeneration-associated genes (RAGs), including well-known RAGs, such as <i>Atf3, Bdnf</i>, and <i>Smad1</i>, that regulate axon growth potential of DRG neurons, thus supporting its role for RAG regulation. Our analyses also predicted HIF-1, STAT, and IRF as potential transcription factors that may collaborate with Tet3 for 5 hmC modifications. Intriguingly, central axotomy resulted in widespread 5 hmC modifications that had little overlap with those of peripheral axotomy, thus potentially constituting a roadblock for regeneration. Our study revealed 5 hmC dynamics as a previously unrecognized epigenetic mechanism underlying the divergent responses after axonal injury.
DOI: 10.6084/m9.figshare.4289894
title: L-2-hydroxyglutarate production arises from non-canonical enzyme function at acidic pH: Docking and MCCE2 calculation data set

description: L-2-hydroxyglutarate production arises from non-canonical enzyme function at acidic pH<br>Contained within are input and output files for the docking and MCCE calculations performed accompanying the manuscript by Intlekofer et al.   <br>Inside the zip file, see the `Docking` folder for files used in the docking procedures. Docking was performed using Maestro as part of Schrodinger release 2015-3.  <br>See the `MCCE` folder for files used for the MCCE2 calculations for Lactate dehydrogenase A. MCCE calculations were performed using MCCE2 (https://sites.google.com/site/mccewiki/install-mcce).  Epik calculations were performed using Schrodinger release 2015-3.
DOI: 10.6084/m9.figshare.4289894.v1
title: L-2-hydroxyglutarate production results from non-canonical enzyme function at acidic pH.zip

description: Contained within are input and output files for the docking and MCCE calculations performed accompanying the manuscript by Intlekofer et al.   <br>Inzide the zip file, see the `Docking` folder for files used in the docking procedures. Docking was performed using Maestro as part of Schrodinger release 2015-3.  <br>See the `MCCE` folder for files used for the MCCE2 calculations for Lactate dehydrogenase A. MCCE calculations were performed using MCCE2 (httpssites.google.comsitemccewikiinstall-mcce).  Epik calculations were performed using Schrodinger release 2015-3.
DOI: 10.6084/m9.figshare.4289894.v3
title: L-2-hydroxyglutarate production arises from non-canonical enzyme function at acidic pH: Docking and MCCE2 calculation data set

description: L-2-hydroxyglutarate production arises from non-canonical enzyme function at acidic pH<br>Contained within are input and output files for the docking and MCCE calculations performed accompanying the manuscript by Intlekofer et al.   <br>Inside the zip file, see the `Docking` folder for files used in the docking procedures. Docking was performed using Maestro as part of Schrodinger release 2015-3.  <br>See the `MCCE` folder for files used for the MCCE2 calculations for Lactate dehydrogenase A. MCCE calculations were performed using MCCE2 (https://sites.google.com/site/mccewiki/install-mcce).  Epik calculations were performed using Schrodinger release 2015-3.
DOI: 10.6084/m9.figshare.4289894.v2
title: Docking and MCCE2 calculations

description: Contained within are input and output files for the docking and MCCE calculations performed accompanying the manuscript by Intlekofer et al.   <br>Inside the zip file, see the `Docking` folder for files used in the docking procedures. Docking was performed using Maestro as part of Schrodinger release 2015-3.  <br>See the `MCCE` folder for files used for the MCCE2 calculations for Lactate dehydrogenase A. MCCE calculations were performed using MCCE2 (https://sites.google.com/site/mccewiki/install-mcce).  Epik calculations were performed using Schrodinger release 2015-3.
DOI: 10.6084/m9.figshare.4290950
title: Assessment of ethnic differences in sunitinib outcome between Caucasian and Asian patients with metastatic renal cell carcinoma: a meta-analysis

description: <b>Background:</b> An increasing number of studies have reported ethnic differences in sunitinib outcome in metastatic renal cell carcinoma (mRCC) patients. However, a comprehensive analysis is still lacking. Therefore, we systematically collected available published data and performed a meta-analysis to compare sunitinib efficacy and toxicity in Asian and Caucasian mRCC patients. <b>Methods:</b> Data were extracted from published results from clinical trials, expanded access program and real-world clinical practice. Progression-free survival (or time to tumor progression), overall survival, objective response rate and adverse events were used as endpoints to evaluate the differences of sunitinib outcome between the two ethnicities. For adverse events, we focused the following clinically relevant side effects: diarrhea, fatigue, mucositis/stomatitis, hand-foot syndrome, hypertension, leukopenia, neutropenia and thrombocytopenia. <b>Results:</b> A total of 33 publications including 9977 patients were available for meta-analysis. The efficacy of sunitinib in Asian patients was similar to that in Caucasian patients. However, Asian patients showed a higher incidence of all grades toxicity of hand-foot syndrome, &gt; grade 2 fatigue, &gt; grade 2 hand-foot syndrome and &gt; grade 2 thrombocytopenia. <b>Conclusion:</b> Ethnic differences in adverse events of sunitinib in mRCC patients existed and dose adjustment in Asian patients may be considered.
DOI: 10.6084/m9.figshare.4290950.v1
title: Assessment of ethnic differences in sunitinib outcome between Caucasian and Asian patients with metastatic renal cell carcinoma: a meta-analysis

description: <b>Background:</b> An increasing number of studies have reported ethnic differences in sunitinib outcome in metastatic renal cell carcinoma (mRCC) patients. However, a comprehensive analysis is still lacking. Therefore, we systematically collected available published data and performed a meta-analysis to compare sunitinib efficacy and toxicity in Asian and Caucasian mRCC patients. <b>Methods:</b> Data were extracted from published results from clinical trials, expanded access program and real-world clinical practice. Progression-free survival (or time to tumor progression), overall survival, objective response rate and adverse events were used as endpoints to evaluate the differences of sunitinib outcome between the two ethnicities. For adverse events, we focused the following clinically relevant side effects: diarrhea, fatigue, mucositis/stomatitis, hand-foot syndrome, hypertension, leukopenia, neutropenia and thrombocytopenia. <b>Results:</b> A total of 33 publications including 9977 patients were available for meta-analysis. The efficacy of sunitinib in Asian patients was similar to that in Caucasian patients. However, Asian patients showed a higher incidence of all grades toxicity of hand-foot syndrome, &gt; grade 2 fatigue, &gt; grade 2 hand-foot syndrome and &gt; grade 2 thrombocytopenia. <b>Conclusion:</b> Ethnic differences in adverse events of sunitinib in mRCC patients existed and dose adjustment in Asian patients may be considered.
DOI: 10.6084/m9.figshare.4291064
title: A novel role for 14-kDa phosphohistidine phosphatase in lamellipodia formation

description: Cell migration involves dynamic regulation of the actin cytoskeleton, which exhibits rapid actin polymerization at the leading edge of migrating cells. This process relies on regulated recruitment of actin nucleators and actin-binding proteins to the leading edge to polymerize new actin filaments. Many of these proteins have been identified, including the actin-related protein (Arp) 2/3 complex, which has emerged as the core player in the initiation of actin polymerization. However, the functional coordination of these proteins is unclear. Previously, we have demonstrated that the 14-kDa phosphohistidine phosphatase (PHP14) is involved in cell migration regulation and affects actin cytoskeleton reorganization. Here, we show that PHP14 may regulate actin remodeling directly and play an important role in dynamic regulation of the actin cytoskeleton. We observed a colocalization of PHP14 with Arp3 and F-actin at the leading edge of migrating cells. Moreover, PHP14 was recruited to the actin remodeling sites in parallel with Arp3 during lamellipodia formation. Furthermore, PHP14 knockdown impaired Arp3 localization at the leading edge of lamellipodia, as well as lamellipodia formation. Most importantly, we found that PHP14 was a novel F-actin-binding protein, displaying an Arp2/3-dependent localization to the leading edge. Collectively, our results indicated a crucial role for PHP14 in the dynamic regulation of the actin cytoskeleton and cell migration.
DOI: 10.6084/m9.figshare.4291064.v1
title: A novel role for 14-kDa phosphohistidine phosphatase in lamellipodia formation

description: Cell migration involves dynamic regulation of the actin cytoskeleton, which exhibits rapid actin polymerization at the leading edge of migrating cells. This process relies on regulated recruitment of actin nucleators and actin-binding proteins to the leading edge to polymerize new actin filaments. Many of these proteins have been identified, including the actin-related protein (Arp) 2/3 complex, which has emerged as the core player in the initiation of actin polymerization. However, the functional coordination of these proteins is unclear. Previously, we have demonstrated that the 14-kDa phosphohistidine phosphatase (PHP14) is involved in cell migration regulation and affects actin cytoskeleton reorganization. Here, we show that PHP14 may regulate actin remodeling directly and play an important role in dynamic regulation of the actin cytoskeleton. We observed a colocalization of PHP14 with Arp3 and F-actin at the leading edge of migrating cells. Moreover, PHP14 was recruited to the actin remodeling sites in parallel with Arp3 during lamellipodia formation. Furthermore, PHP14 knockdown impaired Arp3 localization at the leading edge of lamellipodia, as well as lamellipodia formation. Most importantly, we found that PHP14 was a novel F-actin-binding protein, displaying an Arp2/3-dependent localization to the leading edge. Collectively, our results indicated a crucial role for PHP14 in the dynamic regulation of the actin cytoskeleton and cell migration.
DOI: 10.6084/m9.figshare.4292465
title: Analysis of the intestinal microbial community and inferred functional capacities during the host response to <i>Pneumocystis</i> pneumonia

description: <b>Background:</b><i>Pneumocystis</i> pneumonia is a major cause of morbidity and mortality in patients infected with HIV/AIDS. In this study, we evaluated the intestinal microbial communities associated with the development of experimental <i>Pneumocystis</i> pneumonia, as there is growing evidence that the intestinal microbiota is critical for host defense against fungal pathogens. <b>Methods:</b> C57BL/6 mice were infected with live <i>Pneumocystis murina</i> (<i>P. murina</i>) via intratracheal inoculation and sacrificed 7 and 14 days postinfection for microbiota analysis. In addition, we evaluated the intestinal microbiota from CD4+ T cell depleted mice infected with <i>P. murina</i>. <b>Results:</b> We found that the diversity of the intestinal microbial community was significantly altered by respiratory infection with <i>P. murina</i>. Specifically, mice infected with <i>P. murina</i> had altered microbial populations, as judged by changes in diversity metrics and relative taxa abundances. We also found that CD4+ T cell depleted mice infected with <i>P. murina</i> exhibited significantly altered intestinal microbiota that was distinct from immunocompetent mice infected with <i>P. murina</i>, suggesting that loss of CD4+ T cells may also affects the intestinal microbiota in the setting of <i>Pneumocystis</i> pneumonia. Finally, we employed a predictive metagenomics approach to evaluate various microbial features. We found that <i>Pneumocystis</i> pneumonia significantly alters the intestinal microbiota's inferred functional potential for carbohydrate, energy, and xenobiotic metabolism, as well as signal transduction pathways. <b>Conclusions:</b> Our study provides insight into specific-microbial clades and inferred microbial functional pathways associated with <i>Pneumocystis</i> pneumonia. Our data also suggest a role for the gut-lung axis in host defense in the lung.
DOI: 10.6084/m9.figshare.4292465.v1
title: Analysis of the intestinal microbial community and inferred functional capacities during the host response to <i>Pneumocystis</i> pneumonia

description: <b>Background:</b><i>Pneumocystis</i> pneumonia is a major cause of morbidity and mortality in patients infected with HIV/AIDS. In this study, we evaluated the intestinal microbial communities associated with the development of experimental <i>Pneumocystis</i> pneumonia, as there is growing evidence that the intestinal microbiota is critical for host defense against fungal pathogens. <b>Methods:</b> C57BL/6 mice were infected with live <i>Pneumocystis murina</i> (<i>P. murina</i>) via intratracheal inoculation and sacrificed 7 and 14 days postinfection for microbiota analysis. In addition, we evaluated the intestinal microbiota from CD4+ T cell depleted mice infected with <i>P. murina</i>. <b>Results:</b> We found that the diversity of the intestinal microbial community was significantly altered by respiratory infection with <i>P. murina</i>. Specifically, mice infected with <i>P. murina</i> had altered microbial populations, as judged by changes in diversity metrics and relative taxa abundances. We also found that CD4+ T cell depleted mice infected with <i>P. murina</i> exhibited significantly altered intestinal microbiota that was distinct from immunocompetent mice infected with <i>P. murina</i>, suggesting that loss of CD4+ T cells may also affects the intestinal microbiota in the setting of <i>Pneumocystis</i> pneumonia. Finally, we employed a predictive metagenomics approach to evaluate various microbial features. We found that <i>Pneumocystis</i> pneumonia significantly alters the intestinal microbiota's inferred functional potential for carbohydrate, energy, and xenobiotic metabolism, as well as signal transduction pathways. <b>Conclusions:</b> Our study provides insight into specific-microbial clades and inferred microbial functional pathways associated with <i>Pneumocystis</i> pneumonia. Our data also suggest a role for the gut-lung axis in host defense in the lung.
DOI: 10.6084/m9.figshare.4293386
title: Integrated optimization of location assignment and sequencing in multi-shuttle automated storage and retrieval systems under modified 2<i>n</i>-command cycle pattern

description: This article explores the integrated optimization problem of location assignment and sequencing in multi-shuttle automated storage/retrieval systems under the modified 2<i>n</i>-command cycle pattern. The decision of storage and retrieval (S/R) location assignment and S/R request sequencing are jointly considered. An integer quadratic programming model is formulated to describe this integrated optimization problem. The optimal travel cycles for multi-shuttle S/R machines can be obtained to process S/R requests in the storage and retrieval request order lists by solving the model. The small-sized instances are optimally solved using CPLEX. For large-sized problems, two tabu search algorithms are proposed, in which the first come, first served and nearest neighbour are used to generate initial solutions. Various numerical experiments are conducted to examine the heuristics’ performance and the sensitivity of algorithm parameters. Furthermore, the experimental results are analysed from the viewpoint of practical application, and a parameter list for applying the proposed heuristics is recommended under different real-life scenarios.
DOI: 10.6084/m9.figshare.4299389
title: Long-Term Effects of Acute Stress on the Prefrontal-Limbic System in the Healthy Adult

description: Most
people are exposed to at least one traumatic event during the course of their lives, but large numbers of people do not develop
posttraumatic stress disorders. Although previous studies have shown that
repeated and chronic stress change the brain’s structure and function, few
studies have focused on the long-term
effects of acute
stressful exposure in a nonclinical sample,
especially the morphology and functional connectivity changes in brain regions
implicated in emotional reactivity and emotion regulation. Forty-one months
after the 5/12 Wenchuan earthquake, we investigated the effects of trauma exposure
on the structure and functional connectivity of the brains of trauma-exposed
healthy individuals compared with healthy controls matched for age, sex, and
education. We then used machine-learning algorithms with the brain structural
features to distinguish between the two groups at an individual level. In the trauma-exposed
healthy individuals, our results showed greater gray matter density in
prefrontal-limbic brain systems, including the dorsal anterior cingulate
cortex, medial prefrontal cortex, amygdala
and hippocampus, than in the controls. Further analysis showed stronger
amygdala-hippocampus functional connectivity in the trauma-exposed healthy
compared to the controls. Our findings revealed that survival of traumatic experiences, without developing
PTSD, was associated with greater gray matter density in the prefrontal-limbic
systems related to emotional regulation.
DOI: 10.6084/m9.figshare.4299389.v1
title: Long-Term Effects of Acute Stress on the Prefrontal-Limbic System in the Healthy Adult

description: Most
people are exposed to at least one traumatic event during the course of their lives, but large numbers of people do not develop
posttraumatic stress disorders. Although previous studies have shown that
repeated and chronic stress change the brain’s structure and function, few
studies have focused on the long-term
effects of acute
stressful exposure in a nonclinical sample,
especially the morphology and functional connectivity changes in brain regions
implicated in emotional reactivity and emotion regulation. Forty-one months
after the 5/12 Wenchuan earthquake, we investigated the effects of trauma exposure
on the structure and functional connectivity of the brains of trauma-exposed
healthy individuals compared with healthy controls matched for age, sex, and
education. We then used machine-learning algorithms with the brain structural
features to distinguish between the two groups at an individual level. In the trauma-exposed
healthy individuals, our results showed greater gray matter density in
prefrontal-limbic brain systems, including the dorsal anterior cingulate
cortex, medial prefrontal cortex, amygdala
and hippocampus, than in the controls. Further analysis showed stronger
amygdala-hippocampus functional connectivity in the trauma-exposed healthy
compared to the controls. Our findings revealed that survival of traumatic experiences, without developing
PTSD, was associated with greater gray matter density in the prefrontal-limbic
systems related to emotional regulation.