cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.4738600.v1
title: BRCA1 recruitment to damaged DNA sites is dependent on CDK9

description: Double strand break lesions, the most toxic type of DNA damage, are repaired primarily through 2 distinct pathways: homology-directed recombination (HR) and non-homologous end-joining (NHEJ). BRCA1 and 53BP1, 2 proteins containing the BRCT modular domain, play an important role in DNA damage response (DDR) by orchestrating the decision between HR and NHEJ, but the precise mechanisms regarding both pathways are not entirely understood. Previously, our group identified a putative interaction between BRCA1 and BARD1 (BRCA1-associated RING domain 1) and the cyclin-dependent kinase (CDK9). CDK9 is a component of the positive transcription elongation complex and has been implicated in genome integrity maintenance associated with the replication stress response. Here we show that CDK9 interacts with endogenous BRCA1 and BARD1 mediated by their RING finger and BRCT domains, and describe CDK9 ionizing radiation-induced foci (IRIF) formation and its co-localization with BRCA1 in DNA damage sites. Cells lacking CDK9 are characterized by an altered γ−H2AX foci dynamics after DNA damage, a reduced efficiency in HR but not in NHEJ repair, failure to form BRCA1 and RAD51 IRIF and increased sensitivity to genotoxic agents. These data indicate that CDK9 is a player in the DDR and is consistent with its participation in HR pathway by modulating BRCA1 response.
DOI: 10.6084/m9.figshare.4738594.v1
title: Suppression of the grainyhead transcription factor 2 gene (GRHL2) inhibits the proliferation, migration, invasion and mediates cell cycle arrest of ovarian cancer cells

description: Previously, we have identified the Grainyhead transcription factor 2 gene (GRHL2) as notably hypomethylated in high-grade (HG) serous epithelial ovarian tumors, compared with normal ovarian tissues. GRHL2 is known for its functions in normal tissue development and wound healing. In the context of cancer, the role of GRHL2 is still ambiguous as both tumorigenic and tumor suppressive functions have been reported for this gene, although a role of GRHL2 in maintaining the epithelial status of cancer cells has been suggested. In this study, we report that GRHL2 is strongly overexpressed in both low malignant potential (LMP) and HG serous epithelial ovarian tumors, which probably correlates with its hypomethylated status. Suppression of the GRHL2 expression led to a sharp decrease in cell proliferation, migration and invasion and induced G1 cell cycle arrest in epithelial ovarian cancer (EOC) cells displaying either epithelial (A2780s) or mesenchymal (SKOV3) phenotypes. However, no phenotypic alterations were observed in these EOC cell lines following GRHL2 silencing. Gene expression profiling and consecutive canonical pathway and network analyses confirmed these data, as in both these EOC cell lines, GRHL2 ablation was associated with the downregulation of various genes and pathways implicated in cell growth and proliferation, cell cycle control and cellular metabolism. Taken together, our data are indicative for a strong oncogenic potential of the GRHL2 gene in EOC progression and support recent findings on the role of GRHL2 as one of the major phenotypic stability factors (PSFs) that stabilize the highly aggressive/metastatic hybrid epithelial/mesenchymal (E/M) phenotype of cancer cells.
DOI: 10.6084/m9.figshare.4738591
title: Molecular binding mechanism of 5-hydroxy-1-methylpiperidin-2-one with human serum albumin

description: Molecular binding mechanism of 5-hydroxy-1-methylpiperidin-2-one with human serum albumin
DOI: 10.6084/m9.figshare.4738570
title: Regression Using Pairs vs. Regression on Differences: A Real-life Case Study for a Master's Level Methods Class

description: When teaching regression classes real-life examples help emphasize the importance of understanding theoretical concepts related to methodologies. This can be appreciated after a little reflection on the difficulty of constructing novel questions in regression that test on concepts rather than mere calculations. Interdisciplinary collaborations can be fertile contexts for questions of this type. In this article, we offer a case study that students will find: (1) practical with respect to the question being addressed, (2) compelling in the way it shows how a solid understanding of theory helps answer the question, and (3) enlightening in the way it shows how statisticians contribute to problem solving in interdisciplinary environments. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.4738570.v1
title: Regression Using Pairs vs. Regression on Differences: A Real-life Case Study for a Master's Level Methods Class

description: When teaching regression classes real-life examples help emphasize the importance of understanding theoretical concepts related to methodologies. This can be appreciated after a little reflection on the difficulty of constructing novel questions in regression that test on concepts rather than mere calculations. Interdisciplinary collaborations can be fertile contexts for questions of this type. In this article, we offer a case study that students will find: (1) practical with respect to the question being addressed, (2) compelling in the way it shows how a solid understanding of theory helps answer the question, and (3) enlightening in the way it shows how statisticians contribute to problem solving in interdisciplinary environments. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.4738549
title: Human liver epigenetic alterations in non-alcoholic steatohepatitis are related to insulin action

description: Both genetic and lifestyle factors contribute to the risk of non-alcoholic steatohepatitis (NASH). Additionally, epigenetic modifications may also play a key role in the pathogenesis of NASH. We therefore investigated liver DNA methylation, as a marker for epigenetic alterations, in individuals with simple steatosis and NASH, and further tested if these alterations were associated with clinical phenotypes. Liver biopsies obtained from 95 obese individuals (age: 49.5 ± 7.7 years, BMI: 43 ± 5.7 kg/m<sup>2</sup>, type 2 diabetes [T2D]: 35) as a wedge biopsy during a Roux-en-Y gastric bypass operation were investigated. Thirty-four individuals had a normal liver phenotype, 35 had simple steatosis, and 26 had NASH. Genome-wide DNA methylation pattern was analyzed using the Infinium HumanMethylation450 BeadChip. mRNA expression was analyzed from 42 individuals using the HumanHT-12 Expression BeadChip. We identified 1,292 CpG sites representing 677 unique genes differentially methylated in liver of individuals with NASH (q &lt; 0.001), independently of T2D, age, sex, and BMI. Focusing on the top-ranking 30 and another 37 CpG sites mapped to genes enriched in pathways of metabolism (q = 0.0036) and cancer (q = 0.0001) all together, 59 NASH-associated CpG sites correlated with fasting insulin levels independently of age, fasting glucose, or T2D. From these, we identified 30 correlations between DNA methylation and mRNA expression, for example <i>LDHB</i> (r = −0.45, <i>P</i> = 0.003). We demonstrated that NASH, more than simple steatosis, associates with differential DNA methylation in the human liver. These epigenetic alterations in NASH are linked with insulin metabolism.
DOI: 10.6084/m9.figshare.4738546
title: Targeted DNA demethylation in human cells by fusion of a plant 5-methylcytosine DNA glycosylase to a sequence-specific DNA binding domain

description: DNA methylation is a crucial epigenetic mark associated to gene silencing, and its targeted removal is a major goal of epigenetic editing. In animal cells, DNA demethylation involves iterative 5mC oxidation by TET enzymes followed by replication-dependent dilution and/or replication-independent DNA repair of its oxidized derivatives. In contrast, plants use specific DNA glycosylases that directly excise 5mC and initiate its substitution for unmethylated C in a base excision repair process. In this work, we have fused the catalytic domain of <i>Arabidopsis</i> ROS1 5mC DNA glycosylase (ROS1_CD) to the DNA binding domain of yeast GAL4 (GBD). We show that the resultant GBD-ROS1_CD fusion protein binds specifically a GBD-targeted DNA sequence <i>in vitro</i>. We also found that transient <i>in vivo</i> expression of GBD-ROS1_CD in human cells specifically reactivates transcription of a methylation-silenced reporter gene, and that such reactivation requires both ROS1_CD catalytic activity and GBD binding capacity. Finally, we show that reactivation induced by GBD-ROS1_CD is accompanied by decreased methylation levels at several CpG sites of the targeted promoter. All together, these results show that plant 5mC DNA glycosylases can be used for targeted active DNA demethylation in human cells.
DOI: 10.6084/m9.figshare.4738549.v1
title: Human liver epigenetic alterations in non-alcoholic steatohepatitis are related to insulin action

description: Both genetic and lifestyle factors contribute to the risk of non-alcoholic steatohepatitis (NASH). Additionally, epigenetic modifications may also play a key role in the pathogenesis of NASH. We therefore investigated liver DNA methylation, as a marker for epigenetic alterations, in individuals with simple steatosis and NASH, and further tested if these alterations were associated with clinical phenotypes. Liver biopsies obtained from 95 obese individuals (age: 49.5 ± 7.7 years, BMI: 43 ± 5.7 kg/m<sup>2</sup>, type 2 diabetes [T2D]: 35) as a wedge biopsy during a Roux-en-Y gastric bypass operation were investigated. Thirty-four individuals had a normal liver phenotype, 35 had simple steatosis, and 26 had NASH. Genome-wide DNA methylation pattern was analyzed using the Infinium HumanMethylation450 BeadChip. mRNA expression was analyzed from 42 individuals using the HumanHT-12 Expression BeadChip. We identified 1,292 CpG sites representing 677 unique genes differentially methylated in liver of individuals with NASH (q &lt; 0.001), independently of T2D, age, sex, and BMI. Focusing on the top-ranking 30 and another 37 CpG sites mapped to genes enriched in pathways of metabolism (q = 0.0036) and cancer (q = 0.0001) all together, 59 NASH-associated CpG sites correlated with fasting insulin levels independently of age, fasting glucose, or T2D. From these, we identified 30 correlations between DNA methylation and mRNA expression, for example <i>LDHB</i> (r = −0.45, <i>P</i> = 0.003). We demonstrated that NASH, more than simple steatosis, associates with differential DNA methylation in the human liver. These epigenetic alterations in NASH are linked with insulin metabolism.
DOI: 10.6084/m9.figshare.4738522
title: Vascular plant one-zinc-finger protein 2 is localized both to the nucleus and stress granules under heat stress in <i>Arabidopsis</i>

description: VASCULAR PLANT ONE-ZINC FINGER (VOZ)1/and VOZ2 have an ability to bind to the specific <i>cis</i>-element in the <i>AVP1</i> promoter of <i>Arabidopsis</i>, which function on the PhyB-dependent flowering and possibly in various stress responses as potential transcription factors, although nuclear localization of VOZ proteins is still unclear. In this study, we found that VOZ2 is dispersed throughout the cytoplasm under normal growth conditions, whereas VOZ2 is transferred not only to the nucleus but also to the cytoplasmic foci under heat stress conditions. The VOZ2 foci predominantly co-localized with a marker of stress granules (SGs), which were cytoplasmic granular structures for mRNA storage and decay under abiotic stress conditions. We also demonstrated that GFP-VOZ2 with a nuclear localization signal was rapidly degraded via the ubiquitin/proteasome pathway under the heat stress conditions. Also, stress-related expression of <i>DREB2A</i> in the <i>voz1voz2</i> mutant was significantly upregulated by heat stress as compared with that in the wild-type <i>Arabidopsis</i>. Our results suggest that VOZ2 is localized to SGs and nucleus under heat stress conditions, and functions as a transcriptional repressor of <i>DREB2A</i> in <i>Arabidopsis</i>.
DOI: 10.6084/m9.figshare.4738522.v1
title: Vascular plant one-zinc-finger protein 2 is localized both to the nucleus and stress granules under heat stress in <i>Arabidopsis</i>

description: VASCULAR PLANT ONE-ZINC FINGER (VOZ)1/and VOZ2 have an ability to bind to the specific <i>cis</i>-element in the <i>AVP1</i> promoter of <i>Arabidopsis</i>, which function on the PhyB-dependent flowering and possibly in various stress responses as potential transcription factors, although nuclear localization of VOZ proteins is still unclear. In this study, we found that VOZ2 is dispersed throughout the cytoplasm under normal growth conditions, whereas VOZ2 is transferred not only to the nucleus but also to the cytoplasmic foci under heat stress conditions. The VOZ2 foci predominantly co-localized with a marker of stress granules (SGs), which were cytoplasmic granular structures for mRNA storage and decay under abiotic stress conditions. We also demonstrated that GFP-VOZ2 with a nuclear localization signal was rapidly degraded via the ubiquitin/proteasome pathway under the heat stress conditions. Also, stress-related expression of <i>DREB2A</i> in the <i>voz1voz2</i> mutant was significantly upregulated by heat stress as compared with that in the wild-type <i>Arabidopsis</i>. Our results suggest that VOZ2 is localized to SGs and nucleus under heat stress conditions, and functions as a transcriptional repressor of <i>DREB2A</i> in <i>Arabidopsis</i>.
DOI: 10.6084/m9.figshare.4738375
title: Deuterium dilution technique for body composition assessment: resolving methodological issues in children with moderate acute malnutrition

description: Childhood malnutrition is highly prevalent and associated with high mortality risk. In observational and interventional studies among malnourished children, body composition is increasingly recognised as a key outcome. The deuterium dilution technique has generated high-quality data on body composition in studies of infants and young children in several settings, but its feasibility and accuracy in children suffering from moderate acute malnutrition requires further study. Prior to a large nutritional intervention trial among children with moderate acute malnutrition, we conducted pilot work to develop and adapt the deuterium dilution technique. We refined procedures for administration of isotope doses and collection of saliva. Furthermore, we established that equilibration time in local context is 3 h. These findings and the resulting standard operating procedures are important to improve data quality when using the deuterium dilution technique in malnutrition studies in field conditions, and may encourage a wider use of isotope techniques.
DOI: 10.6084/m9.figshare.4738375.v1
title: Deuterium dilution technique for body composition assessment: resolving methodological issues in children with moderate acute malnutrition

description: Childhood malnutrition is highly prevalent and associated with high mortality risk. In observational and interventional studies among malnourished children, body composition is increasingly recognised as a key outcome. The deuterium dilution technique has generated high-quality data on body composition in studies of infants and young children in several settings, but its feasibility and accuracy in children suffering from moderate acute malnutrition requires further study. Prior to a large nutritional intervention trial among children with moderate acute malnutrition, we conducted pilot work to develop and adapt the deuterium dilution technique. We refined procedures for administration of isotope doses and collection of saliva. Furthermore, we established that equilibration time in local context is 3 h. These findings and the resulting standard operating procedures are important to improve data quality when using the deuterium dilution technique in malnutrition studies in field conditions, and may encourage a wider use of isotope techniques.
DOI: 10.5281/zenodo.4011906
title: Structural role of essential light chains in the apicomplexan glideosome models

description: Presented here are the modelled structures of TgMyoA motor and neck domain bound to MLC1 and TgELC1 or TgELC2. 10 complexes: 5 with TgELC1 5 with TgELC2 In these complexes: TgELC1/2 has chain label A MLC1 has chain label B TgMyoA has chain label C All models contain hydrogens All complexes were energy minimized (1000 steps) in explicit solvent Details of the modeling procedure in the main text of the associated paper
DOI: 10.6084/m9.figshare.4738156
title: Stroke rehabilitation evidence and comorbidity: a systematic scoping review of randomized controlled trials

description: <b>Background</b>: Most strokes occur in the context of other medical diagnoses. Currently, stroke rehabilitation evidence reviews have not synthesized or presented evidence with a focus on comorbidities and correspondingly may not align with current patient population. The purpose of this review was to determine the extent and nature of randomized controlled trial stroke rehabilitation evidence that included patients with multimorbidity. <b>Methods</b>: A systematic scoping review was conducted. Electronic databases were searched using a combination of terms related to “stroke” and “rehabilitation.” Selection criteria captured inpatient rehabilitation studies. Methods were modified to account for the amount of literature, classified by study design, and randomized controlled trials (RCTs) were abstracted. <b>Results</b>: The database search yielded 10771 unique articles. Screening resulted in 428 included RCTs. Three studies explicitly included patients with a comorbid condition. Fifteen percent of articles did not specify additional conditions that were excluded. Impaired cognition was the most commonly excluded condition. Approximately 37% of articles excluded patients who had experienced a previous stroke. Twenty-four percent excluded patients one or more Charlson Index condition, and 83% excluded patients with at least one other medical condition. <b>Conclusions</b>: This review represents a first attempt to map literature on stroke rehabilitation related to co/multimorbidity and identify gaps in existing research. Existing evidence on stroke rehabilitation often excluded individuals with comorbidities. This is problematic as the evidence that is used to generate clinical guidelines may not match the patient typically seen in practice. The use of alternate research methods are therefore needed for studying the care of individuals with stroke and multimorbidity.
DOI: 10.6084/m9.figshare.4738156.v1
title: Stroke rehabilitation evidence and comorbidity: a systematic scoping review of randomized controlled trials

description: <b>Background</b>: Most strokes occur in the context of other medical diagnoses. Currently, stroke rehabilitation evidence reviews have not synthesized or presented evidence with a focus on comorbidities and correspondingly may not align with current patient population. The purpose of this review was to determine the extent and nature of randomized controlled trial stroke rehabilitation evidence that included patients with multimorbidity. <b>Methods</b>: A systematic scoping review was conducted. Electronic databases were searched using a combination of terms related to “stroke” and “rehabilitation.” Selection criteria captured inpatient rehabilitation studies. Methods were modified to account for the amount of literature, classified by study design, and randomized controlled trials (RCTs) were abstracted. <b>Results</b>: The database search yielded 10771 unique articles. Screening resulted in 428 included RCTs. Three studies explicitly included patients with a comorbid condition. Fifteen percent of articles did not specify additional conditions that were excluded. Impaired cognition was the most commonly excluded condition. Approximately 37% of articles excluded patients who had experienced a previous stroke. Twenty-four percent excluded patients one or more Charlson Index condition, and 83% excluded patients with at least one other medical condition. <b>Conclusions</b>: This review represents a first attempt to map literature on stroke rehabilitation related to co/multimorbidity and identify gaps in existing research. Existing evidence on stroke rehabilitation often excluded individuals with comorbidities. This is problematic as the evidence that is used to generate clinical guidelines may not match the patient typically seen in practice. The use of alternate research methods are therefore needed for studying the care of individuals with stroke and multimorbidity.
DOI: 10.6084/m9.figshare.4738153
title: Cost effectiveness of the occupation-based approach for subacute stroke patients: result of a randomized controlled trial

description: <b>Background and purpose:</b> The cost effectiveness of occupational therapy for subacute stroke patients is unclear in the extant literature. Consequently, this study determined the cost effectiveness of the occupation-based approach using Aid for Decision-Making in Occupation Choice (ADOC) for subacute stroke patients compared with an impairment-based approach. <b>Methods:</b> We conducted an economic evaluation from a societal perspective alongside a pilot randomized controlled trial, with a single blind assessor for participants in 10 subacute rehabilitation units in Japan. The intervention group received occupation-based goal setting using ADOC, with interventions focused on meaningful occupations. The control group received an impairment-based approach focused on restoring capacities. For both groups, occupational-therapy intervention was administered more than five times per week, for over 40 min each time, and they received physical and speech therapy prior to discharge. The main outcomes were quality-adjusted life years (QALYs) and total costs. Further, sensitivity analyses were performed to examine the influence of parameter uncertainty on the base case results. <b>Results:</b> The final number of participants was 24 in each of the two groups. In terms of QALYs, the intervention group is significantly higher than the control group (<i>p</i> = 0.001, difference 95% CI: 0.002–0.008) and total costs are not statistically significant. Applying a willingness-to-pay threshold of JPY 5 million/QALY, the probability of the occupation-based approach using ADOC being cost effective was estimated to be 65.3%. <b>Conclusions:</b> The results show that the occupation-based approach is associated with significantly improved QALYs and has potential cost effectiveness, compared with the impairment-based approach.