cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5629990.v2
title: Conserved and unique features of the fission yeast core Atg1 complex

description: Although the human ULK complex mediates phagophore initiation similar to the budding yeast <i>Saccharomyces cerevisiae</i> Atg1 complex, this complex contains ATG101 but not Atg29 and Atg31. Here, we analyzed the fission yeast <i>Schizosaccharomyces pombe</i> Atg1 complex, which has a subunit composition that resembles the human ULK complex. Our pairwise coprecipitation experiments showed that while the interactions between Atg1, Atg13, and Atg17 are conserved, Atg101 does not bind Atg17. Instead, Atg101 interacts with the HORMA domain of Atg13 and this enhances the stability of both proteins. We also found that <i>S. pombe</i> Atg17, the putative scaffold subunit, adopts a rod-shaped structure with no discernible curvature. Interestingly, <i>S. pombe</i> Atg17 binds <i>S. cerevisiae</i> Atg13, Atg29, and Atg31 in vitro, but it cannot complement the function of <i>S. cerevisiae</i> Atg17 in vivo. Furthermore, <i>S. pombe</i> Atg101 cannot substitute for the function of <i>S. cerevisiae</i> Atg29 and Atg31 in vivo. Collectively, our work generates new insights into the subunit organization and structural properties of an Atg101-containing Atg1/ULK complex.
DOI: 10.6084/m9.figshare.5629975
title: Nucleolin phosphorylation regulates PARN deadenylase activity during cellular stress response

description: Nucleolin (NCL) is an abundant stress-responsive, RNA-binding phosphoprotein that controls gene expression by regulating either mRNA stability and/or translation. NCL binds to the AU-rich element (ARE) in the 3′UTR of target mRNAs, mediates miRNA functions in the nearby target sequences, and regulates mRNA deadenylation. However, the mechanism by which NCL phosphorylation affects these functions and the identity of the deadenylase involved, remain largely unexplored. Earlier we demonstrated that NCL phosphorylation is vital for cell cycle progression and proliferation, whereas phosphorylation-deficient NCL at six consensus CK2 sites confers dominant-negative effect on proliferation by increasing p53 expression, possibly mimicking cellular DNA damage conditions. In this study, we show that NCL phosphorylation at those CK2 consensus sites in the N-terminus is necessary to induce deadenylation upon oncogenic stimuli and UV stress. NCL-WT, but not hypophosphorylated NCL-6/S*A, activates poly (A)-specific ribonuclease (PARN) deadenylase activity. We further demonstrate that NCL interacts directly with PARN, and under non-stress conditions also forms (a) complex (es) with factors that regulate deadenylation, such as p53 and the ARE-binding protein HuR. Upon UV stress, the interaction of hypophosphorylated NCL-6/S*A with these proteins is favored. As an RNA-binding protein, NCL interacts with PARN deadenylase substrates such as <i>TP53</i> and <i>BCL2</i> mRNAs, playing a role in their downregulation under non-stress conditions. For the first time, we show that NCL phosphorylation offers specificity to its protein-protein, protein-RNA interactions, resulting in the PARN deadenylase regulation, and hence gene expression, during cellular stress responses.
DOI: 10.6084/m9.figshare.5629990.v1
title: Conserved and unique features of the fission yeast core Atg1 complex

description: Although the human ULK complex mediates phagophore initiation similar to the budding yeast <i>Saccharomyces cerevisiae</i> Atg1 complex, this complex contains ATG101 but not Atg29 and Atg31. Here, we analyzed the fission yeast <i>Schizosaccharomyces pombe</i> Atg1 complex, which has a subunit composition that resembles the human ULK complex. Our pairwise coprecipitation experiments showed that while the interactions between Atg1, Atg13, and Atg17 are conserved, Atg101 does not bind Atg17. Instead, Atg101 interacts with the HORMA domain of Atg13 and this enhances the stability of both proteins. We also found that <i>S. pombe</i> Atg17, the putative scaffold subunit, adopts a rod-shaped structure with no discernible curvature. Interestingly, <i>S. pombe</i> Atg17 binds <i>S. cerevisiae</i> Atg13, Atg29, and Atg31 in vitro, but it cannot complement the function of <i>S. cerevisiae</i> Atg17 in vivo. Furthermore, <i>S. pombe</i> Atg101 cannot substitute for the function of <i>S. cerevisiae</i> Atg29 and Atg31 in vivo. Collectively, our work generates new insights into the subunit organization and structural properties of an Atg101-containing Atg1/ULK complex.
DOI: 10.6084/m9.figshare.5629975.v1
title: Nucleolin phosphorylation regulates PARN deadenylase activity during cellular stress response

description: Nucleolin (NCL) is an abundant stress-responsive, RNA-binding phosphoprotein that controls gene expression by regulating either mRNA stability and/or translation. NCL binds to the AU-rich element (ARE) in the 3′UTR of target mRNAs, mediates miRNA functions in the nearby target sequences, and regulates mRNA deadenylation. However, the mechanism by which NCL phosphorylation affects these functions and the identity of the deadenylase involved, remain largely unexplored. Earlier we demonstrated that NCL phosphorylation is vital for cell cycle progression and proliferation, whereas phosphorylation-deficient NCL at six consensus CK2 sites confers dominant-negative effect on proliferation by increasing p53 expression, possibly mimicking cellular DNA damage conditions. In this study, we show that NCL phosphorylation at those CK2 consensus sites in the N-terminus is necessary to induce deadenylation upon oncogenic stimuli and UV stress. NCL-WT, but not hypophosphorylated NCL-6/S*A, activates poly (A)-specific ribonuclease (PARN) deadenylase activity. We further demonstrate that NCL interacts directly with PARN, and under non-stress conditions also forms (a) complex (es) with factors that regulate deadenylation, such as p53 and the ARE-binding protein HuR. Upon UV stress, the interaction of hypophosphorylated NCL-6/S*A with these proteins is favored. As an RNA-binding protein, NCL interacts with PARN deadenylase substrates such as <i>TP53</i> and <i>BCL2</i> mRNAs, playing a role in their downregulation under non-stress conditions. For the first time, we show that NCL phosphorylation offers specificity to its protein-protein, protein-RNA interactions, resulting in the PARN deadenylase regulation, and hence gene expression, during cellular stress responses.
DOI: 10.6084/m9.figshare.5629972
title: The clinical benefit of hyperthermia in pancreatic cancer: a systematic review

description: <b>Objective:</b> In pancreatic cancer, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of radio(chemo)therapy. The aim of this systematic review is to investigate the validity of the hypothesis that hyperthermia added to radiotherapy and/or chemotherapy improves treatment outcome for pancreatic cancer patients. <b>Methods and materials:</b> We searched MEDLINE and Embase, supplemented by handsearching, for clinical studies involving hyperthermia in pancreatic cancer patients. The quality of studies was evaluated using the Oxford Centre for Evidence-Based Medicine levels of evidence. Primary outcome was treatment efficacy; we calculated overall response rate and the weighted estimate of the population median overall survival (<i>m<sub>p</sub></i>) and compared these between hyperthermia and control cohorts. <b>Results:</b> Overall, 14 studies were included, with 395 patients with locally advanced and/or metastatic pancreatic cancer of whom 248 received hyperthermia. Patients were treated with regional (<i>n</i> = 189), intraoperative (<i>n</i> = 39) or whole-body hyperthermia (<i>n</i> = 20), combined with chemotherapy, radiotherapy or both. Quality of the studies was low, with level of evidence 3 (five studies) and 4. The six studies including a control group showed a longer <i>m<sub>p</sub></i> in the hyperthermia groups than in the control groups (11.7 vs. 5.6 months). Overall response rate, reported in three studies with a control group, was also better for the hyperthermia groups (43.9% vs. 35.3%). <b>Conclusions:</b> Hyperthermia, when added to chemotherapy and/or radiotherapy, may positively affect treatment outcome for patients with pancreatic cancer. However, the quality of the reviewed studies was limited and future randomised controlled trials are needed to establish efficacy.
DOI: 10.6084/m9.figshare.5629972.v1
title: The clinical benefit of hyperthermia in pancreatic cancer: a systematic review

description: <b>Objective:</b> In pancreatic cancer, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of radio(chemo)therapy. The aim of this systematic review is to investigate the validity of the hypothesis that hyperthermia added to radiotherapy and/or chemotherapy improves treatment outcome for pancreatic cancer patients. <b>Methods and materials:</b> We searched MEDLINE and Embase, supplemented by handsearching, for clinical studies involving hyperthermia in pancreatic cancer patients. The quality of studies was evaluated using the Oxford Centre for Evidence-Based Medicine levels of evidence. Primary outcome was treatment efficacy; we calculated overall response rate and the weighted estimate of the population median overall survival (<i>m<sub>p</sub></i>) and compared these between hyperthermia and control cohorts. <b>Results:</b> Overall, 14 studies were included, with 395 patients with locally advanced and/or metastatic pancreatic cancer of whom 248 received hyperthermia. Patients were treated with regional (<i>n</i> = 189), intraoperative (<i>n</i> = 39) or whole-body hyperthermia (<i>n</i> = 20), combined with chemotherapy, radiotherapy or both. Quality of the studies was low, with level of evidence 3 (five studies) and 4. The six studies including a control group showed a longer <i>m<sub>p</sub></i> in the hyperthermia groups than in the control groups (11.7 vs. 5.6 months). Overall response rate, reported in three studies with a control group, was also better for the hyperthermia groups (43.9% vs. 35.3%). <b>Conclusions:</b> Hyperthermia, when added to chemotherapy and/or radiotherapy, may positively affect treatment outcome for patients with pancreatic cancer. However, the quality of the reviewed studies was limited and future randomised controlled trials are needed to establish efficacy.
DOI: 10.6084/m9.figshare.5629732
title: Data from: Do Diamond Firetails (Stagonopleura guttata) recognise the scent of their nest as other Estrildid finches do?

description: Raw data from: Do Diamond Firetails (Stagonopleura guttata) recognise the scent of their nest as other Estrildid finches do?
DOI: 10.6084/m9.figshare.5629732.v1
title: Data from: Do Diamond Firetails (Stagonopleura guttata) recognise the scent of their nest as other Estrildid finches do?

description: Raw data from: Do Diamond Firetails (Stagonopleura guttata) recognise the scent of their nest as other Estrildid finches do?
DOI: 10.15131/shef.data.5629204
title: Shifting Demand for Non Medical Services Evaluation Report

description: This evaluation looked at the feasibility and utility of a city-wide, brief intervention provided by community support workers to link people with non-medical issues to a range of services and support. The GP referral system effectively identified people at high risk of avoidable hospital admissions. Over 90% of patients referred received an assessment from a community support worker (CSW). The approach used by CSWs was consistent with the international evidence base for providing effective peer support. Clients initially self-reported reduced anxiety and social isolation. After being linked, however, there were delays in getting needs met, leading to disengagement and return to the high risk group. Effectiveness of the service is dependent upon the capacity and responsiveness of the sectors to which clients are referred.<br>
DOI: 10.6084/m9.figshare.5629207
title: Identifying the minimum number of microsatellite loci needed to assess population genetic structure: A case study in fly culturing

description: Small, isolated populations are constantly threatened by loss of genetic diversity due to drift. Such situations are found, for instance, in laboratory culturing. In guarding against diversity loss, monitoring of potential changes in population structure is paramount; this monitoring is most often achieved using microsatellite markers, which can be costly in terms of time and money when many loci are scored in large numbers of individuals. Here, we present a case study reducing the number of microsatellites to the minimum necessary to correctly detect the population structure of two <i>Drosophila nigrosparsa</i> populations. The number of loci was gradually reduced from 11 to 1, using the Allelic Richness (AR) and Private Allelic Richness (PAR) as criteria for locus removal. The effect of each reduction step was evaluated by the number of genetic clusters detectable from the data and by the allocation of individuals to the clusters; in the latter, excluding ambiguous individuals was tested to reduce the rate of incorrect assignments. We demonstrate that more than 95% of the individuals can still be correctly assigned when using eight loci and that the major population structure is still visible when using two highly polymorphic loci. The differences between sorting the loci by AR and PAR were negligible. The method presented here will most efficiently reduce genotyping costs when small sets of loci (“core sets”) for long-time use in large-scale population screenings are compiled.
DOI: 10.15131/shef.data.5629204.v1
title: Shifting Demand for Non Medical Services Evaluation Report

description: This evaluation looked at the feasibility and utility of a city-wide, brief intervention provided by community support workers to link people with non-medical issues to a range of services and support. The GP referral system effectively identified people at high risk of avoidable hospital admissions. Over 90% of patients referred received an assessment from a community support worker (CSW). The approach used by CSWs was consistent with the international evidence base for providing effective peer support. Clients initially self-reported reduced anxiety and social isolation. After being linked, however, there were delays in getting needs met, leading to disengagement and return to the high risk group. Effectiveness of the service is dependent upon the capacity and responsiveness of the sectors to which clients are referred.<br>
DOI: 10.6084/m9.figshare.5629207.v1
title: Identifying the minimum number of microsatellite loci needed to assess population genetic structure: A case study in fly culturing

description: Small, isolated populations are constantly threatened by loss of genetic diversity due to drift. Such situations are found, for instance, in laboratory culturing. In guarding against diversity loss, monitoring of potential changes in population structure is paramount; this monitoring is most often achieved using microsatellite markers, which can be costly in terms of time and money when many loci are scored in large numbers of individuals. Here, we present a case study reducing the number of microsatellites to the minimum necessary to correctly detect the population structure of two <i>Drosophila nigrosparsa</i> populations. The number of loci was gradually reduced from 11 to 1, using the Allelic Richness (AR) and Private Allelic Richness (PAR) as criteria for locus removal. The effect of each reduction step was evaluated by the number of genetic clusters detectable from the data and by the allocation of individuals to the clusters; in the latter, excluding ambiguous individuals was tested to reduce the rate of incorrect assignments. We demonstrate that more than 95% of the individuals can still be correctly assigned when using eight loci and that the major population structure is still visible when using two highly polymorphic loci. The differences between sorting the loci by AR and PAR were negligible. The method presented here will most efficiently reduce genotyping costs when small sets of loci (“core sets”) for long-time use in large-scale population screenings are compiled.
DOI: 10.6084/m9.figshare.5628619
title: Understanding concentrated insulins: a systematic review of randomized controlled trials

description: <b>Objective:</b> To compile, analyze, and summarize the literature on concentrated insulins (i.e. concentrations &gt;100 units/mL) from randomized controlled trials and derive guidance on appropriate use of these agents. <b>Methods:</b> Searches were conducted in Medline, Embase, the Cochrane Central Register of Controlled Trials, Trialtrove (through April 2016) and ClinicalTrials.gov (through April 2017) for phase 1–4 clinical studies using concentrated insulins. Selected studies included multiple-arm, randomized controlled trials evaluating subcutaneously administered concentrated insulins. Trial registration numbers (selected studies) were searched in Medline, Embase and Google Scholar (through April 2017). Late-phase studies were graded using guidance from the Agency for Healthcare Research and Quality. <b>Results:</b> Thirty-eight completed trials (7900 participants) and 34 qualifying publications were identified. Four marketed concentrated insulins were evaluated: two long-acting basal (insulin glargine 300 units/mL and insulin degludec 200 units/mL [IDeg200]), one rapid-acting prandial (insulin lispro 200 units/mL [ILis200]), and one prandial/basal (human regular insulin 500 units/mL). Early-phase trials established bioequivalence for IDeg200 and ILis200 with the corresponding 100 units/mL formulations. Efficacy studies showed noninferior glycemic control between comparators for long-acting basal and prandial/basal products with generally low severe hypoglycemia. Six additional concentrated insulins with completed early-phase development were also identified. <b>Conclusion:</b> Concentrated-insulin products demonstrated efficacious and safe outcomes in appropriate patients. Clinical findings (HbA1c and hypoglycemia) and methodology (initiation and titration), patient factors (insulin experience and dosing requirements) and treatment characteristics (bioequivalence, potency and device features) are important considerations. This overview of these and other factors provides essential information and guidance for using concentrated insulins in clinical practice.
DOI: 10.6084/m9.figshare.5628520
title: figshare_create_token.png

description: Götestam Skorpen, C. <i>et al</i>. Influence of disease activity and medications on offspring birth weight, pre-eclampsia and preterm birth in systemic lupus erythematosus: a population-based study. <i>Ann. Rheum. Dis.</i>
DOI: 10.6084/m9.figshare.5628619.v1
title: Understanding concentrated insulins: a systematic review of randomized controlled trials

description: <b>Objective:</b> To compile, analyze, and summarize the literature on concentrated insulins (i.e. concentrations &gt;100 units/mL) from randomized controlled trials and derive guidance on appropriate use of these agents. <b>Methods:</b> Searches were conducted in Medline, Embase, the Cochrane Central Register of Controlled Trials, Trialtrove (through April 2016) and ClinicalTrials.gov (through April 2017) for phase 1–4 clinical studies using concentrated insulins. Selected studies included multiple-arm, randomized controlled trials evaluating subcutaneously administered concentrated insulins. Trial registration numbers (selected studies) were searched in Medline, Embase and Google Scholar (through April 2017). Late-phase studies were graded using guidance from the Agency for Healthcare Research and Quality. <b>Results:</b> Thirty-eight completed trials (7900 participants) and 34 qualifying publications were identified. Four marketed concentrated insulins were evaluated: two long-acting basal (insulin glargine 300 units/mL and insulin degludec 200 units/mL [IDeg200]), one rapid-acting prandial (insulin lispro 200 units/mL [ILis200]), and one prandial/basal (human regular insulin 500 units/mL). Early-phase trials established bioequivalence for IDeg200 and ILis200 with the corresponding 100 units/mL formulations. Efficacy studies showed noninferior glycemic control between comparators for long-acting basal and prandial/basal products with generally low severe hypoglycemia. Six additional concentrated insulins with completed early-phase development were also identified. <b>Conclusion:</b> Concentrated-insulin products demonstrated efficacious and safe outcomes in appropriate patients. Clinical findings (HbA1c and hypoglycemia) and methodology (initiation and titration), patient factors (insulin experience and dosing requirements) and treatment characteristics (bioequivalence, potency and device features) are important considerations. This overview of these and other factors provides essential information and guidance for using concentrated insulins in clinical practice.
DOI: 10.6084/m9.figshare.5628520.v1
title: figshare_create_token.png

description: Götestam Skorpen, C. <i>et al</i>. Influence of disease activity and medications on offspring birth weight, pre-eclampsia and preterm birth in systemic lupus erythematosus: a population-based study. <i>Ann. Rheum. Dis.</i>
DOI: 10.6084/m9.figshare.5627710
title: MCMCglmm Model Parameters from Hovering in the heat: effects of environmental temperature on heat regulation in foraging hummingbirds

description: Phylogenetic MCMCglmm model of the effects of ambient temperature on whole-body and HDA surface temperature.
DOI: 10.6084/m9.figshare.5627710.v1
title: MCMCglmm Model Parameters from Hovering in the heat: effects of environmental temperature on heat regulation in foraging hummingbirds

description: Phylogenetic MCMCglmm model of the effects of ambient temperature on whole-body and HDA surface temperature.
DOI: 10.6084/m9.figshare.5627665
title: Supplementary Table 2 from Distribution, composition and functions of gelatinous tissues in deep-sea fishes

description: Depth ranges for representative taxa. Ranges taken from FishBase (Froese & Pauly, 2017).
DOI: 10.6084/m9.figshare.5627665.v1
title: Supplementary Table 2 from Distribution, composition and functions of gelatinous tissues in deep-sea fishes

description: Depth ranges for representative taxa. Ranges taken from FishBase (Froese & Pauly, 2017).
DOI: 10.6084/m9.figshare.5627590
title: Dataset for: Maturation in Auditory Event-Related Potentials Explains Variation in Language Ability in Children

description: Processing of auditory information in the cortex continues to develop into later childhood and adolescence. Recent research has indicated that intraclass correlation (ICC) is the best method for capturing maturation in auditory event-related potentials (AEPs) of school-age children. However, the sensitivity of the ICC approach in discerning AEP changes in children has not been consistently demonstrated and positive results have not been replicated. We attempted this replication and further explored whether AEP maturation estimated using the ICC approach predicts cognitive and linguistic abilities in addition to chronological age. We measured AEPs in response to simple tones in groups of 7, 8, 9, and 10 year olds with typical development (N = 67), and used ICC to estimate the age equivalent of each child's AEP (AEP-age). Results indicated that ICC differentiated 7-8- from 9-10-year-old children, and that AEP-age predicted both chronological age and significant, unique variance in language ability, but not in nonverbal IQ. Our findings support the view that auditory organization in children reflects both general developmental maturation and more specific development of language skills, and support the future use of AEP-age to identify and understand individual differences in brain maturation in typically developing and clinical populations.