cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5122747.v1
title: Supplementary Material for: Updated Neuronal Scaling Rules for the Brains of Glires (Rodents/Lagomorphs)

description: Brain size scales as different functions of its number of neurons across mammalian orders such as rodents, primates, and insectivores. In rodents, we have previously shown that, across a sample of 6 species, from mouse to capybara, the cerebral cortex, cerebellum and the remaining brain structures increase in size faster than they gain neurons, with an accompanying decrease in neuronal density in these structures [Herculano-Houzel et al.: Proc Natl Acad Sci USA 2006;103:12138–12143]. Important remaining questions are whether such neuronal scaling rules within an order apply equally to all pertaining species, and whether they extend to closely related taxa. Here, we examine whether 4 other species of Rodentia, as well as the closely related rabbit (Lagomorpha), conform to the scaling rules identified previously for rodents. We report the updated neuronal scaling rules obtained for the average values of each species in a way that is directly comparable to the scaling rules that apply to primates [Gabi et al.: Brain Behav Evol 2010;76:32–44], and examine whether the scaling relationships are affected when phylogenetic relatedness in the dataset is accounted for. We have found that the brains of the spiny rat, squirrel, prairie dog and rabbit conform to the neuronal scaling rules that apply to the previous sample of rodents. The conformity to the previous rules of the new set of species, which includes the rabbit, suggests that the cellular scaling rules we have identified apply to rodents in general, and probably to Glires as a whole (rodents/lagomorphs), with one notable exception: the naked mole-rat brain is apparently an outlier, with only about half of the neurons expected from its brain size in its cerebral cortex and cerebellum.
DOI: 10.6084/m9.figshare.5122756.v1
title: Supplementary Material for: Topoisomerase Mutations That Are Associated with High-Level Resistance to Earlier Fluoroquinolones in <i>Staphylococcus aureus</i> Have Less Effect on the Antibacterial Activity of Besifloxacin

description: <i>Background:</i> The impact of mutations in DNA gyrase and topoisomerase IV on minimum inhibitory concentrations (MICs) was investigated to better understand why besifloxacin has a higher potency against <i>Staphylococcus aureus</i> when compared to other fluoroquinolones, which was especially pronounced against ciprofloxacin-resistant isolates. <i>Methods:</i> MICs were determined for 52 clinical isolates against besifloxacin, moxifloxacin, gatifloxacin, ciprofloxacin, and levofloxacin. The genes encoding GyrA, GyrB, ParC, and ParE were sequenced and the potential impact of mutations assessed in light of recent structural data. <i>Results:</i> For all fluoroquinolones tested, the MICs increased with the number of mutations in the quinolone resistance-determining regions. However, this increase was the smallest for besifloxacin and the largest for ciprofloxacin and levofloxacin. In addition to the commonly observed mutations in ParC and GyrA, more unusual mutations in ParE, such as Asp-432→His or Pro-585→Ser, were also detected. <i>Conclusions:</i> Compared to earlier fluoroquinolones, the higher potency of besifloxacin suggests that the drug’s unique combination of a 7-azepinyl ring and an 8-chloro-substituent results in unique interactions with DNA gyrase and topoisomerase IV.
DOI: 10.6084/m9.figshare.5122741
title: Supplementary Material for: Hyperpolarization-Activated Cation Current Contributes to Spontaneous Network Activity in Developing Neocortical Cultures

description: The mechanisms underlying spontaneous burst activity (SBA), appearing in networks of embryonic cortical neurons at the end of the first week in vitro, remain elusive. Here we investigated the contribution of the hyperpolarization-activated cation current (I<sub>h</sub>) to SBA in cortical cultures of GAD67-GFP mice. I<sub>h</sub> current could be detected in GFP-positive large GABAergic interneurons (L-INs) and glutamatergic principal neurons (PNs) as early as DIV 5. Under current-clamp conditions, blockers of I<sub>h</sub> current, ZD7288 and Cs<sup>+</sup>, abolished the voltage sag and rebound depolarization. ZD7288 induced a hyperpolarization concomitant with an increase in the membrane input resistance in L-INs and PNs. Voltage-clamp recordings revealed I<sub>h</sub> as slowly activating inward current with a reversal potential close to –50 mV and a mid-activation point around –90 mV. Both, ZD7288 (1–10 µ<i>M</i>) and Cs<sup>+</sup> (1–2 m<i>M</i>) reduced SBA, spontaneous activity-driven Ca<sup>2+</sup> transients, and frequency as well as amplitude of miniature GABAergic postsynaptic currents. Immunocytochemistry and Western blot demonstrated that HCN1 and HCN2 were the prevalent isoforms of HCN channels expressed in L-INs and PNs. These results suggest an important contribution of HCN channels to the maintenance of SBA in embryonic cortical cultures.
DOI: 10.6084/m9.figshare.5122732
title: Supplementary Material for: Analysis of FOXG1 Is Highly Recommended in Male and Female Patients with Rett Syndrome

description: We screened a cohort of 5 male and 20 female patients with a Rett spectrum disorder for mutations in the coding region of <i>FOXG1</i>, previously shown to cause the congenital variant of Rett syndrome. Two de novo mutations were identified. The first was a novel missense mutation, p.Ala193Thr (c.577G&gt;A), in a male patient with congenital Rett syndrome, and the second was the p.Glu154GlyfsX301 (c.460dupG) truncating mutation in a female with classical Rett syndrome, a mutation that was previously reported in an independent patient. The overall rate of <i>FOXG1</i> mutations in our cohort is 8%. Our findings stress the importance of <i>FOXG1</i> analysis in male patients with Rett syndrome and in female patients when mutations in the <i>MECP2</i> and <i>CDKL5 </i>genes have been excluded.
DOI: 10.6084/m9.figshare.5122738
title: Supplementary Material for: Overexpression of GDF5 through an Adenovirus Vector Stimulates Osteogenesis of Human Mesenchymal Stem Cells in vitro and in vivo

description: The use of stem cells combined with gene therapy could be an important way to facilitate bone regeneration. In this study, the aim was to investigate the potential of growth and differentiation factor-5 (GDF5) to genetically manipulate human mesenchymal stem cells (hMSCs) for bone regeneration. Recombinant adenovirus Ad-GDF5 and Ad-GFP were constructed and identified, and the titer of both were determined. Third-passage hMSCs were infected with adenovirus, and the expression of GDF5 was confirmed by detection of GFP-positive cells, GDF5 mRNA levels, Western blotting, and enzyme-linked immunosorbent assay (ELISA). hMSCs at passage 3 were divided into four groups: (1) an experimental group infected with Ad-GDF5, (2) a positive control group cultured with osteogenic differentiation medium, (3) a control group infected with Ad-GFP cultured with standard medium, and (4) a blank control group cultured with standard medium. Evaluation of cell morphology and proliferation, analysis of the expression of genes related to osteogenic differentiation, von Kossa staining, and immunofluorescent staining of collagen I were used to investigate the osteogenesis of cells among the groups. After culturing the cells for 2 days under each corresponding condition, the cells were detached and subcutaneously injected into the backs of nude mice to evaluate bone formation. Samples were collected for histological staining, protein Western blotting, and micro-computer tomography. When infected with Ad-GDF5, hMSCs could overexpress GDF5 for a prolonged period in vitro and reach a concentration of 160 ng/ml. Cells infected with Ad-GDF5 or cultured in osteogenic medium displayed osteogenic differentiation based on their histological and cellular properties and on their gene and protein expression patterns. Furthermore, Ad-GDF5 showed a better ability to upregulate the expression of collagen I, alkaline phosphatase, and osteocalcin mRNA than the osteogenic medium. Furthermore, Ad-GDF5 expression was associated with enhanced bone formation in vivo. Our findings suggest that hMSCs infected with Ad-GDF5 can differentiate in an osteogenic direction and may be a promising cell source for bone regeneration.
DOI: 10.6084/m9.figshare.5122741.v1
title: Supplementary Material for: Hyperpolarization-Activated Cation Current Contributes to Spontaneous Network Activity in Developing Neocortical Cultures

description: The mechanisms underlying spontaneous burst activity (SBA), appearing in networks of embryonic cortical neurons at the end of the first week in vitro, remain elusive. Here we investigated the contribution of the hyperpolarization-activated cation current (I<sub>h</sub>) to SBA in cortical cultures of GAD67-GFP mice. I<sub>h</sub> current could be detected in GFP-positive large GABAergic interneurons (L-INs) and glutamatergic principal neurons (PNs) as early as DIV 5. Under current-clamp conditions, blockers of I<sub>h</sub> current, ZD7288 and Cs<sup>+</sup>, abolished the voltage sag and rebound depolarization. ZD7288 induced a hyperpolarization concomitant with an increase in the membrane input resistance in L-INs and PNs. Voltage-clamp recordings revealed I<sub>h</sub> as slowly activating inward current with a reversal potential close to –50 mV and a mid-activation point around –90 mV. Both, ZD7288 (1–10 µ<i>M</i>) and Cs<sup>+</sup> (1–2 m<i>M</i>) reduced SBA, spontaneous activity-driven Ca<sup>2+</sup> transients, and frequency as well as amplitude of miniature GABAergic postsynaptic currents. Immunocytochemistry and Western blot demonstrated that HCN1 and HCN2 were the prevalent isoforms of HCN channels expressed in L-INs and PNs. These results suggest an important contribution of HCN channels to the maintenance of SBA in embryonic cortical cultures.
DOI: 10.6084/m9.figshare.5122735
title: Supplementary Material for: AUC-RF: A New Strategy for Genomic Profiling with Random Forest

description: <i>Objective:</i> Genomic profiling, the use of genetic variants at multiple loci simultaneously for the prediction of disease risk, requires the selection of a set of genetic variants that best predicts disease status. The goal of this work was to provide a new selection algorithm for genomic profiling. <i>Methods:</i> We propose a new algorithm for genomic profiling based on optimizing the area under the receiver operating characteristic curve (AUC) of the random forest (RF). The proposed strategy implements a backward elimination process based on the initial ranking of variables. <i>Results and Conclusions:</i> We demonstrate the advantage of using the AUC instead of the classification error as a measure of predictive accuracy of RF. In particular, we show that the use of the classification error is especially inappropriate when dealing with unbalanced data sets. The new procedure for variable selection and prediction, namely AUC-RF, is illustrated with data from a bladder cancer study and also with simulated data. The algorithm is publicly available as an R package, named AUCRF, at http://cran.r-project.org/.
DOI: 10.6084/m9.figshare.5122726
title: Supplementary Material for: Beta-Arrestin2 as a Competitor for GRK2 Interaction with the GLP-1 Receptor upon Receptor Activation

description: The signaling of seven transmembrane receptors/G-protein- coupled receptors (GPCRs) is regulated by a number of receptor interacting proteins, including βarrestins (βarrs) and GPCR kinases (GRKs). In the present report, we have analyzed the interaction pattern between the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), βarr2, and GRK2 using bioluminescence resonance energy transfer assays. We found that βarr2 interacts with the GLP-1R in a biphasic manner with a phosphorylation-independent and a phosphorylation-dependent component. In competition experiments, we observed βarr2 competing with GRK2 for interaction with GLP-1R. We propose a model were βarr2 competes with GRK2 for interaction with the activated and GRK phosphorylated GLP-1R, suggesting a new role of βarr2 in regulating the orchestration of GRK2 functionality.
DOI: 10.6084/m9.figshare.5122735.v1
title: Supplementary Material for: AUC-RF: A New Strategy for Genomic Profiling with Random Forest

description: <i>Objective:</i> Genomic profiling, the use of genetic variants at multiple loci simultaneously for the prediction of disease risk, requires the selection of a set of genetic variants that best predicts disease status. The goal of this work was to provide a new selection algorithm for genomic profiling. <i>Methods:</i> We propose a new algorithm for genomic profiling based on optimizing the area under the receiver operating characteristic curve (AUC) of the random forest (RF). The proposed strategy implements a backward elimination process based on the initial ranking of variables. <i>Results and Conclusions:</i> We demonstrate the advantage of using the AUC instead of the classification error as a measure of predictive accuracy of RF. In particular, we show that the use of the classification error is especially inappropriate when dealing with unbalanced data sets. The new procedure for variable selection and prediction, namely AUC-RF, is illustrated with data from a bladder cancer study and also with simulated data. The algorithm is publicly available as an R package, named AUCRF, at http://cran.r-project.org/.
DOI: 10.6084/m9.figshare.5122720
title: Supplementary Material for: Plasma Phospholipid Long-Chain n-3 Polyunsaturated Fatty Acids and Body Weight Change

description: <i>Objective:</i> We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. <i>Method:</i> A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. <i>Results:</i> The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was –0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: –20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. <i>Conclusion:</i> The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population.
DOI: 10.6084/m9.figshare.5122723
title: Supplementary Material for: Die Bedeutung des Schamempfindens in einzelnen Diagnosegruppen unter Berücksichtigung der Körperscham

description: <i>Hintergrund:</i> Schamgefühle wurden trotz ihrer Relevanz in der bisherigen Psychotherapieforschung vernachlässigt. Dies zeigt sich an den wenigen vorhandenen Forschungsarbeiten und der überwiegend einseitigen Ausrichtung der Forschung zu dispositionellen Aspekten des Schamempfindens. Um die Komplexität dieses Affekts besser abdecken zu können, untersucht die vorliegende Studie die Auswirkungen des aktuellen Schamempfindens und der dispositionellen Schamneigung auf die psychotherapeutische Behandlung in Abhängigkeit von Diagnosegruppen. Bislang gibt es keine empirischen Nachweise zu der Frage, ob einzelne Diagnosegruppen in der ambulanten psychotherapeutischen Behandlung stärker mit Schamgefühlen assoziiert sind als andere. <i>Patienten und Methoden:</i> In einer Fragebogenstudie wurden 273 ambulant behandelte Patienten mit der Experience of Shame Scale (ESS) und dem Test of Self-Conscious Affects (TOSCA) untersucht. Gleichzeitig wurden die Diagnose im Rahmen der Therapie und die subjektive Einschätzung der Schamrelevanz erfasst. Die so gewonnenen Daten wurden mittels Varianzanalyse verglichen, um mögliche Unterschiede im Schamerleben in den einzelnen Diagnosegruppen aufzeigen zu können. <i>Ergebnisse:</i> Obwohl die Mehrheit der Patienten der Bearbeitung von Schamgefühlen eine hohe Relevanz beimisst, unterscheiden sie sich nicht bezüglich der überdauernden Scham- und Schulddisposition, wohl aber im aktuellen Schamerleben. Hier sind es insbesondere Patienten mit einer diagnostizierten Essstörung, die sich in einzelnen Schambereichen – insbesondere Charakterscham und Körperscham – von den anderen Diagnosegruppen unterscheiden. <i>Schlussfolgerungen:</i> In der Erforschung von Schamgefühlen erscheint es wichtig, neben der überdauernden Schamneigung auch unterschiedliche Aspekte des aktuellen Schamerlebens zu berücksichtigen und in die Behandlung mit einzubeziehen. Die Reduktion auf ein globales Konstrukt wird diesem komplexen Affekt in seiner psychotherapeutischen Relevanz nicht gerecht.
DOI: 10.6084/m9.figshare.5122729
title: Supplementary Material for: Signaling via Dopamine D1 and D3 Receptors Oppositely Regulates Cocaine-Induced Structural Remodeling of Dendrites and Spines

description: Repeated exposure to cocaine can induce persistent alterations in the brain. The structural remodeling of dendrites and dendritic spines is thought to play a critical role in cocaine addiction. We previously demonstrated that signaling via dopamine D1 and D3 receptors have opposite effects on cocaine-induced gene expression. Here, we show that cocaine-induced structural remodeling in the nucleus accumbens (NAc) and caudoputamen (CPu) is mediated by D1 receptors and inhibited by D3 receptors. In addition, chronic exposure to cocaine results in an altered number of asymmetric spine synapses via the actions of both D1 and D3 receptors. The contradictory effects of D1 and D3 receptor signaling on cocaine-induced structural remodeling is associated with NMDA-receptor R1 subunit (NR1) phosphorylation, and is dependent upon the activation of extracellular signal-regulated kinase (ERK). In addition, we found that D1 and D3 receptor signaling has contradictory effects upon the activation of the myocyte enhancer factor 2 (MEF2), which is involved in the dendritic remodeling after cocaine treatment. Together, these data suggest that dopamine D1 and D3 receptors differentially regulate the cocaine-induced structural remodeling of dendrites and spines via mechanisms involving the consecutive actions of NR1 phosphorylation, ERK activation, and MEF2 activity in the NAc and CPu.
DOI: 10.6084/m9.figshare.5122717
title: Supplementary Material for: Antiproteinuric Effect of Chemokine C-C Motif Ligand 2 Inhibition in Subjects with Acute Proliferative Lupus Nephritis

description: <i>Background/Aims:</i> To test the role of chemokine C-C motif ligand 2 (CCL2) in the pathogenesis of lupus nephritis (LN), we evaluated the effects of CCL2 inhibition by bindarit therapy in patients with systemic lupus and active renal disease. <i>Methods:</i> In this proof-of-concept, prospective, randomized, double-blind clinical study, 22 subjects with acute LN were assigned on a 1:1 ratio to 24-week treatment with bindarit (1,200 mg/day) or matching placebo. All subjects were on the same standardized steroid background therapy. Urinary CCL2, urinary albumin excretion (UAE), estimated glomerular filtration rate, time to remission and time to relapse of LN were compared between groups. <i>Results:</i> Urinary CCL2 significantly decreased during bindarit therapy (p = 0.008 vs. baseline) with a reduction that approximated 50% at study end. CCL2 reduction was paralleled by a persistent reduction in UAE that averaged 80% vs. baseline and approximated 90% at study end. Renal function recovery was similar and no difference was found in terms of time to remission and time to relapse of LN between treatment arms. Treatment was safe and well tolerated in all patients. <i>Conclusion:</i> In lupus subjects with active nephritis, bindarit significantly reduced albuminuria and urinary CCL2 levels. This study provides the background for longer trials to test renoprotective effect of CCL2 inhibition in LN.
DOI: 10.6084/m9.figshare.5122720.v1
title: Supplementary Material for: Plasma Phospholipid Long-Chain n-3 Polyunsaturated Fatty Acids and Body Weight Change

description: <i>Objective:</i> We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. <i>Method:</i> A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. <i>Results:</i> The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was –0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: –20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. <i>Conclusion:</i> The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population.
DOI: 10.6084/m9.figshare.5122723.v1
title: Supplementary Material for: Die Bedeutung des Schamempfindens in einzelnen Diagnosegruppen unter Berücksichtigung der Körperscham

description: <i>Hintergrund:</i> Schamgefühle wurden trotz ihrer Relevanz in der bisherigen Psychotherapieforschung vernachlässigt. Dies zeigt sich an den wenigen vorhandenen Forschungsarbeiten und der überwiegend einseitigen Ausrichtung der Forschung zu dispositionellen Aspekten des Schamempfindens. Um die Komplexität dieses Affekts besser abdecken zu können, untersucht die vorliegende Studie die Auswirkungen des aktuellen Schamempfindens und der dispositionellen Schamneigung auf die psychotherapeutische Behandlung in Abhängigkeit von Diagnosegruppen. Bislang gibt es keine empirischen Nachweise zu der Frage, ob einzelne Diagnosegruppen in der ambulanten psychotherapeutischen Behandlung stärker mit Schamgefühlen assoziiert sind als andere. <i>Patienten und Methoden:</i> In einer Fragebogenstudie wurden 273 ambulant behandelte Patienten mit der Experience of Shame Scale (ESS) und dem Test of Self-Conscious Affects (TOSCA) untersucht. Gleichzeitig wurden die Diagnose im Rahmen der Therapie und die subjektive Einschätzung der Schamrelevanz erfasst. Die so gewonnenen Daten wurden mittels Varianzanalyse verglichen, um mögliche Unterschiede im Schamerleben in den einzelnen Diagnosegruppen aufzeigen zu können. <i>Ergebnisse:</i> Obwohl die Mehrheit der Patienten der Bearbeitung von Schamgefühlen eine hohe Relevanz beimisst, unterscheiden sie sich nicht bezüglich der überdauernden Scham- und Schulddisposition, wohl aber im aktuellen Schamerleben. Hier sind es insbesondere Patienten mit einer diagnostizierten Essstörung, die sich in einzelnen Schambereichen – insbesondere Charakterscham und Körperscham – von den anderen Diagnosegruppen unterscheiden. <i>Schlussfolgerungen:</i> In der Erforschung von Schamgefühlen erscheint es wichtig, neben der überdauernden Schamneigung auch unterschiedliche Aspekte des aktuellen Schamerlebens zu berücksichtigen und in die Behandlung mit einzubeziehen. Die Reduktion auf ein globales Konstrukt wird diesem komplexen Affekt in seiner psychotherapeutischen Relevanz nicht gerecht.