cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5121736
title: Supplementary Material for: Common Variants Near <i>MC4R:</i> Exploring Gender Effects in Overweight and Obese Children and Adolescents Participating in a Lifestyle Intervention

description: <i>Objective:</i> Association with obesity and increased insulin levels have been reported for two variants (rs17782313 and rs12970134) located downstream of the melanocortin-4 receptor gene <i>(MC4R)</i>. <i>Methods:</i> We investigated whether these variants have sex-specific effects on overweight, obesity and 14 related phenotypes in 889 overweight and obese children and adolescents. We also explored the impact of the variants on weight change in 367 of the 889 cases who participated in an intervention program. Prior to these analyses we showed that both variants were associated with overweight/obesity in the analyzed 889 cases versus 442 normal-weight and lean controls (case-control study). Results: In explorative analyses we observed higher diastolic blood pressure levels in males (rs17782313: β = 2.52 mm Hg per risk allele; p = 0.003) but reduced blood pressure level in females for the same risk allele (β = –1.72 mm Hg; p = 0.039). We also detected a greater BMI standard deviation score (BMI-SDS) reduction in females with the risk allele at rs17782313 (β = 0.086 per risk allele; p = 0.021). Additionally, we observed evidence for an association of the same risk allele with insulin levels (β = 0.029 log (µU/ml); p = 0.044) with no sex-specific effect. For the remaining 11 phenotypes, we observed no evidence for a (sex-specific) association. <i>Conclusions:</i> In sum, our data support the associations of variants rs17782313 and rs12970134 near <i>MC4R</i> with early onset obesity and increased insulin levels. Exploratory evidence for sex-specific effects of the risk alleles were observed for diastolic blood pressure and BMI-SDS reduction.
DOI: 10.6084/m9.figshare.5121739.v1
title: Supplementary Material for: Differential Kidney Proteome Profiling in a Murine Model of Renal Fibrosis under Treatment with Mycophenolate Mofetil

description: <i>Aim:</i> The aim of this study was to investigate the effect of mycophenolate mofetil (MMF) using differential kidney proteome profiling of COL4A3-deficient mice as a model of progressive renal disease. <i>Methods:</i> Histological evaluation of kidney sections was performed. Total protein lysate from kidneys of placebo- and MMF-treated COL4A3-deficient mice was studied for significant differences in protein abundance using 2-dimensional electrophoresis and mass spectrometry. <i>Results:</i> While tubulointerstitial fibrosis in COL4A3-deficient mice was inhibited by MMF, 19 proteins in the kidneys were regulated: 12 with lower (ATPO, TAGL2, CAH1, TPD52, VA0D1, SERPH, GNAL, PSB6, EF1D, OTUB1, NDUS8, and NAPSA) and 7 with higher (ACADM, ACY3, CK054, ACTB/G, ACTB, UBP5, and ACY1) spot intensity. Nine differentially expressed proteins showed interaction potential (ATPO, TPD52, PSB6, EF1D, OTUB1, NAPSA, ACTB, ACTG, and UBP5). <i>Conclusions:</i> The identified proteins take part in different signaling pathways. With the highest probability, the VEGF signaling pathway (TAGL2, EF1D, and ACTB) and hypoxia (CAH1, PSB6, and ACTG) were influenced by MMF in fibrotic conditions. Moreover, MMF may modulate antifibrotic and apoptotic pathways as well as epithelial-mesenchymal transition (EMT). Different signaling pathways may be influenced by MMF therapy. These results suggest an inhibitory effect of MMF on renal EMT in COL4A3-deficient mice. Further studies are necessary to validate these findings.
DOI: 10.6084/m9.figshare.5121727
title: Supplementary Material for: Role of <i>CcpA</i> in Polyhydroxybutyrate Biosynthesis in a Newly Isolated <i>Bacillus</i> sp. MA3.3

description: The <i>ccpA</i> gene was inactivated in the polyhydroxybutyrate (PHB)-producing strain <i>Bacillus</i> sp. MA3.3 in order to reduce glucose catabolite repression over pentoses and develop improved bacterial strains for the production of PHB from lignocellulosic hydrolysates. Mutant <i>Bacillus</i> sp. MSL7 ΔCcpA are unable to grow on glucose and ammonia as sole carbon and nitrogen sources, respectively. Supplementation of glutamate as the nitrogen source or the substitution of the carbon source by xylose allowed the mutant to partially recover its growth performance. RT-PCR showed that CcpA stimulates the expression of the operon (<i>gltAB)</i>,responsible for ammonia assimilation via glutamate in <i>Bacillus </i>sp. MA3.3. Moreover, it was demonstrated that the supplementation of xylose or glutamate was capable of stimulating <i>gltAB</i> operon expression independently of CcpA. In PHB production experiments in mineral media, it has been observed that the glucose catabolite repression over the pentoses was partially released in MSL7. Although the carbohydrate consumption is faster in the <i>ccpA</i> mutant, the biomass and PHB biosynthesis are lower, even with supplementation of glutamate. This is attributed to an increase of acetyl-CoA flux towards the tricarboxylic acid cycle observed in the mutant.
DOI: 10.6084/m9.figshare.5121733.v1
title: Supplementary Material for: The Type I Inositol 1,4,5-Trisphosphate Receptor Interacts with Protein 4.1N to Mediate Neurite Formation through Intracellular Ca<sup>2+</sup> Waves

description: Ca<sup>2+</sup> waves are an important mechanism for encoding Ca<sup>2+</sup> signaling information, but the molecular basis for wave formation and how this regulates neuronal function is not entirely understood. Using nerve growth factor-differentiated PC12 cells as a model system, we investigated the interaction between the type I inositol 1,4,5-trisphosphate receptor (IP3R1) and the cytoskeletal linker, protein 4.1N, to examine the relationship between Ca<sup>2+</sup> wave formation and neurite development. This was examined using RNAi and overexpressed dominant negative binding regions of each protein. Confocal microscopy was used to monitor neurite formation and Ca<sup>2+</sup> waves. Knockdown of IP3R1 or 4.1N attenuated neurite formation, as did binding regions of IP3R1 and 4.1N, which colocalized with endogenous 4.1N and IP3R1, respectively. Upon stimulation with the IP3-producing agonist carbachol, both RNAi and dominant negative molecules shifted signaling events from waves to homogeneous patterns of Ca<sup>2+</sup> release. These findings provide evidence that IP3R1 localization, via protein 4.1N, is necessary for Ca<sup>2+</sup> wave formation, which in turn mediates neurite formation.
DOI: 10.6084/m9.figshare.5121745.v1
title: Supplementary Material for: Conserved although Very Different Karyotypes in Gliridae and Sciuridae and Their Contribution to Chromosomal Signatures in Glires

description: Rodents represent the largest order of living mammals. It comprises 5 sub-orders, among which Sciuromorpha (Sciuridae, Gliridae and Aplodontiidae) are assumed to occupy a basal position in rodent evolution. Banded karyotypes of some representatives of the Sciuridae family have been compared to each other, and comparisons with man were performed using chromosome paintings. Sciuridae karyotypes have conserved several eutherian ancestral syntenies. Like Sciuridae, Gliridae possess some chromosomes easily comparable with those of Primates. Comparisons of Gliridae and Sciuridae chromosomes with those of the presumed eutherian ancestor provide information about their chromosomal evolution and their position among Rodentia. Although both Sciuridae and Gliridae karyotypes are relatively conserved, they display many differences, indicating their early divergence. The reconstruction of their chromosomal evolution allowed us to propose the composition of their presumed ancestral karyotypes, with 2n = 48 and 2n = 38 for Gliridae and Sciuridae, respectively. Since rodent emergence, a single rearrangement is common to these 2 families. It formed a chromosome with fragments homologous to human chromosomes 4-8p-4-12-22, not detected in other rodents, and thus characteristic for the Sciuromorpha. This allowed us to reassess the chromosomal signatures of Rodentia. Finally, we show that the speed of chromosomal evolution in Gliridae is intermediate between that of Sciuridae (low) and Muridae (high).
DOI: 10.6084/m9.figshare.5121724
title: Supplementary Material for: Analysis of Sexually Dimorphic Expression of Genes at Early Gonadogenesis of Pejerrey <i>Odontesthes bonariensis</i> Using a Heterologous Microarray

description: The process of morphological development of a differentiated gonad from an undifferentiated primordium is a very important step of gonadogenesis. Studies on sexually dimorphic gene expression are important to increase our understanding of this process and to investigate how environmental factors such as temperature can regulate gonadal development. The aim of this study was to identify putative genes involved in sex differentiation in pejerrey <i>(Odontesthes bonariensis) </i>reared at male- and female-producing temperatures (MPT and FPT, respectively) using a microarray heterologous from the medaka <i>(Oryzias latipes)</i>, a closely phylogenetic species. Genes related to numerous processes presented higher expression at MPT, including those involved in muscular contraction, metabolic pathways, developmental processes, and reproduction. Genes induced by FPT were classified under the gene ontology terms of response to stimulus, transport and proteolysis. From genes selected for validation, at MPT <i>ndrg3</i> expression was observed in the somatic cells, whereas <i>pen-2</i> was detected in germ cells in the caudal portion of the gonads, where no apoptotic signals were observed. Finally, <i>hsp90</i> was highly expressed in somatic cells of the gonads at the FPT. The results suggest that the interplay of pro-apoptotic and anti-apoptotic genes is important during the masculinization process and for the prevention of sterility following exposure to warm temperatures.
DOI: 10.6084/m9.figshare.5121730
title: Supplementary Material for: Evolution of Patchily Distributed Proteins Shared between Eukaryotes and Prokaryotes: <i>Dictyostelium</i> as a Case Study

description: Protein families are often patchily distributed in the tree of life; they are present in distantly related organisms, but absent in more closely related lineages. This could either be the result of lateral gene transfer between ancestors of organisms that encode them, or losses in the lineages that lack them. Here a novel approach is developed to study the evolution of patchily distributed proteins shared between prokaryotes and eukaryotes. Proteins encoded in the genome of cellular slime mold <i>Dictyostelium discoideum</i> and a restricted number of other lineages, including at least one prokaryote, were identified. Analyses of the phylogenetic distribution of 49 such patchily distributed protein families showed conflicts with organismal phylogenies; 25 are shared with the distantly related amoeboflagellate <i>Naegleria</i> (Excavata), whereas only two are present in the more closely related <i>Entamoeba</i>. Most protein families show unexpected topologies in phylogenetic analyses; eukaryotes are polyphyletic in 85% of the trees. These observations suggest that gene transfers have been an important mechanism for the distribution of patchily distributed proteins across all domains of life. Further studies of this exchangeable gene fraction are needed for a better understanding of the origin and evolution of eukaryotic genes and the diversification process of eukaryotes.
DOI: 10.6084/m9.figshare.5121736.v1
title: Supplementary Material for: Common Variants Near <i>MC4R:</i> Exploring Gender Effects in Overweight and Obese Children and Adolescents Participating in a Lifestyle Intervention

description: <i>Objective:</i> Association with obesity and increased insulin levels have been reported for two variants (rs17782313 and rs12970134) located downstream of the melanocortin-4 receptor gene <i>(MC4R)</i>. <i>Methods:</i> We investigated whether these variants have sex-specific effects on overweight, obesity and 14 related phenotypes in 889 overweight and obese children and adolescents. We also explored the impact of the variants on weight change in 367 of the 889 cases who participated in an intervention program. Prior to these analyses we showed that both variants were associated with overweight/obesity in the analyzed 889 cases versus 442 normal-weight and lean controls (case-control study). Results: In explorative analyses we observed higher diastolic blood pressure levels in males (rs17782313: β = 2.52 mm Hg per risk allele; p = 0.003) but reduced blood pressure level in females for the same risk allele (β = –1.72 mm Hg; p = 0.039). We also detected a greater BMI standard deviation score (BMI-SDS) reduction in females with the risk allele at rs17782313 (β = 0.086 per risk allele; p = 0.021). Additionally, we observed evidence for an association of the same risk allele with insulin levels (β = 0.029 log (µU/ml); p = 0.044) with no sex-specific effect. For the remaining 11 phenotypes, we observed no evidence for a (sex-specific) association. <i>Conclusions:</i> In sum, our data support the associations of variants rs17782313 and rs12970134 near <i>MC4R</i> with early onset obesity and increased insulin levels. Exploratory evidence for sex-specific effects of the risk alleles were observed for diastolic blood pressure and BMI-SDS reduction.
DOI: 10.6084/m9.figshare.5121727.v1
title: Supplementary Material for: Role of <i>CcpA</i> in Polyhydroxybutyrate Biosynthesis in a Newly Isolated <i>Bacillus</i> sp. MA3.3

description: The <i>ccpA</i> gene was inactivated in the polyhydroxybutyrate (PHB)-producing strain <i>Bacillus</i> sp. MA3.3 in order to reduce glucose catabolite repression over pentoses and develop improved bacterial strains for the production of PHB from lignocellulosic hydrolysates. Mutant <i>Bacillus</i> sp. MSL7 ΔCcpA are unable to grow on glucose and ammonia as sole carbon and nitrogen sources, respectively. Supplementation of glutamate as the nitrogen source or the substitution of the carbon source by xylose allowed the mutant to partially recover its growth performance. RT-PCR showed that CcpA stimulates the expression of the operon (<i>gltAB)</i>,responsible for ammonia assimilation via glutamate in <i>Bacillus </i>sp. MA3.3. Moreover, it was demonstrated that the supplementation of xylose or glutamate was capable of stimulating <i>gltAB</i> operon expression independently of CcpA. In PHB production experiments in mineral media, it has been observed that the glucose catabolite repression over the pentoses was partially released in MSL7. Although the carbohydrate consumption is faster in the <i>ccpA</i> mutant, the biomass and PHB biosynthesis are lower, even with supplementation of glutamate. This is attributed to an increase of acetyl-CoA flux towards the tricarboxylic acid cycle observed in the mutant.
DOI: 10.6084/m9.figshare.5121718
title: Supplementary Material for: Risk of Macrovascular Complications in Type 2 Diabetes Mellitus: Endothelial Microparticle Profiles

description: <i>Background:</i> While the adverse impact of diabetes on microvessels is well known, the risks of macroangiopathy are less well recognized. Here, we determine the differential risk and endothelial microparticle (EMP) profile of vascular complications in type 2 diabetes mellitus. <i>Methods:</i> Macroangiopathy was evaluated for cerebrovascular disease, coronary artery disease and peripheral artery disease; microangiopathy was evaluated for retinopathy, nephropathy and peripheral neuropathy. Clinical and laboratory factors were compared among 149 patients with no vascular complications or with microangiopathic and/or macroangiopathic complications. EMPs were also examined by flow cytometry using CD31, CD42b, annexin V (AV), and CD62E antibodies in the peripheral blood of patients. <i>Results:</i> Diabetes of long duration, an elevated hemoglobin A1c (HbA1c) and concomitant hypertension were significantly associated with the occurrence of vascular complications. Dyslipidemia and a high body mass index were significantly associated with macroangiopathy, while diabetes of long duration and a high concentration of HbA1c were associated with microangiopathy. The EMP (CD31+/CD42b–, CD31+/AV+) levels were higher in patients with macroangiopathy than in patients with microangiopathy and no complications. The EMP level was also independently associated with macroangiopathy in diabetic patients. <i>Conclusions:</i> Microangiopathy and macroangiopathy in diabetic patients appear to have a different pathophysiological basis. The measurement of EMP would be helpful to differentiate the risk of diabetic vascular complications.
DOI: 10.6084/m9.figshare.5121706
title: Supplementary Material for: Therapieeffekte und Responder-Analysen bei Patientinnen mit Essstörungen: Eine naturalistische Studie

description: <i>Hintergrund:</i> Es gibt bisher einige kontrolliert randomisierte Studien (RCTs), die die Wirksamkeit der kognitiven Verhaltenstherapie (KVT) bei Essstörungen belegen, aber kaum Befunde über Effektstärken unter Praxisbedingungen. Da aber die überwiegende Anzahl ambulanter Psychotherapien bei Essstörungen in der Routineversorgung durchgeführt wird, erscheinen gerade hierfür Wirksamkeitsnachweise notwendig. <i>Patienten und Methode:</i> Die Stichprobe bestand aus 123 Frauen, die als Hauptdiagnose eine Essstörung gemä&zslig; dem Diagnostischen und Statistischen Manual Psychischer Störungen (DSM-IV) aufwiesen. Alle erhielten eine Manual-orientierte essstörungsspezifische KVT. Outcome-Maße bildeten Skalen des Eating Disorder Inventory-2 (EDI-2), des Brief Symptom Inventorys (BSI) und das Beck-Depressionsinventar (BDI). Es wurden Effektstärken berechnet und Responder- sowie Remissionsanalysen durchgeführt. Die Berechnungen wurden sowohl anhand der Intention-to-Treat (ITT)- als auch der Completer-Stichprobe (Completer) dargestellt. Ergebnisse: Auf den Essstörungsskalen zeigten sich Verbesserungen mit Effektstärken nach Cohen zwischen d = 0,50 bis d = 1,59 (ITT) und d = 0,34 bis d = 2,53 (Completer). Die störungsübergreifenden Outcome-Maße des BDI und BSI wiesen Werte von d = 0,89 bis d = 1,08 (BDI-ITT) sowie d = 0,65 bis d = 0,82 (Global Severity Index (GSI)-ITT) auf. Die Responder-Raten lagen für Patientinnen mit Anorexia nervosa bei 48,1%, mit Bulimia nervosa bei 50,8% und mit Essstörung nicht näher bezeichnet (NNB) bei 47,1%. <i>Schlussfolgerungen:</i> In der vorliegenden naturalistischen Studie ließen sich ähnliche, teilweise bessere Effektstärken als in RCTs hinsichtlich der Wirksamkeit der KVT bei Essstörungen finden. Es werden die Vergleichbarkeit der Ergebnisse mit RCTs sowie therapeutische Implikationen unter besonderer Beachtung von Unterschieden zwischen einzelnen Essstörungsformen diskutiert.
DOI: 10.6084/m9.figshare.5121709
title: Supplementary Material for: Überprüfung des aktuellen Stressbewältigungsverhaltens bulimischer Frauen in einer sozialen Interaktion

description: <i>Hintergrund:</i> Frühere Studien zeigten ein dysfunktionales Stressbewältigungsverhalten für Frauen mit Essstörungen. Insbesondere ein geringeres Maß an problem- und ein erhöhtes Maß an emotions- und vermeidungsorientiertem Stressbewältigungsverhalten im Vergleich zu Gesunden wurde beschrieben. Die meisten Untersuchungen fokussierten dabei auf habituelles Coping, während die Untersuchung von aktuellem, situationsbezogenem Coping bisweilen aussteht. Unklar ist zudem, inwieweit aktuelles, situationsbezogenes Coping durch das Selbstwertgefühl, dysfunktionale Einstellungen und Alexithymie beeinflusst wird. <i>Methode:</i> Mittels des Stress-Verarbeitungs-Fragebogens 42-aktuell (SVF 42-ak) wurde das aktuelle Stressbewältigungsverhalten bei 26 Frauen mit Bulimia nervosa (BN) und 27 weiblichen Personen einer Kontrollgruppe (KG) in einem sozial ambivalenten Rollenspiel untersucht. Der Einfluss des Selbstwerts (Rosenberg Selfesteem Scale, RSS), dysfunktionaler Einstellungen (Dysfunctional Attitude Scale, DAS) und von Schwierigkeiten der Emotionswahrnehmung (Toronto Alexithymia Scale, TAS) auf das aktuelle Coping wurde überprüft. <i>Ergebnisse:</i> Die BN-Gruppe zeigte im Vergleich zur KG-Gruppe ein erhöhtes Maß an aktuellem, emotionalen Coping (d = 1,96). Im problem- (d = 0,31) und vermeidungsorientierten Coping (d = 0,27) ergaben sich keine Unterschiede. Der Selbstwert als Hauptprädiktor klärte in der Regressionsanalyse nahezu 70% (R2 = 0,676) der Varianz des emotionalen Copings auf und korrelierte signifikant mit dem Grad dysfunktionaler Einstellungen (r = –0,791) und Alexithymie (r = –0,782). <i>Schlussfolgerung:</i> Die Ergebnisse sprechen für einen übergeordneten Einfluss des Selbstwerts auf das aktuelle Coping.
DOI: 10.6084/m9.figshare.5121712
title: Supplementary Material for: Gamma-1-Syntrophin Mediates Trafficking of Gamma-Enolase towards the Plasma Membrane and Enhances Its Neurotrophic Activity

description: Syntrophins are scaffold proteins that can bind several signaling molecules and localize them to the plasma membrane. We demonstrate here that in neuroblastoma SH-SY5Y cells, brain-specific γ<sub>1</sub>-syntrophin binds the neurotrophic factor γ-enolase through its PDZ domain, and translocates it to the plasma membrane, as shown by immunoprecipitation, surface plasmon resonance, fluorescence colocalization and flow cytometry. Extensive colocalization of γ<sub>1</sub>-syntrophin and γ-enolase was observed in neurite growth cones in differentiated SH-SY5Y cells. Silencing of the γ<sub>1</sub>-syntrophin gene by RNA interference significantly reduced the re-distribution of γ-enolase to the plasma membrane and impaired its neurotrophic effects. We demonstrated that an intact C-terminal end of γ-enolase is essential for its γ<sub>1</sub>-syntrophin-assisted trafficking. The cleavage of two amino acids at the C-terminal end of γ-enolase by the carboxypeptidase cathepsin X prevents binding with the γ<sub>1</sub>-syntrophin PDZ domain. Collectively, these data demonstrate that γ<sub>1</sub>-syntrophin participates in γ-enolase translocation towards the plasma membrane, a pre-requisite for its neurotrophic activity. By disrupting this γ<sub>1</sub>-syntrophin-guided subcellular distribution, cathepsin X reduces γ-enolase-induced neurotrophic signaling.
DOI: 10.6084/m9.figshare.5121715
title: Supplementary Material for: Chronic Obstructive Pulmonary Disease-Specific Gene Expression Signatures of Alveolar Macrophages as well as Peripheral Blood Monocytes Overlap and Correlate with Lung Function

description: <i>Background:</i> Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by progressive airflow limitation and significant extrapulmonary (systemic) effects that lead to co-morbid conditions, though the pathomechanism of COPD is largely undetermined. Alveolar macrophages (AM) derived from peripheral monocytes (MO) appear to play a key role in initiating and/or sustaining disease progression. <i>Objectives:</i> To identify disease- and cell type-specific gene expression profiles and potential overlaps in those in order to diagnose COPD, characterize its progression and determine the effect of drug treatment. <i>Method:</i> Global gene expression analysis was used for primary screening in order to obtain expression signatures of AMs and circulating MOs of COPD patients and healthy controls. The results of microarray analyses of AMs (20 controls and 26 COPD patients) and MOs (16 controls and 22 COPD patients) were confirmed and validated by real-time quantitative polymerase chain reaction. <i>Results:</i> We have identified gene sets specifically associated with COPD in AMs and MOs. There were overlapping genes between the two cell types. Our data also show that COPD-specific gene expression signatures in AMs and MOs correlate with percent of predicted FEV<sub>1</sub>. <i>Conclusion:</i> Disease-specific and overlapping gene expression signatures can be defined in lung-derived macrophages and also in circulating monocytes. Some of the validated expression changes in both cell types correlate with lung function and therefore could serve as biomarkers of disease progression.