cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5120458.v1
title: Supplementary Material for: Distinct Gene Expression Profiles: Nodal versus Extranodal Diffuse Large B-Cell Lymphoma

description: <i>Introduction:</i> Approximately one third of diffuse large B-cell lymphomas (DLBCL) arises from tissues different from the lymph node. Perceived differences in outcome between extranodal and nodal DLBCL raise the possibility that these subgroups may represent different biological and clinical entities. <i>Methods:</i> Microarray GeneChip technology was used for global gene expression profiles from nodal (n = 19) and extranodal (n = 8) DLBCL, to examine possible differences between these subgroups. Quantitative RT-PCR was employed for validation of microarray data. Differential expression levels of p16 (CDKN2A) were confirmed by means of immunohistochemistry on a tissue microarray comprising more than 200 lymphoma samples. <i>Results:</i> A total of 218, over (124)- and underexpressed (94) genes were found to be differentially expressed in extranodal DLBCL compared with nodal DLBCL, including cytokines/chemokines, chromosome-replication-related genes and DNA repair genes. Quantitative RT-PCR confirmed the microarray data. A higher rate of p16 positivity was found in extranodal lymphomas. However, prognostic importance of p16 was associated with nodal rather than extranodal lymphomas. <i>Conclusion:</i> Our data suggest that a better distinction of these subgroups based on molecular classifiers is feasible and may greatly facilitate the determination of specific relevant clinical features and therapeutic implications of DLBCL with primary extranodal or nodal location.
DOI: 10.6084/m9.figshare.5120443
title: Supplementary Material for: Multipotential Neural Precursors Transplanted into the Metachromatic Leukodystrophy Brain Fail to Generate Oligodendrocytes but Contribute to Limit Brain Dysfunction

description: Neural stem cells appear to be best suited for regenerative therapy in neurological diseases. However, the effects of high levels of potentially toxic substances such as sulfatides – which accumulate in metachromatic leukodystrophy (MLD) – on this regenerative ability are still largely unclear. To start addressing this question, in vitro and in vivo experiments were used to examine the behavior of multipotential neural precursors exposed to abnormally high levels of sulfatides. Following transplantation of dissociated neurospheres into the brain of presymptomatic MLD pups, the majority of donor-derived cells were distributed in a caudal to rostral direction, with higher numbers in the cortex. Most if not all of the donor cells acquired an astroglial phenotype. We found no evidence of oligodendrocyte or neuronal commitment of transplanted cells in long-term-treated MLD mice (e.g. up to 1.5 years of age). This was in line with our in vitro findings of sulfatides blocking oligodendrocyte formation after induction of differentiation in sulfatide-treated epidermal growth factor/fibroblast growth factor responsive neurospheres. Transplanted MLD mice showed an improved arylsulfatase A (ARSA) activity and a significant amelioration of sulfatide metabolism, neurodegeneration and motor-learning/memory deficits. Furthermore, transplanted cells were shown to act as a source of ARSA enzyme that accumulated in endogenous brain cells, indicating the occurrence of enzyme cross-correction between transplanted and host cells. These results provide a first insight into the effect of sulfatides on the stemness properties of neural stem cells and on the effects of the MLD environment on the in vivo expectations of using neural stem cells in cell therapy.
DOI: 10.6084/m9.figshare.5120449.v1
title: Supplementary Material for: Effect of Dietary Calcium and Dairy Proteins on the Adipose Tissue Gene Expression Profile in Diet-Induced Obesity

description: <i>Background/Aims:</i> Calcium and dairy proteins have been postulated to explain why the intake of dairy products correlates inversely with body mass index in several populations. We have shown that a high-calcium diet with whey protein attenuates weight gain and now we describe the effects of this diet on adipose tissue gene expression. <i>Methods:</i> Nine-week-old C57Bl/6J mice were divided into two groups (n = 10/group). The control diet was a standard high-fat diet (60% of energy) low in calcium (0.4%). The whey protein diet was a high-calcium (1.8%), high-fat diet with whey protein. After the 21-week treatment, adipose tissue transcript profiling (2 mice/group) was performed using Affymetrix Mouse Genome 430 2.0. <i>Results:</i> The high-calcium diet with whey protein altered the expression of 129 genes (± 1.2 fold). Quantitative RT-PCR analysis confirmed the significant up-regulation of Adrb3 (p = 0.002) and leptin (p = 0.0019) in the high-calcium whey group. Insulin and adipocytokine signaling pathways were enriched among the up-regulated genes and the fatty acid metabolism pathway among the down-regulated genes. <i>Conclusions:</i> High-calcium diet with whey protein significantly modifies adipose tissue gene expression. These preliminary findings reveal that targets of a high-calcium diet with whey protein include genes for Adrb3 and leptin, and help to explain how the intake of dairy products might attenuate obesity.
DOI: 10.6084/m9.figshare.5120452.v1
title: Supplementary Material for: A 4,103 marker integrated physical and comparative map of the horse genome

description: A comprehensive second-generation whole genome radiation hybrid (RH II), cytogenetic and comparative map of the horse genome (2n = 64) has been developed using the 5000rad horse × hamster radiation hybrid panel and fluorescence in situ hybridization (FISH). The map contains 4,103 markers (3,816 RH; 1,144 FISH) assigned to all 31 pairs of autosomes and the X chromosome. The RH maps of individual chromosomes are anchored and oriented using 857 cytogenetic markers. The overall resolution of the map is one marker per 775 kilobase pairs (kb), which represents a more than five-fold improvement over the first-generation map. The RH II incorporates 920 markers shared jointly with the two recently reported meiotic maps. Consequently the two maps were aligned with the RH II maps of individual autosomes and the X chromosome. Additionally, a comparative map of the horse genome was generated by connecting 1,904 loci on the horse map with genome sequences available for eight diverse vertebrates to highlight regions of evolutionarily conserved syntenies, linkages, and chromosomal breakpoints. The integrated map thus obtained presents the most comprehensive information on the physical and comparative organization of the equine genome and will assist future assemblies of whole genome BAC fingerprint maps and the genome sequence. It will also serve as a tool to identify genes governing health, disease and performance traits in horses and assist us in understanding the evolution of the equine genome in relation to other species.
DOI: 10.6084/m9.figshare.5120437
title: Supplementary Material for: Gas Embolism Caused by Portal Vein Gas: Case Report and Literature Review

description: <i>Introduction:</i> We describe a case of pulmonary gas embolism caused by portal vein gas (PVG) observed using echocardiography. Echography revealed gas flowing through the hepatic vein, inferior vena cava, right atrium, and right ventricle, as well as pulmonary hypertension. The patient was diagnosed as having pulmonary gas embolism caused by PVG. <i>Objective:</i> We consider PVG routes to pulmonary circulation, diagnosis of gas embolism caused by PVG, and treatment of gas embolism caused by PVG.<i>Methods:</i> We reviewed reports of eight cases of gas embolism caused by PVG and compared these cases to cases of gas embolism without PVG. <i>Results:</i> Mortality of gas embolism caused by PVG was 67%, positive blood culture was observed in six cases, and pulmonary edema was seen in three cases. PVG initially excites microbubble formation, which causes tissue damage in the liver and liver abscess. A large volume of PVG causes portal obstruction. As a result, portal hypertension, a portosystemic shunt or gastrointestinal congestion can occur. PVG can travel to the systemic vein through the liver or portosystemic shunt without anomaly and cause pulmonary gas embolism, followed by arterial embolism. In this environment, sepsis easily occurs. Echocardiography is useful for diagnosis of gas embolism caused by PVG, but the gas can be seen intermittently. The view of pulmonary edema is important for pulmonary gas embolism caused by PVG. <i>Conclusion:</i> It is important to treat the underlying disease, but PVG must be considered and treated as the gas embolism’s source.
DOI: 10.6084/m9.figshare.5120446
title: Supplementary Material for: Evolution of Family 18 Glycoside Hydrolases: Diversity, Domain Structures and Phylogenetic Relationships

description: Chitin and its derivates have many industrial and medical uses. There is a demand for chitin-modifying enzymes with new or modified properties and as microorganisms are the primary degraders of chitin in the environment, they provide a source of chitin-modifying enzymes with novel properties. We have analyzed the diversity, domain structure and phylogenetic relationships between family 18 chitinases based on complete genome sequences of bacteria, archaea, viruses, fungi, plants and animals. Our study shows that family 18 chitinases are divided into three main clusters, A, B and C. Clusters A and B both contain family 18 chitinases from bacteria, fungi and plants, suggesting that the differentiation of cluster A and B chitinases preceded the appearance of the eukaryotic lineage. Subgroups within clusters can have specific domain structures, as well as specific amino acid replacements in catalytic sites, which imply functional adaptation. This work provides a comprehensive overview of the evolutionary relationships of family 18 chitinases and provides a context for further investigations on functional aspects of family 18 chitinases in ecology and biotechnology.
DOI: 10.6084/m9.figshare.5120437.v1
title: Supplementary Material for: Gas Embolism Caused by Portal Vein Gas: Case Report and Literature Review

description: <i>Introduction:</i> We describe a case of pulmonary gas embolism caused by portal vein gas (PVG) observed using echocardiography. Echography revealed gas flowing through the hepatic vein, inferior vena cava, right atrium, and right ventricle, as well as pulmonary hypertension. The patient was diagnosed as having pulmonary gas embolism caused by PVG. <i>Objective:</i> We consider PVG routes to pulmonary circulation, diagnosis of gas embolism caused by PVG, and treatment of gas embolism caused by PVG.<i>Methods:</i> We reviewed reports of eight cases of gas embolism caused by PVG and compared these cases to cases of gas embolism without PVG. <i>Results:</i> Mortality of gas embolism caused by PVG was 67%, positive blood culture was observed in six cases, and pulmonary edema was seen in three cases. PVG initially excites microbubble formation, which causes tissue damage in the liver and liver abscess. A large volume of PVG causes portal obstruction. As a result, portal hypertension, a portosystemic shunt or gastrointestinal congestion can occur. PVG can travel to the systemic vein through the liver or portosystemic shunt without anomaly and cause pulmonary gas embolism, followed by arterial embolism. In this environment, sepsis easily occurs. Echocardiography is useful for diagnosis of gas embolism caused by PVG, but the gas can be seen intermittently. The view of pulmonary edema is important for pulmonary gas embolism caused by PVG. <i>Conclusion:</i> It is important to treat the underlying disease, but PVG must be considered and treated as the gas embolism’s source.
DOI: 10.6084/m9.figshare.5120440
title: Supplementary Material for: Cohort Changes in Cognitive Function among Danish Centenarians

description: <i>Background/Aim:</i> The objective was to examine cohort changes in cognitive function in 2 cohorts of centenarians born 10 years apart. <i>Methods:</i> The Longitudinal Study of Danish Centenarians comprises all Danes reaching the age of 100 in the period April 1, 1995 through May 31, 1996. A total of 207 out of 276 persons participated (75%). The Danish 1905 Cohort Survey includes all individuals born in 1905. In total, 225 out of 364 persons who reached the age of 100 in the cohort participated in the most recent 2005 follow-up (62%). In both cohorts, cognitive function was assessed using the Mini-Mental State Examination. <i>Results:</i> There were no significant differences in cognitive score between the two centenarian birth cohorts. However, modest tendencies were seen towards better cognitive functioning for the centenarians in the 1905 cohort living at home compared to the home-dwelling ones in the 1895 cohort and worse cognitive performance for the centenarians in the 1905 group living in nursing homes compared to the nursing home dwellers in the 1895 cohort. <i>Conclusion:</i> The increasing number of centenarians may not entail larger proportions of cognitively impaired individuals in this extreme age group.
DOI: 10.6084/m9.figshare.5120428
title: Supplementary Material for: Attenuated Activation of Macrophage TLR9 by DNA from Virulent Mycobacteria

description: Alveolar macrophages are the first line of host defence against mycobacteria, but an insufficient host response allows survival of bacteria within macrophages. We aimed to investigate the role of Toll-like receptor 9 (TLR9) activation in macrophage defence against mycobacteria. Human in vitrodifferentiated macrophages as well as human and mouse alveolar macrophages showed TLR9 mRNA and protein expression. The cells were markedly activated by DNA isolated from attenuated mycobacterial strains (H37Ra and <i>Mycobacterium bovis</i> BCG) as assessed by measuring cytokine expression by real-time PCR, whereas synthetic phosphorothioate-modified oligonucleotides had a much lower potency to activate human macrophages. Intracellular replication of H37Ra was higher in macrophages isolated from TLR9-deficient mice than in macrophages from wild-type mice, whereas H37Rv showed equal survival in cells from wild-type or mutant mice. Increased bacterial survival in mouse macrophages was accompanied by altered cytokine production as determined by Luminex bead assays. In vivo infection experiments also showed differential cytokine production in TLR9-deficient mice compared to wild-type animals. Both human monocyte-derived macrophages as well as human alveolar macrophages showed reduced activation upon treatment with DNA isolated from bacteria from virulent (<i>M. bovis </i>and H37Rv) compared to attenuated mycobacteria. We suggest attenuated TLR9 activation contributes to the insufficient host response against virulent mycobacteria.
DOI: 10.6084/m9.figshare.5120431
title: Supplementary Material for: <i>LPA</i> and <i>PLG</i> Sequence Variation and Kringle IV-2 Copy Number in Two Populations

description: <i>Background/Aims:</i> Lp(a) levels have long been recognized as a potential risk factor for coronary heart disease that is almost completely under genetic control. Much of the genetics impacting Lp(a) levels has been attributed to the highly polymorphic <i>LPA</i> kringle IV-2 copy number variant, and most of the variance in Lp(a) levels in populations of European-descent is inversely correlated with kringle IV copy number. However, less of the variance is explained in African-descent populations for the same structural variation. African-descent populations have, on average, higher levels of Lp(a), suggesting other genetic factors contribute to Lp(a) level variability across populations. <i>Methods:</i> To identify potential cis-acting factors, we re-sequenced the gene <i>LPA</i> for single nucleotide polymorphism (SNP) discovery in 23 European-Americans and 24 African-Americans. We also re- sequenced the neighboring gene plasminogen <i>(PLG)</i> and genotyped the kringle IV copy number variant in the same reference samples. <i>Results:</i> These data are the most comprehensive description of sequence variation in <i>LPA</i> and its relationship with the kringle IV copy number variant. With these data, we demonstrate that only a fraction of <i>LPA</i> sequence diversity has been previously documented. Also, we identify several high frequency SNPs present in the African-American sample but absent in the European-American sample. Finally, we show that SNPs within <i>PLG </i>are not in linkage disequilibrium with SNPs in <i>LPA</i>, and we show that kringle IV copy number variation is not in linkage disequilibrium with either <i>LPA</i> or <i>PLG</i> SNPs. <i>Conclusions:</i> Together, these data suggest that <i>LPA</i> SNPs could independently contribute to Lp(a) levels in the general population.
DOI: 10.6084/m9.figshare.5120434
title: Supplementary Material for: Prothrombotic Gene Variation in Patients with Large and Small Vessel Disease

description: The classification of ischemic stroke into different subtypes is supported in genetic association studies. While several gene variants have been identified as being associated with ischemia subtypes, most studies have not been powered to study subtypes separately. We investigated 887 patients with nondisabling cerebral ischemia of arterial origin and classified ischemia as being caused by large or small vessel disease (LVD or SVD), primarily based on neuroimaging findings. In total, 621 patients had LVD and 266 SVD. The coagulation factor XIII subunit B gene (F13B) His95Arg variant was more common in patients with LVD (mean prevalence difference 9.9%; 95% CI 4.7–15). None of 21 other prothrombotic gene variants was associated with LVD or SVD. Many gene variants may not be specific for one subtype. We could not replicate the genetic associations identified in previous smaller previous studies. Thus claims about genetic associations with specific subtypes of ischemia should be interpreted with caution. The association between F13B His95Arg and LVD requires replication.
DOI: 10.6084/m9.figshare.5120440.v1
title: Supplementary Material for: Cohort Changes in Cognitive Function among Danish Centenarians

description: <i>Background/Aim:</i> The objective was to examine cohort changes in cognitive function in 2 cohorts of centenarians born 10 years apart. <i>Methods:</i> The Longitudinal Study of Danish Centenarians comprises all Danes reaching the age of 100 in the period April 1, 1995 through May 31, 1996. A total of 207 out of 276 persons participated (75%). The Danish 1905 Cohort Survey includes all individuals born in 1905. In total, 225 out of 364 persons who reached the age of 100 in the cohort participated in the most recent 2005 follow-up (62%). In both cohorts, cognitive function was assessed using the Mini-Mental State Examination. <i>Results:</i> There were no significant differences in cognitive score between the two centenarian birth cohorts. However, modest tendencies were seen towards better cognitive functioning for the centenarians in the 1905 cohort living at home compared to the home-dwelling ones in the 1895 cohort and worse cognitive performance for the centenarians in the 1905 group living in nursing homes compared to the nursing home dwellers in the 1895 cohort. <i>Conclusion:</i> The increasing number of centenarians may not entail larger proportions of cognitively impaired individuals in this extreme age group.
DOI: 10.6084/m9.figshare.5120446.v1
title: Supplementary Material for: Evolution of Family 18 Glycoside Hydrolases: Diversity, Domain Structures and Phylogenetic Relationships

description: Chitin and its derivates have many industrial and medical uses. There is a demand for chitin-modifying enzymes with new or modified properties and as microorganisms are the primary degraders of chitin in the environment, they provide a source of chitin-modifying enzymes with novel properties. We have analyzed the diversity, domain structure and phylogenetic relationships between family 18 chitinases based on complete genome sequences of bacteria, archaea, viruses, fungi, plants and animals. Our study shows that family 18 chitinases are divided into three main clusters, A, B and C. Clusters A and B both contain family 18 chitinases from bacteria, fungi and plants, suggesting that the differentiation of cluster A and B chitinases preceded the appearance of the eukaryotic lineage. Subgroups within clusters can have specific domain structures, as well as specific amino acid replacements in catalytic sites, which imply functional adaptation. This work provides a comprehensive overview of the evolutionary relationships of family 18 chitinases and provides a context for further investigations on functional aspects of family 18 chitinases in ecology and biotechnology.
DOI: 10.6084/m9.figshare.5120425
title: Supplementary Material for: Identification of Genes Targeted by CpG Island Methylator Phenotype in Neuroblastomas, and Their Possible Integrative Involvement in Poor Prognosis

description: <i>Background/Aims:</i> CpG island (CGI) methylator phenotype (CIMP) is strongly associated with poor prognosis in neuroblastomas (NBLs; hazard ratios 7–22). Methylation of nonpromoter CGIs is useful to detect the presence of the CIMP, while the poor prognosis is considered to be caused by gene silencing due to promoter methylation. Here, promoter CGIs targeted by the CIMP were searched for. <i>Methods:</i> A genome-wide screening was performed by methylation-sensitive representational difference analysis of CIMP(+) and CIMP(–) NBLs. <i>Results:</i> Promoter CGIs of 9 genes were methylated in CIMP(+) NBL cell lines and caused silencing of their downstream genes. On analysis of 90 clinical specimens, <i>CYP26C1,</i><i>FERD3L </i>(<i>N-TWIST</i>), <i>CRYBA2</i> and <i>PCDHGC4 </i>were methylated at significantly higher incidences in CIMP(+) NBLs than CIMP(–) NBLs, while the difference was unclear for <i>NPY</i>, <i>SPAG6</i>, <i>DDIT4L</i>, <i>CHR3SYT</i> and <i>C6Orf141</i>. Methylation of <i>CYP26C1 </i>and <i>FERD3L</i> was significantly associated with poor prognosis, but weaker than the presence of the CIMP. Treatment of an NBL cell line with a demethylating agent caused demethylation of multiple promoter CGIs, and enhanced 13-<i>cis</i>-retinoic acid-induced neuronal differentiation. <i>Conclusion:</i> Our results indicate that the CIMP causes poor prognosis of NBLs by inducing methylation of multiple promoter CGIs with various incidences.
DOI: 10.6084/m9.figshare.5120422
title: Supplementary Material for: Treatment of Painful Limbs/Moving Extremities with Botulinum Toxin Type A Injections

description: Medicine