cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5104663
title: Supplementary Material for: The Endothelin-1 Pathway and the Development of Cardiovascular Defects in the Haemodynamically Challenged Chicken Embryo

description: <i>Background/Aims:</i> Ligating the right lateral vitelline vein of chicken embryos (venous clip) results in cardiovascular malformations. These abnormalities are similar to malformations observed in knockout mice studies of components of the endothelin-1 (ET-1)/endothelin-converting enzyme-1/endothelin-A receptor pathway. In previous studies we demonstrated that cardiac <i>ET-1</i> expression is decreased 3 h after clipping, and ventricular diastolic filling is disturbed after 2 days. Therefore, we hypothesise that ET-1-related processes are involved in the development of functional and morphological cardiovascular defects after venous clip. <i>Methods:</i> In this study, ET-1 and endothelin receptor antagonists (BQ-123, BQ-788 and PD145065) were infused into the HH18 embryonic circulation. Immediate haemodynamic effects on the embryonic heart and extra-embryonic vitelline veins were examined by Doppler and micro-particle image velocimetry. Ventricular diastolic filling characteristics were studied at HH24, followed by cardiovascular morphologic investigation (HH35). <i>Results:</i> ET-1 and its receptor antagonists induced haemodynamic effects at HH18. At HH24, a reduced diastolic ventricular passive filling component was demonstrated, which was compensated by an increased active filling component. Thinner ventricular myocardium was shown in 42% of experimental embryos. <i>Conclusion:</i> We conclude that cardiovascular malformations after venous clipping arise from a combination of haemodynamic changes and altered gene expression patterns and levels, including those of the endothelin pathway.
DOI: 10.6084/m9.figshare.5104654
title: Supplementary Material for: PNAS-2: A Novel Gene Probably Participating in Leukemogenesis

description: <i>Objective:</i>As<sub>4</sub>S<sub>4</sub> is an effective drug for the treatment of acute promyelocytic leukemia but its mechanism of action remains largely unknown. In a previous study, we identified PNAS-2, a human apoptosis-related protein gene, using gene expression profiling. In this study, we tried to clarify the role of PNAS-2 in apoptosis and leukemogenesis. <i>Methods:</i> NB4 and U937 leukemia cell lines and serial clinical samples were studied. RNA interference (RNAi) and RNA overexpression were used to address the potential role of PNAS-2 in apoptosis. PNAS-2 expression was examined using Northern blot in multiple tissues, and real-time PCR was applied to analyze PNAS-2 expression in various patient samples. <i>Results:</i> Functional analyses of PNAS-2 by RNAi and RNA overexpression indicate PNAS-2 is an anti-apoptosis gene. PNAS-2 expression is significantly increased in de novo or relapsed acute leukemia, but in patients in complete remission PNAS-2 levels decrease to levels comparable to those found in normal controls. In carcinomas, PNAS-2 expression was not upregulated, indicating that PNAS-2 overexpression was specific for leukemia. <i>Conclusion:</i> Based on the preliminary data, we suggest that the PNAS-2 gene functions as an anti-apoptotic gene and probably participates in leukemogenesis.
DOI: 10.6084/m9.figshare.5104660
title: Supplementary Material for: Fugu <i>(Takifugu rubripes)</i> Sexual Differentiation: CYP19 Regulation and Aromatase Inhibitor Induced Testicular Development

description: In order to assess the involvement of aromatase CYP19 isoforms and endogenous sex steroids in gonadal sex differentiation and development of the Japanese fugu <i>(Takifugu rubripes)</i>, an aromatase inhibitor (AI, fadrozole) was administered to developing fishes from the ‘first feeding’ till the 100th day after hatching. It was observed that ovarian cavity formation was inhibited by fadrozole at doses of 500 and 1000 µg/g diet, which was followed by testicular differentiation in all treated fugu. In the non-treated fugu, <i>CYP19A</i> was predominantly expressed in the ovary and <i>CYP19B</i> in the brain (in both sexes), although both were expressed interchangeably at low levels. An exceptionally high expression of <i>CYP19B</i> was also evident in testis throughout the study period. Both forms of CYP19 mRNA showed low levels of expression in brain and gonad with no significant differences between the two AI treatments. AI treatment inhibited <i>CYP19A</i> mRNA in trunk during the crucial period of ovarian cavity formation and <i>CYP19B</i> in gonad and brain by the end of gonadal sex differentiation. An elevation of testosterone and 11-ketotestosterone was observed which can be associated with the down-regulation of the circulating 17β-estradiol production during the AI treatment period. After stopping AI treatment, both circulating estrogen and androgen were normalized. The current results suggest that suppression of <i>CYP19A</i> before and during morphological sex differentiation inhibits ovarian cavity formation in fugu. Furthermore, non-detectable limits of 17β-estradiol and high testosterone levels by the end of the gonadal differentiation period can be ascribed to inhibition of <i>CYP19B</i>, suggesting that conversion of 17β-estradiol from testosterone is plausibly regulated by CYP19B, and that this factor (CYP19B) may play an important role in AI-induced testicular development after gonadal sex differentiation through regulation of the testosterone–17β-estradiol balance in fugu.
DOI: 10.6084/m9.figshare.5104666.v1
title: Supplementary Material for: How Neuronal Migration Contributes to the Morphogenesis of the CNS: Insights from the Zebrafish

description: We used transgenic zebrafish expressing GFP or YFP in subpopulations of neurons to study the migration, homing process and axon extension of groups of CNS neurons in different regions of the zebrafish brain. We found that extensive migration takes place at all levels of the CNS and gives rise to nuclei or cell populations with specific identities. Here, we describe 4 previously unknown or only partially characterized migratory events taking place in the zebrafish telencephalon and rhombic lip, using 3 different transgenic lines, and identify the phenotypes of the cells undertaking these migrations. The migration of a subgroup of mitral cell precursors from the dorsocaudal telencephalon to the olfactory bulb, visualized in the <i>tg(tbr1:YFP)</i> transgenic line, is coupled with morphogenetic transformation of the dorsal telencephalon. The <i>tg(1.4dlx5a-6a:GFP)</i> transgenic line provides a means to analyze the migration of GABAergic interneurons from the ventral to the dorsal telencephalon, thus extending the occurrence of this migration to another vertebrate. The <i>tg(Xeom:GFP)</i> transgenic line provides the first demonstration of the dorsoventral migration of glutamatergic septal neurons, present in mammals and now described in fish, thus reconciling the contrasting evidence of dorsal patterning genes <i>(tbr1, eomes)</i> expressed in a ventral cell population. Furthermore, migration studies in the <i>tg(1.4dlx5a-6a:GFP)</i> and <i>tg(Xeom:GFP)</i> lines help determine the origin of 2 important cell populations in the fish cerebellum: projection neurons and Purkinje cells. These examples reinforce the concept that migratory events contribute to the distribution of cell types with diverse identities through the CNS and that zebrafish transgenic lines represent excellent tools to study these events.
DOI: 10.6084/m9.figshare.5104651
title: Supplementary Material for: Dietary Supplementation with Lactic Acid Bacteria Attenuates the Development of Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice in a Strain-Dependent Manner

description: <i>Background:</i> Dietary supplementation with lactic acid bacteria (LAB) is a potential approach to the prevention and manipulation of allergic diseases such as atopic dermatitis (AD). However, the influence of different bacterial strains and their immunomodulating capacities is still largely unknown. <i>Methods:</i> AD-like skin lesions were induced by sensitization to and repeated challenges with picrylchloride in the Th2-skewed NC/Nga mouse strain. The effects of LAB supplementation were assessed over time by monitoring clinical scores and plasma IgE levels. In some cases, mast cell infiltration, cutaneous hypersensitivity responses and cytokine mRNA expression in auricles were also examined. Additionally, cytokine production in vitro and cytokine mRNA accumulation in major lymphoid tissues were measured, comparing <i>Lactobacillus paracasei</i> KW3110 with <i>L. rhamnosus</i> GG (LGG). <i>Results:</i> Supplementation with KW3110 significantly reduced the development of AD-like skin lesions, accompanied by less mast cell infiltration and lower plasma IgE levels. KW3110 also suppressed immediate hypersensitivity reactions and IL-4 mRNA expression in the auricles. These preventive effects sustained when supplementation was terminated; moreover, inhibitory effects were also observed even when supplementation was initiated after the onset of symptoms. In accordance with its effects on IL-12 and IL-4 production in vitro, KW3110 prevented the emergence of clinical symptoms more effectively than LGG in vivo. <i>Conclusions:</i> Supplementation with KW3110 significantly attenuated the onset and exacerbation of AD-like symptoms in NC/Nga mice. The effects were more prominent than those obtained with LGG, suggesting the importance of differences between LAB strains and their immunomodulating capacity.
DOI: 10.6084/m9.figshare.5104654.v1
title: Supplementary Material for: PNAS-2: A Novel Gene Probably Participating in Leukemogenesis

description: <i>Objective:</i>As<sub>4</sub>S<sub>4</sub> is an effective drug for the treatment of acute promyelocytic leukemia but its mechanism of action remains largely unknown. In a previous study, we identified PNAS-2, a human apoptosis-related protein gene, using gene expression profiling. In this study, we tried to clarify the role of PNAS-2 in apoptosis and leukemogenesis. <i>Methods:</i> NB4 and U937 leukemia cell lines and serial clinical samples were studied. RNA interference (RNAi) and RNA overexpression were used to address the potential role of PNAS-2 in apoptosis. PNAS-2 expression was examined using Northern blot in multiple tissues, and real-time PCR was applied to analyze PNAS-2 expression in various patient samples. <i>Results:</i> Functional analyses of PNAS-2 by RNAi and RNA overexpression indicate PNAS-2 is an anti-apoptosis gene. PNAS-2 expression is significantly increased in de novo or relapsed acute leukemia, but in patients in complete remission PNAS-2 levels decrease to levels comparable to those found in normal controls. In carcinomas, PNAS-2 expression was not upregulated, indicating that PNAS-2 overexpression was specific for leukemia. <i>Conclusion:</i> Based on the preliminary data, we suggest that the PNAS-2 gene functions as an anti-apoptotic gene and probably participates in leukemogenesis.
DOI: 10.6084/m9.figshare.5104657.v1
title: Supplementary Material for: Extending the Platinum-Free Interval with a Non-Platinum Therapy in Platinum-Sensitive Recurrent Ovarian Cancer

description: <i>Background:</i> It has been proposed that extending the platinum-free interval with intervening non-platinum therapy increases the efficacy of a later re-treatment with platinum in platinum-sensitive recurrent ovarian cancer. This hypothesis is based on data from small series and although it has not been validated prospectively, this strategy has entered general practice in Italy in the last years. The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000–2002 in 37 Italian centres. Data were collected between April and September 2005. <i>Methods:</i> Patients with recurrent ovarian cancer with a platinum-free interval &gt;6 months were eligible. 493 patient files were collected and 428 were eligible and analyzed. <i>Results:</i> The interval from the end of the 1st line to relapse was 6–12 months in 164 patients (39.5%) and &gt;12 months in 251 cases (60.5%). Patients received a 2nd (100%), 3rd (80.1%), 4th (50.2%), 5th (28.3%), and 6th (11.9%) line of chemotherapy. At 2nd line 282 (65.9%) received platinum (group A), while 146 (34.1%) received non-platinum chemotherapy (group B). In the latter group, 67 patients received platinum at later progression (group B1), while 79 never received platinum (group B2). Median time to platinum re-treatment was 20 and 23.1 months in patients of groups A and B1, respectively. The response rate to the first platinum received was 74.4 and 57.4% in groups A and B1, respectively (p = 0.02). Group B2 was characterized by the worst response rate and survival. At multivariate analysis time of first platinum re-treatment (2nd line vs. later; p = 0.0132; OR = 2.34) and age (p = 0.0029; OR = 2.41) was independently associated with a higher possibility of response to platinum. <i>Conclusions:</i> With the limits of a retrospective study, our data question the hypothesis that extending the platinum-free interval with an intervening non-platinum therapy in patients with recurrent platinum-sensitive ovarian cancer improves the response rate of a further platinum re-treatment.
DOI: 10.6084/m9.figshare.5104660.v1
title: Supplementary Material for: Fugu <i>(Takifugu rubripes)</i> Sexual Differentiation: CYP19 Regulation and Aromatase Inhibitor Induced Testicular Development

description: In order to assess the involvement of aromatase CYP19 isoforms and endogenous sex steroids in gonadal sex differentiation and development of the Japanese fugu <i>(Takifugu rubripes)</i>, an aromatase inhibitor (AI, fadrozole) was administered to developing fishes from the ‘first feeding’ till the 100th day after hatching. It was observed that ovarian cavity formation was inhibited by fadrozole at doses of 500 and 1000 µg/g diet, which was followed by testicular differentiation in all treated fugu. In the non-treated fugu, <i>CYP19A</i> was predominantly expressed in the ovary and <i>CYP19B</i> in the brain (in both sexes), although both were expressed interchangeably at low levels. An exceptionally high expression of <i>CYP19B</i> was also evident in testis throughout the study period. Both forms of CYP19 mRNA showed low levels of expression in brain and gonad with no significant differences between the two AI treatments. AI treatment inhibited <i>CYP19A</i> mRNA in trunk during the crucial period of ovarian cavity formation and <i>CYP19B</i> in gonad and brain by the end of gonadal sex differentiation. An elevation of testosterone and 11-ketotestosterone was observed which can be associated with the down-regulation of the circulating 17β-estradiol production during the AI treatment period. After stopping AI treatment, both circulating estrogen and androgen were normalized. The current results suggest that suppression of <i>CYP19A</i> before and during morphological sex differentiation inhibits ovarian cavity formation in fugu. Furthermore, non-detectable limits of 17β-estradiol and high testosterone levels by the end of the gonadal differentiation period can be ascribed to inhibition of <i>CYP19B</i>, suggesting that conversion of 17β-estradiol from testosterone is plausibly regulated by CYP19B, and that this factor (CYP19B) may play an important role in AI-induced testicular development after gonadal sex differentiation through regulation of the testosterone–17β-estradiol balance in fugu.
DOI: 10.6084/m9.figshare.5104648
title: Supplementary Material for: Assessment of Suitability of Thrombolysis in Middle Cerebral Artery Infarction: A Proof of Concept Study of a Stereologically-Based Technique

description: <i>Background:</i> The extent of cerebral ischemia, assessed by the Alberta Stroke Program Early CT Score (ASPECTS) method and unaided visual determination of the CT Summit Criterion, correlates with increased risk of intracerebral hemorrhage following rt-PA administration. Concerns about the accuracy of the unaided visual assessment in the estimation of infarct size and the conservative nature of the ASPECTS method led us to develop a new method (MCAGrid) based on stereological grid counting and a digital atlas of the middle cerebral artery (MCA) infarct territory. <i>Methods:</i> We tested the hypotheses that the stereological method increases the accuracy of infarct estimation and that the number of patients deemed eligible for thrombolysis is greater with this method than with existing methods. Four experienced radiologists with extensive neuroradiological experience examined the CT images of 19 patients with MCA territory stroke and determined patient eligibility for thrombolysis by: unaided visual determination of the CT Summit Criterion, MCAGrid, and the ASPECTS score. The χ<sup>2</sup> test was used to compare the differences in the number of patients deemed ‘eligible’ for thrombolysis by the 3 imaging methods. Further, the unaided visual assessment and MCAGrid were compared with volumes calculated following manual segmentation of infarct, and the sensitivity, specificity and positive and negative likelihood ratios for these techniques were calculated. <i>Results:</i> In general, MCAGrid was better than unaided visual assessment in the prediction of &gt;1/3 involvement of the MCA territory by infarct. The number of patients considered as ‘eligible’ for thrombolysis based on imaging criteria was significantly lower when ASPECTS criteria (15/76) were used than when unaided visual determination of the CT Summit Criterion (32/76; p &lt; 0.01) or MCAGrid (59/76; p &lt; 0.001) criteria were used. <i>Conclusion:</i> The choice of methods for rating infarct extent affects the number of patients ‘eligible’ for thrombolysis significantly. Furthermore, MCAGrid increased the accuracy with which infarct extent was estimated. These results provide justification for a prospective study of this technique in the setting of acute stroke.
DOI: 10.6084/m9.figshare.5104639
title: Supplementary Material for: Recombinant Major Urinary Proteins of the Mouse in Specific IgE and IgG Testing

description: <i>Background:</i> Recombinant allergens are preferred over natural allergen extracts in measuring antibodies. We tested the use of recombinant variants of the major mouse allergen Mus m 1 in detection of mouse-specific antibodies in sera of laboratory animal workers and children. <i>Methods:</i> Six recombinant major urinary proteins (MUPs) were produced and antibody-binding capacity was compared to natural Mus m 1 and to mouse urine extract. In a specific subset, cross-reactivity of MUP with Mus m 1 and between the different recombinant MUPs was determined. <i>Results:</i> For IgE antibodies, MUP8 showed high cross-reactivity with Mus m 1. MUP8-specific IgE was found in 55% of the mouse urine IgE-positive sera. Specific IgG and IgG4 antibodies against natural Mus m 1 correlated strongly with antibodies against recombinant MUP8 and were cross-reactive. IgG4 levels against MUP8 and mouse urine extract correlated, but detection of mouse urine-specific IgG4 in the absence of MUP-specific IgG4 was not uncommon. Cross-reactivity of IgG antibodies between MUP8 and Mus m 1 as well as between the different MUPs was high and inhibition varied between 54 and 99%. <i>Conclusion:</i> The mouse allergen Mus m 1 can be replaced in antibody testing by recombinant MUP8. Other MUPs, except MUP4, are interchangeable with MUP8. However, mouse urine extract showed better detection of both mouse-specific IgE and IgG4 levels. Other components in the mouse urine, like mouse albumin and other yet unidentified components, also induce IgE and IgG(4) antibodies.
DOI: 10.6084/m9.figshare.5104642
title: Supplementary Material for: Laparoscopic Treatment of Simultaneous Tumors in the Liver and Kidney

description: <i>Background/Aims:</i> To report our experience with laparoscopic treatment of liver tumors during right-sided transperitoneal laparoscopic nephrectomy. <i>Methods:</i> Two patients undergoing transperitoneal laparoscopic radical nephrectomy on the right side each had a concomitant tumor in the right lobe of the liver. The first patient was incidentally found to have a lesion suspicious for metastatic disease. The second had a known asymptomatic giant hemangioma of the liver. <i>Results:</i> Total operative time was 130 and 101 min. Estimated blood loss was 400 and 300 ml. There were no complications. The first patient had bilateral papillary renal cell carcinoma and concomitant fibroadipose tissue within the liver. The second patient presented with clear cell carcinoma of the right kidney and a cavernous hemangioma of the liver. <i>Conclusions:</i> When indicated, simultaneous right-sided kidney and liver tumors may be treated by a combined laparoscopic transperitoneal approach. Laparoscopic expertise is advised.
DOI: 10.6084/m9.figshare.5104645
title: Supplementary Material for: Exclusion of <i>NFYB </i>as candidate gene for congenital splay leg in piglets and radiation hybrid mapping of further five homologous porcine genes from human chromosome 12 (HSA12)

description: Nuclear transcription factor Y, beta (<i>NFYB)</i> was evaluated as candidate gene for congenital splay leg in piglets based on data from differential display and QTL analysis. We mapped <i>NFYB</i> to pig chromosome 5 (SSC5). By assigning further five porcine genes from the corresponding region on human chromosome (HSA) 12q23.3→ q24.11 to SSC5 and 14 we could confine an evolutionary breakpoint from an interval of more than 10 Mb to less than 400 kb. Comparative sequence analysis of the coding region of <i>NFYB</i> in healthy and splay leg piglets revealed no polymorphism. Inter-species conservation of the codons ranges from 87% to 95% between pig, human, cow, dog, rat and mouse, respectively. The expression of <i>NFYB</i> in M. biceps femoris was not different between healthy and splay leg piglets. However, healthy male piglets had a significantly higher expression than females. Our results exclude <i>NFYB</i> as candidate gene for congenital splay leg but provide a basis for selection of further candidates for the disease from SSC5.
DOI: 10.6084/m9.figshare.5104636
title: Supplementary Material for: The Phylogeography of African Brazilians

description: <i>Background/Aims:</i> Approximately four million Africans were taken as slaves to Brazil, where they interbred extensively with Amerindians and Europeans. We have previously shown that while most White Brazilians carry Y chromosomes of European origin, they display high proportions of African and Amerindian mtDNA lineages, because of sex-biased genetic admixture. <i>Methods:</i> We studied the Y chromosome and mtDNA haplogroup structure of 120 Black males from Sao Paulo, Brazil. <i>Results:</i> Only 48% of the Y chromosomes, but 85% of the mtDNA haplogroups were characteristic of sub-Saharan Africa, confirming our previous observation of sexually biased mating. We mined literature data for mtDNA and Y chromosome haplogroup frequencies for African native populations from regions involved in Atlantic Slave Trade. Principal Components Analysis and Bayesian analysis of population structure revealed no genetic differentiation of Y chromosome marker frequencies between the African regions. However, mtDNA examination unraveled considerable genetic structure, with three clusters at Central-West Africa, West Africa and Southeast Africa. A hypothesis is proposed to explain this structure. <i>Conclusion:</i> Using these mtDNA data we could obtain for the first time an estimate of the relative ancestral contribution of Central-West (0.445), West (0.431) and Southeast Africa (0.123) to African Brazilians from Sao Paulo. These estimates are consistent with historical information.