cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5120815.v1
title: Supplementary Material for: CNGA2 Contributes to ATP-Induced Noncapacitative Ca<sup>2+</sup> Influx in Vascular Endothelial Cells

description: <i>Background/Aims:</i> ATP can activate several Ca<sup>2+</sup> influx channels in vascular endothelial cells. For example, it stimulates TRPC channels via capacitative and noncapacitative Ca<sup>2+</sup> entry (CCE and non-CCE, respectively) mechanisms; it also directly acts on P2X purinoceptors, resulting in Ca<sup>2+</sup> influx. In the present study, we tested the hypothesis that cyclic nucleotide-gated (CNG) channels also contribute to ATP-induced non-CCE. <i>Methods:</i> Two selective inhibitors of CNG channels, <i>L</i>-<i>cis</i>-diltiazem and LY-83583, and CNGA2-specific siRNA were used to study the involvement of CNGA2 in ATP-induced non-CCE in endothelial cells. Ca<sup>2+</sup> influx was studied using Ca<sup>2+</sup>-sensitive fluorescence dyes Fluo-3 and Fluo-4. <i>Results/Conclusion:</i><i>L</i>-<i>cis</i>-diltiazem and LY-83583 markedly reduced ATP-induced non-CCE in 3 types of endothelial cells including the H5V endothelial cell line, the primary cultured bovine aortic endothelial cells and the endothelial cells within isolated mouse aortic strips. The CNGA2-specific siRNA also reduced the ATP-induced non-CCE in H5V endothelial cells. The Ca<sup>2+</sup> influx was inhibited by Rp-8-CPT-cAMPS, MDL-12330A, SQ-22536 and MRS-2179, but not by ODQ or NF-157. Taken together, the present study demonstrated that CNGA2 channels contribute to ATP-induced non-CCE in vascular endothelial cells. It is likely that ATP acts through P2Y<sub>1 </sub>receptors and adenylyl cyclases to stimulate CNGA2.
DOI: 10.6084/m9.figshare.5120818.v1
title: Supplementary Material for: Is There a Decline in the Vascular Event Rate after Transient Ischemic Attack or Stroke in Antiplatelet Trials?

description: <i>Background:</i> We examined the baseline characteristics and the rates of serious vascular events in randomized clinical trials after cerebral ischemia of presumed arterial origin to identify study features that predict vascular event incidence and to identify whether event rates have declined over time. <i>Methods:</i> We performed a systematic review to identify all published randomized controlled trials of patients with stroke or transient ischemic attack of presumed arterial origin that included an aspirin arm. We performed metaregression to analyze whether baseline features of included patients, design features and the year of study start and publication influenced vascular event rates under aspirin treatment. <i>Results:</i> Included studies comprised 23,247 patients who had 3,615 serious vascular events. Baseline characteristics of patients included in the different trials varied substantially over time. In multivariate metaregression analysis a shorter maximum allowed delay from symptom onset to randomization (p = 0.012) and a double-blind design were associated with higher annual event rates (p = 0.014). Event rates did not significantly decrease over time (p = 0.242). <i>Conclusion:</i> The baseline characteristics of patients included in trials that study antiplatelet agents have changed over time. The strongest predictors for higher event rates are a double-blind design and a short delay between symptom onset and randomization. An important reduction in event rates over time could not be demonstrated.
DOI: 10.6084/m9.figshare.5120809.v1
title: Supplementary Material for: The 450-Band Resolution G- and R-Banded Standard Karyotype of the Donkey (<i>Equus asinus</i>, 2n = 62)

description: Donkey chromosomes were earlier characterized separately by C-, G- and R-banding techniques. However, direct comparisons between G- and R-banding patterns have still not been carried out in this species. The present study reports this comparison at the 450-band level by using replication G- and R-banding patterns. Two sets of synchronized lymphocyte cultures were set up to obtain early (GBA+CBA-banding) and late (RBA-banding) BrdU incorporation. Slides were stained with acridine orange and observed under a fluorescence microscope. Reverse GBA+CBA- and RBA-banded karyotypes at the 450-band level were constructed. To verify G- and R-banding patterns in some acrocentric chromosomes, sequential GBA+CBA/Ag-NORs and RBA/Ag-NORs were also performed. The results of CBA-banding patterns obtained in 12 animals from 2 breeds showed a pronounced polymorphism of heterochromatin, especially in EAS1q-prox. Ideogrammatic representations of G- and R-banded karyotypes were constructed using only one common G- and R-banding nomenclature. In the present study both G- and R-banding patterns and relative ideograms are presented as standard karyotype for this species at the 450-band level.
DOI: 10.6084/m9.figshare.5120800
title: Supplementary Material for: Mechanism of Visual Sensations Experienced during Pars Plana Vitrectomy under Retrobulbar Anesthesia

description: <i>Purpose:</i> To investigate the visual sensations experienced by patients during vitrectomy under retrobulbar anesthesia. <i>Methods:</i> 30 men and 45 women with a mean age of 65.3 ± 10.6 years underwent vitrectomy under retrobulbar anesthesia for macular disease. 28 eyes had an idiopathic epiretinal membrane, 13 had an idiopathic macular hole, 32 had macular edema (17 diabetic retinopathy and 15 retinal vein occlusion), and 2 had submacular hemorrhage. 49 patients with nonmacular disease underwent similar vitrectomy procedures and were used for comparison. An interview was conducted with the patient about his/her visual sensations during and within 3 h of the vitrectomy. <i>Results:</i> 70 (93.3%) of the patients reported seeing lights, 53 (70.7%) reported seeing colors, and 48 (64.0%) reported seeing movements or moving objects. Of the patients who reported seeing movements or moving objects, 44 (58.7%) reported seeing surgical instruments, and 5 (6.7%) saw the surgeon’s fingers or hands. Patients with macular diseases tended to report more visual sensations than patients with nonmacular diseases. The patients’ description and drawings appeared to arise mainly from the shadows cast by the intravitreal objects, and some patients perceived highly accurate details including the movements and color of the objects. <i>Conclusions:</i> Visual sensations are experienced by approximately 90% of the patients, and there may be a common mechanism by which patients perceive the intravitreal objects that are not focused on by the retina through the eye’s optical system.
DOI: 10.6084/m9.figshare.5120803
title: Supplementary Material for: DNase I Inhibits a Late Phase of Reactive Oxygen Species Production in Neutrophils

description: Neutrophils kill bacteria on extracellular complexes of DNA fibers and bactericidal proteins known as neutrophil extracellular traps (NETs). The NET composition and the bactericidal mechanisms they use are not fully understood. Here, we show that treatment with deoxyribonuclease (DNase I) impairs a late oxidative response elicited by Gram-positive and Gram-negative bacteria and also by phorbol ester. Isoluminol-dependent chemiluminescence elicited by opsonized <i>Listeria monocytogenes</i>-stimulated neutrophils was inhibited by DNase I, and the DNase inhibitory effect was also evident when phagocytosis was blocked, suggesting that DNase inhibits an extracellular mechanism of reactive oxygen species (ROS) generation. The DNase inhibitory effect was independent of actin polymerization. Phagocytosis and cell viability were not impaired by DNase I. Immunofluorescence analysis shows that myeloperoxidase is present on NETs. Furthermore, granular proteins were detected in NETs from Rab27a-deficient neutrophils which have deficient exocytosis, suggesting that exocytosis and granular protein distribution on NETs proceed by independent mechanisms. NADPH oxidase subunits were also detected on NETs, and the detection of extracellular trap-associated NADPH oxidase subunits was abolished by treatment with DNase I and dependent on cell stimulation. In vitro analyses demonstrate that MPO and NADPH oxidase activity are not directly inhibited by DNase I, suggesting that its effect on ROS production depends on NET disassembly. Altogether, our data suggest that inhibition of ROS production by microorganism-derived DNase would contribute to their ability to evade killing.
DOI: 10.6084/m9.figshare.5120806
title: Supplementary Material for: PPARγ1-Induced Caveolin-1 Enhances Cholesterol Efflux and Attenuates Atherosclerosis in Apolipoprotein E-Deficient Mice

description: <i>Objective:</i> Caveolin-1 (Cav-1) may positively or negatively influence the development of atherosclerosis, depending on the cell type and the metabolic pathways regulated by this protein. We investigate the effects of Cav-1 on cholesterol efflux in RAW264.7 infected with AdPPARγ1 and whether Cav-1 could attenuate established atherosclerotic lesions in PPARγ1-treated apoE-deficient mice. <i>Methods and Results:</i> Compared with AdGFP control, PPARγ1 and Cav-1 were constitutively overexpressed in AdPPARγ1-infected RAW264.7 cells, which stimulated cholesterol efflux to apolipoprotein A-I. Using a small interfering RNA approach (Cav-1-siRNA) we achieved an efficient and specific knockdown of caveolin-1 expression (80%), which resulted in a remarkable reduction of cholesterol efflux in RAW264.7 cells . Moreover, PPARγ1-treated Cav-1-siRNA RAW264.7 cells showed more ability to stimulate cholesterol efflux than Cav-1-siRNA RAW264.7 cells, but far less than control-siRNA RAW264.7 cells and PPARγ1-treated RAW264.7 cells. In addition, 40-week-old apoE-deficient mice fed a Western-type diet and infected for 4 weeks with AdPPARγ1 showed induced Cav-1 expression in aortic vascular endothelial cells, smooth muscle cells and macrophages, as well as attenuated established atherosclerotic lesions. <i>Conclusions:</i> PPARγ1 gene therapy could induce Cav-1 expression and enhance cholesterol efflux and attenuate atherosclerosis in apoE-deficient mice.
DOI: 10.6084/m9.figshare.5120812.v1
title: Supplementary Material for: Nitric Oxide Suppresses Cerebral Vasomotion by sGC-Independent Effects on Ryanodine Receptors and Voltage-Gated Calcium Channels

description: <i>Background/Aims:</i> In cerebral arteries, nitric oxide (NO) release plays a key role in suppressing vasomotion. Our aim was to establish the pathways affected by NO in rat middle cerebral arteries. <i>Methods:</i> In isolated segments of artery, isometric tension and simultaneous measurements of either smooth muscle membrane potential or intracellular [Ca<sup>2+</sup>] ([Ca<sup>2+</sup>]<sub>SMC</sub>) changes were recorded. <i>Results:</i> In the absence of <i>L</i>-NAME, asynchronous propagating Ca<sup>2+</sup> waves were recorded that were sensitive to block with ryanodine, but not nifedipine. <i>L</i>-NAME stimulated pronounced vasomotion and synchronous Ca<sup>2+</sup> oscillations with close temporal coupling between membrane potential, tone and [Ca<sup>2+</sup>]<sub>SMC</sub>. If nifedipine was applied together with <i>L</i>-NAME, [Ca<sup>2+</sup>]<sub>SMC</sub> decreased and synchronous Ca<sup>2+</sup> oscillations were lost, but asynchronous propagating Ca<sup>2+</sup> waves persisted. Vasomotion was similarly evoked by either iberiotoxin, or by ryanodine, and to a lesser extent by ODQ. Exogenous application of NONOate stimulated endothelium-independent hyperpolarization and relaxation of either <i>L</i>-NAME-induced or spontaneous arterial tone. NO-evoked hyperpolarization involved activation of BK<sub>Ca</sub> channels via ryanodine receptors (RYRs), with little involvement of sGC. Further, in whole cell mode, NO inhibited current through L-type voltage-gated Ca<sup>2+</sup> channels (VGCC), which was independent of both voltage and sGC. <i>Conclusion:</i> NO exerts sGC-independent actions at RYRs and at VGCC, both of which normally suppress cerebral artery myogenic tone.
DOI: 10.6084/m9.figshare.5120800.v1
title: Supplementary Material for: Mechanism of Visual Sensations Experienced during Pars Plana Vitrectomy under Retrobulbar Anesthesia

description: <i>Purpose:</i> To investigate the visual sensations experienced by patients during vitrectomy under retrobulbar anesthesia. <i>Methods:</i> 30 men and 45 women with a mean age of 65.3 ± 10.6 years underwent vitrectomy under retrobulbar anesthesia for macular disease. 28 eyes had an idiopathic epiretinal membrane, 13 had an idiopathic macular hole, 32 had macular edema (17 diabetic retinopathy and 15 retinal vein occlusion), and 2 had submacular hemorrhage. 49 patients with nonmacular disease underwent similar vitrectomy procedures and were used for comparison. An interview was conducted with the patient about his/her visual sensations during and within 3 h of the vitrectomy. <i>Results:</i> 70 (93.3%) of the patients reported seeing lights, 53 (70.7%) reported seeing colors, and 48 (64.0%) reported seeing movements or moving objects. Of the patients who reported seeing movements or moving objects, 44 (58.7%) reported seeing surgical instruments, and 5 (6.7%) saw the surgeon’s fingers or hands. Patients with macular diseases tended to report more visual sensations than patients with nonmacular diseases. The patients’ description and drawings appeared to arise mainly from the shadows cast by the intravitreal objects, and some patients perceived highly accurate details including the movements and color of the objects. <i>Conclusions:</i> Visual sensations are experienced by approximately 90% of the patients, and there may be a common mechanism by which patients perceive the intravitreal objects that are not focused on by the retina through the eye’s optical system.
DOI: 10.6084/m9.figshare.5120794
title: Supplementary Material for: Cytoarchitecture of a Cichlid Fish Telencephalon

description: Although the telencephalon of ray-finned fishes has garnered considerable attention from comparative neuroanatomists, detailed descriptions of telencephalic organization are available for only a few species. This necessarily limits our understanding of telencephalic evolution, particularly in light of the extraordinary diversity of ray-finned fishes. Thus, we have charted the cyctoarchitecture of the telencephalon of the African cichlid fish, <i>Astatotilapia (Haplochromis) burtoni</i>. We examined tissue sectioned in the transverse plane, and categorized cell groups based on size, shape, and staining intensity of cells, the density and distribution of cells, cell-poor zones, and relationship of cell groups to the anterior commissure and external sulci. In addition, to facilitate visualization of the transitions among cell groups, we aligned and animated a series of 100 sequential brain sections. We found that the <i>A. burtoni</i> telencephalon was similar to other percomorphs in being highly elaborated with many distinct cell groups. In the pallium, Dm, Dl, and Dc had a large number of cell groups, whereas Dd and Dp were more uniform. Although we recognized many similarities between the pallium of <i>A. burtoni </i>and other teleosts, we also recognized two cell groups (Dl-g and Dm-2) that might represent specializations of cichlids. We found that the subpallium had a similar organization to that of other ray-finned fishes.
DOI: 10.6084/m9.figshare.5120788
title: Supplementary Material for: Phenotypic Analyses and Mutation Screening of the <i>SLC26A4</i> and <i>FOXI1</i> Genes in 101 Taiwanese Families with Bilateral Nonsyndromic Enlarged Vestibular Aqueduct (DFNB4) or Pendred Syndrome

description: Recessive mutations in the <i>SLC26A4</i> gene are responsible for nonsyndromic enlarged vestibular aqueduct (EVA) and Pendred syndrome. However, in some affected families, only 1 or 0 mutated allele can be identified, as well as no clear correlation between <i>SLC26A4</i> genotypes and clinical phenotypes, hampering the accuracy of genetic counseling. To elucidate the genetic composition of nonsyndromic EVA and Pendred syndrome, we screened related genomic fragments, including the <i>SLC26A4</i> coding regions, the <i>SLC26A4</i> promoter and the <i>FOXI1 </i>transcription factor gene, in 101 Taiwanese families, and analyzed their phenotypic and genotypic results. Mutation screening in the <i>SLC26A4</i> coding regions by direct sequencing and quantitative polymerase chain reaction detected 2 mutations in 63 (62%) families, 1 mutation in 24 (24%) families and no mutation in 14 (14%) families. The radiological findings, the presence of goiters and the audiological results were not different among probands (i.e. index cases of the families) with different <i>SLC26A4</i> genotypes. Specifically, probands heterozygous for <i>SLC26A4</i> mutations demonstrated clinical features indistinguishable from those of probands with 2 mutated alleles, implicating that there might be undetected mutations. However, except for a variant (c.–2554G&gt;A of <i>SLC26A4</i>) with possible pathological consequences, no definite mutation was detected after extensive screening in the <i>SLC26A4</i> promoter and <i>FOXI1</i>. In other words, in most Taiwanese families nonsyndromic EVA or Pendred syndrome might not result from aberrance in the transcriptional control of <i>SLC26A4</i> by <i>FOXI1</i>. Meanwhile, exploration of undetected mutations in the <i>SLC26A4</i> noncoding regions revealed 9 divergent haplotypes among the 21 no-mutation-detected <i>SLC26A4</i> alleles of the c.919-2A&gt;G heterozygotes, indicating that there might be no common and predominant mutations in the <i>SLC26A4</i> introns.
DOI: 10.6084/m9.figshare.5120791
title: Supplementary Material for: Signaling Pathways of the TREM-1- and TLR4-Mediated Neutrophil Oxidative Burst

description: The triggering receptor expressed on myeloid cells 1 (TREM-1) is involved in the innate inflammatory response to microbial infections. Activation and expression of TREM-1 by polymorphonuclear neutrophils (PMN) occurs in concert with Toll-like receptors (TLR) such as TLR4 for bacterial lipopolysaccharide. However, it is currently unclear how this is mediated on a molecular level. Using pharmacological inhibitors and Western blot analysis we demonstrate that phosphatidyl inositide 3-kinase, phospholipase C and the mitogen-activated kinase p38MAPK are essential for the TREM-1- and TLR4-induced oxidative burst of human PMN. The activation of protein kinase B and extracellular signal-related kinase show characteristic phosphorylation patterns upon single or co-ligation indicating individual activation pathways of both receptors. Taken together, we provide new insights into the mechanisms how TREM-1 and TLR interact creating synergistic activation in PMN. These results shed a new light on our understanding of how the innate inflammatory responses are regulated and might contribute to the development of future concepts for the treatment of severe inflammatory conditions such as sepsis.
DOI: 10.6084/m9.figshare.5120794.v1
title: Supplementary Material for: Cytoarchitecture of a Cichlid Fish Telencephalon

description: Although the telencephalon of ray-finned fishes has garnered considerable attention from comparative neuroanatomists, detailed descriptions of telencephalic organization are available for only a few species. This necessarily limits our understanding of telencephalic evolution, particularly in light of the extraordinary diversity of ray-finned fishes. Thus, we have charted the cyctoarchitecture of the telencephalon of the African cichlid fish, <i>Astatotilapia (Haplochromis) burtoni</i>. We examined tissue sectioned in the transverse plane, and categorized cell groups based on size, shape, and staining intensity of cells, the density and distribution of cells, cell-poor zones, and relationship of cell groups to the anterior commissure and external sulci. In addition, to facilitate visualization of the transitions among cell groups, we aligned and animated a series of 100 sequential brain sections. We found that the <i>A. burtoni</i> telencephalon was similar to other percomorphs in being highly elaborated with many distinct cell groups. In the pallium, Dm, Dl, and Dc had a large number of cell groups, whereas Dd and Dp were more uniform. Although we recognized many similarities between the pallium of <i>A. burtoni </i>and other teleosts, we also recognized two cell groups (Dl-g and Dm-2) that might represent specializations of cichlids. We found that the subpallium had a similar organization to that of other ray-finned fishes.
DOI: 10.6084/m9.figshare.5120779
title: Supplementary Material for: A Powerful Two-Stage Association Test Using Case-Control and Case-Parents Genotype Data

description: <i>Objective:</i> The performance of association tests based on case-control or case-parents substudy alone can be improved by jointly using genetic data from two substudies. However, genetic data from different sources may not be combinable due to population stratification. We propose a two-stage association test based on using combinability tests in stage 1 and association tests in stage 2. <i>Methods:</i> The combinability tests are designed for testing that genotype data from different sources have same genotype frequencies and relative risks. The association tests are well known tests in the literature. We propose a method to adjust the significance levels at two stages so that the overall type I error rate of the two-stage test can be controlled at the desired level. <i>Results:</i> The simulation results confirm that the two-stage test has empirical type I error rates approximately equal to the predetermined levels while making substantially fewer false negatives than the usual test based only on case-parents substudy. <i>Conclusion:</i> It is advantageous to combinecase-control and case-parents data into a single analysis.The two-stage test has significant power improvement when the family-based test has weak or moderate power performance and is robust to the effect of population stratification.
DOI: 10.6084/m9.figshare.5120785
title: Supplementary Material for: A Case for the Worldwide Collection of Primary Benign Brain Tumors

description: <i>Background:</i> Incidence data on malignant tumors are reported by the International Agency for Research on Cancer, with 189,485 new malignant brain tumors globally in 2002. However, collection and reporting of benign brain tumors are not universal. The objective here is to encourage the collection of primary benign brain tumors worldwide. <i>Methods:</i> Worldwide numbers of primary benign brain tumors were estimated through published articles and cancer registry reports presenting directly or indirectly reported benign incidence rates or frequencies for regions or countries. <i>Results:</i> An estimated 186,678 benign brain tumors were diagnosed worldwide in 2002. The estimated numbers of benign brain tumors were higher in females than males (105,918 vs. 80,759). Since many countries do not report primary benign brain tumors, the incidence rate estimates vary significantly by region. <i>Conclusions:</i> This is the first survey to assess worldwide numbers of benign brain tumors. Under-reporting, non-standardized collection, lack of age-adjustment, and other causes of the varying incidence rates must be considered. However, the estimated number of benign brain tumors approximately equals, and could exceed, the number of malignant brain tumors globally. Registration of primary benign brain histologies in different geographical areas and ethnicities could provide clues to the underlying causes of these tumors.
DOI: 10.6084/m9.figshare.5120782
title: Supplementary Material for: Dietary Fat and Coronary Heart Disease: Summary of Evidence from Prospective Cohort and Randomised Controlled Trials

description: Medicine