cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5121682
title: Supplementary Material for: Temsirolimus Is Highly Effective as Third-Line Treatment in Chromophobe Renal Cell Cancer

description: We report unexpectedly high efficacy of temsirolimus as third-line treatment in a patient with metastatic chromophobe renal cell carcinoma. After failure of two sequentially administered tyrosine kinase inhibitors, treatment with temsirolimus resulted in a prolonged partial remission of 14 months, and the response is still continuing. Up to now, no data from randomized clinical studies have been published addressing the question of efficacy of temsirolimus as third-line treatment after failure of tyrosine kinase inhibitors. The case presented here implies that temsirolimus could be a viable option for patients with metastatic chromophobe renal cell carcinoma.
DOI: 10.6084/m9.figshare.5121685.v1
title: Supplementary Material for: Androgen Receptor Mutations Are Associated with Altered Epigenomic Programming as Evidenced by <i>HOXA5</i> Methylation

description: Male external genital differentiation is accompanied by implementation of a long-term, male-specific gene expression pattern indicating androgen programming in cultured genital fibroblasts. We hypothesized the existence of an epigenetic background contributing to this phenomenon. DNA methylation levels in 2 normal scrotal fibroblast strains from 46,XY males compared to 2 labia majora fibroblast strains from 46,XY females with complete androgen insensitivity syndrome (AIS) due to androgen receptor (AR) mutations were analyzed by Illumina GoldenGate methylation arrays®. Results were validated with pyrosequencing in labia majora fibroblast strains from fifteen 46,XY patients and compared to nine normal male scrotal fibroblast strains. <i>HOXA5</i> showed a significantly higher methylation level in complete AIS. This finding was confirmed by bisulfite pyrosequencing of 14 CpG positions within the <i>HOXA5</i> promoter in the same strains. Extension of the 2 groups revealed a constant low <i>HOXA5</i> methylation pattern in the controls in contrast to a highly variable methylation pattern in the AIS patients. <i>HOXA5</i> represents a candidate gene of androgen-mediated promoter methylation. The constantly low <i>HOXA5</i> DNA methylation level of normal male scrotal fibroblast strains and the frequently high methylation levels in labia majora fibroblast strains in AIS indicate for the first time that androgen programming in sexual differentiation is not restricted to global gene transcription but also occurs at the epigenetic level.
DOI: 10.6084/m9.figshare.5121688
title: Supplementary Material for: Regulatory T Cells Control Type I Food Allergy to Beta-Lactoglobulin in Mice

description: <i>Background:</i> Regulatory T cells contribute to peripheral immune tolerance, yet their ability to control immediate-type hypersensitivity (ITH) reactions involved in IgE-mediated food allergy is still poorly documented. <i>Objectives:</i> We investigated in mice whether CD4+CD25+ regulatory T cells could control ITH to β-lactoglobulin (BLG), a major allergen in cow’s milk. <i>Methods:</i> C3H/HeOuJ mice were sensitized by repeated oral gavage with BLG plus cholera toxin as adjuvant and orally challenged with BLG alone to elicit allergic symptoms. Mice were treated with the anti-CD25 mAb (PC61) before sensitization. Oral sensitization (afferent phase of ITH) was assessed by production of BLG-specific serum antibodies and Th1/Th2-type cytokines by specific CD4+ T cells in mesenteric lymph nodes. ITH was elicited by oral BLG challenge (efferent phase of ITH) and we monitored symptom scores, numbers and function of intestinal mast cells and serum level of the mucosal mast cell protease mMCP-1. <i>Results:</i> Upon oral BLG challenge, orally sensitized mice developed only mild clinical signs. Anti-CD25 mAb-treated mice exhibited enhancement of both BLG-specific CD4+ T cell priming with IL-4, IL-5, IL-13 and IFN-γ production and total IgE, and BLG-specific IgE, IgG1 and IgG2a in serum. Anti-CD25 mAb treatment caused more severe symptoms upon BLG challenge, which correlated with enhanced serum levels of the mucosal mast cell protease mMCP-1. <i>Conclusions:</i> These data document that constitutive CD4+CD25+ regulatory T cells alleviate clinical signs of ITH to dietary BLG by modulating the priming of BLG-specific T and B cell responses during oral sensitization and enhancing mast cell degranulation.
DOI: 10.6084/m9.figshare.5121673
title: Supplementary Material for: Association Tests for X-Chromosomal Markers – A Comparison of Different Test Statistics

description: <i>Objective:</i> Genome-wide association studies have successfully elucidated the genetic background of complex diseases, but X chromosomal data have usually not been analyzed. A reason for this is that there is no consensus approach for the analysis taking into account the specific features of X chromosomal data. This contribution evaluates test statistics proposed for X chromosomal markers regarding type I error frequencies and power. <i>Methods:</i> We performed extensive simulation studies covering a wide range of different settings. Besides characteristics of the general population, we investigated sex-balanced or unbalanced sampling procedures as well as sex-specific effect sizes, allele frequencies and prevalence. Finally, we applied the test statistics to an association data set on Crohn’s disease. <i>Results:</i> Simulation results imply that in addition to standard quality control, sex-specific allele frequencies should be checked to control for type I errors. Furthermore, we observed distinct differences in power between test statistics which are determined by sampling design and sex specificity of effect sizes. Analysis of the Crohn’s disease data detects two previously unknown genetic regions on the X chromosome. <i>Conclusion:</i> Although no test is uniformly most powerful under all settings, recommendations are offered as to which test performs best under certain conditions.
DOI: 10.6084/m9.figshare.5121676
title: Supplementary Material for: Nuclear Receptor Coactivators Are Coexpressed with Steroid Receptors and Regulated by Estradiol in Mouse Brain

description: <i>Background/Aims:</i> The steroid hormones, including estradiol (E) and progesterone, act in the brain to regulate female reproductive behavior and physiology. These hormones mediate many of their biological effects by binding to their respective intracellular receptors. The receptors for estrogens (ER) and progestins (PR) interact with nuclear receptor coactivators to initiate transcription of steroid-responsive genes. Work from our laboratory and others reveals that nuclear receptor coactivators, including steroid receptor coactivator-1 (SRC-1) and SRC-2, function in brain to modulate ER-mediated induction of the PR gene and hormone-dependent behaviors. In order for steroid receptors and coactivators to function together, both must be expressed in the same cells. <i>Methods:</i> Triple-label immunofluorescence was used to determine if E-induced PR cells also express SRC-1 or SRC-2 in reproductively relevant brain regions of the female mouse. <i>Results:</i> The majority of E-induced PR cells in the medial preoptic area (61%), ventromedial nucleus of the hypothalamus (63%) and arcuate nucleus (76%) coexpressed both SRC-1 and SRC-2. A smaller proportion of PR cells expressed either SRC-1 or SRC-2, while a few PR cells expressed neither coactivator. In addition, compared to control animals, 17β-estradiol benzoate (EB) treatment increased SRC-1 levels in the arcuate nucleus, but not the medial preoptic area or the ventromedial nucleus of the hypothalamus. EB did not alter SRC-2 expression in any of the three brain regions analyzed. <i>Conclusions:</i> Taken together, the present findings identify a population of cells in which steroid receptors and nuclear receptor coactivators may interact to modulate steroid sensitivity in brain and regulate hormone-dependent behaviors in female mice. Given that cell culture studies reveal that SRC-1 and SRC-2 can mediate distinct steroid-signaling pathways, the present findings suggest that steroids can produce a variety of complex responses in these specialized brain cells.
DOI: 10.6084/m9.figshare.5121673.v1
title: Supplementary Material for: Association Tests for X-Chromosomal Markers – A Comparison of Different Test Statistics

description: <i>Objective:</i> Genome-wide association studies have successfully elucidated the genetic background of complex diseases, but X chromosomal data have usually not been analyzed. A reason for this is that there is no consensus approach for the analysis taking into account the specific features of X chromosomal data. This contribution evaluates test statistics proposed for X chromosomal markers regarding type I error frequencies and power. <i>Methods:</i> We performed extensive simulation studies covering a wide range of different settings. Besides characteristics of the general population, we investigated sex-balanced or unbalanced sampling procedures as well as sex-specific effect sizes, allele frequencies and prevalence. Finally, we applied the test statistics to an association data set on Crohn’s disease. <i>Results:</i> Simulation results imply that in addition to standard quality control, sex-specific allele frequencies should be checked to control for type I errors. Furthermore, we observed distinct differences in power between test statistics which are determined by sampling design and sex specificity of effect sizes. Analysis of the Crohn’s disease data detects two previously unknown genetic regions on the X chromosome. <i>Conclusion:</i> Although no test is uniformly most powerful under all settings, recommendations are offered as to which test performs best under certain conditions.
DOI: 10.6084/m9.figshare.5121679.v1
title: Supplementary Material for: Brain Activity Supporting Working Memory Accuracy in Patients with Paranoid Schizophrenia: A Functional Magnetic Resonance Imaging Study

description: <i>Background:</i> Dysfunctional working memory (WM) has been recognized as one of the most consistent deficits in schizophrenia. Studies that investigated the neural correlates of WM-related pathology by comparing patients with schizophrenia and control participants have produced controversial results, reporting task-related hyper- or hypoactivity in frontoparietal networks. <i>Method:</i> We addressed this question by comparing BOLD signals for accurate responses during a WM task for emotional faces between a homogeneous group of high-performing patients and a control group. <i>Results:</i> Our results confirm previous findings of left prefrontal hyperactivity contrasted with hypoactivity in right prefrontal cortex to support WM performance. We also extend previous work by reporting enhanced activity in higher visual areas of patients during encoding and maintenance. <i>Conclusion:</i> Our findings and those of the literature can be integrated into a model, where preserved visual cognition in high-functioning patients with hypofrontality is explained by activation of contralateral homologue areas combined with enhanced recruitment of sensory areas.
DOI: 10.6084/m9.figshare.5121667
title: Supplementary Material for: Primate Prefrontal Cortex Evolution: Human Brains Are the Extreme of a Lateralized Ape Trend

description: The prefrontal cortex is commonly associated with cognitive capacities related to human uniqueness: purposeful actions towards higher-level goals, complex social information processing, introspection, and language. Comparative investigations of the prefrontal cortex may thus shed more light on the neural underpinnings of what makes us human. Using histological data from 19 anthropoid primate species (6 apes including humans and 13 monkeys), we investigate cross-species relative size changes along the anterior (prefrontal) and posterior (motor) axes of the cytoarchitectonically defined frontal lobe in both hemispheres. Results reveal different scaling coefficients in the left versus right prefrontal hemisphere, suggest that the primary factor underlying the evolution of primate brain architecture is left hemispheric prefrontal hyperscaling, and indicate that humans are the extreme of a left prefrontal ape specialization in relative white to grey matter volume. These results demonstrate a neural adaptive shift distinguishing the ape from the monkey radiation possibly related to a cognitive grade shift between (great) apes and other primates.
DOI: 10.6084/m9.figshare.5121670
title: Supplementary Material for: Developmental Expression Mapping of a Gene Implicated in Multiple Neurodevelopmental Disorders, <i>A2bp1 (Fox1)</i>

description: The neuronal transcription splicing factor, <i>A2BP1,</i> has been implicated in a variety of neurodevelopmental disorders; however, the role of <i>A2BP1</i> in brain development and gene regulatory function remains to be explicated. Here, we map <i>A2bp1</i> gene expression, focusing on the developing forebrain of the C57BL6J mouse. Early in forebrain development, <i>A2bp1 </i>expression is highly reminiscent of the expression of genes marking postmitotic GABAergic cells emanating from the ventral telencephalon during migration to the dorsal pallium. Ventral pallial expression remains low after the migratory period. Broader dorsal pallial expression becomes more evident late prenatally and early postnatally. This is paralleled by dense, restricted expression in the ventrobasal dorsal thalamic complex and mid-hypothalamic region. Outside of the forebrain, there is significant expression in motor pathways. These data indicate that <i>A2BP1</i> mutations may clinically affect very selective forebrain neuron types from early periods of development.
DOI: 10.6084/m9.figshare.5121682.v1
title: Supplementary Material for: Temsirolimus Is Highly Effective as Third-Line Treatment in Chromophobe Renal Cell Cancer

description: We report unexpectedly high efficacy of temsirolimus as third-line treatment in a patient with metastatic chromophobe renal cell carcinoma. After failure of two sequentially administered tyrosine kinase inhibitors, treatment with temsirolimus resulted in a prolonged partial remission of 14 months, and the response is still continuing. Up to now, no data from randomized clinical studies have been published addressing the question of efficacy of temsirolimus as third-line treatment after failure of tyrosine kinase inhibitors. The case presented here implies that temsirolimus could be a viable option for patients with metastatic chromophobe renal cell carcinoma.
DOI: 10.6084/m9.figshare.5121664
title: Supplementary Material for: Retinal Pigment Epithelium Cell Alignment on Nanostructured Collagen Matrices

description: We investigated attachment and migration of human retinal pigment epithelial cells (primary, SV40-transfected and ARPE-19) on nanoscopically defined, two-dimensional matrices composed of parallel-aligned collagen type I fibrils. These matrices were used non-cross-linked (native) or after riboflavin/UV-A cross-linking to study cell attachment and migration by time-lapse video microscopy. Expression of collagen type I and IV, MMP-2 and of the collagen-binding integrin subunit α<sub>2</sub> were examined by immunofluorescence and Western blotting. SV40-RPE cells quickly attached to the nanostructured collagen matrices and aligned along the collagen fibrils. However, they disrupted both native and cross-linked collagen matrices within 5 h. Primary RPE cells aligned more slowly without destroying either native or cross-linked substrates. Compared to primary RPE cells, ARPE-19 cells showed reduced alignment but partially disrupted the matrices within 20 h after seeding. Expression of the collagen type I-binding integrin subunit α<sub>2</sub> was highest in SV40-RPE cells, lower in primary RPE cells and almost undetectable in ARPE-19 cells. Thus, integrin α<sub>2</sub> expression levels directly correlated with the degree of cell alignment in all examined RPE cell types. Specific integrin subunit α<sub>2</sub>-mediated matrix binding was verified by preincubation with an α<sub>2</sub>-function-blocking antibody, which impaired cell adhesion and alignment to varying degrees in primary and SV40-RPE cells. Since native matrices supported extended and directed primary RPE cell growth, optimizing the matrix production procedure may in the future yield nanostructured collagen matrices serving as transferable cell sheet carriers.
DOI: 10.6084/m9.figshare.5121670.v1
title: Supplementary Material for: Developmental Expression Mapping of a Gene Implicated in Multiple Neurodevelopmental Disorders, <i>A2bp1 (Fox1)</i>

description: The neuronal transcription splicing factor, <i>A2BP1,</i> has been implicated in a variety of neurodevelopmental disorders; however, the role of <i>A2BP1</i> in brain development and gene regulatory function remains to be explicated. Here, we map <i>A2bp1</i> gene expression, focusing on the developing forebrain of the C57BL6J mouse. Early in forebrain development, <i>A2bp1 </i>expression is highly reminiscent of the expression of genes marking postmitotic GABAergic cells emanating from the ventral telencephalon during migration to the dorsal pallium. Ventral pallial expression remains low after the migratory period. Broader dorsal pallial expression becomes more evident late prenatally and early postnatally. This is paralleled by dense, restricted expression in the ventrobasal dorsal thalamic complex and mid-hypothalamic region. Outside of the forebrain, there is significant expression in motor pathways. These data indicate that <i>A2BP1</i> mutations may clinically affect very selective forebrain neuron types from early periods of development.
DOI: 10.6084/m9.figshare.5121658
title: Supplementary Material for: Clinical and Radiological Outcomes after Intracranial Atherosclerotic Stroke: A Comprehensive Approach Comparing Stroke Subtypes

description: <i>Background:</i> We previously reported that intracranial large-artery atherosclerotic stroke (ICAS) had a relatively large salvageable area of less severe hypoperfusion. However, information regarding the outcome after ICAS is lacking. We hypothesized ICAS would show more favorable clinical and radiological outcomes than other stroke mechanisms. <i>Methods:</i> Consecutive patients underwent admission (n = 149) and follow-up (n = 80) multiparametric magnetic resonance imaging (MRI) for acute middle cerebral artery infarcts within 6 h of symptom onset. T<sub>max</sub> perfusion lesion maps were generated. We assessed the difference in the degree of infarct growth ([follow-up diffusion-weighted imaging (DWI) volume – initial DWI volume]/initial penumbra volume) and the presence of excellent long-term outcome [defined as a modified Rankin scale (mRS) score ≤2 and a modified Barthel index (mBI) ≧90 at 3 months]. <i>Results:</i> Of 149 patients, 24 (16.1%) had ICAS, 75 (50.3%) had cardioembolic stroke, 21 (14.1%) had extracranial large-artery atherosclerotic stroke, and 29 (19.5%) had cryptogenic embolic stroke. Despite a higher recurrence rate in patients with ICAS compared to other subtypes (p = 0.026), the long-term outcome was better in ICAS (p = 0.003 for an mRS score ≤2 and p = 0.004 for an mBI ≧90). Among 80 patients who underwent follow-up MRI, patients who had minimal infarct growth (less than 10%) were more prevalent among the patients with ICAS (p = 0.004). Multivariate testing revealed that ICAS was independently associated with both excellent long-term outcome (OR = 3.45; 95% CI = 1.11–10.78) and minimal infarct growth (OR = 10.40; 95% CI = 1.20–90.11). <i>Conclusion:</i> Our data show that patients with ICAS have favorable clinical and radiological outcomes compared with other subtypes.
DOI: 10.6084/m9.figshare.5121661
title: Supplementary Material for: Early Repolarisation Syndrome and Ischemic Stroke: Is There a Link?

description: Medicine
DOI: 10.6084/m9.figshare.5121652
title: Supplementary Material for: Regulation of Gap Junctional Communication by Astrocytic Mitochondrial K<sub>ATP</sub> Channels following Neurotoxin Administration in in vitro and in vivo Models

description: It is known that neuronal ATP-sensitive potassium (K<sub>ATP</sub>) channels and astrocytic gap junctions (GJs) are involved in the mechanism underlying neurodisorders. The K<sub>ATP</sub> channels exist also in glial cells, and the objective of this study was to determine whether the astrocytic K<sub>ATP</sub> channels exert their effect on neurotoxin-induced neurodysfunction through regulating the astrocytic GJ function. The results showed that diazoxide, a selective mitochondrial K<sub>ATP</sub> (mitoK<sub>ATP</sub>) channel opener, enhanced the GJ coupling, but 5-hydroxydecanoate, a selective mitoK<sub>ATP</sub> channel blocker that significantly inhibits GJ coupling in vitro did not. Activation of astrocytic mitoK<sub>ATP</sub> channels alleviated kainic acid-induced dysfunction of GJ intercellular communication. Finally, activation of mitoK<sub>ATP</sub> channels improved the astrocytic GJ coupling in the hippocampus after seizures due to the colabeling of GJ subunit connexin 43 and connexin 45 with glial marker and was increased substantially by the administration of diazoxide. Western blot demonstrated that the mitoK<sub>ATP</sub> channels regulated the expression of connexin 43 (P2; active form) and connexin 45 in the epileptic hippocampus. These findings demonstrate that activation of astrocytic mitoK<sub>ATP</sub> channels improves the GJ function in astrocytes, indicating that the effect of the astrocytic mitoK<sub>ATP</sub> channels on neurotoxin-induced neurodysfunction might be, in part, through the regulation of the GJ-coupled spatial buffering in the hippocampus.
DOI: 10.6084/m9.figshare.5121655
title: Supplementary Material for: Tooth Size Variation Related to Age in Amboseli Baboons

description: We measured the molar size from a single population of wild baboons from Amboseli (Kenya), both females (n = 57) and males (n = 50). All the females were of known age; the males represented a mix of known-age individuals (n = 31) and individuals with ages estimated to within 2 years (n = 19). The results showed a significant reduction in the mesiodistal length of teeth in both sexes as a function of age. Overall patterns of age-related change in tooth size did not change whether we included or excluded the individuals of estimated age, but patterns of statistical significance changed as a result of changed sample sizes. Our results demonstrate that tooth length is directly related to age due to interproximal wearing caused by M2 and M3 compression loads. Dental studies in primates, including both fossil and extant species, are mostly based on specimens obtained from osteological collections of varying origins, for which the age at death of each individual in the sample is not known. Researchers should take into account the phenomenon of interproximal attrition leading to reduced tooth size when measuring tooth length for ondontometric purposes.