cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5122828
title: Supplementary Material for: Phenotyping of Tianma-Stimulated Differentiated Rat Neuronal B104 Cells by Quantitative Proteomics

description: <i>Gastrodia elata blume</i> (tianma) is a traditional Chinese herb often used in the treatment of convulsions, headaches, and hypertension. Although interest in neuronal-related actions of tianma is increasing, minimal studies have been conducted to determine its specific effects on neuronal cells. This study was designed to examine the effects of tianma on the metabolism in differentiated neuroblastoma cells using the isobaric tag for relative and absolute quantitation (iTRAQ) technology. Stimulation of these cells with tianma caused changes in the expression of 38 proteins that were subsequently classified according to their physiological functions and association with neurodegenerative diseases. We identified six proteins with altered functional activities in neurodegenerative disease states that were modulated by tianma: triosephosphate isomerase (Tpi1), peptidyl-prolyl cis-trans isomerase A (Ppia), neural cell adhesion molecule 1 (Ncam1), ubiquitin carboxyl-terminal hydrolase isozyme L1 (Uchl1), septin-2 (Sept2) and heat shock protein 90 (Hsp90aa1). We postulate that tianma mediates its neuroprotective effects via upregulation of Ncam1, Hsp90aa1, Tpi1 and Ppia while downregulating Sept2 and Uchl1. These changes in protein expression aid in the restoration of the intracellular environment to a metabolically balanced state, promoting cell survival. Based on these observed data, we conclude that tianma has therapeutic potential, especially for neurodegenerative diseases.
DOI: 10.6084/m9.figshare.5122831.v1
title: Supplementary Material for: Immune Dysregulation in Chronic Stress: A Quantitative and Functional Assessment of Regulatory T Cells

description: <i>Objective:</i> Chronic stress is closely related to immune dysfunction. Immune parameters have been analyzed in many ways in humans and animals under chronic stress. Recently, it has been proved that FoxP3+ regulatory T cells (Tregs) play a key role in immune regulation in vivo. However, it has not yet been elucidated how Tregs respond to chronic stress in vivo. Therefore, in the present study, we investigated the frequency of and functional changes in Tregs from mice under chronic stress. <i>Methods:</i> Spleen cells were separated from C57/BL6 mice that had been exposed to immobilization stress for 3 weeks. The frequencies of FoxP3+ and CD4+ CD25+ cells were analyzed by flow cytometry. CD4+CD25– cells (effector T cells, Teffs), CD4+CD25+ cells (Tregs) and CD4– cells (antigen-presenting cells, APCs) were separated for the functional assessment of the proliferative activity of Teffs, the suppressive activity of Tregs and the feeder activity of APCs. <i>Results:</i> The results showed that chronic immobilization stress significantly increased the frequencies of CD4+CD25+ and CD4+FoxP3+ cells. Chronic immobilization stress also enhanced the suppressive function of CD4+ CD25+ Tregs. On the other hand, the proliferative activity of Teffs and the feeder activity of APCs were decreased in the mice under chronic immobilization stress. <i>Conclusion:</i> Taken together, it is suggested that increased number and function of Tregs may actively contribute to the immune dysfunction in chronic immobilization stress, synergizing with the decreased function of Teffs and APCs.
DOI: 10.6084/m9.figshare.5122822
title: Supplementary Material for: AGO Recommendations for Diagnosis and Treatment of Patients with Primary and Metastatic Breast Cancer. Update 2011

description: Medicine
DOI: 10.6084/m9.figshare.5122816
title: IFN-α-based treatment of patients with chronic HCV show increased levels of cells with myeloid-derived suppressor cell phenotype and of IDO and NOS

description: <b>Introduction:</b> Hepatitis C virus (HCV) infection causes chronic hepatitis, which is often associated with suppressed anti-HCV immune responses. We have recently reported accumulation of myeloid-derived suppressor cells (MDSCs) and suppressed immunity in cancer patients. <b>Aim:</b> The main aim of this study was to determine whether chronic HCV patients harbor high of MDSCs in general and in nonresponders to IFN-based therapy in particular as well as to analyze the immune suppressive molecules. <b>Methods:</b> Peripheral blood samples withdrawn from 154 patients with chronic HCV infection and were categorized into responders and nonresponders based on viral titer upon IFN-α treatment. <b>Results:</b> The relative and absolute numbers of MDSCs defined as Lin<sup>−</sup>/HLA-DR<sup>−</sup>/CD33<sup>+</sup>/CD11b<sup>+</sup> increased in all HCV patients, where they were higher in nonresponders than in responders. Additionally, the levels of MDSCs after 4–6 months of treatment in responders were lower than during the course of treatment. The responders also showed higher levels of IL-2 coincided with increased numbers of dendritic cells (DCs), CD4<sup>+</sup> and CD8<sup>+</sup> T cells. The levels of total NOS and IDO were also higher in nonresponders as compared to responders and healthy controls, while the expression levels of CD3ζ was lower in responders as compared to nonresponders and healthy volunteers. <b>Conclusion:</b> Chronic HCV patients harbor high numbers of MDSCs, which are higher in nonresponders than in responders. The higher numbers of MDSCs associated with increases in the suppressing factors.
DOI: 10.6084/m9.figshare.5122819
title: Supplementary Material for: Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia Can Present as Frontotemporal Dementia Syndrome

description: <i>Background/Aims:</i> We review the characteristics of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP) and determine prevalence of behavioral variant of frontotemporal dementia (bvFTD) features in ALSP. <i>Methods:</i> Clinical and pathological information was abstracted from histopathologically confirmed ALSP cases identified by a systematic literature search. A new case of ALSP presenting as bvFTD was also described. <i>Results:</i> We retrieved 51 ALSP cases. Mean age of onset was 42.2 years. Mean disease duration was 6.2 years, with 24 cases lasting 4 years or fewer. Fourteen cases had 3 or more of the 6 key bvFTD features. White matter hyperintensities on T<sub>2</sub>-weighted MRI, motor symptoms, seizures and amnesia were common. <i>Conclusion:</i> ALSP can underlie FTD syndrome, as well as rapidly progressive dementia.
DOI: 10.6084/m9.figshare.5122810
title: Supplementary Material for: Age-Related Changes in the Elastic Tissue of the Human Aorta

description: <i>Background:</i> Age-related arterial alterations affecting cells, matrix and biomolecules are the main culprit for initiation and progression of cardiovascular disease. The objective of this study is to gain further insights into the complex mechanism of elastic tissue ageing in human aortic blood vessels. <i>Methods:</i> One hundred and nineteen human aortic tissue samples were collected from adult patients (101 males, 18 females; age 40–86 years) undergoing coronary artery bypass grafting. Overall extracellular matrix architecture was examined by multiphoton laser scanning microscopy and histology. Matrix metalloproteinases 2 and 9, corresponding tissue inhibitors 1 and 2 as well as desmosine were determined. mRNA levels of tropoelastin were assessed by quantitative RT-PCR. <i>Results:</i> Age-related destruction of the vascular elastic laminas as well as a loss of interlamina cross-links were observed by laser scanning microscopy. These results were confirmed by histology indicating increasing interlamina gaps. There were no significant differences in matrix turnover or desmosine content. A steady decrease in tropoelastin mRNA by about 50% per 10 years of age increase was observed. <i>Conclusions:</i> Our findings indicate that ageing is accompanied by a destruction of the elastic vascular structure. However, tropoelastin expression analysis suggests that elastogenesis occurs throughout life with constantly decreasing levels.
DOI: 10.6084/m9.figshare.5122816.v1
title: IFN-α-based treatment of patients with chronic HCV show increased levels of cells with myeloid-derived suppressor cell phenotype and of IDO and NOS

description: <b>Introduction:</b> Hepatitis C virus (HCV) infection causes chronic hepatitis, which is often associated with suppressed anti-HCV immune responses. We have recently reported accumulation of myeloid-derived suppressor cells (MDSCs) and suppressed immunity in cancer patients. <b>Aim:</b> The main aim of this study was to determine whether chronic HCV patients harbor high of MDSCs in general and in nonresponders to IFN-based therapy in particular as well as to analyze the immune suppressive molecules. <b>Methods:</b> Peripheral blood samples withdrawn from 154 patients with chronic HCV infection and were categorized into responders and nonresponders based on viral titer upon IFN-α treatment. <b>Results:</b> The relative and absolute numbers of MDSCs defined as Lin<sup>−</sup>/HLA-DR<sup>−</sup>/CD33<sup>+</sup>/CD11b<sup>+</sup> increased in all HCV patients, where they were higher in nonresponders than in responders. Additionally, the levels of MDSCs after 4–6 months of treatment in responders were lower than during the course of treatment. The responders also showed higher levels of IL-2 coincided with increased numbers of dendritic cells (DCs), CD4<sup>+</sup> and CD8<sup>+</sup> T cells. The levels of total NOS and IDO were also higher in nonresponders as compared to responders and healthy controls, while the expression levels of CD3ζ was lower in responders as compared to nonresponders and healthy volunteers. <b>Conclusion:</b> Chronic HCV patients harbor high numbers of MDSCs, which are higher in nonresponders than in responders. The higher numbers of MDSCs associated with increases in the suppressing factors.
DOI: 10.6084/m9.figshare.5122819.v1
title: Supplementary Material for: Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia Can Present as Frontotemporal Dementia Syndrome

description: <i>Background/Aims:</i> We review the characteristics of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP) and determine prevalence of behavioral variant of frontotemporal dementia (bvFTD) features in ALSP. <i>Methods:</i> Clinical and pathological information was abstracted from histopathologically confirmed ALSP cases identified by a systematic literature search. A new case of ALSP presenting as bvFTD was also described. <i>Results:</i> We retrieved 51 ALSP cases. Mean age of onset was 42.2 years. Mean disease duration was 6.2 years, with 24 cases lasting 4 years or fewer. Fourteen cases had 3 or more of the 6 key bvFTD features. White matter hyperintensities on T<sub>2</sub>-weighted MRI, motor symptoms, seizures and amnesia were common. <i>Conclusion:</i> ALSP can underlie FTD syndrome, as well as rapidly progressive dementia.
DOI: 10.6084/m9.figshare.5122798
title: Supplementary Material for: Developmental Profiles and Thyroid Hormone Regulation of Brain Transcripts in Frogs: A Species Comparison with Emphasis on <i>Physalaemus</i> <i>pustulosus</i>

description: In amphibians, thyroid hormones (THs) are considered key regulators of brain remodeling during metamorphosis, while sex steroids (estrogens and androgens) control sexual differentiation and gonadal development. However, these two endocrine axes can interact during tadpole brain development. Previously, we demonstrated that THs affect sex steroid-related gene expression in the developing brain of <i>Silurana tropicalis</i> and <i>Rana pipiens</i>; however, the gene expression changes differed between species. We chose to study a third anuran species, <i>Physalaemus</i><i>pustulosus,</i> to test new hypotheses about the role of THs in the regulation of brain gene expression. We first established developmental transcript profiles of TH- and sex steroid-related genes in the brain of <i>P. pustulosus.</i> Then, following the same protocols as in our previous studies, we investigated triiodothyronine (T3) regulation of brain transcripts in premetamorphic<i> P.</i><i>pustulosus</i> and then compared the results with our previous two studies. In the case of TH-related genes, TH receptor beta <i>(trbeta)</i> and deiodinase type 3 <i>(dio3),</i> mRNA developmental profiles were similar in the three species and with respect to other species in the published literature. However, the profiles of TH receptor alpha <i>(tralpha)</i> and deiodinase type 2 <i>(dio2)</i> mRNA revealed differences between anuran species. Among the three anurans we have studied, the direction of the T3 regulation of TH-related genes was overall similar, but the magnitude of gene expression change differed depending on the rate of metamorphosis in a given species. For the sex steroid-related genes, each species exhibited similar developmental profiles but differed in their response to T3. In <i>P. pustulosus</i>, T3 reduced the expression of aromatase <i>(cyp19)</i> while increasing mRNA levels of androgen and estrogen receptors. These results are similar to previous research in <i>R. pipiens</i> but differ from data for <i>S. tropicalis,</i> for which we found an increase in androgen synthesis enzymes but no effect on <i>cyp19.</i> Together, we propose that T3 has the potential to induce the brain androgen system in anurans. This could be achieved by increasing androgen synthesis enzymes <i>(S. tropicalis)</i> or by decreasing estrogen synthesis (due to a decrease in <i>cyp19</i> in <i>P. pustulosus</i> and <i>R. pipiens</i>). In conclusion, we demonstrated that mechanisms of hormone interactions differ between anuran species, but in all cases T3 appears to affect the balance of sex steroids in the brain, stimulating the androgen system. We have shown that the regulation of sex steroid-related genes by T3 is more similar among closely related species than species with similar reproductive and developmental characteristics.
DOI: 10.6084/m9.figshare.5122804
title: Supplementary Material for: Challenges of Interpreting Copy Number Variation in Syndromic and Non-Syndromic Congenital Heart Defects

description: Array comparative genomic hybridization (aCGH) has led to an increased detection of causal chromosomal imbalances in individuals with congenital heart defects (CHD). The introduction of aCGH as a diagnostic tool in a clinical cardiogenetic setting entails numerous challenges. Based on our own experience as well as those of others described in the literature, we outline the state of the art and attempt to answer a number of outstanding questions such as the detection frequency of causal imbalances in different patient populations, the added value of higher-resolution arrays, and the existence of predictive factors in syndromic cases. We introduce a step-by-step approach for clinical interpretation of copy number variants (CNV) detected in CHD, which is primarily based on gene content and overlap with known chromosomal syndromes, rather than on CNV inheritance and size. Based on this algorithm, we have reclassified the detected aberrations in aCGH studies for their causality for syndromic and non-syndromic CHD. From this literature overview, supplemented with own investigations in a cohort of 46 sporadic patients with severe non-syndromic CHD, it seems clear that the frequency of causal CNVs in non-syndromic CHD populations is lower than that in syndromic CNV populations (3.6 vs. 19%). Moreover, causal CNVs in non-syndromic CHD mostly involve imbalances with a moderate effect size and reduced penetrance, whereas the majority of causal imbalances in syndromic CHD consistently affects human development and significantly reduces reproductive fitness.
DOI: 10.6084/m9.figshare.5122807
title: Supplementary Material for: XX SRY-Negative True Hermaphrodism in Two Dogs: Clinical, Morphological, Genetic and Cytogenetic Studies

description: This work aimed at giving a deeper insight into peculiar cases of intersexuality occurring in dogs and known as XX true hermaphrodism due to the existence of both testicular and ovarian tissue in one or both gonads in the presence of an XX chromosome constitution. Clinical, histological and genetic approaches were used in the study of an 8-month-old Cocker Spaniel dog and a 3-year-old mixed-breed Pitbull, both showing a female phenotype, clitoromegaly and male behavior. A normal female karyotype (2n = 78,XX) was noticed, and polymerase chain reaction failed to detect <i>SRY</i> in genomic DNA obtained from peripheral blood lymphocytes of both dogs. The reproductive tract was removed by standard ovariohysterectomy and processed for histology. Thereafter, a normal female phenotype was reconstructed by vaginoplasty. Histological examination revealed bilateral ovotestis in both cases: the gonads showed immature testicular parenchyma containing seminiferous tubules, Sertoli and Leydig cells, but no signs of spermatogenesis, together with differently developed ovarian follicles containing oocytes. In the ovotestes, steroidogenesis was detected by P450c17-immunoreactivity in Leydig cells as well as in theca cells, whereas no MIS-immunoreactivity was shown by the Sertoli cells. Genital tracts of Wolffian and Müllerian origin co-existed in both subjects. Both dogs belong to the very rare cases in which testicular tissue develops in the absence of the key gene, <i>SRY.</i> Up to date very few genetic events have been associated with this abnormal sexual differentiation: <i>SOX9 </i>over-expression and <i>RSPO1</i> mutation. Nevertheless, neither of them has been found in these dogs.
DOI: 10.6084/m9.figshare.5122798.v1
title: Supplementary Material for: Developmental Profiles and Thyroid Hormone Regulation of Brain Transcripts in Frogs: A Species Comparison with Emphasis on <i>Physalaemus</i> <i>pustulosus</i>

description: In amphibians, thyroid hormones (THs) are considered key regulators of brain remodeling during metamorphosis, while sex steroids (estrogens and androgens) control sexual differentiation and gonadal development. However, these two endocrine axes can interact during tadpole brain development. Previously, we demonstrated that THs affect sex steroid-related gene expression in the developing brain of <i>Silurana tropicalis</i> and <i>Rana pipiens</i>; however, the gene expression changes differed between species. We chose to study a third anuran species, <i>Physalaemus</i><i>pustulosus,</i> to test new hypotheses about the role of THs in the regulation of brain gene expression. We first established developmental transcript profiles of TH- and sex steroid-related genes in the brain of <i>P. pustulosus.</i> Then, following the same protocols as in our previous studies, we investigated triiodothyronine (T3) regulation of brain transcripts in premetamorphic<i> P.</i><i>pustulosus</i> and then compared the results with our previous two studies. In the case of TH-related genes, TH receptor beta <i>(trbeta)</i> and deiodinase type 3 <i>(dio3),</i> mRNA developmental profiles were similar in the three species and with respect to other species in the published literature. However, the profiles of TH receptor alpha <i>(tralpha)</i> and deiodinase type 2 <i>(dio2)</i> mRNA revealed differences between anuran species. Among the three anurans we have studied, the direction of the T3 regulation of TH-related genes was overall similar, but the magnitude of gene expression change differed depending on the rate of metamorphosis in a given species. For the sex steroid-related genes, each species exhibited similar developmental profiles but differed in their response to T3. In <i>P. pustulosus</i>, T3 reduced the expression of aromatase <i>(cyp19)</i> while increasing mRNA levels of androgen and estrogen receptors. These results are similar to previous research in <i>R. pipiens</i> but differ from data for <i>S. tropicalis,</i> for which we found an increase in androgen synthesis enzymes but no effect on <i>cyp19.</i> Together, we propose that T3 has the potential to induce the brain androgen system in anurans. This could be achieved by increasing androgen synthesis enzymes <i>(S. tropicalis)</i> or by decreasing estrogen synthesis (due to a decrease in <i>cyp19</i> in <i>P. pustulosus</i> and <i>R. pipiens</i>). In conclusion, we demonstrated that mechanisms of hormone interactions differ between anuran species, but in all cases T3 appears to affect the balance of sex steroids in the brain, stimulating the androgen system. We have shown that the regulation of sex steroid-related genes by T3 is more similar among closely related species than species with similar reproductive and developmental characteristics.
DOI: 10.6084/m9.figshare.5122801
title: Supplementary Material for: Effective Subthalamic Nucleus Deep Brain Stimulation Sites May Differ for Tremor, Bradykinesia and Gait Disturbances in Parkinson’s Disease

description: <i>Background/Aims:</i> Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective therapy for Parkinson’s disease (PD). This study investigates whether improvement for particular PD symptoms varies differentially with respect to stimulation location in the STN. <i>Methods:</i> Ten PD patients treated with bilateral STN DBS were enrolled in the study. Each electrode contact was stimulated independently to assess for changes in tremor, bradykinesia, and gait. Electrode contacts were localized via MRI. A novel iterative volumetric analysis was used to search the contact space for stimulation regions corresponding to alleviation of specific symptoms. <i>Results:</i> Tremor was best controlled with DBS applied to the more dorsal, anterior, and medial areas of the contact space. Improvement in bradykinesia was seen largely within the middle of the contact space. Gait improvement was observed with ventral contacts, likely bordering the ventral boundaries of the STN. <i>Conclusion:</i> The iterative volumetric analysis is a valuable tool in identifying anatomic regions responsive to DBS across a subject population treated for PD. In the subjects tested, overlapping efficacy for all symptoms was observed in the region of the STN, but anatomic variances in the responsiveness for tremor, bradykinesia, and gait were found.
DOI: 10.6084/m9.figshare.5122807.v1
title: Supplementary Material for: XX SRY-Negative True Hermaphrodism in Two Dogs: Clinical, Morphological, Genetic and Cytogenetic Studies

description: This work aimed at giving a deeper insight into peculiar cases of intersexuality occurring in dogs and known as XX true hermaphrodism due to the existence of both testicular and ovarian tissue in one or both gonads in the presence of an XX chromosome constitution. Clinical, histological and genetic approaches were used in the study of an 8-month-old Cocker Spaniel dog and a 3-year-old mixed-breed Pitbull, both showing a female phenotype, clitoromegaly and male behavior. A normal female karyotype (2n = 78,XX) was noticed, and polymerase chain reaction failed to detect <i>SRY</i> in genomic DNA obtained from peripheral blood lymphocytes of both dogs. The reproductive tract was removed by standard ovariohysterectomy and processed for histology. Thereafter, a normal female phenotype was reconstructed by vaginoplasty. Histological examination revealed bilateral ovotestis in both cases: the gonads showed immature testicular parenchyma containing seminiferous tubules, Sertoli and Leydig cells, but no signs of spermatogenesis, together with differently developed ovarian follicles containing oocytes. In the ovotestes, steroidogenesis was detected by P450c17-immunoreactivity in Leydig cells as well as in theca cells, whereas no MIS-immunoreactivity was shown by the Sertoli cells. Genital tracts of Wolffian and Müllerian origin co-existed in both subjects. Both dogs belong to the very rare cases in which testicular tissue develops in the absence of the key gene, <i>SRY.</i> Up to date very few genetic events have been associated with this abnormal sexual differentiation: <i>SOX9 </i>over-expression and <i>RSPO1</i> mutation. Nevertheless, neither of them has been found in these dogs.