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CXCL12-Mediated Guidance of Migrating Embryonic Stem Cell-Derived Neural Progenitors Transplanted into the Hippocampus Nathaniel W Hartman, Joseph E Carpentino, Kristi LaMonica, ... more(7) Public Library of Science 2010-12-31 Stem cell therapies for neurodegenerative disorders require accurate delivery of the transplanted cells to the sites of damage. Numerous studies have established that fluid injections to the hippocampus can induce lesions in the dentate gyrus (DG) that lead to cell death within the upper blade. Using a mouse model of temporal lobe epilepsy, we previously observed that embryonic stem cell-derived neural progenitors (ESNPs) survive and differentiate within the granule cell layer after stereotaxic delivery to the DG, replacing the endogenous cells of the upper blade. To investigate the mechanisms for ESNP migration and repair in the DG, we examined the role of the chemokine CXCL12 in mice subjected to kainic acid-induced seizures. We now show that ESNPs transplanted into the DG show extensive migration through the upper blade, along the septotemporal axis of the hippocampus. Seizures upregulate CXCL12 and infusion of the CXCR4 antagonist AMD3100 by osmotic minipump attenuated ESNP migration. We also demonstrate that seizures promote the differentiation of transplanted ESNPs toward neuronal rather than astrocyte fates. These findings suggest that ESNPs transplanted into the adult rodent hippocampus migrate in response to cytokine-mediated signals.
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Subject 의과학, 인문사회과학 Source PLOS URL http://dx.doi.org/10.1371/journal.pone.0015856view Article Title CXCL12-Mediated Guidance of Migrating Embryonic Stem Cell-Derived Neural Progenitors Transplanted into the HippocampusAuthors Nathaniel W Hartman; Joseph E Carpentino; Kristi LaMonica; Danielle E Mor; Janice R Naegele; Laura Grabel; Rafael LindenAbstract Stem cell therapies for neurodegenerative disorders require accurate delivery of the transplanted cells to the sites of damage. Numerous studies have established that fluid injections to the hippocampus can induce lesions in the dentate gyrus (DG) that lead to cell death within the upper blade. Using a mouse model of temporal lobe epilepsy, we previously observed that embryonic stem cell-derived neural progenitors (ESNPs) survive and differentiate within the granule cell layer after stereotaxic delivery to the DG, replacing the endogenous cells of the upper blade. To investigate the mechanisms for ESNP migration and repair in the DG, we examined the role of the chemokine CXCL12 in mice subjected to kainic acid-induced seizures. We now show that ESNPs transplanted into the DG show extensive migration through the upper blade, along the septotemporal axis of the hippocampus. Seizures upregulate CXCL12 and infusion of the CXCR4 antagonist AMD3100 by osmotic minipump attenuated ESNP migration. We also demonstrate that seizures promote the differentiation of transplanted ESNPs toward neuronal rather than astrocyte fates. These findings suggest that ESNPs transplanted into the adult rodent hippocampus migrate in response to cytokine-mediated signals.Is Part Of PLoS ONE 2010-12-31 , Vol.5 (12) Identifier EISSN: 1932-6203 ; PISSN: DOI 10.1371/journal.pone.0015856Publisher Public Library of ScienceCategory /Biology and life sciences/Cell biology/Cellular types/Animal cells/Neurons; /Biology and life sciences/Developmental biology/Cell differentiation; /Biology and life sciences/Cell biology/Cell motility/Chemotaxis/Chemokines; /Biology and life sciences/Developmental biology/Cell differentiation/Neuronal differentiation; /Biology and life sciences/Biochemistry/Proteins/Cytoskeletal proteins/Nestin; /Medicine and health sciences/Surgical and invasive medical procedures/Blood and lymphatic system procedures/Stem cell transplantation; /Medicine and health sciences/Surgical and invasive medical procedures/Transplantation/Cell transplantation/Stem cell transplantation; /Biology and life sciences/Anatomy/Brain/Hippocampus; /Medicine and health sciences/Anatomy/Brain/Hippocampus; /Biology and life sciences/Cell biology/Cell motility/Cell migration/Neuron migration; /Biology and life sciences/Developmental biology/Cell migration/Neuron migration; /Biology and life sciences/Neuroscience/Cellular neuroscience/NeuronsLicense Hartman et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Ancient DNA of the Extinct Lava Shearwater (Puffinus olsoni) from the Canary Islands Reveals Incipient Differentiation within the P. puffinus Complex Oscar Ramirez, Juan Carlos Illera, Juan Carlos Rando, ... more(7) Public Library of Science 2010-12-31 Background: The loss of species during the Holocene was, dramatically more important on islands than on continents. Seabirds from islands are very vulnerable to human-induced alterations such as habitat destruction, hunting and exotic predators. For example, in the genus Puffinus (family Procellariidae) the extinction of at least five species has been recorded during the Holocene, two of them coming from the Canary Islands. Methodology/Principal Findings: We used bones of the two extinct Canary shearwaters (P. olsoni and P. holeae) to obtain genetic data, for use in providing insights into the differentiation process within the genus Puffinus. Although mitochondrial DNA (mtDNA) cytochrome b sequences were successfully retrieved from four Holocene specimens of the extinct Lava shearwater (P. olsoni) from Fuerteventura (Canary Islands), the P. holeae specimens yielded no DNA. Only one haplotype was detected in P. olsoni, suggesting a low genetic diversity within this species. Conclusions: The phylogenetic analyses based on the DNA data reveal that: (i) the “Puffinus puffinus complex”, an assemblage of species defined using osteological characteristics (P. puffinus, P. olsoni, P. mauretanicus, P. yelkouan and probably P. holeae), shows unresolved phylogenetic relationships; (ii) despite the differences in body size and proportions, P. olsoni and the extant P. puffinus are sister species. Several hypotheses can be considered to explain the incipient differentiation between P. olsoni and P. puffinus.
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Subject 의과학, 인문사회과학 Source PLOS URL http://dx.doi.org/10.1371/journal.pone.0016072view Article Title Ancient DNA of the Extinct Lava Shearwater (Puffinus olsoni) from the Canary Islands Reveals Incipient Differentiation within the P. puffinus ComplexAuthors Oscar Ramirez; Juan Carlos Illera; Juan Carlos Rando; Jacob Gonzalez-Solis; Josep Antoni Alcover; Carles Lalueza-Fox; M Thomas P GilbertAbstract Background: The loss of species during the Holocene was, dramatically more important on islands than on continents. Seabirds from islands are very vulnerable to human-induced alterations such as habitat destruction, hunting and exotic predators. For example, in the genus Puffinus (family Procellariidae) the extinction of at least five species has been recorded during the Holocene, two of them coming from the Canary Islands. Methodology/Principal Findings: We used bones of the two extinct Canary shearwaters (P. olsoni and P. holeae) to obtain genetic data, for use in providing insights into the differentiation process within the genus Puffinus. Although mitochondrial DNA (mtDNA) cytochrome b sequences were successfully retrieved from four Holocene specimens of the extinct Lava shearwater (P. olsoni) from Fuerteventura (Canary Islands), the P. holeae specimens yielded no DNA. Only one haplotype was detected in P. olsoni, suggesting a low genetic diversity within this species. Conclusions: The phylogenetic analyses based on the DNA data reveal that: (i) the “Puffinus puffinus complex”, an assemblage of species defined using osteological characteristics (P. puffinus, P. olsoni, P. mauretanicus, P. yelkouan and probably P. holeae), shows unresolved phylogenetic relationships; (ii) despite the differences in body size and proportions, P. olsoni and the extant P. puffinus are sister species. Several hypotheses can be considered to explain the incipient differentiation between P. olsoni and P. puffinus.Is Part Of PLoS ONE 2010-12-31 , Vol.5 (12) Identifier EISSN: 1932-6203 ; PISSN: DOI 10.1371/journal.pone.0016072Publisher Public Library of ScienceCategory /Biology and life sciences/Paleontology/Paleogenetics; /Research and analysis methods/Molecular biology techniques/Molecular biology assays and analysis techniques/Phylogenetic analysis; /Biology and life sciences/Genetics/DNA/Forms of DNA/Mitochondrial DNA; /Earth sciences/Paleontology/Paleogenetics; /Biology and life sciences/Evolutionary biology/Evolutionary processes/Species extinction; /Earth sciences/Paleontology/Paleogenetics/Ancient DNA; /Biology and life sciences/Paleontology/Paleogenetics/Ancient DNA; /Biology and life sciences/Genetics/DNA/Ancient DNA; /Biology and life sciences/Molecular biology/Molecular biology techniques/Molecular biology assays and analysis techniques/Phylogenetic analysis; /Biology and life sciences/Biochemistry/Nucleic acids/DNA/Forms of DNA/Mitochondrial DNA; /Biology and life sciences/Biochemistry/Nucleic acids/DNA/Ancient DNA; /Biology and life sciences/Conservation biology/Species extinction; /Ecology and environmental sciences/Conservation science/Conservation biology/Species extinction; /Earth sciences/Geology/Geologic time/Cenozoic era/Quaternary period/Holocene epoch; /Biology and life sciences/Organisms/Animals/Vertebrates/Amniotes/Birds/Seabirds; /Biology and life sciences/Anatomy/Osteology; /Medicine and health sciences/Anatomy/OsteologyLicense Ramirez et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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The CD40-Autophagy Pathway Is Needed for Host Protection Despite IFN-Γ-Dependent Immunity and CD40 Induces Autophagy via Control of P21 Levels Jose-Andres C Portillo, Genevieve Okenka, Erin Reed, ... more(12) Public Library of Science 2010-12-31 Autophagy degrades pathogens in vitro. The autophagy gene Atg5 has been reported to be required for IFN-γ-dependent host protection in vivo. However, these protective effects occur independently of autophagosome formation. Thus, the in vivo role of classic autophagy in protection conferred by adaptive immunity and how adaptive immunity triggers autophagy are incompletely understood. Employing biochemical, genetic and morphological studies, we found that CD40 upregulates the autophagy molecule Beclin 1 in microglia and triggers killing of Toxoplasma gondii dependent on the autophagy machinery. Infected CD40−/− mice failed to upregulate Beclin 1 in microglia/macrophages in vivo. Autophagy-deficient Beclin 1+/− mice, mice with deficiency of the autophagy protein Atg7 targeted to microglia/macrophages as well as CD40−/− mice exhibited impaired killing of T. gondii and were susceptible to cerebral and ocular toxoplasmosis. Susceptibility to toxoplasmosis occurred despite upregulation of IFN-γ, TNF-α and NOS2, preservation of IFN-γ-induced microglia/macrophage anti-T. gondii activity and the generation of anti-T. gondii T cell immunity. CD40 upregulated Beclin 1 and triggered killing of T. gondii by decreasing protein levels of p21, a molecule that degrades Beclin 1. These studies identified CD40-p21-Beclin 1 as a pathway by which adaptive immunity stimulates autophagy. In addition, they support that autophagy is a mechanism through which CD40-dependent immunity mediates in vivo protection and that the CD40-autophagic machinery is needed for host resistance despite IFN-γ.
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Subject 의과학, 인문사회과학 Source PLOS URL http://dx.doi.org/10.1371/journal.pone.0014472view Article Title The CD40-Autophagy Pathway Is Needed for Host Protection Despite IFN-Γ-Dependent Immunity and CD40 Induces Autophagy via Control of P21 LevelsAuthors Jose-Andres C Portillo; Genevieve Okenka; Erin Reed; Angela Subauste; Jennifer Van Grol; Katrin Gentil; Masaaki Komatsu; Keiji Tanaka; Gary Landreth; Beth Levine; Carlos S Subauste; Gordon LangsleyAbstract Autophagy degrades pathogens in vitro. The autophagy gene Atg5 has been reported to be required for IFN-γ-dependent host protection in vivo. However, these protective effects occur independently of autophagosome formation. Thus, the in vivo role of classic autophagy in protection conferred by adaptive immunity and how adaptive immunity triggers autophagy are incompletely understood. Employing biochemical, genetic and morphological studies, we found that CD40 upregulates the autophagy molecule Beclin 1 in microglia and triggers killing of Toxoplasma gondii dependent on the autophagy machinery. Infected CD40−/− mice failed to upregulate Beclin 1 in microglia/macrophages in vivo. Autophagy-deficient Beclin 1+/− mice, mice with deficiency of the autophagy protein Atg7 targeted to microglia/macrophages as well as CD40−/− mice exhibited impaired killing of T. gondii and were susceptible to cerebral and ocular toxoplasmosis. Susceptibility to toxoplasmosis occurred despite upregulation of IFN-γ, TNF-α and NOS2, preservation of IFN-γ-induced microglia/macrophage anti-T. gondii activity and the generation of anti-T. gondii T cell immunity. CD40 upregulated Beclin 1 and triggered killing of T. gondii by decreasing protein levels of p21, a molecule that degrades Beclin 1. These studies identified CD40-p21-Beclin 1 as a pathway by which adaptive immunity stimulates autophagy. In addition, they support that autophagy is a mechanism through which CD40-dependent immunity mediates in vivo protection and that the CD40-autophagic machinery is needed for host resistance despite IFN-γ.Is Part Of PLoS ONE 2010-12-31 , Vol.5 (12) Identifier EISSN: 1932-6203 ; PISSN: DOI 10.1371/journal.pone.0014472Publisher Public Library of ScienceCategory /Medicine and health sciences/Parasitic diseases; /Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/T cells; /Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Macrophages; /Biology and life sciences/Cell biology/Cellular types/Animal cells/Glial cells/Microglial cells; /Medicine and health sciences/Ophthalmology/Eye diseases; /Biology and life sciences/Cell biology/Cell processes/Cell death/Autophagic cell death; /Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/T cells; /Biology and life sciences/Immunology/Immune cells/White blood cells/T cells; /Medicine and health sciences/Immunology/Immune cells/White blood cells/T cells; /Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Macrophages; /Medicine and health sciences/Immunology/Immune cells/White blood cells/Macrophages; /Biology and life sciences/Immunology/Immune cells/White blood cells/Macrophages; /Biology and life sciences/Organisms/Protozoans/Parasitic protozoans/Toxoplasma/Toxoplasma gondii; /Medicine and health sciences/Parasitic diseases/Protozoan infections/ToxoplasmosisLicense Portillo et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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A Knowledge-Based Weighting Framework to Boost the Power of Genome-Wide Association Studies Miao-Xin Li, Pak C Sham, Stacey S Cherny, ... more(5) Public Library of Science 2010-12-31 Background: We are moving to second-wave analysis of genome-wide association studies (GWAS), characterized by comprehensive bioinformatical and statistical evaluation of genetic associations. Existing biological knowledge is very valuable for GWAS, which may help improve their detection power particularly for disease susceptibility loci of moderate effect size. However, a challenging question is how to utilize available resources that are very heterogeneous to quantitatively evaluate the statistic significances. Methodology/Principal Findings: We present a novel knowledge-based weighting framework to boost power of the GWAS and insightfully strengthen their explorative performance for follow-up replication and deep sequencing. Built upon diverse integrated biological knowledge, this framework directly models both the prior functional information and the association significances emerging from GWAS to optimally highlight single nucleotide polymorphisms (SNPs) for subsequent replication. In the theoretical calculation and computer simulation, it shows great potential to achieve extra over 15% power to identify an association signal of moderate strength or to use hundreds of whole-genome subjects fewer to approach similar power. In a case study on late-onset Alzheimer disease (LOAD) for a proof of principle, it highlighted some genes, which showed positive association with LOAD in previous independent studies, and two important LOAD related pathways. These genes and pathways could be originally ignored due to involved SNPs only having moderate association significance. Conclusions/Significance: With user-friendly implementation in an open-source Java package, this powerful framework will provide an important complementary solution to identify more true susceptibility loci with modest or even small effect size in current GWAS for complex diseases.
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Subject 의과학, 인문사회과학 Source PLOS URL http://dx.doi.org/10.1371/journal.pone.0014480view Article Title A Knowledge-Based Weighting Framework to Boost the Power of Genome-Wide Association StudiesAuthors Miao-Xin Li; Pak C Sham; Stacey S Cherny; You-Qiang Song; Thomas MailundAbstract Background: We are moving to second-wave analysis of genome-wide association studies (GWAS), characterized by comprehensive bioinformatical and statistical evaluation of genetic associations. Existing biological knowledge is very valuable for GWAS, which may help improve their detection power particularly for disease susceptibility loci of moderate effect size. However, a challenging question is how to utilize available resources that are very heterogeneous to quantitatively evaluate the statistic significances. Methodology/Principal Findings: We present a novel knowledge-based weighting framework to boost power of the GWAS and insightfully strengthen their explorative performance for follow-up replication and deep sequencing. Built upon diverse integrated biological knowledge, this framework directly models both the prior functional information and the association significances emerging from GWAS to optimally highlight single nucleotide polymorphisms (SNPs) for subsequent replication. In the theoretical calculation and computer simulation, it shows great potential to achieve extra over 15% power to identify an association signal of moderate strength or to use hundreds of whole-genome subjects fewer to approach similar power. In a case study on late-onset Alzheimer disease (LOAD) for a proof of principle, it highlighted some genes, which showed positive association with LOAD in previous independent studies, and two important LOAD related pathways. These genes and pathways could be originally ignored due to involved SNPs only having moderate association significance. Conclusions/Significance: With user-friendly implementation in an open-source Java package, this powerful framework will provide an important complementary solution to identify more true susceptibility loci with modest or even small effect size in current GWAS for complex diseases.Is Part Of PLoS ONE 2010-12-31 , Vol.5 (12) Identifier EISSN: 1932-6203 ; PISSN: DOI 10.1371/journal.pone.0014480Publisher Public Library of ScienceCategory /Computer and information sciences/Computer modeling; /Biology and life sciences/Genetics/Human genetics; /Biology and life sciences/Genetics/Genetic loci; /Biology and life sciences/Genetics/Genetics of disease; /Research and analysis methods/Database and informatics methods/Bioinformatics; /Biology and life sciences/Genetics/Human genetics/Genome-wide association studies; /Biology and life sciences/Computational biology/Genome analysis/Genomic databases; /Biology and life sciences/Genetics/Genomics/Genome analysis/Genomic databases; /Biology and life sciences/Genetics/Genomics/Genome analysis/Genome-wide association studies; /Biology and life sciences/Computational biology/Genome analysis/Genome-wide association studies; /Research and analysis methods/Database and informatics methods/Biological databases/Genomic databases; /Biology and life sciences/Genetics/Gene expression/Gene regulation/MicroRNAs; /Biology and life sciences/Biochemistry/Nucleic acids/RNA/Non-coding RNA/MicroRNAsLicense Li et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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The Brain Reaction to Viewing Faces of Opposite- and Same-Sex Romantic Partners Semir Zeki, John Paul Romaya, Angela Sirigu... more(3) Public Library of Science 2010-12-31 We pursued our functional magnetic resonance imaging (fMRI) studies of the neural correlates of romantic love in 24 subjects, half of whom were female (6 heterosexual and 6 homosexual) and half male (6 heterosexual and 6 homosexual). We compared the pattern of activity produced in their brains when they viewed the faces of their loved partners with that produced when they viewed the faces of friends of the same sex to whom they were romantically indifferent. The pattern of activation and de-activation was very similar in the brains of males and females, and heterosexuals and homosexuals. We could therefore detect no difference in activation patterns between these groups.
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Subject 의과학, 인문사회과학 Source PLOS URL http://dx.doi.org/10.1371/journal.pone.0015802view Article Title The Brain Reaction to Viewing Faces of Opposite- and Same-Sex Romantic PartnersAuthors Semir Zeki; John Paul Romaya; Angela SiriguAbstract We pursued our functional magnetic resonance imaging (fMRI) studies of the neural correlates of romantic love in 24 subjects, half of whom were female (6 heterosexual and 6 homosexual) and half male (6 heterosexual and 6 homosexual). We compared the pattern of activity produced in their brains when they viewed the faces of their loved partners with that produced when they viewed the faces of friends of the same sex to whom they were romantically indifferent. The pattern of activation and de-activation was very similar in the brains of males and females, and heterosexuals and homosexuals. We could therefore detect no difference in activation patterns between these groups.Is Part Of PLoS ONE 2010-12-31 , Vol.5 (12) Identifier EISSN: 1932-6203 ; PISSN: DOI 10.1371/journal.pone.0015802Publisher Public Library of ScienceCategory /Biology and life sciences/Neuroscience/Neuroimaging; /Biology and life sciences/Anatomy/Brain/Hippocampus; /Medicine and health sciences/Anatomy/Brain/Hypothalamus; /Medicine and health sciences/Anatomy/Brain/Hippocampus; /Biology and life sciences/Anatomy/Brain/Hypothalamus; /Biology and life sciences/Anatomy/Brain/Cerebral cortex/Cerebellum; /Medicine and health sciences/Anatomy/Brain/Cerebral cortex/Cerebellum; /Biology and life sciences/Physiology/Respiratory physiology; /Medicine and health sciences/Physiology/Respiratory physiology; /Biology and life sciences/Anatomy/Brain/Cerebral cortex/Parietal lobe; /Medicine and health sciences/Anatomy/Brain/Cerebral cortex/Parietal lobe; /Research and analysis methods/Imaging techniques/Neuroimaging; /People and places/Population groupings/Sexuality groupings/Heterosexuals; /People and places/Population groupings/Sexuality groupings/HomosexualsLicense Zeki, Romaya This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Maternal Psychosocial Stress during Pregnancy and Placenta Weight: Evidence from a National Cohort Study Marion Tegethoff, Naomi Greene, Jørn Olsen, ... more(6) Public Library of Science 2010-12-31 Background: To study in a large-scale cohort with prospective data the associations between psychosocial stress during pregnancy and placenta weight at birth. Animal data suggest that the placenta is involved in stress-related fetal programming. Methodology/Principal Findings: We defined a priori two types of psychosocial stress during pregnancy, life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). We estimated the associations of maternal stress during pregnancy with placenta weight at birth, controlled for length of gestation, by predicting gestational age- and sex-specific z-scores of placenta weight through multiple regression analysis, adjusted for potential confounders (N = 78017 singleton pregnancies). Life stress (per increase in stress score by 1, range: 0–18) during pregnancy was associated with increased placenta weight at birth (z-score, reported in 10−3; B, 14.33; CI, 10.12–18.54). In contrast, emotional symptoms during pregnancy were not associated with placenta weight at birth. Conclusions/Significance: Maternal life stress but not emotional symptoms during pregnancy was associated with increased placenta weight at birth; yet, the association-estimate was rather small. Our results may contribute to a better understanding of the role of the placenta in the regulation of intrauterine processes in response to maternal stress.
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Subject 의과학, 인문사회과학 Source PLOS URL http://dx.doi.org/10.1371/journal.pone.0014478view Article Title Maternal Psychosocial Stress during Pregnancy and Placenta Weight: Evidence from a National Cohort StudyAuthors Marion Tegethoff; Naomi Greene; Jørn Olsen; Andrea H Meyer; Gunther Meinlschmidt; Philippa MiddletonAbstract Background: To study in a large-scale cohort with prospective data the associations between psychosocial stress during pregnancy and placenta weight at birth. Animal data suggest that the placenta is involved in stress-related fetal programming. Methodology/Principal Findings: We defined a priori two types of psychosocial stress during pregnancy, life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). We estimated the associations of maternal stress during pregnancy with placenta weight at birth, controlled for length of gestation, by predicting gestational age- and sex-specific z-scores of placenta weight through multiple regression analysis, adjusted for potential confounders (N = 78017 singleton pregnancies). Life stress (per increase in stress score by 1, range: 0–18) during pregnancy was associated with increased placenta weight at birth (z-score, reported in 10−3; B, 14.33; CI, 10.12–18.54). In contrast, emotional symptoms during pregnancy were not associated with placenta weight at birth. Conclusions/Significance: Maternal life stress but not emotional symptoms during pregnancy was associated with increased placenta weight at birth; yet, the association-estimate was rather small. Our results may contribute to a better understanding of the role of the placenta in the regulation of intrauterine processes in response to maternal stress.Is Part Of PLoS ONE 2010-12-31 , Vol.5 (12) Identifier EISSN: 1932-6203 ; PISSN: DOI 10.1371/journal.pone.0014478Publisher Public Library of ScienceCategory /Medicine and health sciences/Mental health and psychiatry/Psychological stress; /Medicine and health sciences/Women's health/Obstetrics and gynecology/Birth/Labor and delivery; /Medicine and health sciences/Health care/Psychological and psychosocial issues; /Biology and life sciences/Developmental biology/Embryology/Placenta; /Medicine and health sciences/Women's health/Obstetrics and gynecology/Birth; /Medicine and health sciences/Women's health/Obstetrics and gynecology/Pregnancy; /Medicine and health sciences/Women's health/Obstetrics and gynecology/Pregnancy/Hypertensive disorders in pregnancy; /Biology and life sciences/Psychology/Psychological stress; /Social sciences/Psychology/Psychological stress; /Medicine and health sciences/Women's health/Maternal health/Birth/Labor and delivery; /Medicine and health sciences/Women's health/Maternal health/Birth; /Medicine and health sciences/Women's health/Maternal health/Pregnancy; /Medicine and health sciences/Women's health/Maternal health/Pregnancy/Hypertensive disorders in pregnancy; /Medicine and health sciences/Physiology/Physiological parameters/Body weight/Birth weight; /Biology and life sciences/Physiology/Physiological parameters/Body weight/Birth weight; /Medicine and health sciences/Anatomy/Reproductive system/Placenta; /Biology and life sciences/Anatomy/Reproductive system/Placenta; /Medicine and health sciences/Vascular medicine/Blood pressure/Hypertension/Hypertensive disorders in pregnancyLicense Tegethoff et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Glucocorticoid-Mediated Inhibition of Angiogenic Changes in Human Endothelial Cells Is Not Caused by Reductions in Cell Proliferation or Migration James J Logie, Sadaf Ali, Kathryn M Marshall, ... more(7) Public Library of Science 2010-12-31 Background: Glucocorticoid-mediated inhibition of angiogenesis is important in physiology, pathophysiology and therapy. However, the mechanisms through which glucocorticoids inhibit growth of new blood vessels have not been established. This study addresses the hypothesis that physiological levels of glucocorticoids inhibit angiogenesis by directly preventing tube formation by endothelial cells. Methodology/Principal Findings: Cultured human umbilical vein (HUVEC) and aortic (HAoEC) endothelial cells were used to determine the influence of glucocorticoids on tube-like structure (TLS) formation, and on cellular proliferation (5-bromo-2′-deoxyuridine (BrdU) incorporation), viability (ATP production) and migration (Boyden chambers). Dexamethasone or cortisol (at physiological concentrations) inhibited both basal and prostaglandin F2α (PGF2α)-induced and vascular endothelial growth factor (VEGF) stimulated TLS formation in endothelial cells (ECs) cultured on Matrigel, effects which were blocked with the glucocorticoid receptor antagonist RU38486. Glucocorticoids had no effect on EC viability, migration or proliferation. Time-lapse imaging showed that cortisol blocked VEGF-stimulated cytoskeletal reorganisation and initialisation of tube formation. Real time PCR suggested that increased expression of thrombospodin-1 contributed to glucocorticoid-mediated inhibition of TLS formation. Conclusions/Significance: We conclude that glucocorticoids interact directly with glucocorticoid receptors on vascular ECs to inhibit TLS formation. This action, which was conserved in ECs from two distinct vascular territories, was due to alterations in cell morphology rather than inhibition of EC viability, migration or proliferation and may be mediated in part by induction of thrombospodin-1. These findings provide important insights into the anti-angiogenic action of endogenous glucocorticoids in health and disease.
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Subject 의과학, 인문사회과학 Source PLOS URL http://dx.doi.org/10.1371/journal.pone.0014476view Article Title Glucocorticoid-Mediated Inhibition of Angiogenic Changes in Human Endothelial Cells Is Not Caused by Reductions in Cell Proliferation or MigrationAuthors James J Logie; Sadaf Ali; Kathryn M Marshall; Margarete M S Heck; Brian R Walker; Patrick W F Hadoke; Pieter H ReitsmaAbstract Background: Glucocorticoid-mediated inhibition of angiogenesis is important in physiology, pathophysiology and therapy. However, the mechanisms through which glucocorticoids inhibit growth of new blood vessels have not been established. This study addresses the hypothesis that physiological levels of glucocorticoids inhibit angiogenesis by directly preventing tube formation by endothelial cells. Methodology/Principal Findings: Cultured human umbilical vein (HUVEC) and aortic (HAoEC) endothelial cells were used to determine the influence of glucocorticoids on tube-like structure (TLS) formation, and on cellular proliferation (5-bromo-2′-deoxyuridine (BrdU) incorporation), viability (ATP production) and migration (Boyden chambers). Dexamethasone or cortisol (at physiological concentrations) inhibited both basal and prostaglandin F2α (PGF2α)-induced and vascular endothelial growth factor (VEGF) stimulated TLS formation in endothelial cells (ECs) cultured on Matrigel, effects which were blocked with the glucocorticoid receptor antagonist RU38486. Glucocorticoids had no effect on EC viability, migration or proliferation. Time-lapse imaging showed that cortisol blocked VEGF-stimulated cytoskeletal reorganisation and initialisation of tube formation. Real time PCR suggested that increased expression of thrombospodin-1 contributed to glucocorticoid-mediated inhibition of TLS formation. Conclusions/Significance: We conclude that glucocorticoids interact directly with glucocorticoid receptors on vascular ECs to inhibit TLS formation. This action, which was conserved in ECs from two distinct vascular territories, was due to alterations in cell morphology rather than inhibition of EC viability, migration or proliferation and may be mediated in part by induction of thrombospodin-1. These findings provide important insights into the anti-angiogenic action of endogenous glucocorticoids in health and disease.Is Part Of PLoS ONE 2010-12-31 , Vol.5 (12) Identifier EISSN: 1932-6203 ; PISSN: DOI 10.1371/journal.pone.0014476Publisher Public Library of ScienceCategory /Biology and life sciences/Cell biology/Cell motility/Cell migration; /Biology and life sciences/Cell biology/Cellular types/Animal cells/Epithelial cells/Endothelial cells; /Biology and life sciences/Cell biology/Cellular structures and organelles/Cytoskeleton; /Biology and life sciences/Biochemistry/Hormones/Lipid hormones/Hydrocortisone; /Biology and life sciences/Developmental biology/Cell migration; /Biology and life sciences/Developmental biology/Angiogenesis; /Biology and life sciences/Biochemistry/Hormones/Steroid hormones/Hydrocortisone; /Medicine and health sciences/Endocrinology/Endocrine physiology/Growth factors; /Physical sciences/Mathematics/Statistics (mathematics)/Statistical methods/Analysis of variance; /Research and analysis methods/Mathematical and statistical techniques/Statistical methods/Analysis of variance; /Medicine and health sciences/Physiology/Cardiovascular physiology/Angiogenesis; /Biology and life sciences/Physiology/Cardiovascular physiology/Angiogenesis; /Biology and life sciences/Physiology/Endocrine physiology/Growth factors; /Medicine and health sciences/Physiology/Endocrine physiology/Growth factors; /Biology and life sciences/Anatomy/Biological tissue/Epithelium/Epithelial cells/Endothelial cells; /Medicine and health sciences/Anatomy/Biological tissue/Epithelium/Epithelial cells/Endothelial cells; /Biology and life sciences/Anatomy/Cardiovascular anatomy/Blood vessels/Veins/Umbilical veins; /Medicine and health sciences/Anatomy/Cardiovascular anatomy/Blood vessels/Veins/Umbilical veinsLicense Logie et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Simultaneous Effects of Light Intensity and Phosphorus Supply on the Sterol Content of Phytoplankton Maike Piepho, Dominik Martin-Creuzburg, Alexander Wacker, ... more(4) Public Library of Science 2010-12-31 Sterol profiles of microalgae and their change with environmental conditions are of great interest in ecological food web research and taxonomic studies alike. Here, we investigated effects of light intensity and phosphorus supply on the sterol content of phytoplankton and assessed potential interactive effects of these important environmental factors on the sterol composition of algae. We identified sterol contents of four common phytoplankton genera, Scenedesmus, Chlamydomonas, Cryptomonas and Cyclotella, and analysed the change in sterol content with varying light intensities in both a high-phosphorus and a low-phosphorus approach. Sterol contents increased significantly with increasing light in three out of four species. Phosphorus-limitation reversed the change of sterol content with light intensity, i.e., sterol content decreased with increasing light at low phosphorus supply. Generally sterol contents were lower in low-phosphorus cultures. In conclusion, both light and phosphorus conditions strongly affect the sterol composition of algae and hence should be considered in ecological and taxonomic studies investigating the biochemical composition of algae. Data suggest a possible sterol limitation of growth and reproduction of herbivorous crustacean zooplankton during summer when high light intensities and low phosphorus supply decrease sterol contents of algae.
PLOS
Subject 의과학, 인문사회과학 Source PLOS URL http://dx.doi.org/10.1371/journal.pone.0015828view Article Title Simultaneous Effects of Light Intensity and Phosphorus Supply on the Sterol Content of PhytoplanktonAuthors Maike Piepho; Dominik Martin-Creuzburg; Alexander Wacker; Wendy A PeerAbstract Sterol profiles of microalgae and their change with environmental conditions are of great interest in ecological food web research and taxonomic studies alike. Here, we investigated effects of light intensity and phosphorus supply on the sterol content of phytoplankton and assessed potential interactive effects of these important environmental factors on the sterol composition of algae. We identified sterol contents of four common phytoplankton genera, Scenedesmus, Chlamydomonas, Cryptomonas and Cyclotella, and analysed the change in sterol content with varying light intensities in both a high-phosphorus and a low-phosphorus approach. Sterol contents increased significantly with increasing light in three out of four species. Phosphorus-limitation reversed the change of sterol content with light intensity, i.e., sterol content decreased with increasing light at low phosphorus supply. Generally sterol contents were lower in low-phosphorus cultures. In conclusion, both light and phosphorus conditions strongly affect the sterol composition of algae and hence should be considered in ecological and taxonomic studies investigating the biochemical composition of algae. Data suggest a possible sterol limitation of growth and reproduction of herbivorous crustacean zooplankton during summer when high light intensities and low phosphorus supply decrease sterol contents of algae.Is Part Of PLoS ONE 2010-12-31 , Vol.5 (12) Identifier EISSN: 1932-6203 ; PISSN: DOI 10.1371/journal.pone.0015828Publisher Public Library of ScienceCategory /Biology and life sciences/Cell biology/Cellular structures and organelles/Cell membranes; /Biology and life sciences/Biochemistry/Lipids/Sterols; /Biology and life sciences/Biochemistry/Lipids/Cholesterol; /Biology and life sciences/Organisms/Plants/Algae/Phytoplankton; /Biology and life sciences/Organisms/Animals/Invertebrates/Plankton/Phytoplankton; /Biology and life sciences/Organisms/Plants/Algae; /Biology and life sciences/Organisms/Animals/Invertebrates/Plankton/Zooplankton; /Biology and life sciences/Organisms/Animals/Invertebrates/Plankton/Zooplankton/Daphnia; /Biology and life sciences/Organisms/Animals/Invertebrates/Arthropoda/CrustaceansLicense Piepho et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Drug-Driven AMPA Receptor Redistribution Mimicked by Selective Dopamine Neuron Stimulation Matthew T C Brown, Camilla Bellone, Manuel Mameli, ... more(11) Public Library of Science 2010-12-31 Background: Addictive drugs have in common that they cause surges in dopamine (DA) concentration in the mesolimbic reward system and elicit synaptic plasticity in DA neurons of the ventral tegmental area (VTA). Cocaine for example drives insertion of GluA2-lacking AMPA receptors (AMPARs) at glutamatergic synapes in DA neurons. However it remains elusive which molecular target of cocaine drives such AMPAR redistribution and whether other addictive drugs (morphine and nicotine) cause similar changes through their effects on the mesolimbic DA system. Methodology / Principal Findings: We used in vitro electrophysiological techniques in wild-type and transgenic mice to observe the modulation of excitatory inputs onto DA neurons by addictive drugs. To observe AMPAR redistribution, post-embedding immunohistochemistry for GluA2 AMPAR subunit was combined with electron microscopy. We also used a double-floxed AAV virus expressing channelrhodopsin together with a DAT Cre mouse line to selectively express ChR2 in VTA DA neurons. We find that in mice where the effect of cocaine on the dopamine transporter (DAT) is specifically blocked, AMPAR redistribution was absent following administration of the drug. Furthermore, addictive drugs known to increase dopamine levels cause a similar AMPAR redistribution. Finally, activating DA VTA neurons optogenetically is sufficient to drive insertion of GluA2-lacking AMPARs, mimicking the changes observed after a single injection of morphine, nicotine or cocaine. Conclusions / Significance: We propose the mesolimbic dopamine system as a point of convergence at which addictive drugs can alter neural circuits. We also show that direct activation of DA neurons is sufficient to drive AMPAR redistribution, which may be a mechanism associated with early steps of non-substance related addictions.
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Subject 의과학, 인문사회과학 Source PLOS URL http://dx.doi.org/10.1371/journal.pone.0015870view Article Title Drug-Driven AMPA Receptor Redistribution Mimicked by Selective Dopamine Neuron StimulationAuthors Matthew T C Brown; Camilla Bellone; Manuel Mameli; Gwenael Labouèbe; Christina Bocklisch; Bénédicte Balland; Lionel Dahan; Rafael Luján; Karl Deisseroth; Christian Lüscher; Olivier Jacques ManzoniAbstract Background: Addictive drugs have in common that they cause surges in dopamine (DA) concentration in the mesolimbic reward system and elicit synaptic plasticity in DA neurons of the ventral tegmental area (VTA). Cocaine for example drives insertion of GluA2-lacking AMPA receptors (AMPARs) at glutamatergic synapes in DA neurons. However it remains elusive which molecular target of cocaine drives such AMPAR redistribution and whether other addictive drugs (morphine and nicotine) cause similar changes through their effects on the mesolimbic DA system. Methodology / Principal Findings: We used in vitro electrophysiological techniques in wild-type and transgenic mice to observe the modulation of excitatory inputs onto DA neurons by addictive drugs. To observe AMPAR redistribution, post-embedding immunohistochemistry for GluA2 AMPAR subunit was combined with electron microscopy. We also used a double-floxed AAV virus expressing channelrhodopsin together with a DAT Cre mouse line to selectively express ChR2 in VTA DA neurons. We find that in mice where the effect of cocaine on the dopamine transporter (DAT) is specifically blocked, AMPAR redistribution was absent following administration of the drug. Furthermore, addictive drugs known to increase dopamine levels cause a similar AMPAR redistribution. Finally, activating DA VTA neurons optogenetically is sufficient to drive insertion of GluA2-lacking AMPARs, mimicking the changes observed after a single injection of morphine, nicotine or cocaine. Conclusions / Significance: We propose the mesolimbic dopamine system as a point of convergence at which addictive drugs can alter neural circuits. We also show that direct activation of DA neurons is sufficient to drive AMPAR redistribution, which may be a mechanism associated with early steps of non-substance related addictions.Is Part Of PLoS ONE 2010-12-31 , Vol.5 (12) Identifier EISSN: 1932-6203 ; PISSN: DOI 10.1371/journal.pone.0015870Publisher Public Library of ScienceCategory /Biology and life sciences/Cell biology/Cellular types/Animal cells/Neurons; /Physical sciences/Chemistry/Chemical compounds/Alkaloids/Cocaine; /Physical sciences/Chemistry/Chemical compounds/Organic compounds/Amines/Catecholamines/Dopamine; /Physical sciences/Physics/Electromagnetic radiation/Light/Light pulses; /Biology and life sciences/Psychology/Addiction/Nicotine addiction; /Medicine and health sciences/Pharmacology/Drugs/Analgesics/Opioids/Morphine; /Physical sciences/Chemistry/Organic chemistry/Organic compounds/Amines/Catecholamines/Dopamine; /Biology and life sciences/Biochemistry/Hormones/Catecholamines/Dopamine; /Medicine and health sciences/Pharmacology/Behavioral pharmacology/Recreational drug use/Cocaine; /Social sciences/Psychology/Addiction/Nicotine addiction; /Medicine and health sciences/Mental health and psychiatry/Substance-related disorders/Nicotine addiction; /Medicine and health sciences/Public and occupational health/Substance-related disorders/Nicotine addiction; /Medicine and health sciences/Pain management/Analgesics/Opioids/Morphine; /Medicine and health sciences/Pharmacology/Drugs/Opioids/Morphine; /Biology and life sciences/Neuroscience/Neurophysiology/Action potentials; /Medicine and health sciences/Public and occupational health/Substance-related disorders/Drug addiction; /Medicine and health sciences/Mental health and psychiatry/Substance-related disorders/Drug addiction; /Biology and life sciences/Psychology/Addiction/Drug addiction; /Social sciences/Psychology/Addiction/Drug addiction; /Biology and life sciences/Biochemistry/Neurochemistry/Neurotransmitters/Biogenic amines/Catecholamines/Dopamine; /Biology and life sciences/Neuroscience/Neurochemistry/Neurotransmitters/Biogenic amines/Catecholamines/Dopamine; /Biology and life sciences/Physiology/Electrophysiology/Neurophysiology/Action potentials; /Medicine and health sciences/Physiology/Electrophysiology/Neurophysiology/Action potentials; /Biology and life sciences/Physiology/Electrophysiology/Membrane potential/Action potentials; /Medicine and health sciences/Physiology/Electrophysiology/Membrane potential/Action potentials; /Biology and life sciences/Neuroscience/Cellular neuroscience/NeuronsLicense Brown et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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The eEF1γ Subunit Contacts RNA Polymerase II and Binds Vimentin Promoter Region Nicoletta Corbi, Enrico Maria Batassa, Cinzia Pisani, ... more(10) Public Library of Science 2010-12-31 Here, we show that the eukaryotic translation elongation factor 1 gamma (eEF1γ) physically interacts with the RNA polymerase II (pol II) core subunit 3 (RPB3), both in isolation and in the context of the holo-enzyme. Importantly, eEF1γ has been recently shown to bind Vimentin mRNA. By chromatin immunoprecipitation experiments, we demonstrate, for the first time, that eEF1γ is also physically present on the genomic locus corresponding to the promoter region of human Vimentin gene. The eEF1γ depletion causes the Vimentin protein to be incorrectly compartmentalised and to severely compromise cellular shape and mitochondria localisation. We demonstrate that eEF1γ partially colocalises with the mitochondrial marker Tom20 and that eEF1γ depletion increases mitochondrial superoxide generation as well as the total levels of carbonylated proteins. Finally, we hypothesise that eEF1γ, in addition to its role in translation elongation complex, is involved in regulating Vimentin gene by contacting both pol II and the Vimentin promoter region and then shuttling/nursing the Vimentin mRNA from its gene locus to its appropriate cellular compartment for translation.
PLOS
Subject 의과학, 인문사회과학 Source PLOS URL http://dx.doi.org/10.1371/journal.pone.0014481view Article Title The eEF1γ Subunit Contacts RNA Polymerase II and Binds Vimentin Promoter RegionAuthors Nicoletta Corbi; Enrico Maria Batassa; Cinzia Pisani; Annalisa Onori; Maria Grazia Di Certo; Georgios Strimpakos; Maurizio Fanciulli; Elisabetta Mattei; Claudio Passananti; Thomas PreissAbstract Here, we show that the eukaryotic translation elongation factor 1 gamma (eEF1γ) physically interacts with the RNA polymerase II (pol II) core subunit 3 (RPB3), both in isolation and in the context of the holo-enzyme. Importantly, eEF1γ has been recently shown to bind Vimentin mRNA. By chromatin immunoprecipitation experiments, we demonstrate, for the first time, that eEF1γ is also physically present on the genomic locus corresponding to the promoter region of human Vimentin gene. The eEF1γ depletion causes the Vimentin protein to be incorrectly compartmentalised and to severely compromise cellular shape and mitochondria localisation. We demonstrate that eEF1γ partially colocalises with the mitochondrial marker Tom20 and that eEF1γ depletion increases mitochondrial superoxide generation as well as the total levels of carbonylated proteins. Finally, we hypothesise that eEF1γ, in addition to its role in translation elongation complex, is involved in regulating Vimentin gene by contacting both pol II and the Vimentin promoter region and then shuttling/nursing the Vimentin mRNA from its gene locus to its appropriate cellular compartment for translation.Is Part Of PLoS ONE 2010-12-31 , Vol.5 (12) Identifier EISSN: 1932-6203 ; PISSN: DOI 10.1371/journal.pone.0014481Publisher Public Library of ScienceCategory /Biology and life sciences/Biochemistry/Proteins/Cytoskeletal proteins; /Research and analysis methods/Biological cultures/Cell cultures/Cultured tumor cells/HeLa cells; /Biology and life sciences/Biochemistry/Bioenergetics/Energy-producing organelles/Mitochondria; /Biology and life sciences/Biochemistry/Proteins/Cytoskeletal proteins/Vimentin; /Research and analysis methods/Precipitation techniques/Immunoprecipitation/Co-immunoprecipitation; /Biology and life sciences/Cell biology/Cellular structures and organelles/Energy-producing organelles/Mitochondria; /Medicine and health sciences/Immunology/Immune system proteins/Antibodies/Monoclonal antibodies; /Biology and life sciences/Immunology/Immune system proteins/Antibodies/Monoclonal antibodies; /Biology and life sciences/Biochemistry/Proteins/Immune system proteins/Antibodies/Monoclonal antibodies; /Biology and life sciences/Biochemistry/Proteins/Regulatory proteins/Elongation factors; /Biology and life sciences/Genetics/Gene expression/Gene regulation/Elongation factors; /Biology and life sciences/Physiology/Immune physiology/Antibodies/Monoclonal antibodies; /Medicine and health sciences/Physiology/Immune physiology/Antibodies/Monoclonal antibodies; /Biology and life sciences/Genetics/Gene expression/Gene regulation/Small interfering RNAs; /Biology and life sciences/Biochemistry/Nucleic acids/RNA/Non-coding RNA/Small interfering RNAs; /Research and analysis methods/Biological cultures/Cell lines/HeLa cellsLicense Corbi et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.