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Sample records for early human germ

  1. New insights into human primordial germ cells and early embryonic development from single-cell analysis.

    PubMed

    Otte, Jörg; Wruck, Wasco; Adjaye, James

    2017-08-01

    Human preimplantation developmental studies are difficult to accomplish due to associated ethical and moral issues. Preimplantation cells are rare and exist only in transient cell states. From a single cell, it is very challenging to analyse the origination of the heterogeneity and complexity inherent to the human body. However, recent advances in single-cell technology and data analysis have provided new insights into the process of early human development and germ cell specification. In this Review, we examine the latest single-cell datasets of human preimplantation embryos and germ cell development, compare them to bulk cell analyses, and interpret their biological implications. © 2017 Federation of European Biochemical Societies.

  2. The fine structure of human germ layers in vivo: clues to the early differentiation of embryonic stem cells in vitro.

    PubMed

    Sathananthan, Henry; Selvaraj, Kamala; Clark, Joan

    2011-08-01

    The fine structure of the three germ layers in human ectopic embryos (stage 7) have been documented by digital light and electron microscopy. The formation of ectoderm, endoderm and mesoderm and notochordal cells, and also the extraembryonic membranes, amnion and yolk sac, are imaged. The germ layers give rise to all the cells and tissues of the human body. Possible clues to the early differentiation of embryonic stem cells (ESC) in vitro were obtained, since these events are more or less mimicked in cultures of ESC derived from the inner cell mass of human blastocysts. The findings are discussed with reference to previous studies on the fine structure of ESC using the same technique. Copyright © 2011. Published by Elsevier Ltd.

  3. Characterization of migratory primordial germ cells in the aorta-gonad-mesonephros of a 4.5-week-old human embryo: a toolbox to evaluate in vitro early gametogenesis.

    PubMed

    Gomes Fernandes, Maria; Bialecka, Monika; Salvatori, Daniela C F; Chuva de Sousa Lopes, Susana M

    2018-05-01

    Which set of antibodies can be used to identify migratory and early post-migratory human primordial germ cells (hPGCs)? We validated the specificity of 33 antibodies for 31 markers, including POU5F1, NANOG, PRDM1 and TFAP2C as specific markers of hPGCs at 4.5 weeks of development of Carnegie stage (CS12-13), whereas KIT and SOX17 also marked the intra-aortic hematopoietic stem cell cluster in the aorta-gonad-mesonephros (AGM). The dynamics of gene expression during germ cell development in mice is well characterized and this knowledge has proved crucial to allow the development of protocols for the in vitro derivation of functional gametes. Although there is a great interest in generating human gametes in vitro, it is still unclear which markers are expressed during the early stages of hPGC development and many studies use markers described in mouse to benchmark differentiation of human PGC-like cells (hPGCLCs). Early post-implantation development differs significantly between mice and humans, and so some germ cells markers, including SOX2, SOX17, IFITM3 and ITGA6 may not identify mPGCs and hPGCs equally well. This immunofluorescence study investigated the expression of putative hPGC markers in the caudal part of a single human embryo at 4.5 weeks of development. We have investigated by immunofluorescence the expression of a set of 33 antibodies for 31 markers, including pluripotency, germ cell, adhesion, migration, surface, mesenchymal and epigenetic markers on paraffin sections of the caudal part, including the AGM region, of a single human embryo (CS12-13). The human material used was anonymously donated with informed consent from elective abortions without medical indication. We observed germ cell specific expression of NANOG, TFAP2C and PRDM1 in POU5F1+ hPGCs in the AGM. The epigenetic markers H3K27me3 and 5mC were sufficient to distinguish hPGCs from the surrounding somatic cells. Some mPGC-markers were not detected in hPGCs, but marked other tissues; whereas

  4. Declaring the Existence of Human Germ-Cell Mutagens

    EPA Science Inventory

    After more than 80 years of searching for human germ-cell mutagens, I think that sufficient evidence already exists for a number of agents to be so considered, and definitive confirmation seems imminent due to the application ofrecently developed genomic techniques. In preparatio...

  5. Characterization of the Epigenetic Changes During Human Gonadal Primordial Germ Cells Reprogramming.

    PubMed

    Eguizabal, C; Herrera, L; De Oñate, L; Montserrat, N; Hajkova, P; Izpisua Belmonte, J C

    2016-09-01

    Epigenetic reprogramming is a central process during mammalian germline development. Genome-wide DNA demethylation in primordial germ cells (PGCs) is a prerequisite for the erasure of epigenetic memory, preventing the transmission of epimutations to the next generation. Apart from DNA demethylation, germline reprogramming has been shown to entail reprogramming of histone marks and chromatin remodelling. Contrary to other animal models, there is limited information about the epigenetic dynamics during early germ cell development in humans. Here, we provide further characterization of the epigenetic configuration of the early human gonadal PGCs. We show that early gonadal human PGCs are DNA hypomethylated and their chromatin is characterized by low H3K9me2 and high H3K27me3 marks. Similarly to previous observations in mice, human gonadal PGCs undergo dynamic chromatin changes concomitant with the erasure of genomic imprints. Interestingly, and contrary to mouse early germ cells, expression of BLIMP1/PRDM1 persists in through all gestational stages in human gonadal PGCs and is associated with nuclear lysine-specific demethylase-1. Our work provides important additional information regarding the chromatin changes associated with human PGCs development between 6 and 13 weeks of gestation in male and female gonads. Stem Cells 2016;34:2418-2428. © 2016 AlphaMed Press.

  6. Germ layer differentiation during early hindgut and cloaca formation in rabbit and pig embryos

    PubMed Central

    Hassoun, Romia; Schwartz, Peter; Rath, Detlef; Viebahn, Christoph; Männer, Jörg

    2010-01-01

    Relative to recent advances in understanding molecular requirements for endoderm differentiation, the dynamics of germ layer morphology and the topographical distribution of molecular factors involved in endoderm formation at the caudal pole of the embryonic disc are still poorly defined. To discover common principles of mammalian germ layer development, pig and rabbit embryos at late gastrulation and early neurulation stages were analysed as species with a human-like embryonic disc morphology, using correlative light and electron microscopy. Close intercellular contact but no direct structural evidence of endoderm formation such as mesenchymal–epithelial transition between posterior primitive streak mesoderm and the emerging posterior endoderm were found. However, a two-step process closely related to posterior germ layer differentiation emerged for the formation of the cloacal membrane: (i) a continuous mesoderm layer and numerous patches of electron-dense flocculent extracellular matrix mark the prospective region of cloacal membrane formation; and (ii) mesoderm cells and all extracellular matrix including the basement membrane are lost locally and close intercellular contact between the endoderm and ectoderm is established. The latter process involves single cells at first and then gradually spreads to form a longitudinally oriented seam-like cloacal membrane. These gradual changes were found from gastrulation to early somite stages in the pig, whereas they were found from early somite to mid-somite stages in the rabbit; in both species cloacal membrane formation is complete prior to secondary neurulation. The results highlight the structural requirements for endoderm formation during development of the hindgut and suggest new mechanisms for the pathogenesis of common urogenital and anorectal malformations. PMID:20874819

  7. Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation

    PubMed Central

    Kee, Kehkooi; Angeles, Vanessa T; Flores, Martha; Nguyen, Ha Nam; Pera, Renee A Reijo

    2009-01-01

    The leading cause of infertility in men and women is quantitative and qualitative defects in human germ cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ cell formation and differentiation due to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages1-8. Here we used a germ cell reporter to quantitate and isolate primordial germ cells derived from both male and female hESCs. Then, by silencing and overexpressing genes that encode germ cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ cell formation and developmental progression. We observed that human DAZL (Deleted in AZoospermia-Like) functions in primordial germ cell formation, whereas closely-related genes, DAZ and BOULE, promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications. PMID:19865085

  8. Vascular endothelial growth factor and nitric oxide synthase expression in human tooth germ development.

    PubMed

    Mastrangelo, F; Sberna, M T; Tettamanti, L; Cantatore, G; Tagliabue, A; Gherlone, E

    2016-01-01

    Vascular Endothelia Growth Factor (VEGF) and Nitric Oxide Synthase (NOS) expression, were evaluated in human tooth germs at two different stages of embryogenesis, to clarify the role of angiogenesis during tooth tissue differentiation and growth. Seventy-two third molar germ specimens were selected during oral surgery. Thirty-six were in the early stage and 36 in the later stage of tooth development. The samples were evaluated with Semi-quantitative Reverse Transcription-Polymerase chain Reaction analyses (RT-PcR), Western blot analysis (WB) and immunohistochemical analysis. Western blot and immunohistochemical analysis showed a VEGF and NOS 1-2-3 positive reaction in all samples analysed. VEGF high positive decrease reaction was observed in stellate reticulum cells, ameloblast and odontoblast clusters in early stage compared to later stage of tooth germ development. Comparable VEGF expression was observed in endothelial cells of early and advanced stage growth. NOS1 and NOS3 expressions showed a high increased value in stellate reticulum cells, and ameloblast and odontoblast clusters in advanced stage compared to early stage of development. The absence or only moderate positive reaction of NOS2 was detected in all the different tissues. Positive NOS2 expression showed in advanced stage of tissue development compared to early stage. The action of VEGF and NOS molecules are important mediators of angiogenesis during dental tissue development. VEGF high positive expression in stellate reticulum cells in the early stage of tooth development compared to the later stage and the other cell types, suggests a critical role of the stellate reticulum during dental embryo-morphogenesis.

  9. Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features

    PubMed Central

    Medrano, Jose V.; Martínez-Arroyo, Ana M.; Míguez, Jose M.; Moreno, Inmaculada; Martínez, Sebastián; Quiñonero, Alicia; Díaz-Gimeno, Patricia; Marqués-Marí, Ana I.; Pellicer, Antonio; Remohí, Jose; Simón, Carlos

    2016-01-01

    The in vitro derivation of human germ cells has attracted interest in the last years, but their direct conversion from human somatic cells has not yet been reported. Here we tested the ability of human male somatic cells to directly convert into a meiotic germ cell-like phenotype by inducing them with a combination of selected key germ cell developmental factors. We started with a pool of 12 candidates that were reduced to 6, demonstrating that ectopic expression of the germ line-related genes PRDM1, PRDM14, LIN28A, DAZL, VASA and SYCP3 induced direct conversion of somatic cells (hFSK (46, XY), and hMSC (46, XY)) into a germ cell-like phenotype in vitro. Induced germ cell-like cells showed a marked switch in their transcriptomic profile and expressed several post-meiotic germ line related markers, showed meiotic progression, evidence of epigenetic reprogramming, and approximately 1% were able to complete meiosis as demonstrated by their haploid status and the expression of several post-meiotic markers. Furthermore, xenotransplantation assays demonstrated that a subset of induced cells properly colonize the spermatogonial niche. Knowledge obtained from this work can be used to create in vitro models to study gamete-related diseases in humans. PMID:27112843

  10. Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential

    PubMed Central

    Mitchell, Rod T; Camacho-Moll, Maria; Macdonald, Joni; Anderson, Richard A; Kelnar, Christopher JH; O’Donnell, Marie; Sharpe, Richard M; Smith, Lee B; Grigor, Ken M; Wallace, W Hamish B; Stoop, Hans; Wolffenbuttel, Katja P; Donat, Roland

    2014-01-01

    Testicular germ cell cancer develops from pre-malignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4+/ MAGEA4−) into pre-spermatogonia (OCT4−/MAGEA4+). Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described, however the importance of these subpopulations in terms of invasive potential has not been reported. We hypothesised that cells expressing an immature (OCT4+/MAGEA4−) germ cell profile would exhibit an increased proliferation rate compared to those with a mature profile (OCT4+/ MAGEA4+). Therefore, we performed triple immunofluorescence and stereology to quantify the different intratubular germ cell neoplasia cell subpopulations, based on expression of germ cell (OCT4, PLAP, AP2γ, MAGEA4, VASA) and proliferation (Ki67) markers, in testis sections from patients with pre-invasive disease, seminoma and non-seminoma. We compared these subpopulations with normal human fetal testis and with seminoma cells. Heterogeneity of protein expression was demonstrated in intratubular germ cell neoplasia cells with respect to gonocyte and spermatogonial markers. It included an embryonic/fetal germ cell subpopulation lacking expression of the definitive intratubular germ cell neoplasia marker OCT4, that did not correspond to a physiological (fetal) germ cell subpopulation. OCT4+/MAGEA4- cells showed a significantly increased rate of proliferation compared with the OCT4+/MAGEA4+ population (12.8 v 3.4%, p<0.0001) irrespective of histological tumour type, reflected in the predominance of OCT4+/MAGEA4− cells in the invasive tumour component. Surprisingly, OCT4+/MAGEA4− cells in patients with pre-invasive disease showed significantly higher proliferation compared to those with seminoma or non-seminoma (18.1 v 10.2 v 7.2%, p<0.05 respectively). In conclusion, this study has demonstrated that OCT4+/MAGEA4

  11. Prenatal exposure to chromium induces early reproductive senescence by increasing germ cell apoptosis and advancing germ cell cyst breakdown in the F1 offspring.

    PubMed

    Sivakumar, Kirthiram K; Stanley, Jone A; Arosh, Joe A; Pepling, Melissa E; Burghardt, Robert C; Banu, Sakhila K

    2014-04-01

    Hexavalent chromium (CrVI), one of the more toxic heavy metals, is widely used in more than 50 industries such as chrome plating, welding, wood processing and tanneries. As one of the world's leading producers of chromium compounds, the U.S. is facing growing challenges in protecting human health against multiple adverse effects of CrVI. CrVI is rapidly converted to CrIII intracellularly, and can induce apoptosis through different mechanisms. Our previous studies demonstrated postnatal exposure to CrVI results in a delay or arrest in follicle development and puberty. Pregnant rats were treated with 25 ppm potassium dichromate (CrVI) from gestational day (GD) 9.5 to 14.5 through drinking water, placentae were removed on GD 20, and total Cr was estimated in the placentae; ovaries were removed from the F1 offspring on postnatal day (PND)-1 and various analyses were performed. Our results show that gestational exposure to CrVI resulted in (i) increased Cr concentration in the placenta, (ii) increased germ cell apoptosis by up-regulating p53/p27-Bax-caspase-3 proteins and by increasing p53-SOD-2 co-localization; (iii) accelerated germ cell cyst (GCC) breakdown; (iv) advanced primordial follicle assembly and primary follicle transition and (v) down regulation of p-AKT, p-ERK and XIAP. As a result of the above events, CrVI induced early reproductive senescence and decrease in litter size in F1 female progeny. Published by Elsevier Inc.

  12. Prenatal exposure to chromium induces early reproductive senescence by increasing germ cell apoptosis and advancing germ cell cyst breakdown in the F1 offspring

    PubMed Central

    Sivakumar, Kirthiram K.; Stanley, Jone A.; Arosh, Joe A.; Pepling, Melissa E.; Burghardt, Robert C.; Banu, Sakhila K.

    2014-01-01

    Hexavalent chromium (CrVI), one of the more toxic heavy metals, is widely used in more than 50 industries such as chrome plating, welding, wood processing and tanneries. As one of the world’s leading producers of chromium compounds, the U.S. is facing growing challenges in protecting human health against multiple adverse effects of CrVI. CrVI is rapidly converted to CrIII intracellularly, and can induce apoptosis through different mechanisms. Our previous studies demonstrated postnatal exposure to CrVI results in a delay or arrest in follicle development and puberty. Pregnant rats were treated with 25 ppm potassium dichromate (CrVI) from gestational day (GD) 9.5 to 14.5 through drinking water, placentae were removed on GD 20, and total Cr was estimated in the placentae; ovaries were removed from the F1 offspring on postnatal day (PND)-1 and various analyses were performed. Our results show that gestational exposure to CrVI resulted in (i) increased Cr concentration in the placenta, (ii) increased germ cell apoptosis by up-regulating p53/p27–Bax–caspase-3 proteins and by increasing p53–SOD-2 co-localization; (iii) accelerated germ cell cyst (GCC) breakdown; (iv) advanced primordial follicle assembly and primary follicle transition and (v) down regulation of p-AKT, p-ERK and XIAP. As a result of the above events, CrVI induced early reproductive senescence and decrease in litter size in F1 female progeny. PMID:24530425

  13. Germ line determinants are not localized early in sea urchin development, but do accumulate in the small micromere lineage.

    PubMed

    Juliano, Celina E; Voronina, Ekaterina; Stack, Christie; Aldrich, Maryanna; Cameron, Andrew R; Wessel, Gary M

    2006-12-01

    Two distinct modes of germ line determination are used throughout the animal kingdom: conditional-an inductive mechanism, and autonomous-an inheritance of maternal factors in early development. This study identifies homologs of germ line determinants in the sea urchin Strongylocentrotus purpuratus to examine its mechanism of germ line determination. A list of conserved germ-line associated genes from diverse organisms was assembled to search the S. purpuratus genome for homologs, and the expression patterns of these genes were examined during embryogenesis by whole mount in situ RNA hybridization and QPCR. Of the 14 genes tested, all transcripts accumulate uniformly during oogenesis and Sp-pumilio, Sp-tudor, Sp-MSY, and Sp-CPEB1 transcripts are also uniformly distributed during embryonic development. Sp-nanos2, Sp-seawi, and Sp-ovo transcripts, however, are enriched in the vegetal plate of the mesenchyme blastula stage and Sp-vasa, Sp-nanos2, Sp-seawi, and Sp-SoxE transcripts are localized in small micromere descendents at the tip of the archenteron during gastrulation and are then enriched in the left coelomic pouch of larvae. The results of this screen suggest that sea urchins conditionally specify their germ line, and support the hypothesis that this mechanism is the basal mode of germ line determination amongst deuterostomes. Furthermore, accumulation of germ line determinants selectively in small micromere descendents supports the hypothesis that these cells contribute to the germ line.

  14. Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors.

    PubMed

    Galli, Uwe M; Sauter, Marlies; Lecher, Bernd; Maurer, Simone; Herbst, Hermann; Roemer, Klaus; Mueller-Lantzsch, Nikolaus

    2005-04-28

    Germ cell tumors (GCTs) are among the most common malignancies in young men. We have previously documented that patients with GCT frequently produce serum antibodies directed against proteins encoded by human endogenous retrovirus (HERV) type K sequences. Transcripts originating from the env gene of HERV-K, including the rec-relative of human immunodeficiency virus rev, are highly expressed in GCTs. We report here that mice that inducibly express HERV-K rec show a disturbed germ cell development and may exhibit, by 19 months of age, changes reminiscent of carcinoma in situ, the predecessor lesion of classic seminoma in humans. This provides the first direct evidence that the expression of a human endogenous retroviral gene previously established as a marker in human germ cell tumors may contribute to organ-specific tumorigenesis in a transgenic mouse model.

  15. Identification of tissues and patterning events required for distinct steps in early migration of zebrafish primordial germ cells.

    PubMed

    Weidinger, G; Wolke, U; Köprunner, M; Klinger, M; Raz, E

    1999-12-01

    zebrafish at the early stages tested, the vasa-expressing cells are committed to the germ cell lineage.

  16. Intermolecular Interactions of Homologs of Germ Plasm Components in Mammalian Germ Cells

    PubMed Central

    Fox, Mark S.; Clark, Amander T.; El Majdoubi, Mohammed; Vigne, Jean-Louis; Urano, Jun; Hostetler, Chris E.; Griswold, Michael D.; Weiner, Richard I.; Pera, Renee A. Reijo

    2007-01-01

    In some species such as flies, worms, frogs, and fish the key to forming and maintaining early germ cell populations is the assembly of germ plasm, microscopically-distinct egg cytoplasm that is rich in RNAs, RNA-binding proteins and ribosomes. Cells which inherit germ plasm are destined for the germ cell lineage. In contrast, in mammals, germ cells are formed and maintained later in development as a result of inductive signaling from one embryonic cell type to another. Research advances, using complementary approaches, including identification of key signaling factors that act during the initial stages of germ cell development, differentiation of germ cells in vitro from mouse and human embryonic stem cells and the demonstration, that homologs of germ plasm components are conserved in mammals, have shed light on key elements in the early development of mammalian germ cells. Here, we use FRET (Fluorescence Resonance Energy Transfer) to demonstrate that living mammalian germ cells possess specific RNA/protein complexes that contain germ plasm homologs, beginning in the earliest stages of development examined. Moreover, we demonstrate that although both human and mouse germ cells and embryonic stem cells express the same proteins, germ cell specific protein/protein interactions distinguish germ cells from precursor embryonic stem cells in vitro; interactions also determine sub-cellular localization of complex components. Finally, we suggest that assembly of similar protein complexes may be central to differentiation of diverse cell lineages and provide useful diagnostic tools for isolation of specific cell types from the assorted types differentiated from embryonic stem cells. PMID:16996493

  17. Global DNA methylation in fetal human germ cells and germ cell tumours: association with differentiation and cisplatin resistance.

    PubMed

    Wermann, Hendrik; Stoop, Hans; Gillis, Ad J M; Honecker, Friedemann; van Gurp, Ruud J H L M; Ammerpohl, Ole; Richter, Julia; Oosterhuis, J Wolter; Bokemeyer, Carsten; Looijenga, Leendert H J

    2010-08-01

    Differences in the global methylation pattern, ie hyper- as well as hypo-methylation, are observed in cancers including germ cell tumours (GCTs). Related to their precursor cells, GCT methylation status differs according to histology. We investigated the methylation pattern of normal fetal, infantile, and adult germ cells (n = 103) and GCTs (n = 251) by immunohistochemical staining for 5-(m)cytidine. The global methylation pattern of male germ cells changes from hypomethylation to hypermethylation, whereas female germ cells remain unmethylated at all stages. Undifferentiated GCTs (seminomas, intratubular germ cell neoplasia unclassified, and gonadoblastomas) are hypomethylated, whereas more differentiated GCTs (teratomas, yolk sac tumours, and choriocarcinomas) show a higher degree of methylation. Embryonal carcinomas show an intermediate pattern. Resistance to cisplatin was assessed in the seminomatous cell line TCam-2 before and after demethylation using 5-azacytidine. Exposure to 5-azacytidine resulted in decreased resistance to cisplatin. Furthermore, after demethylation, the stem cell markers NANOG and POU5F1 (OCT3/4), as well as the germ cell-specific marker VASA, showed increased expression. Following treatment with 5-azacytidine, TCam-2 cells were analysed using a high-throughput methylation screen for changes in the methylation sites of 14,000 genes. Among the genes revealing changes, interesting targets were identified: ie demethylation of KLF11, a putative tumour suppressor gene, and hypermethylation of CFLAR, a gene previously described in treatment resistance in GCTs.

  18. Specific immune cell and cytokine characteristics of human testicular germ cell neoplasia.

    PubMed

    Klein, Britta; Haggeney, Thomas; Fietz, Daniela; Indumathy, Sivanjah; Loveland, Kate L; Hedger, Mark; Kliesch, Sabine; Weidner, Wolfgang; Bergmann, Martin; Schuppe, Hans-Christian

    2016-10-01

    small number of samples. The unique B cell presence and the significantly increased expression level of IL-6 in testicular germ cell neoplasia (P < 0.001) strengthen its special role in this disease. In line with current knowledge on other types of cancer, these results underline the relevance of further investigating the potential of IL-6 as early biomarker and target for therapeutic intervention in testicular germ cell neoplasia. This study (and B.K. in person) was supported by the Deutsche Forschungsgemeinschaft (DFG) as part of the International Research Training Group between Justus Liebig University of Giessen and Monash University, Melbourne (GRK 1871/1) on 'Molecular pathogenesis on male reproductive disorders'. T.H., H.-C.S. and M.B. were supported by the LOEWE focus group 'MIBIE' (male infertility during infection & inflammation)-an excellence initiative of the German state government of Hessen. From the Australian side, K.L. was supported by NHMRC grants (Fellowship, ID1079646 and Project, ID1081987); K.L., S.I. and M.H. received scholarship (S.I.) and research funding (K.L., M.H.) from Monash University. The project also drew support from the Victorian Government's Operational Infrastructure Support Program. The authors have no competing interests to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.For Permissions, please email: journals.permissions@oup.com.

  19. Etiology and early pathogenesis of malignant testicular germ cell tumors: towards possibilities for preinvasive diagnosis

    PubMed Central

    Elzinga-Tinke, Jenny E; Dohle, Gert R; Looijenga, Leendert HJ

    2015-01-01

    Malignant testicular germ cell tumors (TGCT) are the most frequent cancers in Caucasian males (20–40 years) with an 70% increasing incidence the last 20 years, probably due to combined action of (epi)genetic and (micro)environmental factors. It is expected that TGCT have carcinoma in situ (CIS) as their common precursor, originating from an embryonic germ cell blocked in its maturation process. The overall cure rate of TGCT is more than 90%, however, men surviving TGCT can present long-term side effects of systemic cancer treatment. In contrast, men diagnosed and treated for CIS only continue to live without these long-term side effects. Therefore, early detection of CIS has great health benefits, which will require an informative screening method. This review described the etiology and early pathogenesis of TGCT, as well as the possibilities of early detection and future potential of screening men at risk for TGCT. For screening, a well-defined risk profile based on both genetic and environmental risk factors is needed. Since 2009, several genome wide association studies (GWAS) have been published, reporting on single-nucleotide polymorphisms (SNPs) with significant associations in or near the genes KITLG, SPRY4, BAK1, DMRT1, TERT, ATF7IP, HPGDS, MAD1L1, RFWD3, TEX14, and PPM1E, likely to be related to TGCT development. Prenatal, perinatal, and postnatal environmental factors also influence the onset of CIS. A noninvasive early detection method for CIS would be highly beneficial in a clinical setting, for which specific miRNA detection in semen seems to be very promising. Further research is needed to develop a well-defined TGCT risk profile, based on gene-environment interactions, combined with noninvasive detection method for CIS. PMID:25791729

  20. BMP signaling in the human fetal ovary is developmentally regulated and promotes primordial germ cell apoptosis.

    PubMed

    Childs, Andrew J; Kinnell, Hazel L; Collins, Craig S; Hogg, Kirsten; Bayne, Rosemary A L; Green, Samira J; McNeilly, Alan S; Anderson, Richard A

    2010-08-01

    Primordial germ cells (PGCs) are the embryonic precursors of gametes in the adult organism, and their development, differentiation, and survival are regulated by a combination of growth factors collectively known as the germ cell niche. Although many candidate niche components have been identified through studies on mouse PGCs, the growth factor composition of the human PGC niche has not been studied extensively. Here we report a detailed analysis of the expression of components of the bone morphogenetic protein (BMP) signaling apparatus in the human fetal ovary, from postmigratory PGC proliferation to the onset of primordial follicle formation. We find developmentally regulated and reciprocal patterns of expression of BMP2 and BMP4 and identify germ cells to be the exclusive targets of ovarian BMP signaling. By establishing long-term cultures of human fetal ovaries in which PGCs are retained within their physiological niche, we find that BMP4 negatively regulates postmigratory PGC numbers in the human fetal ovary by promoting PGC apoptosis. Finally, we report expression of both muscle segment homeobox (MSX)1 and MSX2 in the human fetal ovary and reveal a selective upregulation of MSX2 expression in human fetal ovary in response to BMP4, suggesting this gene may act as a downstream effector of BMP-induced apoptosis in the ovary, as in other systems. These data reveal for the first time growth factor regulation of human PGC development in a physiologically relevant context and have significant implications for the development of cultures systems for the in vitro maturation of germ cells, and their derivation from pluripotent stem cells.

  1. MEETING REPORT ASSESSING HUMAN GERM-CELL MUTAGENESIS IN THE POST-GENOME ERA: A CELEBRATION OF THE LEGACY OF WILLIAM LAWSON (BILL) RUSSELL

    EPA Science Inventory

    Although numerous germ-cell mutagens have been identified in animal model systems, to date, no human germ-cell mutagens have been confirmed. Because the genomic integrity of our germ cells is essential for the continuation of the human species, a resolution of this enduring conu...

  2. Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors.

    PubMed

    Fizazi, Karim; Culine, Stéphane; Kramar, Andrew; Amato, Robert J; Bouzy, Jeannine; Chen, Isan; Droz, Jean-Pierre; Logothetis, Christopher J

    2004-10-01

    The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Data from 653 patients prospectively recruited in clinical trials were studied. Tumor markers were obtained before chemotherapy and 3 weeks later. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN). A favorable TTN was defined when both AFP and HCG had a favorable decline rate, including cases with normal values. The median follow-up was 50 months (range, 2 to 151 months). Tumor decline rate expressed as a predicted TTN was associated with both progression-free survival (PFS; P <.0001) and overall survival (OS; P <.0001). The 4-year PFS rates were 64% and 38% in patients from the poor-prognosis group who had a favorable and an unfavorable TTN, respectively. The 4-year OS rates were 83% and 58%, respectively. This effect was independent from the initial tumor marker values, the primary tumor site, and the presence of nonpulmonary visceral metastases: tumor marker decline rate remained a strong predictor for both PFS (hazard ratio = 2.5; P =.01) and OS (hazard ratio = 4.6; P =.002) in patients from the IGCCCG poor-prognosis group in multivariate analysis. Early predicted time to tumor marker normalization is an independent prognostic factor in patients with poor-prognosis NSGCT and may be a useful tool in the therapeutic management of these patients.

  3. Production of human CD59-transgenic pigs by embryonic germ cell nuclear transfer

    SciT

    Ahn, Kwang Sung; Won, Ji Young; Park, Jin-Ki

    Research highlights: {yields} Human CD59 (hCD59) gene was introduced into porcine embryonic germ (EG) cells. {yields} hCD59-transgenic EG cells were resistant to hyperacute rejection in cytolytic assay. {yields} hCD59-transgenic pigs were produced by EG cell nuclear transfer. -- Abstract: This study was performed to produce transgenic pigs expressing the human complement regulatory protein CD59 (hCD59) using the nuclear transfer (NT) of embryonic germ (EG) cells, which are undifferentiated stem cells derived from primordial germ cells. Because EG cells can be cultured indefinitely in an undifferentiated state, they may provide an inexhaustible source of nuclear donor cells for NT to producemore » transgenic pigs. A total of 1980 NT embryos derived from hCD59-transgenic EG cells were transferred to ten recipients, resulting in the birth of fifteen piglets from three pregnancies. Among these offspring, ten were alive without overt health problems. Based on PCR analysis, all fifteen piglets were confirmed as hCD59 transgenic. The expression of the hCD59 transgene in the ten living piglets was verified by RT-PCR. Western analysis showed the expression of the hCD59 protein in four of the ten RT-PCR-positive piglets. These results demonstrate that hCD59-transgenic pigs could effectively be produced by EG cell NT and that such transgenic pigs may be used as organ donors in pig-to-human xenotransplantation.« less

  4. Proton Radiotherapy for Pediatric Central Nervous System Germ Cell Tumors: Early Clinical Outcomes

    SciT

    MacDonald, Shannon M., E-mail: smacdonald@partners.or; Trofimov, Alexei; Safai, Sairos

    Purpose: To report early clinical outcomes for children with central nervous system (CNS) germ cell tumors treated with protons; to compare dose distributions for intensity-modulated photon radiotherapy (IMRT), three-dimensional conformal proton radiation (3D-CPT), and intensity-modulated proton therapy with pencil beam scanning (IMPT) for whole-ventricular irradiation with and without an involved-field boost. Methods and Materials: All children with CNS germinoma or nongerminomatous germ cell tumor who received treatment at the Massachusetts General Hospital between 1998 and 2007 were included in this study. The IMRT, 3D-CPT, and IMPT plans were generated and compared for a representative case. Results: Twenty-two patients were treatedmore » with 3D-CPT. At a median follow-up of 28 months, there were no CNS recurrences; 1 patient had a recurrence outside the CNS. Local control, progression-free survival, and overall survival rates were 100%, 95%, and 100%, respectively. Comparable tumor volume coverage was achieved with IMRT, 3D-CPT, and IMPT. Substantial normal tissue sparing was seen with any form of proton therapy as compared with IMRT. The use of IMPT may yield additional sparing of the brain and temporal lobes. Conclusions: Preliminary disease control with proton therapy compares favorably to the literature. Dosimetric comparisons demonstrate the advantage of proton radiation over IMRT for whole-ventricle radiation. Superior dose distributions were accomplished with fewer beam angles utilizing 3D-CPT and scanned protons. Intensity-modulated proton therapy with pencil beam scanning may improve dose distribution as compared with 3D-CPT for this treatment.« less

  5. Genetic modification of the human germ line: The reasons why this project has no future.

    PubMed

    Morange, Michel

    2015-01-01

    Modification of the human germ line has remained a distant but valuable objective for most biologists since the emergence of genetics (and even before). To study the historical transformations of this project, I have selected three periods - the 1930s, at the pinnacle of eugenics, around 1974 when molecular biology triumphed, and today - and have adopted three criteria to estimate the feasibility of this project: the state of scientific knowledge, the existence of suitable tools, and societal demands. Although the long-awaited techniques to modify the germ line are now available, I will show that most of the expectations behind this project have disappeared, or are considered as being reachable by highly different strategies. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  6. Activation of the germ-cell potential of human bone marrow-derived cells by a chemical carcinogen

    PubMed Central

    Liu, Chunfang; Ma, Zhan; Xu, Songtao; Hou, Jun; Hu, Yao; Yu, Yinglu; Liu, Ruilai; Chen, Zhihong; Lu, Yuan

    2014-01-01

    Embryonic/germ cell traits are common in malignant tumors and are thought to be involved in malignant tumor behaviors. The reasons why tumors show strong embryonic/germline traits (displaced germ cells or gametogenic programming reactivation) are controversial. Here, we show that a chemical carcinogen, 3-methyl-cholanthrene (3-MCA), can trigger the germ-cell potential of human bone marrow-derived cells (hBMDCs). 3-MCA promoted the generation of germ cell-like cells from induced hBMDCs that had undergone malignant transformation, whereas similar results were not observed in the parallel hBMDC culture at the same time point. The malignant transformed hBMDCs spontaneously and more efficiently generated into germ cell-like cells even at the single-cell level. The germ cell-like cells from induced hBMDCs were similar to natural germ cells in many aspects, including morphology, gene expression, proliferation, migration, further development, and teratocarcinoma formation. Therefore, our results demonstrate that a chemical carcinogen can reactivate the germline phenotypes of human somatic tissue-derived cells, which might provide a novel idea to tumor biology and therapy. PMID:24998261

  7. [Rhythmic beating cardiomyocytes derived from human embryonic germ (EG) cells in vitro].

    PubMed

    Hua, Jinlian; Xu, Xiaoming; Dou, Zhongying

    2006-10-01

    Embryonic germ (EG) cells are pluripotent cells derived from primordial germ cells (PGCs) of gonads, gonadal ridges and mesenteries, analogies of fetuses,with the ability to undergo both highly self-renewal and multiple differentiation. These cells in vitro can differentiate into derivatives of all three embryonic germ layers when transferred to an in vitro environment and have the ability to form any fully differentiated cells of the body. The aim of this study is to investigate the potentiality of human EG cells differentiation into cardiomyocytes. Inducing human EG cells with the method of murine ES cells differentiation into cardiomyocytes, supplemented with 0.75%-1% DMSO, 20% NBS, 10(-7) mM RA and 20% cardiomyocytes conditioned medium. 20 heart-like (rhythmic beating cell masses were observed in vitro culture and delayed human EG cells, which beat spontaneously from 20-120 times per minute and maintained beating for 2-15 days, periodic acid's staining (PAS), Myoglobin and a-actin immunological histology positive were all positive and reacted with K+, Ca2+ and adrenalin. Relatively unorganized myofibrillar bundles or more organized sarcomeres, z-bands or a gap junction, the presence of desmosomes in a few cells of the cell masses was observed with transmision electron microscope, which initially demonstrated that these cells were cardiomyocytes. We could not get rhythmly beating cardiomyocytes with 0.75%-1% DMSO, 10-7 mM RA and 20% cardiomyocytes conditioned medium,but in which the percentage of cardiac alpha-actin immunostaining positive cells were increased. The results first demonstrated that human EG cells can differentiate into rhythmic beating cardiomyocytes in vitro and suggests that human EG cells may represent a new potent resource for cardiomyocytes transplantation therapy for myocardium infarction.

  8. Three-Step Method for Proliferation and Differentiation of Human Embryonic Stem Cell (hESC)-Derived Male Germ Cells

    PubMed Central

    Lim, Jung Jin; Shim, Myung Sun; Lee, Jeoung Eun; Lee, Dong Ryul

    2014-01-01

    The low efficiency of differentiation into male germ cell (GC)-like cells and haploid germ cells from human embryonic stem cells (hESCs) reflects the culture method employed in the two-dimensional (2D)-microenvironment. In this study, we applied a three-step media and calcium alginate-based 3D-culture system for enhancing the differentiation of hESCs into male germ stem cell (GSC)-like cells and haploid germ cells. In the first step, embryoid bodies (EBs) were derived from hESCs cultured in EB medium for 3 days and re-cultured for 4 additional days in EB medium with BMP4 and RA to specify GSC-like cells. In the second step, the resultant cells were cultured in GC-proliferation medium for 7 days. The GSC-like cells were then propagated after selection using GFR-α1 and were further cultured in GC-proliferation medium for 3 weeks. In the final step, a 3D-co-culture system using calcium alginate encapsulation and testicular somatic cells was applied to induce differentiation into haploid germ cells, and a culture containing approximately 3% male haploid germ cells was obtained after 2 weeks of culture. These results demonstrated that this culture system could be used to efficiently induce GSC-like cells in an EB population and to promote the differentiation of ESCs into haploid male germ cells. PMID:24690677

  9. [Testicular germ cell tumours and early exposures to pesticides: The TESTEPERA pilot study].

    PubMed

    Béranger, Rémi; Blain, Jeffrey; Baudinet, Cédric; Faure, Elodie; Fléchon, Aude; Boyle, Helen; Chasles, Virginie; Charbotel, Barbara; Schüz, Joachim; Fervers, Béatrice

    2014-03-01

    Testicular germ cell tumors (TGCT) represent the most frequent cancer in men aged between 15 and 45 years. Current hypotheses are focusing on environmental exposures occurring during prenatal periods. However, very few studies have explored intra-uterine environmental exposure related to TGCT. TESTEPERA is a pilot case-control study aiming to determine the effectiveness of different recruitment approaches in the French context and to verify our ability to collect relevant data on their prenatal periods. Between 2011 and 2012, 150 male subjects were contacted in the Rhône-Alpes region (58 cases from a cancer center and 92 controls from a regional maternity). Participation rate varied from 33% for cases diagnosed in 2008 vs 68% for cases diagnosed in 2010. Participation rate of controls varied depending on modalities of contact (13% for face-to-face recruitment; 0% for contact by phone only; 50% for face-to-face contact with phone reminder). Data collection allowed precise job identification and geolocation of subjects' addresses. Precision of geolocation was dependent upon the level of urbanization (p < 0.001) but not on the time period (p = 0.52). Our results support the feasibility of a case-control study focusing on the relation between TGCT and environmental pesticide exposures during early and later life.

  10. Localization of early germ cells in a stony coral, Euphyllia ancora: potential implications for a germline stem cell system in coral gametogenesis

    NASA Astrophysics Data System (ADS)

    Shikina, Shinya; Chung, Yi-Jou; Wang, Hsiang-Ming; Chiu, Yi-Ling; Shao, Zih-Fang; Lee, Yan-Horn; Chang, Ching-Fong

    2015-06-01

    Most corals exhibit annual or multiple gametogenic cycles. Thus far, coral gametogenesis has been studied in many species and locations during the past three decades; however, currently, only a few papers exist that describe the origin of germ cells, such as germline stem cells (GSCs), which support the continuous production of gametes in every reproductive cycle. To address this issue, in this study, we focused on and identified piwi gene, which has been used as a marker of germline cells, including GSCs, in various metazoans, in a scleractinian coral, Euphyllia ancora. Reverse-transcription PCR and Western blotting analyses revealed that E. ancora piwi-like ( Eapiwi) is expressed in mesentery tissues where the sites of gametogenesis are located for both sexes. Immunohistochemistry with a specific antibody against Eapiwi revealed strong immunoreactivity in the spermatogonia in males and in the oogonia and early oocytes in females, demonstrating that Eapiwi could be used as an early germ cell marker in E. ancora. Subsequent immunohistochemical analyses regarding the spatial and temporal distribution patterns of early germ cells in mesentery tissues revealed that early germ cells were present throughout the year in the mesentery tissue we examined, regardless of the sexual reproductive cycle. In particular, small numbers of early germ cells were observed in specific sites of mesentery tissues with fully matured gonads in both sexes. These early germ cells were not released together with mature gametes during the spawning period and remained in the mesentery tissues. These results suggested that these early germ cells most likely serve as a reservoir of germline cells and that some of these cells would produce differentiated germ cells for the upcoming sexual reproduction period; hence, these cells would function as GSCs. Our data provide new information for understanding continuous gamete production in corals.

  11. Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice

    PubMed Central

    YANAI, Shogo; HIRANO, Tetsushi; OMOTEHARA, Takuya; TAKADA, Tadashi; YONEDA, Naoki; KUBOTA, Naoto; YAMAMOTO, Anzu; MANTANI, Youhei; YOKOYAMA, Toshifumi; KITAGAWA, Hiroshi; HOSHI, Nobuhiko

    2017-01-01

    Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life. PMID:28579575

  12. Analysis of expression patterns of IGF-1, caspase-3 and HSP-70 in developing human tooth germs.

    PubMed

    Kero, Darko; Kalibovic Govorko, Danijela; Medvedec Mikic, Ivana; Vukojevic, Katarina; Cigic, Livia; Saraga-Babic, Mirna

    2015-10-01

    To analyze expression patterns of IGF-1, caspase-3 and HSP-70 in human incisor and canine tooth germs during the late bud, cap and bell stages of odontogenesis. Head areas or parts of jaw containing teeth from 10 human fetuses aged between 9th and 20th developmental weeks were immunohistochemically analyzed using IGF-1, active caspase-3 and HSP-70 markers. Semi-quantitative analysis of each marker's expression pattern was also performed. During the analyzed period, IGF-1 and HSP-70 were mostly expressed in enamel organ. As development progressed, expression of IGF-1 and HSP-70 became more confined to differentiating tissues in the future cusp tip area, as well as in highly proliferating cervical loops. Few apoptotic bodies highly positive to active caspase-3 were observed in enamel organ and dental papilla from the cap stage onward. However, both enamel epithelia moderately expressed active caspase-3 throughout the investigated period. Expression patterns of IGF-1, active caspase-3 and HSP-70 imply importance of these factors for early human tooth development. IGF-1 and HSP-70 have versatile functions in control of proliferation, differentiation and anti-apoptotic protection of epithelial parts of human enamel organ. Active caspase-3 is partially involved in formation and apoptotic removal of primary enamel knot, although present findings might reflect its ability to perform other non-death functions such as differentiation of hard dental tissues secreting cells and guidance of ingrowth of proliferating cervical loops. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Regulation of proliferation in developing human tooth germs by MSX homeodomain proteins and cyclin-dependent kinase inhibitor p19INK4d.

    PubMed

    Kero, Darko; Vukojevic, Katarina; Stazic, Petra; Sundov, Danijela; Mardesic Brakus, Snjezana; Saraga-Babic, Mirna

    2017-10-02

    Before the secretion of hard dental tissues, tooth germs undergo several distinctive stages of development (dental lamina, bud, cap and bell). Every stage is characterized by specific proliferation patterns, which is regulated by various morphogens, growth factors and homeodomain proteins. The role of MSX homeodomain proteins in odontogenesis is rather complex. Expression domains of genes encoding for murine Msx1/2 during development are observed in tissues containing highly proliferative progenitor cells. Arrest of tooth development in Msx knockout mice can be attributed to impaired proliferation of progenitor cells. In Msx1 knockout mice, these progenitor cells start to differentiate prematurely as they strongly express cyclin-dependent kinase inhibitor p19 INK4d . p19 INK4d induces terminal differentiation of cells by blocking the cell cycle in mitogen-responsive G1 phase. Direct suppression of p19 INK4d by Msx1 protein is, therefore, important for maintaining proliferation of progenitor cells at levels required for the normal progression of tooth development. In this study, we examined the expression patterns of MSX1, MSX2 and p19 INK4d in human incisor tooth germs during the bud, cap and early bell stages of development. The distribution of expression domains of p19 INK4d throughout the investigated period indicates that p19 INK4d plays active role during human tooth development. Furthermore, comparison of expression domains of p19 INK4d with those of MSX1, MSX2 and proliferation markers Ki67, Cyclin A2 and pRb, indicates that MSX-mediated regulation of proliferation in human tooth germs might not be executed by the mechanism similar to one described in developing tooth germs of wild-type mouse.

  14. Zygote arrest 1 gene in pig, cattle and human: evidence of different transcript variants in male and female germ cells

    PubMed Central

    Uzbekova, Svetlana; Roy-Sabau, Monica; Dalbiès-Tran, Rozenn; Perreau, Christine; Papillier, Pascal; Mompart, Florence; Thelie, Aurore; Pennetier, Sophie; Cognie, Juliette; Cadoret, Veronique; Royere, Dominique; Monget, Philippe; Mermillod, Pascal

    2006-01-01

    Background Zygote arrest 1 (ZAR1) is one of the few known oocyte-specific maternal-effect genes essential for the beginning of embryo development discovered in mice. This gene is evolutionary conserved in vertebrates and ZAR1 protein is characterized by the presence of atypical plant homeobox zing finger domain, suggesting its role in transcription regulation. This work was aimed at the study of this gene, which could be one of the key regulators of successful preimplantation development of domestic animals, in pig and cattle, as compared with human. Methods Screenings of somatic cell hybrid panels and in silico research were performed to characterize ZAR1 chromosome localization and sequences. Rapid amplification of cDNA ends was used to obtain full-length cDNAs. Spatio-temporal mRNA expression patterns were studied using Northern blot, reverse transcription coupled to polymerase chain reaction and in situ hybridization. Results We demonstrated that ZAR1 is a single copy gene, positioned on chromosome 8 in pig and 6 in cattle, and several variants of correspondent cDNA were cloned from oocytes. Sequence analysis of ZAR1 cDNAs evidenced numerous short inverted repeats within the coding sequences and putative Pumilio-binding and embryo-deadenylation elements within the 3'-untranslated regions, indicating the potential regulation ways. We showed that ZAR1 expressed exclusively in oocytes in pig ovary, persisted during first cleavages in embryos developed in vivo and declined sharply in morulae and blastocysts. ZAR1 mRNA was also detected in testis, and, at lower level, in hypothalamus and pituitary in both species. For the first time, ZAR1 was localized in testicular germ cells, notably in round spermatids. In addition, in pig, cattle and human only shorter ZAR1 transcript variants resulting from alternative splicing were found in testis as compared to oocyte. Conclusion Our data suggest that in addition to its role in early embryo development highlighted by

  15. Glucose responsive insulin production from human embryonic germ (EG) cell derivatives.

    PubMed

    Clark, Gregory O; Yochem, Robert L; Axelman, Joyce; Sheets, Timothy P; Kaczorowski, David J; Shamblott, Michael J

    2007-05-11

    Type 1 diabetes mellitus subjects millions to a daily burden of disease management, life threatening hypoglycemia and long-term complications such as retinopathy, nephropathy, heart disease, and stroke. Cell transplantation therapies providing a glucose-regulated supply of insulin have been implemented clinically, but are limited by safety, efficacy and supply considerations. Stem cells promise a plentiful and flexible source of cells for transplantation therapies. Here, we show that cells derived from human embryonic germ (EG) cells express markers of definitive endoderm, pancreatic and beta-cell development, glucose sensing, and production of mature insulin. These cells integrate functions necessary for glucose responsive regulation of preproinsulin mRNA and expression of insulin C-peptide in vitro. Following transplantation into mice, cells become insulin and C-peptide immunoreactive and produce plasma C-peptide in response to glucose. These findings suggest that EG cell derivatives may eventually serve as a source of insulin producing cells for the treatment of diabetes.

  16. Market stimulus and genomic justice: evaluating the effects of market access to human germ-line enhancement.

    PubMed

    Crozier, G K D; Hajzler, Christopher

    2010-06-01

    The concept of "market stimulus"--the idea that free markets can play a role in widening access to new technologies--may help support the view that parents should be permitted to purchase germ-line enhancements. However, a critical examination of the topic shows that market stimulus, even if it applies to human genomic interventions, does not provide sufficient reason for deregulating germ-line enhancements because: (1) it could widen the gap between the rich and the poor; (2) even if it does not widen the gap, it might not sufficiently benefit the poor; and (3) it could have harmful effects for future generations.

  17. Metabolomic Response of Human Embryonic Stem Cell Derived Germ-like Cells after Exposure to Steroid Hormones

    EPA Science Inventory

    To assess the potential risks of human exposure to endocrine active compounds (EACs), the mechanisms of toxicity must first be identified and characterized. Currently, there are no robust in vitro models for identifying the mechanisms of toxicity in germ cells resulting from EAC ...

  18. Optimal culture conditions are critical for efficient expansion of human testicular somatic and germ cells in vitro.

    PubMed

    Gat, Itai; Maghen, Leila; Filice, Melissa; Wyse, Brandon; Zohni, Khaled; Jarvi, Keith; Lo, Kirk C; Gauthier Fisher, Andrée; Librach, Clifford

    2017-03-01

    To optimize culture conditions for human testicular somatic cells (TSCs) and spermatogonial stem cells. Basic science study. Urology clinic and stem cell research laboratory. Eight human testicular samples. Testicular tissues were processed by mechanical and enzymatic digestion. Cell suspensions were subjected to differential plating (DP) after which floating cells (representing germ cells) were removed and attached cells (representing TSCs) were cultured for 2 passages (P0-P1) in StemPro-34- or DMEM-F12-based medium. Germ cell cultures were established in both media for 12 days. TSC cultures: proliferation doubling time (PDT), fluorescence-activated cell sorting for CD90, next-generation sequencing for 89 RNA transcripts, immunocytochemistry for TSC and germ cell markers, and conditioned media analysis; germ cell cultures: number of aggregates. TSCs had significantly prolonged PDT in DMEM-F12 versus StemPro-34 (319.6 ± 275.8 h and 110.5 ± 68.3 h, respectively). The proportion of CD90-positive cells increased after P1 in StemPro-34 and DMEM-F12 (90.1 ± 10.8% and 76.5 ± 17.4%, respectively) versus after DP (66.3 ± 7%). Samples from both media after P1 clustered closely in the principle components analysis map whereas those after DP did not. After P1 in either medium, CD90-positive cells expressed TSC markers only, and fibroblast growth factor 2 and bone morphogenetic protein 4 were detected in conditioned medium. A higher number of germ cell aggregates formed in DMEM-F12 (59 ± 39 vs. 28 ± 17, respectively). Use of DMEM-F12 reduces TSC proliferation while preserving their unique characteristics, leading to improved germ cell aggregates formation compared with StemPro-34, the standard basal medium used in the majority of previous reports. Copyright © 2017. Published by Elsevier Inc.

  19. Are There Human Germ-Cell Mutagens? We May Know Soon

    EPA Science Inventory

    The existence of agents that can induce germ-cell mutations in experimental systems has been recognized since 1927 with the discovery of the ability of X-rays to induce such mutations in Drosophila. Since then, various rodent-based assays have been used to identify ~50 germ-cell...

  20. Human primordial germ cell formation is diminished by exposure to environmental toxicants acting through the AHR signaling pathway.

    PubMed

    Kee, Kehkooi; Flores, Martha; Cedars, Marcelle I; Reijo Pera, Renee A

    2010-09-01

    Historically, effects of environmental toxicants on human development have been deduced via epidemiological studies because direct experimental analysis has not been possible. However, in recent years, the derivation of human pluripotent stem cells has provided a potential experimental system to directly probe human development. Here, we used human embryonic stem cells (hESCs) to study the effect of environmental toxicants on human germ cell development, with a focus on differentiation of the founding population of primordial germ cells (PGCs), which will go on to form the oocytes of the adult. We demonstrate that human PGC numbers are specifically reduced by exposure to polycyclic aromatic hydrocarbons (PAHs), a group of toxicants common in air pollutants released from gasoline combustion or tobacco smoke. Further, we demonstrate that the adverse effects of PAH exposure are mediated through the aromatic hydrocarbon receptor (AHR) and BAX pathway. This study demonstrates the utility of hESCs as a model system for direct examination of the molecular and genetic pathways of environmental toxicants on human germ cell development.

  1. Isolation, characterization and propagation of mitotically active germ cells from adult mouse and human ovaries

    PubMed Central

    Woods, Dori C; Tilly, Jonathan L

    2017-01-01

    Accruing evidence indicates that production of new oocytes (oogenesis) and their enclosure by somatic cells (folliculogenesis) are processes not limited to the perinatal period in mammals. Endpoints ranging from oocyte counts to genetic lineage tracing and transplantation experiments support a paradigm shift in reproductive biology involving active renewal of oocyte-containing follicles during postnatal life. The recent purification of mitotically active oocyte progenitor cells, termed female germline stem cells (fGSCs) or oogonial stem cells (OSCs), from mouse and human ovaries opens up new avenues for research into the biology and clinical utility of these cells. Here we detail methods for the isolation of mouse and human OSCs from adult ovarian tissue, cultivation of the cells after purification, and characterization of the cells before and after ex vivo expansion. The latter methods include analysis of germ cell–specific markers and in vitro oogenesis, as well as the use of intraovarian transplantation to test the oocyte-forming potential of OSCs in vivo. PMID:23598447

  2. Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

    PubMed Central

    2013-01-01

    Background Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. Methods We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. Results TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. Conclusions We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies. PMID:23937707

  3. YKL-40 is differentially expressed in human embryonic stem cells and in cell progeny of the three germ layers.

    PubMed

    Brøchner, Christian B; Johansen, Julia S; Larsen, Lars A; Bak, Mads; Mikkelsen, Hanne B; Byskov, Anne Grete; Andersen, Claus Yding; Møllgård, Kjeld

    2012-03-01

    The secreted glycoprotein YKL-40 participates in cell differentiation, inflammation, and cancer progression. High YKL-40 expression is reported during early human development, but its functions are unknown. Six human embryonic stem cell (hESC) lines were cultured in an atmosphere of low or high oxygen tension, in culture medium with or without basic fibroblast growth factor, and on feeder layers comprising mouse embryonic fibroblasts or human foreskin fibroblasts to evaluate whether hESCs and their progeny produced YKL-40 and to characterize YKL-40 expression during differentiation. Secreted YKL-40 protein and YKL-40 mRNA expression were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative RT-PCR. Serial-sectioned colonies were stained for YKL-40 protein and for pluripotent hESC (OCT4, NANOG) and germ layer (HNF-3β, PDX1, CD34, p63, nestin, PAX6) markers. Double-labeling showed YKL-40 expression in OCT4-positive hESCs, PAX6-positive neuroectodermal cells, and HNF-3β-positive endodermal cells. The differentiating progeny showed strong YKL-40 expression. Abrupt transition between YKL-40 and OCT4-positive hESCs and YKL-40-positive ecto- and neuroectodermal lineages was observed within the same epithelial-like layer. YKL-40-positive cells within deeper layers lacked contact with OCT4-positive cells. YKL-40 may be important in initial cell differentiation from hESCs toward ectoderm and neuroectoderm, with retained epithelial morphology, whereas later differentiation into endoderm and mesoderm involves a transition into the deeper layers of the colony.

  4. Glucose responsive insulin production from human embryonic germ (EG) cell derivatives

    SciT

    Clark, Gregory O.; Yochem, Robert L.; Axelman, Joyce

    2007-05-11

    Type 1 diabetes mellitus subjects millions to a daily burden of disease management, life threatening hypoglycemia and long-term complications such as retinopathy, nephropathy, heart disease, and stroke. Cell transplantation therapies providing a glucose-regulated supply of insulin have been implemented clinically, but are limited by safety, efficacy and supply considerations. Stem cells promise a plentiful and flexible source of cells for transplantation therapies. Here, we show that cells derived from human embryonic germ (EG) cells express markers of definitive endoderm, pancreatic and {beta}-cell development, glucose sensing, and production of mature insulin. These cells integrate functions necessary for glucose responsive regulation ofmore » preproinsulin mRNA and expression of insulin C-peptide in vitro. Following transplantation into mice, cells become insulin and C-peptide immunoreactive and produce plasma C-peptide in response to glucose. These findings suggest that EG cell derivatives may eventually serve as a source of insulin producing cells for the treatment of diabetes.« less

  5. Bmp 2 and bmp 7 induce odonto- and osteogenesis of human tooth germ stem cells.

    PubMed

    Taşlı, P Neslihan; Aydın, Safa; Yalvaç, Mehmet Emir; Sahin, Fikrettin

    2014-03-01

    Bone morphogenetic proteins (BMPs) initiate, promote, and maintain odontogenesis and osteogenesis. In this study, we studied the effect of bone morphogenic protein 2 (BMP 2) and bone morphogenic protein 7 (BMP 7) as differentiation inducers in tooth and bone regeneration. We compared the effect of BMP 2 and BMP 7 on odontogenic and osteogenic differentiation of human tooth germ stem cells (hTGSCs). Third molar-derived hTGSCs were characterized with mesenchymal stem cell surface markers by flow cytometry. BMP 2 and BMP 7 were transfected into hTGSCs and the cells were seeded onto six-well plates. One day after the transfection, hTGSCs were treated with odontogenic and osteogenic mediums for 14 days. For confirmation of odontogenic and osteogenic differentiation, mRNA levels of BMP2, BMP 7, collagen type 1 (COL1A), osteocalsin (OCN), and dentin sialophosphoprotein (DSPP) genes were measured by quantitative real-time PCR. In addition to this, immunocytochemistry was performed by odontogenic and osteogenic antibodies and mineralization obtained by von Kossa staining. Our results showed that the BMP 2 and BMP 7 both promoted odontogenic and osteogenic differentiation of hTGSCs. Data indicated that BMP 2 treatment and BMP 7 treatment induce odontogenic differentiation without affecting each other, whereas they induce osteogenic differentiation by triggering expression of each other. These findings provide a feasible tool for tooth and bone tissue engineering.

  6. MicroRNAs: From Female Fertility, Germ Cells, and Stem Cells to Cancer in Humans

    PubMed Central

    Virant-Klun, Irma; Ståhlberg, Anders; Kubista, Mikael; Skutella, Thomas

    2016-01-01

    MicroRNAs are a family of naturally occurring small noncoding RNA molecules that play an important regulatory role in gene expression. They are suggested to regulate a large proportion of protein encoding genes by mediating the translational suppression and posttranscriptional control of gene expression. Recent findings show that microRNAs are emerging as important regulators of cellular differentiation and dedifferentiation, and are deeply involved in developmental processes including human preimplantation development. They keep a balance between pluripotency and differentiation in the embryo and embryonic stem cells. Moreover, it became evident that dysregulation of microRNA expression may play a fundamental role in progression and dissemination of different cancers including ovarian cancer. The interest is still increased by the discovery of exosomes, that is, cell-derived vesicles, which can carry different proteins but also microRNAs between different cells and are involved in cell-to-cell communication. MicroRNAs, together with exosomes, have a great potential to be used for prognosis, therapy, and biomarkers of different diseases including infertility. The aim of this review paper is to summarize the existent knowledge on microRNAs related to female fertility and cancer: from primordial germ cells and ovarian function, germinal stem cells, oocytes, and embryos to embryonic stem cells. PMID:26664407

  7. Experimental Germ Tube Induction in Candida albicans: An Evaluation of the Effect of Sodium Bicarbonate on Morphogenesis and Comparison with Pooled Human Serum.

    PubMed

    Matare, Tapiwa; Nziramasanga, Pasipanodya; Gwanzura, Lovemore; Robertson, Valerie

    2017-01-01

    The potential of NaHCO 3 versus human serum to induce germ tube formation in Candida albicans was investigated. A total of 100 isolates were obtained from oral swabs of patients presenting with thrush. Approval for the study was granted by the Joint Research Ethics Committee (JREC/23/08). Confirmed C. albicans isolates by routine methods were tested for germ tube induction using 5 different concentrations of Tris-maleate buffered NaHCO 3 and Tris-maleate buffer control. Standard control strains included were C. albicans (ATCC 10231) and C. krusei (ATCC 6258). Microculture was done in 20  μ L inoculums on microscope slides for 3 hours at 37°C. The rate of germ tube formation at 10-minute intervals was determined on 100 isolates using the optimum 20 mM Tris-maleate buffered NaHCO 3 concentration. Parallel germ tube formation using human serum was done in test tubes. The optimum concentration of NaHCO 3 in Tris-maleate buffer for germ tube induction was 20 mM for 67% of isolates. Only 21% of isolates formed germ tubes in Tris-maleate buffer control. There was no significant difference in induction between human serum and Tris-maleate buffered NaHCO 3 . Tris-maleate buffered NaHCO 3 induced germ tube formation in C. albicans isolates at rates similar to human serum.

  8. Expression of the oncoprotein gankyrin and phosphorylated retinoblastoma protein in human testis and testicular germ cell tumor.

    PubMed

    Ando, Satoshi; Matsuoka, Taeko; Kawai, Koji; Sugita, Shintaro; Joraku, Akira; Kojima, Takahiro; Suetomi, Takahiro; Miyazaki, Jun; Fujita, Jun; Nishiyama, Hiroyuki

    2014-10-01

    The oncoprotein, gankyrin, is known to facilitate cell proliferation through phosphorylation and degradation of retinoblastoma protein. In the present study, we evaluated the expression of gankyrin and phosphorylated retinoblastoma protein in human testis and testicular germ cell tumors. The effects of suppression of gankyrin by locked nucleic acid on phosphorylation status of retinoblastoma and cell proliferation were analyzed using western blot analysis and testicular tumor cell line NEC8. The expressions of gankyrin, retinoblastoma and retinoblastoma protein were analyzed in 93 testicular germ cell tumor samples and five normal human testis by immunohistochemistry. The retinoblastoma protein expression was determined using an antibody to retinoblastoma protein, Ser795. Gankyrin was expressed in NEC8 cells as well as a normal human testis and testicular tumors. Suppression of gankyrin by locked nucleic acid led to suppression of retinoblastoma protein and cell proliferation in NEC8 cells. Immunohistochemistry of normal testis showed that gankyrin is expressed dominantly in spermatocytes. In testicular germ cell tumors, high expressions of gankyrin and phosphorylated-retinoblastoma protein were observed in seminoma and embryonal carcinoma, whereas the expressions of both proteins were weak in histological subtypes of non-seminoma. Growing teratoma and testicular malignant transformation tissues expressed phosphorylated-retinoblastoma protein strongly, but gankyrin faintly. Gankyrin is dominantly expressed in normal spermatocytes and seminoma/embryonal carcinoma, and its expression correlates well with retinoblastoma protein expression except in the growing teratoma and testicular malignant transformation cases. These data provide new insights into the molecular mechanisms of normal spermatogenesis and pathogenesis of testicular germ cell tumors. © 2014 The Japanese Urological Association.

  9. Effects of environmental Bisphenol A exposures on germ cell development and Leydig cell function in the human fetal testis

    PubMed Central

    Guerquin, Marie-Justine; Matilionyte, Gabriele; Kilcoyne, Karen; N’Tumba-Byn, Thierry; Messiaen, Sébastien; Deceuninck, Yoann; Pozzi-Gaudin, Stéphanie; Benachi, Alexandra; Livera, Gabriel; Antignac, Jean-Philippe; Mitchell, Rod; Rouiller-Fabre, Virginie

    2018-01-01

    Background Using an organotypic culture system termed human Fetal Testis Assay (hFeTA) we previously showed that 0.01 μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models. Methods Using the hFeTA system, first trimester testes were cultured for 3 days with 0.01 to 10 μM BPA. For xenografts, adult castrate male nude mice were injected with hCG and grafted with first trimester testes. Host mice received 10 μM BPA (~ 500 μg/kg/day) in their drinking water for 5 weeks. Plasma levels of total and unconjugated BPA were 0.10 μM and 0.038 μM respectively. Mice grafted with second trimester testes received 0.5 and 50 μg/kg/day BPA by oral gavage for 5 weeks. Results With first trimester human testes, using the hFeTA model, 10 μM BPA increased germ cell apoptosis. In xenografts, germ cell density was also reduced by BPA exposure. Importantly, BPA exposure significantly decreased the percentage of germ cells expressing the pluripotency marker AP-2γ, whilst the percentage of those expressing the pre-spermatogonial marker MAGE-A4 significantly increased. BPA exposure did not affect hCG-stimulated androgen production in first and second trimester xenografts as evaluated by both plasma testosterone level and seminal vesicle weight in host mice. Conclusions Exposure to BPA at environmentally relevant concentrations impairs germ cell development in first trimester human fetal testis, whilst gonadotrophin-stimulated testosterone production was unaffected in both first and second trimester testis. Studies using first trimester human fetal testis demonstrate the complementarity of the FeTA and xenograft models for determining the respective short-term and long term effects of environmental

  10. DNA damage in human germ cell exposed to the some food additives in vitro.

    PubMed

    Pandir, Dilek

    2016-08-01

    The use of food additives has increased enormously in modern food technology but they have adverse effects in human healthy. The aim of this study was to investigate the DNA damage of some food additives such as citric acid (CA), benzoic acid (BA), brilliant blue (BB) and sunset yellow (SY) which were investigated in human male germ cells using comet assay. The sperm cells were incubated with different concentrations of these food additives (50, 100, 200 and 500 μg/mL) for 1 h at 32 °C. The results showed for CA, BA, BB and SY a dose dependent increase in tail DNA%, tail length and tail moment in human sperm when compared to control group. When control values were compared in the studied parameters in the treatment concentrations, SY was found to exhibit the highest level of DNA damage followed by BB > BA > CA. However, none of the food additives affected the tail DNA%, tail length and tail moment at 50 and 100 μg/mL. At 200 μg/mL of SY, the tail DNA% and tail length of sperm were 95.80 ± 0.28 and 42.56 ± 4.66, for BB the values were 95.06 ± 2.30 and 39.56 ± 3.78, whereas for BA the values were 89.05 ± 2.78 and 31.50 ± 0.71, for CA the values were 88.59 ± 6.45 and 13.59 ± 2.74, respectively. However, only the highest concentration of the used food additives significantly affected the studied parameters of sperm DNA. The present results indicate that SY and BB are more harmful than BA and CA to human sperm in vitro.

  11. In vitro differentiation of human tooth germ stem cells into endothelial- and epithelial-like cells.

    PubMed

    Doğan, Ayşegül; Demirci, Selami; Şahin, Fikrettin

    2015-01-01

    Current clinical techniques in dental practice include stem cell and tissue engineering applications. Dental stem cells are promising primary cell source for mainly tooth tissue engineering. Interaction of mesenchymal stem cell with epithelial and endothelial cells is strictly required for an intact tooth morphogenesis. Therefore, it is important to investigate whether human tooth germ stem cells (hTGSCs) derived from wisdom tooth are suitable for endothelial and epithelial cell transformation in dental tissue regeneration approaches. Differentiation into endothelial and epithelial cell lineages were mimicked under defined conditions, confirmed by real time PCR, western blotting and immunocytochemical analysis by qualitative and quantitative methods. HUVECs and HaCaT cells were used as positive controls for the endothelial and epithelial differentiation assays, respectively. Immunocytochemical and western blotting analysis revealed that terminally differentiated cells expressed cell-lineage markers including CD31, VEGFR2, VE-Cadherin, vWF (endothelial cell markers), and cytokeratin (CK)-17, CK-19, EpCaM, vimentin (epithelial cell markers) in significant levels with respect to undifferentiated control cells. Moreover, high expression levels of VEGFR1, VEGFR2, VEGF, CK-18, and CK-19 genes were detected in differentiated endothelial and epithelial-like cells. Endothelial-like cells derived from hTGSCs were cultured on Matrigel, tube-like structure formations were followed as an indication for functional endothelial differentiation. hTGSCs successfully differentiate into various cell types with a broad range of functional abilities using an in vitro approach. These findings suggest that hTGSCs may serve a potential stem cell source for tissue engineering and cell therapy of epithelial and endothelial tissue. © 2014 International Federation for Cell Biology.

  12. DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

    SciT

    Marchetti, Francesco; Wyrobek, Andrew J.

    Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization.more » During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.« less

  13. Expression of GFP under the control of the RNA helicase VASA permits fluorescence-activated cell sorting isolation of human primordial germ cells.

    PubMed

    Tilgner, Katarzyna; Atkinson, Stuart P; Yung, Sun; Golebiewska, Anna; Stojkovic, Miodrag; Moreno, Ruben; Lako, Majlinda; Armstrong, Lyle

    2010-01-01

    The isolation of significant numbers of human primordial germ cells at several developmental stages is important for investigations of the mechanisms by which they are able to undergo epigenetic reprogramming. Only small numbers of these cells can be obtained from embryos of appropriate developmental stages, so the differentiation of human embryonic stem cells is essential to obtain sufficient numbers of primordial germ cells to permit epigenetic examination. Despite progress in the enrichment of human primordial germ cells using fluorescence-activated cell sorting (FACS), there is still no definitive marker of the germ cell phenotype. Expression of the widely conserved RNA helicase VASA is restricted to germline cells, but in contrast to species such as Mus musculus in which reporter constructs expressing green fluorescent protein (GFP) under the control of a Vasa promoter have been developed, such reporter systems are lacking in human in vitro models. We report here the generation and characterization of human embryonic stem cell lines stably carrying a VASA-pEGFP-1 reporter construct that expresses GFP in a population of differentiating human embryonic stem cells that show expression of characteristic markers of primordial germ cells. This population shows a different pattern of chromatin modifications to those obtained by FACS enrichment of Stage Specific Antigen one expressing cells in our previous publication.

  14. Ultrastructural visualisation of proteoglycans in early unmineralised dentine of rat tooth germs stained with cuprolinic blue.

    PubMed Central

    Tenorio, D; Reid, A R; Katchburian, E

    1990-01-01

    The ultrastructural distribution and localisation of proteoglycans (PGs) of early developing rat dentine were examined using cuprolinic blue in a critical electrolyte concentration procedure. Results show that the cuprolinic blue method produces images of higher morphological quality than other cationic dyes. PGs appeared as ribbon-like electron-opaque precipitates of various sizes, ranging between 1.4 and 0.2 microns in length, distributed throughout the matrix and in close association with well preserved matrix vesicles and collagen fibrils. Matrix vesicles revealed tightly packed PG filaments which appeared to be attached to their membrane. It is possible that the close association of PG filaments with matrix vesicles and collagen indicates that PGs are related to the process of mineralisation of dentine. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:2384338

  15. An in vitro model demonstrates the potential of neoplastic human germ cells to influence the tumour microenvironment.

    PubMed

    Klein, B; Schuppe, H-C; Bergmann, M; Hedger, M P; Loveland, B E; Loveland, K L

    2017-07-01

    Testicular germ cell tumours (TGCT) typically contain high numbers of infiltrating immune cells, yet the functional nature and consequences of interactions between GCNIS (germ cell neoplasia in situ) or seminoma cells and immune cells remain unknown. A co-culture model using the seminoma-derived TCam-2 cell line and peripheral blood mononuclear cells (PBMC, n = 7 healthy donors) was established to investigate how tumour and immune cells each contribute to the cytokine microenvironment associated with TGCT. Three different co-culture approaches were employed: direct contact during culture to simulate in situ cellular interactions occurring within seminomas (n = 9); indirect contact using well inserts to mimic GCNIS, in which a basement membrane separates the neoplastic germ cells and immune cells (n = 3); and PBMC stimulation prior to direct contact during culture to overcome the potential lack of immune cell activation (n = 3). Transcript levels for key cytokines in PBMC and TCam-2 cell fractions were determined using RT-qPCR. TCam-2 cell fractions showed an immediate increase (within 24 h) in several cytokine mRNAs after direct contact with PBMC, whereas immune cell fractions did not. The high levels of interleukin-6 (IL6) mRNA and protein associated with TCam-2 cells implicate this cytokine as important to seminoma physiology. Use of PBMCs from different donors revealed a robust, repeatable pattern of changes in TCam-2 and PBMC cytokine mRNAs, independent of potential inter-donor variation in immune cell responsiveness. This in vitro model recapitulated previous data from clinical TGCT biopsies, revealing similar cytokine expression profiles and indicating its suitability for exploring the in vivo circumstances of TGCT. Despite the limitations of using a cell line to mimic in vivo events, these results indicate how neoplastic germ cells can directly shape the surrounding tumour microenvironment, including by influencing local immune responses. IL6

  16. A role for Lin28 in primordial germ cell development and germ cell malignancy

    PubMed Central

    West, Jason A.; Viswanathan, Srinivas R.; Yabuuchi, Akiko; Cunniff, Kerianne; Takeuchi, Ayumu; Park, In-Hyun; Sero, Julia E.; Zhu, Hao; Perez-Atayde, Antonio; Frazier, A. Lindsay; Surani, M. Azim; Daley, George Q.

    2009-01-01

    The rarity and inaccessibility of the earliest primordial germ cells (PGCs) in the mouse embryo thwarts efforts to investigate molecular mechanisms of germ cell specification. Stella marks the minute founder population of the germ lineage1,2. Here we differentiate mouse embryonic stem cells (ESCs) carrying a Stella transgenic reporter into putative PGCs in vitro. The Stella+ cells possess a transcriptional profile similar to embryo-derived PGCs, and like their counterparts in vivo, lose imprints in a time-dependent manner. Using inhibitory RNAs to screen candidate genes for effects on the development of Stella+ cells in vitro, we discovered that Lin28, a negative regulator of let-7 microRNA processing3-6, is essential for proper PGC development. We further show that Blimp1, a let-7 target and a master regulator of PGC specification7-9, can rescue the effect of Lin28-deficiency during PGC development, thereby establishing a mechanism of action for Lin28 during PGC specification. Over-expression of Lin28 promotes formation of Stella+ cells in vitro and PGCs in chimeric embryos, and is associated with human germ cell tumours. The differentiation of putative PGCs from ESCs in vitro recapitulates the early stages of gamete development in vivo, and provides an accessible system for discovering novel genes involved in germ cell development and malignancy. PMID:19578360

  17. Human chorionic gonadotropin-induced hyperthyroidism in germ cell cancer--a case presentation and review of the literature.

    PubMed

    Voigt, Wieland; Maher, Gita; Wolf, Hans-Heinrich; Schmoll, Hans-Joachim

    2007-06-01

    Human chorionic gonadotropin (hCG)-induced hyperthyroidism represents a rare paraneoplastic syndrome in hCG-secreting testicular cancer. In most cases, this hyperthyroidism remains subclinical. hCG belongs to the family of glycoprotein hormones with structural homology to thyroid- stimulating hormone (TSH). The thyrotropic potency and thereby the degree of cross reactivity of hCG is determined by several factors, such as content of sialic acid or lack of the C-terminal tail. In the absence of clinical signs of hyperthyroidism, treatment usually consists of specific antitumor therapy which will result in normalization of thyroid function if hCG declines. Where there are clinical signs of hyperthyroidism, overlapping thyreostatic treatment is recommended. Here, we report of a young man presenting biochemical signs of hyperthyroidism without clinical signs at the time of diagnosis of non-seminomatous germ cell cancer. Beta-hCG initially exceeded 1,000,000 IU/ml and declined close to normal at the end of cancer treatment. Concomitantly, thyroid hormones returned to the normal range without any thyreostatic therapy. We observed a significant correlation of neta-hCG and thyroid hormones in linear regression analysis (r2 = 0.98, p< 0.05). A concise overview of potential mechanisms of hCG-induced hyperthyroidism in germ cell cancer but also in pregnancy is given and the case discussed according to the cited literature.

  18. The HOX genes are expressed, in vivo, in human tooth germs: in vitro cAMP exposure of dental pulp cells results in parallel HOX network activation and neuronal differentiation.

    PubMed

    D'Antò, Vincenzo; Cantile, Monica; D'Armiento, Maria; Schiavo, Giulia; Spagnuolo, Gianrico; Terracciano, Luigi; Vecchione, Raffaela; Cillo, Clemente

    2006-03-01

    Homeobox-containing genes play a crucial role in odontogenesis. After the detection of Dlx and Msx genes in overlapping domains along maxillary and mandibular processes, a homeobox odontogenic code has been proposed to explain the interaction between different homeobox genes during dental lamina patterning. No role has so far been assigned to the Hox gene network in the homeobox odontogenic code due to studies on specific Hox genes and evolutionary considerations. Despite its involvement in early patterning during embryonal development, the HOX gene network, the most repeat-poor regions of the human genome, controls the phenotype identity of adult eukaryotic cells. Here, according to our results, the HOX gene network appears to be active in human tooth germs between 18 and 24 weeks of development. The immunohistochemical localization of specific HOX proteins mostly concerns the epithelial tooth germ compartment. Furthermore, only a few genes of the network are active in embryonal retromolar tissues, as well as in ectomesenchymal dental pulp cells (DPC) grown in vitro from adult human molar. Exposure of DPCs to cAMP induces the expression of from three to nine total HOX genes of the network in parallel with phenotype modifications with traits of neuronal differentiation. Our observations suggest that: (i) by combining its component genes, the HOX gene network determines the phenotype identity of epithelial and ectomesenchymal cells interacting in the generation of human tooth germ; (ii) cAMP treatment activates the HOX network and induces, in parallel, a neuronal-like phenotype in human primary ectomesenchymal dental pulp cells. 2005 Wiley-Liss, Inc.

  19. Deregulation of EZH2 expression in human spermatogenic disorders and testicular germ cell tumors.

    PubMed

    Hinz, Stefan; Magheli, Ahmed; Weikert, Steffen; Schulze, Wolfgang; Krause, Hans; Schrader, Mark; Miller, Kurt; Kempkensteffen, Carsten

    2010-10-01

    Enhancer of Zeste 2 (EZH2) is an epigenetic transcriptional repressor involved in cell cycle control and cell fate decisions. Since these processes play key roles during intact spermatogenesis, deregulation of EZH2 expression may contribute to the development and progression of benign and malignant testicular diseases. The objective of this study was to investigate the expression profile of EZH2 in testicular germ cell tumors (TGCT) and spermatogenic defects. Real-time RT-PCR was applied to quantify the m-RNA expression of EZH2 in 64 seminomas 36 non-seminomas, 4 carcinomas in situ (CIS), 40 samples harboring impaired spermatogenesis and 24 normal testicular reference biopsies. EZH2 was expressed in 99% of TGCT samples and in all biopsies with intact spermatogenesis. Its expression levels were highest in normal testicular tissue, and continuously decreased with malignant transformation to CIS and further progression to invasive TGCT (P < 0.001). EZH2 tumor levels were not related to the histological TGCT subtype or clinical tumor stage. Comparison of distinct stages of spermatogenic failure revealed an inverse association of EZH2 levels to the severity of the spermatogenic defect (P < 0.001). Our data strongly suggest that in TGCT EZH2 does not exert its often assumed oncogenic properties during malignant transformation and progression. High EZH2 levels in normal testicular tissue and the inverse association of its expression levels with the severity of spermatogenic failure point to its potential value as a molecular marker for spermatogenic defects and may indicate an important physiological role of EZH2 during intact spermatogenesis.

  20. WHEAT GERM CELL-FREE TRANSLATION, PURIFICATION, AND ASSEMBLY OF A FUNCTIONAL HUMAN STEAROYL-COA DESATURASE COMPLEX

    PubMed Central

    Goren, Michael A.; Fox, Brian G.

    2008-01-01

    A wheat germ cell-free extract was used to perform in vitro translation of human stearoyl-CoA desaturase in the presence of unilamelar liposomes, and near complete transfer of the expressed integral membrane protein into the liposome was observed. Moreover, co-translation of the desaturase along with human cytochrome b5 led to transfer of both membrane proteins into the liposomes. A simple, single step purification via centrifugation in a density gradient yielded proteoliposomes with the desaturase in high purity as judged by capillary electrophoresis. After in vitro reconstitution of the non-heme iron and heme active sites, the function of the reconstituted enzyme complex was demonstrated by conversion of stearoyl-CoA to oleoyl-CoA. This simple translation approach obviates the use of detergents or other lipids to stabilize and isolate a catalytically active integral membrane enzyme. The applicability of cell-free translation to the assembly and purification of other integral membrane protein complexes is discussed. PMID:18765284

  1. Wheat germ cell-free translation, purification, and assembly of a functional human stearoyl-CoA desaturase complex.

    PubMed

    Goren, Michael A; Fox, Brian G

    2008-12-01

    A wheat germ cell-free extract was used to perform in vitro translation of human stearoyl-CoA desaturase in the presence of unilamelar liposomes, and near complete transfer of the expressed integral membrane protein into the liposome was observed. Moreover, co-translation of the desaturase along with human cytochrome b(5) led to transfer of both membrane proteins into the liposomes. A simple, single step purification via centrifugation in a density gradient yielded proteoliposomes with the desaturase in high purity as judged by capillary electrophoresis. After in vitro reconstitution of the non-heme iron and heme active sites, the function of the reconstituted enzyme complex was demonstrated by conversion of stearoyl-CoA to oleoyl-CoA. This simple translation approach obviates the use of detergents or other lipids to stabilize and isolate a catalytically active integral membrane enzyme. The applicability of cell-free translation to the assembly and purification of other integral membrane protein complexes is discussed.

  2. Role of maternal Xenopus syntabulin in germ plasm aggregation and primordial germ cell specification.

    PubMed

    Oh, Denise; Houston, Douglas W

    2017-12-15

    The localization and organization of mitochondria- and ribonucleoprotein granule-rich germ plasm is essential for many aspects of germ cell development. In Xenopus, germ plasm is maternally inherited and is required for the specification of primordial germ cells (PGCs). Germ plasm is aggregated into larger patches during egg activation and cleavage and is ultimately translocated perinuclearly during gastrulation. Although microtubule dynamics and a kinesin (Kif4a) have been implicated in Xenopus germ plasm localization, little is known about how germ plasm distribution is regulated. Here, we identify a role for maternal Xenopus Syntabulin in the aggregation of germ plasm following fertilization. We show that depletion of sybu mRNA using antisense oligonucleotides injected into oocytes results in defects in the aggregation and perinuclear transport of germ plasm and subsequently in reduced PGC numbers. Using live imaging analysis, we also characterize a novel role for Sybu in the collection of germ plasm in vegetal cleavage furrows by surface contraction waves. Additionally, we show that a localized kinesin-like protein, Kif3b, is also required for germ plasm aggregation and that Sybu functionally interacts with Kif3b and Kif4a in germ plasm aggregation. Overall, these data suggest multiple coordinate roles for kinesins and adaptor proteins in controlling the localization and distribution of a cytoplasmic determinant in early development. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Human second trimester amniotic fluid cells are able to create embryoid body-like structures in vitro and to show typical expression profiles of embryonic and primordial germ cells.

    PubMed

    Antonucci, Ivana; Di Pietro, Roberta; Alfonsi, Melissa; Centurione, Maria Antonietta; Centurione, Lucia; Sancilio, Silvia; Pelagatti, Francesca; D'Amico, Maria Angela; Di Baldassarre, Angela; Piattelli, Adriano; Tetè, Stefano; Palka, Giandomenico; Borlongan, Cesar V; Stuppia, Liborio

    2014-01-01

    Human amniotic fluid-derived stem cells (AFSCs) represent a novel class of broadly multipotent stem cells sharing characteristics of both embryonic and adult stem cells. However, both the origin of these cells and their actual properties in terms of pluripotent differentiation potential are still debated. In order to verify the presence of features of pluripotency in human second trimester AFSCs, we have investigated the ability of these cells to form in vitro three-dimensional aggregates, known as embryoid bodies (EBs), and to express specific genes of embryonic stem cells (ESCs) and primordial germ cells (PGCs). EBs were obtained after 5 days of AFSC culture in suspension and showed positivity for alkaline phosphatase (AP) staining and for specific markers of pluripotency (OCT4 and SOX2). Moreover, EB-derived cells showed the expression of specific transcripts of the three germ layers. RT-PCR analysis, carried out at different culture times (second, third, fourth, fifth, and eighth passages), revealed the presence of specific markers of ESCs (such as FGF4 and DAPPA4), as well as of markers typical of PGCs and, in particular, genes involved in early stages of germ cell development (Fragilis, Stella, Vasa, c-Kit, Rnf17). Finally, the expression of genes related to the control of DNA methylation (DNMT3A, DNMT3b1, DNMT1, DNMT3L, MBD1, MBD2, MBD3, MDB4, MeCP2), as well as the lack of inactivation of the X-chromosome in female samples, was also demonstrated. Taken together, these data provide further evidence for the presence of common features among human AFSCs, PGCs, and ESCs.

  4. Boron enhances odontogenic and osteogenic differentiation of human tooth germ stem cells (hTGSCs) in vitro.

    PubMed

    Taşlı, Pakize Neslihan; Doğan, Ayşegül; Demirci, Selami; Şahin, Fikrettin

    2013-06-01

    Stem cell technology has been a great hope for the treatment of many common problems such as Parkinson's disease, Alzheimer's disease, diabetes, cancer, and tissue regeneration. Therefore, the main challenge in hard tissue engineering is to make a successful combination of stem cells and efficient inductors in the concept of stem cell differentiation into odontogenic and osteogenic cell types. Although some boron derivatives have been reported to promote bone and teeth growth in vivo, the molecular mechanism of bone formation has not been elucidated yet. Different concentrations of sodium pentaborate pentahydrate (NaB) were prepared for the analysis of cell toxicity and differentiation evaluations. The odontogenic, osteogenic differentiation and biomineralization of human tooth germ stem cells (hTGSCs) were evaluated by analyzing the mRNA expression levels, odontogenic and osteogenic protein expressions, alkaline phosphatase (ALP) activity, mineralization, and calcium deposits. The NaB-treated group displayed the highest ALP activity and expression of osteo- and odontogenic-related genes and proteins compared to the other groups and baseline. In the current study, increased in vitro odontogenic and osteogenic differentiation capacity of hTGSCs by NaB application has been shown for the first time. The study offers considerable promise for the development of new scaffold systems combined with NaB in both functional bone and tooth tissue engineering.

  5. HISTORY OF GERM CELL MUTAGENESIS

    EPA Science Inventory

    Much of the early work on germ cell mutation analysis was conducted with nonmammalian species, but this historical overview will begin with the rodent studies that provided quantitative data on induced mutations. The initial studies of mutation induction utilized the newly develo...

  6. Epigenome regulation during germ cell specification and development from pluripotent stem cells.

    PubMed

    Kurimoto, Kazuki; Saitou, Mitinori

    2018-06-13

    Germ cells undergo epigenome reprogramming for proper development of the next generation. The realization of germ cell derivation from human and mouse pluripotent stem cells offers unprecedented opportunity for investigation of germline development. Primordial germ cells reconstituted in vitro (PGC-like cells [PGCLCs]) show progressive dilution of genomic DNA methylation, tightly linked with chromatin remodeling, during their specification. PGCLCs can be further expanded by plane culture, allowing maintenance of the gene-expression profiles of early PGCs and continuance of the DNA methylation erasure, thereby establishing an epigenetic `blank slate'. PGCLCs undergo further epigenome regulation to acquire the male or female fates. These findings will provide a foundation for basic germ cell biology and for in-depth evaluations of in vitro gametogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. A Human Anti-Insulin IgG Autoantibody Apparently Arises Through Clonal Selection from an Insulin-Specific “Germ-Line” Natural Antibody Template

    PubMed Central

    Ichiyoshi, Yuji; Zhou, Min; Casali, Paolo

    2015-01-01

    We analyzed the structural correlates underlying the insulin-dependent selection of the specific anti-insulin IgG1 κ mAb13-producing cell clone, derived from a patient with insulin-dependent diabetes mellitus treated with recombinant human insulin. First, we cloned the germ-line genes that putatively gave rise to the expressed VH and Vκ segments and used them to generate the full (unmutated) “germ-line revertant” of the “wild-type” (somatically mutated) mAb13, using recombinant PCR methods and an in vitro human Cγ1 and Cκ expression system. The full “germ-line revertant” bound insulin specifically and in a dose-saturable fashion, but with a relative avidity (Avrel) more than three-fold lower than that of its wild-type counterpart (Avrel, 1.69 × 10−8 vs 4.91 × 10−9 g/μl). Second, we established, by reassorting wild-type and germ-line revertant forms of the mAb13 VH and Vκ segments, that the increased Avrel for insulin of mAb13 when compared with its full “germ-line revertant” counterpart was entirely dependent on the mutations in the VH not those in the Vκ chain. Third, we determined, by site-directed mutagenesis experiments, that of the three mutations in the mAb13 VH segment (Ser→Gly, Ser→Thr, and Ser→Arg at positions 31, 56, and 58, respectively), only Arg58 was crucial in increasing the mAb13 Avrel (from 1.44 × 10−8 to 5.14 × 10−9 g/μl) and affinity (Kd, from 189 to 59 nM) for insulin. The affinity enhancement mediated by the VH segment Arg58 residue reflected about a threefold decrease in dissociation rate constant (Koff, from 4.92 × 10−3 to 1.54 × 10−3 s−1)but not an increase in association rate constant (Kon, from 2.60 × 104 to 2.61 × 104 M−1 s−1), and it contrasted with the complete loss of insulin binding resulting from the substitution of the VH segment Asn52 by Lys. The present findings suggest that human insulin, a self Ag, has the potential to recruit a natural autoantibody-producing cell precursor

  8. Ovarian Germ Cell Tumors Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

    Cancer.gov

    Ovarian germ cell tumors form in germ (egg) cells in the ovary. Ovarian germ cell tumors usually occur in teenage girls or young women and most often affect just one ovary. They are usually cured if found and treated early. Learn about signs and symptoms, tests to diagnose, and stages of ovarian germ cell tumors.

  9. Isolation and characterization of stem cells derived from human third molar tooth germs of young adults: implications in neo-vascularization, osteo-, adipo- and neurogenesis.

    PubMed

    Yalvac, M E; Ramazanoglu, M; Rizvanov, A A; Sahin, F; Bayrak, O F; Salli, U; Palotás, A; Kose, G T

    2010-04-01

    A number of studies have reported in the last decade that human tooth germs contain multipotent cells that give rise to dental and peri-odontal structures. The dental pulp, third molars in particular, have been shown to be a significant stem cell source. In this study, we isolated and characterized human tooth germ stem cells (hTGSCs) from third molars and assessed the expression of developmentally important transcription factors, such as oct4, sox2, klf4, nanog and c-myc, to determine their pluri-potency. Flow-cytometry analysis revealed that hTGSCs were positive for CD73, CD90, CD105 and CD166, but negative for CD34, CD45 and CD133, suggesting that these cells are mesenchymal-like stem cells. Under specific culture conditions, hTGSCs differentiated into osteogenic, adipogenic and neurogenic cells, as well as formed tube-like structures in Matrigel assay. hTGSCs showed significant levels of expression of sox2 and c-myc messenger RNA (mRNA), and a very high level of expression of klf4 mRNA when compared with human embryonic stem cells. This study reports for the first time that hTGSCs express developmentally important transcription factors that could render hTGSCs an attractive candidate for future somatic cell re-programming studies to differentiate germs into various tissue types, such as neurons and vascular structures. In addition, these multipotential hTGSCs could be important stem cell sources for autologous transplantation.

  10. Discovering human germ cell mutagens with whole genome sequencing: Insights from power calculations reveal the importance of controlling for between-family variability.

    PubMed

    Webster, R J; Williams, A; Marchetti, F; Yauk, C L

    2018-07-01

    Mutations in germ cells pose potential genetic risks to offspring. However, de novo mutations are rare events that are spread across the genome and are difficult to detect. Thus, studies in this area have generally been under-powered, and no human germ cell mutagen has been identified. Whole Genome Sequencing (WGS) of human pedigrees has been proposed as an approach to overcome these technical and statistical challenges. WGS enables analysis of a much wider breadth of the genome than traditional approaches. Here, we performed power analyses to determine the feasibility of using WGS in human families to identify germ cell mutagens. Different statistical models were compared in the power analyses (ANOVA and multiple regression for one-child families, and mixed effect model sampling between two to four siblings per family). Assumptions were made based on parameters from the existing literature, such as the mutation-by-paternal age effect. We explored two scenarios: a constant effect due to an exposure that occurred in the past, and an accumulating effect where the exposure is continuing. Our analysis revealed the importance of modeling inter-family variability of the mutation-by-paternal age effect. Statistical power was improved by models accounting for the family-to-family variability. Our power analyses suggest that sufficient statistical power can be attained with 4-28 four-sibling families per treatment group, when the increase in mutations ranges from 40 to 10% respectively. Modeling family variability using mixed effect models provided a reduction in sample size compared to a multiple regression approach. Much larger sample sizes were required to detect an interaction effect between environmental exposures and paternal age. These findings inform study design and statistical modeling approaches to improve power and reduce sequencing costs for future studies in this area. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  11. Why Should I Care about Germs?

    MedlinePlus

    ... The term germs is really just a generic word for four different types of organisms: bacteria, viruses, fungi, and protozoa. Bacteria are tiny, single-celled organisms that are found throughout nature, including in the bodies of human ...

  12. The Biology of the Germ line in Echinoderms

    PubMed Central

    Wessel, Gary M.; Brayboy, Lynae; Fresques, Tara; Gustafson, Eric A.; Oulhen, Nathalie; Ramos, Isabela; Reich, Adrian; Swartz, S. Zachary; Yajima, Mamiko; Zazueta, Vanessa

    2014-01-01

    SUMMARY The formation of the germ line in an embryo marks a fresh round of reproductive potential. The developmental stage and location within the embryo where the primordial germ cells (PGCs) form, however, differs markedly among species. In many animals, the germ line is formed by an inherited mechanism, in which molecules made and selectively partitioned within the oocyte drive the early development of cells that acquire this material to a germ-line fate. In contrast, the germ line of other animals is fated by an inductive mechanism that involves signaling between cells that directs this specialized fate. In this review, we explore the mechanisms of germ-line determination in echinoderms, an early-branching sister group to the chordates. One member of the phylum, sea urchins, appears to use an inherited mechanism of germ-line formation, whereas their relatives, the sea stars, appear to use an inductive mechanism. We first integrate the experimental results currently available for germ line determination in the sea urchin, for which considerable new information is available, and then broaden the investigation to the lesser-known mechanisms in sea stars and other echinoderms. Even with this limited insight, it appears that sea stars, and perhaps the majority of the echinoderm taxon, rely on inductive mechanisms for germ-line fate determination. This enables a strongly contrasted picture for germ-line determination in this phylum, but one for which transitions between different modes of germ-line determination might now be experimentally addressed. PMID:23900765

  13. Malignant mixed germ cell tumour of ovary--an unusual combination and review of literature.

    PubMed

    Goyal, Lajya Devi; Kaur, Sharanjit; Kawatra, Kanwardeep

    2014-11-04

    Mixed germ cell tumours of the ovary are malignant neoplasms of the ovary comprising of two or more types of germ cell components. Most of the malignant mixed germ cell tumours consists of dysgerminoma accompanied by endodermal sinus tumours, immature teratoma or choriocarcinoma. There are only few case reports of mixed germ cell tumours with different combinations of malignant components. We report a very rare case of mixed germ cell tumours consisted of malignant components of endodermal sinus tumour, emryonal carcinoma, and benign component of teratomatuos and trophoblastic differentiation. This is the first case report in the literature with both benign and malignant component of type described to best of our knowledge. Patient was an 18 year old girl, who presented with pain abdomen, abdominal mass and irregular bleeding. Ultrasound and CT scan showed a huge mass with solid and cystic component. Tumour markers i.e alpha feto- protein (AFP), human chorionic gonadotropin (hCG), lactate dehydrogenate (LDH) and Ca-125 were raised. We performed fertility sparing surgery by preserving one ovary, tube and uterus. Conclusion: Malingnant mixed germ cell tumours of ovary are highly aggressive neoplasm and early intervention and fertility sparing surgery is required for any adolescent girl presenting with rapidly enlarging pelvic mass.

  14. Prenatal ultrasound and postmortem histologic evaluation of tooth germs: an observational, transversal study.

    PubMed

    Seabra, Mariana; Felino, António; Nogueira, Rosete; Valente, Francisco; Braga, Ana Cristina; Vaz, Paula

    2015-05-12

    Hypodontia is the most frequent developmental anomaly of the orofacial complex, and its detection in prenatal ultrasound may indicate the presence of congenital malformations, genetic syndromes and chromosomal abnormalities. To date, only a few studies have evaluated the histological relationship of human tooth germs identified by two-dimensional (2D) ultrasonography. In order to analyze whether two-dimensional ultrasonography of tooth germs may be successfully used for identifying genetic syndromes, prenatal ultrasound images of fetal tooth germs obtained from a Portuguese population sample were compared with histological images obtained from fetal autopsies. Observational, descriptive, transversal study. The study protocol followed the ethical principles outlined by the Helsinki Declaration and was approved by the Ethics Committee of the School of Dental Medicine, University of Porto (FMDUP, Porto, Portugal) and of the Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/EPE, Porto, Portugal) as well as by the CGC Genetics Embryofetal Pathology Laboratory. Eighty-five fetuses examined by prenatal ultrasound screening from May 2011 to August 2012 had an indication for autopsy following spontaneous fetal death or medical termination of pregnancy. Of the 85 fetuses, 37 (43.5%) were randomly selected for tooth germ evaluation by routine histopathological analysis. Fetuses who were up to 30 weeks of gestation, and whose histological pieces were not representative of all maxillary tooth germs was excluded. Twenty four fetus between the 13(th) and 30(th) weeks of gestation fulfilled the parameters to autopsy. Twenty four fetuses were submitted to histological evaluation and were determined the exact number, morphology, and mineralization of their tooth germs. All tooth germs were identifiable with ultrasonography as early as the 13(th) week of gestation. Of the fetuses autopsied, 41.7% had hypodontia (29.1% maxillary hypodontia and 20.9% mandibular hypodontia). This

  15. Convergent evolution of germ granule nucleators: A hypothesis.

    PubMed

    Kulkarni, Arpita; Extavour, Cassandra G

    2017-10-01

    Germ cells have been considered "the ultimate stem cell" because they alone, during normal development of sexually reproducing organisms, are able to give rise to all organismal cell types. Morphological descriptions of a specialized cytoplasm termed 'germ plasm' and associated electron dense ribonucleoprotein (RNP) structures called 'germ granules' within germ cells date back as early as the 1800s. Both germ plasm and germ granules are implicated in germ line specification across metazoans. However, at a molecular level, little is currently understood about the molecular mechanisms that assemble these entities in germ cells. The discovery that in some animals, the gene products of a small number of lineage-specific genes initiate the assembly (also termed nucleation) of germ granules and/or germ plasm is the first step towards facilitating a better understanding of these complex biological processes. Here, we draw on research spanning over 100years that supports the hypothesis that these nucleator genes may have evolved convergently, allowing them to perform analogous roles across animal lineages. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Constitutive activation of B-Raf in the mouse germ line provides a model for human cardio-facio-cutaneous syndrome.

    PubMed

    Urosevic, Jelena; Sauzeau, Vincent; Soto-Montenegro, María L; Reig, Santiago; Desco, Manuel; Wright, Emma M Burkitt; Cañamero, Marta; Mulero, Francisca; Ortega, Sagrario; Bustelo, Xosé R; Barbacid, Mariano

    2011-03-22

    RASopathies are a class of developmental syndromes that result from congenital mutations in key elements of the RAS/RAF/MEK signaling pathway. A well-recognized RASopathy is the cardio-facio-cutaneous (CFC) syndrome characterized by a distinctive facial appearance, heart defects, and mental retardation. Clinically diagnosed CFC patients carry germ-line mutations in four different genes, B-RAF, MEK1, MEK2, and K-RAS. B-RAF is by far the most commonly mutated locus, displaying mutations that most often result in constitutive activation of the B-RAF kinase. Here, we describe a mouse model for CFC generated by germ-line expression of a B-RafLSLV600E allele. This targeted allele allows low levels of expression of B-RafV600E, a constitutively active B-Raf kinase first identified in human melanoma. B-Raf+/LSLV600E mice are viable and display several of the characteristic features observed in CFC patients, including reduced life span, small size, facial dysmorphism, cardiomegaly, and epileptic seizures. These mice also show up-regulation of specific catecholamines and cataracts, two features detected in a low percentage of CFC patients. In addition, B-Raf+/LSLV600E mice develop neuroendocrine tumors, a pathology not observed in CFC patients. These mice may provide a means of better understanding the pathophysiology of at least some of the clinical features present in CFC patients. Moreover, they may serve as a tool to evaluate the potential therapeutic efficacy of B-RAF inhibitors and establish the precise window at which they could be effective against this congenital syndrome.

  17. What Are Germs?

    MedlinePlus

    ... like fevers, sniffles, rashes, coughing, vomiting, and diarrhea. How do doctors figure out what germs are doing? They take a closer look. By looking at samples of blood, urine, and other fluids under a ...

  18. Lin28a regulates germ cell pool size and fertility

    PubMed Central

    Shinoda, Gen; de Soysa, T. Yvanka; Seligson, Marc T.; Yabuuchi, Akiko; Fujiwara, Yuko; Huang, Pei Yi; Hagan, John P.; Gregory, Richard I.; Moss, Eric G.; Daley, George Q.

    2013-01-01

    Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. PMID:23378032

  19. Human-specific subcellular compartmentalization of P-element induced wimpy testis-like (PIWIL) granules during germ cell development and spermatogenesis.

    PubMed

    Gomes Fernandes, Maria; He, Nannan; Wang, Fang; Van Iperen, Liesbeth; Eguizabal, Cristina; Matorras, Roberto; Roelen, Bernard A J; Chuva De Sousa Lopes, Susana M

    2018-02-01

    What is the dynamics of expression of P-element induced wimpy testis-like (PIWIL) proteins in the germline during human fetal development and spermatogenesis? PIWIL1, PIWIL2, PIWIL3 and PIWIL4 were expressed in a sex-specific fashion in human germ cells (GC) during development and adulthood. PIWILs showed a mutually exclusive pattern of subcellular localization. PIWILs were present in the intermitochondrial cement and a single large granule in meiotic GC and their expression was different from that observed in mice, highlighting species-differences. In mice, PIWIL proteins play prominent roles in male infertility. PIWIL mouse mutants show either post-meiotic arrest at the round spermatid stage (PIWIL1) or arrest at the zygotene-pachytene stage of meiosis I (PIWIL2 and PIWIL4) in males, while females remain fertile. Recent studies have reported a robust piRNA pool in human fetal ovary. This is a qualitative analysis of PIWILs expression in paraffin-embedded fetal human male (N = 8), female gonads (N = 6) and adult testes (N = 5), and bioinformatics analysis of online available single-cell transcriptomics data of human fetal germ cells (n = 242). Human fetal gonads from elective abortion without medical indication and adult testes biopsies were donated for research with informed consent. Samples were fixed, paraffin-embedded and analyzed by immunofluorescence to study the temporal and cellular localization of PIWIL1, PIWIL2, PIWIL3 and PIWIL4. PIWIL1, PIWIL2 and PIWIL4 showed a mutually exclusive pattern of subcellular localization, particularly in female oocytes. To our surprise, PIWIL1 immunostaining revealed the presence of a single dense paranuclear body, resembling the chromatoid body of haploid spermatocytes, in meiotic oocytes. Moreover, in contrast to mice, PIWIL4, but not PIWIL2, localized to the intermitochondrial cement. PIWIL3 was not expressed in GC during development. The upregulation of PIWIL transcripts correlated with the transcription of markers

  20. Differentiation of Mesenchymal Stem Cells from Human Umbilical Cord Tissue into Odontoblast-Like Cells Using the Conditioned Medium of Tooth Germ Cells In Vitro

    PubMed Central

    Li, Tian Xia; Yuan, Jie; Chen, Yan; Pan, Li Jie; Song, Chun; Bi, Liang Jia; Jiao, Xiao Hui

    2013-01-01

    The easily accessible mesenchymal stem cells in the Wharton's jelly of human umbilical cord tissue (hUCMSCs) have excellent proliferation and differentiation potential, but it remains unclear whether hUCMSCs can differentiate into odontoblasts. In this study, mesenchymal stem cells were isolated from the Wharton's jelly of human umbilical cord tissue using the simple method of tissue blocks culture attachment. UCMSC surface marker expression was then evaluated for the isolated cells using flow cytometry. The third-passage hUCMSCs induced by conditioned medium from developing tooth germ cells (TGC-CM) displayed high alkaline phosphatase (ALP) levels (P < 0.001), an enhanced ability to proliferate (P < 0.05), and the presence of mineralized nodules. These effects were not observed in cells treated with regular medium. After induction of hUCMSCs, the results of reverse transcriptional polymerase chain reaction (PCR) indicated that the dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP1) genes were significantly tested. Additionally, dentin sialoprotein (DSP) and DMP1 demonstrated significant levels of staining in an immunofluorescence analysis. In contrast, the control cells failed to display the characteristics of odontoblasts. Taken together, these results suggest that hUCMSCs can be induced to differentiate into odontoblast-like cells with TGC-CM and provide a novel strategy for tooth regeneration research. PMID:23762828

  1. Serial lectin affinity chromatography with concavalin A and wheat germ agglutinin demonstrates altered asparagine-linked sugar-chain structures of prostatic acid phosphatase in human prostate carcinoma.

    PubMed

    Yoshida, K I; Honda, M; Arai, K; Hosoya, Y; Moriguchi, H; Sumi, S; Ueda, Y; Kitahara, S

    1997-08-01

    Differences between human prostate carcinoma (PCA, five cases) and benign prostatic hyperplasia (BPH, five cases) in asparagine-linked (Asn) sugar-chain structure of prostatic acid phosphatase (PAP) were investigated using lectin affinity chromatography with concanavalin A (Con A) and wheat germ agglutinin (WGA). PAP activities were significantly decreased in PCA-derived PAP, while no significant differences between the two PAP preparations were observed in the enzymatic properties (Michaelis-Menten value, optimal pH, thermal stability, and inhibition study). In these PAP preparations, all activities were found only in the fractions which bound strongly to the Con A column and were undetectable in the Con A unbound fractions and in the fractions which bound weakly to the Con A column. The relative amounts of PAP which bound strongly to the Con A column but passed through the WGA column, were significantly greater in BPH-derived PAP than in PCA-derived PAP. In contrast, the relative amounts of PAP which bound strongly to the Con A column and bound to the WGA column, were significantly greater in PCA-derived PAP than in BPH-derived PAP. The findings suggest that Asn-linked sugar-chain structures are altered during oncogenesis in human prostate and also suggest that studies of qualitative differences of sugar-chain structures of PAP might lead to a useful diagnostic tool for PCA.

  2. Black carp vasa identifies embryonic and gonadal germ cells.

    PubMed

    Xue, Ting; Yu, Miao; Pan, Qihua; Wang, Yizhou; Fang, Jian; Li, Lingyu; Deng, Yu; Chen, Kai; Wang, Qian; Chen, Tiansheng

    2017-07-01

    Identification of molecular markers is an essential step in the study of germ cells. Vasa is an RNA helicase and a well-known germ cell marker that plays a crucial role in germ cell development. Here, we identified the Vasa homolog termed Mpvasa as the first germ cell marker in black carp (Mylopharyngodon piceus). First, a 2819-bp full-length Mpvasa complementary DNA (cDNA) was cloned by PCR using degenerated primers of conserved sequences and gene-specific primers. The Mpvasa cDNA sequence encodes a 637-amino acid protein that contains eight conserved characteristic motifs of the DEAD box protein family, and shares high identity to grass carp (81%) and zebrafish (74%) vasa homologs. Second, Mpvasa expression was restricted to the gonad in adulthood by RT-PCR and Western blot analysis. The dynamic patterns of temporal-spatial expression of Mpvasa during gametogenesis were examined by in situ hybridization, and Mpvasa transcripts were strictly detected in gonadal germ cells throughout oogenesis, predominantly in immature oocytes (stage I, II, and III oocytes). Third, Mpvasa transcripts were highly detected in unfertilized eggs and early embryos, and the signal indicated a dynamic migration of the primordial germ cells during embryogenesis, suggesting that Mpvasa transcripts were maternally inherited and specifically distributed in germ cells. Taken together, these results demonstrated that Mpvasa is an applicable molecular marker for identification of gonadal and embryonic germ cells, which facilitates the isolation and utilization of germ cells in black carp.

  3. Germ line mechanics – and unfinished business

    PubMed Central

    Wessel, Gary M.

    2016-01-01

    Primordial germ cells are usually made early in the development of an organism. These are the mother of all stem cells that are necessary for propagation of the species, yet use highly diverse mechanisms between organisms. How they are specified, and when and where they form, are central to developmental biology. Using diverse organisms to study this development is illuminating for understanding the mechanics these cells use in this essential function, and for identifying the breadth of evolutionary changes that have occurred between species. This essay emphasizes how echinoderms may contribute to the patch-work quilt of our understanding of germ line formation during embryogenesis. PMID:26970000

  4. Germ Line Mechanics--And Unfinished Business.

    PubMed

    Wessel, Gary M

    2016-01-01

    Primordial germ cells are usually made early in the development of an organism. These are the mother of all stem cells that are necessary for propagation of the species, yet use highly diverse mechanisms between organisms. How they are specified, and when and where they form, are central to developmental biology. Using diverse organisms to study this development is illuminating for understanding the mechanics these cells use in this essential function and for identifying the breadth of evolutionary changes that have occurred between species. This essay emphasizes how echinoderms may contribute to the patchwork quilt of our understanding of germ line formation during embryogenesis. © 2016 Elsevier Inc. All rights reserved.

  5. Is Tobacco Smoke a Germ-Cell Mutagen?

    EPA Science Inventory

    Although no international organization exists to declare whether an agent is a germ-cell mutagen, tobacco smoke may be a human germ-cell mutagen. In the mouse, tobacco smoke induces a significant increase in the mutation frequency at an expanded simple tandem repeat (ESTR) locus....

  6. Establishment of the Vertebrate Germ Layers.

    PubMed

    Tseng, Wei-Chia; Munisha, Mumingjiang; Gutierrez, Juan B; Dougan, Scott T

    2017-01-01

    The process of germ layer formation is a universal feature of animal development. The germ layers separate the cells that produce the internal organs and tissues from those that produce the nervous system and outer tissues. Their discovery in the early nineteenth century transformed embryology from a purely descriptive field into a rigorous scientific discipline, in which hypotheses could be tested by observation and experimentation. By systematically addressing the questions of how the germ layers are formed and how they generate overall body plan, scientists have made fundamental contributions to the fields of evolution, cell signaling, morphogenesis, and stem cell biology. At each step, this work was advanced by the development of innovative methods of observing cell behavior in vivo and in culture. Here, we take an historical approach to describe our current understanding of vertebrate germ layer formation as it relates to the long-standing questions of developmental biology. By comparing how germ layers form in distantly related vertebrate species, we find that highly conserved molecular pathways can be adapted to perform the same function in dramatically different embryonic environments.

  7. Extragonadal Germ Cell Cancer (EGC)

    MedlinePlus

    The Testicular Cancer Resource Center Extragonadal Germ Cell Cancer (EGC) 95% of all testicular tumors are germ cell tumors. That is, the tumors originate in the sperm forming cells in the testicles ( ...

  8. Ovarian Germ Cell Tumors Treatment

    MedlinePlus

    ... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview ... types of treatment for patients with ovarian germ cell tumors. Different types of treatment are available for ...

  9. Expanding the Oro-Dental and Mutational Spectra of Kabuki Syndrome and Expression of KMT2D and KDM6A in Human Tooth Germs

    PubMed Central

    Porntaveetus, Thantrira; Abid, Mushriq F; Theerapanon, Thanakorn; Srichomthong, Chalurmpon; Ohazama, Atsushi; Kawasaki, Katsushige; Kawasaki, Maiko; Suphapeetiporn, Kanya; Sharpe, Paul T.; Shotelersuk, Vorasuk

    2018-01-01

    Kabuki syndrome is a rare genetic disorder characterized by distinct dysmorphic facial features, intellectual disability, and multiple developmental abnormalities. Despite more than 350 documented cases, the oro-dental spectrum associated with kabuki syndrome and expression of KMT2D (histone-lysine N-methyltransferase 2D) or KDM6A (lysine-specific demethylase 6A) genes in tooth development have not been well defined. Here, we report seven unrelated Thai patients with Kabuki syndrome having congenital absence of teeth, malocclusion, high-arched palate, micrognathia, and deviated tooth shape and size. Exome sequencing successfully identified that six patients were heterozygous for mutations in KMT2D, and one in KDM6A. Six were novel mutations, of which five were in KMT2D and one in KDM6A. They were truncating mutations including four frameshift deletions and two nonsense mutations. The predicted non-functional KMT2D and KDM6A proteins are expected to cause disease by haploinsufficiency. Our study expands oro-dental, medical, and mutational spectra associated with Kabuki syndrome. We also demonstrate for the first time that KMT2D and KDM6A are expressed in the dental epithelium of human tooth germs. PMID:29725259

  10. A germ cell determinant reveals parallel pathways for germ line development in Caenorhabditis elegans.

    PubMed

    Mainpal, Rana; Nance, Jeremy; Yanowitz, Judith L

    2015-10-15

    Despite the central importance of germ cells for transmission of genetic material, our understanding of the molecular programs that control primordial germ cell (PGC) specification and differentiation are limited. Here, we present findings that X chromosome NonDisjunction factor-1 (XND-1), known for its role in regulating meiotic crossover formation, is an early determinant of germ cell fates in Caenorhabditis elegans. xnd-1 mutant embryos display a novel 'one PGC' phenotype as a result of G2 cell cycle arrest of the P4 blastomere. Larvae and adults display smaller germ lines and reduced brood size consistent with a role for XND-1 in germ cell proliferation. Maternal XND-1 proteins are found in the P4 lineage and are exclusively localized to the nucleus in PGCs, Z2 and Z3. Zygotic XND-1 turns on shortly thereafter, at the ∼300-cell stage, making XND-1 the earliest zygotically expressed gene in worm PGCs. Strikingly, a subset of xnd-1 mutants lack germ cells, a phenotype shared with nos-2, a member of the conserved Nanos family of germline determinants. We generated a nos-2 null allele and show that nos-2; xnd-1 double mutants display synthetic sterility. Further removal of nos-1 leads to almost complete sterility, with the vast majority of animals without germ cells. Sterility in xnd-1 mutants is correlated with an increase in transcriptional activation-associated histone modification and aberrant expression of somatic transgenes. Together, these data strongly suggest that xnd-1 defines a new branch for PGC development that functions redundantly with nos-2 and nos-1 to promote germline fates by maintaining transcriptional quiescence and regulating germ cell proliferation. © 2015. Published by The Company of Biologists Ltd.

  11. Sympathetic activation during early pregnancy in humans

    PubMed Central

    Jarvis, Sara S; Shibata, Shigeki; Bivens, Tiffany B; Okada, Yoshiyuki; Casey, Brian M; Levine, Benjamin D; Fu, Qi

    2012-01-01

    Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min−1, 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min−1; main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm−5; P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.−1 min−1; P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml−1, P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml−1, P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications. PMID:22687610

  12. Functional Analysis of the Drosophila Embryonic Germ Cell Transcriptome by RNA Interference

    PubMed Central

    Bujna, Ágnes; Vilmos, Péter; Spirohn, Kerstin; Boutros, Michael; Erdélyi, Miklós

    2014-01-01

    In Drosophila melanogaster, primordial germ cells are specified at the posterior pole of the very early embryo. This process is regulated by the posterior localized germ plasm that contains a large number of RNAs of maternal origin. Transcription in the primordial germ cells is actively down-regulated until germ cell fate is established. Bulk expression of the zygotic genes commences concomitantly with the degradation of the maternal transcripts. Thus, during embryogenesis, maternally provided and zygotically transcribed mRNAs determine germ cell development collectively. In an effort to identify novel genes involved in the regulation of germ cell behavior, we carried out a large-scale RNAi screen targeting both maternal and zygotic components of the embryonic germ line transcriptome. We identified 48 genes necessary for distinct stages in germ cell development. We found pebble and fascetto to be essential for germ cell migration and germ cell division, respectively. Our data uncover a previously unanticipated role of mei-P26 in maintenance of embryonic germ cell fate. We also performed systematic co-RNAi experiments, through which we found a low rate of functional redundancy among homologous gene pairs. As our data indicate a high degree of evolutionary conservation in genetic regulation of germ cell development, they are likely to provide valuable insights into the biology of the germ line in general. PMID:24896584

  13. AiGERM: A logic programming front end for GERM

    NASA Technical Reports Server (NTRS)

    Hashim, Safaa H.

    1990-01-01

    AiGerm (Artificially Intelligent Graphical Entity Relation Modeler) is a relational data base query and programming language front end for MCC (Mission Control Center)/STP's (Space Test Program) Germ (Graphical Entity Relational Modeling) system. It is intended as an add-on component of the Germ system to be used for navigating very large networks of information. It can also function as an expert system shell for prototyping knowledge-based systems. AiGerm provides an interface between the programming language and Germ.

  14. Secondary nocturnal enuresis related to central diabetes insipidus as an early manifestation of intracranial germinomatous germ cell tumors in a series of male youngsters.

    PubMed

    Papaefthimiou, Apostolos; Kyrgios, Ioannis; Kotanidou, Eleni P; Maggana, Ioanna; Mouzaki, Konstantina; Galli-Tsinopoulou, Assimina

    2015-02-01

    Nocturnal enuresis is a common symptom in children. It is usually attributed to benign causes and diagnostic evaluation is not carried out. We report three male young patients initially presenting with short stature and nocturnal enuresis, related to diabetes insipidus, caused by intracranial germinomatous germ cell tumors. In all three cases, water deprivation tests confirmed diabetes insipidus. Extensive endocrinological investigation also showed further hormone deficiencies. Magnetic resonance imaging of the brain revealed the presence of a central nervous system lesion and histology confirmed the final diagnosis. Surgery, radiation with or without chemotherapy was conducted and the patients were treated with hormone replacement therapies. The patients after a long follow-up were free of disease. We present these cases to alert clinicians to bear in mind that the presence of an intracranial germinomatous germ cell tumor should at least be considered in a child presenting with bed wetting, especially if additional symptoms and signs, including late onset puberty and growth delay or morning hypernatremia, may coexist. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Cadmium contamination of early human milk.

    PubMed

    Sikorski, R; Paszkowski, T; Radomański, T; Szkoda, J

    1989-01-01

    The concentration of cadmium was measured by flame atomic absorption spectrometry in colostrum samples obtained from 110 women on the 4th postpartum day. Detectable amounts of cadmium were found in 95% of the examined samples and the geometric mean of the determined values was 0.002 mg/kg. In 3 cases (2.7%, the examined neonates received via mother's milk an amount of cadmium exceeding the maximum daily intake level for this metal. Maternal age, parity and place of residence did not affect the determined cadmium levels of milk. Cadmium content in the early human milk of current smokers did not differ significantly from that of nonsmoking mothers.

  16. Antitumor Activities and Apoptosis-regulated Mechanisms of Fermented Wheat Germ Extract in the Transplantation Tumor Model of Human HT-29 Cells in Nude Mice.

    PubMed

    Zhang, Jia Yan; Xiao, Xiang; Dong, Ying; Wu, Jing; Zhou, Xing Hua

    2015-10-01

    A subcutaneous transplantation tumor model of human HT-29 cells in nude mice was established to evaluate anticarcinogenic activities, and the apoptosis-regulated mechanism effect of aqueous extract of fermented wheat germ with Lactobacillus plantarum dy-1 (LFWGE). The HT-29 cells were transplanted via subcutaneous injection of 1×107 cells into the right flank of each nude mouse. Then, nude mice were treated for 30 d with LFWGE (high-dose 2 g/kg/d; low-dose 1 g/kg/d) and for 7 d with 5-fluorouracil (5-FU, 25 mg/kg/d) by gavage and intraperitoneal injection, respectively. An inhibition of tumor growth was observed. Tumor volume and weights decreased significantly in both groups of nude mice treated with LFWGE. In addition, the cell apoptosis rate of the LFWGE group (2 g/kg/d, 60.1%±4.4%; 1 g/kg/d, 58.6%±6.9%) was significantly higher than that of the control group (11.5%±1.6%) and 5-FU group (32.1%±3.5%) as measured by the TUNEL assay. Moreover, the real-time fluorescent quantitative PCR and Western blot method further confirmed these enhancing apoptosis and growth inhibition effects. The involvement of LFWGE in inducing apoptosis was confirmed by the expression of Bax, Bcl-2, Caspase-3, and CyclinD1. The results showed that LFWGE could induce subcutaneous transplantation tumor apoptosis in nude mice and could be as a natural nutrient supplements or chemopreventive agent in the treatment of human colon cancer. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  17. Early Complementopathy after Multiple Injuries in Humans

    PubMed Central

    Burk, Anne-Maud; Martin, Myriam; Flierl, Michael A.; Rittirsch, Daniel; Helm, Matthias; Lampl, Lorenz; Bruckner, Uwe; Stahl, Gregory L.; Blom, Anna M.; Perl, Mario; Gebhard, Florian; Huber-Lang, Markus

    2012-01-01

    After severe tissue injury, innate immunity mounts a robust systemic inflammatory response. However, little is known about the immediate impact of multiple trauma on early complement function in humans. In the present study we hypothesized that multiple trauma results in immediate activation, consumption and dysfunction of the complement cascade and that the resulting severe “complementopathy” may be associated with morbidity and mortality. Therefore a prospective multicenter study with 25 healthy volunteers and 40 polytrauma patients (mean injury severity score [ISS] = 30.3 ± 2.9) was performed. After polytrauma serum was collected as early as possible at the scene, upon admission to the emergency room and 4, 12, 24, 120 and 240 hours post trauma and analysed for the complement profile. Complement hemolytic activity (CH-50) was massively reduced within the first 24 h after injury, recovered only 5 days after trauma and discriminated between lethal and non-lethal 28-day outcome. Serum levels of the complement activation products C3a and C5a were significantly elevated throughout the entire observation period and correlated with the severity of traumatic brain injury and survival. The soluble terminal complement complex SC5b-9 and mannose-binding lectin (MBL) showed a biphasic response after trauma. Key fluid phase inhibitors of complement, such as C4b-binding protein (C4BP) and factor I, were significantly diminished early after trauma. The present data indicate an almost synchronically rapid activation and dysfunction of complement suggesting a trauma-induced “complementopathy” early after injury. These events may participate to the impairment of the innate immune response observed after severe trauma. PMID:22258234

  18. Human Mesenchymal Stem Cells Derived From Limb Bud Can Differentiate into All Three Embryonic Germ Layers Lineages

    PubMed Central

    Jiao, Fei; Wang, Juan; Dong, Zhao-lun; Wu, Min-juan; Zhao, Ting-bao; Li, Dan-dan

    2012-01-01

    Abstract Mesenchymal stem cells (MSCs) have been isolated from many sources, including adults and fetuses. Previous studies have demonstrated that, compared with their adult counterpart, fetal MSCs with several remarkable advantages may be a better resource for clinical applications. In this study, we successfully isolated a rapidly proliferating cell population from limb bud of aborted fetus and termed them “human limb bud–derived mesenchymal stem cells” (hLB-MSCs). Characteristics of their morphology, phenotype, cell cycle, and differentiation properties were analyzed. These adherent cell populations have a typically spindle-shaped morphology. Flow cytometry analysis showed that hLB-MSCs are positive for CD13, CD29, CD90, CD105, and CD106, but negative for CD3, CD4, CD5, CD11b, CD14, CD15, CD34, CD45, CD45RA, and HLA-DR. The detection of cell cycle from different passages indicated that hLB-MSCs have a similar potential for propagation during long culture in vitro. The most novel finding here is that, in addition to their mesodermal differentiation (osteoblasts and adipocytes), hLB-MSCs can also differentiated into extramesenchymal lineages, such as neural (ectoderm) and hepatic (endoderm) progenies. These results indicate that hLB-MSCs have a high level of plasticity and can differentiate into cell lineages from all three embryonic layers in vitro. PMID:22775353

  19. Human mesenchymal stem cells derived from limb bud can differentiate into all three embryonic germ layers lineages.

    PubMed

    Jiao, Fei; Wang, Juan; Dong, Zhao-Lun; Wu, Min-Juan; Zhao, Ting-Bao; Li, Dan-Dan; Wang, Xin

    2012-08-01

    Mesenchymal stem cells (MSCs) have been isolated from many sources, including adults and fetuses. Previous studies have demonstrated that, compared with their adult counterpart, fetal MSCs with several remarkable advantages may be a better resource for clinical applications. In this study, we successfully isolated a rapidly proliferating cell population from limb bud of aborted fetus and termed them "human limb bud-derived mesenchymal stem cells" (hLB-MSCs). Characteristics of their morphology, phenotype, cell cycle, and differentiation properties were analyzed. These adherent cell populations have a typically spindle-shaped morphology. Flow cytometry analysis showed that hLB-MSCs are positive for CD13, CD29, CD90, CD105, and CD106, but negative for CD3, CD4, CD5, CD11b, CD14, CD15, CD34, CD45, CD45RA, and HLA-DR. The detection of cell cycle from different passages indicated that hLB-MSCs have a similar potential for propagation during long culture in vitro. The most novel finding here is that, in addition to their mesodermal differentiation (osteoblasts and adipocytes), hLB-MSCs can also differentiated into extramesenchymal lineages, such as neural (ectoderm) and hepatic (endoderm) progenies. These results indicate that hLB-MSCs have a high level of plasticity and can differentiate into cell lineages from all three embryonic layers in vitro.

  20. [Proliferative capacity of mesenchymal stem cells from human fetal bone marrow and their ability to differentiate into the derivative cell types of three embryonic germ layers].

    PubMed

    Wang, Yue-Chun; Zhang, Yuan

    2008-06-25

    Strong proliferative capacity and the ability to differentiate into the derivative cell types of three embryonic germ layers are the two important characteristics of embryonic stem cells. To study whether the mesenchymal stem cells from human fetal bone marrow (hfBM-MSCs) possess these embryonic stem cell-like biological characteristics, hfBM-MSCs were isolated from bone barrows and further purified according to the different adherence of different kinds of cells to the wall of culture flask. The cell cycle of hfBM-MSCs and MSC-specific surface markers such as CD29, CD44, etc were identified using flow cytometry. The expressions of human telomerase reverse transcriptase (hTERT), the embryonic stem cell-specific antigens, such as Oct4 and SSEA-4 were detected with immunocytochemistry at the protein level and were also tested by RT-PCR at the mRNA level. Then, hfBM-MSCs were induced to differentiate toward neuron cells, adipose cells, and islet B cells under certain conditions. It was found that 92.3% passage-4 hfBM-MSCs and 96.1% passage-5 hfBM-MSCs were at G(0)/G(1) phase respectively. hfBM-MSCs expressed CD44, CD106 and adhesion molecule CD29, but not antigens of hematopoietic cells CD34 and CD45, and almost not antigens related to graft-versus-host disease (GVHD), such as HLA-DR, CD40 and CD80. hfBM-MSCs expressed the embryonic stem cell-specific antigens such as Oct4, SSEA-4, and also hTERT. Exposure of these cells to various inductive agents resulted in morphological changes towards neuron-like cells, adipose-like cells, and islet B-like cells and they were tested to be positive for related characteristic markers. These results suggest that there are plenty of MSCs in human fetal bone marrow, and hfBM-MSCs possess the embryonic stem cell-like biological characteristics, moreover, they have a lower immunogenic nature. Thus, hfBM-MSCs provide an ideal source for tissue engineering and cellular therapeutics.

  1. Development without germ cells: the role of the germ line in zebrafish sex differentiation.

    PubMed

    Slanchev, Krasimir; Stebler, Jürg; de la Cueva-Méndez, Guillermo; Raz, Erez

    2005-03-15

    The progenitors of the gametes, the primordial germ cells (PGCs) are typically specified early in the development in positions, which are distinct from the gonad. These cells then migrate toward the gonad where they differentiate into sperms and eggs. Here, we study the role of the germ cells in somatic development and particularly the role of the germ line in the sex differentiation in zebrafish. To this end, we ablated the germ cells using two independent methods and followed the development of the experimental fish. First, PGCs were ablated by knocking down the function of dead end, a gene important for the survival of this lineage. Second, a method to eliminate the PGCs using the toxin-antitoxin components of the parD bacterial genetic system was used. Specifically, we expressed a bacterial toxin Kid preferentially in the PGCs and at the same time protected somatic cells by uniformly expressing the specific antidote Kis. Our results demonstrate an unexpected role for the germ line in promoting female development because PGC-ablated fish invariably developed as males.

  2. Development without germ cells: The role of the germ line in zebrafish sex differentiation

    PubMed Central

    Slanchev, Krasimir; Stebler, Jürg; de la Cueva-Méndez, Guillermo; Raz, Erez

    2005-01-01

    The progenitors of the gametes, the primordial germ cells (PGCs) are typically specified early in the development in positions, which are distinct from the gonad. These cells then migrate toward the gonad where they differentiate into sperms and eggs. Here, we study the role of the germ cells in somatic development and particularly the role of the germ line in the sex differentiation in zebrafish. To this end, we ablated the germ cells using two independent methods and followed the development of the experimental fish. First, PGCs were ablated by knocking down the function of dead end, a gene important for the survival of this lineage. Second, a method to eliminate the PGCs using the toxin–antitoxin components of the parD bacterial genetic system was used. Specifically, we expressed a bacterial toxin Kid preferentially in the PGCs and at the same time protected somatic cells by uniformly expressing the specific antidote Kis. Our results demonstrate an unexpected role for the germ line in promoting female development because PGC-ablated fish invariably developed as males. PMID:15728735

  3. Current state of the opportunities for derivation of germ-like cells from pluripotent stem cells: are you a man, or a mouse?

    PubMed Central

    Petkova, Rumena; Arabadjiev, Borislav; Chakarov, Stoyan; Pankov, Roumen

    2014-01-01

    The concept of pluripotency as a prerogative of cells of early mammal embryos and cultured embryonic stem cells (ESC) has been invalidated with the advent of induced pluripotent stem cells. Later, it became clear that the ability to generate all cell types of the adult organism is also a questionable aspect of pluripotency, as there are cell types, such as germ cells, which are difficult to produce from pluripotent stem cells. Recently it has been proposed that there are at least two different states of pluripotency; namely, the naïve, or ground state, and the primed state, which may differ radically in terms of timeline of existence, signalling mechanisms, cell properties, capacity for differentiation into different cell types, etc. Germ-like male and female rodent cells have been successfully produced in vitro from ESC and induced pluripotent stem cells. The attempts to derive primate primordial germ cells (PGC) and germ cells in vitro from pluripotent stem cells, however, still have a low success rate, especially with the female germline. The paper reviews the properties of rodent and primate ESC with regard to their capacity for differentiation in vitro to germ-like cells, outlining the possible caveats to derivation of PGC and germ cells from primate and human pluripotent cells. PMID:26019504

  4. Early androgen exposure and human gender development.

    PubMed

    Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra

    2015-01-01

    During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This

  5. Alu repeated DNAs are differentially methylated in primate germ cells.

    PubMed Central

    Rubin, C M; VandeVoort, C A; Teplitz, R L; Schmid, C W

    1994-01-01

    A significant fraction of Alu repeats in human sperm DNA, previously found to be unmethylated, is nearly completely methylated in DNA from many somatic tissues. A similar fraction of unmethylated Alus is observed here in sperm DNA from rhesus monkey. However, Alus are almost completely methylated at the restriction sites tested in monkey follicular oocyte DNA. The Alu methylation patterns in mature male and female monkey germ cells are consistent with Alu methylation in human germ cell tumors. Alu sequences are hypomethylated in seminoma DNAs and more methylated in a human ovarian dysgerminoma. These results contrast with methylation patterns reported for germ cell single-copy, CpG island, satellite, and L1 sequences. The function of Alu repeats is not known, but differential methylation of Alu repeats in the male and female germ lines suggests that they may serve as markers for genomic imprinting or in maintaining differences in male and female meiosis. Images PMID:7800508

  6. A Mechanism of Male Germ Cell Apoptosis Induced by Bisphenol-A and Nonylphenol Involving ADAM17 and p38 MAPK Activation

    PubMed Central

    Moreno, Ricardo D.

    2014-01-01

    Germ cell apoptosis regulation is pivotal in order to maintain proper daily sperm production. Several reports have shown that endocrine disruptors such as Bisphenol-A (BPA) and Nonylphenol (NP) induce germ cell apoptosis along with a decrease in sperm production. Given their ubiquitous distribution in plastic products used by humans it is important to clarify their mechanism of action. TACE/ADAM17 is a widely distributed extracellular metalloprotease and participates in the physiological apoptosis of germ cells during spermatogenesis. The aims of this work were: 1) to determine whether BPA and NP induce ADAM17 activation; and 2) to study whether ADAM17 and/or ADAM10 are involved in germ cell apoptosis induced by BPA and NP in the pubertal rat testis. A single dose of BPA or NP (50 mg/kg) induces germ cell apoptosis in 21-day-old male rats, which was prevented by a pharmacological inhibitor of ADAM17, but not by an inhibitor of ADAM10. In vitro, we showed that BPA and NP, at similar concentrations to those found in human samples, induce the shedding of exogenous and endogenous (TNF-α) ADAM17 substrates in primary rat Sertoli cell cultures and TM4 cell line. In addition, pharmacological inhibitors of metalloproteases and genetic silencing of ADAM17 prevent the shedding induced in vitro by BPA and NP. Finally, we showed that in vivo BPA and NP induced early activation (phosphorylation) of p38 MAPK and translocation of ADAM17 to the cell surface. Interestingly, the inhibition of p38 MAPK prevents germ cell apoptosis and translocation of ADAM17 to the cell surface. These results show for the first time that xenoestrogens can induce activation of ADAM17 at concentrations similar to those found in human samples, suggesting a mechanism by which they could imbalance para/juxtacrine cell-to-cell-communication and induce germ cell apoptosis. PMID:25474107

  7. Treatment Option Overview (Extragonadal Germ Cell Tumors)

    MedlinePlus

    ... Professional Extragonadal Germ Cell Tumors Treatment Extragonadal Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Extragonadal Germ Cell Tumors Go to Health Professional Version Key Points ...

  8. SALL4 EXPRESSION IN GERM CELL AND NON GERM-CELL TUMORS – A SYSTEMATIC IMMUNOHISTOCHEMICAL STUDY OF 3215 CASES

    PubMed Central

    Miettinen, Markku; Wang, Zengfeng; Mc. Cue, Peter A.; Sarlomo-Rikala, Maarit; Rys, Janusz; Biernat, Wojciech; Lasota, Jerzy; Lee, Yi-Shan

    2014-01-01

    SALL4 transcription factor is associated with embryonic cell pluripotency and has been shown as a useful immunohistochemical marker for germ cell tumors. However, information of SALL4 distribution in normal human tissues and non germ-cell tumors is limited. In this study we examined normal human tissues and 3215 tumors for SALL4 expression using a monoclonal antibody 6E3 and automated immunohistochemistry. In a 10th week embryo, SALL4 was expressed in ovocytes, intestine, kidney, and some hepatocytes. In adult tissues, it was only detected in germ cells. SALL4 was consistently expressed in all germ cell tumors except some trophoblastic tumors and mature components of teratomas, where it was selectively expressed in intestinal-like and some squamous epithelia. In non germ-cell carcinomas, SALL4 was detected in 20% of cases or more of serous carcinoma of ovary, urothelial high-grade carcinoma, and gastric adenocarcinoma (especially the intestinal type). SALL4 was only rarely (≤5%) expressed in mammary, colorectal, prostatic, and squamous cell carcinomas. Many SALL4 positive carcinomas showed poorly differentiated patterns and some showed positivity in most tumor cells mimicking the expression in germ cell tumors. SALL4 was commonly expressed in rhabdoid tumors of kidney and extrarenal sites, and in Wilms tumor. Expression of SALL4 was rare in other mesenchymal and neuroendocrine tumors but was occasionally detected in melanoma, desmoplastic small round cell tumor, epithelioid sarcoma, and rhabdomyosarcoma. All hematopoietic tumors were negative. SALL4 is an excellent marker of non-teratomatous germ cell tumors, but it is also expressed in other tumors, sometimes extensively. Such expression may reflect stem-cell like differentiation and must be considered when using SALL4 as a marker for germ cell tumors. Observed lack of other pluripotency factors, OCT4 and NANOG, in SALL4-positive non-germ cell tumors can also be diagnostically helpful. PMID:24525512

  9. Primordial Germ Cells in Mice

    PubMed Central

    Saitou, Mitinori; Yamaji, Masashi

    2012-01-01

    Germ cell development creates totipotency through genetic as well as epigenetic regulation of the genome function. Primordial germ cells (PGCs) are the first germ cell population established during development and are immediate precursors for both the oocytes and spermatogonia. We here summarize recent findings regarding the mechanism of PGC development in mice. We focus on the transcriptional and signaling mechanism for PGC specification, potential pluripotency, and epigenetic reprogramming in PGCs and strategies for the reconstitution of germ cell development using pluripotent stem cells in culture. Continued studies on germ cell development may lead to the generation of totipotency in vitro, which should have a profound influence on biological science as well as on medicine. PMID:23125014

  10. Insights into female germ cell biology: from in vivo development to in vitro derivations.

    PubMed

    Jung, Dajung; Kee, Kehkooi

    2015-01-01

    Understanding the mechanisms of human germ cell biology is important for developing infertility treatments. However, little is known about the mechanisms that regulate human gametogenesis due to the difficulties in collecting samples, especially germ cells during fetal development. In contrast to the mitotic arrest of spermatogonia stem cells in the fetal testis, female germ cells proceed into meiosis and began folliculogenesis in fetal ovaries. Regulations of these developmental events, including the initiation of meiosis and the endowment of primordial follicles, remain an enigma. Studying the molecular mechanisms of female germ cell biology in the human ovary has been mostly limited to spatiotemporal characterizations of genes or proteins. Recent efforts in utilizing in vitro differentiation system of stem cells to derive germ cells have allowed researchers to begin studying molecular mechanisms during human germ cell development. Meanwhile, the possibility of isolating female germline stem cells in adult ovaries also excites researchers and generates many debates. This review will mainly focus on presenting and discussing recent in vivo and in vitro studies on female germ cell biology in human. The topics will highlight the progress made in understanding the three main stages of germ cell developments: namely, primordial germ cell formation, meiotic initiation, and folliculogenesis.

  11. Development, differentiation and manipulation of chicken germ cells.

    PubMed

    Nakamura, Yoshiaki; Kagami, Hiroshi; Tagami, Takahiro

    2013-01-01

    Germ cells are the only cell type capable of transmitting genetic information to the next generation. During development, they are set aside from all somatic cells of the embryo. In many species, germ cells form at the fringe of the embryo proper and then traverse through several developing somatic tissues on their migration to the emerging gonads. Primordial germ cells (PGCs) are the only cells in developing embryos with the potential to transmit genetic information to the next generation. Unlike other species, in avian embryos, PGCs use blood circulation for transport to the future gonadal region. This unique accessibility of avian PGCs during early development provides an opportunity to collect and transplant PGCs. The recent development of methods for production of germline chimeras by transfer of PGCs, and long-term cultivation methods of chicken PGCs without losing their germline transmission ability have provided important breakthroughs for the preservation of germplasm , for the production of transgenic birds and study the germ cell system. This review will describe the development, migration, differentiation and manipulation of germ cells, and discuss the prospects that germ cell technologies offer for agriculture, biotechnology and academic research. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

  12. The diversity of nanos expression in echinoderm embryos supports different mechanisms in germ cell specification.

    PubMed

    Fresques, Tara; Swartz, Steven Zachary; Juliano, Celina; Morino, Yoshiaki; Kikuchi, Mani; Akasaka, Koji; Wada, Hiroshi; Yajima, Mamiko; Wessel, Gary M

    2016-07-01

    Specification of the germ cell lineage is required for sexual reproduction in all animals. However, the timing and mechanisms of germ cell specification is remarkably diverse in animal development. Echinoderms, such as sea urchins and sea stars, are excellent model systems to study the molecular and cellular mechanisms that contribute to germ cell specification. In several echinoderm embryos tested, the germ cell factor Vasa accumulates broadly during early development and is restricted after gastrulation to cells that contribute to the germ cell lineage. In the sea urchin, however, the germ cell factor Vasa is restricted to a specific lineage by the 32-cell stage. We therefore hypothesized that the germ cell specification program in the sea urchin/Euechinoid lineage has evolved to an earlier developmental time point. To test this hypothesis we determined the expression pattern of a second germ cell factor, Nanos, in four out of five extant echinoderm clades. Here we find that Nanos mRNA does not accumulate until the blastula stage or later during the development of all other echinoderm embryos except those that belong to the Echinoid lineage. Instead, Nanos is expressed in a restricted domain at the 32-128 cell stage in Echinoid embryos. Our results support the model that the germ cell specification program underwent a heterochronic shift in the Echinoid lineage. A comparison of Echinoid and non-Echinoid germ cell specification mechanisms will contribute to our understanding of how these mechanisms have changed during animal evolution. © 2016 Wiley Periodicals, Inc.

  13. Methods to study maternal regulation of germ cell specification in zebrafish

    PubMed Central

    Kaufman, O.H.; Marlow, F.L.

    2016-01-01

    The process by which the germ line is specified in the zebrafish embryo is under the control of maternal gene products that were produced during oogenesis. Zebrafish are highly amenable to microscopic observation of the processes governing maternal germ cell specification because early embryos are transparent, and the germ line is specified rapidly (within 4–5 h post fertilization). Advantages of zebrafish over other models used to study vertebrate germ cell formation include their genetic tractability, the large numbers of progeny, and the easily manipulable genome, all of which make zebrafish an ideal system for studying the genetic regulators and cellular basis of germ cell formation and maintenance. Classical molecular biology techniques, including expression analysis through in situ hybridization and forward genetic screens, have laid the foundation for our understanding of germ cell development in zebrafish. In this chapter, we discuss some of these classic techniques, as well as recent cutting-edge methodologies that have improved our ability to visualize the process of germ cell specification and differentiation, and the tracking of specific molecules involved in these processes. Additionally, we discuss traditional and novel technologies for manipulating the zebrafish genome to identify new components through loss-of-function studies of putative germ cell regulators. Together with the numerous aforementioned advantages of zebrafish as a genetic model for studying development, we believe these new techniques will continue to advance zebrafish to the forefront for investigation of the molecular regulators of germ cell specification and germ line biology. PMID:27312489

  14. The Diversity of Nanos Expression in Echinoderm Embryos Supports Different Mechanisms in Germ Cell Specification

    PubMed Central

    Fresques, Tara; Swartz, S. Zachary; Juliano, Celina; Morino, Yoshiaki; Kikuchi, Mani; Akasaka, Koji; Wada, Hiroshi; Yajima, Mamiko; Wessel, Gary M.

    2016-01-01

    Specification of the germ cell lineage is required for sexual reproduction in all animals. However, the timing and mechanisms of germ cell specification is remarkably diverse in animal development. Echinoderms, such as sea urchins and sea stars, are excellent model systems to study the molecular and cellular mechanisms that contribute to germ cell specification. In several echinoderm embryos tested, the germ cell factor Vasa accumulates broadly during early development and is restricted after gastrulation to cells that contribute to the germ cell lineage. In the sea urchin, however, the germ cell factor Vasa is restricted to a specific lineage by the 32-cell stage. We therefore hypothesized that the germ cell specification program in the sea urchin/Euechinoid lineage has evolved to an earlier developmental time point. To test this hypothesis we determined the expression pattern of a second germ cell factor, Nanos, in four out of five extant echinoderm clades. Here we find that Nanos mRNA does not accumulate until the blastula stage or later during the development of all other echinoderm embryos except those that belong to the Echinoid lineage. Instead, Nanos is expressed in a restricted domain at the 32–128 cell stage in Echinoid embryos. Our results support the model that the germ cell specification program underwent a heterochronic shift in the Echinoid lineage. A comparison of Echinoid and non-Echinoid germ cell specification mechanisms will contribute to our understanding of how these mechanisms have changed during animal evolution. PMID:27402572

  15. DAZL is essential for stress granule formation implicated in germ cell survival upon heat stress.

    PubMed

    Kim, Byunghyuk; Cooke, Howard J; Rhee, Kunsoo

    2012-02-01

    Mammalian male germ cells should be maintained below body temperature for proper development. Here, we investigated how male germ cells respond to heat stress. A short exposure of mouse testes to core body temperature induced phosphorylation of eIF2α and the formation of stress granules (SGs) in male germ cells. We observed that DAZL, a germ cell-specific translational regulator, was translocated to SGs upon heat stress. Furthermore, SG assembly activity was significantly diminished in the early male germ cells of Dazl-knockout mice. The DAZL-containing SGs played a protective role against heat stress-induced apoptosis by the sequestration of specific signaling molecules, such as RACK1, and the subsequent blockage of the apoptotic MAPK pathway. Based on these results, we propose that DAZL is an essential component of the SGs, which prevent male germ cells from undergoing apoptosis upon heat stress.

  16. Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation.

    PubMed

    Suchorska, Wiktoria Maria; Augustyniak, Ewelina; Łukjanow, Magdalena

    2017-04-01

    Despite the well-demonstrated efficacy of stem cell (SC) therapy, this approach has a number of key drawbacks. One important concern is the response of pluripotent SCs to treatment with ionizing radiation (IR), given that SCs used in regenerative medicine will eventually be exposed to IR for diagnostic or treatment‑associated purposes. Therefore, the aim of the present study was to examine and compare early IR‑induced responses of pluripotent SCs to assess their radioresistance and radiosensitivity. In the present study, 3 cell lines; human embryonic SCs (hESCs), human induced pluripotent SCs (hiPSCs) and primary human dermal fibroblasts (PHDFs); were exposed to IR at doses ranging from 0 to 15 gray (Gy). Double strand breaks (DSBs), and the gene expression of the following DNA repair genes were analyzed: P53; RAD51; BRCA2; PRKDC; and XRCC4. hiPSCs demonstrated greater radioresistance, as fewer DSBs were identified, compared with hESCs. Both pluripotent SC lines exhibited distinct gene expression profiles in the most common DNA repair genes that are involved in homologous recombination, non‑homologous end‑joining and enhanced DNA damage response following IR exposure. Although hESCs and hiPSCs are equivalent in terms of capacity for pluripotency and differentiation into 3 germ layers, the results of the present study indicate that these 2 types of SCs differ in gene expression following exposure to IR. Consequently, further research is required to determine whether hiPSCs and hESCs are equally safe for application in clinical practice. The present study contributes to a greater understanding of DNA damage response (DDR) mechanisms activated in pluripotent SCs and may aid in the future development of safe SC‑based clinical protocols.

  17. Comparative study of MSX-2, DLX-5, and DLX-7 gene expression during early human tooth development.

    PubMed

    Davideau, J L; Demri, P; Hotton, D; Gu, T T; MacDougall, M; Sharpe, P; Forest, N; Berdal, A

    1999-12-01

    Msx and Dlx family transcription factors are key elements of craniofacial development and act in specific combinations with growth factors to control the position and shape of various skeletal structures in mice. In humans, the mutations of MSX and DLX genes are associated with specific syndromes, such as tooth agenesis, craniosynostosis, and tricho-dento-osseous syndrome. To establish some relationships between those reported human syndromes, previous experimental data in mice, and the expression patterns of MSX and DLX homeogenes in the human dentition, we investigated MSX-2, DLX-5, and DLX-7 expression patterns and compared them in orofacial tissues of 7.5- to 9-wk-old human embryos by using in situ hybridization. Our data showed that MSX-2 was strongly expressed in the progenitor cells of human orofacial skeletal structures, including mandible and maxilla bones, Meckel's cartilage, and tooth germs, as shown for DLX-5. DLX-7 expression was restricted to the vestibular lamina and, later on, to the vestibular part of dental epithelium. The comparison of MSX-2, DLX-5, and DLX-7 expression patterns during the early stages of development of different human tooth types showed the existence of spatially ordered sequences of homeogene expression along the vestibular/lingual axis of dental epithelium. The expression of MSX-2 in enamel knot, as well as the coincident expression of MSX-2, DLX-5, and DLX-7 in a restricted vestibular area of dental epithelium, suggests the existence of various organizing centers involved in the control of human tooth morphogenesis.

  18. Teleoperation support for early human planetary missions.

    PubMed

    Genta, Giancarlo; Perino, Maria Antonietta

    2005-12-01

    A renewed interest in human exploration is flourishing among all the major spacefaring nations. In fact, in the complex scene of planned future space activities, the development of a Moon base and the human exploration of Mars might have the potential to renew the enthusiasm in expanding the human presence beyond the boundaries of Earth. Various initiatives have been undertaken to define scenarios and identify the required infrastructures and related technology innovations. The typical proposed approach follows a multistep strategy, starting with a series of precursor robotic missions to acquire further knowledge of the planet and to select the best potential landing sites, and evolving toward more demanding missions for the development of a surface infrastructure necessary to sustain human presence. The technologies involved in such a demanding enterprise range from typical space technologies, like transportation and propulsion, automation and robotics, rendezvous and docking, entry/reentry, aero-braking, navigation, and deep space communications, to human-specific issues like physiology, psychology, behavioral aspects, and nutritional science for long-duration exposure, that go beyond the traditional boundaries of space activities. Among the required elements to support planetary exploration, both for the precursor robotic missions and to sustain human exploration, rovers and trucks play a key role. A robust level of autonomy will need to be secured to perform preplanned operations, particularly for the surface infrastructure development, and a teleoperated support, either from Earth or from a local base, will enhance the in situ field exploration capability.

  19. Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

    ClinicalTrials.gov

    2015-06-11

    Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Malignant Extragonadal Germ Cell Tumor; Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

  20. Role of Axumin PET Scan in Germ Cell Tumor

    ClinicalTrials.gov

    2018-05-01

    Testis Cancer; Germ Cell Tumor; Testicular Cancer; Germ Cell Tumor of Testis; Germ Cell Tumor, Testicular, Childhood; Testicular Neoplasms; Testicular Germ Cell Tumor; Testicular Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Diseases; Germ Cell Cancer Metastatic; Germ Cell Neoplasm of Retroperitoneum; Germ Cell Cancer, Nos

  1. Dnd Is a Critical Specifier of Primordial Germ Cells in the Medaka Fish.

    PubMed

    Hong, Ni; Li, Mingyou; Yuan, Yongming; Wang, Tiansu; Yi, Meisheng; Xu, Hongyan; Zeng, Huaqiang; Song, Jianxing; Hong, Yunhan

    2016-03-08

    Primordial germ cell (PGC) specification occurs early in development. PGC specifiers have been identified in Drosophila, mouse, and human but remained elusive in most animals. Here we identify the RNA-binding protein Dnd as a critical PGC specifier in the medaka fish (Oryzias latipes). Dnd depletion specifically abolished PGCs, and its overexpression boosted PGCs. We established a single-cell culture procedure enabling lineage tracing in vitro. We show that individual blastomeres from cleavage embryos at the 32- and 64-cell stages are capable of PGC production in culture. Importantly, Dnd overexpression increases PGCs via increasing PGC precursors. Strikingly, dnd RNA forms prominent particles that segregate asymmetrically. Dnd concentrates in germ plasm and stabilizes germ plasm RNA. Therefore, Dnd is a critical specifier of fish PGCs and utilizes particle partition as a previously unidentified mechanism for asymmetric segregation. These findings offer insights into PGC specification and manipulation in medaka as a lower vertebrate model. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Young Children's Enactments of Human Rights in Early Childhood Education

    ERIC Educational Resources Information Center

    Quennerstedt, Ann

    2016-01-01

    This paper explores ways in which human rights become part of and affect young children's everyday practices in early childhood education and, more particularly, how very young children enact human rights in the preschool setting. The study is conducted in a Swedish preschool through observations of the everyday practices of a group of children…

  3. Tuberin and PRAS40 are anti-apoptotic gatekeepers during early human amniotic fluid stem-cell differentiation.

    PubMed

    Fuchs, Christiane; Rosner, Margit; Dolznig, Helmut; Mikula, Mario; Kramer, Nina; Hengstschläger, Markus

    2012-03-01

    Embryoid bodies (EBs) are three-dimensional multicellular aggregates allowing the in vitro investigation of stem-cell differentiation processes mimicking early embryogenesis. Human amniotic fluid stem (AFS) cells harbor high proliferation potential, do not raise the ethical issues of embryonic stem cells, have a lower risk for tumor development, do not need exogenic induction of pluripotency and are chromosomal stable. Starting from a single human AFS cell, EBs can be formed accompanied by the differentiation into cells of all three embryonic germ layers. Here, we report that siRNA-mediated knockdown of the endogenous tuberous sclerosis complex-2 (TSC2) gene product tuberin or of proline-rich Akt substrate of 40 kDa (PRAS40), the two major negative regulators of mammalian target of rapamycin (mTOR), leads to massive apoptotic cell death during EB development of human AFS cells without affecting the endodermal, mesodermal and ectodermal cell differentiation spectrum. Co-knockdown of endogenous mTOR demonstrated these effects to be mTOR-dependent. Our findings prove this enzyme cascade to be an essential anti-apoptotic gatekeeper of stem-cell differentiation during EB formation. These data allow new insights into the regulation of early stem-cell maintenance and differentiation and identify a new role of the tumor suppressor tuberin and the oncogenic protein PRAS40 with the relevance for a more detailed understanding of the pathogenesis of diseases associated with altered activities of these gene products.

  4. Reprogramming primordial germ cells (PGC) to embryonic germ (EG) cells.

    PubMed

    Durcova-Hills, Gabriela; Surani, Azim

    2008-04-01

    In this unit we describe the derivation of pluripotent embryonic germ (EG) cells from mouse primordial germ cells (PGCs) isolated from both 8.5- and 11.5-days post-coitum (dpc) embryos. Once EG cells are derived we explain how to propagate and characterize the cell lines. We introduce readers to PGCs and explain differences between PGCs and their in vitro derivatives EG cells. Finally, we also compare mouse EG cells with ES cells. This unit will be of great interest to anyone interested in PGCs or studying the behavior of cultured PGCs or the derivation of new EG cell lines.

  5. Mechanisms and chemical induction of aneuploidy in rodent germ cells

    SciT

    Mailhes, J B; Marchetti, F

    The objective of this review is to suggest that the advances being made in our understanding of the molecular events surrounding chromosome segregation in non-mammalian and somatic cell models be considered when designing experiments for studying aneuploidy in mammalian germ cells. Accurate chromosome segregation requires the temporal control and unique interactions among a vast array of proteins and cellular organelles. Abnormal function and temporal disarray among these, and others to be inidentified, biochemical reactions and cellular organelles have the potential for predisposing cells to aneuploidy. Although numerous studies have demonstrated that certain chemicals (mainly those that alter microtubule function) canmore » induce aneuploidy in mammalian germ cells, it seems relevant to point out that such data can be influenced by gender, meiotic stage, and time of cell-fixation post-treatment. Additionally, a consensus has not been reached regarding which of several germ cell aneuploidy assays most accurately reflects the human condition. More recent studies have shown that certain kinase, phosphatase, proteasome, and topoisomerase inhibitors can also induce aneuploidy in rodent germ cells. We suggest that molecular approaches be prudently incorporated into mammalian germ cell aneuploidy research in order to eventually understand the causes and mechanisms of human aneuploidy. Such an enormous undertaking would benefit from collaboration among scientists representing several disciplines.« less

  6. Palmitic Acid in Early Human Development.

    PubMed

    Innis, Sheila M

    2016-09-09

    Palmitic acid (16:0) is a saturated fatty acid present in the diet and synthesized endogenously. Although often considered to have adverse effects on chronic disease in adults, 16:0 is an essential component of membrane, secretory, and transport lipids, with crucial roles in protein palmitoylation and signal molecules. At birth, the term infant is 13-15% body fat, with 45-50% 16:0, much of which is derived from endogenous synthesis in the fetus. After birth, the infant accumulates adipose tissue at high rates, reaching 25% body weight as fat by 4-5 months age. Over this time, human milk provides 10% dietary energy as 16:0, but in unusual triglycerides with 16:0 on the glycerol center carbon. This paper reviews the synthesis and oxidation of 16:0 and possible reasons why the infant is endowed with large amounts of fat and 16:0. The marked deviations in tissues with displacement of 16:0 that can occur in infants fed vegetable oil formulas is introduced. Assuming fetal fatty acid synthesis and the unusual delivery of 16:0 in human milk evolved to afford survival advantage to the neonate, it is timely to question if 16:0 is an essential component of tissue lipids whereby both deficiency and excess are detrimental.

  7. Germ cell neoplasia in situ (GCNIS): evolution of the current nomenclature for testicular pre-invasive germ cell malignancy.

    PubMed

    Berney, Daniel M; Looijenga, Leendert H J; Idrees, Muhammad; Oosterhuis, J Wolter; Rajpert-De Meyts, Ewa; Ulbright, Thomas M; Skakkebaek, Niels E

    2016-07-01

    The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity and disagreement on its name. Initially termed 'carcinoma in situ' (CIS), it has also been known as 'intratubular germ cell neoplasia, unclassified' (IGCNU) and 'testicular intraepithelial neoplasia' (TIN). In this paper, we review the history of discovery and controversy concerning these names and introduce the reasoning for uniting behind a new name, endorsed unanimously at the World Health Organization (WHO) consensus classification 2016: germ cell neoplasia in situ (GCNIS). © 2016 John Wiley & Sons Ltd.

  8. General Information about Extragonadal Germ Cell Tumors

    MedlinePlus

    ... Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Extragonadal Germ Cell Tumors Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  9. Treatment Option Overview (Ovarian Germ Cell Tumors)

    MedlinePlus

    ... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview ... types of treatment for patients with ovarian germ cell tumors. Different types of treatment are available for ...

  10. Functional G-Protein-Coupled Receptor (GPCR) Synthesis: The Pharmacological Analysis of Human Histamine H1 Receptor (HRH1) Synthesized by a Wheat Germ Cell-Free Protein Synthesis System Combined with Asolectin Glycerosomes

    PubMed Central

    Suzuki, Yasuyuki; Ogasawara, Tomio; Tanaka, Yuki; Takeda, Hiroyuki; Sawasaki, Tatsuya; Mogi, Masaki; Liu, Shuang; Maeyama, Kazutaka

    2018-01-01

    G-protein-coupled receptors (GPCRs) are membrane proteins distributed on the cell surface, and they may be potential drug targets. However, synthesizing GPCRs in vitro can be challenging. Recently, some cell-free protein synthesis systems have been shown to produce a large amount of membrane protein combined with chemical chaperones that include liposomes and glycerol. Liposomes containing high concentrations of glycerol are known as glycerosomes, which are used in new drug delivery systems. Glycerosomes have greater morphological stability than liposomes. Proteoglycerosomes are defined as glycerosomes that contain membrane proteins. Human histamine H1 receptor (HRH1) is one of the most studied GPCRs. In this study, we synthesized wild-type HRH1 (WT-HRH1) proteoglycerosomes and D107A-HRH1, (in which Asp107 was replaced by Ala) in a wheat germ cell-free protein synthesis system combined with asolectin glycerosomes. The mutant HRH1 has been reported to have low affinity for the H1 antagonist. In this study, the amount of synthesized WT-HRH1 in one synthesis reaction was 434 ± 66.6 μg (7.75 ± 1.19 × 103pmol). The specific binding of [3H]pyrilamine to the WT-HRH1 proteoglycerosomes became saturated as the concentration of the radioligand increased. The dissociation constant (Kd) and maximum density (Bmax) of the synthesized WT-HRH1 were 9.76 ± 1.25 nM and 21.4 ± 0.936 pmol/mg protein, respectively. However, specific binding to D107A-HRH1 was reduced compared with WT-HRH1 and the binding did not become saturated. The findings of this study highlight that HRH1 synthesized using a wheat germ cell-free protein synthesis system combined with glycerosomes has the ability to bind to H1 antagonists. PMID:29467651

  11. Extracranial Germ Cell Tumors—Patient Version

    Cancer.gov

    Extracranial germ cell tumors are tumors that develop from germ cells (fetal cells that give rise to sperm and eggs) and can form in many parts of the body. They are most common in teenagers and can often be cured. Start here to find information on extracranial germ cell tumors treatment.

  12. Extraction and characterization of corn germ proteins

    Our study was conducted to develop methods to extract corn germ protein economically and characterize and identify potential applications of the recovered protein. Protein was extracted from both wet germ and finished (dried) germ using 0.1M NaCl as solvent. The method involved homogenization, sti...

  13. Identification of Potential Germ-Cell Mutagens

    EPA Science Inventory

    The existence of agents that can induce germ-cell mutations in experimental systems has been recognized since 1927 with the discovery of the ability of X-rays to induce such mutations in Drosophila. Various rodent-based germ-cell mutation assays have been developed, and ~50 germ...

  14. Gove's Curriculum and the GERM

    ERIC Educational Resources Information Center

    Wrigley, Terry

    2015-01-01

    This article examines the complex relationship between England's new National Curriculum and the neoliberal reform of education known as GERM. It explores contradictions between economic functionality and Gove's nostalgic traditionalism. It critiques the new curriculum as narrow, age-inappropriate, obsessed with abstract rules, and poorly focused…

  15. EMMPRIN/CD147-encriched membrane vesicles released from malignant human testicular germ cells increase MMP production through tumor-stroma interaction.

    PubMed

    Milia-Argeiti, Eleni; Mourah, Samia; Vallée, Benoit; Huet, Eric; Karamanos, Nikos K; Theocharis, Achilleas D; Menashi, Suzanne

    2014-08-01

    Elevated levels of EMMPRIN/CD147 in cancer tissues have been correlated with tumor progression but the regulation of its expression is not yet understood. Here, the regulation of EMMPRIN expression was investigated in testicular germ cell tumor (TGCTs) cell lines. EMMPRIN expression in seminoma JKT-1 and embryonal carcinoma NT2/D1 cell lines was determined by Western blot, immunofluorescence and qRT-PCR. Membrane vesicles (MVs) secreted from these cells, treated or not with EMMPRIN siRNA, were isolated by differential centrifugations of their conditioned medium. MMP-2 was analyzed by zymography and qRT-PCR. The more aggressive embryonic carcinoma NT2/D1 cells expressed more EMMPRIN mRNA than the seminoma JKT-1 cells, but surprisingly contained less EMMPRIN protein, as determined by immunoblotting and immunostaining. The protein/mRNA discrepancy was not due to accelerated protein degradation in NT2/D1 cells, but by the secretion of EMMPRIN within MVs, as the vesicles released from NT2/D1 contained considerably more EMMPRIN than those released from JKT-1. EMMPRIN-containing MVs obtained from NT2/D1, but not from EMMPRIN-siRNA treated NT2/D1, increased MMP-2 production in fibroblasts to a greater extent than those from JKT-1 cells. The data presented show that the more aggressive embryonic carcinoma cells synthesize more EMMPRIN than seminoma cells, but which they preferentially target to secreted MVs, unlike seminoma cells which retain EMMPRIN within the cell membrane. This cellular event points to a mechanism by which EMMPRIN expressed by malignant testicular cells can exert its MMP inducing effect on distant cells within the tumor microenvironment to promote tumor invasion. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Etoposide damages female germ cells in the developing ovary.

    PubMed

    Stefansdottir, Agnes; Johnston, Zoe C; Powles-Glover, Nicola; Anderson, Richard A; Adams, Ian R; Spears, Norah

    2016-08-11

    As with many anti-cancer drugs, the topoisomerase II inhibitor etoposide is considered safe for administration to women in the second and third trimesters of pregnancy, but assessment of effects on the developing fetus have been limited. The purpose of this research was to examine the effect of etoposide on germ cells in the developing ovary. Mouse ovary tissue culture was used as the experimental model, thus allowing us to examine effects of etoposide on all stages of germ cell development in the same way, in vitro. Fetal ovaries from embryonic day 13.5 CD1 mice or neonatal ovaries from postnatal day 0 CD1 mice were cultured with 50-150 ng ml(-1) or 50-200 ng ml(-1) etoposide respectively, concentrations that are low relative to that in patient serum. When fetal ovaries were treated prior to follicle formation, etoposide resulted in dose-dependent damage, with 150 ng ml(-1) inducing a near-complete absence of healthy follicles. In contrast, treatment of neonatal ovaries, after follicle formation, had no effect on follicle numbers and only a minor effect on follicle health, even at 200 ng ml(-1). The sensitivity of female germ cells to etoposide coincided with topoisomerase IIα expression: in the developing ovary of both mouse and human, topoisomerase IIα was expressed in germ cells only prior to follicle formation. Exposure of pre-follicular ovaries, in which topoisomerase IIα expression was germ cell-specific, resulted in a near-complete elimination of germ cells prior to follicle formation, with the remaining germ cells going on to form unhealthy follicles by the end of culture. In contrast, exposure to follicle-enclosed oocytes, which no longer expressed topoisomerase IIα in the germ cells, had no effect on total follicle numbers or health, the only effect seen specific to transitional follicles. Results indicate the potential for adverse effects on fetal ovarian development if etoposide is administered to pregnant women when germ cells are not yet

  17. Current opinion in germ cell cancer 2000.

    PubMed

    Oliver, R T

    2000-05-01

    Despite its relative rarity compared with the common adult cancers, scientific and clinical interest in germ cell cancer is increasing. From the point of view of epidemiology, the controversy about the relative importance of intrauterine versus postpubertal risk factors has continued. Evidence to support the importance of intrauterine factors comes from reports from Norway, Canada, and the US, confirming the Danish observation that the rising incidence of germ cell cancer is linked to a birth cohort effect; evidence in support of the importance of postpubertal risk comes from three case/control studies demonstrating increased risk linked to postpubertal exposures such as pesticides, plastics, electromagnetic radiation, trauma, and infections. There has been increasing interest in human endogenous retrovirus K10 as a possible factor explaining genetic susceptibility and providing a linkage between the two groups of risk factors. In cytogenetics, progress was reported in identifying the deletion point of the suspected tumor suppressor gene responsible for the i12p marker chromosome abnormality and development of FISH probes for diagnostic purposes. In molecular biology, the importance of DNA repair deficiency in normal germ cells as a factor in the exquisite chemosensitivity of germ cell cancer has been high-lighted by a report demonstrating a low level of the xeroderma pigmentosa group A (XPA) protein and induction of resistance in vitro by adding XPA. In the clinic, progress in positron emission tomography scanning and laparoscopic lymph node staging are leading to changes in outlook on management of stage 1 cases and patients with small residual masses postchemotherapy. Salvage chemotherapy regimens integrating dose dense and vertical dose intensification strategies reported 60% progression-free survival. New drugs such as gemcitabine demonstrated continued therapeutic potential for chemotherapy in these tumors. A report demonstrating the inadequacies of hormone

  18. The Geochemical Earth Reference Model (GERM)

    SciT

    Staudigel, H.; Albarede, F.; Shaw, H.

    The Geochemical Earth Reference Model (GERM) initiative is a grass- roots effort with the goal of establishing a community consensus on a chemical characterization of the Earth, its major reservoirs, and the fluxes between them. Long term goal of GERM is a chemical reservoir characterization analogous to the geophysical effort of the Preliminary Reference Earth Model (PREM). Chemical fluxes between reservoirs are included into GERM to illuminate the long-term chemical evolution of the Earth and to characterize the Earth as a dynamic chemical system. In turn, these fluxes control geological processes and influence hydrosphere-atmosphere-climate dynamics. While these long-term goals aremore » clearly the focus of GERM, the process of establishing GERM itself is just as important as its ultimate goal. The GERM initiative is developed in an open community discussion on the World Wide Web (GERM home page is at http://www-ep.es.llnl. gov/germ/germ-home.html) that is mediated by a series of editors with responsibilities for distinct reservoirs and fluxes. Beginning with the original workshop in Lyons (March 1996) GERM is continued to be developed on the Internet, punctuated by workshops and special sessions at professional meetings. It is planned to complete the first model by mid-1997, followed by a call for papers for a February 1998 GERM conference in La Jolla, California.« less

  19. Primordial Germ Cell Specification and Migration

    PubMed Central

    Marlow, Florence

    2015-01-01

    Primordial germ cells are the progenitor cells that give rise to the gametes. In some animals, the germline is induced by zygotic transcription factors, whereas in others, primordial germ cell specification occurs via inheritance of maternally provided gene products known as germ plasm. Once specified, the primordial germ cells of some animals must acquire motility and migrate to the gonad in order to survive. In all animals examined, perinuclear structures called germ granules form within germ cells. This review focuses on some of the recent studies, conducted by several groups using diverse systems, from invertebrates to vertebrates, which have provided mechanistic insight into the molecular regulation of germ cell specification and migration. PMID:26918157

  20. Ancient gene flow from early modern humans into Eastern Neanderthals.

    PubMed

    Kuhlwilm, Martin; Gronau, Ilan; Hubisz, Melissa J; de Filippo, Cesare; Prado-Martinez, Javier; Kircher, Martin; Fu, Qiaomei; Burbano, Hernán A; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Rudan, Pavao; Brajkovic, Dejana; Kucan, Željko; Gušic, Ivan; Marques-Bonet, Tomas; Andrés, Aida M; Viola, Bence; Pääbo, Svante; Meyer, Matthias; Siepel, Adam; Castellano, Sergi

    2016-02-25

    It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.

  1. Population Dynamics of Early Human Migration in Britain

    PubMed Central

    Vahia, Mayank N.; Ladiwala, Uma; Mahathe, Pavan; Mathur, Deepak

    2016-01-01

    Background Early human migration is largely determined by geography and human needs. These are both deterministic parameters when small populations move into unoccupied areas where conflicts and large group dynamics are not important. The early period of human migration into the British Isles provides such a laboratory which, because of its relative geographical isolation, may allow some insights into the complex dynamics of early human migration and interaction. Method and Results We developed a simulation code based on human affinity to habitable land, as defined by availability of water sources, altitude, and flatness of land, in choosing the path of migration. Movement of people on the British island over the prehistoric period from their initial entry points was simulated on the basis of data from the megalithic period. Topographical and hydro-shed data from satellite databases was used to define habitability, based on distance from water bodies, flatness of the terrain, and altitude above sea level. We simulated population movement based on assumptions of affinity for more habitable places, with the rate of movement tempered by existing populations. We compared results of our computer simulations with genetic data and show that our simulation can predict fairly accurately the points of contacts between different migratory paths. Such comparison also provides more detailed information about the path of peoples’ movement over ~2000 years before the present era. Conclusions We demonstrate an accurate method to simulate prehistoric movements of people based upon current topographical satellite data. Our findings are validated by recently-available genetic data. Our method may prove useful in determining early human population dynamics even when no genetic information is available. PMID:27148959

  2. Early development of synchrony in cortical activations in the human.

    PubMed

    Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

    2016-05-13

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Lost human capital from early-onset chronic depression.

    PubMed

    Berndt, E R; Koran, L M; Finkelstein, S N; Gelenberg, A J; Kornstein, S G; Miller, I M; Thase, M E; Trapp, G A; Keller, M B

    2000-06-01

    Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

  4. Origins and early development of human body knowledge.

    PubMed

    Slaughter, Virginia; Heron, Michelle

    2004-01-01

    As a knowable object, the human body is highly complex. Evidence from several converging lines of research, including psychological studies, neuroimaging and clinical neuropsychology, indicates that human body knowledge is widely distributed in the adult brain, and is instantiated in at least three partially independent levels of representation. Sensorimotor body knowledge is responsible for on-line control and movement of one's own body and may also contribute to the perception of others' moving bodies; visuo-spatial body knowledge specifies detailed structural descriptions of the spatial attributes of the human body; and lexical-semantic body knowledge contains language-based knowledge about the human body. In the first chapter of this Monograph, we outline the evidence for these three hypothesized levels of human body knowledge, then review relevant literature on infants' and young children's human body knowledge in terms of the three-level framework. In Chapters II and III, we report two complimentary series of studies that specifically investigate the emergence of visuo-spatial body knowledge in infancy. Our technique is to compare infants'responses to typical and scrambled human bodies, in order to evaluate when and how infants acquire knowledge about the canonical spatial layout of the human body. Data from a series of visual habituation studies indicate that infants first discriminate scrambled from typical human body picture sat 15 to 18 months of age. Data from object examination studies similarly indicate that infants are sensitive to violations of three-dimensional human body stimuli starting at 15-18 months of age. The overall pattern of data supports several conclusions about the early development of human body knowledge: (a) detailed visuo-spatial knowledge about the human body is first evident in the second year of life, (b) visuo-spatial knowledge of human faces and human bodies are at least partially independent in infancy and (c) infants' initial

  5. Recent developments in testicular germ cell tumor research.

    PubMed

    van de Geijn, Gert-Jan M; Hersmus, Remko; Looijenga, Leendert H J

    2009-03-01

    Testicular germ cell tumors of adolescents and adults (TGCTs; the so-called type II variant) are the most frequent malignancies found in Caucasian males between 20 and 40 years of age. The incidence has increased over the last decades. TGCTs are divided into seminomas and nonseminomas, the latter consisting of the subgroups embryonal carcinoma, yolk-sac tumor, teratoma, and choriocarcinoma. The pathogenesis starts in utero, involving primordial germ cells/gonocytes that are blocked in their differentiation, and develops via the precursor lesion carcinoma in situ toward invasiveness. TGCTs are totipotent and can be considered as stem cell tumors. The developmental capacity of their cell of origin, the primordial germ cells/gonocyte, is demonstrated by the different tumor histologies of the invasive TGCTs. Seminoma represents the germ cell lineage, and embryonal carcinoma is the undifferentiated component, being the stem cell population of the nonseminomas. Somatic differentiation is seen in the teratomas (all lineages), whereas yolk-sac tumors and choriocarcinoma represent extra-embryonal differentiation. Seminomas are highly sensitive to irradiation and (DNA damaging) chemotherapy, whereas most nonseminomatous elements are less susceptible to radiation, although still sensitive to chemotherapy, with the exception of teratoma. To allow early diagnosis and follow up, appropriate markers are mandatory to discriminate between the different subgroups. In this review, a summary will be given related to several recent developments in TGCT research, especially selected because of their putative clinical impact.

  6. An ancient role for nuclear beta-catenin in the evolution of axial polarity and germ layer segregation

    NASA Technical Reports Server (NTRS)

    Wikramanayake, Athula H.; Hong, Melanie; Lee, Patricia N.; Pang, Kevin; Byrum, Christine A.; Bince, Joanna M.; Xu, Ronghui; Martindale, Mark Q.

    2003-01-01

    The human oncogene beta-catenin is a bifunctional protein with critical roles in both cell adhesion and transcriptional regulation in the Wnt pathway. Wnt/beta-catenin signalling has been implicated in developmental processes as diverse as elaboration of embryonic polarity, formation of germ layers, neural patterning, spindle orientation and gap junction communication, but the ancestral function of beta-catenin remains unclear. In many animal embryos, activation of beta-catenin signalling occurs in blastomeres that mark the site of gastrulation and endomesoderm formation, raising the possibility that asymmetric activation of beta-catenin signalling specified embryonic polarity and segregated germ layers in the common ancestor of bilaterally symmetrical animals. To test whether nuclear translocation of beta-catenin is involved in axial identity and/or germ layer formation in 'pre-bilaterians', we examined the in vivo distribution, stability and function of beta-catenin protein in embryos of the sea anemone Nematostella vectensis (Cnidaria, Anthozoa). Here we show that N. vectensis beta-catenin is differentially stabilized along the oral-aboral axis, translocated into nuclei in cells at the site of gastrulation and used to specify entoderm, indicating an evolutionarily ancient role for this protein in early pattern formation.

  7. Early stress and human behavioral development: emerging evolutionary perspectives.

    PubMed

    Del Giudice, M

    2014-08-01

    Stress experienced early in life exerts a powerful, lasting influence on development. Converging empirical findings show that stressful experiences become deeply embedded in the child's neurobiology, with an astonishing range of long-term effects on cognition, emotion, and behavior. In contrast with the prevailing view that such effects are the maladaptive outcomes of 'toxic' stress, adaptive models regard them as manifestations of evolved developmental plasticity. In this paper, I offer a brief introduction to adaptive models of early stress and human behavioral development, with emphasis on recent theoretical contributions and emerging concepts in the field. I begin by contrasting dysregulation models of early stress with their adaptive counterparts; I then introduce life history theory as a unifying framework, and review recent work on predictive adaptive responses (PARs) in human life history development. In particular, I discuss the distinction between forecasting the future state of the environment (external prediction) and forecasting the future state of the organism (internal prediction). Next, I present the adaptive calibration model, an integrative model of individual differences in stress responsivity based on life history concepts. I conclude by examining how maternal-fetal conflict may shape the physiology of prenatal stress and its adaptive and maladaptive effects on postnatal development. In total, I aim to show how theoretical work from evolutionary biology is reshaping the way we think about the role of stress in human development, and provide researchers with an up-to-date conceptual map of this fascinating and rapidly evolving field.

  8. European early modern humans and the fate of the Neandertals

    PubMed Central

    Trinkaus, Erik

    2007-01-01

    A consideration of the morphological aspects of the earliest modern humans in Europe (more than ≈33,000 B.P.) and the subsequent Gravettian human remains indicates that they possess an anatomical pattern congruent with the autapomorphic (derived) morphology of the earliest (Middle Paleolithic) African modern humans. However, they exhibit a variable suite of features that are either distinctive Neandertal traits and/or plesiomorphic (ancestral) aspects that had been lost among the African Middle Paleolithic modern humans. These features include aspects of neurocranial shape, basicranial external morphology, mandibular ramal and symphyseal form, dental morphology and size, and anteroposterior dental proportions, as well as aspects of the clavicles, scapulae, metacarpals, and appendicular proportions. The ubiquitous and variable presence of these morphological features in the European earlier modern human samples can only be parsimoniously explained as a product of modest levels of assimilation of Neandertals into early modern human populations as the latter dispersed across Europe. This interpretation is in agreement with current analyses of recent and past human molecular data. PMID:17452632

  9. Early development of physical aggression and early risk factors for chronic physical aggression in humans.

    PubMed

    Tremblay, Richard E

    2014-01-01

    This chapter describes the state of knowledge on the development of physical aggression from early childhood to adulthood, the long term outcomes of chronic physical aggression during childhood and the risk factors for chronic physical aggression. Unraveling the development of physical aggression is important to understand when and why humans start using physical aggression, to understand why some humans suffer from chronic physical aggression and to understand how to prevent the development of this disorder which causes much distress to the aggressors and their victims. The study of the developmental origins of aggression also sheds light on the reasons why situational prevention of aggression is important at all ages and in all cultures.

  10. From Young Children's Ideas about Germs to Ideas Shaping a Learning Environment

    NASA Astrophysics Data System (ADS)

    Ergazaki, Marida; Saltapida, Konstantina; Zogza, Vassiliki

    2010-11-01

    This paper is concerned with highlighting young children’s ideas about the nature, location and appearance of germs, as well as their reasoning strands about germs’ ontological category and biological functions. Moreover, it is concerned with exploring how all these could be taken into account for shaping a potentially fruitful learning environment. Conducting individual, semi-structured interviews with 35 preschoolers (age 4.5-5.5) of public kindergartens in the broader area of Patras, we attempted to trace their ideas about what germs are, where they may be found, whether they are good or bad and living or non-living and how they might look like in a drawing. Moreover, children were required to attribute a series of biological functions to dogs, chairs and germs, and finally to create a story with germs holding a key-role. The analysis of our qualitative data within the “NVivo” software showed that the informants make a strong association of germs with health and hygiene issues, locate germs mostly in our body and the external environment, are not familiar with the ‘good germs’-idea, and draw germs as ‘human-like’, ‘animal-like’ or ‘abstract’ entities. Moreover, they have significant difficulties not only in employing biological functions as criteria for classifying germs in the category of ‘living’, but also in just attributing such functions to germs using a warrant. Finally, the shift from our findings to a 3-part learning environment aiming at supporting preschoolers in refining their initial conceptualization of germs is thoroughly discussed in the paper.

  11. An ultrastructural study of the effect of neomycin on the colon in the human subject and in the conventional and the germ-free mouse.

    PubMed

    Aluwihare, A P

    1971-05-01

    An electron microscopic study of the colon of normal mice and human subjects and those treated with neomycin is reported; there is a close resemblance between the mouse and human colons. After rapid disinfection of the colon, there is epithelial cell damage due to a toxic effect of the drug, a reduction in epithelial turnover accompanying the change in flora, and an important reduction in the cellularity of the lamina propria mainly due to a reduction in inflammatory cells. The changes in the lamina propria probably represent changes in the antipathogenetic defences of the host.

  12. Ancient gene flow from early modern humans into Eastern Neanderthals

    PubMed Central

    Kuhlwilm, Martin; Gronau, Ilan; Hubisz, Melissa J.; de Filippo, Cesare; Prado-Martinez, Javier; Kircher, Martin; Fu, Qiaomei; Burbano, Hernán A.; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Rudan, Pavao; Brajkovic, Dejana; Kucan, Željko; Gušic, Ivan; Marques-Bonet, Tomas; Andrés, Aida M.; Viola, Bence; Pääbo, Svante; Meyer, Matthias; Siepel, Adam; Castellano, Sergi

    2016-01-01

    It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000–65,000 years ago. Here, we analyze the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and of modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously reported. PMID:26886800

  13. Chromatin associated Sin3A is essential for male germ cell lineage in the mouse

    PubMed Central

    Pellegrino, Jessica; Castrillon, Diego H.; David, Gregory

    2012-01-01

    Spermatogenesis is a complex process that requires coordinated proliferation and differentiation of male germ cells. The molecular events that dictate this process are largely unknown, but are likely to involve highly regulated transcriptional control. In this study, we investigate the contribution of chromatin associated Sin3A in mouse germ cell lineage development. Genetic inactivation of Sin3A in the male germline leads to sterility that results from the early and penetrant apoptotic death observed in Sin3A-deleted germ cells, coincident with the reentry in mitosis. Sin3A-deleted testes exhibit a Sertoli-cell only phenotype, consistent with the absolute requirement for Sin3A in germ cells’ development and/or viability. Interestingly, transcripts analysis revealed that the expression program of Sertoli cells is altered upon inactivation of Sin3A in germ cells. These studies identified a central role for the mammalian Sin3-HDAC complex in the germ cell lineage, and point to an exquisite transcriptional crosstalk between germ cells and their niche to support fertility in mammals. PMID:22820070

  14. Germ cell tumors: Insights from the Drosophila ovary and the mouse testis.

    PubMed

    Salz, Helen K; Dawson, Emily P; Heaney, Jason D

    2017-03-01

    Ovarian and testicular germ cell tumors of young adults are thought to arise from defects in germ cell development, but the molecular mechanisms underlying malignant transformation are poorly understood. In this review, we focus on the biology of germ cell tumor formation in the Drosophila ovary and the mouse testis, for which evidence supports common underlying mechanisms, such as blocking initiation into the differentiation pathway, impaired lineage progression, and sexual identity instability. We then discuss how these concepts inform our understanding of the disease in humans. Mol. Reprod. Dev. 84: 200-211, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Germ cell tumors: Insights from the Drosophila ovary and the mouse testis

    PubMed Central

    Salz, Helen K.; Dawson, Emily P.; Heaney, Jason D.

    2017-01-01

    SUMMARY Ovarian and testicular germ cell tumors of young adults are thought to arise from defects in germ cell development, but the molecular mechanisms underlying malignant transformation are poorly understood. In this review, we focus on the biology of germ cell tumor formation in the Drosophila ovary and the mouse testis, for which the evidence supports common underlying mechanisms such as blocking initiation into the differentiation pathway, impaired lineage progression, and sexual identity instability. We then discuss how these concepts inform our understanding of the disease in humans. PMID:28079292

  16. Ecosystem variability and early human habitats in eastern Africa.

    PubMed

    Magill, Clayton R; Ashley, Gail M; Freeman, Katherine H

    2013-01-22

    The role of savannas during the course of early human evolution has been debated for nearly a century, in part because of difficulties in characterizing local ecosystems from fossil and sediment records. Here, we present high-resolution lipid biomarker and isotopic signatures for organic matter preserved in lake sediments at Olduvai Gorge during a key juncture in human evolution about 2.0 Ma--the emergence and dispersal of Homo erectus (sensu lato). Using published data for modern plants and soils, we construct a framework for ecological interpretations of stable carbon-isotope compositions (expressed as δ(13)C values) of lipid biomarkers from ancient plants. Within this framework, δ(13)C values for sedimentary leaf lipids and total organic carbon from Olduvai Gorge indicate recurrent ecosystem variations, where open C(4) grasslands abruptly transitioned to closed C(3) forests within several hundreds to thousands of years. Carbon-isotopic signatures correlate most strongly with Earth's orbital geometry (precession), and tropical sea-surface temperatures are significant secondary predictors in partial regression analyses. The scale and pace of repeated ecosystem variations at Olduvai Gorge contrast with long-held views of directional or stepwise aridification and grassland expansion in eastern Africa during the early Pleistocene and provide a local perspective on environmental hypotheses of human evolution.

  17. Early human symbolic behavior in the Late Pleistocene of Wallacea.

    PubMed

    Brumm, Adam; Langley, Michelle C; Moore, Mark W; Hakim, Budianto; Ramli, Muhammad; Sumantri, Iwan; Burhan, Basran; Saiful, Andi Muhammad; Siagian, Linda; Suryatman; Sardi, Ratno; Jusdi, Andi; Abdullah; Mubarak, Andi Pampang; Hasliana; Hasrianti; Oktaviana, Adhi Agus; Adhityatama, Shinatria; van den Bergh, Gerrit D; Aubert, Maxime; Zhao, Jian-Xin; Huntley, Jillian; Li, Bo; Roberts, Richard G; Saptomo, E Wahyu; Perston, Yinika; Grün, Rainer

    2017-04-18

    Wallacea, the zone of oceanic islands separating the continental regions of Southeast Asia and Australia, has yielded sparse evidence for the symbolic culture of early modern humans. Here we report evidence for symbolic activity 30,000-22,000 y ago at Leang Bulu Bettue, a cave and rock-shelter site on the Wallacean island of Sulawesi. We describe hitherto undocumented practices of personal ornamentation and portable art, alongside evidence for pigment processing and use in deposits that are the same age as dated rock art in the surrounding karst region. Previously, assemblages of multiple and diverse types of Pleistocene "symbolic" artifacts were entirely unknown from this region. The Leang Bulu Bettue assemblage provides insight into the complexity and diversification of modern human culture during a key period in the global dispersal of our species. It also shows that early inhabitants of Sulawesi fashioned ornaments from body parts of endemic animals, suggesting modern humans integrated exotic faunas and other novel resources into their symbolic world as they colonized the biogeographically unique regions southeast of continental Eurasia.

  18. Early human symbolic behavior in the Late Pleistocene of Wallacea

    PubMed Central

    Brumm, Adam; Hakim, Budianto; Ramli, Muhammad; Sumantri, Iwan; Burhan, Basran; Saiful, Andi Muhammad; Siagian, Linda; Suryatman; Sardi, Ratno; Jusdi, Andi; Abdullah; Mubarak, Andi Pampang; Hasliana; Hasrianti; Oktaviana, Adhi Agus; Adhityatama, Shinatria; van den Bergh, Gerrit D.; Aubert, Maxime; Zhao, Jian-xin; Huntley, Jillian; Li, Bo; Roberts, Richard G.; Saptomo, E. Wahyu; Perston, Yinika; Grün, Rainer

    2017-01-01

    Wallacea, the zone of oceanic islands separating the continental regions of Southeast Asia and Australia, has yielded sparse evidence for the symbolic culture of early modern humans. Here we report evidence for symbolic activity 30,000–22,000 y ago at Leang Bulu Bettue, a cave and rock-shelter site on the Wallacean island of Sulawesi. We describe hitherto undocumented practices of personal ornamentation and portable art, alongside evidence for pigment processing and use in deposits that are the same age as dated rock art in the surrounding karst region. Previously, assemblages of multiple and diverse types of Pleistocene “symbolic” artifacts were entirely unknown from this region. The Leang Bulu Bettue assemblage provides insight into the complexity and diversification of modern human culture during a key period in the global dispersal of our species. It also shows that early inhabitants of Sulawesi fashioned ornaments from body parts of endemic animals, suggesting modern humans integrated exotic faunas and other novel resources into their symbolic world as they colonized the biogeographically unique regions southeast of continental Eurasia. PMID:28373568

  19. Early modern human lithic technology from Jerimalai, East Timor.

    PubMed

    Marwick, Ben; Clarkson, Chris; O'Connor, Sue; Collins, Sophie

    2016-12-01

    Jerimalai is a rock shelter in East Timor with cultural remains dated to 42,000 years ago, making it one of the oldest known sites of modern human activity in island Southeast Asia. It has special global significance for its record of early pelagic fishing and ancient shell fish hooks. It is also of regional significance for its early occupation and comparatively large assemblage of Pleistocene stone artefacts. Three major findings arise from our study of the stone artefacts. First, there is little change in lithic technology over the 42,000 year sequence, with the most noticeable change being the addition of new artefact types and raw materials in the mid-Holocene. Second, the assemblage is dominated by small chert cores and implements rather than pebble tools and choppers, a pattern we argue pattern, we argue, that is common in island SE Asian sites as opposed to mainland SE Asian sites. Third, the Jerimalai assemblage bears a striking resemblance to the assemblage from Liang Bua, argued by the Liang Bua excavation team to be associated with Homo floresiensis. We argue that the near proximity of these two islands along the Indonesian island chain (c.100 km apart), the long antiquity of modern human occupation in the region (as documented at Jerimalai), and the strong resemblance of distinctive flake stone technologies seen at both sites, raises the intriguing possibility that both the Liang Bua and Jerimalai assemblages were created by modern humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Ecosystem variability and early human habitats in eastern Africa

    PubMed Central

    Magill, Clayton R.; Ashley, Gail M.; Freeman, Katherine H.

    2013-01-01

    The role of savannas during the course of early human evolution has been debated for nearly a century, in part because of difficulties in characterizing local ecosystems from fossil and sediment records. Here, we present high-resolution lipid biomarker and isotopic signatures for organic matter preserved in lake sediments at Olduvai Gorge during a key juncture in human evolution about 2.0 Ma—the emergence and dispersal of Homo erectus (sensu lato). Using published data for modern plants and soils, we construct a framework for ecological interpretations of stable carbon-isotope compositions (expressed as δ13C values) of lipid biomarkers from ancient plants. Within this framework, δ13C values for sedimentary leaf lipids and total organic carbon from Olduvai Gorge indicate recurrent ecosystem variations, where open C4 grasslands abruptly transitioned to closed C3 forests within several hundreds to thousands of years. Carbon-isotopic signatures correlate most strongly with Earth’s orbital geometry (precession), and tropical sea-surface temperatures are significant secondary predictors in partial regression analyses. The scale and pace of repeated ecosystem variations at Olduvai Gorge contrast with long-held views of directional or stepwise aridification and grassland expansion in eastern Africa during the early Pleistocene and provide a local perspective on environmental hypotheses of human evolution. PMID:23267092

  1. An early history of human breast cancer: West meets East.

    PubMed

    Yan, Shou-He

    2013-09-01

    Cancer has been increasingly recognized as a global issue. This is especially true in countries like China, where cancer incidence has increased likely because of changes in environment and lifestyle. However, cancer is not a modern disease; early cases have been recorded in ancient medical books in the West and in China. Here, we provide a brief history of cancer, focusing on cancer of the breast, and review the etymology of ai, the Chinese character for cancer. Notable findings from both Western and Chinese traditional medicine are presented to give an overview of the most important, early contributors to our evolving understanding of human breast cancer. We also discuss the earliest historical documents to record patients with breast cancer.

  2. Four queries concerning the metaphysics of early human embryogenesis.

    PubMed

    Howsepian, A A

    2008-04-01

    In this essay, I attempt to provide answers to the following four queries concerning the metaphysics of early human embryogenesis. (1) Following its first cellular fission, is it coherent to claim that one and only one of two "blastomeric" twins of a human zygote is identical with that zygote? (2) Following the fusion of two human pre-embryos, is it coherent to claim that one and only one pre-fusion pre-embryo is identical with that postfusion pre-embryo? (3) Does a live human being come into existence only when its brain comes into existence? (4) At implantation, does a pre-embryo become a mere part of its mother? I argue that either if things have quidditative properties or if criterialism is false, then queries (1) and (2) can be answered in the affirmative; that in light of recent developments in theories of human death and in light of a more "functional" theory of brains, query (3) can be answered in the negative; and that plausible mereological principles require a negative answer to query (4).

  3. Water, plants, and early human habitats in eastern Africa.

    PubMed

    Magill, Clayton R; Ashley, Gail M; Freeman, Katherine H

    2013-01-22

    Water and its influence on plants likely exerted strong adaptive pressures in human evolution. Understanding relationships among water, plants, and early humans is limited both by incomplete terrestrial records of environmental change and by indirect proxy data for water availability. Here we present a continuous record of stable hydrogen-isotope compositions (expressed as δD values) for lipid biomarkers preserved in lake sediments from an early Pleistocene archaeological site in eastern Africa--Olduvai Gorge. We convert sedimentary leaf- and algal-lipid δD values into estimates for ancient source-water δD values by accounting for biochemical, physiological, and environmental influences on isotopic fractionation via published water-lipid enrichment factors for living plants, algae, and recent sediments. Reconstructed precipitation and lake-water δD values, respectively, are consistent with modern isotopic hydrology and reveal that dramatic fluctuations in water availability accompanied ecosystem changes. Drier conditions, indicated by less negative δD values, occur in association with stable carbon-isotopic evidence for open, C(4)-dominated grassland ecosystems. Wetter conditions, indicated by lower δD values, are associated with expanded woody cover across the ancient landscape. Estimates for ancient precipitation amounts, based on reconstructed precipitation δD values, range between approximately 250 and 700 mm · y(-1) and are consistent with modern precipitation data for eastern Africa. We conclude that freshwater availability exerted a substantial influence on eastern African ecosystems and, by extension, was central to early human proliferation during periods of rapid climate change.

  4. Water, plants, and early human habitats in eastern Africa

    PubMed Central

    Magill, Clayton R.; Ashley, Gail M.; Freeman, Katherine H.

    2013-01-01

    Water and its influence on plants likely exerted strong adaptive pressures in human evolution. Understanding relationships among water, plants, and early humans is limited both by incomplete terrestrial records of environmental change and by indirect proxy data for water availability. Here we present a continuous record of stable hydrogen-isotope compositions (expressed as δD values) for lipid biomarkers preserved in lake sediments from an early Pleistocene archaeological site in eastern Africa—Olduvai Gorge. We convert sedimentary leaf- and algal-lipid δD values into estimates for ancient source-water δD values by accounting for biochemical, physiological, and environmental influences on isotopic fractionation via published water–lipid enrichment factors for living plants, algae, and recent sediments. Reconstructed precipitation and lake-water δD values, respectively, are consistent with modern isotopic hydrology and reveal that dramatic fluctuations in water availability accompanied ecosystem changes. Drier conditions, indicated by less negative δD values, occur in association with stable carbon-isotopic evidence for open, C4-dominated grassland ecosystems. Wetter conditions, indicated by lower δD values, are associated with expanded woody cover across the ancient landscape. Estimates for ancient precipitation amounts, based on reconstructed precipitation δD values, range between approximately 250 and 700 mm·y−1 and are consistent with modern precipitation data for eastern Africa. We conclude that freshwater availability exerted a substantial influence on eastern African ecosystems and, by extension, was central to early human proliferation during periods of rapid climate change. PMID:23267102

  5. Revisiting the human seminiferous epithelium cycle.

    PubMed

    Nihi, F; Gomes, M L M; Carvalho, F A R; Reis, A B; Martello, R; Melo, R C N; Almeida, F R C L; Chiarini-Garcia, H

    2017-06-01

    Can all types of testicular germ cells be accurately identified by microscopy techniques and unambiguously distributed in stages of the human seminiferous epithelium cycle (SEC)? By using a high-resolution light microscopy (HRLM) method, which enables an improved visualization of germ cell morphological features, we identified all testicular germ cells in the seminiferous epithelium and precisely grouped them in six well-delimitated SEC stages, thus providing a reliable reference source for staging in man. Morphological characterization of germ cells in human has been done decades ago with the use of conventional histological methods (formaldehyde-based fixative -Zenker-formal- and paraffin embedding). These early studies proposed a classification of the SEC in six stages. However, the use of stages as baseline for morphofunctional evaluations of testicular parenchyma has been difficult because of incomplete morphological identification of germ cells and their random distribution in the human SEC. Testicular tissue from adult and elderly donors with normal spermatogenesis according to Levin's, Johnsen's and Bergmann's scores were used to evaluate germ cell morphology and validate their distribution and frequency in stages throughout human spermatogenesis. Testicular tissue from patients diagnosed with congenital bilateral agenesis of vas deferens (n = 3 adults) or prostate cancer (n = 3 elderly) were fixed in glutaraldehyde and embedded in araldite epoxy resin. Morphological analyses were performed by both light and transmission electron microscopy. HRLM method enabled a reliable morphological identification of all germ cells (spermatogonia, spermatocytes and spermatids) based on high-resolution aspects of euchromatin, heterochromatin and nucleolus. Moreover, acrosomal development of spermatids was clearly revealed. Altogether, our data redefined the limits of each stage leading to a more reliable determination of the SEC in man. Occasionally, germ cells can be

  6. Germ cells are not the primary factor for sexual fate determination in goldfish.

    PubMed

    Goto, Rie; Saito, Taiju; Takeda, Takahiro; Fujimoto, Takafumi; Takagi, Misae; Arai, Katsutoshi; Yamaha, Etsuto

    2012-10-01

    The presence of germ cells in the early gonad is important for sexual fate determination and gonadal development in vertebrates. Recent studies in zebrafish and medaka have shown that a lack of germ cells in the early gonad induces sex reversal in favor of a male phenotype. However, it is uncertain whether the gonadal somatic cells or the germ cells are predominant in determining gonadal fate in other vertebrate. Here, we investigated the role of germ cells in gonadal differentiation in goldfish, a gonochoristic species that possesses an XX-XY genetic sex determination system. The primordial germ cells (PGCs) of the fish were eliminated during embryogenesis by injection of a morpholino oligonucleotide against the dead end gene. Fish without germ cells showed two types of gonadal morphology: one with an ovarian cavity; the other with seminiferous tubules. Next, we tested whether function could be restored to these empty gonads by transplantation of a single PGC into each embryo, and also determined the gonadal sex of the resulting germline chimeras. Transplantation of a single GFP-labeled PGC successfully produced a germline chimera in 42.7% of the embryos. Some of the adult germline chimeras had a developed gonad on one side that contained donor derived germ cells, while the contralateral gonad lacked any early germ cell stages. Female germline chimeras possessed a normal ovary and a germ-cell free ovary-like structure on the contralateral side; this structure was similar to those seen in female morphants. Male germline chimeras possessed a testis and a contralateral empty testis that contained some sperm in the tubular lumens. Analysis of aromatase, foxl2 and amh expression in gonads of morphants and germline chimeras suggested that somatic transdifferentiation did not occur. The offspring of fertile germline chimeras all had the donor-derived phenotype, indicating that germline replacement had occurred and that the transplanted PGC had rescued both female and

  7. Generation of male differentiated germ cells from various types of stem cells.

    PubMed

    Hou, Jingmei; Yang, Shi; Yang, Hao; Liu, Yang; Liu, Yun; Hai, Yanan; Chen, Zheng; Guo, Ying; Gong, Yuehua; Gao, Wei-Qiang; Li, Zheng; He, Zuping

    2014-06-01

    Infertility is a major and largely incurable disease caused by disruption and loss of germ cells. It affects 10-15% of couples, and male factor accounts for half of the cases. To obtain human male germ cells 'especially functional spermatids' is essential for treating male infertility. Currently, much progress has been made on generating male germ cells, including spermatogonia, spermatocytes, and spermatids, from various types of stem cells. These germ cells can also be used in investigation of the pathology of male infertility. In this review, we focused on advances on obtaining male differentiated germ cells from different kinds of stem cells, with an emphasis on the embryonic stem (ES) cells, the induced pluripotent stem (iPS) cells, and spermatogonial stem cells (SSCs). We illustrated the generation of male differentiated germ cells from ES cells, iPS cells and SSCs, and we summarized the phenotype for these stem cells, spermatocytes and spermatids. Moreover, we address the differentiation potentials of ES cells, iPS cells and SSCs. We also highlight the advantages, disadvantages and concerns on derivation of the differentiated male germ cells from several types of stem cells. The ability of generating mature and functional male gametes from stem cells could enable us to understand the precise etiology of male infertility and offer an invaluable source of autologous male gametes for treating male infertility of azoospermia patients. © 2014 Society for Reproduction and Fertility.

  8. Identification of Germ Plasm-Associated Transcripts by Microarray Analysis of Xenopus Vegetal Cortex RNA

    PubMed Central

    Cuykendall, Tawny N.; Houston, Douglas W.

    2011-01-01

    RNA localization is a common mechanism for regulating cell structure and function. Localized RNAs in Xenopus oocytes are critical for early development, including germline specification by the germ plasm. Despite the importance of these localized RNAs, only approximately 25 have been identified and fewer are functionally characterized. Using microarrays, we identified a large set of localized RNAs from the vegetal cortex. Overall, our results indicate a minimum of 275 localized RNAs in oocytes, or 2–3% of maternal transcripts, which are in general agreement with previous findings. We further validated vegetal localization for 24 candidates and further characterized three genes expressed in the germ plasm. We identified novel germ plasm expression for reticulon 3.1, exd2 (a novel exonuclease-domain encoding gene), and a putative noncoding RNA. Further analysis of these and other localized RNAs will likely identify new functions of germ plasm and facilitate the identification of cis-acting RNA localization elements. PMID:20503379

  9. Extragonadal Germ Cell Tumors—Patient Version

    Cancer.gov

    Extragonadal germ cell tumors form in parts of the body outside the gonads. They may begin to grow anywhere in the body, but usually form in the pineal gland in the brain, the chest, the lower part of the spine, or the abdomen. Start here to find information on extragonadal germ cell tumors treatment.

  10. Late Pleistocene climate drivers of early human migration.

    PubMed

    Timmermann, Axel; Friedrich, Tobias

    2016-10-06

    On the basis of fossil and archaeological data it has been hypothesized that the exodus of Homo sapiens out of Africa and into Eurasia between ~50-120 thousand years ago occurred in several orbitally paced migration episodes. Crossing vegetated pluvial corridors from northeastern Africa into the Arabian Peninsula and the Levant and expanding further into Eurasia, Australia and the Americas, early H. sapiens experienced massive time-varying climate and sea level conditions on a variety of timescales. Hitherto it has remained difficult to quantify the effect of glacial- and millennial-scale climate variability on early human dispersal and evolution. Here we present results from a numerical human dispersal model, which is forced by spatiotemporal estimates of climate and sea level changes over the past 125 thousand years. The model simulates the overall dispersal of H. sapiens in close agreement with archaeological and fossil data and features prominent glacial migration waves across the Arabian Peninsula and the Levant region around 106-94, 89-73, 59-47 and 45-29 thousand years ago. The findings document that orbital-scale global climate swings played a key role in shaping Late Pleistocene global population distributions, whereas millennial-scale abrupt climate changes, associated with Dansgaard-Oeschger events, had a more limited regional effect.

  11. Late Pleistocene climate drivers of early human migration

    NASA Astrophysics Data System (ADS)

    Timmermann, Axel; Friedrich, Tobias

    2016-10-01

    On the basis of fossil and archaeological data it has been hypothesized that the exodus of Homo sapiens out of Africa and into Eurasia between ~50-120 thousand years ago occurred in several orbitally paced migration episodes. Crossing vegetated pluvial corridors from northeastern Africa into the Arabian Peninsula and the Levant and expanding further into Eurasia, Australia and the Americas, early H. sapiens experienced massive time-varying climate and sea level conditions on a variety of timescales. Hitherto it has remained difficult to quantify the effect of glacial- and millennial-scale climate variability on early human dispersal and evolution. Here we present results from a numerical human dispersal model, which is forced by spatiotemporal estimates of climate and sea level changes over the past 125 thousand years. The model simulates the overall dispersal of H. sapiens in close agreement with archaeological and fossil data and features prominent glacial migration waves across the Arabian Peninsula and the Levant region around 106-94, 89-73, 59-47 and 45-29 thousand years ago. The findings document that orbital-scale global climate swings played a key role in shaping Late Pleistocene global population distributions, whereas millennial-scale abrupt climate changes, associated with Dansgaard-Oeschger events, had a more limited regional effect.

  12. Early Human Evolution in the Western Palaearctic: Ecological Scenarios

    NASA Astrophysics Data System (ADS)

    Carrión, José S.; Rose, James; Stringer, Chris

    2011-06-01

    This review presents the themes of a special issue dealing with environmental scenarios of human evolution during the Early Pleistocene (2.6-0.78 Ma; MIS 103-MIS 19) and early Middle Pleistocene (0.78-0.47 Ma; MIS 19-base of MIS 12) within the western Palaearctic. This period is one of dramatic changes in the climates and the distribution of Palaearctic biota. These changes have played their role in generating adaptive and phyletic patterns within the human ancestry, involving several species such as Homo habilis, "Homo georgicus", Homo erectus, Homo antecessor and Homo heidelbergensis. In the archaeological record, these species include the Oldowan (Mode 1) and Acheulian (Mode 2) lithic technologies. Taphonomic considerations of palaeoecological research in hominin-bearing sites are provided and evaluated. Syntheses are provided for north Africa, western Asia, the Mediterranean Basin, Britain, and continental Europe. Palaeoenvironmental reconstructions based on multidisciplinary data are given for Ain Boucherit, Ain Hanech and El-Kherba in Algeria, Dmanisi in Georgia, Atapuerca, Cueva Negra, and the Orce Basin in Spain, Monte Poggiolo and Pirro Nord in Italy, Pont-de-Lavaud in France, and Mauer in Germany. The state of the art with the Out of Africa 1 dispersal model is reviewed. A source-sink dynamics model for Palaeolithic Europe is described to explain the morphological disparity of H. heidelbergensis (we will sometimes use the informal name "Heidelbergs") and early Neanderthals. Other aspects debated here are the selective value of habitat mosaics including reconstructions based on mammal and avian databases, and the role of geological instability combined with topographic complexity. This review is completed by addressing the question of whether the appearance of evolutionary trends within hominins is concentrated in regions of highest worldwide biological diversity (biodiversity hotspots). It is concluded that the keys for the activation of evolutionary

  13. UVA phototransduction drives early melanin synthesis in human melanocytes.

    PubMed

    Wicks, Nadine L; Chan, Jason W; Najera, Julia A; Ciriello, Jonathan M; Oancea, Elena

    2011-11-22

    Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% ultraviolet A (UVA) and ~5% ultraviolet B (UVB) at the Earth's surface, promotes melanin synthesis in epidermal melanocytes [2, 3], which protects skin from DNA damage [4, 5]. UVB causes DNA lesions [6] that lead to transcriptional activation of melanin-producing enzymes, resulting in delayed skin pigmentation within days [7]. In contrast, UVA causes primarily oxidative damage [8] and leads to immediate pigment darkening (IPD) within minutes, via an unknown mechanism [9, 10]. No receptor protein directly mediating phototransduction in skin has been identified. Here we demonstrate that exposure of primary human epidermal melanocytes (HEMs) to UVA causes calcium mobilization and early melanin synthesis. Calcium responses were abolished by treatment with G protein or phospholipase C (PLC) inhibitors or by depletion of intracellular calcium stores. We show that the visual photopigment rhodopsin [11] is expressed in HEMs and contributes to UVR phototransduction. Upon UVR exposure, significant melanin production was measured within one hour; cellular melanin continued to increase in a retinal- and calcium-dependent manner up to 5-fold after 24 hr. Our findings identify a novel UVA-sensitive signaling pathway in melanocytes that leads to calcium mobilization and melanin synthesis and may underlie the mechanism of IPD in human skin. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model

    PubMed Central

    Ono, Mitsuaki; Oshima, Masamitsu; Ogawa, Miho; Sonoyama, Wataru; Hara, Emilio Satoshi; Oida, Yasutaka; Shinkawa, Shigehiko; Nakajima, Ryu; Mine, Atsushi; Hayano, Satoru; Fukumoto, Satoshi; Kasugai, Shohei; Yamaguchi, Akira; Tsuji, Takashi; Kuboki, Takuo

    2017-01-01

    Whole-organ regeneration has great potential for the replacement of dysfunctional organs through the reconstruction of a fully functional bioengineered organ using three-dimensional cell manipulation in vitro. Recently, many basic studies of whole-tooth replacement using three-dimensional cell manipulation have been conducted in a mouse model. Further evidence of the practical application to human medicine is required to demonstrate tooth restoration by reconstructing bioengineered tooth germ using a postnatal large-animal model. Herein, we demonstrate functional tooth restoration through the autologous transplantation of bioengineered tooth germ in a postnatal canine model. The bioengineered tooth, which was reconstructed using permanent tooth germ cells, erupted into the jawbone after autologous transplantation and achieved physiological function equivalent to that of a natural tooth. This study represents a substantial advancement in whole-organ replacement therapy through the transplantation of bioengineered organ germ as a practical model for future clinical regenerative medicine. PMID:28300208

  15. [Current progress and future direction in the biology of ovarian germ stem cells in mammals].

    PubMed

    Li, Chao-Hui; Guo, Kun; Zheng, Ping

    2012-12-01

    Whether or not oogenesis continues after birth in mammalian ovaries remains controversial. Since the 1950's, it has been generally accepted that oogenesis takes place during embryogenesis in mammals and ceases at birth. At birth, germ cells in mammalian ovaries have progressed to the diplotene stage of meiotic prophase and have formed primordial follicles with surrounding somatic cells. These primordial follicles represent follicle reserves of the reproductive life. However, this view has been recently challenged by a growing body of evidence showing the isolation and propagation of germ stem cells from mouse and human ovaries. These ovarian germ stem cells are capable of regenerating functional oocytes when transplanted back into recipient ovaries. Despite the discovery of the potential germ stem cells in mammalian ovaries, it remains uncertain whether these cells exist and function in ovaries under physiological conditions. Herein we review the current progress and future direction in this infant area.

  16. Avian germplasm preservation: embryonic stem cells or primordial germ cells?

    PubMed

    Petitte, J N

    2006-02-01

    Presently, avian genetic resources are best maintained as living collections of birds. Unfortunately, these stocks have been under constant pressure to be destroyed because of the decline in the number of Poultry Science Departments and pressures to cut costs at land grant institutions. Cryopreservation of semen is often suggested as a means to bank avian germplasm. However, this is only applicable for single-gene traits and does not allow for full reconstitution of the genetics of the original line. Over the last 15 yr, advances in the manipulation of the early chick embryo, manipulation of primordial germ cells (PGC), and the culture of embryonic stem cells (ESC) suggests that cryopreservation of blastodermal cells, ESC, or PGC might offer a means to preserve the entire genome of highly selected, specialized stocks of poultry. Freezing each of these cell types is possible with varying degrees of efficiency. Similarly, the effectiveness of generating germ line chimeras using blastodermal cells, ESC, or PGC also varies greatly. Other factors that must be considered include the choice of the recipient lines to develop the germ line chimeras and the number of individuals needed to reconstitute the line. Finally, the low efficiency rate of reconstitution and the high cost associated with current technologies makes these approaches prohibitive. Significant challenges remain to be overcome before the entire genome of poultry stocks can be routinely cryoperserved and reconstituted.

  17. DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.

    PubMed

    Isagawa, Takayuki; Nagae, Genta; Shiraki, Nobuaki; Fujita, Takanori; Sato, Noriko; Ishikawa, Shumpei; Kume, Shoen; Aburatani, Hiroyuki

    2011-01-01

    Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental reprogramming occurs by de novo methylation and demethylation. Variance in DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analyzed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions are methylated across all three germ layers and in the three adult somatic tissues. This commonly methylated gene set is enriched in germ cell-associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns by global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Our combined findings indicate that differentiation of ES cells into the three germ layers is accompanied by an increased number of commonly methylated DNA regions and that these tissue-specific alterations in methylation occur for only a small number of genes. DNA methylation at the proximal promoter regions of commonly methylated genes thus appears to be an irreversible mark which functions to fix somatic lineage by repressing the transcription of germ cell-specific genes.

  18. The C-X-C signalling system in the rodent vs primate testis: impact on germ cell niche interaction.

    PubMed

    Heckmann, Laura; Pock, Tim; Tröndle, Ina; Neuhaus, Nina

    2018-05-01

    In zebrafish, action of the chemokine Cxcl12 is mediated through its G-protein-coupled seven-transmembrane domain receptor Cxcr4 and the atypical receptor Cxcr7. Employing this animal model, it was revealed that this Cxcl12 signalling system plays a crucial role for directed migration of primordial germ cells (PGC) during early testicular development. Importantly, subsequent studies indicated that this regulatory mechanism is evolutionarily conserved also in mice. What is more, the functional role of the CXCL12 system does not seem to be limited to early phases of testicular development. Data from mouse studies rather demonstrate that CXCL12 and its receptors are also involved in the homing process of gonocytes into their niches at the basal membrane of the seminiferous tubules. Intriguingly, even the spermatogonial stem cells (SSCs) present in the adult mouse testis appear to maintain the ability to migrate towards a CXCL12 gradient as demonstrated by functional in vitro migration assays and in vivo germ cell transplantation assays. These findings not only indicate a role of the CXCL12 system throughout male germ cell development in mice but also suggest that this system may be evolutionarily conserved. In this review, we take into account the available literature focusing on the localization patterns of the CXCL12 system not only in rodents but also in primates, including the human. Based on these data, we discuss whether the CXCL12 system is also conserved between rodents and primates and discuss the known and potential functional consequences. © 2018 Society for Reproduction and Fertility.

  19. Early Human Testing Initiative Phase 1 Regenerative Life Support Systems

    1995-08-08

    Early Human Testing (EHT) Initiative Phase 1 Regenerative Life Support Systems Laboratory (RLSSL). Nigel Packham activities in the Variable Pressure Growth Chamber which he lived inside for 15 days. A crowd of well-wishers outside the test chamber, at the console are John Lewis, Ed Mohr and Marybeth Edeen (15577). Packham exiting the chamber (15578-81). Packham is the focus of television cameras and reporters (15582-3). Don Henninger interviewed by reporters (15584). Packham is presented with a jacket after his stay in the chamber (15585). Packham inside the wheat growth chamber checking the condition of the plants (15586-7, 15597). Packham exercising on a recumbant bicycle (15588, 15592). Packham, through the window into the growth chamber, displays a handful of wheat plants to console monitor Dan Barta (15589-90). Group portrait of the team conducting the Early Human Testing Initiative Phase 1 Regenerative Life Support Systems test and include, front row, from left: Jeff Dominick and Don Overton and back row, from left, unidentified member, Marybeth Edeen, Nigel Packham, John Lewis, Ed Mohr, Dan Barta and Tim Monk (15591). Harry Halford prepares to send a package through the airlock to Packham (15593). Packham displays a handful of wheat plants (15594). Packham fixes himself a bowl of cereal (15595) and retrieves a carton of milk from the refrigerator (15596). Packham retrieves a package from the airlock (15598). Packham packs up trash in plastic bag (15599-600) and sends it back through the airlock (15601). Packham gets a cup of water (15602) and heats it in the microwave (15603).

  20. Glycoconjugate distribution in early human notochord and axial mesenchyme.

    PubMed

    Götz, W; Quondamatteo, F

    2001-02-01

    Glycosylation patterns of cells and tissues give insights into spatially and temporally regulated developmental processes and can be detected histochemically using plant lectins with specific affinities for sugar moieties. The early development of the vertebral column in man is a process which has never been investigated by lectin histochemistry. Therefore, we studied binding of several lectins (AIA, Con A, GSA II, LFA, LTA, PNA, RCA I, SBA, SNA, WGA) in formaldehyde-fixed sections of the axial mesenchyme of 5 human embryos in Carnegie stages 12-15. During these developmental stages, an unsegmented mesenchyme covers the notochord. Staining patterns did not show striking temporal variations except for SBA which stained the cranial axial mesenchyme only in the early stage 12 embryo and for PNA, of which the staining intensity in the mesenchyme decreased with age. The notochord appeared as a highly glycosylated tissue. Carbohydrates detected may correspond to adhesion molecules or to secreted substances like proteoglycans or proteins which could play an inductive role, for example, for the neural tube. The axial perinotochordal unsegmented mesenchyme showed strong PNA binding. Therefore, its function as a PNA-positive "barrier" tissue is discussed. The endoderm of the primitive gut showed a lectin-binding pattern that was similar to that of the notochord, which may correlate with interactions between these tissues during earlier developmental stages.

  1. A karyometric note on nucleoli in human early granulocytic precursors.

    PubMed

    Smetana, K; Mikulenková, D; Jirásková, I; Klamová, H

    2006-01-01

    The diameter of nucleoli was measured in human bone marrow early granulocytic precursors after visualization by a simple cytochemical method for demonstration of RNA. Such method facilitated to clearly see nucleolar bodies without perinucleolar chromatin, including those of micronucleoli. The bone marrow of patients suffering from chronic myeloid leukaemia (untreated with cytostatics) provided a satisfactory number of both myeloblasts and promyelocytes for nucleolar measurements because of prevailing granulopoiesis. The direct nucleolar measurement was carried out on digitized and processed images on the screen at magnification 4,300x. It seems to be likely that the nucleolar size is directly related to the number of nucleoli per cell. The largest nucleoli were present in both myeloblasts and promyelocytes that possessed a single nucleolus. In contrast, the nucleolar diameter was significantly smaller in cells with multiple nucleoli. However, in cells with small multiple nucleoli, one of them was always larger and dominant with a large number of AgNORs. Such large nucleoli are possibly visible in specimens stained with panoptic procedures or methods staining nuclear chromatin or DNA. It should also be mentioned that both myeloblasts and promyelocytes mostly possessed two nucleoli with the mean diameter close to 1.5 microm. The incidence of early granulocytic precursors classified according to the nucleolar number and size strongly suggested that the various nucleolar number and nucleolar size in these cells might be related to the different stage of the cell cycle and might also explain their heterogeneity.

  2. Early indices of deviance detection in humans and animal models.

    PubMed

    Grimm, Sabine; Escera, Carles; Nelken, Israel

    2016-04-01

    Detecting unexpected stimuli in the environment is a critical function of the auditory system. Responses to unexpected "deviant" sounds are enhanced compared to responses to expected stimuli. At the human scalp, deviance detection is reflected in the mismatch negativity (MMN) and in an enhancement of the middle-latency response (MLR). Single neurons often respond more strongly to a stimulus when rare than when common, a phenomenon termed stimulus-specific adaptation (SSA). Here we compare stimulus-specific adaptation with scalp-recorded deviance-related responses. We conclude that early markers of deviance detection in the time range of the MLR could be a direct correlate of cortical SSA. Both occur at an early level of cortical activation, both are robust findings with low-probability stimuli, and both show properties of genuine deviance detection. Their causal relation with the later scalp-recorded MMN is a key question in this field. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Facilitated early cortical processing of nude human bodies.

    PubMed

    Alho, Jussi; Salminen, Nelli; Sams, Mikko; Hietanen, Jari K; Nummenmaa, Lauri

    2015-07-01

    Functional brain imaging has identified specialized neural systems supporting human body perception. Responses to nude vs. clothed bodies within this system are amplified. However, it remains unresolved whether nude and clothed bodies are processed by same cerebral networks or whether processing of nude bodies recruits additional affective and arousal processing areas. We recorded simultaneous MEG and EEG while participants viewed photographs of clothed and nude bodies. Global field power revealed a peak ∼145ms after stimulus onset to both clothed and nude bodies, and ∼205ms exclusively to nude bodies. Nude-body-sensitive responses were centered first (100-200ms) in the extrastriate and fusiform body areas, and subsequently (200-300ms) in affective-motivational areas including insula and anterior cingulate cortex. We conclude that visibility of sexual features facilitates early cortical processing of human bodies, the purpose of which is presumably to trigger sexual behavior and ultimately ensure reproduction. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Brain anatomical networks in early human brain development.

    PubMed

    Fan, Yong; Shi, Feng; Smith, Jeffrey Keith; Lin, Weili; Gilmore, John H; Shen, Dinggang

    2011-02-01

    Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1 month, 1 year, and 2 years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1 year and 2 years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information. Copyright © 2010. Published by Elsevier Inc.

  5. Early-Stage Aggregation of Human Islet Amyloid Polypeptide

    NASA Astrophysics Data System (ADS)

    Guo, Ashley; de Pablo, Juan

    Human islet amyloid polypeptide (hIAPP, or human amylin) is implicated in the development of type II diabetes. hIAPP is known to aggregate into amyloid fibrils; however, it is prefibrillar oligomeric species, rather than mature fibrils, that are proposed to be cytotoxic. In order to better understand the role of hIAPP aggregation in the onset of disease, as well as to design effective diagnostics and therapeutics, it is crucial to understand the mechanism of early-stage hIAPP aggregation. In this work, we use atomistic molecular dynamics simulations combined with multiple advanced sampling techniques to examine the formation of the hIAPP dimer and trimer. Metadynamics calculations reveal a free energy landscape for the hIAPP dimer, which suggest multiple possible transition pathways. We employ finite temperature string method calculations to identify favorable pathways for dimer and trimer formation, along with relevant free energy barriers and intermediate structures. Results provide valuable insights into the mechanisms and energetics of hIAPP aggregation. In addition, this work demonstrates that the finite temperature string method is an effective tool in the study of protein aggregation. Funded by National Institute of Standards and Technology.

  6. Three-dimensional wet-electrospun poly(lactic acid)/multi-wall carbon nanotubes scaffold induces differentiation of human menstrual blood-derived stem cells into germ-like cells.

    PubMed

    Eyni, Hossein; Ghorbani, Sadegh; Shirazi, Reza; Salari Asl, Leila; P Beiranvand, Shahram; Soleimani, Masoud

    2017-09-01

    Infertility caused by the disruption or absence of germ cells is a major and largely incurable medical problem. Germ cells (i.e., sperm or egg) play a key role in the transmission of genetic and epigenetic information across generations. Generation of gametes derived in vitro from stem cells hold promising prospects which could potentially help infertile men and women. Menstrual blood-derived stem cells are a unique stem cell source. Evidence suggests that menstrual blood-derived stem cells exhibit a multi-lineage potential and have attracted extensive attention in regenerative medicine. To maintain the three-dimensional structure of natural extra cellular matrices in vitro, scaffolds can do this favor and mimic a microenvironment for cell proliferation and differentiation. According to previous studies, poly(lactic acid) and multi-wall carbon nanotubes have been introduced as novel and promising biomaterials for the proliferation and differentiation of stem cells. Some cell types have been successfully grown on a matrix containing carbon nanotubes in tissue engineering but there is no report for this material to support stem cells differentiation into germ cells lineage. This study designed a 3D wet-electrospun poly(lactic acid) and poly(lactic acid)/multi-wall carbon nanotubes composite scaffold to compare infiltration, proliferation, and differentiation potential of menstrual blood-derived stem cells toward germ cell lineage with 2D culture. Our primary data revealed that the fabricated scaffold has mechanical and biological suitable qualities for supporting and attachments of stem cells. The differentiated menstrual blood-derived stem cells tracking in scaffolds using scanning electron microscopy confirmed cell attachment, aggregation, and distribution on the porous scaffold. Based on the differentiation assay by RT-PCR analysis, stem cells and germ-like cells markers were expressed in 3D groups as well as 2D one. It seems that poly(lactic acid

  7. TCGA's Testicular Germ Cell Tumor Study - TCGA

    Cancer.gov

    TCGA network researchers identify molecular characteristics that classify testicular germ cell tumor types, including a separate subset of seminomas defined by KIT mutations. This provides a set of candidate biomarkers for risk stratification and potential therapeutic targeting.

  8. Sex determination in mammalian germ cells

    PubMed Central

    Spiller, Cassy M; Bowles, Josephine

    2015-01-01

    Germ cells are the precursors of the sperm and oocytes and hence are critical for survival of the species. In mammals, they are specified during fetal life, migrate to the developing gonads and then undergo a critical period during which they are instructed, by the soma, to adopt the appropriate sexual fate. In a fetal ovary, germ cells enter meiosis and commit to oogenesis, whereas in a fetal testis, they avoid entry into meiosis and instead undergo mitotic arrest and mature toward spermatogenesis. Here, we discuss what we know so far about the regulation of sex-specific differentiation of germ cells, considering extrinsic molecular cues produced by somatic cells, as well as critical intrinsic changes within the germ cells. This review focuses almost exclusively on our understanding of these events in the mouse model. PMID:25791730

  9. Specifying and protecting germ cell fate

    PubMed Central

    Strome, Susan; Updike, Dustin

    2015-01-01

    Germ cells are the special cells in the body that undergo meiosis to generate gametes and subsequently entire new organisms after fertilization, a process that continues generation after generation. Recent studies have expanded our understanding of the factors and mechanisms that specify germ cell fate, including the partitioning of maternally supplied ‘germ plasm’, inheritance of epigenetic memory and expression of transcription factors crucial for primordial germ cell (PGC) development. Even after PGCs are specified, germline fate is labile and thus requires protective mechanisms, such as global transcriptional repression, chromatin state alteration and translation of only germline-appropriate transcripts. Findings from diverse species continue to provide insights into the shared and divergent needs of these special reproductive cells. PMID:26122616

  10. Germ cell control of testin production is inverse to that of other Sertoli cell products.

    PubMed

    Jégou, B; Pineau, C; Velez de la Calle, J F; Touzalin, A M; Bardin, C W; Cheng, C Y

    1993-06-01

    Recent studies have shown that germ cells can regulate testins, two newly identified Sertoli cell proteins that are associated with junctional complexes. To investigate this possibility, several parameters of Sertoli cell function were investigated over 2-120 days post exposure of the rat testes to x-rays (3 Grays). The irradiation-induced loss of spermatogonia resulted in a maturation-depletion process progressively affecting all germ cell classes. Testis weight began to decrease when the most numerous germ cell type (spermatids) began to decline. A complete or near complete recovery of spermatogenesis and of the testis weight had occurred by day 120 post irradiation. There was no significant change in FSH, epididymal androgen-binding protein, and tubule fluid levels during the first weeks after irradiation, when the seminiferious epithelium was depleted of spermatogonia and germ cells up to early spermatids. In contrast, when the number of the more mature forms of spermatids declined (between day 21 and 54), FSH rose and androgen-binding protein as well as fluid production declined. The subsequent recovery of these parameters was also highly correlated with the number of late spermatids. By contrast, testicular testin contents reacted to the depletion of germ cells with a biphasic increase; a doubling occurred when spermatogonia, spermatocytes, and early spermatids were absent (days 4-28), and a 7-fold rise occurred by day 37 when the number of late spermatids had decreased by 50%. By day 54, when the sperm counts had reached a nadir, testin contents had returned to levels corresponding to about four times the control levels; they progressively recovered thereafter. These observations support the postulate that germ cells negatively regulate testins. This possibility was investigated with in vitro experiments showing that addition of germ cell-conditioned medium to Sertoli cell monolayers inhibited testin secretion in a dose-dependent manner. In conclusion this

  11. Maternal smoking and testicular germ cell tumors.

    PubMed

    McGlynn, Katherine A; Zhang, Yawei; Sakoda, Lori C; Rubertone, Mark V; Erickson, Ralph L; Graubard, Barry I

    2006-10-01

    Testicular germ cell tumors (TGCT) are the most common cancer among men ages 15 to 35 years in the United States. The well-established TGCT risk factors cryptorchism, prior diagnosis of TGCT, and family history of testicular cancer indicate that exposures in early life and/or in the familial setting may be critical to determining risk. Previous reports of familial clustering of lung cancer in mothers and testicular cancers in sons suggest that passive smoking in childhood may be such an exposure. To clarify the relationship of passive smoking exposure to TGCT risk, data from 754 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Data from 1,086 mothers of the cases and controls were also examined. Overall, there was no relationship between maternal [odds ratio (OR), 1.1; 95% confidence interval (95% CI), 0.9-1.3] or paternal smoking (OR, 1.0; 95% CI, 0.8-1.3) and TGCT risk. Although living with a non-parent smoker was marginally related to risk (OR, 1.4; 95% CI, 1.0-2.1), there was no relationship with number of smokers, amount smoked, or duration of smoking. Responses from both case-control participants and mothers also revealed no relationship between either maternal smoking while pregnant or while breast-feeding. Results did not differ by TGCT histology (seminoma, non-seminoma). These results do not support the hypothesis that passive smoking, either in utero or in childhood, is related to risk of TGCT. Other early life exposures, however, may explain the familial clustering of lung cancer in mothers and TGCT in sons.

  12. DAZ Family Proteins, Key Players for Germ Cell Development

    PubMed Central

    Fu, Xia-Fei; Cheng, Shun-Feng; Wang, Lin-Qing; Yin, Shen; De Felici, Massimo; Shen, Wei

    2015-01-01

    DAZ family proteins are found almost exclusively in germ cells in distant animal species. Deletion or mutations of their encoding genes usually severely impair either oogenesis or spermatogenesis or both. The family includes Boule (or Boll), Dazl (or Dazla) and DAZ genes. Boule and Dazl are situated on autosomes while DAZ, exclusive of higher primates, is located on the Y chromosome. Deletion of DAZ gene is the most common causes of infertility in humans. These genes, encoding for RNA binding proteins, contain a highly conserved RNA recognition motif and at least one DAZ repeat encoding for a 24 amino acids sequence able to bind other mRNA binding proteins. Basically, Daz family proteins function as adaptors for target mRNA transport and activators of their translation. In some invertebrate species, BOULE protein play a pivotal role in germline specification and a conserved regulatory role in meiosis. Depending on the species, DAZL is expressed in primordial germ cells (PGCs) and/or pre-meiotic and meiotic germ cells of both sexes. Daz is found in fetal gonocytes, spermatogonia and spermatocytes of adult testes. Here we discuss DAZ family genes in a phylogenic perspective, focusing on the common and distinct features of these genes, and their pivotal roles during gametogenesis evolved during evolution. PMID:26327816

  13. Dissecting Germ Cell Metabolism through Network Modeling.

    PubMed

    Whitmore, Leanne S; Ye, Ping

    2015-01-01

    Metabolic pathways are increasingly postulated to be vital in programming cell fate, including stemness, differentiation, proliferation, and apoptosis. The commitment to meiosis is a critical fate decision for mammalian germ cells, and requires a metabolic derivative of vitamin A, retinoic acid (RA). Recent evidence showed that a pulse of RA is generated in the testis of male mice thereby triggering meiotic commitment. However, enzymes and reactions that regulate this RA pulse have yet to be identified. We developed a mouse germ cell-specific metabolic network with a curated vitamin A pathway. Using this network, we implemented flux balance analysis throughout the initial wave of spermatogenesis to elucidate important reactions and enzymes for the generation and degradation of RA. Our results indicate that primary RA sources in the germ cell include RA import from the extracellular region, release of RA from binding proteins, and metabolism of retinal to RA. Further, in silico knockouts of genes and reactions in the vitamin A pathway predict that deletion of Lipe, hormone-sensitive lipase, disrupts the RA pulse thereby causing spermatogenic defects. Examination of other metabolic pathways reveals that the citric acid cycle is the most active pathway. In addition, we discover that fatty acid synthesis/oxidation are the primary energy sources in the germ cell. In summary, this study predicts enzymes, reactions, and pathways important for germ cell commitment to meiosis. These findings enhance our understanding of the metabolic control of germ cell differentiation and will help guide future experiments to improve reproductive health.

  14. Astronomical Theory of Early Human Migration (Milutin Milankovic Medal Lecture)

    NASA Astrophysics Data System (ADS)

    Timmermann, Axel; Friedrich, Tobias

    2017-04-01

    Our climate system varies on a wide range of timescales, from seasons to several millions of years. A large part of this variability is internally generated as a result of instabilities of the coupled atmosphere-ocean-ice-carbon cycle system. Other modes of variability, such as glacial cycles, are caused by astronomical forcings with periods of 20, 40, 100 thousand years. These so-called Milankovitch Cycles are associated with earth's axis wobble, axis obliquity and shifts in the eccentricity of earth's orbit around the sun, respectively. When these cycles conspire, they can cause the climate system to plunge into an ice-age. This happened last time 110,000 years ago, when Northern Hemisphere summer radiation decreased substantially and ice-sheets started to form as a result. Around 100,000 years ago northern Hemisphere summer moved again closer to the sun and Homo sapiens started to leave Africa across vegetated corridors in Northeastern Africa and the Arabian Peninsula. This first migration wave must have been relatively weak, but it left unequivocal traces in the fossil and archaeological record. Why Homo sapiens embarked on its grand journey across our planet during glacial climate conditions has been subject of an intense debate in various scientific communities. Moreover, the archaeological records of an early exodus around 100 thousand years ago seem to be at odds with paleo-genetic evidences, that place the first dispersal out of Africa around 70-60 thousand years ago. To elucidate what role climate and environmental conditions played in the dispersal of Anatomically Modern Humans out of Africa, we have developed and applied one of the first integrated climate/human migration computer models. The model simulates ice-ages, abrupt climate change, the "peopling" of our planet and captures the arrival time of Homo sapiens in the Levant, Arabian Peninsula, Southern China and Australia in close agreement with paleo climate reconstructions, fossil and

  15. Generation of germ cells in vitro in the era of induced pluripotent stem cells.

    PubMed

    Imamura, Masanori; Hikabe, Orie; Lin, Zachary Yu-Ching; Okano, Hideyuki

    2014-01-01

    Induced pluripotent stem cells (iPSCs) are stem cells that can be artificially generated via "cellular reprogramming" using gene transduction in somatic cells. iPSCs have enormous potential in stem-cell biology as they can give rise to numerous cell lineages, including the three germ layers. An evaluation of germ-line competency by blastocyst injection or tetraploid complementation, however, is critical for determining the developmental potential of mouse iPSCs towards germ cells. Recent studies have demonstrated that primordial germ cells obtained by the in vitro differentiation of iPSCs produce functional gametes as well as healthy offspring. These findings illustrate not only that iPSCs are developmentally similar to embryonic stem cells (ESCs), but also that somatic cells from adult tissues can produce gametes in vitro, that is, if they are reprogrammed into iPSCs. In this review, we discuss past and recent advances in the in vitro differentiation of germ cells using pluripotent stem cells, with an emphasis on ESCs and iPSCs. While this field of research is still at a stage of infancy, it holds great promises for investigating the mechanisms of germ-cell development, especially in humans, and for advancing reproductive and developmental engineering technologies in the future. © 2013 Wiley Periodicals, Inc.

  16. Stage-dependent DAZL localization in stallion germ cells.

    PubMed

    Jung, H J; Song, H; Yoon, M J

    2014-06-10

    Deleted in azoospermia-like (DAZL) is used as a germ cell marker in several species, including mice, rats, pigs, rhesus monkeys, bulls, and humans. Our objectives with this study were to investigate DAZL expression in stallion germ cells by using immunofluorescence, immunocytochemistry, and western blotting, and to determine the effects of reproductive stage and breeding season on the DAZL-positive cell population in seminiferous tubule cross sections. Testes were obtained during routine castration procedures at a large animal clinic and routine field service castration. The reproductive stage of the stallions was classified as pre-pubertal (<1 yr), pubertal (1-1.5 yr), post-pubertal (2-3 yr), or adult (4-8 yr). Using immunofluorescent staining, we showed that DAZL is localized to the cytoplasm of some, but not all, spermatogonia in pre-pubertal and pubertal horses. In the post-pubertal and adult testes, DAZL immunostaining was observed in spermatogonia proximal to the basement membrane of seminiferous tubules; however, few spermatogonia attached to the basement membrane were not immunolabeled. DAZL immunostaining was also observed in primary spermatocytes, but not in secondary spermatocytes, spermatids, or spermatozoa. DAZL protein was not detected in Leydig, Sertoli, or myoid cells of the testes at any reproductive stage. The immunocytochemistry analysis showed that DAZL immunolabeling was also localized to the cytoplasm of isolated germ cells such as spermatogonia or primary spermatocytes. We conclude that DAZL can be used as a marker of pre-meiotic germ cells in stallions. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Circulating tumor cells in patients with testicular germ cell tumors.

    PubMed

    Nastały, Paulina; Ruf, Christian; Becker, Pascal; Bednarz-Knoll, Natalia; Stoupiec, Małgorzata; Kavsur, Refik; Isbarn, Hendrik; Matthies, Cord; Wagner, Walter; Höppner, Dirk; Fisch, Margit; Bokemeyer, Carsten; Ahyai, Sascha; Honecker, Friedemann; Riethdorf, Sabine; Pantel, Klaus

    2014-07-15

    Germ cell tumors (GCTs) represent the most frequent malignancies among young men, but little is known about circulating tumor cells (CTCs) in these tumors. Considering their heterogeneity, CTCs were investigated using two independent assays targeting germ cell tumor and epithelial cell-specific markers, and results were correlated with disease stage, histology, and serum tumor markers. CTCs were enriched from peripheral blood (n = 143 patients) and testicular vein blood (TVB, n = 19 patients) using Ficoll density gradient centrifugation. For CTC detection, a combination of germ cell tumor (anti-SALL4, anti-OCT3/4) and epithelial cell-specific (anti-keratin, anti-EpCAM) antibodies was used. In parallel, 122 corresponding peripheral blood samples were analyzed using the CellSearch system. In total, CTCs were detected in 25 of 143 (17.5%) peripheral blood samples, whereas only 11.5% of patients were CTC-positive when considering exclusively the CellSearch assay. The presence of CTCs in peripheral blood correlated with clinical stage (P < 0.001) with 41% of CTC positivity in patients with metastasized tumors and 100% in patients with relapsed and chemotherapy-refractory disease. Histologically, CTC-positive patients suffered more frequently from nonseminomatous primary tumors (P < 0.001), with higher percentage of yolk sac (P < 0.001) and teratoma (P = 0.004) components. Furthermore, CTC detection was associated with elevated serum levels of α-fetoprotein (AFP; P = 0.025), β-human chorionic gonadotropin (βHCG; P = 0.002), and lactate dehydrogenase (LDH; P = 0.002). Incidence and numbers of CTCs in TVB were much higher than in peripheral blood. The inclusion of germ cell tumor-specific markers improves CTC detection in GCTs. CTCs occur frequently in patients with more aggressive disease, and there is a gradient of CTCs with decreasing numbers from the tumor-draining vein to the periphery. ©2014 American Association for Cancer Research.

  18. Multidimensional representations: The knowledge domain of germs held by students, teachers and medical professionals

    NASA Astrophysics Data System (ADS)

    Rua, Melissa Jo

    evident in the students' understandings and images of microbes. Students also viewed germs as a human problem rather than seeing microorganisms as an independent member of the ecosystem. Teachers' explanations about germs varied in explicitness based on the grade level they taught while medical professionals based their understandings on formal knowledge and tended to use explicit technical language in their explanations of the phenomena.

  19. Fertility-sparing surgery in advanced stage malignant ovarian germ cell tumor: a case report.

    PubMed

    Ghalleb, Montassar; Bouzaiene, Hatem; Slim, Skander; Hadiji, Achraf; Hechiche, Monia; Ben Hassouna, Jamel; Rahal, Khaled

    2017-12-17

    Malignant ovarian germ cell tumor is a rare type of disease, which generally has a good prognosis due to the high chemosensitivity of this type of tumor. Fertility preservation is an important issue because malignant ovarian germ cell tumor commonly affects young women. Although conservation is the standard for early stage, it becomes more debatable as the disease progresses to more advanced stages. Report the case of a patient with an International Federation of Gynecology and Obstetrics Stage IIIc malignant ovarian germ cell tumor, who had conservative surgery and chemotherapy with a good fertility outcome. A 23-year-old North African woman with a left malignant ovarian germ cell tumor stage IIIc was treated by left adnexectomy and omentectomy followed by chemotherapy. A 15-year follow-up showed no signs of relapse, and she completed three full-term natural pregnancies. Malignant ovarian germ cell tumor is a rare ovarian tumor with a good prognosis. It is usually associated with a good fertility outcome in early stages. However, due to the rarity of the disease in advanced stages, the fertility outcome for this group of patients is not clear. This lack of data surrounding advanced stages points to the need for a meta-analysis of all published cases.

  20. Intracranial baroreflex yielding an early cushing response in human.

    PubMed

    Schmidt, E A; Czosnyka, Z; Momjian, S; Czosnyka, M; Bech, R A; Pickard, J D

    2005-01-01

    The Cushing response is a pre-terminal sympatho-adrenal systemic response to very high ICP. Animal studies have demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response. Infusion studies are routine procedures to investigate, by infusing CSF space with saline, the cerebrospinal fluid (CSF) biophysics in patients suspected of hydrocephalus. Our study aims at assessing systemic and cerebral haemodynamic changes during moderate rise of ICP in human. Infusion studies were performed in 34 patients. This is a routine test perform in patients presenting with symptoms of NPH during their pre-shunting assessment. Arterial blood pressure (ABP) and cerebral blood flow velocity (FV) were non-invasively monitored with photoplethysmography and transcranial Doppler. The rise in ICP (8.2 +/- 5.1 mmHg to 25 +/- 8.3 mmHg) was followed by a significant rise in ABP (106.6 +/- 29.7 mmHg to 115.2 +/- 30.1 mmHg), drop in CPP (98.3 +/- 29 mmHg to 90.2 +/- 30.7 mmHg) and decrease in FV (55.6 +/- 17 cm/s to 51.1 +/- 16.3 cm/s). Increasing ICP did not alter heart rate (70.4 +/- 10.4/min to 70.3 +/- 9.1/min) but augmented the heart rate variance (0.046 +/- 0.058 to 0.067 +/- 0.075/min). In a population suspected of hydrocephalus, our study demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response, demonstrating an early Cushing response in human and a putative intracranial baroreflex.

  1. An Organismal CNV Mutator Phenotype Restricted to Early Human Development.

    PubMed

    Liu, Pengfei; Yuan, Bo; Carvalho, Claudia M B; Wuster, Arthur; Walter, Klaudia; Zhang, Ling; Gambin, Tomasz; Chong, Zechen; Campbell, Ian M; Coban Akdemir, Zeynep; Gelowani, Violet; Writzl, Karin; Bacino, Carlos A; Lindsay, Sarah J; Withers, Marjorie; Gonzaga-Jauregui, Claudia; Wiszniewska, Joanna; Scull, Jennifer; Stankiewicz, Paweł; Jhangiani, Shalini N; Muzny, Donna M; Zhang, Feng; Chen, Ken; Gibbs, Richard A; Rautenstrauss, Bernd; Cheung, Sau Wai; Smith, Janice; Breman, Amy; Shaw, Chad A; Patel, Ankita; Hurles, Matthew E; Lupski, James R

    2017-02-23

    De novo copy number variants (dnCNVs) arising at multiple loci in a personal genome have usually been considered to reflect cancer somatic genomic instabilities. We describe a multiple dnCNV (MdnCNV) phenomenon in which individuals with genomic disorders carry five to ten constitutional dnCNVs. These CNVs originate from independent formation incidences, are predominantly tandem duplications or complex gains, exhibit breakpoint junction features reminiscent of replicative repair, and show increased de novo point mutations flanking the rearrangement junctions. The active CNV mutation shower appears to be restricted to a transient perizygotic period. We propose that a defect in the CNV formation process is responsible for the "CNV-mutator state," and this state is dampened after early embryogenesis. The constitutional MdnCNV phenomenon resembles chromosomal instability in various cancers. Investigations of this phenomenon may provide unique access to understanding genomic disorders, structural variant mutagenesis, human evolution, and cancer biology. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

    ClinicalTrials.gov

    2017-12-07

    Childhood Embryonal Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Germ Cell Tumor; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma

  3. Characterization, isolation and culture of primordial germ cells in domestic animals: recent progress and insights from the ovine species.

    PubMed

    Ledda, S; Bogliolo, L; Bebbere, D; Ariu, F; Pirino, S

    2010-09-01

    Primordial germ cell (PGC) allocation, characterization, lineage restriction, and differentiation have been extensively studied in the mouse. Murine PGC can be easily identified using markers as alkaline phosphatase content or the expression of pluripotent markers such as Pou5f1, Nanog, Sox2, Kit, SSEA1, and SSEA4. These tools allowed us to clarify certain aspects of the complex interactions of somatic and germinal cells in the establishment of the germ cell lineage, its segregation from the neighbouring somatic tissue, and the guidance mechanisms during migration that direct most of the germ cells into the genital ridges. Few data are available from other domestic animals and here we reported our preliminary studies on the isolation, characterization, and in vitro culture of sheep PGCs. Sheep PGCs can be identified with the markers previously used in mouse, but, in some cases, these markers are not coherently expressed in the same cell depending on the grade of differentiation and on technical problems related to commercial antibodies used. Pluripotency of PGCs in culture (EGCs) from domestic animals also needs further evaluation even though the derivation of embryonic pluripotent cell lines from large mammals may be an advantage as they are more physiologically similar to the human and perhaps more relevant for clinical translation studies. Comprehensive epigenetic reprogramming of the genome in early germ cells, and derived EGCs including extensive erasure of epigenetic modifications, may be relevant for gaining insight into events that lead to reprogramming and establishment of totipotency. EGCs can differentiate in vitro in a various range of tissues, form embryonic bodies, but in many cases failed to generate tumours when transplanted into immunodeficient mice and are not able to generate germline chimeric animals after their transfer. Such incomplete information clearly indicates the urge to improve the studies on derivation of stem cells in farm animals and

  4. Early Human Occupation on the Northeast Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Rhode, D.; Madsen, D.; Brantingham, P.; Perrault, C.

    2010-12-01

    The Tibetan Plateau presents great challenges for human occupation: low oxygen, high ultraviolet radiation, harsh seasonal climate, low overall biological productivity. How and when early humans were able to cope physiologically, genetically, and behaviorally with these extremes is important for understanding the history of human adaptive flexibility. Our investigations of prehistoric human settlement on the northeast Tibetan Plateau focus on (a) establishing well-dated evidence for occupation of altitudes >3000 m, (b) the environmental context of high altitude adaptation, and (c) relations of hunting and pastoralism to lower-altitude agrarian systems. We observe two major prehistoric settlement patterns in the Qinghai Lake area. The earliest, ~15,000-7500 yr old, consists of small isolated firehearths with sparse associated stone tools and wild mammal remains (1). Numerous hearths often occur in the same localities, indicating repeated short-duration occupations by small hunting parties. A second pattern, ~9000-4000 yr old, was established during the Holocene climatic optimum. These sites represent prolonged seasonal residential occupation, containing dark anthropogenic midden, hearth and pit constructions, abundant stone tools, occasional ceramics, and abundant diverse faunal remains (including medium-large mammals but lacking domestic sheep/yak)(2). These Plateau-margin base camps allowed greater intensity of use of the high Plateau. Residential occupation was strongly influenced by nearby lower-altitude farming communities; development of the socioeconomic landscape along the Yellow River likely played at least as great a role in Plateau occupation patterns as did Holocene environmental changes. Holocene vegetation changes in the NE Tibetan Plateau have been attributed to climate (3) or anthropogenic modification (4). Our results document changes in shrub/tree presence from ~12,000-4000 BP, similar to pollen records, that likely reflect climate rather than

  5. Intratubular Germ Cell Neoplasia of the Testis, Bilateral Testicular Cancer, and Aberrant Histologies.

    PubMed

    Sharma, Pranav; Dhillon, Jasreman; Sexton, Wade J

    2015-08-01

    Intratubular germ cell neoplasia (ITGCN) is a precursor lesion for testicular germ cell tumors, most of which are early stage. ITGCN is also associated with testicular cancer or ITGCN in the contralateral testis, leading to a risk of bilateral testicular malignancy. Testicular biopsy detects most cases, and orchiectomy is the treatment of choice in patients with unilateral ITGCN. Low-dose radiation therapy is recommended in patients with bilateral ITGCN or ITGCN in the solitary testis, but the long-term risks of infertility and hypogonadism need to be discussed with the patient. Rare histologies of primary testicular cancer are also discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Testicular histology and germ cell cytology during spermatogenesis in the Mississippi map turtle, Graptemys pseudogeographica kohnii, from Northeast Arkansas.

    PubMed

    Lancaster, Kelsey; Trauth, Stanley E; Gribbins, Kevin M

    2014-01-01

    The testicular histology and cytology of spermatogenesis in Graptemys pseudogeographica kohnii were examined using specimens collected between July 1996 and May 2004 from counties in northeastern Arkansas. A histological examination of the testes and germ cell cytology indicates a postnuptial testicular cycle of spermatogenesis and a major fall spermiation event. The majority of the germ cell populations in May and June specimens are represented by resting spermatogonia, type A spermatogonia, type B spermatogonia, pre-leptotene spermatocytes, and numerous Sertoli cell nuclei near the basement membrane. The start of proliferation is evident as spermatogonia in metaphase are present near the basal lamina and many of these germ cells have entered meiosis in June seminiferous tubules. Major spermatogenic events occur in the June and July specimens and result in an increased height of the seminiferous epithelium and increased diameter of the seminiferous tubules. The germ cell population during this time is represented by spermatogonia (type A, B, and resting), hypertrophic cells, large populations of early primary spermatocytes, and early round spermatids. By September, the major germ cell population has progressed past meiosis with abundant round and early elongating spermatids dominating the seminiferous epithelium. October seminiferous epithelia are marked by a decreas in height and mature spermatozoa fill the luminal space. Round and elongating spermatids constitute the largest portion of the germ cell population. Following the spermiation event, the testes enter a period of quiescence that lasts till the next spermatogenic cycle, which begins in the subsequent spring. Based on the cytological development of the seminiferous tubules revealed by our study, Graptemys pseudogeographica kohnii demonstrates a temporal germ cell development strategy similar to other temperate reptiles. A single major generation of germ cells progresses through spermatogenesis each year

  7. Testicular histology and germ cell cytology during spermatogenesis in the Mississippi map turtle, Graptemys pseudogeographica kohnii, from Northeast Arkansas

    PubMed Central

    Lancaster, Kelsey; Trauth, Stanley E; Gribbins, Kevin M

    2014-01-01

    The testicular histology and cytology of spermatogenesis in Graptemys pseudogeographica kohnii were examined using specimens collected between July 1996 and May 2004 from counties in northeastern Arkansas. A histological examination of the testes and germ cell cytology indicates a postnuptial testicular cycle of spermatogenesis and a major fall spermiation event. The majority of the germ cell populations in May and June specimens are represented by resting spermatogonia, type A spermatogonia, type B spermatogonia, pre-leptotene spermatocytes, and numerous Sertoli cell nuclei near the basement membrane. The start of proliferation is evident as spermatogonia in metaphase are present near the basal lamina and many of these germ cells have entered meiosis in June seminiferous tubules. Major spermatogenic events occur in the June and July specimens and result in an increased height of the seminiferous epithelium and increased diameter of the seminiferous tubules. The germ cell population during this time is represented by spermatogonia (type A, B, and resting), hypertrophic cells, large populations of early primary spermatocytes, and early round spermatids. By September, the major germ cell population has progressed past meiosis with abundant round and early elongating spermatids dominating the seminiferous epithelium. October seminiferous epithelia are marked by a decreas in height and mature spermatozoa fill the luminal space. Round and elongating spermatids constitute the largest portion of the germ cell population. Following the spermiation event, the testes enter a period of quiescence that lasts till the next spermatogenic cycle, which begins in the subsequent spring. Based on the cytological development of the seminiferous tubules revealed by our study, Graptemys pseudogeographica kohnii demonstrates a temporal germ cell development strategy similar to other temperate reptiles. A single major generation of germ cells progresses through spermatogenesis each year

  8. Gender differences in the induction of chromosomal aberrations and gene mutations in rodent germ cells

    SciT

    Adler, Ilse-Dore; Carere, Angelo; Eichenlaub-Ritter, Ursula

    2007-05-15

    Germ cell mutagenicity testing provides experimental data to quantify genetic risk for exposed human populations. The majority of tests are performed with exposure of males, and female data are relatively rare. The reason for this paucity lies in the differences between male and female germ cell biology. Male germ cells are produced throughout reproductive life and all developmental stages can be ascertained by appropriate breeding schemes. In contrast, the female germ cell pool is limited, meiosis begins during embryogenesis and oocytes are arrested over long periods of time until maturation processes start for small numbers of oocytes during the oestrusmore » cycle in mature females. The literature data are reviewed to point out possible gender differences of germ cells to exogenous agents such as chemicals or ionizing radiation. From the limited information, it can be concluded that male germ cells are more sensitive than female germ cells to the induction of chromosomal aberrations and gene mutations. However, exceptions are described which shed doubt on the extrapolation of experimental data from male rodents to the genetic risk of the human population. Furthermore, the female genome may be more sensitive to mutation induction during peri-conceptional stages compared to the male genome of the zygote. With few exceptions, germ cell experiments have been carried out under high acute exposure to optimize the effects and to compensate for the limited sample size in animal experiments. Human exposure to environmental agents, on the other hand, is usually chronic and involves low doses. Under these conditions, gender differences may become apparent that have not been studied so far. Additionally, data are reviewed that suggest a false impression of safety when responses are negative under high acute exposure of male rodents while a mutational response is induced by low chronic exposure. The classical (morphological) germ cell mutation tests are not performed

  9. Germ stem cells are active in postnatal mouse ovary under physiological conditions

    PubMed Central

    Guo, Kun; Li, Chao-hui; Wang, Xin-yi; He, Da-jian; Zheng, Ping

    2016-01-01

    STUDY HYPOTHESIS Are active ovarian germ stem cells present in postnatal mouse ovaries under physiological conditions? STUDY FINDING Active ovarian germ stem cells exist and function in adult mouse ovaries under physiological conditions. WHAT IS KNOWN ALREADY In vitro studies suggested the existence of germ stem cells in postnatal ovaries of mouse, pig and human. However, in vivo studies provided evidence against the existence of active germ stem cells in postnatal mouse ovaries. Thus, it remains controversial whether such germ stem cells really exist and function in vivo in postnatal mammalian ovaries. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Octamer-binding transcription factor 4 (Oct4)-MerCreMer transgenic mice were crossed with R26R-enhanced yellow fluorescent protein (EYFP) mice to establish a tamoxifen-inducible tracing system so that Oct4-expressing potential ovarian germ stem cells in young adult mice (5–6 weeks old) can be labeled with EYFP. The germ cell activities of DNA replication, mitotic division, entry into meiosis and progression to primordial follicle stage were investigated by means of immunofluorescent staining of ovarian tissues collected at different time points post-tamoxifen injection (1 day, 3 days, 2 months and 4 months). Meiosis entry and primordial follicle formation were also measured by EYFP-labeled single-cell RT–PCR. Germ cell proliferation and mitotic division were examined through 5-bromodeoxyuridine triphosphate incorporation assay. At each time point, ovaries from two to three animals were used for each set of experiment. MAIN RESULTS AND THE ROLE OF CHANCE By labeling the Oct4-expressing small germ cells and tracing their fates for up to 4 months, we observed persistent meiosis entry and primordial follicle replenishment. Furthermore, we captured the transient processes of mitotic DNA replication as well as mitotic division of the marked germ cells at various time periods after tracing. These lines of evidence unambiguously

  10. Differentiation of female Oct4-GFP embryonic stem cells into germ lineage cells.

    PubMed

    Ma, Xin; Li, Peng; Sun, Xiang; Sun, Yifeng; Hu, Rong; Yuan, Ping

    2018-04-01

    Due to high infertility ratio nowadays, it is essential to explore efficient ways of enhancing mammalian reproductivity, in particular female reproductivity. Using female Oct4-GFP embryonic stem cells, we mimic the in vivo development procedure to induce ES cells into epiblast cell-like cells (EpiLCs) and then primordial germ cell-like cells (PGCLCs). GFP positive PGCLCs that showed typical PGC markers and epigenetic modification were efficiently obtained. Further transplantation of the GFP positive PGCLC and native ovary cell mixture into ovary of infertile mice revealed that both MVH and GFP positive cells could be developed in ovary, but no later developmental stage germ cells were observed. This study suggested that Oct4-GFP ES cells may be only suitable for tracing early germ cell development. © 2018 International Federation for Cell Biology.

  11. "Life in a Germ-Free World":

    PubMed Central

    Kirk, Robert G. W.

    2012-01-01

    Summary: This article examines a specific technology, the germ-free "isolator," tracing its development across three sites: (1) the laboratory for the production of standard laboratory animals, (2) agriculture for the efficient production of farm animals, and (3) the hospital for the control and prevention of cross-infection and the protection of individuals from infection. Germ-free technology traveled across the laboratory sciences, clinical and veterinary medicine, and industry, yet failed to become institutionalized outside the laboratory. That germ-free technology worked was not at issue. Working, however, was not enough. Examining the history of a technology that failed to find widespread application reveals the labor involved in aligning cultural, societal, and material factors necessary for successful medical innovation. PMID:23000838

  12. [Germ cell membrane lipids in spermatogenesis].

    PubMed

    Wang, Ting; Shi, Xiao; Quan, Song

    2016-05-01

    Spermatogenesis is a complex developmental process in which a diploid progenitor germ cell transforms into highly specialized spermatozoa. During spermatogenesis, membrane remodeling takes place, and cell membrane permeability and liquidity undergo phase-specific changes, which are all associated with the alteration of membrane lipids. Lipids are important components of the germ cell membrane, whose volume and ratio fluctuate in different phases of spermatogenesis. Abnormal lipid metabolism can cause spermatogenic dysfunction and consequently male infertility. Germ cell membrane lipids are mainly composed of cholesterol, phospholipids and glycolipids, which play critical roles in cell adhesion and signal transduction during spermatogenesis. An insight into the correlation of membrane lipids with spermatogenesis helps us to better understand the mechanisms of spermatogenesis and provide new approaches to the diagnosis and treatment of male infertility.

  13. Key apoptotic pathways for heat-induced programmed germ cell death in the testis.

    PubMed

    Hikim, Amiya P Sinha; Lue, Yanhe; Yamamoto, Cindy M; Vera, Yanira; Rodriguez, Susana; Yen, Pauline H; Soeng, Kevin; Wang, Christina; Swerdloff, Ronald S

    2003-07-01

    Short-term exposure (43 C for 15 min) of the rat testis to mild heat results within 6 h in stage- and cell-specific activation of germ cell apoptosis. Initiation of apoptosis was preceded by a redistribution of Bax from a cytoplasmic to paranuclear localization in heat-susceptible germ cells. Here we show that the relocation of Bax is accompanied by cytosolic translocation of cytochrome c and is associated with activation of the initiator caspase 9 and the executioner caspases 3, 6, and 7 and cleavage of poly(ADP) ribose polymerase. Furthermore, early in apoptosis, a significant amount of Bax also accumulates in endoplasmic reticulum, as assessed by Western blot analyses of fractionated testicular lysates. In additional studies using the FasL-defective gld mice, we have shown that heat-induced germ cell apoptosis is not blocked, thus providing evidence that the Fas signaling system may be dispensable for heat-induced germ cell apoptosis in the testis. Taken together, these results demonstrate that the mitochondria- and possibly also endoplasmic reticulum-dependent pathways are the key apoptotic pathways for heat-induced germ cell death in the testis.

  14. EMMPRIN (basigin/CD147) is involved in the morphogenesis of tooth germ in mouse molars.

    PubMed

    Xie, Ming; Jiao, Ting; Chen, Yuqin; Xu, Chun; Li, Jing; Jiang, Xinquan; Zhang, Fuqiang

    2010-05-01

    The pattern of gene expression for extracellular matrix metalloproteinase inducer (EMMPRIN) was revealed in the tooth germ of mouse mandibular molars using quantitative real-time PCR. In situ hybridization and immunohistochemical study demonstrated the characteristic distribution of EMMPRIN in the different stages of tooth germ development. To investigate the functional role played by EMMPRIN in tooth germ development, EMMPRIN siRNA interference approach was carried out in cultured mouse mandibles at embryonic day 11.0 (E11.0). The results showed that EMMPRIN siRNA-treated explants exhibited a marked growth inhibition of tooth germ compared to the control and scrambled siRNA-treated explants. Meanwhile, a significant increase in MT1-MMP mRNA expression and a reduction in MMP-2, MMP-3, MMP-9, MMP-13 and MT2-MMP mRNA expression were observed in the mouse mandibles following EMMPRIN abrogation. The current results indicate that EMMPRIN could thus be involved in the early stage of tooth germ development and morphogenesis, possibly by regulating the expression of MMP genes.

  15. Zebrafish Staufen1 and Staufen2 are required for the survival and migration of primordial germ cells.

    PubMed

    Ramasamy, Srinivas; Wang, Hui; Quach, Helen Ngoc Bao; Sampath, Karuna

    2006-04-15

    In sexually reproducing organisms, primordial germ cells (PGCs) give rise to the cells of the germ line, the gametes. In many animals, PGCs are set apart from somatic cells early during embryogenesis. Work in Drosophila, C. elegans, Xenopus, and zebrafish has shown that maternally provided localized cytoplasmic determinants specify the germ line in these organisms (Raz, E., 2003. Primordial germ-cell development: the zebrafish perspective. Nat. Rev., Genet. 4, 690--700; Santos, A.C., Lehmann, R., 2004. Germ cell specification and migration in Drosophila and beyond. Curr. Biol. 14, R578-R589). The Drosophila RNA-binding protein, Staufen is required for germ cell formation, and mutations in stau result in a maternal effect grandchild-less phenotype (Schupbach,T., Weischaus, E., 1989. Female sterile mutations on the second chromosome of Drosophila melanogaster:1. Maternal effect mutations. Genetics 121, 101-17). Here we describe the functions of two zebrafish Staufen-related proteins, Stau1 and Stau2. When Stau1 or Stau2 functions are compromised in embryos by injecting antisense morpholino modified oligonucleotides or dominant-negative Stau peptides, germ layer patterning is not affected. However, expression of the PGC marker vasa is not maintained. Furthermore, expression of a green fluorescent protein (GFP):nanos 3'UTR fusion protein in germ cells shows that PGC migration is aberrant, and the mis-migrating PGCs do not survive in Stau-compromised embryos. Stau2 is also required for survival of neurons in the central nervous system (CNS). These phenotypes are rescued by co-injection of Drosophila stau mRNA. Thus, staufen has an evolutionarily conserved function in germ cells. In addition, we have identified a function for Stau proteins in PGC migration.

  16. Male Rat Germ Cells Display Age-Dependent and Cell-Specific Susceptibility in Response to Oxidative Stress Challenges1

    PubMed Central

    Selvaratnam, Johanna; Paul, Catriona; Robaire, Bernard

    2015-01-01

    For decades male germ cells were considered unaffected by aging, due to the fact that males continue to generate sperm into old age; however, evidence indicates that germ cells from aged males are of lower quality than those of young males. The current study examines the effects of aging on pachytene spermatocytes and round spermatids, and is the first study to culture these cells in isolation for an extended period. Our objective is to determine the cell-specific responses germ cells have to aging and oxidative insult. Culturing isolated germ cells from young and aged Brown Norway rats revealed that germ cells from aged males displayed an earlier decline in viability, elevated levels of reactive oxygen species (ROS), and increased spermatocyte DNA damage, compared to young males. Furthermore, oxidative insult by prooxidant 3-morpholinosydnonimine provides insight into how spermatocytes and spermatids manage excess ROS. Genome-wide microarray analyses revealed that several transcripts for antioxidants, Sod1, Cat, and Prdxs, were up-regulated in response to ROS in germ cells from young males while being expressed at lower levels in the aged. In contrast, the expression of DNA damage repair genes Rad50 and Atm were increased in the germ cells from aged animals. Our data indicate that as germ cells undergo spermatogenesis, they adapt and respond to oxidative stress differently, depending on their phase of development, and the process of aging results in redox dysfunction. Thus, even at early stages of spermatogenesis, germ cells from aged males are unable to mount an appropriate response to manage oxidative stress. PMID:26224006

  17. Perspectives on testicular germ cell neoplasms.

    PubMed

    Cheng, Liang; Lyu, Bingjian; Roth, Lawrence M

    2017-01-01

    Our knowledge of testicular germ cell neoplasms has progressed in the last few decades due to the description of germ cell neoplasia in situ (GCNIS) and a variety of specific forms of intratubular germ cell neoplasia, the discovery of isochromosome 12p and its importance in the development of invasiveness in germ cell tumors (GCTs), the identification of specific transcription factors for GCTs, and the recognition that a teratomatous component in mixed GCT represents terminal differentiation. Isochromosome 12p and 12p overrepresentation, collectively referred to as 12p amplification, are fundamental abnormalities that account for many types of malignant GCTs of the testis. Embryonal carcinoma is common in the testis but rare in the ovary, whereas the converse is true for mature cystic teratoma. Spermatocytic tumor occurs only in the testis; it has not been described in the ovary or extragonadal sites. The origin of ovarian mature cystic teratoma is similar to that of prepubertal-type testicular teratoma and dermoid cyst at any age in that it arises from a nontransformed germ cell, whereas postpubertal-type testicular teratoma arises from a malignant germ cell, most commonly through the intermediary of GCNIS. Somatic neoplasms, often referred to as monodermal teratomas, arise not infrequently from mature cystic teratoma of the ovary, whereas such neoplasms are rare in testicular teratoma with the exception of carcinoid. Integration of classical morphologic observations and emerging novel molecular studies will result in better understanding of the pathogenesis of GCTs and will optimize patient therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. The effects of humanin and its analogues on male germ cell apoptosis induced by chemotherapeutic drugs.

    PubMed

    Jia, Yue; Ohanyan, Aikoui; Lue, Yan-He; Swerdloff, Ronald S; Liu, Peter Y; Cohen, Pinchas; Wang, Christina

    2015-04-01

    Human (HN) prevents stress-induced apoptosis in many cells/tissues. In this study we showed that HN ameliorated chemotherapy [cyclophosphamide (CP) and Doxorubicin (DOX)]-induced male germ cell apoptosis both ex vivo in seminiferous tubule cultures and in vivo in the testis. HN acts by several putative mechanisms via binding to: an IL-12 like trimeric membrane receptor; BAX; or insulin-like growth factor binding protein-3 (IGFBP-3, a proapoptotic factor). To understand the mechanisms of HN on male germ cell apoptosis, we studied five HN analogues including: HNG (HN-S14G, a potent agonist), HNG-F6A (no binding to IGFBP-3), HN-S7A (no self-dimerization), HN-C8P (no binding to BAX), and HN-L12A (a HN antagonist) on CP-induced male germ cell apoptosis in mice. CP-induced germ cell apoptosis was inhibited by HN, HNG, HNG-F6A, HN-S7A, and HN-C8P (less effective); but not by HN-L12A. HN-L12A, but not HN-S7A or HN-C8P, blocked the protective effect of HN against CP-induced male germ cell apoptosis. HN, HN-S7A, and HN-C8P restored CP-suppressed STAT3 phosphorylation. These results suggest that HN: (1) decreases DOX (ex vivo) and CP (in vivo) induced male germ cell apoptosis; (2) action is mediated by the membrane receptor/STAT3 with minor contribution by BAX-binding pathway; (3) self-dimerization or binding to IGFBP-3 may not be involved in HN's effect in testis. HN is an important molecule in the regulation of germ cell homeostasis after injury and agonistic analogues may be developed for treating male infertility or protection against chemotherapy side effects.

  19. The Effects of Humanin and Its Analogues on Male Germ Cell Apoptosis Induced by Chemotherapeutic Drugs

    PubMed Central

    Jia, Yue; Ohanyan, Aikoui; Lue, Yan-He; Swerdloff, Ronald S.; Liu, Peter Y.; Cohen, Pinchas; Wang, Christina

    2015-01-01

    Human (HN) prevents stress-induced apoptosis in many cells/tissues. In this study we showed that HN ameliorated chemotherapy (Cyclophosphamide, CP and Doxorubicin, DOX)-induced male germ cell apoptosis both ex vivo in seminiferous tubule cultures and in vivo in the testis. HN acts by several putative mechanisms via binding to: an IL-12 like trimeric membrane receptor; BAX; or Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3, a proapoptotic factor). To understand the mechanisms of HN on male germ cell apoptosis, we studied five HN analogues including: HNG (HN-S14G, a potent agonist), HNG-F6A (no binding to IGFBP-3), HN-S7A (no self-dimerization), HN-C8P (no binding to BAX), and HN-L12A (a HN antagonist) on CP-induced male germ cell apoptosis in mice. CP-induced germ cell apoptosis was inhibited by HN, HNG, HNG-F6A, HN-S7A, and HN-C8P (less effective); but not by HN-L12A. HN-L12A, but not HN-S7A or HN-C8P, blocked the protective effect of HN against CP-induced male germ cell apoptosis. HN, HN-S7A, and HN-C8P restored CP-suppressed STAT3 phosphorylation. These results suggest that HN: 1) decreases DOX (ex vivo) and CP (in vivo) induced male germ cell apoptosis; 2) action is mediated by the membrane receptor/STAT3 with minor contribution by BAX-binding pathway; 3) self-dimerization or binding to IGFBP-3 may not be involved in HN’s effect in testis. HN is an important molecule in the regulation of germ cell homeostasis after injury and agonistic analogues may be developed for treating male infertility or protection against chemotherapy side effects. PMID:25666707

  20. Histone modifications in the male germ line of Drosophila.

    PubMed

    Hennig, Wolfgang; Weyrich, Alexandra

    2013-02-22

    In the male germ line of Drosophila chromatin remains decondensed and highly transcribed during meiotic prophase until it is rapidly compacted. A large proportion of the cell cycle-regulated histone H3.1 is replaced by H3.3, a histone variant encoded outside the histone repeat cluster and not subject to cell cycle controlled expression. We investigated histone modification patterns in testes of D. melanogaster and D. hydei. In somatic cells of the testis envelope and in germ cells these modification patterns differ from those typically seen in eu- and heterochromatin of other somatic cells. During the meiotic prophase some modifications expected in active chromatin are not found or are found at low level. The absence of H4K16ac suggests that dosage compensation does not take place. Certain histone modifications correspond to either the cell cycle-regulated histone H3.1 or to the testis-specific variant H3.3. In spermatogonia we found H3K9 methylation in cytoplasmic histones, most likely corresponding to the H3.3 histone variant. Most histone modifications persist throughout the meiotic divisions. The majority of modifications persist until the early spermatid nuclei, and only a minority further persist until the final chromatin compaction stages before individualization of the spermatozoa. Histone modification patterns in the male germ line differ from expected patterns. They are consistent with an absence of dosage compensation of the X chromosome during the male meiotic prophase. The cell cycle-regulated histone variant H3.1 and H3.3, expressed throughout the cell cycle, also vary in their modification patterns. Postmeiotically, we observed a highly complex pattern of the histone modifications until late spermatid nuclear elongation stages. This may be in part due to postmeiotic transcription and in part to differential histone replacement during chromatin condensation.

  1. General Information about Childhood Extracranial Germ Cell Tumors

    MedlinePlus

    ... Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Childhood Extracranial Germ Cell Tumors Go to ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  2. Treatment Options By Stage (Ovarian Germ Cell Tumors)

    MedlinePlus

    ... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview ... types of treatment for patients with ovarian germ cell tumors. Different types of treatment are available for ...

  3. FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

    SciT

    Sui, Lina, E-mail: linasui@vub.ac.be; Mfopou, Josue K.; Geens, Mieke

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer Deep study the FGF signaling role during DE specification in the context of hESCs. Black-Right-Pointing-Pointer DE differentiation from hESCs has an early dependence on FGF signaling. Black-Right-Pointing-Pointer A serum-free DE protocol is developed based on the findings. Black-Right-Pointing-Pointer The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study,more » we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.« less

  4. Sexual dimorphic expression of dnd in germ cells during sex reversal and its requirement for primordial germ cell survival in protogynous hermaphroditic grouper.

    PubMed

    Sun, Zhi-Hui; Zhou, Li; Li, Zhi; Liu, Xiao-Chun; Li, Shui-Sheng; Wang, Yang; Gui, Jian-Fang

    2017-06-01

    Dead end (dnd), vertebrate-specific germ cell marker, had been demonstrated to be essential for primordial germ cell (PGC) migration and survival, and the link between PGC number and sex change had been revealed in some teleost species, but little is known about dnd in hermaphroditic vertebrates. In the present study, a protogynous hermaphroditic orange-spotted grouper (Epinephelus coioides) dnd homologue (Ecdnd) was identified and characterized. Quantitative real-time PCR and in situ hybridization analysis revealed a dynamic and sexually dimorphic expression pattern in PGCs and germ cells of gonads. During sex changing, the Ecdnd transcript sharply increased in early transitional gonad, reached the highest level at late transitional gonad stage, and decreased after testis maturation. Visualization of zebrafish PGCs by injecting with RFP-Ecdnd-3'UTR RNA and GFP-zfnanos3-3'UTR RNA confirmed importance of Ecdnd 3'UTR for the PGC distribution. In addition, knockdown of EcDnd by using antisense morpholinos (MO) caused the ablation of PGCs in orange-spotted grouper. Therefore, the current data indicate that Ecdnd is essential for PGCs survival and may serve as a useful germ cell marker during gametogenesis in hermaphroditic grouper. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Quantification of healthy and atretic germ cells and follicles in the developing and post-natal ovary of the South American plains vizcacha, Lagostomus maximus: evidence of continuous rise of the germinal reserve.

    PubMed

    Inserra, P I F; Leopardo, N P; Willis, M A; Freysselinard, A L; Vitullo, A D

    2014-02-01

    The female germ line in mammals is subjected to massive cell death that eliminates 60-85% of the germinal reserve by birth and continues from birth to adulthood until the exhaustion of the germinal pool. Germ cell demise occurs mainly through apoptosis by means of a biased expression in favour of pro-apoptotic members of the BCL2 gene family. By contrast, the South American plains vizcacha, Lagostomus maximus, exhibits sustained expression of the anti-apoptotic BCL2 gene throughout gestation and a low incidence of germ cell apoptosis. This led to the proposal that, in the absence of death mechanisms other than apoptosis, the female germ line should increase continuously from foetal life until after birth. In this study, we quantified all healthy germ cells and follicles in the ovaries of L. maximus from early foetal life to day 60 after birth using unbiased stereological methods and detected apoptosis by labelling with TUNEL assay. The healthy germ cell population increased continuously from early-developing ovary reaching a 50 times higher population number by the end of gestation. TUNEL-positive germ cells were <0.5% of the germ cell number, except at mid-gestation (3.62%). Mitotic proliferation, entrance into prophase I stage and primordial follicle formation occurred as overlapping processes from early pregnancy to birth. Germ cell number remained constant in early post-natal life, but a remnant population of non-follicular VASA- and PCNA-positive germ cells still persisted at post-natal day 60. L. maximus is the first mammal so far described in which female germ line develops in the absence of constitutive massive germ cell elimination.

  6. Extragonadal Germ Cell Tumors—Health Professional Version

    Cancer.gov

    Extragonadal germ cell tumors are rare and account for only a small percentage of all germ cell tumors. However, the true incidence of these tumors may be higher than originally thought because of failure to diagnose them properly. Find evidence-based information on extragonadal germ cell tumors treatment.

  7. Extracranial Germ Cell Tumors—Health Professional Version

    Cancer.gov

    Extracranial germ cell tumors (GCTs) arise from primordial germ cells, which migrate during embryogenesis from the yolk sac to the gonads. Childhood extracranial GCTs can be divided into the following two types: gonadal, and extragonadal. Find evidence-based information on extracranial germ cell tumors treatment.

  8. Improvement of dry fractionation ethanol fermentation by partial germ supplementation

    Ethanol fermentation of dry fractionated grits (corn endosperm pieces) containing different levels of germ was studied using the dry grind process. Partial removal of germ fraction allows for marketing the germ fraction and potentially more efficient fermentation. Grits obtained from a dry milling p...

  9. The early Upper Paleolithic human skeleton from the Abrigo do Lagar Velho (Portugal) and modern human emergence in Iberia

    PubMed Central

    Duarte, Cidália; Maurício, João; Pettitt, Paul B.; Souto, Pedro; Trinkaus, Erik; van der Plicht, Hans; Zilhão, João

    1999-01-01

    The discovery of an early Upper Paleolithic human burial at the Abrigo do Lagar Velho, Portugal, has provided evidence of early modern humans from southern Iberia. The remains, the largely complete skeleton of a ≈4-year-old child buried with pierced shell and red ochre, is dated to ca. 24,500 years B.P. The cranium, mandible, dentition, and postcrania present a mosaic of European early modern human and Neandertal features. The temporal bone has an intermediate-sized juxtamastoid eminence. The mandibular mentum osseum and the dental size and proportions, supported by mandibular ramal features, radial tuberosity orientation, and diaphyseal curvature, as well as the pubic proportions align the skeleton with early modern humans. Body proportions, reflected in femorotibial lengths and diaphyseal robusticity plus tibial condylar displacement, as well as mandibular symphyseal retreat and thoracohumeral muscle insertions, align the skeleton with the Neandertals. This morphological mosaic indicates admixture between regional Neandertals and early modern humans dispersing into southern Iberia. It establishes the complexities of the Late Pleistocene emergence of modern humans and refutes strict replacement models of modern human origins. PMID:10377462

  10. Colleges Put the Squeeze on Germs

    ERIC Educational Resources Information Center

    Sander, Libby

    2008-01-01

    A spirited campaign to promote "hand hygiene" is under way at the University of Central Florida Orlando campus, and the urinal toter, known as UCF 5th Guy, is its front line. Like their counterparts at many other institutions, health officials at Central Florida want students to think about the germs that lurk on their hands. And then…

  11. Germ Smart: Children's Activities in Disease Prevention.

    ERIC Educational Resources Information Center

    Scheer, Judith K.

    This booklet is part of the "Children's Activity Series," a set of four supplemental teaching resources that promote awareness about health, family life, and cultural diversity for children in kindergarten through third grade. Nine activities are included in this booklet to help children be "germ smart" help children in kindergarten through third…

  12. Validation of an automated counting procedure for phthalate-induced testicular multinucleated germ cells

    EPA Science Inventory

    In utero exposure to certain phthalate esters results in testicular toxicity, characterized at the tissue level by induction of multinucleated germ cells (MNGs) in rat, mouse, and human fetal testis. Phthalate exposures also result in a decrease in testicular testosterone in rats...

  13. Environmentally Induced Transgenerational Epigenetic Reprogramming of Primordial Germ Cells and the Subsequent Germ Line

    PubMed Central

    Skinner, Michael K.; Haque, Carlos Guerrero-Bosagna M.; Nilsson, Eric; Bhandari, Ramji; McCarrey, John R.

    2013-01-01

    A number of environmental factors (e.g. toxicants) have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation) progeny in regards to the primordial germ cell (PGC) epigenetic reprogramming of the F3 generation (i.e. great-grandchildren). The F3 generation germline transcriptome and epigenome (DNA methylation) were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13) and after cord formation in the testis at embryonic day 16 (E16). A larger number of DNA methylation abnormalities (epimutations) and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided. PMID:23869203

  14. Maternal dazap2 Regulates Germ Granules by Counteracting Dynein in Zebrafish Primordial Germ Cells.

    PubMed

    Forbes, Meredyth M; Rothhämel, Sophie; Jenny, Andreas; Marlow, Florence L

    2015-07-07

    Primordial germ cells (PGCs) are the stem cells of the germline. Generally, germline induction occurs via zygotic factors or the inheritance of maternal determinants called germ plasm (GP). GP is packaged into ribonucleoprotein complexes within oocytes and later promotes the germline fate in embryos. Once PGCs are specified by either mechanism, GP components localize to perinuclear granular-like structures. Although components of zebrafish PGC germ granules have been studied, the maternal factors regulating their assembly and contribution to germ cell development are unknown. Here, we show that the scaffold protein Dazap2 binds to Bucky ball, an essential regulator of oocyte polarity and GP assembly, and colocalizes with the GP in oocytes and in PGCs. Mutational analysis revealed a requirement for maternal Dazap2 (MDazap2) in germ-granule maintenance. Through molecular epistasis analyses, we show that MDazap2 is epistatic to Tdrd7 and maintains germ granules in the embryonic germline by counteracting Dynein activity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Germ Cell-less Promotes Centrosome Segregation to Induce Germ Cell Formation.

    PubMed

    Lerit, Dorothy A; Shebelut, Conrad W; Lawlor, Kristen J; Rusan, Nasser M; Gavis, Elizabeth R; Schedl, Paul; Deshpande, Girish

    2017-01-24

    The primordial germ cells (PGCs) specified during embryogenesis serve as progenitors to the adult germline stem cells. In Drosophila, the proper specification and formation of PGCs require both centrosomes and germ plasm, which contains the germline determinants. Centrosomes are microtubule (MT)-organizing centers that ensure the faithful segregation of germ plasm into PGCs. To date, mechanisms that modulate centrosome behavior to engineer PGC development have remained elusive. Only one germ plasm component, Germ cell-less (Gcl), is known to play a role in PGC formation. Here, we show that Gcl engineers PGC formation by regulating centrosome dynamics. Loss of gcl leads to aberrant centrosome separation and elaboration of the astral MT network, resulting in inefficient germ plasm segregation and aborted PGC cellularization. Importantly, compromising centrosome separation alone is sufficient to mimic the gcl loss-of-function phenotypes. We conclude Gcl functions as a key regulator of centrosome separation required for proper PGC development. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Extraction and demulsification of oil from wheat germ, barley germ, and rice bran using an aqueous enzymatic method

    An aqueous enzymatic method was developed to extract oil from wheat germ. The parameters that influence oil yield were investigated, including wheat germ pretreatment, comparison of various industrial enzymes, pH, ratio of wheat germ to water, reaction time and demulsification. Pretreatment at 180ºC...

  17. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

    DOE PAGES

    Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz; ...

    2017-03-22

    Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

  18. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

    SciT

    Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz

    Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

  19. Early Differentiation within the Animate Domain: Are Humans Something Special?

    ERIC Educational Resources Information Center

    Pauen, Sabina

    2000-01-01

    Two experiments investigated whether preverbal infants distinguish between humans and mammals. Study 1 found that 7-, 9-, and 11-month-olds distinguished humans from mammals in an object-examination task. Study 2 found that 7-month-olds but not 5-month-olds showed evidence for category discrimination with the 2-dimensional color photos of toy…

  20. Germ-Line Recombination Activity of the Widely Used hGFAP-Cre and Nestin-Cre Transgenes

    PubMed Central

    Zhang, Jiong; Dublin, Pavel; Griemsmann, Stephanie; Klein, Alexandra; Brehm, Ralph; Bedner, Peter; Fleischmann, Bernd K.; Steinhäuser, Christian; Theis, Martin

    2013-01-01

    Herein we demonstrate with PCR, immunodetection and reporter gene approaches that the widely used human Glial Fibrillary Acidic Protein (hGFAP)-Cre transgene exhibits spontaneous germ-line recombination activity in leading to deletion in brain, heart and tail tissue with high frequency. The ectopic activity of hGFAP-Cre requires a rigorous control. We likewise observed that a second widely used nestin-Cre transgene shows germ-line deletion. Here we describe procedures to identify mice with germ-line recombination mediated by the hGFAP-Cre and nestin-Cre transgenes. Such control is essential to avoid pleiotropic effects due to germ-line deletion of loxP-flanked target genes and to maintain the CNS-restricted deletion status in transgenic mouse colonies. PMID:24349371

  1. A Role for Caenorhabditis elegans Importin IMA-2 in Germ Line and Embryonic Mitosis

    PubMed Central

    Geles, Kenneth G.; Johnson, Jeffrey J.; Jong, Sena; Adam, Stephen A.

    2002-01-01

    The importin α family of nuclear-cytoplasmic transport factors mediates the nuclear localization of proteins containing classical nuclear localization signals. Metazoan animals express multiple importin α proteins, suggesting their possible roles in cell differentiation and development. Adult Caenorhabditis elegans hermaphrodites express three importin α proteins, IMA-1, IMA-2, and IMA-3, each with a distinct expression and localization pattern. IMA-2 was expressed exclusively in germ line cells from the early embryonic through adult stages. The protein has a dynamic pattern of localization dependent on the stage of the cell cycle. In interphase germ cells and embryonic cells, IMA-2 is cytoplasmic and nuclear envelope associated, whereas in developing oocytes, the protein is cytoplasmic and intranuclear. During mitosis in germ line cells and embryos, IMA-2 surrounded the condensed chromosomes but was not directly associated with the mitotic spindle. The timing of IMA-2 nuclear localization suggested that the protein surrounded the chromosomes after fenestration of the nuclear envelope in prometaphase. Depletion of IMA-2 by RNA-mediated gene interference (RNAi) resulted in embryonic lethality and a terminal aneuploid phenotype. ima-2(RNAi) embryos have severe defects in nuclear envelope formation, accumulating nucleoporins and lamin in the cytoplasm. We conclude that IMA-2 is required for proper chromosome dynamics in germ line and early embryonic mitosis and is involved in nuclear envelope assembly at the conclusion of mitosis. PMID:12221121

  2. DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers

    PubMed Central

    Isagawa, Takayuki; Nagae, Genta; Shiraki, Nobuaki; Fujita, Takanori; Sato, Noriko; Ishikawa, Shumpei; Kume, Shoen; Aburatani, Hiroyuki

    2011-01-01

    Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental reprogramming occurs by de novo methylation and demethylation. Variance in DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analyzed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions are methylated across all three germ layers and in the three adult somatic tissues. This commonly methylated gene set is enriched in germ cell-associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns by global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Our combined findings indicate that differentiation of ES cells into the three germ layers is accompanied by an increased number of commonly methylated DNA regions and that these tissue-specific alterations in methylation occur for only a small number of genes. DNA methylation at the proximal promoter regions of commonly methylated genes thus appears to be an irreversible mark which functions to fix somatic lineage by repressing the transcription of germ cell-specific genes. PMID:22016810

  3. Early Childhood Education Curricula: Human Rights and Citizenship in Early Childhood Education

    ERIC Educational Resources Information Center

    Sounoglou, Marina; Michalopoulou, Aikaterini

    2017-01-01

    This study examines the human rights and the notion of citizenship under the prism of pedagogical science. The methodology that was followed was the experimental method. In a sample of 100 children-experimental group and control group held an intervention program with deepening axes of human rights and the concept of citizenship. The analysis of…

  4. Early-season avian deaths from West Nile virus as warnings of human infection

    Guptill, S.C.; Julian, K.G.; Campbell, G.L.; Price, S.D.; Marfin, A.A.

    2003-01-01

    An analysis of 2001 and 2002 West Nile virus (WNV) surveillance data shows that counties that report WNV-infected dead birds early in the transmission season are more likely to report subsequent WNV disease cases in humans than are counties that do not report early WNV-infected dead birds.

  5. Posterior localization of ApVas1 positions the preformed germ plasm in the sexual oviparous pea aphid Acyrthosiphon pisum

    PubMed Central

    2014-01-01

    Background Germline specification in some animals is driven by the maternally inherited germ plasm during early embryogenesis (inheritance mode), whereas in others it is induced by signals from neighboring cells in mid or late development (induction mode). In the Metazoa, the induction mode appears as a more prevalent and ancestral condition; the inheritance mode is therefore derived. However, regarding germline specification in organisms with asexual and sexual reproduction it has not been clear whether both strategies are used, one for each reproductive phase, or if just one strategy is used for both phases. Previously we have demonstrated that specification of germ cells in the asexual viviparous pea aphid depends on a preformed germ plasm. In this study, we extended this work to investigate how germ cells were specified in the sexual oviparous embryos, aiming to understand whether or not developmental plasticity of germline specification exists in the pea aphid. Results We employed Apvas1, a Drosophila vasa ortholog in the pea aphid, as a germline marker to examine whether germ plasm is preformed during oviparous development, as has already been seen in the viviparous embryos. During oogenesis, Apvas1 mRNA and ApVas1 protein were both evenly distributed. After fertilization, uniform expression of Apvas1 remained in the egg but posterior localization of ApVas1 occurred from the fifth nuclear cycle onward. Posterior co-localization of Apvas1/ApVas1 was first identified in the syncytial blastoderm undergoing cellularization, and later we could detect specific expression of Apvas1/ApVas1 in the morphologically identifiable germ cells of mature embryos. This suggests that Apvas1/ApVas1-positive cells are primordial germ cells and posterior localization of ApVas1 prior to cellularization positions the preformed germ plasm. Conclusions We conclude that both asexual and sexual pea aphids rely on the preformed germ plasm to specify germ cells and that developmental

  6. Early modern human diversity suggests subdivided population structure and a complex out-of-Africa scenario

    PubMed Central

    Gunz, Philipp; Bookstein, Fred L.; Mitteroecker, Philipp; Stadlmayr, Andrea; Seidler, Horst; Weber, Gerhard W.

    2009-01-01

    The interpretation of genetic evidence regarding modern human origins depends, among other things, on assessments of the structure and the variation of ancient populations. Because we lack genetic data from the time when the first anatomically modern humans appeared, between 200,000 and 60,000 years ago, instead we exploit the phenotype of neurocranial geometry to compare the variation in early modern human fossils with that in other groups of fossil Homo and recent modern humans. Variation is assessed as the mean-squared Procrustes distance from the group average shape in a representation based on several hundred neurocranial landmarks and semilandmarks. We find that the early modern group has more shape variation than any other group in our sample, which covers 1.8 million years, and that they are morphologically similar to recent modern humans of diverse geographically dispersed populations but not to archaic groups. Of the currently competing models of modern human origins, some are inconsistent with these findings. Rather than a single out-of-Africa dispersal scenario, we suggest that early modern humans were already divided into different populations in Pleistocene Africa, after which there followed a complex migration pattern. Our conclusions bear implications for the inference of ancient human demography from genetic models and emphasize the importance of focusing research on those early modern humans, in particular, in Africa. PMID:19307568

  7. Molecular biology of testicular germ cell tumors.

    PubMed

    Gonzalez-Exposito, R; Merino, M; Aguayo, C

    2016-06-01

    Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.

  8. Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

    ClinicalTrials.gov

    2017-11-14

    Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

  9. Technology, conflict early warning systems, public health, and human rights.

    PubMed

    Pham, Phuong N; Vinck, Patrick

    2012-12-15

    Public health and conflict early warning are evolving rapidly in response to technology changes for the gathering, management, analysis and communication of data. It is expected that these changes will provide an unprecedented ability to monitor, detect, and respond to crises. One of the potentially most profound and lasting expected change affects the roles of the various actors in providing and sharing information and in responding to early warning. Communities and civil society actors have the opportunity to be empowered as a source of information, analysis, and response, while the role of traditional actors shifts toward supporting those communities and building resilience. However, by creating new roles, relationships, and responsibilities, technology changes raise major concerns and ethical challenges for practitioners, pressing the need for practical guidelines and actionable recommendations in line with existing ethical principles. Copyright © 2012 Pham and Vinck. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

  10. Human evolution. Evolution of early Homo: an integrated biological perspective.

    PubMed

    Antón, Susan C; Potts, Richard; Aiello, Leslie C

    2014-07-04

    Integration of evidence over the past decade has revised understandings about the major adaptations underlying the origin and early evolution of the genus Homo. Many features associated with Homo sapiens, including our large linear bodies, elongated hind limbs, large energy-expensive brains, reduced sexual dimorphism, increased carnivory, and unique life history traits, were once thought to have evolved near the origin of the genus in response to heightened aridity and open habitats in Africa. However, recent analyses of fossil, archaeological, and environmental data indicate that such traits did not arise as a single package. Instead, some arose substantially earlier and some later than previously thought. From ~2.5 to 1.5 million years ago, three lineages of early Homo evolved in a context of habitat instability and fragmentation on seasonal, intergenerational, and evolutionary time scales. These contexts gave a selective advantage to traits, such as dietary flexibility and larger body size, that facilitated survival in shifting environments. Copyright © 2014, American Association for the Advancement of Science.

  11. Gut microbial functional maturation and succession during human early life.

    PubMed

    Cerdó, Tomás; Ruiz, Alicia; Acuña, Inmaculada; Jáuregui, Ruy; Jehmlich, Nico; Haange, Sven-Bastian; von Bergen, Martin; Suárez, Antonio; Campoy, Cristina

    2018-04-24

    The evolutional trajectory of gut microbial colonization from birth has been shown to prime for health later in life. Here, we combined cultivation-independent 16S rRNA gene sequencing and metaproteomics to investigate the functional maturation of gut microbiota in faecal samples from full-term healthy infants collected at 6 and 18 months of age. Phylogenetic analysis of the metaproteomes showed that Bifidobacterium provided the highest number of distinct protein groups. Considerable divergences between taxa abundance and protein phylogeny were observed at all taxonomic ranks. Age had a profound effect on early microbiota where compositional and functional diversity of less dissimilar communities increased with time. Comparisons of the relative abundances of proteins revealed the transition of taxon-associated saccharolytic and fermentation strategies from milk and mucin-derived monosaccharide catabolism feeding acetate/propanoate synthesis to complex food-derived hexoses fuelling butanoate production. Furthermore, co-occurrence network analysis uncovered two anti-correlated modules of functional taxa. A low-connected Bifidobacteriaceae-centred guild of facultative anaerobes was succeeded by a rich club of obligate anaerobes densely interconnected around Lachnospiraceae, underpinning their pivotal roles in microbial ecosystem assemblies. Our findings establish a framework to visualize whole microbial community metabolism and ecosystem succession dynamics, proposing opportunities for microbiota-targeted health-promoting strategies early in life. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

  12. A male contraceptive targeting germ cell adhesion.

    PubMed

    Mruk, Dolores D; Wong, Ching-Hang; Silvestrini, Bruno; Cheng, C Yan

    2006-11-01

    Throughout spermatogenesis, developing germ cells remain attached to Sertoli cells via testis-specific anchoring junctions. If adhesion between these cell types is compromised, germ cells detach from the seminiferous epithelium and infertility often results. Previously, we reported that Adjudin is capable of inducing germ cell loss from the epithelium. In a small subset of animals, however, oral administration of Adjudin (50 mg per kg body weight (b.w.) for 29 d) resulted in adverse effects such as liver inflammation and muscle atrophy. Here, we report a novel approach in which Adjudin is specifically targeted to the testis by conjugating Adjudin to a recombinant follicle-stimulating hormone (FSH) mutant, which serves as its 'carrier'. Using this approach, infertility was induced in adult rats when 0.5 microg Adjudin per kg b.w. was administered intraperitoneally, which was similar to results when 50 mg per kg b.w. was given orally. This represents a substantial increase in Adjudin's selectivity and efficacy as a male contraceptive.

  13. Expression of uncharacterized male germ cell-specific genes and discovery of novel sperm-tail proteins in mice.

    PubMed

    Kwon, Jun Tae; Ham, Sera; Jeon, Suyeon; Kim, Youil; Oh, Seungmin; Cho, Chunghee

    2017-01-01

    The identification and characterization of germ cell-specific genes are essential if we hope to comprehensively understand the mechanisms of spermatogenesis and fertilization. Here, we searched the mouse UniGene databases and identified 13 novel genes as being putatively testis-specific or -predominant. Our in silico and in vitro analyses revealed that the expressions of these genes are testis- and germ cell-specific, and that they are regulated in a stage-specific manner during spermatogenesis. We generated antibodies against the proteins encoded by seven of the genes to facilitate their characterization in male germ cells. Immunoblotting and immunofluorescence analyses revealed that one of these proteins was expressed only in testicular germ cells, three were expressed in both testicular germ cells and testicular sperm, and the remaining three were expressed in sperm of the testicular stages and in mature sperm from the epididymis. Further analysis of the latter three proteins showed that they were all associated with cytoskeletal structures in the sperm flagellum. Among them, MORN5, which is predicted to contain three MORN motifs, is conserved between mouse and human sperm. In conclusion, we herein identify 13 authentic genes with male germ cell-specific expression, and provide comprehensive information about these genes and their encoded products. Our finding will facilitate future investigations into the functional roles of these novel genes in spermatogenesis and sperm functions.

  14. Development of a Human Neurovascular Unit Organotypic Systems Model of Early Brain Development

    EPA Science Inventory

    The inability to model human brain and blood-brain barrier development in vitro poses a major challenge in studies of how chemicals impact early neurogenic periods. During human development, disruption of thyroid hormone (TH) signaling is related to adverse morphological effects ...

  15. Regulation of male germ cell cycle arrest and differentiation by DND1 is modulated by genetic background

    PubMed Central

    Cook, Matthew S.; Munger, Steven C.; Nadeau, Joseph H.; Capel, Blanche

    2011-01-01

    Human germ cell tumors show a strong sensitivity to genetic background similar to Dnd1Ter/Ter mutant mice, where testicular teratomas arise only on the 129/SvJ genetic background. The introduction of the Bax mutation onto mixed background Dnd1Ter/Ter mutants, where teratomas do not typically develop, resulted in a high incidence of teratomas. However, when Dnd1Ter/Ter; Bax–/– double mutants were backcrossed to C57BL/6J, no tumors arose. Dnd1Ter/Ter germ cells show a strong downregulation of male differentiation genes including Nanos2. In susceptible strains, where teratomas initiate around E15.5-E17.5, many mutant germ cells fail to enter mitotic arrest in G0 and do not downregulate the pluripotency markers NANOG, SOX2 and OCT4. We show that DND1 directly binds a group of transcripts that encode negative regulators of the cell cycle, including p27Kip1 and p21Cip1. P27Kip1 and P21Cip1 protein are both significantly decreased in Dnd1Ter/Ter germ cells on all strain backgrounds tested, strongly suggesting that DND1 regulates mitotic arrest in male germ cells through translational regulation of cell cycle genes. Nonetheless, in C57BL/6J mutants, germ cells arrest prior to M-phase of the cell cycle and downregulate NANOG, SOX2 and OCT4. Consistent with their ability to rescue cell cycle arrest, C57BL/6J germ cells overexpress negative regulators of the cell cycle relative to 129/SvJ. This work suggests that reprogramming of pluripotency in germ cells and prevention of tumor formation requires cell cycle arrest, and that differences in the balance of cell cycle regulators between 129/SvJ and C57BL/6 might underlie differences in tumor susceptibility. PMID:21115610

  16. Mitotic Arrest in Teratoma Susceptible Fetal Male Germ Cells

    PubMed Central

    Western, Patrick S.; Ralli, Rachael A.; Wakeling, Stephanie I.; Lo, Camden; van den Bergen, Jocelyn A.; Miles, Denise C.; Sinclair, Andrew H.

    2011-01-01

    Formation of germ cell derived teratomas occurs in mice of the 129/SvJ strain, but not in C57Bl/6 inbred or CD1 outbred mice. Despite this, there have been few comparative studies aimed at determining the similarities and differences between teratoma susceptible and non-susceptible mouse strains. This study examines the entry of fetal germ cells into the male pathway and mitotic arrest in 129T2/SvJ mice. We find that although the entry of fetal germ cells into mitotic arrest is similar between 129T2/SvJ, C57Bl/6 and CD1 mice, there were significant differences in the size and germ cell content of the testis cords in these strains. In 129T2/SvJ mice germ cell mitotic arrest involves upregulation of p27KIP1, p15INK4B, activation of RB, the expression of male germ cell differentiation markers NANOS2, DNMT3L and MILI and repression of the pluripotency network. The germ-line markers DPPA2 and DPPA4 show reciprocal repression and upregulation, respectively, while FGFR3 is substantially enriched in the nucleus of differentiating male germ cells. Further understanding of fetal male germ cell differentiation promises to provide insight into disorders of the testis and germ cell lineage, such as testis tumour formation and infertility. PMID:21674058

  17. Discontinuity of Human Presence at Atapuerca during the Early Middle Pleistocene: A Matter of Ecological Competition?

    PubMed Central

    Rodríguez-Gómez, Guillermo; Mateos, Ana; Martín-González, Jesús Angel; Blasco, Ruth; Rosell, Jordi; Rodríguez, Jesús

    2014-01-01

    Increasing evidence suggests that the European human settlement is older than 1.2 Ma. However, there is a fierce debate about the continuity or discontinuity of the early human settlement of Europe. In particular, evidence of human presence in the interval 0.7−0.5 Ma is scarce in comparison with evidence for the previous and later periods. Here, we present a case study in which the environmental conditions at Sierra de Atapuerca in the early Middle Pleistocene, a period without evidence of human presence, are compared with the conditions in the previous period, for which a relatively intense human occupation is documented. With this objective in mind, the available resources for a human population and the intensity of competition between secondary consumers during the two periods are compared using a mathematical model. The Gran Dolina site TD8 level, dated to 0.7−0.6 Ma, is taken as representative of the period during which Atapuerca was apparently not occupied by humans. Conditions at TD8 are compared with those of the previous period, represented by the TD6-2 level, which has yielded abundant evidence of intense human occupation. The results show that survival opportunities for a hypothetical human population were lower at TD8 than they were at TD6-2. Increased resource competition between secondary consumers arises as a possible explanation for the absence of human occupation at Atapuerca in the early Middle Pleistocene. PMID:25054305

  18. Discontinuity of human presence at Atapuerca during the early Middle Pleistocene: a matter of ecological competition?

    PubMed

    Rodríguez-Gómez, Guillermo; Mateos, Ana; Martín-González, Jesús Angel; Blasco, Ruth; Rosell, Jordi; Rodríguez, Jesús

    2014-01-01

    Increasing evidence suggests that the European human settlement is older than 1.2 Ma. However, there is a fierce debate about the continuity or discontinuity of the early human settlement of Europe. In particular, evidence of human presence in the interval 0.7-0.5 Ma is scarce in comparison with evidence for the previous and later periods. Here, we present a case study in which the environmental conditions at Sierra de Atapuerca in the early Middle Pleistocene, a period without evidence of human presence, are compared with the conditions in the previous period, for which a relatively intense human occupation is documented. With this objective in mind, the available resources for a human population and the intensity of competition between secondary consumers during the two periods are compared using a mathematical model. The Gran Dolina site TD8 level, dated to 0.7-0.6 Ma, is taken as representative of the period during which Atapuerca was apparently not occupied by humans. Conditions at TD8 are compared with those of the previous period, represented by the TD6-2 level, which has yielded abundant evidence of intense human occupation. The results show that survival opportunities for a hypothetical human population were lower at TD8 than they were at TD6-2. Increased resource competition between secondary consumers arises as a possible explanation for the absence of human occupation at Atapuerca in the early Middle Pleistocene.

  19. Germ Cell Development in the Scleractinian Coral Euphyllia ancora (Cnidaria, Anthozoa)

    PubMed Central

    Shikina, Shinya; Chen, Chieh-Jhen; Liou, Jhe-Yu; Shao, Zi-Fan; Chung, Yi-Jou; Lee, Yan-Horn; Chang, Ching-Fong

    2012-01-01

    Sexual reproduction of scleractinian coral is among the most important means of establishing coral populations. However, thus far, little is known about the mechanisms underlying coral gametogenesis. To better understand coral germ cell development, we performed a histological analysis of gametogenesis in Euphyllia ancora and characterized the coral homolog of the Drosophila germline marker gene vasa. The histological analysis revealed that E. ancora gametogenesis occurs in the mesenterial mesoglea between the mesenterial filaments and the retractor muscle bands. The development of germ cells takes approximately one year in females and half a year in males. Staining of tissue sections with an antibody against E. ancora Vasa (Eavas) revealed anti-Eavas immunoreactivity in the oogonia, early oocyte, and developing oocyte, but only faint or undetectable reactivity in developing oocytes that were >150 µm in diameters. In males, Eavas could be detected in the spermatogonia and primary spermatocytes but was only faintly detectable in the secondary spermatocytes, spermatids, and sperms. Furthermore, a reverse transcription-polymerase chain reaction analysis and Western blotting analysis of unfertilized mature eggs proved the presence of Eavas transcripts and proteins, suggesting that Eavas may be a maternal factor. Vasa may represent a germ cell marker for corals, and would allow us to distinguish germ cells from somatic cells in coral bodies that have no distinct organs. PMID:22848529

  20. Germ cell development in the scleractinian coral Euphyllia ancora (Cnidaria, Anthozoa).

    PubMed

    Shikina, Shinya; Chen, Chieh-Jhen; Liou, Jhe-Yu; Shao, Zi-Fan; Chung, Yi-Jou; Lee, Yan-Horn; Chang, Ching-Fong

    2012-01-01

    Sexual reproduction of scleractinian coral is among the most important means of establishing coral populations. However, thus far, little is known about the mechanisms underlying coral gametogenesis. To better understand coral germ cell development, we performed a histological analysis of gametogenesis in Euphyllia ancora and characterized the coral homolog of the Drosophila germline marker gene vasa. The histological analysis revealed that E. ancora gametogenesis occurs in the mesenterial mesoglea between the mesenterial filaments and the retractor muscle bands. The development of germ cells takes approximately one year in females and half a year in males. Staining of tissue sections with an antibody against E. ancora Vasa (Eavas) revealed anti-Eavas immunoreactivity in the oogonia, early oocyte, and developing oocyte, but only faint or undetectable reactivity in developing oocytes that were >150 µm in diameters. In males, Eavas could be detected in the spermatogonia and primary spermatocytes but was only faintly detectable in the secondary spermatocytes, spermatids, and sperms. Furthermore, a reverse transcription-polymerase chain reaction analysis and Western blotting analysis of unfertilized mature eggs proved the presence of Eavas transcripts and proteins, suggesting that Eavas may be a maternal factor. Vasa may represent a germ cell marker for corals, and would allow us to distinguish germ cells from somatic cells in coral bodies that have no distinct organs.

  1. Early human pregnancy serum cytokine levels predict autoimmunity in offspring.

    PubMed

    Lindehammer, Sabina Resic; Björck, Sara; Lynch, Kristian; Brundin, Charlotte; Marsal, Karel; Agardh, Daniel; Fex, Malin

    2011-09-01

    It is generally believed that pregnancy is mediated by a Th2 response, which includes cytokines that promote placental growth and are involved in inducing tolerance to the foetus. If the balance between Th1/and Th2-mediated cytokines is disrupted, systemic and local changes could predispose the foetus to future disease. Therefore, a shift in the Th1/Th2 balance during pregnancy, possibly caused by underlying environmental factors, could be associated with post-partum autoimmune disease in the offspring. Based on this presumption, we used celiac disease as a model to investigate whether autoimmunity is triggered in the foetus during early pregnancy, observed as changes in the mother's cytokine profile. Ten cytokines were measured by electro-chemi-luminescent multiplex ELISA in serum samples obtained from mothers during early pregnancy. Cases included women with children who had developed verified celiac disease before the age of 5, who were compared with other women as matched controls. We observed that 7 out of 10 cytokine levels were significantly increased in our case mothers when compared to controls. Five of these belonged to what is generally known as a Th1-mediated response (TNFα, IFNγ, IL-2, IL-1β and IL-12) and two were Th2 cytokines (IL-13 and IL-10). However, the IL-10 cytokine is known to have features from both arms of the immune system. These results were confirmed in a logistic regression model where five out of the initial seven cytokines remained. This study suggests that increase in Th1 serum cytokines may be associated with celiac disease in offspring.

  2. Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors

    ClinicalTrials.gov

    2018-06-08

    Germ Cell Tumor; Teratoma; Choriocarcinoma; Germinoma; Mixed Germ Cell Tumor; Yolk Sac Tumor; Childhood Teratoma; Malignant Germ Cell Neoplasm; Extragonadal Seminoma; Non-seminomatous Germ Cell Tumor; Seminoma

  3. Early human communication helps in understanding language evolution.

    PubMed

    Lenti Boero, Daniela

    2014-12-01

    Building a theory on extant species, as Ackermann et al. do, is a useful contribution to the field of language evolution. Here, I add another living model that might be of interest: human language ontogeny in the first year of life. A better knowledge of this phase might help in understanding two more topics among the "several building blocks of a comprehensive theory of the evolution of spoken language" indicated in their conclusion by Ackermann et al., that is, the foundation of the co-evolution of linguistic motor skills with the auditory skills underlying speech perception, and the possible phylogenetic interactions of protospeech production with referential capabilities.

  4. Confirmation of germ-line transmission in the red fluorescence protein (RFP) transgenic cloned male cat.

    PubMed

    Cho, Su-Jin; Lee, Young S; Lee, Jae-Ik; Bang, Jae-Il; Yang, Jing; Klassen, Henry; Kong, Il-Keun

    2010-12-01

    The production of transgenic animals is highly desirable for biotechnology and basic research. We investigated the reproductive ability of a red fluorescence protein (RFP) transgenic cloned male cat (RFP TG cat) by natural mating with a domestic female cat. The RFP expression levels were examined in early embryogenesis, tissues from 45-day-old two fetuses, and four RFP TG cat offspring. The RFP gene was detected in tissue samples from one dead kitten, including several organs and the skin. Also, under a fluorescent light source, we were able to directly detect the RFP expression of in in vitro-produced blastocysts derived with sperm from the RFP TG cat. These results indicate that the RFP TG cat exhibits normal reproductive fertility, stable germ-line transmission of the RFP transgene, and characteristic RFP expression in its offspring. We isolated feline neural progenitor cells from a 45-day-old fetus derived from the natural mating of the RFP TG cat with a domestic female cat. Isolated brain and retinal progenitor cells were successfully passaged at least four times post isolation (day 23), and showed a high RFP expression level. This method of producing genetically modified cloned cats will be important for generating biomedical models of human diseases.

  5. Edwin Grant Dexter: an early researcher in human behavioral biometeorology.

    PubMed

    Stewart, Alan E

    2015-06-01

    Edwin Grant Dexter (1868-1938) was one of the first researchers to study empirically the effects of specific weather conditions on human behavior. Dexter (1904) published his findings in a book, Weather influences. The author's purposes in this article were to (1) describe briefly Dexter's professional life and examine the historical contexts and motivations that led Dexter to conduct some of the first empirical behavioral biometeorological studies of the time, (2) describe the methods Dexter used to examine weather-behavior relationships and briefly characterize the results that he reported in Weather influences, and (3) provide a historical analysis of Dexter's work and assess its significance for human behavioral biometeorology. Dexter's Weather influences, while demonstrating an exemplary approach to weather, health, and behavior relationships, came at the end of a long era of such studies, as health, social, and meteorological sciences were turning to different paradigms to advance their fields. For these reasons, Dexter's approach and contributions may not have been fully recognized at the time and are, consequently, worthy of consideration by contemporary biometeorologists.

  6. Edwin Grant Dexter: an early researcher in human behavioral biometeorology

    NASA Astrophysics Data System (ADS)

    Stewart, Alan E.

    2015-06-01

    Edwin Grant Dexter (1868-1938) was one of the first researchers to study empirically the effects of specific weather conditions on human behavior. Dexter (1904) published his findings in a book, Weather influences. The author's purposes in this article were to (1) describe briefly Dexter's professional life and examine the historical contexts and motivations that led Dexter to conduct some of the first empirical behavioral biometeorological studies of the time, (2) describe the methods Dexter used to examine weather-behavior relationships and briefly characterize the results that he reported in Weather influences, and (3) provide a historical analysis of Dexter's work and assess its significance for human behavioral biometeorology. Dexter's Weather influences, while demonstrating an exemplary approach to weather, health, and behavior relationships, came at the end of a long era of such studies, as health, social, and meteorological sciences were turning to different paradigms to advance their fields. For these reasons, Dexter's approach and contributions may not have been fully recognized at the time and are, consequently, worthy of consideration by contemporary biometeorologists.

  7. HAZARD IDENTIFICATION: EFFICIENCY OF SHORT-TERM TESTS IN IDENTIFYING GERM CELL MUTAGENS AND PUTATIVE NONGENOTOXIC CARCINOGENS

    EPA Science Inventory

    For more than a decade, mutagenicity tests have had a clearly defined role in the identification of potential human mutagens and an ancillary role in the identification of potential human carcinogens. he efficiency of short-term tests in identifying germ cell mutagens has been ex...

  8. When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome?

    PubMed

    Van Saen, D; Vloeberghs, V; Gies, I; Mateizel, I; Sermon, K; De Schepper, Jean; Tournaye, H; Goossens, E

    2018-06-01

    .0%). Germ cells were detectable in testicular biopsies from 21% of adult men for whom no spermatozoa could be retrieved by TESE and in 31.5% of peripubertal KS boys. Very small numbers of spermatogonia (0.03-0.06 spermatogonia/tubule) were detected in three out of four (75%) prepubertal patients. At a foetal age, the number of germ cells was similar for KS and control samples. Increased signs of fibrosis were not present at foetal and prepubertal ages, but peripubertal and adult KS patients showed high levels of fibrosis. N/A. Only four prepubertal biopsies were included in this study, but they all showed a very low germ cell number. A high variability in the number of spermatogonia per mm2 was observed in the limited (n = 5) number of foetal biopsies. However, testicular biopsies from prepubertal and foetal Klinefelter patients are difficult to obtain. Testicular tissue banking at a prepubertal age has been suggested as a potential method for fertility preservation in early diagnosed KS boys. However, our results show that a reduction in germ cell number has already taken place in childhood. Therefore, offering testicular tissue banking in young KS boys to prevent subsequent sterility might be a questionable strategy. However, this should be confirmed in a larger study population. This project was funded by the scientific Fund Willy Gepts from the UZ Brussel (D.V.S., J.D.S.), grants from the Vrije Universiteit Brussel (E.G.) and a Methusalem grant (K.S.). D.V.S is a post-doctoral fellow of the Fonds Wetenschappelijk Onderzoek (FWO; 12M2815N). No conflict of interest is declared.

  9. Early embryonic sensitivity to cyclophosphamide in cardiac differentiation from human embryonic stem cells.

    PubMed

    Zhu, Ming-Xia; Zhao, Jin-Yuan; Chen, Gui-An; Guan, Li

    2011-09-01

    hESCs (human embryonic stem cells) can differentiate into tissue derivatives of all three germ layers in vitro and mimic the development of the embryo in vivo. In this study, we have investigated the potential of an hESC-based assay for the detection of toxicity to cardiac differentiation in embryonic development. First of all, we developed the protocol of cardiac induction from hESCs according to our previous work and distinguished cardiac precursor cells and late mature cardiomyocytes from differentiated cells, demonstrated by the Q-PCR (quantitative real-time PCR), immunocytochemistry and flow cytometry analysis. In order to test whether CPA (cyclophosphamide) induces developmental and cellular toxicity in the human embryo, we exposed the differentiating cells from hESCs to CPA (a well-known proteratogen) at different stages. We have found that a high concentration of CPA could inhibit cardiac differentiation of hESCs. Two separate exposure intervals were used to determine the effects of CPA on cardiac precursor cells and late mature cardiomyocytes respectively. The cardiac precursor cells were sensitive to CPA in non-cytotoxic concentrations for the expression of the cardiac-specific mRNA markers Nkx2.5 (NK2 transcription factor related, locus 5), GATA-4 (GATA binding protein 4 transcription factor) and TNNT2 (troponin T type 2). Non-cytotoxic CPA concentrations did not affect the mRNA markers' expression in late mature cardiomyocytes, indicating that cardiac precursors were more sensitive to CPA than late cardiomyocytes in cardiogenesis. We set up the in vitro developmental toxicity test model so as to reduce the number of test animals and expenses without compromising the safety of consumers and patients. Furthermore, such in vitro methods may be possibly suited to test a large number of chemicals than the classical employed in vivo tests.

  10. mga genosensor for early detection of human rheumatic heart disease.

    PubMed

    Singh, Swati; Kaushal, Ankur; Khare, Shashi; Kumar, Ashok

    2014-05-01

    The 5' amino-labeled DNA probe complementary to mga gene of Streptococcus pyogenes was immobilized on carboxylated multiwall carbon nanotubes electrode and hybridized with 0.1-100 ng/6 μl single-stranded genomic DNA (ssG-DNA) of S. pyogenes from throat swab of suspected rheumatic heart disease (RHD) patients. Electrochemical response was measured by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance (EI). The sensitivity of the sensor was 106.03 (μA/cm(2))/ng and limit of detection (LOD) was found 0.014 ng/6 μl with regression coefficient (R(2)) of 0.921 using DPV. The genosensor was characterized by FTIR and SEM, and electrode was found stable for 6 months on storage at 4 °C with 5-6 % loss in initial DPV current. mga genosensor is the first report on RHD sensor which can save life of several suspected patients by early diagnosis in 30 min.

  11. Germ Plasm Biogenesis--An Oskar-Centric Perspective.

    PubMed

    Lehmann, Ruth

    2016-01-01

    Germ granules are the hallmark of all germ cells. These membrane-less, electron-dense structures were first observed over 100 years ago. Today, their role in regulating and processing transcripts critical for the establishment, maintenance, and protection of germ cells is well established, and pathways outlining the biochemical mechanisms and physical properties associated with their biogenesis are emerging. © 2016 Elsevier Inc. All rights reserved.

  12. Early Modern Humans and Morphological Variation in Southeast Asia: Fossil Evidence from Tam Pa Ling, Laos

    PubMed Central

    Demeter, Fabrice; Shackelford, Laura; Westaway, Kira; Duringer, Philippe; Bacon, Anne-Marie; Ponche, Jean-Luc; Wu, Xiujie; Sayavongkhamdy, Thongsa; Zhao, Jian-Xin; Barnes, Lani; Boyon, Marc; Sichanthongtip, Phonephanh; Sénégas, Frank; Karpoff, Anne-Marie; Patole-Edoumba, Elise; Coppens, Yves; Braga, José

    2015-01-01

    Little is known about the timing of modern human emergence and occupation in Eastern Eurasia. However a rapid migration out of Africa into Southeast Asia by at least 60 ka is supported by archaeological, paleogenetic and paleoanthropological data. Recent discoveries in Laos, a modern human cranium (TPL1) from Tam Pa Ling‘s cave, provided the first evidence for the presence of early modern humans in mainland Southeast Asia by 63-46 ka. In the current study, a complete human mandible representing a second individual, TPL 2, is described using discrete traits and geometric morphometrics with an emphasis on determining its population affinity. The TPL2 mandible has a chin and other discrete traits consistent with early modern humans, but it retains a robust lateral corpus and internal corporal morphology typical of archaic humans across the Old World. The mosaic morphology of TPL2 and the fully modern human morphology of TPL1 suggest that a large range of morphological variation was present in early modern human populations residing in the eastern Eurasia by MIS 3. PMID:25849125

  13. The early development and evolution of the human brain.

    PubMed

    Crawford, M A

    1990-01-01

    signal transduction also use high proportions of n-3 fatty acids. However, the n-6 fatty acids also find a place, in the inositol phosphoglyceride (IPG) which appears to be involved with calcium ion transport and hence signal activation and reception. Even in the photoreceptor, the IPG is an arachidonic acid rich phosphoglyceride. THE EVOLUTION OF MAMMALS AND THE LARGE BRAIN: The dominance of n-3 fatty acids in the food chain, persisted until the end of the Cretaceous period when the flowering plants followed on the disappearance of the giant cycads and ferns. A new set of species, the mammals, then evolved with a requirement for n-6 fatty acids for reproduction. This dependance was coincident with the flowering plants which for the first time produced protected seeds: these introduced a rich source of n-6 fatty acids. The brain size of the mammals tended to be relatively larger (that is in relation to body size) by comparison with the previous reptilian or egg laying systems. This process led to the large human brain. A crucial difference between man and other animals, is undoubtedly the extent to which the brain and its peripheral attributes have been developed. This paper will address the possibility that the potential for the evolution of the large human brain may have been released by the evolving human primate occupying an ecological niche which offered a rich source of those nutrients specifically required for the brain. That niche is at the land/water interface.

  14. Molecular biological features of male germ cell differentiation

    PubMed Central

    HIROSE, MIKA; TOKUHIRO, KEIZO; TAINAKA, HITOSHI; MIYAGAWA, YASUSHI; TSUJIMURA, AKIRA; OKUYAMA, AKIHIKO; NISHIMUNE, YOSHITAKE

    2007-01-01

    Somatic cell differentiation is required throughout the life of a multicellular organism to maintain homeostasis. In contrast, germ cells have only one specific function; to preserve the species by conveying the parental genes to the next generation. Recent studies of the development and molecular biology of the male germ cell have identified many genes, or isoforms, that are specifically expressed in the male germ cell. In the present review, we consider the unique features of male germ cell differentiation. (Reprod Med Biol 2007; 6: 1–9) PMID:29699260

  15. Germ tube-specific antigens of Candida albicans cell walls

    SciT

    Sundstrom, P.R.

    1986-01-01

    Studies were performed to characterize the surface differences between blastospores and germ tubes of the pathogenic, dimorphic yeast, Candida albicans, and to identify components of yeast cells responsible for these differences. Investigation of surfaces differences of the two growth forms was facilitated by the production of rabbit antiserum prepared against Formalin-treated yeast possessing germ tubes. To prepare antiserum specific for germ tubes, this serum was adsorbed with stationary phase blastospores. Whereas the unadsorbed antiserum reacted with both blastospore and germ tube forms by immunofluorescence and Enzyme-Linked Immunosorbent Assay, the adsorbed antiserum did not react with blastospores but detected germ tube-specificmore » antigens in hyphal forms. The differences between blastospores and germ tubes of Candida albicans, were further studied by comparing enzymatic digests of cell walls of both growth forms in radiolabeled organisms. Organisms were labeled either on the surface with /sup 125/I, or metabolically with (/sup 35/S) methionine or (/sup 3/H) mannose. Three-surface-located components (as shown by antibody adsorption and elution experiments) were precipitated from Zymolase digests. All three components were mannoproteins as shown by their ability to bind Concanavalin A, and to be labeled in protein labeling procedures, and two of these (200,000 and 155,000 molecular weight) were germ tube specific, as shown by their ability to be precipitated by germ tube-specific antiserum. Monoclonal antibodies were prepared to C. albicans, using blastospores bearing germ tubes as immunogen.« less

  16. Cytokeratin expression in mouse lacrimal gland germ epithelium.

    PubMed

    Hirayama, Masatoshi; Liu, Ying; Kawakita, Tetsuya; Shimmura, Shigeto; Tsubota, Kazuo

    2016-05-01

    The lacrimal gland secretes tear fluids that protect the ocular surface epithelium, and its dysfunction leads to dry eye disease (DED). The functional restoration of the lacrimal gland by engraftment of a bioengineered lacrimal gland using lacrimal gland germ epithelial cells has been proposed to cure DED in mice. Here, we investigate the expression profile of cytokeratins in the lacrimal gland germ epithelium to clarify their unique characteristics. We performed quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC) analysis to clarify the expression profile of cytokeratin in the lacrimal gland germ epithelium. The mRNA expression of keratin (KRT) 5, KRT8, KRT14, KRT15, and KRT18 in the lacrimal gland germ epithelium was increased compared with that in mouse embryonic stem cells and the lacrimal gland germ mesenchyme, as analyzed by Q-PCR. The expression level of KRT15 increased in the transition from stem cells to lacrimal gland germ epithelium, then decreased as the lacrimal gland matured. IHC revealed that the expression set of these cytokeratins in the lacrimal gland germ epithelium was different from that in the adult lacrimal gland. The expression of KRT15 was observed in the lacrimal gland germ epithelium, and it segmentalized into some of the basal cells in the intercanulated duct in mature gland. We determined the expression profile of cytokeratins in the lacrimal gland epithelium, and identified KRT15 as a candidate unique cellular marker for the lacrimal gland germ epithelium. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman.

    PubMed

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels.

  18. HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse

    PubMed Central

    Lim, Shu Ly; Geoghegan, Joel; Hempfling, Anna-Lena; Bergmann, Martin; Goodnow, Christopher C.; Ormandy, Christopher J.; Wong, Lee; Mann, Jeff; Scott, Hamish S.; Jamsai, Duangporn; Adelson, David L.

    2015-01-01

    piRNAs are critical for transposable element (TE) repression and germ cell survival during the early phases of spermatogenesis, however, their role in adult germ cells and the relative importance of piRNA methylation is poorly defined in mammals. Using a mouse model of HEN methyltransferase 1 (HENMT1) loss-of-function, RNA-Seq and a range of RNA assays we show that HENMT1 is required for the 2’ O-methylation of mammalian piRNAs. HENMT1 loss leads to piRNA instability, reduced piRNA bulk and length, and ultimately male sterility characterized by a germ cell arrest at the elongating germ cell phase of spermatogenesis. HENMT1 loss-of-function, and the concomitant loss of piRNAs, resulted in TE de-repression in adult meiotic and haploid germ cells, and the precocious, and selective, expression of many haploid-transcripts in meiotic cells. Precocious expression was associated with a more active chromatin state in meiotic cells, elevated levels of DNA damage and a catastrophic deregulation of the haploid germ cell gene expression. Collectively these results define a critical role for HENMT1 and piRNAs in the maintenance of TE repression in adult germ cells and setting the spermatogenic program. PMID:26496356

  19. Separation of somatic and germ cells is required to establish primate spermatogonial cultures.

    PubMed

    Langenstroth, Daniel; Kossack, Nina; Westernströer, Birgit; Wistuba, Joachim; Behr, Rüdiger; Gromoll, Jörg; Schlatt, Stefan

    2014-09-01

    Can primate spermatogonial cultures be optimized by application of separation steps and well defined culture conditions? We identified the cell fraction which provides the best source for primate spermatogonia when prolonged culture is desired. Man and marmoset show similar characteristics in regard to germ cell development and function. Several protocols for isolation and culture of human testis-derived germline stem cells have been described. Subsequent analysis revealed doubts on the germline origin of these cells and characterized them as mesenchymal stem cells or fibroblasts. Studies using marmosets as preclinical model confirmed that the published isolation protocols did not lead to propagation of germline cells. Testicular cells derived from nine adult marmoset monkeys (Callithrix jacchus) were cultured for 1, 3, 6 and 11 days and consecutively analyzed for the presence of spermatogonia, differentiating germ cells and testicular somatic cells. Testicular tissue of nine adult marmoset monkeys was enzymatically dissociated and subjected to two different cell culture approaches. In the first approach all cells were kept in the same dish (non-separate culture, n = 5). In the second approach the supernatant cells were transferred into a new dish 24 h after seeding and subsequently supernatant and attached cells were cultured separately (separate culture, n = 4). Real-time quantitative PCR and immunofluorescence were used to analyze the expression of reliable germ cell and somatic markers throughout the culture period. Germ cell transplantation assays and subsequent wholemount analyses were performed to functionally evaluate the colonization of spermatogonial cells. This is the first report revealing an efficient isolation and culture of putative marmoset spermatogonial stem cells with colonization ability. Our results indicate that a separation of spermatogonia from testicular somatic cells is a crucial step during cell preparation. We identified the overgrowth

  20. Germ cell specification and ovary structure in the rotifer Brachionus plicatilis.

    PubMed

    Smith, James M; Cridge, Andrew G; Dearden, Peter K

    2010-08-02

    The segregation of the germline from somatic tissues is an essential process in the development of all animals. Specification of the primordial germ cells (PGCs) takes place via different strategies across animal phyla; either specified early in embryogenesis by the inheritance of maternal determinants in the cytoplasm of the oocyte ('preformation') or selected later in embryonic development from undifferentiated precursors by a localized inductive signal ('epigenesis'). Here we investigate the specification and development of the germ cells in the rotifer Brachionus plicatilis, a member of the poorly-characterized superphyla Lophotrochozoa, by isolating the Brachionus homologues of the conserved germ cell markers vasa and nanos, and examining their expression using in situ hybridization. Bpvasa and Bpnos RNA expression have very similar distributions in the Brachionus ovary, showing ubiquitous expression in the vitellarium, with higher levels in the putative germ cell cluster. Bpvas RNA expression is present in freshly laid eggs, remaining ubiquitous in embryos until at least the 96 cell stage after which expression narrows to a small cluster of cells at the putative posterior of the embryo, consistent with the developing ovary. Bpnos RNA expression is also present in just-laid eggs but expression is much reduced by the four-cell stage and absent by the 16-cell stage. Shortly before hatching of the juvenile rotifer from the egg, Bpnos RNA expression is re-activated, located in a subset of posterior cells similar to those expressing Bpvas at the same stage. The observed expression of vasa and nanos in the developing B. plicatilis embryo implies an epigenetic origin of primordial germ cells in Rotifer.

  1. Germ cell specification and ovary structure in the rotifer Brachionus plicatilis

    PubMed Central

    2010-01-01

    Background The segregation of the germline from somatic tissues is an essential process in the development of all animals. Specification of the primordial germ cells (PGCs) takes place via different strategies across animal phyla; either specified early in embryogenesis by the inheritance of maternal determinants in the cytoplasm of the oocyte ('preformation') or selected later in embryonic development from undifferentiated precursors by a localized inductive signal ('epigenesis'). Here we investigate the specification and development of the germ cells in the rotifer Brachionus plicatilis, a member of the poorly-characterized superphyla Lophotrochozoa, by isolating the Brachionus homologues of the conserved germ cell markers vasa and nanos, and examining their expression using in situ hybridization. Results Bpvasa and Bpnos RNA expression have very similar distributions in the Brachionus ovary, showing ubiquitous expression in the vitellarium, with higher levels in the putative germ cell cluster. Bpvas RNA expression is present in freshly laid eggs, remaining ubiquitous in embryos until at least the 96 cell stage after which expression narrows to a small cluster of cells at the putative posterior of the embryo, consistent with the developing ovary. Bpnos RNA expression is also present in just-laid eggs but expression is much reduced by the four-cell stage and absent by the 16-cell stage. Shortly before hatching of the juvenile rotifer from the egg, Bpnos RNA expression is re-activated, located in a subset of posterior cells similar to those expressing Bpvas at the same stage. Conclusions The observed expression of vasa and nanos in the developing B. plicatilis embryo implies an epigenetic origin of primordial germ cells in Rotifer. PMID:20849649

  2. Sensitivity of spore germination and germ tube elongation of Saccharina japonica to metal exposure.

    PubMed

    Han, Taejun; Kong, Jeong-Ae; Kang, Hee-Gyu; Kim, Seon-Jin; Jin, Gyo-Sun; Choi, Hoon; Brown, Murray T

    2011-11-01

    The sensitivity of early life stages of the brown seaweed Saccharina japonica to six metals (Cd, Cu, Hg, Ni, Pb, Zn) and two waste-water samples were investigated and a new toxicity bioassay developed. The two endpoints used were spore germination and germ tube elongation with an exposure time of 24 h. Optimal test conditions determined for photon irradiance, pH, salinity and temperature were darkness, pH 8, 35‰ and 15°C, respectively. The toxicity ranking of five metals was: Hg (EC(50) of 41 and 42 μg l(-1)) > Cu (120 and 81 μg l(-1)) > Ni (2,009 and 1,360 μg l(-1)) > Zn (3,024 and 3,897 μg l(-1)) > Pb (4,760 and 4,429 μg l(-1)) > Cd (15,052 and 7,541 μg l(-1)) for germination and germ tube elongation, respectively. The sensitivities to Cd, Cu and Ni were greater in germ tube elongation than in germination process. When tested against two different waste-water samples (processed animal and printed circuit board waste-water) values of EC(50) were between 21.29 and 32.02% for germination and between 5.33 and 8.98% for germ tube elongation. Despite differences in their chemical composition, the toxic effects of waste-water samples, as indicated by EC(50) values, did not differ significantly for the same endpoints. The CV range for both germination and germ tube elongation was between 4.61 and 37.69%, indicating high levels of precision of the tests. The results compare favourably with those from more established test procedures employing micro- and macroalgae. The advantages and potential limitations of the bioassay for the assessment of anthropogenic impacts on coastal ecosystems and commercial cultivation areas in near-shore environments are discussed.

  3. Autosomal Genes of Autosomal/X-Linked Duplicated Gene Pairs and Germ-Line Proliferation in Caenorhabditis elegans

    PubMed Central

    Maciejowski, John; Ahn, James Hyungsoo; Cipriani, Patricia Giselle; Killian, Darrell J.; Chaudhary, Aisha L.; Lee, Ji Inn; Voutev, Roumen; Johnsen, Robert C.; Baillie, David L.; Gunsalus, Kristin C.; Fitch, David H. A.; Hubbard, E. Jane Albert

    2005-01-01

    We report molecular genetic studies of three genes involved in early germ-line proliferation in Caenorhabditis elegans that lend unexpected insight into a germ-line/soma functional separation of autosomal/X-linked duplicated gene pairs. In a genetic screen for germ-line proliferation-defective mutants, we identified mutations in rpl-11.1 (L11 protein of the large ribosomal subunit), pab-1 [a poly(A)-binding protein], and glp-3/eft-3 (an elongation factor 1-α homolog). All three are members of autosome/X gene pairs. Consistent with a germ-line-restricted function of rpl-11.1 and pab-1, mutations in these genes extend life span and cause gigantism. We further examined the RNAi phenotypes of the three sets of rpl genes (rpl-11, rpl-24, and rpl-25) and found that for the two rpl genes with autosomal/X-linked pairs (rpl-11 and rpl-25), zygotic germ-line function is carried by the autosomal copy. Available RNAi results for highly conserved autosomal/X-linked gene pairs suggest that other duplicated genes may follow a similar trend. The three rpl and the pab-1/2 duplications predate the divergence between C. elegans and C. briggsae, while the eft-3/4 duplication appears to have occurred in the lineage to C. elegans after it diverged from C. briggsae. The duplicated C. briggsae orthologs of the three C. elegans autosomal/X-linked gene pairs also display functional differences between paralogs. We present hypotheses for evolutionary mechanisms that may underlie germ-line/soma subfunctionalization of duplicated genes, taking into account the role of X chromosome silencing in the germ line and analogous mammalian phenomena. PMID:15687263

  4. Topology of the germ plasm and development of primordial germ cells in inverted amphibian eggs

    NASA Technical Reports Server (NTRS)

    Wakahara, M.; Neff, A. W.; Malacinski, G. M.

    1984-01-01

    Inverted Xenopus eggs have reduced numbers of primordial germ cells (PGCs). The extent of the reduction varies from spawning to spawning. Histologic examination revealed that PGC counts were lowest in inverted eggs which displayed the greatest amount of shift in the vegetal mass of large yolk platelets, although the germ plasm itself always remained localized in the egg's original vegetal hemisphere. Even at blastulation the germ plasm continued to be localized in the egg's original vegetal hemisphere. In many cases, however, it was confined to the periphery of the embryo, which probably accounts for the reduced PGC number in some tadpoles. In other cases it may have been dispersed and therefore not detectable in histologic analyses. Although the altered site of involution in inverted embryos did not influence PGC development, subsequent cell movement patterns apparently did. Those embryos which displayed the largest degree of pattern reversal at the tail-bud stage also exhibited the most extreme reduction in PGC numbers. A brief cold shock (4 degrees C, 10 min) prior to first cleavage leads to a further reduction in PGC numbers in inverted embryos, probably as a result of the displacement of the germ plasm away from its original vegetal pole location.

  5. A giant testicular mixed germ cell tumour.

    PubMed

    Reekhaye, A; Harris, A; Nagarajan, S; Chadwick, D

    2016-11-01

    We present a case that we believe to be the largest mixed germ cell testicular tumour reported in the United Kingdom. A 23-year-old male was admitted to our urology department with a large scrotal swelling. The patient was found to have a giant left testicular tumour and a solitary lung metastasis at presentation. He underwent an emergency radical orchidectomy and subsequently received four cycles of bleomycin, etoposide and cisplatin chemotherapy. Four months after starting treatment, the tumour markers had normalised and a repeat staging computed tomography showed no active disease. The tumour reached that size because of the patient's failure to seek medical attention due to fear and embarrassment.

  6. Function of FEZF1 during early neural differentiation of human embryonic stem cells.

    PubMed

    Liu, Xin; Su, Pei; Lu, Lisha; Feng, Zicen; Wang, Hongtao; Zhou, Jiaxi

    2018-01-01

    The understanding of the mechanism underlying human neural development has been hampered due to lack of a cellular system and complicated ethical issues. Human embryonic stem cells (hESCs) provide an invaluable model for dissecting human development because of unlimited self-renewal and the capacity to differentiate into nearly all cell types in the human body. In this study, using a chemical defined neural induction protocol and molecular profiling, we identified Fez family zinc finger 1 (FEZF1) as a potential regulator of early human neural development. FEZF1 is rapidly up-regulated during neural differentiation in hESCs and expressed before PAX6, a well-established marker of early human neural induction. We generated FEZF1-knockout H1 hESC lines using CRISPR-CAS9 technology and found that depletion of FEZF1 abrogates neural differentiation of hESCs. Moreover, loss of FEZF1 impairs the pluripotency exit of hESCs during neural specification, which partially explains the neural induction defect caused by FEZF1 deletion. However, enforced expression of FEZF1 itself fails to drive neural differentiation in hESCs, suggesting that FEZF1 is necessary but not sufficient for neural differentiation from hESCs. Taken together, our findings identify one of the earliest regulators expressed upon neural induction and provide insight into early neural development in human.

  7. A late Pleistocene human presence at Huaca Prieta, Peru, and early Pacific Coastal adaptations

    NASA Astrophysics Data System (ADS)

    Dillehay, Tom D.; Bonavia, Duccio; Goodbred, Steve L.; Pino, Mario; Vásquez, Victor; Tham, Teresa Rosales

    2012-05-01

    Archaeological excavations in deep pre-mound levels at Huaca Prieta in northern Peru have yielded new evidence of late Pleistocene cultural deposits that shed insights into the early human occupation of the Pacific coast of South America. Radiocarbon dates place this occupation between ~ 14,200 and 13,300 cal yr BP. The cultural evidence shares certain basic technological and subsistence traits, including maritime resources and simple flake tools, with previously discovered late Pleistocene sites along the Pacific coast of Peru and Chile. The results help to expand our knowledge of early maritime societies and human adaption to changing coastal environments.

  8. High early life mortality in free-ranging dogs is largely influenced by humans

    PubMed Central

    Paul, Manabi; Sen Majumder, Sreejani; Sau, Shubhra; Nandi, Anjan K.; Bhadra, Anindita

    2016-01-01

    Free-ranging dogs are a ubiquitous part of human habitations in many developing countries, leading a life of scavengers dependent on human wastes for survival. The effective management of free-ranging dogs calls for understanding of their population dynamics. Life expectancy at birth and early life mortality are important factors that shape life-histories of mammals. We carried out a five year-long census based study in seven locations of West Bengal, India, to understand the pattern of population growth and factors affecting early life mortality in free-ranging dogs. We observed high rates of mortality, with only ~19% of the 364 pups from 95 observed litters surviving till the reproductive age; 63% of total mortality being human influenced. While living near people increases resource availability for dogs, it also has deep adverse impacts on their population growth, making the dog-human relationship on streets highly complex. PMID:26804633

  9. Intratumoral hemorrhage because of primary spinal mixed germ cell tumor presenting with atypical radiological features in an adult.

    PubMed

    Yamamoto, Junkoh; Takahashi, Mayu; Nakano, Yoshiteru; Saito, Takeshi; Kitagawa, Takehiro; Ueta, Kunihiro; Miyaoka, Ryo; Nakamura, Eiichiro; Nishizawa, Shigeru

    2013-10-01

    Germ cell tumors are known to arise in the central nervous system, usually in the intracranial regions. However, primary spinal mixed germ cell tumors are extremely rare. This is the first reported case of intratumoral hemorrhage because of a primary spinal mixed germ cell tumor consisting of germinoma and immature teratoma in the conus medullaris of an adult patient that presented with rapid changes on magnetic resonance image (MRI). We report this rare case and discuss the clinical manifestations of an intramedullary spinal mixed germ cell tumor in adult. A case report. A 42-year-old woman experienced buttock numbness, and a spinal cord tumor was observed on the conus medullaris on MRI. The patient was scheduled for an operation in 1 month, but she developed sudden-onset neurologic deterioration. Rapid progression of the tumor was observed on follow-up MRI. The tumor was removed by emergency surgery and was identified as a primary mixed germinoma and immature teratoma. The patient received adjuvant chemotherapy and radiotherapy after gross total resection. The neurologic deficit of the patient was relieved, and recurrence of the tumor was not observed 26 months after the surgery. We present this rare case and emphasize the necessity of precise diagnosis and early treatment of primary spinal germ cell tumor. Close observation on MRI is required after surgery, and adjuvant chemotherapy and radiotherapy should be considered according to the pathologic features. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses

    PubMed Central

    Sun, Xiangjie; Zeng, Hui; Kumar, Amrita; Belser, Jessica A.; Maines, Taronna R.

    2016-01-01

    ABSTRACT A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans. IMPORTANCE Avian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary

  11. Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses.

    PubMed

    Sun, Xiangjie; Zeng, Hui; Kumar, Amrita; Belser, Jessica A; Maines, Taronna R; Tumpey, Terrence M

    2016-12-15

    A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans. Avian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary endothelial damage

  12. Glucose 6-phosphate dehydrogenase deficiency enhances germ cell apoptosis and causes defective embryogenesis in Caenorhabditis elegans

    PubMed Central

    Yang, H-C; Chen, T-L; Wu, Y-H; Cheng, K-P; Lin, Y-H; Cheng, M-L; Ho, H-Y; Lo, S J; Chiu, D T-Y

    2013-01-01

    Glucose 6-phosphate dehydrogenase (G6PD) deficiency, known as favism, is classically manifested by hemolytic anemia in human. More recently, it has been shown that mild G6PD deficiency moderately affects cardiac function, whereas severe G6PD deficiency leads to embryonic lethality in mice. How G6PD deficiency affects organisms has not been fully elucidated due to the lack of a suitable animal model. In this study, G6PD-deficient Caenorhabditis elegans was established by RNA interference (RNAi) knockdown to delineate the role of G6PD in animal physiology. Upon G6PD RNAi knockdown, G6PD activity was significantly hampered in C. elegans in parallel with increased oxidative stress and DNA oxidative damage. Phenotypically, G6PD-knockdown enhanced germ cell apoptosis (2-fold increase), reduced egg production (65% of mock), and hatching (10% of mock). To determine whether oxidative stress is associated with G6PD knockdown-induced reproduction defects, C. elegans was challenged with a short-term hydrogen peroxide (H2O2). The early phase egg production of both mock and G6PD-knockdown C. elegans were significantly affected by H2O2. However, H2O2-induced germ cell apoptosis was more dramatic in mock than that in G6PD-deficient C. elegans. To investigate the signaling pathways involved in defective oogenesis and embryogenesis caused by G6PD knockdown, mutants of p53 and mitogen-activated protein kinase (MAPK) pathways were examined. Despite the upregulation of CEP-1 (p53), cep-1 mutation did not affect egg production and hatching in G6PD-deficient C. elegans. Neither pmk-1 nor mek-1 mutation significantly affected egg production, whereas sek-1 mutation further decreased egg production in G6PD-deficient C. elegans. Intriguingly, loss of function of sek-1 or mek-1 dramatically rescued defective hatching (8.3- and 9.6-fold increase, respectively) induced by G6PD knockdown. Taken together, these findings show that G6PD knockdown reduces egg production and hatching in C. elegans

  13. Glucose 6-phosphate dehydrogenase deficiency enhances germ cell apoptosis and causes defective embryogenesis in Caenorhabditis elegans.

    PubMed

    Yang, H-C; Chen, T-L; Wu, Y-H; Cheng, K-P; Lin, Y-H; Cheng, M-L; Ho, H-Y; Lo, S J; Chiu, D T-Y

    2013-05-02

    Glucose 6-phosphate dehydrogenase (G6PD) deficiency, known as favism, is classically manifested by hemolytic anemia in human. More recently, it has been shown that mild G6PD deficiency moderately affects cardiac function, whereas severe G6PD deficiency leads to embryonic lethality in mice. How G6PD deficiency affects organisms has not been fully elucidated due to the lack of a suitable animal model. In this study, G6PD-deficient Caenorhabditis elegans was established by RNA interference (RNAi) knockdown to delineate the role of G6PD in animal physiology. Upon G6PD RNAi knockdown, G6PD activity was significantly hampered in C. elegans in parallel with increased oxidative stress and DNA oxidative damage. Phenotypically, G6PD-knockdown enhanced germ cell apoptosis (2-fold increase), reduced egg production (65% of mock), and hatching (10% of mock). To determine whether oxidative stress is associated with G6PD knockdown-induced reproduction defects, C. elegans was challenged with a short-term hydrogen peroxide (H2O2). The early phase egg production of both mock and G6PD-knockdown C. elegans were significantly affected by H2O2. However, H2O2-induced germ cell apoptosis was more dramatic in mock than that in G6PD-deficient C. elegans. To investigate the signaling pathways involved in defective oogenesis and embryogenesis caused by G6PD knockdown, mutants of p53 and mitogen-activated protein kinase (MAPK) pathways were examined. Despite the upregulation of CEP-1 (p53), cep-1 mutation did not affect egg production and hatching in G6PD-deficient C. elegans. Neither pmk-1 nor mek-1 mutation significantly affected egg production, whereas sek-1 mutation further decreased egg production in G6PD-deficient C. elegans. Intriguingly, loss of function of sek-1 or mek-1 dramatically rescued defective hatching (8.3- and 9.6-fold increase, respectively) induced by G6PD knockdown. Taken together, these findings show that G6PD knockdown reduces egg production and hatching in C. elegans

  14. Germ line genome editing in clinics: the approaches, objectives and global society

    PubMed Central

    2017-01-01

    Genome editing allows for the versatile genetic modification of somatic cells, germ cells and embryos. In particular, CRISPR/Cas9 is worldwide used in biomedical research. Although the first report on Cas9-mediated gene modification in human embryos focused on the prevention of a genetic disease in offspring, it raised profound ethical and social concerns over the safety of subsequent generations and the potential misuse of genome editing for human enhancement. The present article considers germ line genome editing approaches from various clinical and ethical viewpoints and explores its objectives. The risks and benefits of the following three likely objectives are assessed: the prevention of monogenic diseases, personalized assisted reproductive technology (ART) and genetic enhancement. Although genetic enhancement should be avoided, the international regulatory landscape suggests the inevitability of this misuse at ART centers. Under these circumstances, possible regulatory responses and the potential roles of public dialogue are discussed. PMID:26615180

  15. Germ line genome editing in clinics: the approaches, objectives and global society.

    PubMed

    Ishii, Tetsuya

    2017-01-01

    Genome editing allows for the versatile genetic modification of somatic cells, germ cells and embryos. In particular, CRISPR/Cas9 is worldwide used in biomedical research. Although the first report on Cas9-mediated gene modification in human embryos focused on the prevention of a genetic disease in offspring, it raised profound ethical and social concerns over the safety of subsequent generations and the potential misuse of genome editing for human enhancement. The present article considers germ line genome editing approaches from various clinical and ethical viewpoints and explores its objectives. The risks and benefits of the following three likely objectives are assessed: the prevention of monogenic diseases, personalized assisted reproductive technology (ART) and genetic enhancement. Although genetic enhancement should be avoided, the international regulatory landscape suggests the inevitability of this misuse at ART centers. Under these circumstances, possible regulatory responses and the potential roles of public dialogue are discussed. © The Author 2015. Published by Oxford University Press.

  16. Genomic evolution and chemoresistance in germ-cell tumours.

    PubMed

    Taylor-Weiner, Amaro; Zack, Travis; O'Donnell, Elizabeth; Guerriero, Jennifer L; Bernard, Brandon; Reddy, Anita; Han, G Celine; AlDubayan, Saud; Amin-Mansour, Ali; Schumacher, Steven E; Litchfield, Kevin; Turnbull, Clare; Gabriel, Stacey; Beroukhim, Rameen; Getz, Gad; Carter, Scott L; Hirsch, Michelle S; Letai, Anthony; Sweeney, Christopher; Van Allen, Eliezer M

    2016-11-30

    Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes. GCTs are histologically heterogeneous and distinctly curable with chemotherapy. Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs, but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types. These tumours also acquire KRAS mutations during the development from precursor to primary disease, and primary testicular GCTs (TGCTs) are uniformly wild type for TP53. In addition, by functional measurement of apoptotic signalling (BH3 profiling) of fresh tumour and adjacent tissue, we find that primary TGCTs have high mitochondrial priming that facilitates chemotherapy-induced apoptosis. Finally, by phylogenetic analysis of serial TGCTs that emerge with chemotherapy resistance, we show how TGCTs gain additional reciprocal loss of heterozygosity and that this is associated with loss of pluripotency markers (NANOG and POU5F1) in chemoresistant teratomas or transformed carcinomas. Our results demonstrate the distinct genomic features underlying the origins of this disease and associated with the chemosensitivity phenotype, as well as the rare progression to chemoresistance. These results identify the convergence of cancer genomics, mitochondrial priming and GCT evolution, and may provide insights into chemosensitivity and resistance in other cancers.

  17. Germ cell transplantation in an azoospermic Klinefelter bull.

    PubMed

    Joerg, Hannes; Janett, Fredi; Schlatt, Stefan; Mueller, Simone; Graphodatskaya, Daria; Suwattana, Duangsmorn; Asai, Mika; Stranzinger, Gerald

    2003-12-01

    Germ cell transplantation is a technique that transfers donor testicular cells into recipient testes. A population of germ cells can colonize the recipient testis, initiate spermatogenesis, and produce sperm capable of fertilization. In the present study, a nonmosaic Klinefelter bull was used as a germ cell recipient. The donor cell suspension was introduced into the rete testis using ultrasound-guided puncture. A pulsatile administration of GnRH was performed to stimulate spermatogenesis. The molecular approach to detect donor cells was done by a quantitative polymerase chain reaction with allele discrimination based on a genetic mutation between donor and recipient. Therefore, a known genetic mutation, associated with coat-color phenotype, was used to calculate the ratio of donor to recipient cells in the biopsy specimens and ejaculates for 10 mo. After slaughtering, meiotic preparations were performed. The injected germ cells did not undergo spermatogenesis. Six months after germ cell transplantation, the donor cells were rejected, which indicates that the donor cells could not incorporate in the testis. The hormone stimulation showed that the testosterone-producing Leydig cells were functionally intact. Despite subfertility therapy, neither the recipient nor the donor cells underwent spermatogenesis. Therefore, nonmosaic Klinefelter bulls are not suitable as germ cell recipients. Future germ cell recipients in cattle could be mosaic Klinefelters, interspecies hybrids, bulls with Sertoli cell-only syndrome, or bulls with disrupted germ cell migration caused by RNA interference.

  18. Editorial Introduction [to Female Germ Cells: Biology and Genetic Risk

    EPA Science Inventory

    This is an editorial introduction to the special issue of utation Research, titled, emale Germ Cells: Biology and Genetic isk, which is an attempt to present a collection of papers that emphasize the distinct properties of female germ cells and their characteristic response to mu...

  19. Cellular mechanics of germ band retraction in Drosophila.

    PubMed

    Lynch, Holley E; Crews, Sarah M; Rosenthal, Brett; Kim, Elliott; Gish, Robert; Echiverri, Karl; Hutson, M Shane

    2013-12-15

    Germ band retraction involves a dramatic rearrangement of the tissues on the surface of the Drosophila embryo. As germ band retraction commences, one tissue, the germ band, wraps around another, the amnioserosa. Through retraction the two tissues move cohesively as the highly elongated cells of the amnioserosa contract and the germ band moves so it is only on one side of the embryo. To understand the mechanical drivers of this process, we designed a series of laser ablations that suggest a mechanical role for the amnioserosa. First, we find that during mid retraction, segments in the curve of the germ band are under anisotropic tension. The largest tensions are in the direction in which the amnioserosa contracts. Second, ablating one lateral flank of the amnioserosa reduces the observed force anisotropy and leads to retraction failures. The other intact flank of amnioserosa is insufficient to drive retraction, but can support some germ band cell elongation and is thus not a full phenocopy of ush mutants. Another ablation-induced failure in retraction can phenocopy mys mutants, and does so by targeting amnioserosa cells in the same region where the mutant fails to adhere to the germ band. We conclude that the amnioserosa must play a key, but assistive, mechanical role that aids uncurling of the germ band. © 2013 Elsevier Inc. All rights reserved.

  20. Cellular Mechanics of Germ Band Retraction in Drosophila

    PubMed Central

    Lynch, Holley E.; Crews, Sarah M.; Rosenthal, Brett; Kim, Elliott; Gish, Robert; Echiverri, Karl; Hutson, M. Shane

    2013-01-01

    Germ band retraction involves a dramatic rearrangement of the tissues on the surface of the Drosophila embryo. As germ band retraction commences, one tissue, the germ band, wraps around another, the amnioserosa. Through retraction the two tissues move cohesively as the highly elongated cells of the amnioserosa contract and the germ band moves so it is only on one side of the embryo. To understand the mechanical drivers of this process, we designed a series of laser ablations that suggest a mechanical role for the amnioserosa. First, we find that during mid retraction, segments in the curve of the germ band are under anisotropic tension. The largest tensions are in the direction in which the amnioserosa contracts. Second, ablating one lateral flank of the amnioserosa reduces the observed force anisotropy and leads to retraction failures. The other intact flank of amnioserosa is insufficient to drive retraction, but can support some germ band cell elongation and is thus not a full phenocopy of ush mutants. Another ablation-induced failure in retraction can phenocopy mys mutants, and does so by targeting amnioserosa cells in the same region where the mutant fails to adhere to the germ band. We conclude that the amnioserosa must play a key, but assistive, mechanical role that aids uncurling of the germ band. PMID:24135149

  1. The Formation of Germ Cell for Organizational Learning

    ERIC Educational Resources Information Center

    Ivaldi, Silvia; Scaratti, Giuseppe

    2016-01-01

    Purpose: The aim of the paper is to analyze the process of "germ cell" formation by framing it as an opportunity for promoting organizational learning and transformation. The paper aims to specifically answer two research questions: Why does the "germ cell" have a pivotal role in organization's transformation? and Which…

  2. Rearrangement of Immunoglobulin Genes in Shark Germ Cells

    PubMed Central

    Lee, Susan S.; Fitch, David; Flajnik, Martin F.; Hsu, Ellen

    2000-01-01

    The variable (V), (diversity [D]), and joining (J) region recombinases (recombination activating genes [RAGs]) can perform like transposases and are thought to have initiated development of the adaptive immune system in early vertebrates by splitting archaic V genes with transposable elements. In cartilaginous fishes, the immunoglobulin (Ig) light chain genes are organized as multiple VJ-constant (C) clusters; some loci are capable of rearrangement while others contain fused VJ. The latter may be key to understanding the evolutionary role of RAG. Are they relics of the archaic genes, or are they results of rearrangement in germ cells? Our data suggest that some fused VJ genes are not only recently rearranged, but also resulted from RAG-like activity involving hairpin intermediates. Expression studies show that these, like some other germline-joined Ig sequences, are expressed at significant levels only early in ontogeny. We suggest that a rejoined Ig gene may not merely be a sequence restricting antibody diversity, but is potentially a novel receptor no longer tied to somatic RAG expression and rearrangement. From the combined data, we arrived at the unexpected conclusion that, in some vertebrates, RAG is still an active force in changing the genome. PMID:10811858

  3. Early Motherhood and Harsh Parenting: The Role of Human, Social, and Cultural Capital

    ERIC Educational Resources Information Center

    Lee, Yookyong

    2009-01-01

    Objective: This study examined the role of maternal human, social, and cultural capital in the relationship between early motherhood and harsh parenting behavior. Methods: This study used data from the Fragile Families and Child Wellbeing (FFCW) Study. Harsh parenting behaviors by mothers who were 19 years or younger at birth of the focal child (n…

  4. Human Development, Early Childhood Care and Education and Family Welfare. Compendium of Researches, Volume III.

    ERIC Educational Resources Information Center

    Saraswathi, T. S., Ed.; And Others

    This volume encompasses 44 research studies that were conducted mainly by graduate students in the Department of Human Development and Family Studies, M.S. University of Baroda, India. The studies are organized in six broad categories: (1) child care in tribal, rural and urban poor, and institutional settings; (2) early childhood care and…

  5. Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

    PubMed

    Cooke, Gerard M

    2014-01-01

    The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

  6. Primary Cortical Folding in the Human Newborn: An Early Marker of Later Functional Development

    ERIC Educational Resources Information Center

    Dubois, J.; Benders, M.; Borradori-Tolsa, C.; Cachia, A.; Lazeyras, F.; Leuchter, R. Ha-Vinh; Sizonenko, S. V.; Warfield, S. K.; Mangin, J. F.; Huppi, P. S.

    2008-01-01

    In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be…

  7. The early spread and epidemic ignition of HIV-1 in human populations

    PubMed Central

    Faria, Nuno R.; Rambaut, Andrew; Suchard, Marc A.; Baele, Guy; Bedford, Trevor; Ward, Melissa J.; Tatem, Andrew J.; Sousa, João D.; Arinaminpathy, Nimalan; Pépin, Jacques; Posada, David; Peeters, Martine; Pybus, Oliver G.; Lemey, Philippe

    2014-01-01

    Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations. PMID:25278604

  8. HIV epidemiology. The early spread and epidemic ignition of HIV-1 in human populations.

    PubMed

    Faria, Nuno R; Rambaut, Andrew; Suchard, Marc A; Baele, Guy; Bedford, Trevor; Ward, Melissa J; Tatem, Andrew J; Sousa, João D; Arinaminpathy, Nimalan; Pépin, Jacques; Posada, David; Peeters, Martine; Pybus, Oliver G; Lemey, Philippe

    2014-10-03

    Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations. Copyright © 2014, American Association for the Advancement of Science.

  9. Forces directing germ-band extension in Drosophila embryos.

    PubMed

    Kong, Deqing; Wolf, Fred; Großhans, Jörg

    2017-04-01

    Body axis elongation by convergent extension is a conserved developmental process found in all metazoans. Drosophila embryonic germ-band extension is an important morphogenetic process during embryogenesis, by which the length of the germ-band is more than doubled along the anterior-posterior axis. This lengthening is achieved by typical convergent extension, i.e. narrowing the lateral epidermis along the dorsal-ventral axis and simultaneous extension along the anterior-posterior axis. Germ-band extension is largely driven by cell intercalation, whose directionality is determined by the planar polarity of the tissue and ultimately by the anterior-posterior patterning system. In addition, extrinsic tensile forces originating from the invaginating endoderm induce cell shape changes, which transiently contribute to germ-band extension. Here, we review recent progress in understanding of the role of mechanical forces in germ-band extension. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Mammalian X Chromosome Dosage Compensation: Perspectives From the Germ Line.

    PubMed

    Sangrithi, Mahesh N; Turner, James M A

    2018-06-01

    Sex chromosomes are advantageous to mammals, allowing them to adopt a genetic rather than environmental sex determination system. However, sex chromosome evolution also carries a burden, because it results in an imbalance in gene dosage between females (XX) and males (XY). This imbalance is resolved by X dosage compensation, which comprises both X chromosome inactivation and X chromosome upregulation. X dosage compensation has been well characterized in the soma, but not in the germ line. Germ cells face a special challenge, because genome wide reprogramming erases epigenetic marks responsible for maintaining the X dosage compensated state. Here we explain how evolution has influenced the gene content and germ line specialization of the mammalian sex chromosomes. We discuss new research uncovering unusual X dosage compensation states in germ cells, which we postulate influence sexual dimorphisms in germ line development and cause infertility in individuals with sex chromosome aneuploidy. © 2018 The Authors. BioEssays Published by Periodicals, Inc.

  11. Controlled fire use in early humans might have triggered the evolutionary emergence of tuberculosis.

    PubMed

    Chisholm, Rebecca H; Trauer, James M; Curnoe, Darren; Tanaka, Mark M

    2016-08-09

    Tuberculosis (TB) is caused by the Mycobacterium tuberculosis complex (MTBC), a wildly successful group of organisms and the leading cause of death resulting from a single bacterial pathogen worldwide. It is generally accepted that MTBC established itself in human populations in Africa and that animal-infecting strains diverged from human strains. However, the precise causal factors of TB emergence remain unknown. Here, we propose that the advent of controlled fire use in early humans created the ideal conditions for the emergence of TB as a transmissible disease. This hypothesis is supported by mathematical modeling together with a synthesis of evidence from epidemiology, evolutionary genetics, and paleoanthropology.

  12. Origin and development of the germ line in sea stars

    PubMed Central

    Wessel, Gary M.; Fresques, Tara; Kiyomoto, Masato; Yajima, Mamiko; Zazueta, Vanesa

    2014-01-01

    This review summarizes and integrates our current understanding of how sea stars make gametes. Although little is known of the mechanism of germ line formation in these animals, recent results point to specific cells and to cohorts of molecules in the embryos and larvae that may lay the ground work for future research efforts. A coelomic outpocketing forms in the posterior of the gut in larvae, referred to as the posterior enterocoel (PE), that when removed, significantly reduces the number of germ cell later in larval growth. This same PE structure also selectively accumulates several germ-line associated factors – vasa, nanos, piwi – and excludes factors involved in somatic cell fate. Since its formation is relatively late in development, these germ cells may form by inductive mechanisms. When integrated into the morphological observations of germ cells and gonad development in larvae, juveniles, and adults, the field of germ line determination appears to have a good model system to study inductive germ line determination to complement the recent work on the molecular mechanisms in mice. We hope this review will also guide investigators interested in germ line determination and regulation of the germ line in how these animals can help in this research field. The review is not intended to be comprehensive – sea star reproduction has been studied over 100 years and many reviews are comprehensive in their coverage of, for example, seasonal growth of the gonads in response to light, nutrient, and temperature. Rather the intent of this review is to help the reader focus on new experimental results attached to the historical underpinnings of how the germ cell functions in sea stars with particular emphasis to clarify the important areas of priority for future research. PMID:24648114

  13. Germ-line engineering, freedom, and future generations.

    PubMed

    Cooke, Elizabeth F

    2003-02-01

    New technologies in germ-line engineering have raised many questions about obligations to future generations. In this article, I focus on the importance of increasing freedom and the equality of freedom for present and future generations, because these two ideals are necessary for a just society and because they are most threatened by the wide-scale privatisation of GLE technologies. However, there are ambiguities in applying these ideals to the issue of genetic technologies. I argue that Amartya Sen's capability theory can be used as a framework to ensure freedom and equality in the use of GLE technology. Capability theory articulates the goal of equalising real freedom by bringing all people up to a threshold of basic human capabilities. Sen's capability theory can clarify the proper moral goal of GLE insofar as this technology could be used to bring people up to certain basic human capabilities, thereby increasing their real freedom. And by increasing the freedom of those who lack basic human capabilities, GLE can aid in decreasing the inequalities of freedom among classes of people.

  14. Early Pleistocene third metacarpal from Kenya and the evolution of modern human-like hand morphology

    PubMed Central

    Ward, Carol V.; Tocheri, Matthew W.; Plavcan, J. Michael; Brown, Francis H.; Manthi, Fredrick Kyalo

    2014-01-01

    Despite discoveries of relatively complete hands from two early hominin species (Ardipithecus ramidus and Australopithecus sediba) and partial hands from another (Australopithecus afarensis), fundamental questions remain about the evolution of human-like hand anatomy and function. These questions are driven by the paucity of hand fossils in the hominin fossil record between 800,000 and 1.8 My old, a time interval well documented for the emergence and subsequent proliferation of Acheulian technology (shaped bifacial stone tools). Modern and Middle to Late Pleistocene humans share a suite of derived features in the thumb, wrist, and radial carpometacarpal joints that is noticeably absent in early hominins. Here we show that one of the most distinctive features of this suite in the Middle Pleistocene to recent human hand, the third metacarpal styloid process, was present ∼1.42 Mya in an East African hominin from Kaitio, West Turkana, Kenya. This fossil thus provides the earliest unambiguous evidence for the evolution of a key shared derived characteristic of modern human and Neandertal hand morphology and suggests that the distinctive complex of radial carpometacarpal joint features in the human hand arose early in the evolution of the genus Homo and probably in Homo erectus sensu lato. PMID:24344276

  15. Earliest evidence of modern human life history in North African early Homo sapiens.

    PubMed

    Smith, Tanya M; Tafforeau, Paul; Reid, Donald J; Grün, Rainer; Eggins, Stephen; Boutakiout, Mohamed; Hublin, Jean-Jacques

    2007-04-10

    Recent developmental studies demonstrate that early fossil hominins possessed shorter growth periods than living humans, implying disparate life histories. Analyses of incremental features in teeth provide an accurate means of assessing the age at death of developing dentitions, facilitating direct comparisons with fossil and modern humans. It is currently unknown when and where the prolonged modern human developmental condition originated. Here, an application of x-ray synchrotron microtomography reveals that an early Homo sapiens juvenile from Morocco dated at 160,000 years before present displays an equivalent degree of tooth development to modern European children at the same age. Crown formation times in the juvenile's macrodont dentition are higher than modern human mean values, whereas root development is accelerated relative to modern humans but is less than living apes and some fossil hominins. The juvenile from Jebel Irhoud is currently the oldest-known member of Homo with a developmental pattern (degree of eruption, developmental stage, and crown formation time) that is more similar to modern H. sapiens than to earlier members of Homo. This study also underscores the continuing importance of North Africa for understanding the origins of human anatomical and behavioral modernity. Corresponding biological and cultural changes may have appeared relatively late in the course of human evolution.

  16. Testicular seminomatous mixed germ cell tumor with choriocarcinoma and teratoma with secondary somatic malignancy: a case report.

    PubMed

    Aneja, Amandeep; Bhattacharyya, Siddharth; Mydlo, Jack; Inniss, Susan

    2014-01-01

    Testicular tumors are a heterogeneous group of neoplasms exhibiting diverse histopathology and can be classified as seminomatous and non-seminomatous germ cell tumor types. Mixed germ cell tumors contain more than one germ cell component and various combinations have been reported. Here, we present a rare case of a mixed germ cell tumor composed of seminoma, choriocarcinoma and teratoma with a secondary somatic malignancy. A 31-year-old Caucasian man presented with splenic rupture to our hospital. A right-sided testicular swelling had been present for 6 months and his alpha-fetoprotein, beta-human chorionic gonadotropin, and lactose dehydrogenase were increased. An ultrasound of his scrotum revealed an enlarged right testis with heterogeneous echogenicity. Multiple hypervascular lesions were noted in his liver and spleen. He underwent transcatheter embolization therapy of his splenic artery followed by splenectomy and right-sided orchiectomy. A computed tomography scan also showed metastasis to both lungs. During his last follow up after four cycles of cisplatin-based chemotherapy, the level of tumor markers had decreased, decreases in the size of his liver and pulmonary lesions were noted but new sclerotic lesions were evident in his thoracolumbar region raising concern for bony metastasis. Prognosis of testicular tumor depends mainly on the clinical stage, but emergence of a sarcomatous component presents a challenge in the treatment of germ cell tumors and the histological subtype of this component can be used as a guide to specific chemotherapy in these patients.

  17. Alleviative effect of quercetin on germ cells intoxicated by 3-methyl-4-nitrophenol from diesel exhaust particles*

    PubMed Central

    Bu, Tong-liang; Jia, Yu-dong; Lin, Jin-xing; Mi, Yu-ling; Zhang, Cai-qiao

    2012-01-01

    As a component of diesel exhaust particles, 3-methyl-4-nitrophenol (4-nitro-m-cresol, PNMC) is also a metabolite of the insecticide fenitrothion and imposes hazardous effects on human health. In the present study, the alleviative effect of a common antioxidant flavonoid quercetin on mouse germ cells intoxicated by PNMC was investigated. Results showed that a single intraperitoneal injection of PNMC at 100 mg/kg induced severe testicular damage after one week. PNMC-treated mice showed a significant loss of germ cells (approximate 40% loss of round germ cells). PNMC caused an increase of hydroxyl radical and hydrogen peroxide production and lipid peroxidation, as well as a decrease in glutathione level, superoxide dismutase and glutathione peroxidase activities. Furthermore, treatment of PNMC increased expression of the pro-apoptotic protein Bax and decreased expression of the anti-apoptotic protein Bcl-XL in germ cells. In addition, testicular caspase-3 activity was significantly up-regulated and germ cell apoptosis was significantly increased in the PNMC-treated mice. In contrast, combined administration of quercetin at 75 mg/kg significantly attenuated PNMC-induced testicular toxicity. These results indicate that the antioxidant quercetin displays a remarkable protective effect on PNMC-induced oxidative damage in mouse testes and may represent an efficient supplement to attenuate reproductive toxicity by environmental toxicants to ensure healthy sperm production. PMID:22467373

  18. Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors

    ClinicalTrials.gov

    2017-01-20

    Recurrent Extragonadal Seminoma; Recurrent Malignant Extragonadal Germ Cell Tumor; Recurrent Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage III Testicular Cancer; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

  19. Early childhood development in Rwanda: a policy analysis of the human rights legal framework.

    PubMed

    Binagwaho, Agnes; Scott, Kirstin W; Harward, Sardis H

    2016-01-12

    Early childhood development (ECD) is a critical period that continues to impact human health and productivity throughout the lifetime. Failing to provide policies and programs that support optimal developmental attainment when such services are financially and logistically feasible can result in negative population health, education and economic consequences that might otherwise be avoided. Rwanda, with its commitment to rights-based policy and program planning, serves as a case study for examination of the national, regional, and global human rights legal frameworks that inform ECD service delivery. In this essay, we summarize key causes and consequences of the loss of early developmental potential and how this relates to the human rights legal framework in Rwanda. We contend that sub-optimal early developmental attainment constitutes a violation of individuals' rights to health, education, and economic prosperity. These rights are widely recognized in global, regional and national human rights instruments, and are guaranteed by Rwanda's constitution. Recent policy implementation by several Rwandan ministries has increased access to health and social services that promote achievement of full developmental potential. These ECD-centric activities are characterized by an integrated approach to strengthening the services provided by several public sectors. Combining population level activities with those at the local level, led by local community health workers and women's councils, can bolster community education and ensure uptake of ECD services. Realization of the human rights to health, education, and economic prosperity requires and benefits from attention to the period of ECD, as early childhood has the potential to be an opportunity for expedient intervention or the first case of human rights neglect in a lifetime of rights violations. Efforts to improve ECD services and outcomes at the population level require multisector collaboration at the highest echelons

  20. Early childhood development: impact of national human development, family poverty, parenting practices and access to early childhood education.

    PubMed

    Tran, T D; Luchters, S; Fisher, J

    2017-05-01

    This study was to describe and quantify the relationships among family poverty, parents' caregiving practices, access to education and the development of children living in low- and middle-income countries (LAMIC). We conducted a secondary analysis of data collected in UNICEF's Multiple Indicator Cluster Surveys (MICS). Early childhood development was assessed in four domains: language-cognitive, physical, socio-emotional and approaches to learning. Countries were classified into three groups on the basis of the Human Development Index (HDI). Overall, data from 97 731 children aged 36 to 59 months from 35 LAMIC were included in the after analyses. The mean child development scale score was 4.93 out of a maximum score of 10 (95%CI 4.90 to 4.97) in low-HDI countries and 7.08 (95%CI 7.05 to 7.12) in high-HDI countries. Family poverty was associated with lower child development scores in all countries. The total indirect effect of family poverty on child development score via attending early childhood education, care for the child at home and use of harsh punishments at home was -0.13 SD (77.8% of the total effect) in low-HDI countries, -0.09 SD (23.8% of the total effect) in medium-HDI countries and -0.02 SD (6.9% of the total effect) in high-HDI countries. Children in the most disadvantaged position in their societies and children living in low-HDI countries are at the greatest risk of failing to reach their developmental potential. Optimizing care for child development at home is essential to reduce the adverse effects of poverty on children's early development and subsequent life. © 2016 John Wiley & Sons Ltd.

  1. Characterization of germ cell-specific expression of the orphan nuclear receptor, germ cell nuclear factor.

    PubMed

    Katz, D; Niederberger, C; Slaughter, G R; Cooney, A J

    1997-10-01

    Nuclear receptors, such as those for androgens, estrogens, and progesterones, control many reproductive processes. Proteins with structures similar to these receptors, but for which ligands have not yet been identified, have been termed orphan nuclear receptors. One of these orphans, germ cell nuclear factor (GCNF), has been shown to be germ cell specific in the adult and, therefore, may also participate in the regulation of reproductive functions. In this paper, we examine more closely the expression patterns of GCNF in germ cells to begin to define spatio-temporal domains of its activity. In situ hybridization showed that GCNF messenger RNA (mRNA) is lacking in the testis of hypogonadal mutant mice, which lack developed spermatids, but is present in the wild-type testis. Thus, GCNF is, indeed, germ cell specific in the adult male. Quantitation of the specific in situ hybridization signal in wild-type testis reveals that GCNF mRNA is most abundant in stage VII round spermatids. Similarly, Northern analysis and specific in situ hybridization show that GCNF expression first occurs in testis of 20-day-old mice, when round spermatids first emerge. Therefore, in the male, GCNF expression occurs postmeiotically and may participate in the morphological changes of the maturing spermatids. In contrast, female expression of GCNF is shown in growing oocytes that have not completed the first meiotic division. Thus, GCNF in the female is expressed before the completion of meiosis. Finally, the nature of the two different mRNAs that hybridize to the GCNF complementary DNA was studied. Although both messages contain the DNA binding domain, only the larger message is recognized by a probe from the extreme 3' untranslated region. In situ hybridization with these differential probes demonstrates that both messages are present in growing oocytes. In addition, the coding region and portions of the 3' untranslated region of the GCNF complementary DNA are conserved in the rat.

  2. Starch grains on human teeth reveal early broad crop diet in northern Peru

    PubMed Central

    Piperno, Dolores R.; Dillehay, Tom D.

    2008-01-01

    Previous research indicates that the Ñanchoc Valley in northern Peru was an important locus of early and middle Holocene human settlement, and that between 9200 and 5500 14C yr B.P. the valley inhabitants adopted major crop plants such as squash (Cucurbita moschata), peanuts (Arachis sp.), and cotton (Gossypium barbadense). We report here an examination of starch grains preserved in the calculus of human teeth from these sites that provides direct evidence for the early consumption of cultivated squash and peanuts along with two other major food plants not previously detected. Starch from the seeds of Phaseolus and Inga feuillei, the flesh of Cucurbita moschata fruits, and the nuts of Arachis was routinely present on numerous teeth that date to between 8210 and 6970 14C yr B.P. Early plant diets appear to have been diverse and stable through time and were rich in cultivated foods typical of later Andean agriculture. Our data provide early archaeological evidence for Phaseolus beans and I. feuillei, an important tree crop, and indicate that effective food production systems that contributed significant dietary inputs were present in the Ñanchoc region by 8000 14C yr B.P. Starch grain studies of dental remains document plants and edible parts of them not normally preserved in archaeological records and can assume primary roles as direct indicators of ancient human diets and agriculture. PMID:19066222

  3. The Lin28/Let-7 System in Early Human Embryonic Tissue and Ectopic Pregnancy

    PubMed Central

    Steffani, Liliana; Martínez, Sebastián; Monterde, Mercedes; Ferri, Blanca; Núñez, Maria Jose; AinhoaRomero-Espinós; Zamora, Omar; Gurrea, Marta; Sangiao-Alvarellos, Susana; Vega, Olivia; Simón, Carlos; Pellicer, Antonio; Tena-Sempere, Manuel

    2014-01-01

    Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7–9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤6-weeks) and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤6-weeks) of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (de)regulated pathways in the pathophysiology of ectopic pregnancy in humans. PMID:24498170

  4. Cell-based interventions for neurologic conditions: ethical challenges for early human trials.

    PubMed

    Mathews, D J H; Sugarman, J; Bok, H; Blass, D M; Coyle, J T; Duggan, P; Finkel, J; Greely, H T; Hillis, A; Hoke, A; Johnson, R; Johnston, M; Kahn, J; Kerr, D; Kurtzberg, J; Liao, S M; McDonald, J W; McKhann, G; Nelson, K B; Rao, M; Regenberg, A; Siegel, A W; Smith, K; Solter, D; Song, H; Vescovi, A; Young, W; Gearhart, J D; Faden, R

    2008-07-22

    Attempts to translate basic stem cell research into treatments for neurologic diseases and injury are well under way. With a clinical trial for one such treatment approved and in progress in the United States, and additional proposals under review, we must begin to address the ethical issues raised by such early forays into human clinical trials for cell-based interventions for neurologic conditions. An interdisciplinary working group composed of experts in neuroscience, cell biology, bioethics, law, and transplantation, along with leading disease researchers, was convened twice over 2 years to identify and deliberate on the scientific and ethical issues raised by the transition from preclinical to clinical research of cell-based interventions for neurologic conditions. While the relevant ethical issues are in many respects standard challenges of human subjects research, they are heightened in complexity by the novelty of the science, the focus on the CNS, and the political climate in which the science is proceeding. Distinctive challenges confronting US scientists, administrators, institutional review boards, stem cell research oversight committees, and others who will need to make decisions about work involving stem cells and their derivatives and evaluate the ethics of early human trials include evaluating the risks, safety, and benefits of these trials, determining and evaluating cell line provenance, and determining inclusion criteria, informed consent, and the ethics of conducting early human trials in the public spotlight. Further study and deliberation by stakeholders is required to move toward professional and institutional policies and practices governing this research.

  5. Experimental vitrification of human compacted morulae and early blastocysts using fine diameter plastic micropipettes.

    PubMed

    Cremades, N; Sousa, M; Silva, J; Viana, P; Sousa, S; Oliveira, C; Teixeira da Silva, J; Barros, A

    2004-02-01

    Vitrification of human blastocysts has been successfully applied using grids, straws and cryoloops. We assessed the survival rate of human compacted morulae and early blastocysts vitrified in pipette tips with a smaller inner diameter and solution volume than the previously described open pulled straw (OPS) method. Excess day 5 human embryos (n = 63) were experimentally vitrified in vessels. Embryos were incubated at 37 degrees C with sperm preparation medium (SPM) for 1 min, SPM + 7.5% ethylene glycol (EG)/dimethylsulphoxide (DMSO) for 3 min, and SPM + 16.5% EG + 16.5% DMSO + 0.67 mol/l sucrose for 25 s. They were then aspirated (0.5 microl) into a plastic micropipette tip (0.36 mm inner diameter), exposed to liquid nitrogen (LN(2)) vapour for 2 min before being placed into a pre-cooled cryotube, which was then closed and plunged into LN(2). Embryos were warmed and diluted using 0.33 mol/l and 0.2 mol/l sucrose. The survival rate for compacted morulae was 73% (22/30) and 82% (27/33) for early blastocysts. The survival rates of human compacted morulae and early blastocysts after vitrification with this simple technique are similar to those reported in the literature achieved by slow cooling and other vitrification protocols.

  6. A Re-Appraisal of the Early Andean Human Remains from Lauricocha in Peru

    PubMed Central

    Kuzminsky, Susan; Rohland, Nadin; Santos, Fabrício R.; Kaulicke, Peter; Valverde, Guido; Richards, Stephen M.; Nordenfelt, Susanne; Seidenberg, Verena; Mallick, Swapan; Cooper, Alan; Reich, David; Haak, Wolfgang

    2015-01-01

    The discovery of human remains from the Lauricocha cave in the Central Andean highlands in the 1960’s provided the first direct evidence for human presence in the high altitude Andes. The skeletons found at this site were ascribed to the Early to Middle Holocene and represented the oldest known population of Western South America, and thus were used in several studies addressing the early population history of the continent. However, later excavations at Lauricocha led to doubts regarding the antiquity of the site. Here, we provide new dating, craniometric, and genetic evidence for this iconic site. We obtained new radiocarbon dates, generated complete mitochondrial genomes and nuclear SNP data from five individuals, and re-analyzed the human remains of Lauricocha to revise the initial morphological and craniometric analysis conducted in the 1960’s. We show that Lauricocha was indeed occupied in the Early to Middle Holocene but the temporal spread of dates we obtained from the human remains show that they do not qualify as a single contemporaneous population. However, the genetic results from five of the individuals fall within the spectrum of genetic diversity observed in pre-Columbian and modern Native Central American populations. PMID:26061688

  7. Welcome to the Twilight Zone: a forgotten early phase of human evolutionary studies.

    PubMed

    Delisle, Richard G

    2012-06-01

    The field of paleoanthropology arose out of a strange and unacknowledged early phase of development prior to about the 1930s. It is often assumed that a key pillar of the discipline, the unity of humankind--the notion that humans are clearly separated phylogenetically (genealogically) from other non-human primates--was widely accepted from the inception of paleoanthropology around 1860. However, a final consensus on this fundamental question only appeared later on in the 20th century. This paper will focus on two key areas of disagreement, which reveal the unsettled state of this question during this early period: the question of uncertainty with respect to the number, identity and boundary of primate species (including humans) which prevailed in the 18th, 19th and early 20th centuries; and the matter of uncertainty with respect to the nature of the phylogenetic relationships among the various human populations and the other primate species which prevailed between 1864 and 1931. Consideration of these matters reveals that the modern research structure that paleoanthropologists take for granted today is much more recent than believed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Sunagawa, Mayumi; Mangala, Lingegowda; Zhang, Ye; Kahdim, Munira; Wilson, Bobby; Cucinotta, Francis A.; Wu, Honglu

    2011-01-01

    Tumor formation in humans or animals is a multi-step process. An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

  9. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

    NASA Astrophysics Data System (ADS)

    Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

    2017-03-01

    Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

  10. Retrotransposons Mimic Germ Plasm Determinants to Promote Transgenerational Inheritance.

    PubMed

    Tiwari, Bhavana; Kurtz, Paula; Jones, Amanda E; Wylie, Annika; Amatruda, James F; Boggupalli, Devi Prasad; Gonsalvez, Graydon B; Abrams, John M

    2017-10-09

    Retrotransposons are a pervasive class of mobile elements present in the genomes of virtually all forms of life [1, 2]. In metazoans, these are preferentially active in the germline, which, in turn, mounts defenses that restrain their activity [3, 4]. Here we report that certain classes of retrotransposons ensure transgenerational inheritance by invading presumptive germ cells before they are formed. Using sensitized Drosophila and zebrafish models, we found that diverse classes of retrotransposons migrate to the germ plasm, a specialized region of the oocyte that prefigures germ cells and specifies the germline of descendants in the fertilized egg. In Drosophila, we found evidence for a "stowaway" model, whereby Tahre retroelements traffic to the germ plasm by mimicking oskar RNAs and engaging the Staufen-dependent active transport machinery. Consistent with this, germ plasm determinants attracted retroelement RNAs even when these components were ectopically positioned in bipolar oocytes. Likewise, vertebrate retrotransposons similarly migrated to the germ plasm in zebrafish oocytes. Together, these results suggest that germ plasm targeting represents a fitness strategy adopted by some retrotransposons to ensure transgenerational propagation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. The making of a germ panic, then and now.

    PubMed Central

    Tomes, N

    2000-01-01

    Over the last 2 decades, a heightened interest in germs has been evident in many aspects of American popular culture, including news coverage, advertisements, and entertainment media. Although clearly a response to the AIDS epidemic and other recent disease outbreaks, current obsessions with germs have some striking parallels with a similar period of intense anxiety about disease germs that occurred between 1900 and 1940. A comparison of these 2 periods of germ "panic" suggests some of the long-term cultural trends that contributed to their making. Both germ panics reflected anxieties about societal incorporation, associated with expanding markets, transportation networks, and mass immigration. They were also shaped by new trends in public health education, journalism, advertising, and entertainment media. In comparison to the first germ panic, the current discourse about the "revenge of the superbugs" is considerably more pessimistic because of increasing worries about the environment, suspicions of governmental authority, and distrust of expert knowledge. Yet, as popular anxieties about infectious disease have increased, public health scientists have been attracting favorable coverage in their role as "medical detectives" on the trail of the "killer germ." PMID:10667179

  12. Chlamydospore production and germ-tube formation by auxotrophs of Candida albicans.

    PubMed

    Balish, E

    1973-04-01

    A prototrophic strain and 21 auxotrophic strains of Candida albicans were assessed for their capacity to produce chlamydospores and germ tubes. All of the mutants were able to produce germ-tubes in human serum but only two mutants produced them in defined medium with L-alpha-amino-n-butyric acid as the sole source of nitrogen. Most auxotrophs were not able to produce chlamydospores on corn meal agar with 1% Tween 80, but they could be induced to do so if the medium was supplemented with their growth requirement(s). Although L-cysteine was able to support the growth of two methionine mutants, it did not support chlamydospore formation when added to corn meal agar with 1% Tween 80. Mutants of C. albicans that do not form chlamydospores could be incorrectly identified in laboratories that rely on chlamydospore formation for identification.

  13. Functions of Huntingtin in Germ Layer Specification and Organogenesis

    PubMed Central

    Nguyen, Giang D.; Molero, Aldrin E.; Gokhan, Solen; Mehler, Mark F.

    2013-01-01

    Huntington’s disease (HD) is a neurodegenerative disease caused by abnormal polyglutamine expansion in the huntingtin protein (Htt). Although both Htt and the HD pathogenic mutation (mHtt) are implicated in early developmental events, their individual involvement has not been adequately explored. In order to better define the developmental functions and pathological consequences of the normal and mutant proteins, respectively, we employed embryonic stem cell (ESC) expansion, differentiation and induction experiments using huntingtin knock-out (KO) and mutant huntingtin knock-in (Q111) mouse ESC lines. In KO ESCs, we observed impairments in the spontaneous specification and survival of ectodermal and mesodermal lineages during embryoid body formation and under inductive conditions using retinoic acid and Wnt3A, respectively. Ablation of BAX improves cell survival, but failed to correct defects in germ layer specification. In addition, we observed ensuing impairments in the specification and maturation of neural, hepatic, pancreatic and cardiomyocyte lineages. These developmental deficits occurred in concert with alterations in Notch, Hes1 and STAT3 signaling pathways. Moreover, in Q111 ESCs, we observed differential developmental stage-specific alterations in lineage specification and maturation. We also observed changes in Notch/STAT3 expression and activation. Our observations underscore essential roles of Htt in the specification of ectoderm, endoderm and mesoderm, in the specification of neural and non-neural organ-specific lineages, as well as cell survival during early embryogenesis. Remarkably, these developmental events are differentially deregulated by mHtt, raising the possibility that HD-associated early developmental impairments may contribute not only to region-specific neurodegeneration, but also to non-neural co-morbidities. PMID:23967334

  14. Expression of germline markers in three species of amphioxus supports a preformation mechanism of germ cell development in cephalochordates

    PubMed Central

    2013-01-01

    Background In a previous study, we showed that the cephalochordate amphioxus Branchiostoma floridae has localized maternal transcripts of conserved germ cell markers Vasa and Nanos in its early embryos. These results provided strong evidence to support a preformation mechanism for primordial germ cell (PGC) development in B. floridae. Results In this study, we further characterize the expression of B. floridae homologs of Piwi and Tudor, which play important roles in germline development in diverse metazoan animals. We show that maternal mRNA of one of the identified Piwi-like homologs, Bf-Piwil1, also colocalizes with Vasa in the vegetal germ plasm and has zygotic expression in both the putative PGCs and the tail bud, suggesting it may function in both germline and somatic stem cells. More interestingly, one Tudor family gene, Bf-Tdrd7, is only expressed maternally and colocalizes with Vasa in germ plasm, suggesting that it may function exclusively in germ cell specification. To evaluate the conservation of the preformation mechanism among amphioxus species, we further analyze Vasa, Nanos, Piwil1, and Tdrd7 expression in two Asian amphioxus species, B. belcheri and B. japonicum. Their maternal transcripts all localize in similar patterns to those seen in B. floridae. In addition, we labeled putative PGCs with Vasa antibody to trace their dynamic distribution in developing larvae. Conclusions We identify additional germ plasm components in amphioxus and demonstrate the molecular distinction between the putative germline stem cells and somatic stem cells. Moreover, our results suggest that preformation may be a conserved mechanism for PGC specification among Branchiostoma species. Our Vasa antibody staining results suggest that after the late neurula stage, amphioxus PGCs probably proliferate with the tail bud cells during posterior elongation and are deposited near the forming myomere boundaries. Subsequently, these PGCs would concentrate at the ventral tip of the

  15. Cabazitaxel overcomes cisplatin resistance in germ cell tumour cells.

    PubMed

    Gerwing, Mirjam; Jacobsen, Christine; Dyshlovoy, Sergey; Hauschild, Jessica; Rohlfing, Tina; Oing, Christoph; Venz, Simone; Oldenburg, Jan; Oechsle, Karin; Bokemeyer, Carsten; von Amsberg, Gunhild; Honecker, Friedemann

    2016-09-01

    Cisplatin-based chemotherapy is highly effective in metastasized germ cell tumours (GCT). However, 10-30 % of patients develop resistance to cisplatin, requiring salvage therapy. We investigated the in vitro activity of paclitaxel and the novel taxane cabazitaxel in cisplatin-sensitive and -resistant GCT cell lines. In vitro activity of paclitaxel and cabazitaxel was determined by proliferation assays, and mode of action of cabazitaxel was assessed by western blotting and two screening approaches, i.e. whole proteome analysis and a human apoptosis array. Activity of paclitaxel and cabazitaxel was not affected by cisplatin resistance, suggesting that there is no cross-resistance between these agents in vitro. Cabazitaxel treatment showed a strong inhibitory effect on colony formation capacity. Cabazitaxel induced classical apoptosis in all cell lines, reflected by cleavage of PARP and caspase 3, without inducing specific changes in the cell cycle distribution. Using the proteomic and human apoptosis array screening approaches, differential regulation of several proteins, including members of the bcl-2 family, was found, giving first insights into the mode of action of cabazitaxel in GCT. Cabazitaxel shows promising in vitro activity in GCT cells, independent of levels of cisplatin resistance.

  16. Noninvasive analysis of volatile biomarkers in human emanations for health and early disease diagnosis.

    PubMed

    Kataoka, Hiroyuki; Saito, Keita; Kato, Hisato; Masuda, Kazufumi

    2013-06-01

    Early disease diagnosis is crucial for human healthcare and successful therapy. Since any changes in homeostatic balance can alter human emanations, the components of breath exhalations and skin emissions may be diagnostic biomarkers for various diseases and metabolic disorders. Since hundreds of endogenous and exogenous volatile organic compounds (VOCs) are released from the human body, analysis of these VOCs may be a noninvasive, painless, and easy diagnostic tool. Sampling and preconcentration by sorbent tubes/traps and solid-phase microextraction, in combination with GC or GC-MS, are usually used to analyze VOCs. In addition, GC-MS-olfactometry is useful for simultaneous analysis of odorants and odor quality. Direct MS techniques are also useful for the online real-time detection of VOCs. This review focuses on recent developments in sampling and analysis of volatile biomarkers in human odors and/or emanations, and discusses future use of VOC analysis.

  17. WDR62 Regulates Early Neural and Glial Progenitor Specification of Human Pluripotent Stem Cells

    PubMed Central

    Alshawaf, Abdullah J.; Antonic, Ana; Skafidas, Efstratios

    2017-01-01

    Mutations in WD40-repeat protein 62 (WDR62) are commonly associated with primary microcephaly and other developmental cortical malformations. We used human pluripotent stem cells (hPSC) to examine WDR62 function during human neural differentiation and model early stages of human corticogenesis. Neurospheres lacking WDR62 expression showed decreased expression of intermediate progenitor marker, TBR2, and also glial marker, S100β. In contrast, inhibition of c-Jun N-terminal kinase (JNK) signalling during hPSC neural differentiation induced upregulation of WDR62 with a corresponding increase in neural and glial progenitor markers, PAX6 and EAAT1, respectively. These findings may signify a role of WDR62 in specifying intermediate neural and glial progenitors during human pluripotent stem cell differentiation. PMID:28690640

  18. Volcanic ash layers illuminate the resilience of Neanderthals and early modern humans to natural hazards.

    PubMed

    Lowe, John; Barton, Nick; Blockley, Simon; Ramsey, Christopher Bronk; Cullen, Victoria L; Davies, William; Gamble, Clive; Grant, Katharine; Hardiman, Mark; Housley, Rupert; Lane, Christine S; Lee, Sharen; Lewis, Mark; MacLeod, Alison; Menzies, Martin; Müller, Wolfgang; Pollard, Mark; Price, Catherine; Roberts, Andrew P; Rohling, Eelco J; Satow, Chris; Smith, Victoria C; Stringer, Chris B; Tomlinson, Emma L; White, Dustin; Albert, Paul; Arienzo, Ilenia; Barker, Graeme; Boric, Dusan; Carandente, Antonio; Civetta, Lucia; Ferrier, Catherine; Guadelli, Jean-Luc; Karkanas, Panagiotis; Koumouzelis, Margarita; Müller, Ulrich C; Orsi, Giovanni; Pross, Jörg; Rosi, Mauro; Shalamanov-Korobar, Ljiljiana; Sirakov, Nikolay; Tzedakis, Polychronis C

    2012-08-21

    Marked changes in human dispersal and development during the Middle to Upper Paleolithic transition have been attributed to massive volcanic eruption and/or severe climatic deterioration. We test this concept using records of volcanic ash layers of the Campanian Ignimbrite eruption dated to ca. 40,000 y ago (40 ka B.P.). The distribution of the Campanian Ignimbrite has been enhanced by the discovery of cryptotephra deposits (volcanic ash layers that are not visible to the naked eye) in archaeological cave sequences. They enable us to synchronize archaeological and paleoclimatic records through the period of transition from Neanderthal to the earliest anatomically modern human populations in Europe. Our results confirm that the combined effects of a major volcanic eruption and severe climatic cooling failed to have lasting impacts on Neanderthals or early modern humans in Europe. We infer that modern humans proved a greater competitive threat to indigenous populations than natural disasters.

  19. Volcanic ash layers illuminate the resilience of Neanderthals and early modern humans to natural hazards

    PubMed Central

    Lowe, John; Barton, Nick; Blockley, Simon; Ramsey, Christopher Bronk; Cullen, Victoria L.; Davies, William; Gamble, Clive; Grant, Katharine; Hardiman, Mark; Housley, Rupert; Lane, Christine S.; Lee, Sharen; Lewis, Mark; MacLeod, Alison; Menzies, Martin; Müller, Wolfgang; Pollard, Mark; Price, Catherine; Roberts, Andrew P.; Rohling, Eelco J.; Satow, Chris; Smith, Victoria C.; Stringer, Chris B.; Tomlinson, Emma L.; White, Dustin; Albert, Paul; Arienzo, Ilenia; Barker, Graeme; Borić, Dušan; Carandente, Antonio; Civetta, Lucia; Ferrier, Catherine; Guadelli, Jean-Luc; Karkanas, Panagiotis; Koumouzelis, Margarita; Müller, Ulrich C.; Orsi, Giovanni; Pross, Jörg; Rosi, Mauro; Shalamanov-Korobar, Ljiljiana; Sirakov, Nikolay; Tzedakis, Polychronis C.

    2012-01-01

    Marked changes in human dispersal and development during the Middle to Upper Paleolithic transition have been attributed to massive volcanic eruption and/or severe climatic deterioration. We test this concept using records of volcanic ash layers of the Campanian Ignimbrite eruption dated to ca. 40,000 y ago (40 ka B.P.). The distribution of the Campanian Ignimbrite has been enhanced by the discovery of cryptotephra deposits (volcanic ash layers that are not visible to the naked eye) in archaeological cave sequences. They enable us to synchronize archaeological and paleoclimatic records through the period of transition from Neanderthal to the earliest anatomically modern human populations in Europe. Our results confirm that the combined effects of a major volcanic eruption and severe climatic cooling failed to have lasting impacts on Neanderthals or early modern humans in Europe. We infer that modern humans proved a greater competitive threat to indigenous populations than natural disasters. PMID:22826222

  20. Origin of Clothing Lice Indicates Early Clothing Use by Anatomically Modern Humans in Africa

    PubMed Central

    Toups, Melissa A.; Kitchen, Andrew; Light, Jessica E.; Reed, David L.

    2011-01-01

    Clothing use is an important modern behavior that contributed to the successful expansion of humans into higher latitudes and cold climates. Previous research suggests that clothing use originated anywhere between 40,000 and 3 Ma, though there is little direct archaeological, fossil, or genetic evidence to support more specific estimates. Since clothing lice evolved from head louse ancestors once humans adopted clothing, dating the emergence of clothing lice may provide more specific estimates of the origin of clothing use. Here, we use a Bayesian coalescent modeling approach to estimate that clothing lice diverged from head louse ancestors at least by 83,000 and possibly as early as 170,000 years ago. Our analysis suggests that the use of clothing likely originated with anatomically modern humans in Africa and reinforces a broad trend of modern human developments in Africa during the Middle to Late Pleistocene. PMID:20823373

  1. Poultry genetic resource conservation using primordial germ cells

    PubMed Central

    NAKAMURA, Yoshiaki

    2016-01-01

    The majority of poultry genetic resources are maintained in situ in living populations. However, in situ conservation of poultry genetic resources always carries the risk of loss owing to pathogen outbreaks, genetic problems, breeding cessation, or natural disasters. Cryobanking of germplasm in birds has been limited to the use of semen, preventing conservation of the W chromosome and mitochondrial DNA. A further challenge is posed by the structure of avian eggs, which restricts the cryopreservation of ova and fertilized embryos, a technique widely used for mammalian species. By using a unique biological property and accessibility of avian primordial germ cells (PGCs), precursor cells for gametes, which temporally circulate in the vasculature during early development, an avian PGC transplantation technique has been established. To date, several techniques for PGC manipulation including purification, cryopreservation, depletion, and long-term culture have been developed in chickens. PGC transplantation combined with recent advanced PGC manipulation techniques have enabled ex situ conservation of poultry genetic resources in their complete form. Here, the updated technologies for avian PGC manipulation are introduced, and then the concept of a poultry PGC-bank is proposed by considering the biological properties of avian PGCs. PMID:27210834

  2. [On the road to a new humanity: the reception of psychoanalysis in the early Kinderladen movement].

    PubMed

    Kauders, Anthony D

    2014-01-01

    In the late 1960s a group of students in West Germany founded the so-called Kinderläden (day care centers) in order to experiment with new forms of early childhood education. Members of the early Kinderladen movement in particular pursued a radically utopian approach that, they hoped, would engender new human beings. With the aid of psychoanalytic writings, especially those of Wilhelm Reich, they sought to create subjects that would overcome repressive bourgeois norms and live out their sexuality freely. This reliance on Reich entailed a new interpretation of the "base", as psychoanalytic drive theory supplanted Marxist theory. As such, the early Kinderladen ac- tivists regarded the "basis" of society in biological, psychological, and pedagogic rather than economic terms.

  3. Early humans' egalitarian politics: runaway synergistic competition under an adapted veil of ignorance.

    PubMed

    Harvey, Marc

    2014-09-01

    This paper proposes a model of human uniqueness based on an unusual distinction between two contrasted kinds of political competition and political status: (1) antagonistic competition, in quest of dominance (antagonistic status), a zero-sum, self-limiting game whose stake--who takes what, when, how--summarizes a classical definition of politics (Lasswell 1936), and (2) synergistic competition, in quest of merit (synergistic status), a positive-sum, self-reinforcing game whose stake becomes "who brings what to a team's common good." In this view, Rawls's (1971) famous virtual "veil of ignorance" mainly conceals politics' antagonistic stakes so as to devise the principles of a just, egalitarian society, yet without providing any means to enforce these ideals (Sen 2009). Instead, this paper proposes that human uniqueness flourished under a real "adapted veil of ignorance" concealing the steady inflation of synergistic politics which resulted from early humans' sturdy egalitarianism. This proposition divides into four parts: (1) early humans first stumbled on a purely cultural means to enforce a unique kind of within-team antagonistic equality--dyadic balanced deterrence thanks to handheld weapons (Chapais 2008); (2) this cultural innovation is thus closely tied to humans' darkest side, but it also launched the cumulative evolution of humans' brightest qualities--egalitarian team synergy and solidarity, together with the associated synergistic intelligence, culture, and communications; (3) runaway synergistic competition for differential merit among antagonistically equal obligate teammates is the single politically selective mechanism behind the cumulative evolution of all these brighter qualities, but numerous factors to be clarified here conceal this mighty evolutionary driver; (4) this veil of ignorance persists today, which explains why humans' unique prosocial capacities are still not clearly understood by science. The purpose of this paper is to start lifting

  4. Classification of human pathogen bacteria for early screening using electronic nose

    NASA Astrophysics Data System (ADS)

    Zulkifli, Syahida Amani; Mohamad, Che Wan Syarifah Robiah; Abdullah, Abu Hassan

    2017-10-01

    This paper present human pathogen bacteria for early screening using electronic nose. Electronic nose (E-nose) known as gas sensor array is a device that analyze the odor measurement give the fast response and less time consuming for clinical diagnosis. Many bacterial pathogens could lead to life threatening infections. Accurate and rapid diagnosis is crucial for the successful management of these infections disease. The conventional method need more time to detect the growth of bacterial. Alternatively, the bacteria are Pseudomonas aeruginosa and Shigella cultured on different media agar can be detected and classifies according to the volatile compound in shorter time using electronic nose (E-nose). Then, the data from electronic nose (E-nose) is processed using statistical method which is principal component analysis (PCA). The study shows the capability of electronic nose (E-nose) for early screening for bacterial infection in human stomach.

  5. 3D quantitative analysis of early decomposition changes of the human face.

    PubMed

    Caplova, Zuzana; Gibelli, Daniele Maria; Poppa, Pasquale; Cummaudo, Marco; Obertova, Zuzana; Sforza, Chiarella; Cattaneo, Cristina

    2018-03-01

    Decomposition of the human body and human face is influenced, among other things, by environmental conditions. The early decomposition changes that modify the appearance of the face may hamper the recognition and identification of the deceased. Quantitative assessment of those changes may provide important information for forensic identification. This report presents a pilot 3D quantitative approach of tracking early decomposition changes of a single cadaver in controlled environmental conditions by summarizing the change with weekly morphological descriptions. The root mean square (RMS) value was used to evaluate the changes of the face after death. The results showed a high correlation (r = 0.863) between the measured RMS and the time since death. RMS values of each scan are presented, as well as the average weekly RMS values. The quantification of decomposition changes could improve the accuracy of antemortem facial approximation and potentially could allow the direct comparisons of antemortem and postmortem 3D scans.

  6. Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses.

    PubMed

    Fang, Shisong; Bai, Tian; Yang, Lei; Wang, Xin; Peng, Bo; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Zhu, Wenfei; Wang, Dayan; Cheng, Jinquan; Shu, Yuelong

    2016-08-03

    Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance.

  7. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

    PubMed

    Self, Matthew W; Peters, Judith C; Possel, Jessy K; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C; Roelfsema, Pieter R

    2016-03-01

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex.

  8. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex

    PubMed Central

    Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C.; Roelfsema, Pieter R.

    2016-01-01

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons’ receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex. PMID:27015604

  9. Early Upper Paleolithic in Eastern Europe and implications for the dispersal of modern humans.

    PubMed

    Anikovich, M V; Sinitsyn, A A; Hoffecker, John F; Holliday, Vance T; Popov, V V; Lisitsyn, S N; Forman, Steven L; Levkovskaya, G M; Pospelova, G A; Kuz'mina, I E; Burova, N D; Goldberg, Paul; Macphail, Richard I; Giaccio, Biagio; Praslov, N D

    2007-01-12

    Radiocarbon and optically stimulated luminescence dating and magnetic stratigraphy indicate Upper Paleolithic occupation-probably representing modern humans-at archaeological sites on the Don River in Russia 45,000 to 42,000 years ago. The oldest levels at Kostenki underlie a volcanic ash horizon identified as the Campanian Ignimbrite Y5 tephra that is dated elsewhere to about 40,000 years ago. The occupation layers contain bone and ivory artifacts, including possible figurative art, and fossil shells imported more than 500 kilometers. Thus, modern humans appeared on the central plain of Eastern Europe as early as anywhere else in northern Eurasia.

  10. Exome sequencing of bilateral testicular germ cell tumors suggests independent development lineages.

    PubMed

    Brabrand, Sigmund; Johannessen, Bjarne; Axcrona, Ulrika; Kraggerud, Sigrid M; Berg, Kaja G; Bakken, Anne C; Bruun, Jarle; Fosså, Sophie D; Lothe, Ragnhild A; Lehne, Gustav; Skotheim, Rolf I

    2015-02-01

    Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors), of these three patients in whom both tumors were available (six tumors) and two patients each with only one available tumor (two tumors). Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21), some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA), and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  11. Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis

    PubMed Central

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E.; Alagaratnam, Sharmini; Skotheim, Rolf I.; Abeler, Vera M.

    2013-01-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/β-catenin and TGF-β/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors. PMID:23575763

  12. Sex Reversal in Zebrafish fancl Mutants Is Caused by Tp53-Mediated Germ Cell Apoptosis

    PubMed Central

    Rodríguez-Marí, Adriana; Cañestro, Cristian; BreMiller, Ruth A.; Nguyen-Johnson, Alexandria; Asakawa, Kazuhide; Kawakami, Koichi; Postlethwait, John H.

    2010-01-01

    The molecular genetic mechanisms of sex determination are not known for most vertebrates, including zebrafish. We identified a mutation in the zebrafish fancl gene that causes homozygous mutants to develop as fertile males due to female-to-male sex reversal. Fancl is a member of the Fanconi Anemia/BRCA DNA repair pathway. Experiments showed that zebrafish fancl was expressed in developing germ cells in bipotential gonads at the critical time of sexual fate determination. Caspase-3 immunoassays revealed increased germ cell apoptosis in fancl mutants that compromised oocyte survival. In the absence of oocytes surviving through meiosis, somatic cells of mutant gonads did not maintain expression of the ovary gene cyp19a1a and did not down-regulate expression of the early testis gene amh; consequently, gonads masculinized and became testes. Remarkably, results showed that the introduction of a tp53 (p53) mutation into fancl mutants rescued the sex-reversal phenotype by reducing germ cell apoptosis and, thus, allowed fancl mutants to become fertile females. Our results show that Fancl function is not essential for spermatogonia and oogonia to become sperm or mature oocytes, but instead suggest that Fancl function is involved in the survival of developing oocytes through meiosis. This work reveals that Tp53-mediated germ cell apoptosis induces sex reversal after the mutation of a DNA–repair pathway gene by compromising the survival of oocytes and suggests the existence of an oocyte-derived signal that biases gonad fate towards the female developmental pathway and thereby controls zebrafish sex determination. PMID:20661450

  13. Visualization of early influenza A virus trafficking in human dendritic cells using STED microscopy.

    PubMed

    Baharom, Faezzah; Thomas, Oliver S; Lepzien, Rico; Mellman, Ira; Chalouni, Cécile; Smed-Sörensen, Anna

    2017-01-01

    Influenza A viruses (IAV) primarily target respiratory epithelial cells, but can also replicate in immune cells, including human dendritic cells (DCs). Super-resolution microscopy provides a novel method of visualizing viral trafficking by overcoming the resolution limit imposed by conventional light microscopy, without the laborious sample preparation of electron microscopy. Using three-color Stimulated Emission Depletion (STED) microscopy, we visualized input IAV nucleoprotein (NP), early and late endosomal compartments (EEA1 and LAMP1 respectively), and HLA-DR (DC membrane/cytosol) by immunofluorescence in human DCs. Surface bound IAV were internalized within 5 min of infection. The association of virus particles with early endosomes peaked at 5 min when 50% of NP+ signals were also EEA1+. Peak association with late endosomes occurred at 15 min when 60% of NP+ signals were LAMP1+. At 30 min of infection, the majority of NP signals were in the nucleus. Our findings illustrate that early IAV trafficking in human DCs proceeds via the classical endocytic pathway.

  14. Quantitative analysis of fluoride-induced hypermineralization of developing enamel in neonatal hamster tooth germs

    NASA Astrophysics Data System (ADS)

    Tros, G. H. J.; Lyaruu, D. M.; Vis, R. D.

    1993-10-01

    A procedure was developed for analysing the effect of fluoride on mineralization in the enamel of neonatal hamster molars during amelogenesis by means of the quantitative determination of the mineral content. In this procedure the distribution of calcium and mineral concentration was determined in sections containing developing tooth enamel mineral embedded in an organic epoxy resin matrix by means of the micro-PIXE technique. This allowed the determination of the calcium content along preselected tracks with a spatial resolution of 2 μm using a microprobe PIXE setup with a 3 MeV proton beam of 10 to 50 pA with a spot size of 2 μm in the track direction. In this procedure the X-ray yield is used as a measure for the calcium content. The thickness of each sample section is determined independently by measuring the energy loss of α-particles from a calibration source upon passing through the sample. The sample is considered as consisting of two bulk materials, allowing the correction for X-ray self-absorption and the calculation of the calcium concentration. The procedure was applied for measuring the distribution of mineral concentration in 2 μm thick sections taken from tooth germs of hamsters administered with NaF. The measurements indicated that a single intraperitoneal administration of 20 mg NaF/kg body weight to 4-to-5-day-old hamsters leads within 24 h to hypermineralization of certain focal enamel surface areas containing cystic lesions under transitional and early secretory ameloblasts. The mineral concentration there is substantially increased due to the fluoride treatment (35%, instead of 5 to 10% as in the controls), indicating that the normal mineralization process has been seriously disturbed. Furthermore it is found that using this technique the mineral concentration peaks at about 70% at the dentine-enamel junction, which is comparable to that reported for human dentine using other techniques.

  15. Lipid phosphate phosphatase activity regulates dispersal and bilateral sorting of embryonic germ cells in Drosophila

    PubMed Central

    Renault, Andrew D.; Kunwar, Prabhat S.; Lehmann, Ruth

    2010-01-01

    In Drosophila, germ cell survival and directionality of migration are controlled by two lipid phosphate phosphatases (LPP), wunen (wun) and wunen-2 (wun2). wun wun2 double mutant analysis reveals that the two genes, hereafter collectively called wunens, act redundantly in primordial germ cells. We find that wunens mediate germ cell-germ cell repulsion and that this repulsion is necessary for germ cell dispersal and proper transepithelial migration at the onset of migration and for the equal sorting of the germ cells between the two embryonic gonads during their migration. We propose that this dispersal function optimizes adult fecundity by assuring maximal germ cell occupancy of both gonads. Furthermore, we find that the requirement for wunens in germ cell survival can be eliminated by blocking germ cell migration. We suggest that this essential function of Wunen is needed to maintain cell integrity in actively migrating germ cells. PMID:20431117

  16. Early parental care is important for hippocampal maturation: evidence from brain morphology in humans.

    PubMed

    Rao, Hengyi; Betancourt, Laura; Giannetta, Joan M; Brodsky, Nancy L; Korczykowski, Marc; Avants, Brian B; Gee, James C; Wang, Jiongjiong; Hurt, Hallam; Detre, John A; Farah, Martha J

    2010-01-01

    The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation.

  17. Eight Ways to Guard Against Germs in Everyday Life

    MedlinePlus

    ... disinfecting an eFlow ® technology nebulizer: Do not use antibacterial soap or white liquid dish soap, like Ivory ® ... against these germs by limiting time spent doing activities that would put you in frequent contact with ...

  18. Impact of gut microbiota on the fly's germ line.

    PubMed

    Elgart, Michael; Stern, Shay; Salton, Orit; Gnainsky, Yulia; Heifetz, Yael; Soen, Yoav

    2016-04-15

    Unlike vertically transmitted endosymbionts, which have broad effects on their host's germ line, the extracellular gut microbiota is transmitted horizontally and is not known to influence the germ line. Here we provide evidence supporting the influence of these gut bacteria on the germ line of Drosophila melanogaster. Removal of the gut bacteria represses oogenesis, expedites maternal-to-zygotic-transition in the offspring and unmasks hidden phenotypic variation in mutants. We further show that the main impact on oogenesis is linked to the lack of gut Acetobacter species, and we identify the Drosophila Aldehyde dehydrogenase (Aldh) gene as an apparent mediator of repressed oogenesis in Acetobacter-depleted flies. The finding of interactions between the gut microbiota and the germ line has implications for reproduction, developmental robustness and adaptation.

  19. Germ Tube Growth Inhibitor from Cronartium comandrae Aeciospores

    PubMed Central

    Eppstein, Deborah A.; Tainter, F. H.

    1979-01-01

    Two compounds showing self-inhibitory action during germination of aeciospores of the comandra blister rust fungus (Cronartium comandrae Pk.) were extracted from these aeciospores by shaking with 0.2 M NH4HCO3 (pH 7.8) for 4 h. One of these, the germination self inhibitor (D. A. Eppstein and F. H. Tainter, Phytopathology 66:1395-1397, 1976), was removed from the ammonium bicarbonate buffer by using chloroform. The water layer which remained contained a substance which, at ca. 10−4 M concentration, had no apparent effect on germ tube emergence but which inhibited normal germ tube growth. Linear germ tube growth ceased or a dendritic or vesicular pattern of growth resulted, depending on the concentration of inhibitor added to extracted germinating spores. The germ tube growth inhibitor appears to be a peptide with a molecular weight of ca. 2,000. Images PMID:16345335

  20. Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung transplantation.

    PubMed

    Shah, Ashish S; Leffell, M Sue; Lucas, Donna; Zachary, Andrea A

    2009-02-01

    Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.

  1. Immunohistochemical Markers of Neural Progenitor Cells in the Early Embryonic Human Cerebral Cortex

    PubMed Central

    Vinci, L.; Ravarino, A.; Fanos, V.; Naccarato, A.G.; Senes, G.; Gerosa, C.; Bevilacqua, G.; Faa, G.; Ambu, R.

    2016-01-01

    The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development. To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tβ4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation. PMID:26972711

  2. Spermiogenesis and exchange of basic nuclear proteins are impaired in male germ cells lacking Camk4.

    PubMed

    Wu, J Y; Ribar, T J; Cummings, D E; Burton, K A; McKnight, G S; Means, A R

    2000-08-01

    Ca2+/calmodulin-dependent protein kinase IV (Camk4; also known as CaMKIV), a multifunctional serine/threonine protein kinase with limited tissue distribution, has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells. In the mouse testis, however, Camk4 is expressed in spermatids and associated with chromatin and nuclear matrix. Elongating spermatids are not transcriptionally active, raising the possibility that Camk4 has a novel function in male germ cells. To investigate the role of Camk4 in spermatogenesis, we have generated mice with a targeted deletion of the gene Camk4. Male Camk4-/- mice are infertile with impairment of spermiogenesis in late elongating spermatids. The sequential deposition of sperm basic nuclear proteins on chromatin is disrupted, with a specific loss of protamine-2 and prolonged retention of transition protein-2 (Tnp2) in step-15 spermatids. Protamine-2 is phosphorylated by Camk4 in vitro, implicating a connection between Camk4 signalling and the exchange of basic nuclear proteins in mammalian male germ cells. Defects in protamine-2 have been identified in sperm of infertile men, suggesting that our results may have clinical implications for the understanding of human male infertility.

  3. Use of Stirred Suspension Bioreactors for Male Germ Cell Enrichment.

    PubMed

    Sakib, Sadman; Dores, Camila; Rancourt, Derrick; Dobrinski, Ina

    2016-01-01

    Spermatogenesis is a stem cell based system. Both therapeutic and biomedical research applications of spermatogonial stem cells require a large number of cells. However, there are only few germ line stem cells in the testis, contained in the fraction of undifferentiated spermatogonia. The lack of specific markers makes it difficult to isolate these cells. The long term maintenance and proliferation of nonrodent germ cells in culture has so far been met with limited success, partially due to the lack of highly enriched starting populations. Differential plating, which depends on the differential adhesion properties of testicular somatic and germ cells to tissue culture dishes, has been the method of choice for germ cell enrichment, especially for nonrodent germ cells. However, for large animals, this process becomes labor intensive and increases variability due to the need for extensive handling. Here, we describe the use of stirred suspension bioreactors, as a novel system for enriching undifferentiated germ cells from 1-week-old pigs. This method capitalizes on the adherent properties of somatic cells within a controlled environment, thus promoting the enrichment of progenitor cells with minimal handling and variability.

  4. Germ-line induction of the Caenorhabditis elegans vulva

    PubMed Central

    Thompson, Beth E.; Lamont, Liana B.; Kimble, Judith

    2006-01-01

    Development of the Caenorhabditis elegans vulva serves as a paradigm for intercellular signaling during animal development. In wild-type animals, the somatic gonadal anchor cell generates the LIN-3/EGF ligand to induce vulval fates in the underlying hypodermis, whereas FBF, FOG-1, and FOG-3 control germ-line development. Here we report that FBF functions redundantly with FOG-1 and FOG-3 to control vulval induction: animals lacking FBF and either FOG-1 or FOG-3 have multiple vulvae, the Muv phenotype. The fog; fbf Muv phenotype is generated by aberrant induction of vulval precursor cells (VPCs): in wild-type animals, three VPCs are induced to form a single vulva, but, in fog; fbf mutants, four or five VPCs are typically induced, resulting in ectopic vulvae. Laser ablation experiments and mosaic analyses demonstrate that the germ line is critical for the fog; fbf Muv phenotype. Consistent with that site of action, we detect FBF and FOG-1 in the germ line but not in the VPCs. The simplest interpretation is that FOG-1, FOG-3, and FBF act in the germ line to influence vulval fates. The LIN-3/EGF ligand may be the germ-line signal to the VPCs: the fog; fbf Muv phenotype depends on LIN-3 activity, and the lin-3 3′ UTR possesses an FBF binding element. Our findings reveal new insights into germ line-to-soma signals and the role of PUF proteins in animal development. PMID:16407099

  5. Effects of early human handling on the pain sensitivity of young lambs.

    PubMed

    Guesgen, Mirjam J; Beausoleil, Ngaio J; Stewart, Mairi

    2013-01-01

    Pain sensitivity of lambs changes over the first weeks of life. However, the effects of early treatments such as human handling on pain sensitivity are unknown for this species. This study investigated the effects of regular early gentle human handling on the pain sensitivity of lambs, indicated by their behavioural responses to tail docking. Prospective part-blinded experimental study. Twenty-nine singleton Coopworth lambs (females n=14, males n=15). Starting at one day of age, lambs were either handled twice daily for 2 weeks (Handled), were kept in the presence of lambs who were being handled but were not handled themselves (Presence), or were exposed to a human only during routine feeding and care (Control). At 3 weeks of age, all lambs were tail docked using rubber rings. Changes in behaviour due to docking were calculated and change data were analyzed using two-way anova with treatment and test pen as main factors. All lambs showed significant increases in the frequency and duration of behaviours indicative of pain, including 'abnormal' behaviours, and decreases in the frequency and duration of 'normal' behaviours after docking. Handled lambs showed a smaller increase in the time spent lying abnormally after docking than did Control lambs (mean transformed change in proportion of 30 minutes spent±SE: Control 0.55±0.04; Handled 0.38±0.03; Presence 0.48±0.03; C versus H t=3.45, p=0.007). These results provide some evidence that handling early in life may reduce subsequent pain sensitivity in lambs. While the behavioural effects of handling on pain behaviour were subtle, the results suggest, at the very least, that early handling does not increase pain sensitivity in lambs and suggests there is still flexibility postnatally in the pain processing system of a precocial species. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  6. The human early-life exposome (HELIX): project rationale and design.

    PubMed

    Vrijheid, Martine; Slama, Rémy; Robinson, Oliver; Chatzi, Leda; Coen, Muireann; van den Hazel, Peter; Thomsen, Cathrine; Wright, John; Athersuch, Toby J; Avellana, Narcis; Basagaña, Xavier; Brochot, Celine; Bucchini, Luca; Bustamante, Mariona; Carracedo, Angel; Casas, Maribel; Estivill, Xavier; Fairley, Lesley; van Gent, Diana; Gonzalez, Juan R; Granum, Berit; Gražulevičienė, Regina; Gutzkow, Kristine B; Julvez, Jordi; Keun, Hector C; Kogevinas, Manolis; McEachan, Rosemary R C; Meltzer, Helle Margrete; Sabidó, Eduard; Schwarze, Per E; Siroux, Valérie; Sunyer, Jordi; Want, Elizabeth J; Zeman, Florence; Nieuwenhuijsen, Mark J

    2014-06-01

    Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onward, complementing the genome. The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "early-life exposome." Here we describe the general design of the project. In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother-child pairs, and biomarkers will be measured in a subset of 1,200 mother-child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

  7. Electromechanical properties of human osteoarthritic and asymptomatic articular cartilage are sensitive and early detectors of degeneration.

    PubMed

    Hadjab, I; Sim, S; Karhula, S S; Kauppinen, S; Garon, M; Quenneville, E; Lavigne, P; Lehenkari, P P; Saarakkala, S; Buschmann, M D

    2018-03-01

    To evaluate cross-correlations of ex vivo electromechanical properties with cartilage and subchondral bone plate thickness, as well as their sensitivity and specificity regarding early cartilage degeneration in human tibial plateau. Six pairs of tibial plateaus were assessed ex vivo using an electromechanical probe (Arthro-BST) which measures a quantitative parameter (QP) reflecting articular cartilage compression-induced streaming potentials. Cartilage thickness was then measured with an automated thickness mapping technique using Mach-1 multiaxial mechanical tester. Subsequently, a visual assessment was performed by an experienced orthopedic surgeon using the International Cartilage Repair Society (ICRS) grading system. Each tibial plateau was finally evaluated with μCT scanner to determine the subchondral-bone plate thickness over the entire surface. Cross-correlations between assessments decreased with increasing degeneration level. Moreover, electromechanical QP and subchondral-bone plate thickness increased strongly with ICRS grade (ρ = 0.86 and ρ = 0.54 respectively), while cartilage thickness slightly increased (ρ = 0.27). Sensitivity and specificity analysis revealed that the electromechanical QP is the most performant to distinguish between different early degeneration stages, followed by subchondral-bone plate thickness and then cartilage thickness. Lastly, effect sizes of cartilage and subchondral-bone properties were established to evaluate whether cartilage or bone showed the most noticeable changes between normal (ICRS 0) and each early degenerative stage. Thus, the effect sizes of cartilage electromechanical QP were almost twice those of the subchondral-bone plate thickness, indicating greater sensitivity of electromechanical measurements to detect early osteoarthritis. The potential of electromechanical properties for the diagnosis of early human cartilage degeneration was highlighted and supported by cartilage thickness and

  8. Monitoring of human populations for early markers of cadmium toxicity: A review

    SciT

    Fowler, Bruce A.

    2009-08-01

    Exposure of human populations to cadmium (Cd) from air, food and water may produce effects in organs such as the kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Since Cd has been identified as a human carcinogen, biomarkers for early detection of susceptibility to cancer are of an importance to public health. The ability to document Cd exposure and uptake of this element through biological monitoring is a first step towards understanding its health effects. Interpretation and application of biological monitoring data for predicting human health outcomes require correlation with biological measures of organ system responses to the documented exposure.more » Essential to this understanding is the detection and linkage of early biological responses toxic effects in target cell populations. Fortunately, advances in cell biology have resulted in the development of pre-clinical biological markers (biomarkers) that demonstrate measurable and characteristic molecular changes in organ systems following chemical exposures that occur prior to the onset of overt clinical disease or development of cancer. Technical advances have rendered a number of these biomarkers practical for monitoring Cd-exposed human populations. Biomarkers will be increasingly important in relation to monitoring effects from the exposure to new Cd-based high technology materials. For example, cadmium-selenium (CdSe), nano-materials made from combinations of these elements have greatly altered cellular uptake characteristics due to particle size. These differences may greatly alter effects at the target cell level and hence risks for organ toxicities from such exposures. The value of validated biomarkers for early detection of systemic Cd-induced effects in humans cannot be underestimated due to the rapid expansion of nano-material technologies. This review will attempt to briefly summarize the applications, to date, of biomarker endpoints for assessing target organ system

  9. Monitoring of human populations for early markers of cadmium toxicity: a review.

    PubMed

    Fowler, Bruce A

    2009-08-01

    Exposure of human populations to cadmium (Cd) from air, food and water may produce effects in organs such as the kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Since Cd has been identified as a human carcinogen, biomarkers for early detection of susceptibility to cancer are of an importance to public health. The ability to document Cd exposure and uptake of this element through biological monitoring is a first step towards understanding its health effects. Interpretation and application of biological monitoring data for predicting human health outcomes require correlation with biological measures of organ system responses to the documented exposure. Essential to this understanding is the detection and linkage of early biological responses toxic effects in target cell populations. Fortunately, advances in cell biology have resulted in the development of pre-clinical biological markers (biomarkers) that demonstrate measurable and characteristic molecular changes in organ systems following chemical exposures that occur prior to the onset of overt clinical disease or development of cancer. Technical advances have rendered a number of these biomarkers practical for monitoring Cd-exposed human populations. Biomarkers will be increasingly important in relation to monitoring effects from the exposure to new Cd-based high technology materials. For example, cadmium-selenium (CdSe), nano-materials made from combinations of these elements have greatly altered cellular uptake characteristics due to particle size. These differences may greatly alter effects at the target cell level and hence risks for organ toxicities from such exposures. The value of validated biomarkers for early detection of systemic Cd-induced effects in humans cannot be underestimated due to the rapid expansion of nano-material technologies. This review will attempt to briefly summarize the applications, to date, of biomarker endpoints for assessing target organ system effects in

  10. Transient translational quiescence in primordial germ cells

    PubMed Central

    Oulhen, Nathalie; Swartz, S. Zachary; Laird, Jessica; Mascaro, Alexandra

    2017-01-01

    Stem cells in animals often exhibit a slow cell cycle and/or low transcriptional activity referred to as quiescence. Here, we report that the translational activity in the primordial germ cells (PGCs) of the sea urchin embryo (Strongylocentrotus purpuratus) is quiescent. We measured new protein synthesis with O-propargyl-puromycin and L-homopropargylglycine Click-iT technologies, and determined that these cells synthesize protein at only 6% the level of their adjacent somatic cells. Knockdown of translation of the RNA-binding protein Nanos2 by morpholino antisense oligonucleotides, or knockout of the Nanos2 gene by CRISPR/Cas9 resulted in a significant, but partial, increase (47%) in general translation specifically in the PGCs. We found that the mRNA of the translation factor eEF1A is excluded from the PGCs in a Nanos2-dependent manner, a consequence of a Nanos/Pumilio response element (PRE) in its 3′UTR. In addition to eEF1A, the cytoplasmic pH of the PGCs appears to repress translation and simply increasing the pH also significantly restores translation selectively in the PGCs. We conclude that the PGCs of this sea urchin institute parallel pathways to quiesce translation thoroughly but transiently. PMID:28235822

  11. Tools to Support Human Factors and Systems Engineering Interactions During Early Analysis

    NASA Technical Reports Server (NTRS)

    Thronesbery, Carroll; Malin, Jane T.; Holden, Kritina; Smith, Danielle Paige

    2005-01-01

    We describe an approach and existing software tool support for effective interactions between human factors engineers and systems engineers in early analysis activities during system acquisition. We examine the tasks performed during this stage, emphasizing those tasks where system engineers and human engineers interact. The Concept of Operations (ConOps) document is an important product during this phase, and particular attention is paid to its influences on subsequent acquisition activities. Understanding this influence helps ConOps authors describe a complete system concept that guides subsequent acquisition activities. We identify commonly used system engineering and human engineering tools and examine how they can support the specific tasks associated with system definition. We identify possible gaps in the support of these tasks, the largest of which appears to be creating the ConOps document itself. Finally, we outline the goals of our future empirical investigations of tools to support system concept definition.

  12. Tools to Support Human Factors and Systems Engineering Interactions During Early Analysis

    NASA Technical Reports Server (NTRS)

    Thronesbery, Carroll; Malin, Jane T.; Holden, Kritina; Smith, Danielle Paige

    2006-01-01

    We describe an approach and existing software tool support for effective interactions between human factors engineers and systems engineers in early analysis activities during system acquisition. We examine the tasks performed during this stage, emphasizing those tasks where system engineers and human engineers interact. The Concept of Operations (ConOps) document is an important product during this phase, and particular attention is paid to its influences on subsequent acquisition activities. Understanding this influence helps ConOps authors describe a complete system concept that guides subsequent acquisition activities. We identify commonly used system engineering and human engineering tools and examine how they can support the specific tasks associated with system definition. We identify possible gaps in the support of these tasks, the largest of which appears to be creating the ConOps document itself. Finally, we outline the goals of our future empirical investigations of tools to support system concept definition.

  13. Germ-line and somatic EPHA2 coding variants in lens aging and cataract.

    PubMed

    Bennett, Thomas M; M'Hamdi, Oussama; Hejtmancik, J Fielding; Shiels, Alan

    2017-01-01

    Rare germ-line mutations in the coding regions of the human EPHA2 gene (EPHA2) have been associated with inherited forms of pediatric cataract, whereas, frequent, non-coding, single nucleotide variants (SNVs) have been associated with age-related cataract. Here we sought to determine if germ-line EPHA2 coding SNVs were associated with age-related cataract in a case-control DNA panel (> 50 years) and if somatic EPHA2 coding SNVs were associated with lens aging and/or cataract in a post-mortem lens DNA panel (> 48 years). Micro-fluidic PCR amplification followed by targeted amplicon (exon) next-generation (deep) sequencing of EPHA2 (17-exons) afforded high read-depth coverage (1000x) for > 82% of reads in the cataract case-control panel (161 cases, 64 controls) and > 70% of reads in the post-mortem lens panel (35 clear lens pairs, 22 cataract lens pairs). Novel and reference (known) missense SNVs in EPHA2 that were predicted in silico to be functionally damaging were found in both cases and controls from the age-related cataract panel at variant allele frequencies (VAFs) consistent with germ-line transmission (VAF > 20%). Similarly, both novel and reference missense SNVs in EPHA2 were found in the post-mortem lens panel at VAFs consistent with a somatic origin (VAF > 3%). The majority of SNVs found in the cataract case-control panel and post-mortem lens panel were transitions and many occurred at di-pyrimidine sites that are susceptible to ultraviolet (UV) radiation induced mutation. These data suggest that novel germ-line (blood) and somatic (lens) coding SNVs in EPHA2 that are predicted to be functionally deleterious occur in adults over 50 years of age. However, both types of EPHA2 coding variants were present at comparable levels in individuals with or without age-related cataract making simple genotype-phenotype correlations inconclusive.

  14. Germ-line and somatic EPHA2 coding variants in lens aging and cataract

    PubMed Central

    Bennett, Thomas M.; M’Hamdi, Oussama; Hejtmancik, J. Fielding

    2017-01-01

    Rare germ-line mutations in the coding regions of the human EPHA2 gene (EPHA2) have been associated with inherited forms of pediatric cataract, whereas, frequent, non-coding, single nucleotide variants (SNVs) have been associated with age-related cataract. Here we sought to determine if germ-line EPHA2 coding SNVs were associated with age-related cataract in a case-control DNA panel (> 50 years) and if somatic EPHA2 coding SNVs were associated with lens aging and/or cataract in a post-mortem lens DNA panel (> 48 years). Micro-fluidic PCR amplification followed by targeted amplicon (exon) next-generation (deep) sequencing of EPHA2 (17-exons) afforded high read-depth coverage (1000x) for > 82% of reads in the cataract case-control panel (161 cases, 64 controls) and > 70% of reads in the post-mortem lens panel (35 clear lens pairs, 22 cataract lens pairs). Novel and reference (known) missense SNVs in EPHA2 that were predicted in silico to be functionally damaging were found in both cases and controls from the age-related cataract panel at variant allele frequencies (VAFs) consistent with germ-line transmission (VAF > 20%). Similarly, both novel and reference missense SNVs in EPHA2 were found in the post-mortem lens panel at VAFs consistent with a somatic origin (VAF > 3%). The majority of SNVs found in the cataract case-control panel and post-mortem lens panel were transitions and many occurred at di-pyrimidine sites that are susceptible to ultraviolet (UV) radiation induced mutation. These data suggest that novel germ-line (blood) and somatic (lens) coding SNVs in EPHA2 that are predicted to be functionally deleterious occur in adults over 50 years of age. However, both types of EPHA2 coding variants were present at comparable levels in individuals with or without age-related cataract making simple genotype-phenotype correlations inconclusive. PMID:29267365

  15. NANOG priming before full reprogramming may generate germ cell tumours.

    PubMed

    Grad, I; Hibaoui, Y; Jaconi, M; Chicha, L; Bergström-Tengzelius, R; Sailani, M R; Pelte, M F; Dahoun, S; Mitsiadis, T A; Töhönen, V; Bouillaguet, S; Antonarakis, S E; Kere, J; Zucchelli, M; Hovatta, O; Feki, A

    2011-11-09

    Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality. However, stem cells and cancer cells share many common characteristics; therefore, it is crucial to be able to discriminate between them. We generated two induced pluripotent stem cell (iPSC) lines, with NANOG pre-transduction followed by OCT3/4, SOX2, and LIN28 overexpression. One of the cell lines, CHiPS W, showed normal pluripotent stem cell characteristics, while the other, CHiPS A, though expressing pluripotency markers, failed to differentiate and gave rise to germ cell-like tumours in vivo. Comparative genomic hybridisation analysis of the generated iPS lines revealed that they were genetically more stable than human embryonic stem cell counterparts. This analysis proved to be predictive for the differentiation potential of analysed cells. Moreover, the CHiPS A line expressed a lower ratio of p53/p21 when compared to CHiPS W. NANOG pre-induction followed by OCT3/4, SOX2, MYC, and KLF4 induction resulted in the same tumour-inducing phenotype. These results underline the importance of a re-examination of the role of NANOG during reprogramming. Moreover, this reprogramming method may provide insights into primordial cell tumour formation and cancer stem cell transformation.

  16. Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection.

    PubMed

    Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

    2017-03-01

    Little research focuses on the association between immune thrombocytopenic purpura and human immunodeficiency virus infection in Taiwan. This study investigated whether immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection in Taiwan. We conducted a retrospective population-based cohort study using data of individuals enrolled in Taiwan National Health Insurance Program. There were 5472 subjects aged 1-84 years with a new diagnosis of immune thrombocytopenic purpura as the purpura group since 1998-2010 and 21,887 sex-matched and age-matched, randomly selected subjects without immune thrombocytopenic purpura as the non-purpura group. The incidence of human immunodeficiency virus infection at the end of 2011 was measured in both groups. We used the multivariable Cox proportional hazards regression model to measure the hazard ratio and 95 % confidence interval (CI) for the association between immune thrombocytopenic purpura and human immunodeficiency virus infection. The overall incidence of human immunodeficiency virus infection was 6.47-fold higher in the purpura group than that in the non-purpura group (3.78 vs. 0.58 per 10,000 person-years, 95 % CI 5.83-7.18). After controlling for potential confounding factors, the adjusted HR of human immunodeficiency virus infection was 6.3 (95 % CI 2.58-15.4) for the purpura group, as compared with the non-purpura group. We conclude that individuals with immune thrombocytopenic purpura are 6.47-fold more likely to have human immunodeficiency virus infection than those without immune thrombocytopenic purpura. We suggest not all patients, but only those who have risk factors for human immunodeficiency virus infection should receive testing for undiagnosed human immunodeficiency virus infection when they develop immune thrombocytopenic purpura.

  17. Application of Carnegie stages of development to unify human and baboon ultrasound findings early in pregnancy.

    PubMed

    Santolaya-Forgas, Joaquin; De Leon-Luis, Juan; Friel, Lara A; Wolf, Roman

    2007-09-01

    The objective of this study was to determine if very early ultrasonographic measurements obtained from human and baboon are comparable. For this purpose, the gestational, amniotic and yolk sacs, embryonic crown rump length (CRL) and heart rate were measured ultrasonographically between 35 and 47 days from the mean day of a three-day mating period in baboons (n=18) and between 42 to 58 days from fertilization as calculated from the CRL measurements in human pregnancies (n=82). Ultrasonographic measurements from both species were then plotted in the same graph using Carnegie stages of embryonic development as the independent variable to allow for visual comparisons. Mean gestational age at ultrasonographic studies was significantly different for humans and baboons (50.4 vs. 41 days, respectively; p>0.01). Significant correlations (p>0.01) were noted between ultrasonographic measurements and Carnegie stages of development in both humans and baboons. Only the gestational and the yolk sacs were significantly smaller in baboons than in humans (p>0.05). The findings that embryonic CRL, extra-embryonic space and heart rate are very similar between the 17th and 23rd Carnegie developmental stages make the baboon a promising surrogate of human pregnancy for investigations using celocentesis.

  18. Basic fibroblast growth factor promotes the development of human ovarian early follicles during growth in vitro.

    PubMed

    Wang, Tian-ren; Yan, Li-ying; Yan, Jie; Lu, Cui-ling; Xia, Xi; Yin, Tai-lang; Zhu, Xiao-hui; Gao, Jiang-man; Ding, Ting; Hu, Wei-hong; Guo, Hong-yan; Li, Rong; Qiao, Jie

    2014-03-01

    What is the effect of basic fibroblast growth factor (bFGF) on the growth of individual early human follicles in a three-dimensional (3D) culture system in vitro? The addition of 200 ng bFGF/ml improves human early follicle growth, survival and viability during growth in vitro. It has been demonstrated that bFGF enhances primordial follicle development in human ovarian tissue culture. However, the growth and survival of individual early follicles in encapsulated 3D culture have not been reported. The maturation in vitro of human ovarian follicles was investigated. Ovarian tissue (n= 11) was obtained from 11 women during laparoscopic surgery for gynecological disease, after obtaining written informed consent. One hundred and fifty-four early follicles were isolated by enzymic digestion and mechanical disruption. They were individually encapsulated into alginate (1% w/v) and randomly assigned to be cultured with 0, 100, 200 or 300 ng bFGF/ml for 8 days. Individual follicles were cultured in minimum essential medium α (αMEM) supplemented with bFGF. Follicle survival and growth were assessed by microscopy. Follicle viability was evaluated under confocal laser scanning microscope following Calcein-AM and Ethidium homodimer-I (Ca-AM/EthD-I) staining. After 8 days in culture, all 154 follicles had increased in size. The diameter and survival rate of the follicles and the percentage with good viability were significantly higher in the group cultured with 200 ng bFGF/ml than in the group without bFGF (P < 0.05). The percentage of follicles in the pre-antral stage was significantly higher in the 200 ng bFGF/ml group than in the group without bFGF (P < 0.05), while the percentages of primordial and primary follicles were significantly lower (P < 0.05). The study focuses on the effect of bFGF on the development of individual human early follicles in 3D culture in vitro and has limited ability to reveal the specific effect of bFGF at each different stage. The findings

  19. Skeletal variation among early Holocene North American humans: implications for origins and diversity in the Americas.

    PubMed

    Auerbach, Benjamin M

    2012-12-01

    The movement of humans into the Americas remains a major topic of debate among scientific disciplines. Central to this discussion is ascertaining the timing and migratory routes of the earliest colonizers, in addition to understanding their ancestry. Molecular studies have recently argued that the colonizing population was isolated from other Asian populations for an extended period before proceeding to colonize the Americas. This research has suggested that Beringia was the location of this "incubation," though archaeological and skeletal data have not yet supported this hypothesis. This study employs the remains of the five most complete North American male early Holocene skeletons to examine patterns of human morphology at the earliest observable time period. Stature, body mass, body breadth, and limb proportions are examined in the context of male skeletal samples representing the range of morphological variation in North America in the last two millennia of the Holocene. These are also compared with a global sample. Results indicate that early Holocene males have variable postcranial morphologies, but all share the common trait of wide bodies. This trait, which is retained in more recent indigenous North American groups, is associated with adaptations to cold climates. Peoples from the Americas exhibit wider bodies than other populations sampled globally. This pattern suggests the common ancestral population of all of these indigenous American groups had reduced morphological variation in this trait. Furthermore, this provides support for a single, possibly high latitude location for the genetic isolation of ancestors of the human colonizers of the Americas. Copyright © 2012 Wiley Periodicals, Inc.

  20. Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research

    PubMed Central

    Pembrey, Marcus; Saffery, Richard; Bygren, Lars Olov

    2014-01-01

    Mammalian experiments provide clear evidence of male line transgenerational effects on health and development from paternal or ancestral early-life exposures such as diet or stress. The few human observational studies to date suggest (male line) transgenerational effects exist that cannot easily be attributed to cultural and/or genetic inheritance. Here we summarise relevant studies, drawing attention to exposure sensitive periods in early life and sex differences in transmission and offspring outcomes. Thus, variation, or changes, in the parental/ancestral environment may influence phenotypic variation for better or worse in the next generation(s), and so contribute to common, non-communicable disease risk including sex differences. We argue that life-course epidemiology should be reframed to include exposures from previous generations, keeping an open mind as to the mechanisms that transmit this information to offspring. Finally, we discuss animal experiments, including the role of epigenetic inheritance and non-coding RNAs, in terms of what lessons can be learnt for designing and interpreting human studies. This review was developed initially as a position paper by the multidisciplinary Network in Epigenetic Epidemiology to encourage transgenerational research in human cohorts. PMID:25062846

  1. Heatwave early warning systems and adaptation advice to reduce human health consequences of heatwaves.

    PubMed

    Lowe, Dianne; Ebi, Kristie L; Forsberg, Bertil

    2011-12-01

    With climate change, there has been an increase in the frequency, intensity and duration of heatwave events. In response to the devastating mortality and morbidity of recent heatwave events, many countries have introduced heatwave early warning systems (HEWS). HEWS are designed to reduce the avoidable human health consequences of heatwaves through timely notification of prevention measures to vulnerable populations. To identify the key characteristics of HEWS in European countries to help inform modification of current, and development of, new systems and plans. We searched the internet to identify HEWS policy or government documents for 33 European countries and requested information from relevant organizations. We translated the HEWS documents and extracted details on the trigger indicators, thresholds for action, notification strategies, message intermediaries, communication and dissemination strategies, prevention strategies recommended and specified target audiences. Twelve European countries have HEWS. Although there are many similarities among the HEWS, there also are differences in key characteristics that could inform improvements in heatwave early warning plans.

  2. Types of neural cells in the spinal ganglia of human embryos and early fetuses.

    PubMed

    Olszewska, B; Woźniak, W; Gardner, E; O'Rahilly, R

    1979-01-01

    Spinal ganglial of human embryos and fetuses ranging in C.-R. length from 15 to 74 mm and in age from 6 1/2 to 11 postovulatory weeks were studied by light and electron microscopy. A sequence of events in differentiation and maturation enabled five types of cells to be distinguished: 1. apolar, undifferentiated neuroblasts are the main cells at 6 1/2 to 7 1/2 weeks; 2. early bipolar neuroblasts (strictly speaking, types 2 to 5 are immature neurons) predominate at the end of the embryonic period proper (8 postovulatory weeks); 3. intermediate bipolar neuroblasts are characteristic of the early fetal period; 4. late bipolar neuroblasts, in which two proceses arise separately from one pole of the cell, appear at about 10 postovulatory weeks; 5. unipolar neuroblasts are found within another week and, by that time, cells of types 1 and 2 are no longer present.

  3. Culture and art: Importance of art practice, not aesthetics, to early human culture.

    PubMed

    Zaidel, Dahlia W

    2018-01-01

    Art is expressed in multiple formats in today's human cultures. Physical traces of stone tools and other archaeological landmarks suggest early nonart cultural behavior and symbolic cognition in the early Homo sapiens (HS) who emerged ~300,000-200,000 years ago in Africa. Fundamental to art expression is the neural underpinning for symbolic cognition, and material art is considered its prime example. However, prior to producing material art, HS could have exploited symbolically through art-rooted biological neural pathways for social purpose, namely, those controlling interpersonal motoric coordination and sound codependence. Aesthetics would not have been the primary purpose; arguments for group dance and rhythmical musical sounds are offered here. In addition, triggers for symbolic body painting are discussed. These cultural art formats could well have preceded material art and would have enhanced unity, inclusiveness, and cooperative behavior, contributing significantly to already existing nonart cultural practices. © 2018 Elsevier B.V. All rights reserved.

  4. Gene expression analyses of the spatio-temporal relationships of human medulloblastoma subgroups during early human neurogenesis.

    PubMed

    Hooper, Cornelia M; Hawes, Susan M; Kees, Ursula R; Gottardo, Nicholas G; Dallas, Peter B

    2014-01-01

    Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified - WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s) of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options. To address this issue, the gene expression profiles of normal human neural tissues and cell types representing a broad neuro-developmental continuum, were compared to those of two independent cohorts of primary human medulloblastoma specimens. Clustering, co-expression network, and gene expression analyses revealed that WNT and SHH medulloblastoma may be derived from distinct neural stem cell populations during early embryonic development, while the transcriptional profiles of Group 3 and Group 4 medulloblastoma resemble cerebellar granule neuron precursors at weeks 10-15 and 20-30 of embryogenesis, respectively. Our data indicate that Group 3 medulloblastoma may arise through abnormal neuronal differentiation, whereas deregulation of synaptic pruning-associated apoptosis may be driving Group 4 tumorigenesis. Overall, these data provide significant new insight into the spatio-temporal relationships and molecular pathogenesis of the human medulloblastoma subgroups, and provide an important framework for the development of more refined model systems, and ultimately improved therapeutic strategies.

  5. Gene Expression Analyses of the Spatio-Temporal Relationships of Human Medulloblastoma Subgroups during Early Human Neurogenesis

    PubMed Central

    Hooper, Cornelia M.; Hawes, Susan M.; Kees, Ursula R.; Gottardo, Nicholas G.; Dallas, Peter B.

    2014-01-01

    Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified – WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s) of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options. To address this issue, the gene expression profiles of normal human neural tissues and cell types representing a broad neuro-developmental continuum, were compared to those of two independent cohorts of primary human medulloblastoma specimens. Clustering, co-expression network, and gene expression analyses revealed that WNT and SHH medulloblastoma may be derived from distinct neural stem cell populations during early embryonic development, while the transcriptional profiles of Group 3 and Group 4 medulloblastoma resemble cerebellar granule neuron precursors at weeks 10–15 and 20–30 of embryogenesis, respectively. Our data indicate that Group 3 medulloblastoma may arise through abnormal neuronal differentiation, whereas deregulation of synaptic pruning-associated apoptosis may be driving Group 4 tumorigenesis. Overall, these data provide significant new insight into the spatio-temporal relationships and molecular pathogenesis of the human medulloblastoma subgroups, and provide an important framework for the development of more refined model systems, and ultimately improved therapeutic strategies. PMID:25412507

  6. Defining the Genomic Signature of Totipotency and Pluripotency during Early Human Development

    PubMed Central

    Galan, Amparo; Diaz-Gimeno, Patricia; Poo, Maria Eugenia; Valbuena, Diana; Sanchez, Eva; Ruiz, Veronica; Dopazo, Joaquin; Montaner, David; Conesa, Ana; Simon, Carlos

    2013-01-01

    The genetic mechanisms governing human pre-implantation embryo development and the in vitro counterparts, human embryonic stem cells (hESCs), still remain incomplete. Previous global genome studies demonstrated that totipotent blastomeres from day-3 human embryos and pluripotent inner cell masses (ICMs) from blastocysts, display unique and differing transcriptomes. Nevertheless, comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. To understand early human stages evolution, we developed an undifferentiation network signature (UNS) and applied it to a differential gene expression profile between single blastomeres from day-3 embryos, ICMs and hESCs. This allowed us to establish a unique signature composed of highly interconnected genes characteristic of totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro pluripotency (107 genes), and which are also proprietary according to functional analysis. This systems biology approach has led to an improved understanding of the molecular and signaling processes governing human pre-implantation embryo development, as well as enabling us to comprehend how hESCs might adapt to in vitro culture conditions. PMID:23614026

  7. New Archaeological Evidence for an Early Human Presence at Monte Verde, Chile.

    PubMed

    Dillehay, Tom D; Ocampo, Carlos; Saavedra, José; Sawakuchi, Andre Oliveira; Vega, Rodrigo M; Pino, Mario; Collins, Michael B; Scott Cummings, Linda; Arregui, Iván; Villagran, Ximena S; Hartmann, Gelvam A; Mella, Mauricio; González, Andrea; Dix, George

    2015-01-01

    Questions surrounding the chronology, place, and character of the initial human colonization of the Americas are a long-standing focus of debate. Interdisciplinary debate continues over the timing of entry, the rapidity and direction of dispersion, the variety of human responses to diverse habitats, the criteria for evaluating the validity of early sites, and the differences and similarities between colonization in North and South America. Despite recent advances in our understanding of these issues, archaeology still faces challenges in defining interdisciplinary research problems, assessing the reliability of the data, and applying new interpretative models. As the debates and challenges continue, new studies take place and previous research reexamined. Here we discuss recent exploratory excavation at and interdisciplinary data from the Monte Verde area in Chile to further our understanding of the first peopling of the Americas. New evidence of stone artifacts, faunal remains, and burned areas suggests discrete horizons of ephemeral human activity in a sandur plain setting radiocarbon and luminescence dated between at least ~18,500 and 14,500 cal BP. Based on multiple lines of evidence, including sedimentary proxies and artifact analysis, we present the probable anthropogenic origins and wider implications of this evidence. In a non-glacial cold climate environment of the south-central Andes, which is challenging for human occupation and for the preservation of hunter-gatherer sites, these horizons provide insight into an earlier context of late Pleistocene human behavior in northern Patagonia.

  8. New Archaeological Evidence for an Early Human Presence at Monte Verde, Chile

    PubMed Central

    Dillehay, Tom D.; Ocampo, Carlos; Saavedra, José; Sawakuchi, Andre Oliveira; Vega, Rodrigo M.; Pino, Mario; Collins, Michael B.; Scott Cummings, Linda; Arregui, Iván; Villagran, Ximena S.; Hartmann, Gelvam A.; Mella, Mauricio; González, Andrea; Dix, George

    2015-01-01

    Questions surrounding the chronology, place, and character of the initial human colonization of the Americas are a long-standing focus of debate. Interdisciplinary debate continues over the timing of entry, the rapidity and direction of dispersion, the variety of human responses to diverse habitats, the criteria for evaluating the validity of early sites, and the differences and similarities between colonization in North and South America. Despite recent advances in our understanding of these issues, archaeology still faces challenges in defining interdisciplinary research problems, assessing the reliability of the data, and applying new interpretative models. As the debates and challenges continue, new studies take place and previous research reexamined. Here we discuss recent exploratory excavation at and interdisciplinary data from the Monte Verde area in Chile to further our understanding of the first peopling of the Americas. New evidence of stone artifacts, faunal remains, and burned areas suggests discrete horizons of ephemeral human activity in a sandur plain setting radiocarbon and luminescence dated between at least ~18,500 and 14,500 cal BP. Based on multiple lines of evidence, including sedimentary proxies and artifact analysis, we present the probable anthropogenic origins and wider implications of this evidence. In a non-glacial cold climate environment of the south-central Andes, which is challenging for human occupation and for the preservation of hunter-gatherer sites, these horizons provide insight into an earlier context of late Pleistocene human behavior in northern Patagonia. PMID:26580202

  9. Folding and Homodimerization of Wheat Germ Agglutinin

    PubMed Central

    Portillo-Téllez, María del Carmen; Bello, Martiniano; Salcedo, Guillermo; Gutiérrez, Gabriel; Gómez-Vidales, Virginia; García-Hernández, Enrique

    2011-01-01

    Wheat germ agglutinin (WGA) is emblematic of proteins that specialize in the recognition of carbohydrates. It was the first lectin reported to have a capacity for discriminating between normal and malignant cells. Since then, it has become a preferred model for basic research and is frequently considered in the development of biomedical and biotechnological applications. However, the molecular basis for the structural stability of this homodimeric lectin remains largely unknown, a situation that limits the rational manipulation and modification of its function. In this work we performed a thermodynamic characterization of WGA folding and self-association processes as a function of pH and temperature by using differential scanning and isothermal dilution calorimetry. WGA is monomeric at pH 2, and one of its four hevein-like domains is unfolded at room temperature. Under such conditions, the agglutinin exhibits a fully reversible thermal unfolding that consists of three two-state transitions. At higher pH values, the protein forms weak, nonobligate dimers. This behavior contrasts with that observed for the other plant lectins studied thus far, which form strong, obligate oligomers, indicating a distinctly different molecular basis for WGA function. For dimer formation, the four domains must be properly folded. Nevertheless, depending on the solution conditions, self-association may be coupled with folding of the labile domain. Therefore, dimerization may proceed as a rigid-body-like association or a folding-by-binding event. This hybrid behavior is not seen in other plant lectins. The emerging molecular picture for the WGA assembly highlights the need for a reexamination of existing ligand-binding data in the literature. PMID:21943423

  10. Differential expression of conserved germ line markers and delayed segregation of male and female primordial germ cells in a hermaphrodite, the leech helobdella.

    PubMed

    Cho, Sung-Jin; Vallès, Yvonne; Weisblat, David A

    2014-02-01

    In sexually reproducing animals, primordial germ cells (PGCs) are often set aside early in embryogenesis, a strategy that minimizes the risk of genomic damage associated with replication and mitosis during the cell cycle. Here, we have used germ line markers (piwi, vasa, and nanos) and microinjected cell lineage tracers to show that PGC specification in the leech genus Helobdella follows a different scenario: in this hermaphrodite, the male and female PGCs segregate from somatic lineages only after more than 20 rounds of zygotic mitosis; the male and female PGCs share the same (mesodermal) cell lineage for 19 rounds of zygotic mitosis. Moreover, while all three markers are expressed in both male and female reproductive tissues of the adult, they are expressed differentially between the male and female PGCs of the developing embryo: piwi and vasa are expressed preferentially in female PGCs at a time when nanos is expressed preferentially in male PGCs. A priori, the delayed segregation of male and female PGCs from somatic tissues and from one another increases the probability of mutations affecting both male and female PGCs of a given individual. We speculate that this suite of features, combined with a capacity for self-fertilization, may contribute to the dramatically rearranged genome of Helobdella robusta relative to other animals.

  11. Differential Expression of Conserved Germ Line Markers and Delayed Segregation of Male and Female Primordial Germ Cells in a Hermaphrodite, the Leech Helobdella

    PubMed Central

    Cho, Sung-Jin; Vallès, Yvonne; Weisblat, David A.

    2014-01-01

    In sexually reproducing animals, primordial germ cells (PGCs) are often set aside early in embryogenesis, a strategy that minimizes the risk of genomic damage associated with replication and mitosis during the cell cycle. Here, we have used germ line markers (piwi, vasa, and nanos) and microinjected cell lineage tracers to show that PGC specification in the leech genus Helobdella follows a different scenario: in this hermaphrodite, the male and female PGCs segregate from somatic lineages only after more than 20 rounds of zygotic mitosis; the male and female PGCs share the same (mesodermal) cell lineage for 19 rounds of zygotic mitosis. Moreover, while all three markers are expressed in both male and female reproductive tissues of the adult, they are expressed differentially between the male and female PGCs of the developing embryo: piwi and vasa are expressed preferentially in female PGCs at a time when nanos is expressed preferentially in male PGCs. A priori, the delayed segregation of male and female PGCs from somatic tissues and from one another increases the probability of mutations affecting both male and female PGCs of a given individual. We speculate that this suite of features, combined with a capacity for self-fertilization, may contribute to the dramatically rearranged genome of Helobdella robusta relative to other animals. PMID:24217283

  12. Early Detection of Human Epileptic Seizures Based on Intracortical Local Field Potentials

    PubMed Central

    Park, Yun S.; Hochberg, Leigh R.; Eskandar, Emad N.; Cash, Sydney S.; Truccolo, Wilson

    2014-01-01

    The unpredictability of re-occurring seizures dramatically impacts the quality of life and autonomy of people with epilepsy. Reliable early seizure detection could open new therapeutic possibilities and thus substantially improve quality of life and autonomy. Though many seizure detection studies have shown the potential of scalp electroencephalogram (EEG) and intracranial EEG (iEEG) signals, reliable early detection of human seizures remains elusive in practice. Here, we examined the use of intracortical local field potentials (LFPs) recorded from 4×4-mm2 96-microelectrode arrays (MEA) for early detection of human epileptic seizures. We adopted a framework consisting of (1) sampling of intracortical LFPs; (2) denoising of LFPs with the Kalman filter; (3) spectral power estimation in specific frequency bands using 1-sec moving time windows; (4) extraction of statistical features, such as the mean, variance, and Fano factor (calculated across channels) of the power in each frequency band; and (5) cost-sensitive support vector machine (SVM) classification of ictal and interictal samples. We tested the framework in one-participant dataset, including 4 seizures and corresponding interictal recordings preceding each seizure. The participant was a 52-year-old woman suffering from complex partial seizures. LFPs were recorded from an MEA implanted in the participant’s left middle temporal gyrus. In this participant, spectral power in 0.3–10 Hz, 20–55 Hz, and 125–250 Hz changed significantly between ictal and interictal epochs. The examined seizure detection framework provided an event-wise sensitivity of 100% (4/4) and only one 20-sec-long false positive event in interictal recordings (likely an undetected subclinical event under further visual inspection), and a detection latency of 4.35 ± 2.21 sec (mean ± std) with respect to iEEG-identified seizure onsets. These preliminary results indicate that intracortical MEA recordings may provide key signals to quickly

  13. Plant foods and the dietary ecology of Neanderthals and early modern humans.

    PubMed

    Henry, Amanda G; Brooks, Alison S; Piperno, Dolores R

    2014-04-01

    One of the most important challenges in anthropology is understanding the disappearance of Neanderthals. Previous research suggests that Neanderthals had a narrower diet than early modern humans, in part because they lacked various social and technological advances that lead to greater dietary variety, such as a sexual division of labor and the use of complex projectile weapons. The wider diet of early modern humans would have provided more calories and nutrients, increasing fertility, decreasing mortality and supporting large population sizes, allowing them to out-compete Neanderthals. However, this model for Neanderthal dietary behavior is based on analysis of animal remains, stable isotopes, and other methods that provide evidence only of animal food in the diet. This model does not take into account the potential role of plant food. Here we present results from the first broad comparison of plant foods in the diets of Neanderthals and early modern humans from several populations in Europe, the Near East, and Africa. Our data comes from the analysis of plant microremains (starch grains and phytoliths) in dental calculus and on stone tools. Our results suggest that both species consumed a similarly wide array of plant foods, including foods that are often considered low-ranked, like underground storage organs and grass seeds. Plants were consumed across the entire range of individuals and sites we examined, and none of the expected predictors of variation (species, geographic region, or associated stone tool technology) had a strong influence on the number of plant species consumed. Our data suggest that Neanderthal dietary ecology was more complex than previously thought. This implies that the relationship between Neanderthal technology, social behavior, and food acquisition strategies must be better explored. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Maternal syntabulin is required for dorsal axis formation and is a germ plasm component in Xenopus.

    PubMed

    Colozza, Gabriele; De Robertis, Edward M

    2014-07-01

    In amphibians and teleosts, early embryonic axial development is driven by maternally deposited mRNAs and proteins, called dorsal determinants, which migrate to the presumptive dorsal side of the embryo in a microtubule-dependent manner after fertilization. Syntabulin is an adapter protein that binds to kinesin KIF5B and to the transmembrane protein Syntaxin1. In zebrafish, a mutation in Syntabulin causes complete embryo ventralization. It is unknown whether Syntabulin plays an analogous role during early development of other species, a question addressed here in Xenopus laevis. in situ hybridization of syntabulin mRNA was carried out at different stages of Xenopus development. In oocytes, syntabulin transcripts were localized to the vegetal cortex of large oocytes and the mitochondrial cloud of very young oocytes. We extended the zebrafish data by finding that during cleavage Xenopus syntabulin mRNA localized to the germ plasm and was later expressed in primordial germ cells (PGCs). This new finding suggested a role for Syntabulin during germ cell differentiation. The functional role of maternal syntabulin mRNA was investigated by knock-down with phosphorothioate DNA antisense oligos followed by oocyte transfer. The results showed that syntabulin mRNA depletion caused the complete loss of dorso-anterior axis formation in frog embryos. Consistent with the ventralized phenotype, syntabulin-depleted embryos displayed severe reduction of dorsal markers and ubiquitous transcription of the ventral marker sizzled. Syntabulin was required for the maternal Wnt/β-Catenin signal, since ventralization could be completely rescued by injection of β-catenin (or syntabulin) mRNA. The data suggest an evolutionarily conserved role for Syntabulin, a protein that bridges microtubule motors and membrane vesicles, during dorso-ventral axis formation in the vertebrates. Copyright © 2013 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  15. Fake news and post-truth pronouncements in general and in early human development.

    PubMed

    Grech, Victor

    2017-12-01

    Fake news and post-truth pronouncements are increasingly common, and are unfortunately also progressively being applied to the sciences, including the medical sciences. This editorial briefly reviews this unsavoury trend and highlights recent debunking of fake truths in early human development. Science is arguably the last metanarrative with any significant cachet in the postmodern period. We, as scientists, must strive to ensure that our work is transparent and of the highest possible standard so as to continue to uphold science's integrity and probity. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Early experience with human papillomavirus vaccine introduction in the United States, Canada and Australia.

    PubMed

    Shefer, Abigail; Markowitz, Lauri; Deeks, Shelley; Tam, Theresa; Irwin, Kathleen; Garland, Suzanne M; Schuchat, Anne

    2008-08-19

    Successful incorporation of a new vaccine into a nation's vaccination program requires addressing a number of issues, including: 1) establishing national recommendations; 2) assuring education of and acceptance by the public and medical community; 3) establishing and maintaining an appropriate infrastructure for vaccine delivery; 4) financing the vaccine and the program, in addition to political will. This article reviews the early experience with implementation of human papillomavirus (HPV) vaccination programs. It focuses on the United States of America and Canada and provides a brief report on Australia, where introduction is underway.

  17. Analytical modeling of the mechanics of early invasion of a merozoite into a human erythrocyte.

    PubMed

    Abdalrahman, Tamer; Franz, Thomas

    2017-12-01

    In this study, we used a continuum model based on contact mechanics to understand the mechanics of merozoite invasion into human erythrocytes. This model allows us to evaluate the indentation force and work as well as the contact pressure between the merozoite and erythrocyte for an early stage of invasion (γ = 10%). The model predicted an indentation force of 1.3e -11 N and an indentation work of 1e -18 J. The present analytical model can be considered as a useful tool not only for investigations in mechanobiology and biomechanics but also to explore novel therapeutic targets for malaria and other parasite infections.

  18. Elevated mutation rates in the germ line of first- and second-generation offspring of irradiated male mice

    PubMed Central

    Barber, Ruth; Plumb, Mark A.; Boulton, Emma; Roux, Isabelle; Dubrova, Yuri E.

    2002-01-01

    Mutation rates at two expanded simple tandem repeat loci were studied in the germ line of first- and second-generation offspring of inbred male CBA/H, C57BL/6, and BALB/c mice exposed to either high linear energy transfer fission neutrons or low linear energy transfer x-rays. Paternal CBA/H exposure to either x-rays or fission neutrons resulted in increased mutation rates in the germ line of two subsequent generations. Comparable transgenerational effects were observed also in neutron-irradiated C57BL/6 and x-irradiated BALB/c mice. The levels of spontaneous mutation rates and radiation-induced transgenerational instability varied between strains (BALB/c>CBA/H>C57BL/6). Pre- and postmeiotic paternal exposure resulted in similar increases in mutation rate in the germ line of both generations of CBA/H mice, which together with our previous results suggests that radiation-induced expanded simple tandem repeat instability is manifested in diploid cells after fertilization. The remarkable finding that radiation-induced germ-line instability persists for at least two generations raises important issues of risk evaluation in humans. PMID:11997464

  19. Preference for language in early infancy: the human language bias is not speech specific.

    PubMed

    Krentz, Ursula C; Corina, David P

    2008-01-01

    Fundamental to infants' acquisition of their native language is an inherent interest in the language spoken around them over non-linguistic environmental sounds. The following studies explored whether the bias for linguistic signals in hearing infants is specific to speech, or reflects a general bias for all human language, spoken and signed. Results indicate that 6-month-old infants prefer an unfamiliar, visual-gestural language (American Sign Language) over non-linguistic pantomime, but 10-month-olds do not. These data provide evidence against a speech-specific bias in early infancy and provide insights into those properties of human languages that may underlie this language-general attentional bias.

  20. Human radiation studies: Remembering the early years. Oral history of Julie Langham Grilly, February 3, 1995

    SciT

    NONE

    1995-09-01

    Julie Langham Grilly was interviewed by representatives of the US DOE Office of Human Radiation Experiments (OHRE) being the widow of Dr. Wright Langham, an investigator of principal interest of the committee. Her extensive experience with research at LANL was also of interest to the committee. Following a brief biographical sketch, Ms. Grilly relates her early postwar experience and her knowledge of Wright Langham`s involvement in animal research at Los Alamos, radiolanthanum tests on monkeys, Eniwetok tissue examinations, research on tritium uptake in humans, plutonium injections, tritium injections, EDTA, and etc. In addition to illuminating her former husband as amore » researcher and as an individual, she also relates her remembrances of Louis Hempelman, Enrico Fermi, Oppenheimer, Edward Teller, and many others.« less

  1. Early human use of anadromous salmon in North America at 11,500 y ago

    PubMed Central

    Halffman, Carrin M.; Potter, Ben A.; McKinney, Holly J.; Finney, Bruce P.; Rodrigues, Antonia T.; Yang, Dongya Y.; Kemp, Brian M.

    2015-01-01

    Salmon represented a critical resource for prehistoric foragers along the North Pacific Rim, and continue to be economically and culturally important; however, the origins of salmon exploitation remain unresolved. Here we report 11,500-y-old salmon associated with a cooking hearth and human burials from the Upward Sun River Site, near the modern extreme edge of salmon habitat in central Alaska. This represents the earliest known human use of salmon in North America. Ancient DNA analyses establish the species as Oncorhynchus keta (chum salmon), and stable isotope analyses indicate anadromy, suggesting that salmon runs were established by at least the terminal Pleistocene. The early use of this resource has important implications for Paleoindian land use, economy, and expansions into northwest North America. PMID:26392548

  2. Early human use of anadromous salmon in North America at 11,500 y ago.

    PubMed

    Halffman, Carrin M; Potter, Ben A; McKinney, Holly J; Finney, Bruce P; Rodrigues, Antonia T; Yang, Dongya Y; Kemp, Brian M

    2015-10-06

    Salmon represented a critical resource for prehistoric foragers along the North Pacific Rim, and continue to be economically and culturally important; however, the origins of salmon exploitation remain unresolved. Here we report 11,500-y-old salmon associated with a cooking hearth and human burials from the Upward Sun River Site, near the modern extreme edge of salmon habitat in central Alaska. This represents the earliest known human use of salmon in North America. Ancient DNA analyses establish the species as Oncorhynchus keta (chum salmon), and stable isotope analyses indicate anadromy, suggesting that salmon runs were established by at least the terminal Pleistocene. The early use of this resource has important implications for Paleoindian land use, economy, and expansions into northwest North America.

  3. Continuity or discontinuity in the European Early Pleistocene human settlement: the Atapuerca evidence

    NASA Astrophysics Data System (ADS)

    Bermúdez de Castro, José María; Martinón-Torres, María; Blasco, Ruth; Rosell, Jordi; Carbonell, Eudald

    2013-09-01

    The nature, timing, pattern, favourable circumstances and impediments of the human occupation of the European continent during the Early Pleistocene are hot topics in Quaternary studies. In particular, the problem of the (dis) continuity of the settlement of Europe in this period is an important matter of discussion, which has been approached in the last decade from different points of view. The Gran Dolina (TD) and Sima del Elefante (TE) cave sites in the Sierra de Atapuerca, (Spain) include large and quasi-continuous stratigraphic sequences that stretch back from at least 1.2 million years ago (Ma) to the Matuyama/Brunhes boundary. The archaeological and paleontological record from these sites can help to test different hypotheses about the character of the human settlement in this region and period. Furthermore, the TD6 level has yielded a large collection of human fossil remains attributed to Homo antecessor. According to different geochronological methods, as well as to paleomagnetic and biostratigraphical analyses, these hominins belong to an age range of 0.96-0.80 Ma. Unfortunately, the finding in 2007 of some human fossil remains in the TE9 level, dated to about 1.22 Ma, was not enough to conclude whether H. antecessor had deep roots in the European Early Pleistocene. A set of derived features of H. antecessor shared with both the Neanderthal lineage and modern humans suggests that this species is related, and not far, from the most recent common ancestor (MRCA) of Homo neanderthalensis and Homo sapiens. If we assume that there was a lineal biological relationship between the TE9 and TD6 hominins, we should reconsider many of the conclusions achieved in previous paleontological and genetic studies. In addition, we would be obliged to build a highly complicated paleogeographical scenario for the origin of the MRCA. Although continuity in the settlement of Europe during the entire late Early Pleistocene is not discarded (e.g. in refuge areas), it seems that

  4. Composition and molecular weight distribution of carob germ protein fractions.

    PubMed

    Smith, Brennan M; Bean, Scott R; Schober, Tilman J; Tilley, Michael; Herald, Thomas J; Aramouni, Fadi

    2010-07-14

    Biochemical properties of carob germ proteins were analyzed using a combination of selective extraction, reversed-phase high-performance liquid chromatography (RP-HPLC), size exclusion chromatography (SEC) coupled with multiangle laser light scattering (SEC-MALS), and electrophoretic analysis. Using a modified Osborne extraction procedure, carob germ flour proteins were found to contain approximately 32% albumin and globulin and approximately 68% glutelin with no prolamins detected. The albumin and globulin fraction was found to contain low amounts of disulfide-bonded polymers with relatively low M(w) ranging up to 5 x 10(6) Da. The glutelin fraction, however, was found to contain large amounts of high molecular weight disulfide-bonded polymers with M(w) up to 8 x 10(7) Da. When extracted under nonreducing conditions and divided into soluble and insoluble proteins as typically done for wheat gluten, carob germ proteins were found to be almost entirely ( approximately 95%) in the soluble fraction with only ( approximately 5%) in the insoluble fraction. As in wheat, SEC-MALS analysis showed that the insoluble proteins had a greater M(w) than the soluble proteins and ranged up to 8 x 10(7) Da. The lower M(w) distribution of the polymeric proteins of carob germ flour may account for differences in functionality between wheat and carob germ flour.

  5. Consensus on the management of intracranial germ-cell tumours.

    PubMed

    Murray, Matthew J; Bartels, Ute; Nishikawa, Ryo; Fangusaro, Jason; Matsutani, Masao; Nicholson, James C

    2015-09-01

    The management of intracranial germ-cell tumours is complex because of varied clinical presentations, tumour sites, treatments and outcomes, and the need for multidisciplinary input. Participants of the 2013 Third International CNS Germ Cell Tumour Symposium (Cambridge, UK) agreed to undertake a multidisciplinary Delphi process to identify consensus in the clinical management of intracranial germ-cell tumours. 77 delegates from the symposium were selected as suitable experts in the field and were invited to participate in the Delphi survey, of which 64 (83%) responded to the invitation. Invited participants represented multiple disciplines from Asia, Australasia, Europe, and the Americas. 38 consensus statements encompassing aspects of intracranial germ-cell tumour work-up, staging, treatment, and follow-up were prepared. To achieve consensus, statements required at least 70% agreement from at least 60% of respondents. Overall, 34 (89%) of 38 statements met consensus criteria. This international Delphi approach has defined key areas of consensus that will help guide and streamline clinical management of patients with intracranial germ-cell tumours. Additionally, the Delphi approach identified areas of different understanding and clinical practice internationally in the management of these tumours, areas which should be the focus of future collaborative studies. Such efforts should translate into improved patient outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Physicochemical properties of nixtamalized corn flours with and without germ.

    PubMed

    Vega Rojas, Lineth J; Rojas Molina, Isela; Gutiérrez Cortez, Elsa; Rincón Londoño, Natalia; Acosta Osorio, Andrés A; Del Real López, Alicia; Rodríguez García, Mario E

    2017-04-01

    This research studied the influence of the germ components on the physicochemical properties of cooked corn and nixtamalized corn flours as a function of the calcium hydroxide content (from 0 to 2.1 w/w) and steeping time (between 0 and 9h). A linear relationship was found between calcium content in germ and steeping time used during nixtamalization process. X-ray diffraction analysis showed that calcium carbonate is formed into the germ structure to 2.1 w/w of calcium hydroxide and 9h steeping time. The presence of the germ improves the development of peak viscosity in flours, and it is related to the increases in calcium concentration in germ and the formation of amylose-lipid complexes. No significant changes were observed in palmitic, stearic, oleic and linoleic acids of corn oil. The levels of further corn oil deterioration were 2.1 w/w of calcium hydroxide concentration and 9h of steeping time. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Primary Culture System for Germ Cells from Caenorhabditis elegans Tumorous Germline Mutants

    PubMed Central

    Vagasi, Alexandra S.; Rahman, Mohammad M.; Chaudhari, Snehal N.; Kipreos, Edward T.

    2017-01-01

    The Caenorhabditis elegans germ line is an important model system for the study of germ stem cells. Wild-type C. elegans germ cells are syncytial and therefore cannot be isolated in in vitro cultures. In contrast, the germ cells from tumorous mutants can be fully cellularized and isolated intact from the mutant animals. Here we describe a detailed protocol for the isolation of germ cells from tumorous mutants that allows the germ cells to be maintained for extended periods in an in vitro primary culture. This protocol has been adapted from Chaudhari et al., 2016. PMID:28868332

  8. Spectroscopic imaging of the pilocarpine model of human epilepsy suggests that early NAA reduction predicts epilepsy.

    PubMed

    Gomes, W A; Lado, F A; de Lanerolle, N C; Takahashi, K; Pan, C; Hetherington, H P

    2007-08-01

    Reduced hippocampal N-acetyl aspartate (NAA) is commonly observed in patients with advanced, chronic temporal lobe epilepsy (TLE). It is unclear, however, whether an NAA deficit is also present during the clinically quiescent latent period that characterizes early TLE. This question has important implications for the use of MR spectroscopic imaging (MRSI) in the early identification of patients at risk for TLE. To determine whether NAA is diminished during the latent period, we obtained high-resolution (1)H spectroscopic imaging during the latent period of the rat pilocarpine model of human TLE. We used actively detuneable surface reception and volume transmission coils to enhance sensitivity and a semiautomated voxel shifting method to accurately position voxels within the hippocampi. During the latent period, 2 and 7 d following pilocarpine treatment, hippocampal NAA was significantly reduced by 27.5 +/- 6.9% (P < 0.001) and 17.3 +/- 6.9% (P < 0.001) at 2 and 7 d, respectively. Quantitative estimates of neuronal loss at 7 d (2.3 +/- 7.7% reduction; P = 0.58, not significant) demonstrate that the NAA deficit is not due to neuron loss and therefore likely represents metabolic impairment of hippocampal neurons during the latent phase. Therefore, spectroscopic imaging provides an early marker for metabolic dysfunction in this model of TLE.

  9. Primary cortical folding in the human newborn: an early marker of later functional development.

    PubMed

    Dubois, J; Benders, M; Borradori-Tolsa, C; Cachia, A; Lazeyras, F; Ha-Vinh Leuchter, R; Sizonenko, S V; Warfield, S K; Mangin, J F; Hüppi, P S

    2008-08-01

    In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26-36 weeks of gestational age), and defined early 'endophenotypes' of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants' outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infant's behaviour (APIB).

  10. Neural Correlates of Natural Human Echolocation in Early and Late Blind Echolocation Experts

    PubMed Central

    Thaler, Lore; Arnott, Stephen R.; Goodale, Melvyn A.

    2011-01-01

    Background A small number of blind people are adept at echolocating silent objects simply by producing mouth clicks and listening to the returning echoes. Yet the neural architecture underlying this type of aid-free human echolocation has not been investigated. To tackle this question, we recruited echolocation experts, one early- and one late-blind, and measured functional brain activity in each of them while they listened to their own echolocation sounds. Results When we compared brain activity for sounds that contained both clicks and the returning echoes with brain activity for control sounds that did not contain the echoes, but were otherwise acoustically matched, we found activity in calcarine cortex in both individuals. Importantly, for the same comparison, we did not observe a difference in activity in auditory cortex. In the early-blind, but not the late-blind participant, we also found that the calcarine activity was greater for echoes reflected from surfaces located in contralateral space. Finally, in both individuals, we found activation in middle temporal and nearby cortical regions when they listened to echoes reflected from moving targets. Conclusions These findings suggest that processing of click-echoes recruits brain regions typically devoted to vision rather than audition in both early and late blind echolocation experts. PMID:21633496

  11. IL-2 Enhances Gut Homing Potential of Human Naive Regulatory T Cells Early in Life.

    PubMed

    Hsu, Peter S; Lai, Catherine L; Hu, Mingjing; Santner-Nanan, Brigitte; Dahlstrom, Jane E; Lee, Cheng Hiang; Ajmal, Ayesha; Bullman, Amanda; Arbuckle, Susan; Al Saedi, Ahmed; Gacis, Lou; Nambiar, Reta; Williams, Andrew; Wong, Melanie; Campbell, Dianne E; Nanan, Ralph

    2018-06-15

    Recent evidence suggests early environmental factors are important for gut immune tolerance. Although the role of regulatory T (Treg) cells for gut immune homeostasis is well established, the development and tissue homing characteristics of Treg cells in children have not been studied in detail. In this article, we studied the development and homing characteristics of human peripheral blood Treg cell subsets and potential mechanisms inducing homing molecule expression in healthy children. We found contrasting patterns of circulating Treg cell gut and skin tropism, with abundant β7 integrin + Treg cells at birth and increasing cutaneous lymphocyte Ag (CLA + ) Treg cells later in life. β7 integrin + Treg cells were predominantly naive, suggesting acquisition of Treg cell gut tropism early in development. In vitro, IL-7 enhanced gut homing but reduced skin homing molecule expression in conventional T cells, whereas IL-2 induced a similar effect only in Treg cells. This effect was more pronounced in cord compared with adult blood. Our results suggest that early in life, naive Treg cells may be driven for gut tropism by their increased sensitivity to IL-2-induced β7 integrin upregulation, implicating a potential role of IL-2 in gut immune tolerance during this critical period of development. Copyright © 2018 by The American Association of Immunologists, Inc.

  12. Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques.

    PubMed

    Hessell, Ann J; Jaworski, J Pablo; Epson, Erin; Matsuda, Kenta; Pandey, Shilpi; Kahl, Christoph; Reed, Jason; Sutton, William F; Hammond, Katherine B; Cheever, Tracy A; Barnette, Philip T; Legasse, Alfred W; Planer, Shannon; Stanton, Jeffrey J; Pegu, Amarendra; Chen, Xuejun; Wang, Keyun; Siess, Don; Burke, David; Park, Byung S; Axthelm, Michael K; Lewis, Anne; Hirsch, Vanessa M; Graham, Barney S; Mascola, John R; Sacha, Jonah B; Haigwood, Nancy L

    2016-04-01

    Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIVSF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8(+) T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.

  13. Analysis of early thrombus dynamics in a humanized mouse laser injury model.

    PubMed

    Wang, Weiwei; Lindsey, John P; Chen, Jianchun; Diacovo, Thomas G; King, Michael R

    2014-01-01

    Platelet aggregation and thrombus formation at the site of injury is a dynamic process that involves the continuous addition of new platelets as well as thrombus rupture. In the early stages of hemostasis (within minutes after vessel injury) this process can be visualized by transfusing fluorescently labeled human platelets and observing their deposition and detachment. These two counterbalancing events help the developing thrombus reach a steady-state morphology, where it is large enough to cover the injured vessel surface but not too large to form a severe thrombotic occlusion. In this study, the spatial and temporal aspects of early stage thrombus dynamics which result from laser-induced injury on arterioles of cremaster muscle in the humanized mouse were visualized using fluorescent microscopy. It was found that rolling platelets show preference for the upstream region while tethering/detaching platelets were primarily found downstream. It was also determined that the platelet deposition rate is relatively steady, whereas the effective thrombus coverage area does not increase at a constant rate. By introducing a new method to graphically represent the real time in vivo physiological shear stress environment, we conclude that the thrombus continuously changes shape by regional growth and decay, and neither dominates in the high shear stress region.

  14. The influence of Weismann's germ-plasm theory on the distinction between learned and innate behavior.

    PubMed

    Johnston, T D

    1995-04-01

    Since the early twentieth century it has been common in both psychology and behavioral biology to draw a sharp distinction between learned and innate behavior, or elements of behavior. The persistence of this dichotomy may be attributed in part to the fundamental importance of the separation of inherited and acquired characters within neo-Darwinian evolutionary theory, one of the essential foundations for the modern study of behavior. A cornerstone of early neo-Darwinian thought was August Weismann's theory of the germ plasm, which proposed a segregation between germinal and somatic cells during development, thus ruling out the possibility that acquired characters could be inherited. This denial of Lamarckian hereditary mechanisms became one of the hallmarks of neo-Darwinism, as opposed to classical Darwinism. Within the neo-Darwinian framework it thus became important, as Weismann himself pointed out, to distinguish sharply between inherited and acquired characters. Although the dichotomy has frequently been criticized it remains tenacious, surfacing in different guises as older versions of it became terminologically unacceptable. The analysis offered here suggests that this tenacity may partly be explained by the implications of Weismann's germ-plasm theory, and its modern incarnation in the central dogma of molecular genetics, and by the central thematic position of those ideas in the neo-Darwinian foundations of modern behavioral biology.

  15. Aging impairs double-strand break repair by homologous recombination in Drosophila germ cells.

    PubMed

    Delabaere, Laetitia; Ertl, Henry A; Massey, Dashiell J; Hofley, Carolyn M; Sohail, Faraz; Bienenstock, Elisa J; Sebastian, Hans; Chiolo, Irene; LaRocque, Jeannine R

    2017-04-01

    Aging is characterized by genome instability, which contributes to cancer formation and cell lethality leading to organismal decline. The high levels of DNA double-strand breaks (DSBs) observed in old cells and premature aging syndromes are likely a primary source of genome instability, but the underlying cause of their formation is still unclear. DSBs might result from higher levels of damage or repair defects emerging with advancing age, but repair pathways in old organisms are still poorly understood. Here, we show that premeiotic germline cells of young and old flies have distinct differences in their ability to repair DSBs by the error-free pathway homologous recombination (HR). Repair of DSBs induced by either ionizing radiation (IR) or the endonuclease I-SceI is markedly defective in older flies. This correlates with a remarkable reduction in HR repair measured with the DR-white DSB repair reporter assay. Strikingly, most of this repair defect is already present at 8 days of age. Finally, HR defects correlate with increased expression of early HR components and increased recruitment of Rad51 to damage in older organisms. Thus, we propose that the defect in the HR pathway for germ cells in older flies occurs following Rad51 recruitment. These data reveal that DSB repair defects arise early in the aging process and suggest that HR deficiencies are a leading cause of genome instability in germ cells of older animals. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  16. Efficient isolation of human metapneumovirus using MNT-1, a human malignant melanoma cell line with early and distinct cytopathic effects.

    PubMed

    Sato, Ko; Watanabe, Oshi; Ohmiya, Suguru; Chiba, Fumiko; Suzuki, Akira; Okamoto, Michiko; Younghuang, Jiang; Hata, Akihiro; Nonaka, Hiroyuki; Kitaoka, Setsuko; Nagai, Yukio; Kawamura, Kazuhisa; Hayashi, Masahiro; Kumaki, Satoru; Suzuki, Tamio; Kawakami, Kazuyoshi; Nishimura, Hidekazu

    2017-11-01

    Isolation of human metapneumovirus (HMPV) from clinical specimens is currently inefficient because of the lack of a cell culture system in which a distinct cytopathic effect (CPE) occurs. The cell lines LLC-MK2, Vero and Vero E6 are used for isolation of HMPV; however, the CPE in these cell lines is subtle and usually requires a long observation period and sometimes blind passages. Thus, a cell line in which an early and distinct CPE occurs following HMPV inoculation is highly desired by clinical virology laboratories. In this study, it was demonstrated that, in the human malignant melanoma cell line MNT-1, obvious syncytium formation occurs shortly after inoculation with HMPV-positive clinical specimens. In addition, the growth and efficiency of isolation of HMPV were greater using MNT-1 than using any other conventional cell line. Addition of this cell line to our routine viral isolation system for clinical specimens markedly enhanced isolation frequency, allowing isolation-based surveillance. MNT-1 has the potential to facilitate clinical and epidemiological studies of HMPV. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  17. Developmental plasticity of bacterial colonies and consortia in germ-free and gnotobiotic settings

    PubMed Central

    2012-01-01

    Background Bacteria grown on semi-solid media can build two types of multicellular structures, depending on the circumstances. Bodies (colonies) arise when a single clone is grown axenically (germ-free), whereas multispecies chimeric consortia contain monoclonal microcolonies of participants. Growth of an axenic colony, mutual interactions of colonies, and negotiation of the morphospace in consortial ecosystems are results of intricate regulatory and metabolic networks. Multicellular structures developed by Serratia sp. are characteristically shaped and colored, forming patterns that reflect their growth conditions (in particular medium composition and the presence of other bacteria). Results Building on our previous work, we developed a model system for studying ontogeny of multicellular bacterial structures formed by five Serratia sp. morphotypes of two species grown in either "germ-free" or "gnotobiotic" settings (i.e. in the presence of bacteria of other conspecific morphotype, other Serratia species, or E. coli). Monoclonal bodies show regular and reproducible macroscopic appearance of the colony, as well as microscopic pattern of its growing margin. Standard development can be modified in a characteristic and reproducible manner in close vicinity of other bacterial structures (or in the presence of their products). Encounters of colonies with neighbors of a different morphotype or species reveal relationships of dominance, cooperation, or submission; multiple interactions can be summarized in "rock – paper – scissors" network of interrelationships. Chimerical (mixed) plantings consisting of two morphotypes usually produced a “consortium” whose structure is consistent with the model derived from interaction patterns observed in colonies. Conclusions Our results suggest that development of a bacterial colony can be considered analogous to embryogenesis in animals, plants, or fungi: to proceed, early stages require thorough insulation from the rest of

  18. A More-than-Social Movement: The Post-Human Condition of Quality in the Early Years

    ERIC Educational Resources Information Center

    Arndt, Sonja; Tesar, Marek

    2016-01-01

    This article explores quality in early childhood education by de-elevating the importance of the human subject and experience, and heightening instead a focus on and tensions with the post-human. The argument traces the intricate web of "qualities" woven throughout entanglements of subjects, objects and things that constitute what is…

  19. The (Bio)Politicization of Neuroscience in Australian Early Years Policies: Fostering Brain-Resources "as" Human Capital

    ERIC Educational Resources Information Center

    Millei, Zsuzsa; Joronen, Mikko

    2016-01-01

    At the present, human capital theory (HCT) and neuroscience reasoning are dominant frameworks in early childhood education and care (ECEC) worldwide. Popular since the 1960s, HCT has provided an economic understanding of human beings and offered strategies to manage the population with the promise of bringing improvements to nations. Neuroscience…

  20. The Early Development of Human Mirror Mechanisms: Evidence from Electromyographic Recordings at 3 and 6 Months

    ERIC Educational Resources Information Center

    Turati, Chiara; Natale, Elena; Bolognini, Nadia; Senna, Irene; Picozzi, Marta; Longhi, Elena; Cassia, Viola Macchi

    2013-01-01

    In primates and adult humans direct understanding of others' action is provided by mirror mechanisms matching action observation and action execution (e.g. Casile, Caggiano & Ferrari, 2011). Despite the growing body of evidence detailing the existence of these mechanisms in the adult human brain, their origins and early development are…

  1. Early Detection of Human Focal Seizures Based on Cortical Multiunit Activity

    PubMed Central

    Park, Yun S.; Hochberg, Leigh R.; Eskandar, Emad N.; Cash, Sydney S.; Truccolo, Wilson

    2014-01-01

    Approximately 50 million people in the world suffer from epileptic seizures. Reliable early seizure detection could bring significantly beneficial therapeutic alternatives. In recent decades, most approaches have relied on scalp EEG and intracranial EEG signals, but practical early detection for closed-loop seizure control remains challenging. In this study, we present preliminary analyses of an early detection approach based on intracortical neuronal multiunit activity (MUA) recorded from a 96-microelectrode array (MEA). The approach consists of (1) MUA detection from broadband field potentials recorded at 30 kHz by the MEA; (2) MUA feature extraction; (3) cost-sensitive support vector machine classification of ictal and interictal samples; and (4) Kalman-filtering postprocessing. MUA was here defined as the number of threshold crossing (spike counts) applied to the 300 Hz – 6 kHz bandpass filtered local field potentials in 0.1 sec time windows. MUA features explored in this study included the mean, variance, and Fano-factor, computed across the MEA channels. In addition, we used the leading eigenvalues of MUA spatial and temporal correlation matrices computed in 1-sec moving time windows. We assessed the seizure detection approach on out-of-sample data from one-participant recordings with six seizure events and 4.73-hour interictal data. The proposed MUA-based detection approach yielded a 100% sensitivity (6/6) and no false positives, and a latency of 4.17 ± 2.27 sec (mean ± SD) with respect to ECoG-identified seizure onsets. These preliminary results indicate intracortical MUA may be a useful signal for early detection of human epileptic seizures. PMID:25571313

  2. Endoscopic Histologic Mapping of a Mixed Germ Pineal Tumor.

    PubMed

    Velásquez, Carlos; Rivero-Garvía, Mónica; Rivas, Eloy; Cañizares, María de Los Angeles; Mayorga-Buiza, María José; Márquez-Rivas, Javier

    2016-11-01

    The accurate histologic diagnosis of germ cell tumors in the pineal region is a keystone for determining the best treatment strategy and prognosis. This situation poses a challenge for the neuropathologist, considering the lack of a standarized procedure to obtain biopsy samples, which results in few and small specimens, which are not suitable for diagnosis. We report a case in which a pineal region mixed germ cell tumor was accurately diagnosed by performing histologic mapping through a dual burr-hole endoscopic approach. The technical pitfalls and other considerations necessary for obtaining an accurate diagnosis in this tumor subgroup are specified. In addition, the histologic analysis regarding the sampling technique used is described. The supraorbital frontal endoscopic approach enables the surgeon to perform histologic mapping of pineal region tumors, allowing standarization of the procedure used to obtain the specimens. This approach could result in a more accurate diagnosis, especially in mixed germ cell neoplasms. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Postchemotherapy changes in testicular germ cell tumours: biology and morphology.

    PubMed

    Berney, Daniel M; Lu, Yong-Jie; Shamash, Jonathan; Idrees, Muhammad

    2017-01-01

    Advances in modern chemotherapy and targeted treatments have resulted in lengthened survival in a variety of tumour types in the last decade. Increasingly in the 21st century, postchemotherapy resections are considered as a possible mode of treatment. Due to their exquisite chemosensitivity, resection of postchemotherapy masses has long been part of the armamentarium of treatment in testicular germ cell neoplasia, which has resulted in a variety of new morphological variants being described after treatment. Here we discuss the possible reasons for germ cell tumour chemosensitivity and hypotheses on the biological pathways leading to resistance to treatment, as well as an outline of the diverse morphology of those tumours which prove recalcitrant to standard treatment methods. The large range of morphologies and their diagnostic challenges may throw light upon the future problems to be encountered in non-germ cell solid tumour pathology, as the resection of postchemotherapy masses becomes increasingly important in patient management. © 2016 John Wiley & Sons Ltd.

  4. The Phylogenetic Origin of oskar Coincided with the Origin of Maternally Provisioned Germ Plasm and Pole Cells at the Base of the Holometabola

    PubMed Central

    Lynch, Jeremy A.; Özüak, Orhan; Khila, Abderrahman; Abouheif, Ehab; Desplan, Claude; Roth, Siegfried

    2011-01-01

    The establishment of the germline is a critical, yet surprisingly evolutionarily labile, event in the development of sexually reproducing animals. In the fly Drosophila, germ cells acquire their fate early during development through the inheritance of the germ plasm, a specialized maternal cytoplasm localized at the posterior pole of the oocyte. The gene oskar (osk) is both necessary and sufficient for assembling this substance. Both maternal germ plasm and oskar are evolutionary novelties within the insects, as the germline is specified by zygotic induction in basally branching insects, and osk has until now only been detected in dipterans. In order to understand the origin of these evolutionary novelties, we used comparative genomics, parental RNAi, and gene expression analyses in multiple insect species. We have found that the origin of osk and its role in specifying the germline coincided with the innovation of maternal germ plasm and pole cells at the base of the holometabolous insects and that losses of osk are correlated with changes in germline determination strategies within the Holometabola. Our results indicate that the invention of the novel gene osk was a key innovation that allowed the transition from the ancestral late zygotic mode of germline induction to a maternally controlled establishment of the germline found in many holometabolous insect species. We propose that the ancestral role of osk was to connect an upstream network ancestrally involved in mRNA localization and translational control to a downstream regulatory network ancestrally involved in executing the germ cell program. PMID:21552321

  5. Xenogenesis in teleost fish through generation of germ-line chimeras by single primordial germ cell transplantation.

    PubMed

    Saito, Taiju; Goto-Kazeto, Rie; Arai, Katsutoshi; Yamaha, Etsuro

    2008-01-01

    Primordial germ cells (PGCs) are the only cells in developing embryos with the potential to transmit genetic information to the next generation. PGCs therefore have the potential to be of value for gene banking and cryopreservation, particularly via the production of donor gametes with germ-line chimeras. Currently, it is not clear how many PGCs are required for germ-line differentiation and formation of gonadal structures. In the present study, we achieved complete germ-line replacement between two related teleost species, the pearl danio (Danio albolineatus) and the zebrafish (Danio rerio), with transplantation of a single PGC into each host embryo. We isolated and transplanted a single PGC into each blastula-stage, zebrafish embryo. Development of host germ-line cells was prevented by an antisense dead end morpholino oligonucleotide. In many host embryos, the transplanted donor PGC successfully migrated toward the gonadal anlage without undergoing cell division. At the gonadal anlage, the PGC differentiated to form one normally sized gonad rather than the pair of gonads usually present. Offspring were obtained from natural spawning of these chimeras. Analyses of morphology and DNA showed that the offspring were of donor origin. We extended our study to confirm that transplanted single PGCs of goldfish (Carassius auratus) and loach (Misgurnus anguillicaudatus) can similarly differentiate into sperm in zebrafish host embryos. Our results show that xenogenesis is realistic and practical across species, genus, and family barriers and can be achieved by the transplantation of a single PGC from a donor species.

  6. Identification of a putative germ plasm in the amphipod Parhyale hawaiensis

    PubMed Central

    2013-01-01

    Background Specification of the germ line is an essential event during the embryonic development of sexually reproducing animals, as germ line cells are uniquely capable of giving rise to the next generation. Animal germ cells arise through either inheritance of a specialized, maternally supplied cytoplasm called 'germ plasm’ or though inductive signaling by somatic cells. Our understanding of germ cell determination is based largely on a small number of model organisms. To better understand the evolution of germ cell specification, we are investigating this process in the amphipod crustacean Parhyale hawaiensis. Experimental evidence from previous studies demonstrated that Parhyale germ cells are specified through inheritance of a maternally supplied cytoplasmic determinant; however, this determinant has not been identified. Results Here we show that the one-cell stage Parhyale embryo has a distinct cytoplasmic region that can be identified by morphology as well as the localization of germ line-associated RNAs. Removal of this cytoplasmic region results in a loss of embryonic germ cells, supporting the hypothesis that it is required for specification of the germ line. Surprisingly, we found that removal of this distinct cytoplasm also results in aberrant somatic cell behaviors, as embryos fail to gastrulate. Conclusions Parhyale hawaiensis embryos have a specialized cytoplasm that is required for specification of the germ line. Our data provide the first functional evidence of a putative germ plasm in a crustacean and provide the basis for comparative functional analysis of germ plasm formation within non-insect arthropods. PMID:24314239

  7. Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells*

    PubMed Central

    Lin, Shu; Yuan, Zuo-Fei; Han, Yumiao; Marchione, Dylan M.; Garcia, Benjamin A.

    2016-01-01

    How histone post-translational modifications (PTMs) are inherited through the cell cycle remains poorly understood. Canonical histones are made in the S phase of the cell cycle. Combining mass spectrometry-based technologies and stable isotope labeling by amino acids in cell culture, we question the distribution of multiple histone PTMs on old versus new histones in synchronized human cells. We show that histone PTMs can be grouped into three categories according to their distributions. Most lysine mono-methylation and acetylation PTMs are either symmetrically distributed on old and new histones or are enriched on new histones. In contrast, most di- and tri-methylation PTMs are enriched on old histones, suggesting that the inheritance of different PTMs is regulated distinctly. Intriguingly, old and new histones are distinct in their phosphorylation status during early mitosis in the following three human cell types: HeLa, 293T, and human foreskin fibroblast cells. The mitotic hallmark H3S10ph is predominantly associated with old H3 at early mitosis and becomes symmetric with the progression of mitosis. This same distribution was observed with other mitotic phosphorylation marks, including H3T3/T6ph, H3.1/2S28ph, and H1.4S26ph but not S28/S31ph on the H3 variant H3.3. Although H3S10ph often associates with the neighboring Lys-9 di- or tri-methylations, they are not required for the asymmetric distribution of Ser-10 phosphorylation on the same H3 tail. Inhibition of the kinase Aurora B does not change the distribution despite significant reduction of H3S10ph levels. However, K9me2 abundance on the new H3 is significantly reduced after Aurora B inhibition, suggesting a cross-talk between H3S10ph and H3K9me2. PMID:27226594

  8. [Establishment of sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo].

    PubMed

    Jiang, Hua; Feng, You-Ji; Xie, Yi; Han, Jin-Lan; Wang, Zack; Chen, Tong

    2008-10-14

    To establish a sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo. Human embryonic stem were (hESCs) were cultured on the mouse embryo fibroblasts and then were induced to differentiate to form three-dimensional EB. The hEBs were cultured in media containing various angiogenesis-related factors: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), endostatin, angiostatin, and platelet factor (PF)-4 of different concentrations for 3 days to observe the sprouting of the hEBs. 3, 3, 3', 3'-tetramethylindo-carbocyanine perchlorate labeled acetylated low density lipoprotein (Dil-AcLDL) was added onto the hEBs foe 4 h Immunofluorescence assay was used to observe if Dil-AcLDL was absorbed and if CD31 was expressed so as to determine the existence of embryonic endothelial cells in the sprouting structures. The ideal culturing condition was analyzed. The differentiated EBs formed sprouting structures in the collagen I matrix containing VEGF and FGF. The sprouts among individual EBs were able to link to each other and form vascular network-like structures. In the presence of VEGF and FGF, the sprouts branching from the EBs assimilated Dil-AcLDL, expressed CD31 and formed a 3-dimensional cylindrical organization. The concentrations of growth factors ideally stimulating sprouting growth were 100 ng/ml of VEGF and 50 ng/ml of FGF. The networks among the EBs were abolished by the angiostatin, endostatin, and PF4. The sprouting from hEBs accumulates embryonic endothelial cells and the sprouting network-like structures are indeed endothelial in nature. Inducing of sprouting EBs is an ideal model that mimics early embryonic vasculogenesis in humans.

  9. Calcium-activated potassium channels as potential early markers of human cervical cancer

    PubMed Central

    Ramírez, Ana; Vera, Eunice; Gamboa-Domínguez, Armando; Lambert, Paul; Gariglio, Patricio; Camacho, Javier

    2018-01-01

    Cervical cancer is a major cause of cancer-associated mortality in women in developing countries. Thus, novel early markers are required. Ion channels have gained great interest as tumor markers, including cervical cancer. The calcium-activated potassium channel KCNMA1 (subunit α-1 from subfamily M) has been associated with different malignancies, including tumors such as breast and ovarian cancer that are influenced by hormones. The KCNMA1 channel blocker iberiotoxin decreases the proliferation of HeLa cervical cancer cells. Nevertheless, KCNMA1 channel expression during cervical carcinogenesis remains elusive. Therefore, KCNMA1 expression was studied in cervical cancer development. FVB transgenic mice expressing the E7-oncogene of high-risk human papilloma virus, and non-transgenic mice were treated with estradiol-releasing pellets during 3 or 6 months to induce cervical lesions. Twenty-four human cervical biopsies from non-cancerous, low- or high-grade intraepithelial lesions, or cervical cancer were also studied. mRNA and protein expression was assessed by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively. Cervical dysplasia and carcinoma were observed only in the transgenic mice treated with estradiol for 3 and 6 months, respectively. Estradiol treatment increased KCNMA1 mRNA and protein expression in all groups; however, the highest levels were observed in the transgenic mice with carcinoma. KCNMA1 protein expression in the squamous cells of the transformation zone was observed only in the transgenic mice with cervical dysplasia or cancer. Human biopsies from non-cancerous cervix did not display KCNMA1 protein expression; in contrast, the majority of the tissues with cervical lesions (16/18) displayed KCNMA1 protein expression. The lowest channel immunostaining intensity was observed in biopsies from low-grade dysplasia and the strongest in the carcinoma tissues. These results suggest KCNMA1 channels as

  10. Oocyte formation by mitotically-active germ cells purified from ovaries of reproductive age women

    PubMed Central

    White, Yvonne A. R.; Woods, Dori C.; Takai, Yasushi; Ishihara, Osamu; Seki, Hiroyuki; Tilly, Jonathan L.

    2012-01-01

    Germline stem cells that produce oocytes in vitro and fertilization-competent eggs in vivo have been identified in and isolated from adult mouse ovaries. Here we describe and validate a FACS-based protocol that can be used with adult mouse ovaries and human ovarian cortical tissue to purify rare mitotically-active cells that exhibit a gene expression profile consistent with primitive germ cells. Once established in vitro, these cells can be expanded for months and spontaneously generate 35–50 µm oocytes, as determined by morphology, gene expression and attainment of haploid (1n) status. Injection of the human germline cells, engineered to stably express GFP, into human ovarian cortical biopsies leads to formation of follicles containing GFP-positive oocytes 1–2 weeks after xenotransplantation into immunodeficient female mice. Thus, ovaries of reproductive-age women, like adult mice, possess rare mitotically-active germ cells that can be propagated in vitro as well as generate oocytes in vitro and in vivo. PMID:22366948

  11. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women.

    PubMed

    White, Yvonne A R; Woods, Dori C; Takai, Yasushi; Ishihara, Osamu; Seki, Hiroyuki; Tilly, Jonathan L

    2012-02-26

    Germline stem cells that produce oocytes in vitro and fertilization-competent eggs in vivo have been identified in and isolated from adult mouse ovaries. Here we describe and validate a fluorescence-activated cell sorting-based protocol that can be used with adult mouse ovaries and human ovarian cortical tissue to purify rare mitotically active cells that have a gene expression profile that is consistent with primitive germ cells. Once established in vitro, these cells can be expanded for months and can spontaneously generate 35- to 50-μm oocytes, as determined by morphology, gene expression and haploid (1n) status. Injection of the human germline cells, engineered to stably express GFP, into human ovarian cortical biopsies leads to formation of follicles containing GFP-positive oocytes 1-2 weeks after xenotransplantation into immunodeficient female mice. Thus, ovaries of reproductive-age women, similar to adult mice, possess rare mitotically active germ cells that can be propagated in vitro as well as generate oocytes in vitro and in vivo.

  12. Early afterdepolarizations promote transmural reentry in ischemic human ventricles with reduced repolarization reserve

    PubMed Central

    Dutta, Sara; Mincholé, Ana; Zacur, Ernesto; Quinn, T. Alexander; Taggart, Peter; Rodriguez, Blanca

    2016-01-01

    Aims Acute ischemia is a major cause of sudden arrhythmic death, further promoted by potassium current blockers. Macro-reentry around the ischemic region and early afterdepolarizations (EADs) caused by electrotonic current have been suggested as potential mechanisms in animal and isolated cell studies. However, ventricular and human-specific arrhythmia mechanisms and their modulation by repolarization reserve remain unclear. The goal of this paper is to unravel multiscale mechanisms underlying the modulation of arrhythmic risk by potassium current (IKr) block in human ventricles with acute regional ischemia. Methods and results A human ventricular biophysically-detailed model, with acute regional ischemia is constructed by integrating experimental knowledge on the electrophysiological ionic alterations caused by coronary occlusion. Arrhythmic risk is evaluated by determining the vulnerable window (VW) for reentry following ectopy at the ischemic border zone. Macro-reentry around the ischemic region is the main reentrant mechanism in the ischemic human ventricle with increased repolarization reserve due to the ATP-sensitive potassium current (IK(ATP)) activation. Prolongation of refractoriness by 4% caused by 30% IKr reduction counteracts the establishment of macro-reentry and reduces the VW for reentry (by 23.5%). However, a further decrease in repolarization reserve (50% IKr reduction) is less anti-arrhythmic despite further prolongation of refractoriness. This is due to the establishment of transmural reentry enabled by electrotonically-triggered EADs in the ischemic border zone. EADs are produced by L-type calcium current (ICaL) reactivation due to prolonged low amplitude electrotonic current injected during the repolarization phase. Conclusions Electrotonically-triggered EADs are identified as a potential mechanism facilitating intramural reentry in a regionally-ischemic human ventricles model with reduced repolarization reserve. PMID:26850675

  13. Early embryo mortality in natural human reproduction: What the data say

    PubMed Central

    Jarvis, Gavin E.

    2017-01-01

    How many human embryos die between fertilisation and birth under natural conditions? It is widely accepted that natural human embryo mortality is high, particularly during the first weeks after fertilisation, with total prenatal losses of 70% and higher frequently claimed. However, the first external sign of pregnancy occurs two weeks after fertilisation with a missed menstrual period, and establishing the fate of embryos before this is challenging. Calculations are additionally hampered by a lack of data on the efficiency of fertilisation under natural conditions. Four distinct sources are used to justify quantitative claims regarding embryo loss: (i) a hypothesis published by Roberts & Lowe in The Lancet  is widely cited but has no practical quantitative value; (ii) life table analyses give consistent assessments of clinical pregnancy loss, but cannot illuminate losses at earlier stages of development; (iii) studies that measure human chorionic gonadotrophin (hCG) reveal losses in the second week of development and beyond, but not before; and (iv) the classic studies of Hertig and Rock offer the only direct insight into the fate of human embryos from fertilisation under natural conditions. Re-examination of Hertig’s data demonstrates that his estimates for fertilisation rate and early embryo loss are highly imprecise and casts doubt on the validity of his numerical analysis. A recent re-analysis of hCG study data concluded that approximately 40-60% of embryos may be lost between fertilisation and birth, although this will vary substantially between individual women. In conclusion, natural human embryo mortality is lower than often claimed and widely accepted. Estimates for total prenatal mortality of 70% or higher are exaggerated and not supported by the available data. PMID:28580126

  14. The PUF binding landscape in metazoan germ cells

    PubMed Central

    Prasad, Aman; Porter, Douglas F.; Kroll-Conner, Peggy L.; Mohanty, Ipsita; Ryan, Anne R.; Crittenden, Sarah L.; Wickens, Marvin; Kimble, Judith

    2016-01-01

    PUF (Pumilio/FBF) proteins are RNA-binding proteins and conserved stem cell regulators. The Caenorhabditis elegans PUF proteins FBF-1 and FBF-2 (collectively FBF) regulate mRNAs in germ cells. Without FBF, adult germlines lose all stem cells. A major gap in our understanding of PUF proteins, including FBF, is a global view of their binding sites in their native context (i.e., their “binding landscape”). To understand the interactions underlying FBF function, we used iCLIP (individual-nucleotide resolution UV crosslinking and immunoprecipitation) to determine binding landscapes of C. elegans FBF-1 and FBF-2 in the germline tissue of intact animals. Multiple iCLIP peak-calling methods were compared to maximize identification of both established FBF binding sites and positive control target mRNAs in our iCLIP data. We discovered that FBF-1 and FBF-2 bind to RNAs through canonical as well as alternate motifs. We also analyzed crosslinking-induced mutations to map binding sites precisely and to identify key nucleotides that may be critical for FBF–RNA interactions. FBF-1 and FBF-2 can bind sites in the 5′UTR, coding region, or 3′UTR, but have a strong bias for the 3′ end of transcripts. FBF-1 and FBF-2 have strongly overlapping target profiles, including mRNAs and noncoding RNAs. From a statistically robust list of 1404 common FBF targets, 847 were previously unknown, 154 were related to cell cycle regulation, three were lincRNAs, and 335 were shared with the human PUF protein PUM2. PMID:27165521

  15. Identification of a subgroup with worse prognosis among patients with poor-risk testicular germ cell tumor.

    PubMed

    Kojima, Takahiro; Kawai, Koji; Tsuchiya, Kunihiko; Abe, Takashige; Shinohara, Nobuo; Tanaka, Toshiaki; Masumori, Naoya; Yamada, Shigeyuki; Arai, Yoichi; Narita, Shintaro; Tsuchiya, Norihiko; Habuchi, Tomonori; Nishiyama, Hiroyuki

    2015-10-01

    To clarify the significance of the International Germ Cell Cancer Collaborative Group classification in the 2000s, especially in intermediate- and poor-prognosis testicular germ cell tumor in Japan. We retrospectively analyzed 117 patients with intermediate- and poor-prognosis testicular non-seminomatous germ cell tumor treated at five university hospitals in Japan between 2000 and 2010. Data collected included age, levels of tumor markers, spread to non-pulmonary visceral metastases, treatment details and survival. The median follow-up period of all patients was 57 months. A total of 50 patients (43%) were classified as having intermediate prognosis, and 67 patients (57%) as poor prognosis according to the International Germ Cell Cancer Collaborative Group classification. As first-line chemotherapy, 92 patients (79%) received bleomycin, etoposide and cisplatin. Of all patients, 74 patients (63%) received second-line chemotherapy. The most commonly used second-line chemotherapy regimens were a combination of taxanes, ifosfamide and platinum in 49 cases (66%). Overall, 33 patients (28%) received third-line chemotherapy. A total of 88 patients (75%) underwent post-chemotherapy surgery. The 5-year overall survival for intermediate (n = 50) and poor prognosis (n = 67) was 89% and 83% (P = 0.21), respectively. In poor prognosis patients, patients with two or more risk factors (any of high lactic dehydrogenase, alpha-fetoprotein and human chorionic gonadotropin levels, and presence of non-pulmonary visceral metastases) had significantly worse survival than those with only one risk factor (71% and 91%, respectively, P = 0.01). The 5-year overall survivals of poor-prognosis testicular non-seminomatous germ cell tumor patients reached 83%. Further stratification of poor-prognosis patients based on a number of risk factors has the potential to further identify those with poorer prognosis. © 2015 The Japanese Urological Association.

  16. The interactions of dietary tomato powder and soy germ on prostate carcinogenesis in the TRAMP model

    PubMed Central

    Zuniga, Krystle E.; Clinton, Steven K; Erdman, John W.

    2013-01-01

    The interactions between bioactive rich food components within a complex human diet for the inhibition of prostate carcinogenesis (PCa) are largely unknown and difficult to quantify in humans. Tomato and soy products have each shown anti-PCa activity in laboratory studies. The objective of this study was to determine the efficacy of dietary tomato and soy germ, alone and in combination, for the inhibition of prostate carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. At 4 weeks of age, male C57BL/6 × FVB TRAMP mice (n=119) were randomized to consume: AIN-93G control, 10% whole tomato powder (TP), 2% soy germ powder (SG) or 10% tomato powder with 2% soy germ powder (TP+SG) for 14 weeks. 100% of mice fed the control diet had PCa, while PCa incidence was significantly lower in mice consuming TP (61%, p<0.001), SG (66%, p<0.001) and TP+SG (45%, p<0.001). Although the protection offered by the combination of TP and SG was not synergistic, it was the most effective intervention. TP, SG and TP+SG increased apoptotic index (AI) and modestly reduced the proliferative index (PI) in the prostate epithelium of TRAMP mice exhibiting primarily prostatic intraepithelial neoplasia. The dramatic reduction in the PI/AI ratio by the dietary interventions suggests that the control mice experience a stronger stimulus for malignant progression in the prostate microenvironment. Maximally effective and safe strategies for PCa prevention may result from optimizing combinations of nutrients and bioactives through an orchestration of dietary patterns. PMID:23592738

  17. Germ-line gene therapy and the medical imperative.

    PubMed

    Munson, Ronald; Davis, Lawrence H

    1992-06-01

    Somatic cell gene therapy has yielded promising results. If germ cell gene therapy can be developed, the promise is even greater: hundreds of genetic diseases might be virtually eliminated. But some claim the procedure is morally unacceptable. We thoroughly and sympathetically examine several possible reasons for this claim but find them inadequate. There is no moral reason, then, not to develop and employ germ-line gene therapy. Taking the offensive, we argue next that medicine has a prima facie moral obligation to do so.

  18. Early adolescent childbearing in low- and middle-income countries: associations with income inequity, human development and gender equality.

    PubMed

    Decker, Michele R; Kalamar, Amanda; Tunçalp, Özge; Hindin, Michelle J

    2017-03-01

    Reducing unwanted adolescent childbearing is a global priority. Little is known about how national-level economic and human development indicators relate to early adolescent childbearing. This ecological study evaluates associations of Gross Domestic Product (GDP), GINI index, Human Development Index (HDI) and Gender-related Development Index (GDI; i.e. the HDI adjusted for gender disparities) with early adolescent childbearing in 27 low- and middle-income countries (LMICs) across three time periods. Among women ages 18–24, prevalence estimates for early birth (<16 years) were calculated by nation, and weighted linear regressions evaluated associations between national indicators and early childbearing. To examine temporal trends, analyses were stratified by year groupings. Early adolescent childbearing declined over time, with the greatest change observed in Bangladesh (31.49% in 1996/7 to 19.69% in 2011). In adjusted models, GDI was negatively associated with early childbearing, i.e. early childbearing prevalence decreased as GDI increased. In the most recent time period, relative to the lowest GDI group, the average prevalence of early childbearing was significantly lower in the middle (-12.40, P < 0.00) and upper (-10.96, P = 0.03) tertiles after adjustment for the other indicators. These other indicators showed no consistent association with early childbearing. As national-level GDI increased, early adolescent childbearing declined. The GDI, which reflects human development adjusted for gender disparities in educational and economic prospects, was more consistently related to early adolescent childbearing than the absolute development prospects as given by the HDI. While creating gender equality is an important goal in and of itself, the findings emphasize the potential for improved national-level gender equitable development as a means to improve adolescents’ sexual and reproductive health.

  19. Localization of type IV collagen a 1 to a 6 chains in basement membrane during mouse molar germ development.

    PubMed

    Nagai, N; Nakano, K; Sado, Y; Naito, I; Gunduz, M; Tsujigiwa, H; Nagatsuka, H; Ninomiya, Y; Siar, C H

    2001-10-01

    The dental basement membrane (BM) putatively mediates epithelial-mesenchymal interactions during tooth morphogenesis and cytodifferentiation. Type IV collagen alpha chains, a major network-forming protein of the dental BM, was studied and results disclosed distinct expression patterns at different stages of mouse molar germ development. At the dental placode and bud stage, the BM of the oral epithelium expressed alpha 1, alpha 2, alpha 5 and alpha 6 chains while the gubernaculum dentis, in addition to the above four chains, also expressed a 4 chain. An asymmetrical expression for alpha 4, alpha 5 and alpha 6 chains was observed at the bud stage. At the early bell stage, the BM associated with the inner enamel epithelium (IEE) of molar germ expressed alpha 1, alpha 2 and alpha 4 chains while the BM of the outer enamel epithelium (OEE) expressed only alpha 1 and a 2 chains. With the onset of dentinogenesis, the collagen a chain profile of the IEE BM gradually disappeared. Howeverfrom the early to late bell stage, the gubernaculum dentis consistently expressed alpha 1, alpha 2, alpha 5 and a 6 chains resembling fetal oral mucosa. These findings suggest that stage- and position-specific distribution of type IV collagen alpha subunits occur during molar germ development and that these changes are essential for molar morphogenesis and cytodifferentiation.

  20. Early manifestation of arm-leg coordination during stepping on a surface in human neonates.

    PubMed

    La Scaleia, Valentina; Ivanenko, Y; Fabiano, A; Sylos-Labini, F; Cappellini, G; Picone, S; Paolillo, P; Di Paolo, A; Lacquaniti, F

    2018-04-01

    The accomplishment of mature locomotor movements relies upon the integrated coordination of the lower and upper limbs and the trunk. Human adults normally swing their arms and a quadrupedal limb coordination persists during bipedal walking despite a strong corticospinal control of the upper extremities that allows to uncouple this connection during voluntary activities. Here we investigated arm-leg coordination during stepping responses on a surface in human neonates. In eight neonates, we found the overt presence of alternating arm-leg oscillations, the arms moving up and down in alternation with ipsilateral lower limb movements. These neonates moved the diagonal limbs together, and the peak of the arm-to-trunk angle (i.e., maximum vertical excursion of the arm) occurred around the end of the ipsilateral stance phase, as it occurs during typical adult walking. Although episodes of arm-leg coordination were sporadic in our sample of neonates, their presence provides significant evidence for a neural coupling between the upper and lower limbs during early ontogenesis of locomotion in humans.

  1. Differential expression of the major immediate early gene of human cytomegalovirus.

    PubMed

    Tsutsui, Y; Nogami-Satake, T

    1990-01-01

    We prepared a murine monoclonal antibody reactive to a human cytomegalovirus (HCMV)-induced nuclear protein with an Mr of 68,000. Expression of the 68K protein was compared with the major immediate early (IE) 72K protein in various cell types after infection with HCMV or microinjection of plasmid DNA containing the major IE gene. The 68K nuclear protein was detected 2 to 3 h after appearance of the 72K protein in human embryonal lung (HEL) cells infected with HCMV. The 68K protein was distributed throughout the cytoplasm in the late phase of infection, while the 72K protein remained chiefly in the nucleus. The 68K protein was barely detected in the cells under IE conditions by immunoprecipitation, but, together with the 72K protein, it was expressed after microinjection of cloned DNA, containing only the major IE region (region 1), into the nuclei of HEL cells. The 72K protein was expressed in nuclei 2 h after microinjection, whereas the 68K protein was detected 4 to 5 h after the injection. The 68K protein was expressed after microinjection in non-permissive rodent fibroblasts or non-permissive transformed human cells in which these proteins were not expressed after viral infection. Immunoprecipitations after chase-labelling from IE conditions or after partial digestions suggested that the 68K protein is neither a degradation nor a modification product of the major IE 72K protein.

  2. KDR (VEGFR2) identifies a conserved human and murine hepatic progenitor and instructs early liver development

    PubMed Central

    Goldman, Orit; Han, Songyan; Sourrisseau, Marion; Dziedzic, Noelle; Hamou, Wissam; Corneo, Barbara; D’Souza, Sunita; Sato, Thomas; Kotton, Darrell N.; Bissig, Karl-Dimiter; Kalir, Tamara; Jacobs, Adam; Evans, Todd; Evans, Matthew J.; Gouon-Evans, Valerie

    2013-01-01

    SUMMARY Understanding the fetal hepatic niche is essential for optimizing the generation of functional hepatocyte-like (hepatic) cells from human embryonic stem cells (hESCs). Here, we show that KDR (VEGFR2), previously assumed to be mostly restricted to mesodermal lineages, marks a hESC-derived hepatic progenitor. hESC-derived endoderm cells do not express KDR, but when cultured in media supporting hepatic differentiation, generate KDR+ hepatic progenitors and KDR- hepatic cells. KDR+ progenitors require active KDR signaling both to instruct their own differentiation into hepatic cells, and to support non-cell-autonomously the functional maturation of co-cultured KDR- hepatic cells. Analysis of human fetal livers suggests that similar progenitors are present in human livers. Lineage tracing in mice provides in vivo evidence of a KDR+ hepatic progenitor for fetal hepatoblasts and subsequently adult hepatocytes and cholangiocytes. Altogether, our findings reveal that KDR is a conserved marker for endoderm-derived hepatic progenitors, and a functional receptor instructing early liver development. PMID:23746980

  3. Angiogenin Expression during Early Human Placental Development; Association with Blood Vessel Formation

    PubMed Central

    Pavlov, Nadine; Guibourdenche, Jean; Degrelle, Séverine A.; Evain-Brion, Danièle

    2014-01-01

    The placenta is a transient organ essential for fetal development. During human placental development, chorionic villi grow in coordination with a large capillary network resulting from both vasculogenesis and angiogenesis. Angiogenin is one of the most potent inducers of neovascularisation in experimental models in vivo. We and others have previously mapped angiogenin expression in the human term placenta. Here, we explored angiogenin involvement in early human placental development. We studied, angiogenin expression by in situ hybridisation and/or by RT-PCR in tissues and primary cultured trophoblastic cells and angiogenin cellular distribution by coimmunolabelling with cell markers: CD31 (PECAM-1), vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), Tie-2, von Willebrand factor, CD34, erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Extravillous and villous cytotrophoblasts, isolated and differentiated in vitro, expressed and secreted angiogenin. Angiogenin was detected in villous trophoblastic layers, and structured and nascent fetal vessels. In decidua, it was expressed by glandular epithelial cells, vascular cells and macrophages. The observed pattern of angiogenin expression is compatible with a role in blood vessel formation and in cross-talk between trophoblasts and endothelial cells. In view of angiogenin properties, we suggest that angiogenin may participate in placental vasculogenesis and organogenesis. PMID:25093183

  4. Early variability in the conceptualisation of "sustainable development and human factors".

    PubMed

    Thatcher, Andrew

    2012-01-01

    The sub-discipline of "sustainable development and human factors" is relatively new, first being used in 2006 with a Technical Committee of the IEA being established only in 2009 and a similar special interest group on "green ergonomics" at the Institute of Ergonomics and Human Factors being established in 2010. In general though, the definitions and practice of "sustainable development" is highly contentious and ambiguous across a range of disciplines. This paper examines the diversity of definitions and approaches to sustainable development and human factors in the early papers in this sub-discipline. An examination of 45 chapters and papers (from 2008 to 2011) reveals a surprising consistency in the definitions used for sustainable development but also a large proportion of the papers where no definitions are given at all. The majority of papers were, however, biased towards an economic capital and social capital emphasis, which is to be expected of work traditionally in the ergonomics paradigm. Further, most papers were theoretical in nature demonstrating a great opportunity for empirical work. The variability in definitions is discussed in relation to the future challenges facing the growth of this emergent sub-discipline and opportunities for further theoretical and empirical work.

  5. CX43 expression, phosphorylation, and distribution in the normal and autoimmune orchitic testis with a look at gap junctions joining germ cell to germ cell.

    PubMed

    Pelletier, R-Marc; Akpovi, Casimir D; Chen, Li; Day, Robert; Vitale, María L

    2011-01-01

    Spermatogenesis requires connexin 43 (Cx43).This study examines normal gene transcription, translation, and phosphorylation of Cx43 to define its role on germ cell growth and Sertoli cell's differentiation, and identifies abnormalities arising from spontaneous autoimmune orchitis (AIO) in mink, a seasonal breeder and a natural model for autoimmunity. Northern blot analysis detected 2.8- and a 3.7-kb Cx43 mRNA bands in seminiferous tubule-enriched fractions. Cx43 mRNA increased in seminiferous tubule-enriched fractions throughout development and then seasonally with the completion of spermatogenesis. Cx43 protein levels increased transiently during the colonization of the tubules by the early-stage spermatocytes. Cx43 phosphorylated (PCx43) and nonphosphorylated (NPCx43) in Ser368 decreased during the periods of completion of meiosis and Sertoli cell differentiation, while Cx43 mRNA remained elevated throughout. PCx43 labeled chiefly the plasma membrane except by stage VII when vesicles were also labeled in Sertoli cells. Vesicles and lysosomes in Sertoli cells and the Golgi apparatus in the round spermatids were NPCx43 positive. A decrease in Cx43 gene expression was matched by a Cx43 protein increase in the early, not the late, phase of AIO. Total Cx43 and PCx43 decreased with the advance of orchitis. The study makes a novel finding of gap junctions connecting germ cells. The data indicate that Cx43 protein expression and phosphorylation in Ser368 are stage-specific events that may locally influence the acquisition of meiotic competence and the Sertoli cell differentiation in normal testis. AIO modifies Cx43 levels, suggesting changes in Cx43-mediated intercommunication and spermatogenic activity in response to cytokines imbalances in Sertoli cells.

  6. Differences between the endocytosis of horseradish peroxidase and its conjugate with wheat germ agglutinin by cultured fibroblasts.

    PubMed

    Stieber, A; Gonatas, J O; Gonatas, N K

    1984-04-01

    A covalent conjugate of wheat germ agglutinin (WGA) with horseradish peroxidase (HRP) was used for a morphologic study of its adsorptive endocytosis by cultured human fibroblasts. Initial binding at 4 degrees C of the conjugate was observed over the entire plasma membrane, including "coated" and smooth pits. Endocytosis of HRP and the WGA-HRP conjugate was observed in lysosomes, but only the conjugate was seen in a cisterna of the Golgi apparatus (GERL), and in adjacent coated vesicles.

  7. Childhood Extracranial Germ Cell Tumors Treatment (PDQ®)—Patient Version

    Cancer.gov

    Childhood extracranial germ cell tumors treatment options include surgery, observation, and chemotherapy. Learn more about newly diagnosed and recurrent extracranial germ cell tumors in this expert-reviewed summary.

  8. Ovarian Germ Cell Tumors Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Ovarian germ cell tumors treatment options include surgery, chemotherapy, and radiation therapy. Get detailed treatment information for newly diagnosed or recurrent germ cell tumors in this summary for clinicians.

  9. Proactive Integration of Planetary Protection Needs Into Early Design Phases of Human Exploration Missions

    NASA Astrophysics Data System (ADS)

    Race, Margaret; Conley, Catharine

    yet been developed. Looking ahead, it is recognized that these planetary protection policies will apply to both governmental and non-governmental entities for the more than 100 countries that are signatories to the Outer SpaceTreaty. Fortunately, planetary protection controls for human missions are supportive of many other important mission needs, such as maximizing closed-loop and recycling capabilities to minimize mass required, minimizing exposure of humans to planetary materials for multiple health reasons, and minimizing contamination of planetary samples and environments during exploration and science activities. Currently, there is progress on a number of fronts in translating the basic COSPAR PP Principles and Implementation Guidelines into information that links with early engineering and process considerations. For example, an IAA Study Group on Planetary Protection and Human Missions is engaging robotic and human mission developers and scientists in exploring detailed technical, engineering and operational approaches by which planetary protection objectives can be accomplished for human missions in synergism with robotic exploration and in view of other constraints. This on-going study aims to highlight important information for the early stages of planning, and identify key research and technology development (R&TD) areas for further consideration and work. Such R&TD challenges provide opportunities for individuals, institutions and agencies of emerging countries to be involved in international exploration efforts. In January 2014, the study group presented an Interim Report to the IAA Heads of Agencies Summit in Washington DC. Subsequently, the group has continued to work on expanding the initial technical recommendations and findings, focusing especially on information useful to mission architects and designers as they integrate PP considerations in their varied plans-- scientific, commercial and otherwise. Already the findings and recommendations

  10. Humanizing Aggregated Data: Developing Personas to Prioritize User Needs for Earthquake Early Warning

    NASA Astrophysics Data System (ADS)

    Burkett, E. R.; Jayanty, N. K.; Sellnow, D. D.; Given, D. D.; DeGroot, R. M.

    2016-12-01

    Methods that use storytelling to gather and synthesize data from people can be advantageous in understanding user needs and designing successful communication products. Using a multidisciplinary approach, we research and prioritize user needs for the ShakeAlert Earthquake Early Warning system (http://pubs.usgs.gov/fs/2014/3083/), drawing on best practices from social and behavioral science, risk communication, and human-centered design. We apply quantitative and qualitative human data collection methods including user surveys, interviews, journey maps, personas, and scenarios. Human-centered design methods leverage storytelling (a) in the acquisition of qualitative behavioral data (e.g. with journey mapping), (b) through goal-driven behaviors and needs that are synthesized into a persona as a composite model of the data, and (c) within context scenarios (the story plot or projected circumstances) in which the persona is placed in context to inform the design of relevant and usable products or services. ShakeAlert, operated by the USGS and partners, has transitioned into a production prototype phase in which users are permitted to begin testing pilot implementations to take protective actions in response to an earthquake alert. While a subset of responses will be automated (e.g., opening fire house doors), other applications of the technology will alert individuals by broadcast, public address, or mobile device notifications and require self-protective behavioral decisions (e.g., "Drop, Cover, and Hold On"). To better understand ShakeAlert user decisions and needs, we use human-centered design methods to synthesize aggregated behavioral data into "personas," which model the common behavioral patterns that can be used to guide plans for the ShakeAlert interface, messaging, and training. We present user data, methods, and resulting personas that will inform decisions moving forward to shape ShakeAlert messaging and training that will be most usable by alert recipients.

  11. The scent of disease: human body odor contains an early chemosensory cue of sickness.

    PubMed

    Olsson, Mats J; Lundström, Johan N; Kimball, Bruce A; Gordon, Amy R; Karshikoff, Bianka; Hosseini, Nishteman; Sorjonen, Kimmo; Olgart Höglund, Caroline; Solares, Carmen; Soop, Anne; Axelsson, John; Lekander, Mats

    2014-03-01

    Observational studies have suggested that with time, some diseases result in a characteristic odor emanating from different sources on the body of a sick individual. Evolutionarily, however, it would be more advantageous if the innate immune response were detectable by healthy individuals as a first line of defense against infection by various pathogens, to optimize avoidance of contagion. We activated the innate immune system in healthy individuals by injecting them with endotoxin (lipopolysaccharide). Within just a few hours, endotoxin-exposed individuals had a more aversive body odor relative to when they were exposed to a placebo. Moreover, this effect was statistically mediated by the individuals' level of immune activation. This chemosensory detection of the early innate immune response in humans represents the first experimental evidence that disease smells and supports the notion of a "behavioral immune response" that protects healthy individuals from sick ones by altering patterns of interpersonal contact.

  12. Ultrafast microfluidic mixer for tracking the early folding kinetics of human telomere G-quadruplex.

    PubMed

    Li, Ying; Liu, Chao; Feng, Xiaojun; Xu, Youzhi; Liu, Bi-Feng

    2014-05-06

    The folding of G-quadruplex is hypothesized to undergo a complex process, from the formation of a hairpin structure to a triplex intermediate and to the final G-quadruplex. Currently, no experimental evidence has been found for the hairpin formation, because it folds in the time regime of 10-100 μs, entailing the development of microfluidic mixers with a mixing time of less than 10 μs. In this paper, we reported an ultrarapid micromixer with a mixing time of 5.5 μs, which represents the fastest turbulent micromixer to our best knowledge. Evaluations of the micromixer were conducted to confirm its mixing efficiency for small molecules and macromolecules. This new micromixer enabled us to interrogate the hairpin formation in the early folding process of human telomere G-quadruplex. The experimental kinetic evidence for the formation of hairpin was obtained for the first time.

  13. Improving human activity recognition and its application in early stroke diagnosis.

    PubMed

    Villar, José R; González, Silvia; Sedano, Javier; Chira, Camelia; Trejo-Gabriel-Galan, Jose M

    2015-06-01

    The development of efficient stroke-detection methods is of significant importance in today's society due to the effects and impact of stroke on health and economy worldwide. This study focuses on Human Activity Recognition (HAR), which is a key component in developing an early stroke-diagnosis tool. An overview of the proposed global approach able to discriminate normal resting from stroke-related paralysis is detailed. The main contributions include an extension of the Genetic Fuzzy Finite State Machine (GFFSM) method and a new hybrid feature selection (FS) algorithm involving Principal Component Analysis (PCA) and a voting scheme putting the cross-validation results together. Experimental results show that the proposed approach is a well-performing HAR tool that can be successfully embedded in devices.

  14. Early human bone response to laser metal sintering surface topography: a histologic report.

    PubMed

    Mangano, Carlo; Piattelli, Adriano; d'Avila, Susana; Iezzi, Giovanna; Mangano, Francesco; Onuma, Tatiana; Shibli, Jamil Awad

    2010-01-01

    This histologic report evaluated the early human bone response to a direct laser metal sintering implant surface retrieved after a short period of healing. A selective laser sintering procedure using a Ti-6Al-4V alloy powder with a particle size of 25-45 microm prepared this surface topography. One experimental microimplant was inserted into the anterior mandible of a patient during conventional implant surgery of the jaw. The microimplant and surrounding tissues were removed after 2 months of unloaded healing and were prepared for histomorphometric analysis. Histologically, the peri-implant bone appeared in close contact with the implant surface, whereas marrow spaces could be detected in other areas along with prominently stained cement lines. The mean of bone-to-implant contact was 69.51%. The results of this histologic report suggest that the laser metal sintering surface could be a promising alternative to conventional implant surface topographies.

  15. [Early human transplants: 60th anniversary of the first successful kidney transplants].

    PubMed

    Gentili, Marc E

    2015-11-01

    First kidney transplant attempts begin with the 20th century: improving vascular sutures, understanding the phenomena of rejection or tolerance, then progress in HLA groups enable early success in the second half of the century. Definition of brain death, use of corticosteroids, radiotherapy and prime immunosuppressors promote the development of transplants. Discover of cyclosporine in the 1980s, and legislative developments augur a new era. Many advances are arising: use of stem cells from the donor, enhancement of Maastricht 3 donor or living donation. Finally organ transplantation remains an immense human adventure, but also scientific and ethic. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  16. The influence of early embryo traits on human embryonic stem cell derivation efficiency.

    PubMed

    O'Leary, Thomas; Heindryckx, Björn; Lierman, Sylvie; Van der Jeught, Margot; Menten, Björn; Deforce, Dieter; Cornelissen, Ria; de Sousa Lopes, Susana Chuva; De Sutter, Petra

    2011-05-01

    Despite its prognostic value in in vitro fertilization, early embryo morphology is not reported on in the derivation of human embryonic stem cell (hESC) lines. Standard hESC derivation does rely on blastocyst development and its efficiency is highly correlated to inner cell mass (ICM) quality. Poor-quality embryos (PQEs) donated for hESC derivation may have a range of cleavage-stage abnormalities that are known to compromise further development. This study was implemented to determine whether specific PQEs traits influence the efficiency of good-quality ICMs to derive new hESC lines. We found that although the types of PQEs investigated were all able to make blastocysts with good-quality ICMs, the ICMs were unequal in their ability to derive hESCs. Good-quality ICMs from embryos with multiple poor-quality traits were unable to generate hESC lines, in contrast to good-quality ICMs from embryos with a single poor-quality trait. In addition, our data suggest a direct correlation between the number of ICM cells present in the blastocyst and its capacity to derive new hESC lines. This study is the first to demonstrate that ICM quality alone is an incomplete indicator of hESC derivation and that application of in vitro fertilization-based early embryo scoring can help predict hESC derivation efficiency. Experiments aiming to quantify, improve upon, or compare hESC derivation efficiency should thus take into consideration early embryo morphology scoring for the comparison of groups with equal developmental competence.

  17. Early light deprivation effects on human cone-driven retinal function.

    PubMed

    Esposito Veneruso, Paolo; Ziccardi, Lucia; Magli, Giulia; Parisi, Vincenzo; Falsini, Benedetto; Magli, Adriano

    2017-03-01

    To assess whether the early light deprivation induced by congenital cataract may influence the cone-driven retinal function in humans. Forty-one patients affected by congenital cataract (CC) who had undergone uncomplicated cataract extraction surgery and intraocular lens implant, and 14 healthy subjects (HS) were enrolled. All patients underwent complete ophthalmological and orthoptic evaluations and best-corrected visual acuity (BCVA) measurement; light-adapted full-field electroretinograms (ERG) and photopic negative responses (PhNR) were recorded to obtain a reliable measurement of the outer/inner retinal function and of the retinal ganglion cells' function respectively. Mean values of light-adapted ERG a- and b-wave and PhNR amplitude of CC eyes were significantly reduced and photopic ERG b-wave implicit time mean values were significantly delayed when compared to HS ones. When studying photopic ERG mean amplitudes at 5 ms, significant differences were found when comparing CC and control eyes. In CC eyes, statistically significant correlations were found between a- and b- wave amplitudes and PhNR amplitudes. No significant correlations were found between ERG parameters and BCVA, as well as between the age of CC patients at surgery and the time elapsed from lens extraction. No significant differences were found when functional parameters of bilateral and unilateral congenital cataract (uCC) eyes were compared, however uCC eyes showed significant differences when compared with contralateral healthy eyes. We found a significant impairment of cone-driven retinal responses in patients with a history of congenital cataract. These changes might result from the long-lasting effects of early light deprivation on the cone retinal pathways. Our findings support the relevance of retinal involvement in deficits induced by early light deprivation. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  18. Distinct expression patterns for type II topoisomerases IIA and IIB in the early foetal human telencephalon.

    PubMed

    Harkin, Lauren F; Gerrelli, Dianne; Gold Diaz, Diana C; Santos, Chloe; Alzu'bi, Ayman; Austin, Caroline A; Clowry, Gavin J

    2016-03-01

    TOP2A and TOP2B are type II topoisomerase enzymes that have important but distinct roles in DNA replication and RNA transcription. Recently, TOP2B has been implicated in the transcription of long genes in particular that play crucial roles in neural development and are susceptible to mutations contributing to neurodevelopmental conditions such as autism and schizophrenia. This study maps their expression in the early foetal human telencephalon between 9 and 12 post-conceptional weeks. TOP2A immunoreactivity was restricted to cell nuclei of the proliferative layers of the cortex and ganglionic eminences (GE), including the ventricular zone and subventricular zone (SVZ) closely matching expression of the proliferation marker KI67. Comparison with sections immunolabelled for NKX2.1, a medial GE (MGE) marker, and PAX6, a cortical progenitor cell and lateral GE (LGE) marker, revealed that TOP2A-expressing cells were more abundant in MGE than the LGE. In the cortex, TOP2B is expressed in cell nuclei in both proliferative (SVZ) and post-mitotic compartments (intermediate zone and cortical plate) as revealed by comparison with immunostaining for PAX6 and the post-mitotic neuron marker TBR1. However, co-expression with KI67 was rare. In the GE, TOP2B was also expressed by proliferative and post-mitotic compartments. In situ hybridisation studies confirmed these patterns of expression, except that TOP2A mRNA is restricted to cells in the G2/M phase of division. Thus, during early development, TOP2A is likely to have a role in cell proliferation, whereas TOP2B is expressed in post-mitotic cells and may be important in controlling expression of long genes even at this early stage. © 2015 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

  19. Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization.

    PubMed

    Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H Irene

    2014-02-01

    To determine whether serum hyperglycosylated human chorionic gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF-ET). Cohort Academic assisted reproduction center. Consecutive patients undergoing IVF-ET INTERVENTION(S): Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Ongoing pregnancy beyond 9 weeks of gestation. Ongoing pregnancy (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG. However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67, respectively). The diagnostic test characteristics were similar between the D16 hhCG and hCG levels. In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. In this early assessment, hhCG was superior to traditional hCG and highly predictive of ongoing pregnancies. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Malocclusion in Early Anatomically Modern Human: A Reflection on the Etiology of Modern Dental Misalignment

    PubMed Central

    Sarig, Rachel; Slon, Viviane; Abbas, Janan; May, Hila; Shpack, Nir; Vardimon, Alexander Dan; Hershkovitz, Israel

    2013-01-01

    Malocclusions are common in modern populations. Yet, as the study of occlusion requires an almost intact dentition in both the maxilla and mandible, searching for the ultimate cause of malocclusion is a challenge: relatively little ancient material is available for research on occlusal states. The Qafzeh 9 skull is unique, as its preserved dentition allowed us to investigate the presence and manifestations of malocclusion. The aim of this study was thus to examine the occlusal condition in the Qafzeh 9 specimen in light of modern knowledge regarding the etiology of malocclusion. We revealed a pathologic occlusion in the Qafzeh 9 skull that probably originated in the early developmental stage of the dentition, and was aggravated by forces applied by mastication. When arch continuity is interrupted due to misalignment of teeth as in this case, force transmission is not equal on both sides, causing intra-arch outcomes such as mesialization of the teeth, midline deviation, rotations and the aggravation of crowding. All are evident in the Qafzeh 9 skull: the midline deviates to the left; the incisors rotate mesio-buccally; the left segment is constricted; the left first molar is buccally positioned and the left premolars palatally tilted. The inter-arch evaluation revealed anterior cross bite with functional shift that might affect force transmission and bite force. In conclusion, the findings of the current study suggest that malocclusion of developmental origin was already present in early anatomically modern humans (AMH) (the present case being the oldest known case, dated to ca. 100,000 years); that there is no basis to the notion that early AMH had a better adjustment between teeth and jaw size; and that jaw-teeth size discrepancy could be found in prehistoric populations and is not a recent phenomenon. PMID:24278319

  1. Ranging in Human Sonar: Effects of Additional Early Reflections and Exploratory Head Movements

    PubMed Central

    Wallmeier, Ludwig; Wiegrebe, Lutz

    2014-01-01

    Many blind people rely on echoes from self-produced sounds to assess their environment. It has been shown that human subjects can use echolocation for directional localization and orientation in a room, but echo-acoustic distance perception - e.g. to determine one's position in a room - has received little scientific attention, and systematic studies on the influence of additional early reflections and exploratory head movements are lacking. This study investigates echo-acoustic distance discrimination in virtual echo-acoustic space, using the impulse responses of a real corridor. Six blindfolded sighted subjects and a blind echolocation expert had to discriminate between two positions in the virtual corridor, which differed by their distance to the front wall, but not to the lateral walls. To solve this task, participants evaluated echoes that were generated in real time from self-produced vocalizations. Across experimental conditions, we systematically varied the restrictions for head rotations, the subjects' orientation in virtual space and the reference position. Three key results were observed. First, all participants successfully solved the task with discrimination thresholds below 1 m for all reference distances (0.75–4 m). Performance was best for the smallest reference distance of 0.75 m, with thresholds around 20 cm. Second, distance discrimination performance was relatively robust against additional early reflections, compared to other echolocation tasks like directional localization. Third, free head rotations during echolocation can improve distance discrimination performance in complex environmental settings. However, head movements do not necessarily provide a benefit over static echolocation from an optimal single orientation. These results show that accurate distance discrimination through echolocation is possible over a wide range of reference distances and environmental conditions. This is an important functional benefit of human echolocation

  2. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    PubMed Central

    Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

    2016-01-01

    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

  3. Early human speciation, brain expansion and dispersal influenced by African climate pulses.

    PubMed

    Shultz, Susanne; Maslin, Mark

    2013-01-01

    Early human evolution is characterised by pulsed speciation and dispersal events that cannot be explained fully by global or continental paleoclimate records. We propose that the collated record of ephemeral East African Rift System (EARS) lakes could be a proxy for the regional paleoclimate conditions experienced by early hominins. Here we show that the presence of these lakes is associated with low levels of dust deposition in both West African and Mediterranean records, but is not associated with long-term global cooling and aridification of East Africa. Hominin expansion and diversification seem to be associated with climate pulses characterized by the precession-forced appearance and disappearance of deep EARS lakes. The most profound period for hominin evolution occurs at about 1.9 Ma; with the highest recorded diversity of hominin species, the appearance of Homo (sensu stricto) and major dispersal events out of East Africa into Eurasia. During this period, ephemeral deep-freshwater lakes appeared along the whole length of the EARS, fundamentally changing the local environment. The relationship between the local environment and hominin brain expansion is less clear. The major step-wise expansion in brain size around 1.9 Ma when Homo appeared was coeval with the occurrence of ephemeral deep lakes. Subsequent incremental increases in brain size are associated with dry periods with few if any lakes. Plio-Pleistocene East African climate pulses as evinced by the paleo-lake records seem, therefore, fundamental to hominin speciation, encephalisation and migration.

  4. Heatwave Early W