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Primary intracranial germ cell tumours  

Microsoft Academic Search

A histological study has been made of a retrospective series of 17 primary intracranial germ cell tumours found in a collection of 3550 intracranial neoplasms (incidence of 0.48%). All, except for two differentiated teratomas (one extracerebral in a neonate and another in the lateral ventricle), were situated in the midline in persons aged 5 to 37 years (13 males, 4

K. Jellinger



Primary central nervous system germ cell tumors.  


The prognosis of primary germ cell tumors (germinal neoplasms) of the central nervous system varies, depending on the histology and size of tumor and the extent of disease at diagnosis. Although some patients receive therapy without a tissue diagnosis, it is strongly recommended that tumor tissue samples be obtained for accurate histologic diagnosis. Modern neurosurgical navigation techniques have made tissue sampling by stereotactic biopsy a safe and rapid method of determining tumor histology. Depending on tumor location, open surgical biopsy may be required in some patients. Typically, germinomas are exquisitely radiosensitive, although preirradiation chemotherapy reduces the total radiation exposure and may increase the cure rate. Induction cisplatin-based chemotherapy, followed by low-dose involved field radiotherapy, has excellent overall and relapse-free survival rates and is the optimal treatment for patients with germinomas. This combined chemoradiotherapy approach is associated with minimal endocrinopathy and minimal neurocognitive dysfunction. Patients with relapses after low-dose radiation therapy can respond well to salvage therapy (chemotherapy or chemoradiotherapy) without significant sequelae. Patients with nongerminomas respond best to chemotherapy combined with radiation, although the response and cure rates are lower compared to germinomas. Patients with residual masses and normal tumor markers after primary therapy should have a second-look resection because most patients have residual teratoma or necrotic tissue and can be spared additional chemotherapy or radiation. Pure mature teratomas are cured only by surgical extirpation. Immature central nervous system teratomas appear to benefit from radical surgical resection, but higher doses of locally directed radiotherapy are required with no benefit from the usual chemotherapy. PMID:14585229

Kaur, Hanspreet; Singh, Deepjot; Peereboom, David M



Surgery in the management of primary intracranial germ cell tumors  

Microsoft Academic Search

Surgery plays an important part in the overall management of primary central nervous system (CNS) germ cell tumors. While\\u000a the general surgical objectives in patients with these neoplasms are similar to those with other types of CNS tumors, to obtain\\u000a an accurate histopathologic diagnosis and to contribute towards improving patient survival the unique features of germ cell\\u000a tumors have necessitated

Howard L. Weiner; Jonathan L. Finlay



Regulation of germ layer formation by pluripotency factors during embryogenesis  

PubMed Central

The classical pluripotency factors Oct4, Klf4, Sox2, and Nanog are required for the maintenance of pluripotency and self-renewal of embryonic stem (ES) cells and can reprogram terminally differentiated cells into a pluripotent state. Alteration in the levels of these factors in ES cells will cause differentiation into different lineages, suggesting that they are critical determinants of cell fates. These factors show dynamic expression patterns during embryogenesis, in particular in the pluripotent or multipotent cells of an early stage embryo, implying that they are involved in the cell fate decision during early embryonic development. Functions and the underlying molecular mechanisms have been extensively studied for these factors in ES cells under cultured conditions. However, this does not mean that the results also hold true for intact embryos. In the review, I have summarized and discussed the findings on the functions and the underlying mechanisms of the classical pluripotency factors during early embryogenesis, in particular during germ layer formation.



Spinal intradural primary germ cell tumour—review of literature and case report  

Microsoft Academic Search

Background  Primary spinal cord germ cell tumour is a rare tumour. We herein review the tumour characteristics, associated risk factors,\\u000a treatment policy, and patterns of failure of primary intradural germ cell tumour.\\u000a \\u000a \\u000a \\u000a Method  We conducted a PUBMED search using a combination of keywords such as “spinal germ cell tumor,” “germinoma,” “extradural,”\\u000a “intradural,” “intramedullary,” “extramedullary,” and identified 19 cases of primary spinal germ

Ahitagni Biswas; Tarun Puri; Shikha Goyal; Ruchika Gupta; Muneer Eesa; Pramod Kumar Julka; Goura Kishor Rath



Germ layer specification and axial patterning in the embryonic development of the freshwater planarian Schmidtea polychroa.  


Although patterning during regeneration in adult planarians has been studied extensively, very little is known about how the initial planarian body plan arises during embryogenesis. Herein, we analyze the process of embryo patterning in the species Schmidtea polychroa by comparing the expression of genes involved in the establishment of the metazoan body plan. Planarians present a derived ectolecithic spiralian development characterized by dispersed cleavage within a yolk syncytium and an early transient embryo capable of feeding on the maternally supplied yolk cells. During this stage of development, we only found evidence of canonical Wnt pathway, mostly associated with the development of its transient pharynx. At these stages, genes involved in gastrulation (snail) and germ layer determination (foxA and twist) are specifically expressed in migrating blastomeres and those giving rise to the temporary gut and pharyngeal muscle. After yolk ingestion, the embryo expresses core components of the canonical Wnt pathway and the BMP pathway, suggesting that the definitive axial identities are established late. These data support the division of planarian development into two separate morphogenetic stages: a highly divergent gastrulation stage, which segregates the three germ layers and establishes the primary organization of the feeding embryo; and subsequent metamorphosis, based on totipotent blastomeres, which establishes the definitive adult body plan using mechanisms that are similar to those used during regeneration and homeostasis in the adult. PMID:20100474

Martín-Durán, José María; Amaya, Enrique; Romero, Rafael



Primary Goods, Germ-Line Enhancements, and Children  

Microsoft Academic Search

Germ-line genetic engineering procedures may influence the lives of untold millions of people far into the future. These techniques change the genetic material that is passed on to offspring and thus have the potential to change the human race as we know it. Because the effects are so enduring, this powerful technique must be used with caution. We must decide

Grant Maki



Primary testicular seminoma in a patient with a history of extragonadal non-seminomatous germ cell carcinoma  

Microsoft Academic Search

Extragonadal germ cell carcinoma represents between 3% and 5% of all germ cell carcinomas. A metachronous primary germ cell carcinoma is exceedingly rare in these patients. We report the eighth case, which occurred in a 29-year-old man who presented with testicular seminoma 7 years after his initial presentation with extragonadal non-seminomatous germ cell carcinoma. The seven other patients also presented

Matthew Allaway; Unyime O Nseyo



Correlation of endoscopic biopsy with tumor marker status in primary intracranial germ cell tumors  

Microsoft Academic Search

Summary  We retrospectively analyzed the results of eight patients who underwent endoscopic biopsy of a newly diagnosed primary intracranial germ cell tumor (GCT), and correlated tumor pathology with serum and cerebrospinal fluid (CSF) tumor markers and treatment outcome in order to determine the reliability of GCT sampling by this method. A biopsy diagnosis was made in each patient, and the tumor

Neal Luther; Mark A. Edgar; Ira J. Dunkel; Mark M. Souweidane



Pre-epithelial mucus layer in the colon of conventional and germ-free rats  

Microsoft Academic Search

Summary  The pre-epithelial mucus layer (PML) and epithelial mucins were studied by mucin histochemistry in 10m-thick celloidinstabilized cryostat sections in the proximal and distal colon of conventional and germ-free rats aged 120 and 350 days. No continuous PML was found in the proximal colon. A continuous mucus blanket, of fairly homogenous thickness, was observed in the distal colon, where the PML-thickness

L. Szentkuti; H. Riedesel; M.-L. Enss; K. Gaertner; W. von Engelhardt



Quantitative differences in tissue surface tension influence zebrafish germ layer positioning  

PubMed Central

This study provides direct functional evidence that differential adhesion, measurable as quantitative differences in tissue surface tension, influences spatial positioning between zebrafish germ layer tissues. We show that embryonic ectodermal and mesendodermal tissues generated by mRNA-overexpression behave on long-time scales like immiscible fluids. When mixed in hanging drop culture, their cells segregate into discrete phases with ectoderm adopting an internal position relative to the mesendoderm. The position adopted directly correlates with differences in tissue surface tension. We also show that germ layer tissues from untreated embryos, when extirpated and placed in culture, adopt a configuration similar to those of their mRNA-overexpressing counterparts. Down-regulating E-cadherin expression in the ectoderm leads to reduced surface tension and results in phase reversal with E-cadherin-depleted ectoderm cells now adopting an external position relative to the mesendoderm. These results show that in vitro cell sorting of zebrafish mesendoderm and ectoderm tissues is specified by tissue interfacial tensions. We perform a mathematical analysis indicating that tissue interfacial tension between actively motile cells contributes to the spatial organization and dynamics of these zebrafish germ layers in vivo.

Schotz, Eva-Maria; Burdine, Rebecca D.; Julicher, Frank; Steinberg, Malcolm S.; Heisenberg, Carl-Philipp; Foty, Ramsey A.



Some new thoughts on evolution: the role of the germ layers.  


At an early stage of embryonic development, the animal body divides itself into the three germ layers - the ectoderm, mesoderm and entoderm. It is proposed that this division repeats a fundamental functional differentiation of cells in phylogeny. The tasks of life have been divided into three groups, each germ layer specializing in one of them. The task of the entoderm is metabolism and homeostasis, that of the mesoderm is the structural organization of the body, that of the ectoderm interactions with the environment. In effect, the entoderm is the chemist of the body, the mesoderm its architect and engineer, the ectoderm deals with its external affairs. It is proposed that cognitive and reasoning faculties are inherent in every germ layer and when they separate, they all take an equal share. Each performs its complex and multitudinous tasks by virtue of its faculty of conceptual thought, except that the entoderm and mesoderm began to develop that faculty millions of years before the ectoderm. PMID:10867759

Seely, S



Differences in Transcription Patterns between Induced Pluripotent Stem Cells Produced from the Same Germ Layer Are Erased upon Differentiation  

PubMed Central

Little is known about differences between induced pluripotent stem cells produced from tissues originating from the same germ layer. We have generated human myoblast-derived iPS cells by retroviral transduction of human primary myoblasts with the OCT3/4, SOX2, KLF4 and MYC coding sequences and compared them to iPS produced from human primary fibroblasts. When cultivated in vitro, these iPS cells proved similar to human embryonic stem cells in terms of morphology, expression of embryonic stemness markers and gene promoter methylation patterns. Embryonic bodies were derived that expressed endodermal, mesodermal as well as ectodermal markers. A comparative analysis of transcription patterns revealed significant differences in the gene expression pattern between myoblast- and fibroblast-derived iPS cells. However, these differences were reduced in the mesenchymal stem cells derived from the two iPS cell types were compared.

Pirozhkova, Iryna; Robert, Thomas; Guegan, Justine; Bilhou-Nabera, Chrystele; Busato, Florence; Tost, Jorg; Carnac, Gilles; Laoudj-Chenivesse, Dalila; Lipinski, Marc; Vassetzky, Yegor



Treatment of a primary intracranial germ cell tumor with systemic chemotherapy  

Microsoft Academic Search

Primary germ cell neoplasms of the central nervous system (CNS) are rare tumors which generally respond to radiotherapy. Experience is limited in managing the refractory patient. We report a patient whose suprasellar dysgerminoma responded completely to 5,000 rad. Seven years later, disease recurrence was refractory to an additional 4,000 rad. Theorizing that the ''blood-brain barrier'' was no longer intact after

Jeffrey J. Kirshner; Sandra J. Ginsberg; Alicia V. Fitzpatrick; Robert L. Comis



RPLND or Primary Chemotherapy in Clinical Stage IIA/B Nonseminomatous Germ Cell Tumors?  

Microsoft Academic Search

Background: In order to reduce therapy–related morbidity in patients with nonseminomatous testicular germ cell tumors in clinical stage IIA/B, we performed a prospective multicenter trial comparing the standard retroperitoneal lymph node dissection (RPLND) +2 cycles of chemotherapy (arm A) with 3–4 cycles of primary chemotherapy (arm B).Methods: From February 1991 to July 1995, 57 participating centers from Germany and Austria

Lothar Weissbach; Henning Flechtner; Uwe Pichlmeier; Michael Hartmann; Lutz Keller



EphrinB/EphB Signaling Controls Embryonic Germ Layer Separation by Contact-Induced Cell Detachment  

PubMed Central

Background The primordial organization of the metazoan body is achieved during gastrulation by the establishment of the germ layers. Adhesion differences between ectoderm, mesoderm, and endoderm cells could in principle be sufficient to maintain germ layer integrity and prevent intermixing. However, in organisms as diverse as fly, fish, or amphibian, the ectoderm-mesoderm boundary not only keeps these germ layers separated, but the ectoderm also serves as substratum for mesoderm migration, and the boundary must be compatible with repeated cell attachment and detachment. Principal Findings We show that localized detachment resulting from contact-induced signals at the boundary is at the core of ectoderm-mesoderm segregation. Cells alternate between adhesion and detachment, and detachment requires ephrinB/EphB signaling. Multiple ephrinB ligands and EphB receptors are expressed on each side of the boundary, and tissue separation depends on forward signaling across the boundary in both directions, involving partially redundant ligands and receptors and activation of Rac and RhoA. Conclusion This mechanism differs from a simple differential adhesion process of germ layer formation. Instead, it involves localized responses to signals exchanged at the tissue boundary and an attachment/detachment cycle which allows for cell migration across a cellular substratum.

Rohani, Nazanin; Canty, Laura; Luu, Olivia



Virus-Like Particles in 3-Methylcholathrene-Induced Primary and Transplanted Sarcomas of Germ-Free Rodents.  

National Technical Information Service (NTIS)

Primary and serially transplanted 3-methylcholanthrene-induced sarcomas of germ-free mice and rats and the thymuses of tumor-bearing and tumor-free experimental animals were examined by electron microscopy for virus particles. The results can be summarize...

M. Kajima M. Pollard



Relationship between primary and metastatic testicular germ cell tumors: a clinicopathologic analysis of 100 cases.  


Testicular germ cell tumors (GCTs) commonly metastasize to the retroperitoneal lymph nodes (RPLNs). We evaluated 100 cases of RPLN dissection specimens with viable GCTs after chemotherapy and compared them with their corresponding orchiectomy specimens. The mean age of patients was 28 years (range, 15-58 years). The testicular tumors consisted of mixed GCT (n = 72), teratoma (n = 18), seminoma (n = 4), embryonal carcinoma (n = 3), yolk sac tumor (n = 1), and no viable tumor (n = 2). Somatic malignant components were found in 5 cases. The metastatic tumors in the RPLNs consisted of only teratoma (n = 77) and non-teratomatous GCT (n = 23). Twenty-one patients had only teratoma in the RPLNs but not in the testis, and 10 patients had metastatic non-teratomatous GCT components that were not observed in the testis. Six patients had somatic malignant components in the RPLNs, but only one of them had such a component in the testis. Overall, 13 patients died of disease in a mean of 42 months, and the patients with only teratoma in the RPLNs had a lower mortality rate (9%) than those with non-teratomatous components (26%) (P = .044). One patient with somatic components in the primary GCT and 3 patients with somatic components in the metastases died of disease. Our study demonstrates that there is frequent discordance of histologic composition between primary and metastatic testicular GCTs. Teratoma is the most common component in treated GCTs and is usually associated with a more favorable clinical outcome than non-teratomatous GCTs. The presence of somatic components in the RPLNs metastasis indicates a poor prognosis. PMID:23856516

Tarrant, William P; Czerniak, Bogdan A; Guo, Charles C



Heterochromatin protein 1? overexpression in P19 embryonal carcinoma cells elicits spontaneous differentiation into the three germ layers.  


P19 embryonal carcinoma (EC) cells are pluripotent stem cells and have numerous morphological and biochemical properties in common with embryonic stem (ES) cells. However, P19 cells differentiate very ineffectively as embryoid bodies (EBs) without the specific chemical inducers whereas ES cells exhibit spontaneous differentiation to the three germ layers. Recently the heterochromatin protein 1 (HP1) family protein HP1?, which is an epigenetic modulator that binds histone H3 methylated at lysine 9, is shown to be associated with the progression from pluripotent to differentiated status in ES cells. Therefore, to study the role of HP1? in the differentiation capacity of P19 cells, we have established a HP1?-overexpressing P19 cell line (HPl?-P19). Similar to the parental P19 cells, undifferentiated HP1?-P19 cells continued to express pluripotency marker genes. However, HP1?-P19 cells exhibited significant morphological differentiation including beating cardiomyocytes, as well as Tuj1-positive neuronal cells and Sox17-positive endodermal cells after EB formation under a normal culture condition. Moreover, real-time RT-qPCR analysis revealed that HP1?-P19 EB cells expressed various differentiation marker genes. Thus, HP1?-P19 cells could give rise to all three germ layers in EBs without any drug treatment. Therefore, HP1? affects the spontaneous differentiation potential of P19 cells, and might play major roles in the decision of cell fates in pluripotent stem cells. PMID:23313480

Morikawa, Kumi; Ikeda, Nobuhito; Hisatome, Ichiro; Shirayoshi, Yasuaki



Differential requirement for the dual functions of ?-catenin in embryonic stem cell self-renewal and germ layer formation  

PubMed Central

Canonical Wnt-signalling has been implicated in mouse and human embryonic stem cell (ESC) maintenance, however its requirement is controversial. ?-catenin is the key component in this highly conserved Wnt pathway, acting as a transcriptional transactivator. Yet, ?-catenin has additional roles at the plasma membrane regulating cell-cell adhesion, complicating the analyses of cells/tissues lacking ?-catenin. We report here the generation of a ?-catenin deficient mouse ESC (mESC) line and show that self-renewal is maintained in absence of ?-catenin. Cell-adhesion is partially rescued by plakoglobin up-regulation, but fails to be maintained during differentiation. When differentiated as aggregates, wild-type mESCs form descendents of all three germ layers, while mesendodermal germ layer formation and neuronal differentiation are defective in ?-catenin deficient mESCs. A Tcf/Lef-signalling defective ?-catenin variant, which re-establishes cadherin-mediated cell-adhesion, rescues definitive endoderm and neuroepithelial formation, suggesting that ?-catenin cell-adhesion function is more important than its signalling function for these processes.

Lyashenko, Natalia; Winter, Markus; Migliorini, Domenico; Biechele, Travis; Moon, Randall T.; Hartmann, Christine



Retrovirus-encoded transformation-specific polyproteins: expression coordinated with malignant phenotype in cells from different germ layers.  

PubMed Central

A transformation-associated polyprotein designated "gag-x" was previously shown to be induced by the feline sarcoma virus (FeSV) after the nonproductive transformation of rat or mink cells. We found that this protein was also expressed in cells derived from the native species (cat) with or without the production of feline leukemia helper virus (FeLV) and that cats could mount a humoral antibody response to the transformation-specific (x) portion of the molecule. Such antisera also reacted with the feline oncornavirus-associated cell membrane antigen (FOCMA) by membrane immunofluorescence. Expression of the gag-x protein was coordinated with malignant phenotype in that both transformed cat fibroblasts and cultured cells from a FeSV-induced melanoma expressed antigenically indistinguishable proteins of the same size. These cells are derived from different embryonic germ layers, suggesting that such transformation-related proteins may function in a pleiotropic manner when introduced by a virus. Images

Chen, A P; Essex, M; Shadduck, J A; Niederkorn, J Y; Albert, D



Human Embryonic Stem Cells and Germ Cell Development  

Microsoft Academic Search

\\u000a Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of blastocysts and are characterized by the ability\\u000a to differentiate into the three primary germ layers. Evidence shows, however, that the cells of the ICM and derived ESCs are\\u000a not identical. Expression of early germ cell–specific markers in undifferentiated ESCs and the ability of ESCs to differentiate\\u000a into

Nina J. Kossack; Joerg Gromoll; Renee A. Reijo Pera


Fighting Germs  


... Bad breath Acne Hair care Douching Makeup Tanning Tattoos and piercing Cosmetic surgery Fighting Germs Fighting Germs ... share needles or other items used for drugs, tattoos, or piercings. Things like dirty needles and drug ...


Glo Germ  

NSDL National Science Digital Library

This experiment helped a group of friends actually see how germs are spread. They were able to see how following health tips (like sneezing into your elbow instead of your hand) helped limit the amount of germs spread to others.

Tv, Agonfly


Transcriptional profiling of endogenous germ layer precursor cells identifies dusp4 as an essential gene in zebrafish endoderm specification.  


A major goal for developmental biologists is to define the behaviors and molecular contents of differentiating cells. We have devised a strategy for isolating cells from diverse embryonic regions and stages in the zebrafish, using computer-guided laser photoconversion of injected Kaede protein and flow cytometry. This strategy enabled us to perform a genome-wide transcriptome comparison of germ layer precursor cells. Mesendoderm and ectoderm precursors cells isolated by this method differentiated appropriately in transplantation assays. Microarray analysis of these cells reidentified known genes at least as efficiently as previously reported strategies that relied on artificial mesendoderm activation or inhibition. We also identified a large set of uncharacterized mesendoderm-enriched genes as well as ectoderm-enriched genes. Loss-of-function studies revealed that one of these genes, the MAP kinase inhibitor dusp4, is essential for early development. Embryos injected with antisense morpholino oligonucleotides that targeted Dusp4 displayed necrosis of head tissues. Marker analysis during late gastrulation revealed a specific loss of sox17, but not of other endoderm markers, and analysis at later stages revealed a loss of foregut and pancreatic endoderm. This specific loss of sox17 establishes a new class of endoderm specification defect. PMID:18719100

Brown, Jamie L; Snir, Mirit; Noushmehr, Houtan; Kirby, Martha; Hong, Sung-Kook; Elkahloun, Abdel G; Feldman, Benjamin



ES cell pluripotency and germ-layer formation require the SWI/SNF chromatin remodeling component BAF250a.  


ATP-dependent chromatin remodeling complexes are a notable group of epigenetic modifiers that use the energy of ATP hydrolysis to change the structure of chromatin, thereby altering its accessibility to nuclear factors. BAF250a (ARID1a) is a unique and defining subunit of the BAF chromatin remodeling complex with the potential to facilitate chromosome alterations critical during development. Our studies show that ablation of BAF250a in early mouse embryos results in developmental arrest (about embryonic day 6.5) and absence of the mesodermal layer, indicating its critical role in early germ-layer formation. Moreover, BAF250a deficiency compromises ES cell pluripotency, severely inhibits self-renewal, and promotes differentiation into primitive endoderm-like cells under normal feeder-free culture conditions. Interestingly, this phenotype can be partially rescued by the presence of embryonic fibroblast cells. DNA microarray, immunostaining, and RNA analyses revealed that BAF250a-mediated chromatin remodeling contributes to the proper expression of numerous genes involved in ES cell self-renewal, including Sox2, Utf1, and Oct4. Furthermore, the pluripotency defects in BAF250a mutant ES cells appear to be cell lineage-specific. For example, embryoid body-based analyses demonstrated that BAF250a-ablated stem cells are defective in differentiating into fully functional mesoderm-derived cardiomyocytes and adipocytes but are capable of differentiating into ectoderm-derived neurons. Our results suggest that BAF250a is a key component of the gene regulatory machinery in ES cells controlling self-renewal, differentiation, and cell lineage decisions. PMID:18448678

Gao, Xiaolin; Tate, Peri; Hu, Ping; Tjian, Robert; Skarnes, William C; Wang, Zhong



A shift in germ layer allocation is correlated with large egg size and facultative planktotrophy in the echinoid Clypeaster rosaceus.  


Egg size is a correlate of larval evolution in marine embryos. Comparing species with different egg sizes that develop via similar larvae reveals the flexibility and the constraints underlying larval forms. Clypeaster rosaceus is an echinoid that develops via a facultatively planktotrophic pluteus larva. Unlike most echinoids that develop via plutei, C. rosaceus (1) has a larger egg, with a correspondingly smaller ratio of surface area to volume, and (2) forms a large left coelom early in development. Given these characteristics, we predicted underlying changes in the allocation of embryonic tissues to germ layers. With a low surface-to-volume ratio, the C. rosaceus pluteus likely requires relatively less ectoderm than a typical pluteus, whereas the early formation of a large left coelom likely requires relatively more mesoderm than a typical pluteus. We tested this hypothesis by examining the cell lineage of C. rosaceus. We found that the boundary between ectoderm and endoderm in C. rosaceus has shifted relative to echinoids with more typical planktotrophic plutei and extends to or above the third cleavage plane at the equator of the embryo. This indicates a smaller proportional allocation to ectoderm and a larger proportional allocation to endomesoderm compared to echinoids with smaller egg sizes. On the basis of this observation, we develop a new model for the transition from obligate planktotrophy to lecithotrophy. We argue that species with larger eggs may allocate proportionally more tissue to structures selected for accelerated development. In the case of C. rosaceus, the larval cell lineage apportions more cells to endomesoderm and less to ectoderm due to the smaller surface-to-volume ratio of its larger eggs and the early formation of a large left coelom. PMID:23995743

Zigler, Kirk S; Raff, Rudolf A



Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries  

PubMed Central

Intracranial germ cell tumors (GCTs) are relatively rare. Their incidence has been considered to be higher in East Asia than in the United States. This study estimates the incidence of CNS GCTs in Japan and the United States, investigates gender discrepancies in each country, and describes treatment outcomes. Data on primary CNS GCTs from 4 databases were utilized: population-based malignant incidence data from (1) the Japan Cancer Surveillance Research Group (2004–2006; 14 registries), malignant and nonmalignant incidence data from (2) the Surveillance, Epidemiology, and End Results Program (2004–2008; 17 registries), and hospital-based observed survival data from (3) the Brain Tumor Registry of Japan (1984–2000) and (4) the US National Cancer Data Base (1990–2003). Incidence rates per 100 000 for malignant GCTs were not statistically significantly different between Japan (males = 0.143, females = 0.046) and the United States (males = 0.118, females = 0.030). The malignant incidence-rate ratio was higher for pineal GCTs versus nonpineal (ie, the rest of the brain) GCTs in Japan (11.5:1 vs 1.9:1, respectively) and the United States (16.0:1 vs 1.7:1, respectively). In general, 5-year survival estimates were high: over 75% for all GCTs, and over 81% for germinomas, regardless of the type of treatment in either Japan or the United States. The incidence of primary GCTs is similar between Japan and the United States and has the same gender-based patterns by location. High rates of survival were observed in both countries.

McCarthy, Bridget J.; Shibui, Soichiro; Kayama, Takamasa; Miyaoka, Etsuo; Narita, Yoshitaka; Murakami, Michiko; Matsuda, Ayako; Matsuda, Tomohiro; Sobue, Tomotaka; Palis, Bryan E.; Dolecek, Therese A.; Kruchko, Carol; Engelhard, Herbert H.; Villano, J. Lee



Primary CNS Teratocarcinoma  

PubMed Central

Primary central nervous system (CNS) teratomas are rare tumors that consist of all three germ cell layers. We describe a young man with a primary malignant CNS teratocarcinoma presenting as leptomeningeal carcinomatosis. Diagnosis of primary CNS teratocarcinomas is challenging; relentless pursuit of the diagnosis must follow even if early ancillary studies are inconclusive.

Vitorovic, Danilo; Rosenblum, Jordan; Thomas, Chinnamma; Lee, John; Biller, Jose



Fetal cardiac mesenchymal stem cells express embryonal markers and exhibit differentiation into cells of all three germ layers  

PubMed Central

AIM: To study the expression of embryonal markers by fetal cardiac mesenchymal stem cells (fC-MSC) and their differentiation into cells of all the germ layers. METHODS: Ten independent cultures of rat fC-MSC were set up from cells derived from individual or pooled fetal hearts and studies given below were carried out at passages 3, 6, 15 and 21. The phenotypic markers CD29, CD31, CD34, CD45, CD73, CD90, CD105, CD166 and HLA-DR were analyzed by flow cytometry. The expression of embryonal markers Oct-4, Nanog, Sox-2, SSEA-1, SSEA-3, SSEA-4, TRA-1-60 and TRA 1-81 were studied by immunocytochemistry. The fC-MSC treated with specific induction medium were evaluated for their differentiation into (1) adipocytes and osteocytes (mesodermal cells) by Oil Red O and Alizarin Red staining, respectively, as well as by expression of lipoprotein lipase, PPAR?2 genes in adipocytes and osteopontin and RUNX2 genes in osteocytes by reverse-transcription polymerase chain reaction (RT-PCR); (2) neuronal (ectodermal) cells by expression of neuronal Filament-160 and Glial Fibrillar Acidic Protein by RT-PCR and immunocytochemistry; and (3) hepatocytic (endodermal) cells by expression of albumin by RT-PCR and immunocytochemistry, glycogen deposits by Periodic Acid Schiff staining and excretion of urea into the culture supernatant. RESULTS: The fC-MSC expressed CD29, CD73, CD90, CD105, CD166 but lacked expression of CD31, CD34, CD45 and HLA-DR. They expressed embryonal markers, viz. Oct-4, Nanog, Sox-2, SSEA-1, SSEA-3, SSEA-4, TRA-1-81 but not TRA-1-60. On treatment with specific induction media, they differentiated into adipocytes and osteocytes, neuronal cells and hepatocytic cells. CONCLUSION: Our results together suggest that fC-MSC are primitive stem cell types with a high degree of plasticity and, in addition to their suitability for cardiovascular regenerative therapy, they may have a wide spectrum of therapeutic applications in regenerative medicine.

Srikanth, Garikipati Venkata Naga; Tripathy, Naresh Kumar; Nityanand, Soniya



Trainee Primary Teachers' Ideas about the Ozone Layer.  

ERIC Educational Resources Information Center

Survey results reveal trainee primary teachers are well informed about the nature and location of the ozone layer and appreciated that it screens the earth from ultraviolet (UV) rays, although some thought that it protects the earth from acid rain. Identifies themes in students' thinking and groups of students with different concepts. (LZ)

Boyes, Edward; And Others



Trainee Primary Teachers' Ideas about the Ozone Layer.  

ERIC Educational Resources Information Center

|Survey results reveal trainee primary teachers are well informed about the nature and location of the ozone layer and appreciated that it screens the earth from ultraviolet (UV) rays, although some thought that it protects the earth from acid rain. Identifies themes in students' thinking and groups of students with different concepts. (LZ)|

Boyes, Edward; And Others



Podoplanin expression in primary central nervous system germ cell tumors: a useful histological marker for the diagnosis of germinoma  

Microsoft Academic Search

Podoplanin, a mucin-like transmembrane sialoglycoprotein, promotes platelet aggregation and may be involved in cancer cell migration, invasion, metastasis, and malignant progression. Podoplanin\\/aggrus is highly expressed in testicular seminoma, suggesting that it may be a sensitive marker for testicular seminomas. Here we investigated the expression of podoplanin in central nervous system (CNS) germ cell tumors (GCTs) by immunohistochemical staining of tumor

Kazuhiko Mishima; Yukinari Kato; Mika K. Kaneko; Youya Nakazawa; Akiko Kunita; Naoya Fujita; Takashi Tsuruo; Ryo Nishikawa; Takanori Hirose; Masao Matsutani



Germ Tag  

NSDL National Science Digital Library

In this version of tag, a large group of learners model how the body fights infection. Learners act as germs, as lymphocytes, and as the body's cells threatened by germs. After playing one round, subsequent rounds can use different numbers of germs and/or lymphocytes to see how the infection rate is changed. When learners set up a free account at Kinetic City, they can answer bonus questions at the end of the activity as a quick assessment. They can also keep track of their progress in all of the Kinetic City activities, and compare their progress to other participants worldwide.

Science, American A.



Influence of commercially derived lipids and a surfactant on the mode of germination and process of germ-tube formation in primary conidia of two species of Erynia subgenus Neopandora (Zygomycotina: Entomophthorales  

Microsoft Academic Search

Primary conidia of the entomopathogens Erynia (subgenus Neopandora) delphacis (1 isolate) and Erynia ( Neopandora) neoaphidis\\u000a (3 isolates) were stimulated to form germ-tubes with Tween 20 and with free, long-chain fatty acids, each incorporated into\\u000a Entomophthora complete medium (ECM). When combined with other basal media (three tested), these compounds did not stimulate\\u000a germ-tube formation. Triacylglycerols and vegetable oils, added to

Aviva Uziel; Robert G. Kenneth



Cross-Layer Based Approach for Primary Signal Detection in Wireless Cognitive Networks (PREPRINT).  

National Technical Information Service (NTIS)

Cross-layer approach in cognitive wireless networks is proposed for efficient use of spectrum by detecting primary signals. The detection may be false detection of primary signal, missed detection of primary signal, or correct detection of primary signal....

Y. B. Reddy



Prophetic Germs  

Microsoft Academic Search

MY desire in this controversy has been to bring the Duke of Argyll's theory to the test of fact. But I cannot obtain from him any statement of fact which tends to support his belief in prophetic germs. He cites the well-known observation that in the growth of the individual from the egg, organs pass through rudimentary stages, during which

E. Ray Lankester



In vitro male germ cell cultures of zebrafish.  


Transgenic modification of sperm before fertilization has the advantages of a much shorter timeline for the production of transgenic animals. A culture system using primary cultures of zebrafish male germ cells, in which the differentiation of spermatogonia to functional sperm can occur in vitro, allows us to introduce foreign DNA into the cultured sperm and to produce transgenics from the sperm. This chapter describes methods for the co-culture of male germ cells and a Sertoli cell feeder layer and the introduction of foreign DNA with retroviruses. This male germ cell culture system should prove useful not only in producing genetically modified sperm, but also in analyzing the regulatory function of Sertoli cells for spermatogenesis in vertebrates. PMID:16828310

Sakai, Noriyoshi



Germ cell differentiation from pluripotent cells.  


Infertility is a medical condition with an increasing impact in Western societies with causes linked to toxins, genetics, and aging (primarily delay of motherhood). Within the different pathologies that can lead to infertility, poor quality or reduced quantity of gametes plays an important role. Gamete donation and therefore demand on donated sperm and eggs in fertility clinics is increasing. It is hoped that a better understanding of the conditions related to poor gamete quality may allow scientists to design rational treatments. However, to date, relatively little is known about human germ cell development in large part due to the inaccessibility of human development to molecular genetic analysis. It is hoped that pluripotent human embryonic stem cells and induced pluripotent stem cells may provide an accessible in vitro model to study germline development; these cells are able to differentiate to cells of all three primary embryonic germ layers, as well as to germ cells in vitro. We review the state of the art in germline differentiation from pluripotent stem cells. PMID:23329632

Medrano, Jose V; Pera, Renee A Reijo; Simón, Carlos



Immortalized Germ Cells Undergo Meiosis in vitro  

Microsoft Academic Search

Establishing mammalian germ-cell lines capable of differentiation in vitro would greatly facilitate the study of gametogenesis and the meiotic process that is so fundamental for reproduction and the maintenance of genetic diversity of the species. We have established two germ-cell lines[GC-2spd(ts) and GC-3spc(ts)] by cotransfecting primary mouse testicular germ cells with the simian virus 40 large tumor antigen gene and

Marie-Claude Hofmann; Rex A. Hess; Erwin Goldberg; Jose Luis Millan



The key enzyme of the sialic Acid metabolism is involved in embryoid body formation and expression of marker genes of germ layer formation.  


The bi-functional enzyme UDP-N-acetyl-2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme of the sialic acid biosynthesis. Sialic acids are negatively charged nine carbon amino sugars and are found on most glycoproteins and many glycolipids in terminal positions, where they are involved in a variety of biological important molecular interactions. Inactivation of the GNE by homologous recombination results in early embryonic lethality in mice. Here, we report that GNE-deficient embryonic stem cells express less differentiation markers compared to wild-type embryonic stem cells. As a result, GNE-deficient embryonic stem cells fail to form proper embryoid bodies (EB) within the first day of culture. However, when culturing these cells in the presence of sialic acids for three days, also GNE-deficient embryonic stem cells form normal EBs. In contrast, when culturing these cells in sialic acid reduced medium, GNE-deficient embryonic stem cells proliferate faster and form larger EBs without any change in the expression of markers of the germ layers. PMID:24129184

Weidemann, Wenke; Hering, Jessica; Bennmann, Dorit; Thate, Annett; Horstkorte, Rüdiger



Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations  

Microsoft Academic Search

BACKGROUND: Intracranial pediatric germ cell tumors (GCTs) are rare and heterogeneous neoplasms and vary in histological differentiation, prognosis and clinical behavior. Germinoma and mature teratoma are GCTs that have a good prognosis, while other types of GCTs, termed nongerminomatous malignant germ cell tumors (NGMGCTs), are tumors with an intermediate or poor prognosis. The second group of tumors requires more extensive

Hsei-Wei Wang; Yu-Hsuan Wu; Jui-Yu Hsieh; Muh-Lii Liang; Meng-En Chao; Da-Jung Liu; Ming-Ta Hsu; Tai-Tong Wong



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

PubMed Central

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.

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



Snail and the microRNA-200 Family Act in Opposition to Regulate Epithelial-to-Mesenchymal Transition and Germ Layer Fate Restriction in Differentiating ESCs  

PubMed Central

The reprogramming of somatic cells to inducible pluripotent stem cells requires a mesenchymal-to-epithelial transition. While differentiating ESCs can undergo the reverse process or epithelial-to-mesenchymal transition (EMT), little is known about the role of EMT in ESC differentiation and fate commitment. Here, we show that Snail homolog 1 (Snail) is expressed during ESC differentiation and is capable of inducing EMT on day 2 of ESC differentiation. Induction of EMT by Snail promotes mesoderm commitment while repressing markers of the primitive ectoderm and epiblast. Snail's impact on differentiation can be partly explained through its regulation of a number of ESC-associated microRNAs, including the microRNA-200 (miR-200) family. The miR-200 family is normally expressed in ESCs but is downregulated in a Wnt-dependent manner during EMT. Maintenance of miR-200 expression stalls differentiating ESCs at the epiblast-like stem cell (EpiSC) stage. Consistent with a role for activin in maintaining the EpiSC state, we find that inhibition of activin signaling decreases miR-200 expression and allows EMT to proceed with a bias toward neuroectoderm commitment. Furthermore, miR-200 requires activin to efficiently maintain cells at the epiblast stage. Together, these findings demonstrate that Snail and miR-200 act in opposition to regulate EMT and exit from the EpiSC stage toward induction of germ layer fates. By modulating expression levels of Snail, activin, and miR-200, we are able to control the order in which cells undergo EMT and transition out of the EpiSC state. Stem Cells 2011;29:764–776

Gill, Jennifer G; Langer, Ellen M; Lindsley, R Coleman; Cai, Mi; Murphy, Theresa L; Kyba, Michael; Murphy, Kenneth M



Snail and the microRNA-200 family act in opposition to regulate epithelial-to-mesenchymal transition and germ layer fate restriction in differentiating ESCs.  


The reprogramming of somatic cells to inducible pluripotent stem cells requires a mesenchymal-to-epithelial transition. While differentiating ESCs can undergo the reverse process or epithelial-to-mesenchymal transition (EMT), little is known about the role of EMT in ESC differentiation and fate commitment. Here, we show that Snail homolog 1 (Snail) is expressed during ESC differentiation and is capable of inducing EMT on day 2 of ESC differentiation. Induction of EMT by Snail promotes mesoderm commitment while repressing markers of the primitive ectoderm and epiblast. Snail's impact on differentiation can be partly explained through its regulation of a number of ESC-associated microRNAs, including the microRNA-200 (miR-200) family. The miR-200 family is normally expressed in ESCs but is downregulated in a Wnt-dependent manner during EMT. Maintenance of miR-200 expression stalls differentiating ESCs at the epiblast-like stem cell (EpiSC) stage. Consistent with a role for activin in maintaining the EpiSC state, we find that inhibition of activin signaling decreases miR-200 expression and allows EMT to proceed with a bias toward neuroectoderm commitment. Furthermore, miR-200 requires activin to efficiently maintain cells at the epiblast stage. Together, these findings demonstrate that Snail and miR-200 act in opposition to regulate EMT and exit from the EpiSC stage toward induction of germ layer fates. By modulating expression levels of Snail, activin, and miR-200, we are able to control the order in which cells undergo EMT and transition out of the EpiSC state. PMID:21394833

Gill, Jennifer G; Langer, Ellen M; Lindsley, R Coleman; Cai, Mi; Murphy, Theresa L; Kyba, Michael; Murphy, Kenneth M



Boundary layers as the primary transport regions of the earth's magnetotail  

Microsoft Academic Search

A comprehensive survey of ISEE and IMP LEPEDEA plasma measurements in the earth's magnetotail reveals that the magnetospheric boundary layer and the plasma sheet boundary layer are the primary transport regions there. These plasma measurements also distinguish various components of the plasma sheet, including the central plasma sheet and plasma sheet boundary layer. A significant new result reported here is

T. E. Eastman; L. A. Frank; C. Y. Huang



First-line sequential high-dose VIP chemotherapy with autologous transplantation for patients with primary mediastinal nonseminomatous germ cell tumours: a prospective trial.  


To determine the efficacy of first-line sequential high-dose VIP chemotherapy (HD-VIP) in patients with primary mediastinal nonseminomatous germ cell tumours (GCT), 28 patients were enrolled on a German multicentre trial. High-Dose VIP chemotherapy consisted of 3-4 cycles of dose-intensive etoposide and ifosfamide plus cisplatin, q22days, each cycle followed by autologous peripheral blood stem cell transplantation plus granulocyte-colony stimulating factor (G-CSF) support. One cycle of standard-dose VIP was applied to harvest peripheral blood stem cells. Ten patients had mediastinal involvement as the only manifestation (36 %), 18 of 28 patients had additional metastatic sites, such as lung (n=17; 61%), liver (n=7; 25%), bone (n=5; 18%), lymph nodes (n=3; 11%) and CNS (n=3; 11%). Median follow-up was 43 months (range, 7-113) for all patients and 52 months (range, 22-113) for surviving patients. Nineteen of 28 patients obtained a disease-free status; 11 with HD-VIP alone and eight with adjunctive surgery. In addition, one of the four patients with marker negative partial remission after HD-VIP without resection of residual masses is currently alive. Two patients developed recurrence of GCT or teratoma. Two patients have died due to an associated haematologic disorder. The 2-year progression-free survival and overall survival rates are 64 and 68%, respectively. This report represents a subgroup analysis of 28 patients with mediastinal nonsemina within the German first-line study for 'poor prognosis' GCT. Compared to data of an international database analysis including 253 patients with mediastinal nonseminoma treated with conventional chemotherapy, the results may indicate that HD-VIP results in an approximately 15% survival improvement. PMID:12838296

Bokemeyer, C; Schleucher, N; Metzner, B; Thomas, M; Rick, O; Schmoll, H-J; Kollmannsberger, C; Boehlke, I; Kanz, L; Hartmann, J T



Characterisation and Germline Transmission of Cultured Avian Primordial Germ Cells  

PubMed Central

Background Avian primordial germ cells (PGCs) have significant potential to be used as a cell-based system for the study and preservation of avian germplasm, and the genetic modification of the avian genome. It was previously reported that PGCs from chicken embryos can be propagated in culture and contribute to the germ cell lineage of host birds. Principal Findings We confirm these results by demonstrating that PGCs from a different layer breed of chickens can be propagated for extended periods in vitro. We demonstrate that intracellular signalling through PI3K and MEK is necessary for PGC growth. We carried out an initial characterisation of these cells. We find that cultured PGCs contain large lipid vacuoles, are glycogen rich, and express the stem cell marker, SSEA-1. These cells also express the germ cell-specific proteins CVH and CDH. Unexpectedly, using RT-PCR we show that cultured PGCs express the pluripotency genes c-Myc, cKlf4, cPouV, cSox2, and cNanog. Finally, we demonstrate that the cultured PGCs will migrate to and colonise the forming gonad of host embryos. Male PGCs will colonise the female gonad and enter meiosis, but are lost from the gonad during sexual development. In male hosts, cultured PGCs form functional gametes as demonstrated by the generation of viable offspring. Conclusions The establishment of in vitro cultures of germline competent avian PGCs offers a unique system for the study of early germ cell differentiation and also a comparative system for mammalian germ cell development. Primary PGC lines will form the basis of an alternative technique for the preservation of avian germplasm and will be a valuable tool for transgenic technology, with both research and industrial applications.

Macdonald, Joni; Glover, James D.; Taylor, Lorna; Sang, Helen M.; McGrew, Michael J.



Germ-Line Variants in Methyl-Group Metabolism Genes and Susceptibility to DNA Methylation in Normal Tissues and Human Primary Tumors1  

Microsoft Academic Search

Aberrant DNA methylation is recognized as being a common feature of human neoplasia. CpG island hypermethylation and global genomic hy- pomethylation occur simultaneously in the cancer cell. However, very little is known about the interindividual inherited susceptibility to these epigenetic processes. To address this matter, we have genotyped in 233 cancer patients (with colorectal, breast, or lung tumors), four germ-line

Maria F. Paz; Sonia Avila; Mario F. Fraga; Marina Pollan; Gabriel Capella; Miquel Angel Peinado; Montserrat Sanchez-Cespedes; James G. Herman; Manel Esteller


Pyramidal Neuron Number in Layer 3 of Primary Auditory Cortex of Subjects with Schizophrenia  

PubMed Central

Individuals with schizophrenia demonstrate impairments of sensory processing within primary auditory cortex. We have previously identified lower densities of dendritic spines and axon boutons, and smaller mean pyramidal neuron somal volume, in layer 3 of the primary auditory cortex in subjects with schizophrenia, all of which might reflect fewer layer 3 pyramidal neurons in schizophrenia. To examine this hypothesis, we developed a robust stereological method based upon unbiased principles for estimation of total volume and pyramidal neuron numbers for each layer of a cortical area. Our method generates both a systematic, uniformly random set of mapping sections as well as a set of randomly rotated sections cut orthogonal to the pial surface, within the region of interest. We applied our approach in twelve subjects with schizophrenia, each matched to a normal comparison subject. Primary auditory cortex volume was assessed using Cavalieri’s method. The relative and absolute volume of each cortical layer and, within layer 3, the number and density of pyramidal neurons was estimated using our novel approach. Subject groups did not differ in regional volume, layer volumes, or pyramidal neuron number, although pyramidal neuron density was significantly greater in subjects with schizophrenia. These findings suggest that previously observed lower densities of dendritic spines and axon boutons reflect fewer numbers per neuron, and contribute to greater neuronal density via a reduced neuropil. Our approach represents a powerful new method for stereologic estimation of features of interest within individual layers of cerebral cortex, with applications beyond the current study.

Dorph-Petersen, Karl-Anton; Delevich, Kristen M.; Marcsisin, Michael J.; Zhang, Wei; Sampson, Allan R.; Gundersen, Hans J?rgen G.; Lewis, David A.; Sweet, Robert A.



Intracranial Germ Cell Tumors  

Microsoft Academic Search

\\u000a Germ cell tumors originating from the gonads may also occur in the central nervous system (CNS). They arise from primordial\\u000a germ cells that were trapped within neural tissue during the process of migration at the time of early embryogenesis [20].\\u000a Intracranial germ cell tumors include six subtypes classified by the World Health Organization: germinoma, embryonal carcinoma,\\u000a yolk sac tumor (endodermal

Kyu-Chang Wang; Seung-Ki Kim; Sung-Hye Park; Ji Hoon Phi; Byung-Kyu Cho


Primary degeneration of the granular layer of the cerebellum (Norman type)  

Microsoft Academic Search

Purkinje cells, impregnated with the rapid Golgi method, in a patient with primary degeneration of the granular layer showed abnormal orientation of the perikaryon and dendrites, reduction in size of the dendritic arbor, absence of spiny branchlets, and large numbers of stubby spines and hypertrophic spines on secondary dendritic branches; stubby spines and thorn-like formations were seldom observed on the

I. Ferrer; J. Sirvent; J. M. Manresa; E. Galofré; E. Fernández-Alvarez; M. Pineda



Convergence of magno- and parvocellular pathways in layer 4B of macaque primary visual cortex  

Microsoft Academic Search

EARLY visual processing is characterized by two independent parallel pathways: the magnocellular stream, which carries information useful for motion analysis, and the parvocellular stream, which carries information useful for analyses of shape and colour1-3. Although increasing anatomical and physiological evidence indicates some degree of convergence of the two streams, the pathway through layer 4B of primary visual cortex (VI) and

Atomu Sawatari; Edward M. Callaway



Cocaine preferentially enhances sensory processing in the upper layers of the primary sensory cortex.  


Sensory systems are believed to play an important role in drug addiction, particularly in triggering craving and relapse, and it has been shown in previous studies that administration of cocaine can enhance evoked responses in the primary sensory cortex of experimental animals. Primary sensory cortex comprises a multi-layered structure to which a variety of roles have been assigned; an understanding of how cocaine affects evoked activity in these different layers may shed light on how drug-associated sensory cues gain control over behavior. The aim of the present study was to examine how cocaine affects whisker sensory responses in different layers of the primary sensory (barrel) cortex. Field potential and multi-unit activity were recorded from the cortex of anesthetized rats using 16 channel linear probes during repetitive (air puff) stimulation of the whiskers. In control conditions (under saline, i.v.), responses strongly adapted to the repeated sensory stimulation. Following an i.v. injection of cocaine (0.5 mg/kg, i.v.), this adaptation was strongly attenuated, giving each stimulus a more equal representation and weight. Attenuation of adaptation was more marked in the upper cortical layers in both field potential and multi-unit data. Indeed, in these layers, not only was adaptation attenuated but multi-unit response amplitudes under cocaine exceeded those under saline for stimuli occurring early in the train. The results extend our previous findings concerning the enhancement by cocaine of primary sensory responses. Insofar as enhanced neural responses equate to enhanced stimulus salience, the results indicate that cocaine may play a previously under-appreciated role in the formation of associations between drug and drug-related environmental cues by enhancing stimulus salience. The associative process itself may be assisted by a preferential action in the upper cortical layers, thought to be involved in learning and plasticity. PMID:17367949

Devonshire, I M; Mayhew, J E W; Overton, P G



In vitro generation of germ cells from murine embryonic stem cells  

Microsoft Academic Search

The demonstration of germ cell and haploid gamete development from embryonic stem cells (ESCs) in vitro has engendered a unique set of possibilities for the study of germ cell development and the associated epigenetic phenomenon. The process of embryoid body (EB) differentiation, like teratoma formation, signifies a spontaneous differentiation of ESCs into cells of all three germ layers, and it

Jason A West; In-Hyun Park; George Q Daley; Niels Geijsen



Genomic Landscape of Developing Male Germ Cells  

PubMed Central

Spermatogenesis is a highly orchestrated developmental process by which spermatogonia develop into mature spermatozoa. This process involves many testis- or male germ cell-specific gene products whose expressions are strictly regulated. In the past decade the advent of high-throughput gene expression analytical techniques has made functional genomic studies of this process, particularly in model animals such as mice and rats, feasible and practical. These studies have just begun to reveal the complexity of the genomic landscape of the developing male germ cells. Over 50% of the mouse and rat genome are expressed during testicular development. Among transcripts present in germ cells, 40% – 60% are uncharacterized. A number of genes, and consequently their associated biological pathways, are differentially expressed at different stages of spermatogenesis. Developing male germ cells present a rich repertoire of genetic processes. Tissue-specific as well as spermatogenesis stage-specific alternative splicing of genes exemplifies the complexity of genome expression. In addition to this layer of control, discoveries of abundant presence of antisense transcripts, expressed psuedogenes, non-coding RNAs (ncRNA) including long ncRNAs, microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), and retrogenes all point to the presence of multiple layers of expression and functional regulation in male germ cells. It is anticipated that application of systems biology approaches will further our understanding of the regulatory mechanism of spermatogenesis.†

Lee, Tin-Lap; Pang, Alan Lap-Yin; Rennert, Owen M.; Chan, Wai-Yee



Analysis of salvage treatments for germ cell cancer patients who have relapsed after primary high-dose chemotherapy plus autologous stem cell support.  


The aim of this study was to identify treatment strategies and therapeutic or clinical factors that predict for response to salvage therapy and survival in patients with metastatic 'Indiana advanced' or International Germ-Cell Cancer Collaborative Group (IGCCCG) poor prognosis' germ cell cancer (GCT) failing first-line sequential high-dose chemotherapy plus autologous stem cell support (HD-CT). A total of 58 'poor prognosis' patients who had relapsed after HD-CT were identified within two large prospective German first-line HD-CT trials (n=286) performed between March 1993 and March 2001. Salvage treatment consisted of the following: cisplatin-based conventional dose CTx+/-resection (19/58; 33%), non-cisplatin based CTx (16/58; 28%) or salvage HD-CT (14/58; 24%)+/-resection; resection (n=3) and/or radiation (n=5) only: 7 patients (12%); no specific therapy: 2 patients. 21 (38%) patients responded favourably (Complete Response (CR)/Partial Response (PR) marker-negative) to salvage therapy. The use of salvage HD-CT (2-year survival 48%; P=0.03, the complete resection of residual masses (2-year survival 42%; P=0.015) as well as a favourable response to salvage therapy (2-year survival: 31%, P=0.014) were the only variables on univariate analysis associated with an improved survival. The estimated 2-year overall survival rate is 32% (95% Confidence Interval CI: 29-45%). Approximately 30% of patients relapsing after first-line HD-CT will survive>2 years, particularly those patients who can be treated with a second HD-CT +and/or surgical resection. If feasible, complete surgical resection of residual tumours appears to be the most efficient treatment. PMID:12651203

Kollmannsberger, C; Schleucher, N; Rick, O; Metzner, B; Hartmann, J T; Schöffski, P; Beyer, J; Casper, J; Sosada, M; Schmoll, H-J; Böhlke, I; Meisner, C; Kanz, L; Bokemeyer, C



Layer-specific diffusion weighted imaging in human primary visual cortex in vitro.  


One of the most prominent characteristics of the human neocortex is its laminated structure. The first person to observe this was Francesco Gennari in the second half the 18th century: in the middle of the depth of primary visual cortex, myelinated fibres are so abundant that he could observe them with bare eyes as a white line. Because of its saliency, the stria of Gennari has a rich history in cyto- and myeloarchitectural research as well as in magnetic resonance (MR) microscopy. In the present paper we show for the first time the layered structure of the human neocortex with ex vivo diffusion weighted imaging (DWI). To achieve the necessary spatial and angular resolution, primary visual cortex samples were scanned on an 11.7 T small-animal MR system to characterize the diffusion properties of the cortical laminae and the stria of Gennari in particular. The results demonstrated that fractional anisotropy varied over cortical depth, showing reduced anisotropy in the stria of Gennari, the inner band of Baillarger and the deepest layer of the cortex. Orientation density functions showed multiple components in the stria of Gennari and deeper layers of the cortex. Potential applications of layer-specific diffusion imaging include characterization of clinical abnormalities, cortical mapping and (intra)cortical tractography. We conclude that future high-resolution in vivo cortical DWI investigations should take into account the layer-specificity of the diffusion properties. PMID:23347559

Kleinnijenhuis, Michiel; Zerbi, Valerio; Küsters, Benno; Slump, Cornelis H; Barth, Markus; van Cappellen van Walsum, Anne-Marie



Embryonic germ cell lines and their derivation from mouse primordial germ cells.  


When primordial germ cells of the mouse are cultured on feeder layers with the addition of the polypeptide signalling molecules leukaemia inhibitory factor, Steel factor and basic fibroblast growth factor they give rise to cells that resemble undifferentiated blastocyst-derived embryonic stem cells. These primordial germ cell-derived embryonic germ cells (EG cells) can be induced to differentiate extensively in culture and also form teratocarcinomas when injected into nude mice. Additionally, they contribute to chimeras when injected into host blastocysts. We have derived multiple EG cell lines from 8.5 days post coitum (dpc) embryos of C57BL/6 inbred mice. Four independent EG cell lines with normal male karyotypes have formed chimeras (up to 70% coat colour chimerism) when injected into BALB/c host blastocysts. Chimeric mice from all four cell lines are fertile, but only those from one line have transmitted coat colour markers through the germline. Studies have also been carried out to determine whether gonadal primordial germ cells can give rise to pluripotent EG cells. Germ cells from gonads of 15.5 dpc C57BL/6 embryos and newborn mice failed to produce EG cell lines. EG cell lines capable of forming teratocarcinomas and coat colour chimeras have been established from primordial germ cells of 12.5 dpc genital ridges. We are currently testing the genomic imprinting status of the insulin-like growth factor type 2 receptor gene (Igf2r) in our different EG cell lines. PMID:7835148

Labosky, P A; Barlow, D P; Hogan, B L



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

PubMed Central

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.

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



Conserved expression pattern of chicken DAZL in primordial germ cells and germ-line cells.  


The autosomal gene deleted in azoospermia-like (DAZL), which was identified as a member of the deleted in azoospermia (DAZ) family, is homologous to the Drosophila gene BOULE. The authors investigated the sequence similarities of chicken DAZL (cDAZL) with several invertebrate and vertebrate DAZL proteins using CLUSTAL X. A comparison of the primary sequence of cDAZL with other DAZL proteins indicated significant similarities: 70-82% with reptiles, 63-68% with mammals, 51-67% with amphibians, and 42-49% with fishes. The conserved expression pattern of cDAZL was examined by reverse transcription-PCR, quantitative real-time PCR, and in situ hybridization during primordial germ cell (PGC) settlement in the gonads and germ-line development. Among several tissues examined on embryonic day E6.5, DAZL expression was detected specifically in male and female gonads. Quantitative real-time PCR and in situ hybridization revealed strong cDAZL expression in PGCs. When the PGCs differentiated into germ cells, cDAZL expression was slightly decreased; however, expression was continuously detected in germ-line cells until the adult stage. We inferred that cDAZL expression was conserved in PGCs and during germ-line differentiation until the adult stage, making them a valuable molecular marker for studies of PGC differentiation and germ-line development in chickens. PMID:20537692

Rengaraj, D; Zheng, Y H; Kang, K S; Park, K J; Lee, B R; Lee, S I; Choi, J W; Han, J Y




Microsoft Academic Search

Intracranial germ cell tumors are a heterogeneous group of lesions which occur in children and adults. Within the classification of intracranial germ cell tumors, there are a variety of different tumor types which carry different prognoses. The diagnosis of an intracranial germ cell tumor usually requires histological informa- tion, but a subgroup of tumors will secrete specific tumor markers, including

J Bjornsson; B Scheithauer; H Okazakl; R W Leech



Germs and Hygiene  


... Avoiding touching your eyes, nose or mouth Hand washing is one of the most effective and most overlooked ways to stop disease. Soap and water work well to kill germs. Wash for at least 20 seconds and rub your hands briskly. Disposable hand wipes or gel sanitizers also work well.


Germs and the Body  

NSDL National Science Digital Library

This Science NetLinks lesson explores germs, where they exist, and how they can affect the body. It also addresses a common misconception that students of all ages may have - that factors important to health are beyond their personal control. In studying bacteria, students will also learn preventative measures they can take to stay healthy.

Science Netlinks;



Human growth-differentiation factor 3 (hGDF3): developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours  

Microsoft Academic Search

We describe the cloning and initial characterization of a novel cDNA from human embryonal carcinoma (EC) cells. This cDNA, which we named human growth differentiation factor 3 (hGDF3), encodes the homologue of mouse GDF3, a TGF? superfamily member belonging to the Growth\\/Differentiation Factors. We have analysed the expression of hGDF3 in human embryonal carcinoma cell lines and in primary testicular

Andrea AD Caricasole; Ron HN van Schaik; Laura M Zeinstra; Cristel DJ Wierikx; Ruud JHLM van Gurp; Mirjam van den Pol; Leendert HJ Looijenga; J Wolter Oosterhuis; Martin F Pera; Andrew Ward; Diederik de Bruijn; Piet Kramer; Frank H de Jong; Adriana JM van den Eijnden-van Raaij; AAD Caricasole



Malignant retroperitoneal and abdominal germ cell tumors: An intergroup study  

Microsoft Academic Search

Background\\/Purpose: This randomized study examined survival (S) and event-free survival (EFS) rates using high-or standard-dose cisplatin-based combination chemotherapy and surgical resection for this subset of germ cell tumors. Methods: Twenty-six of 317 patients enrolled on the POG 9049\\/COG 8882 intergroup study for malignant germ cell tumors had abdomen or retroperitoneum as the primary site. Twenty-five of 26 were eligible for

D. Billmire; C. Vinocur; F. Rescorla; P. Colombani; B. Cushing; E. Hawkins; M. Davis; W. B. London; S. Lauer; R. Giller



Less germs, less mucus, less snot: teachers' and health workers' perceptions of the benefits and barriers of ear health programs in lower primary school classes.  


This study explored health and education professionals' perceptions of the health benefits and barriers of different ear health programs used in lower primary school classes in two district education areas in the Goldfields South East Health Region, Western Australia. Health and education staff providing services to children in kindergarten to year three primary school classes were sent a questionnaire about ear health programs provided in their school. Sixty-one questionnaires were returned from 43 teachers, 14 community health nurses, three Aboriginal health workers and one teacher's assistant. Some schools implemented all the ear health programs examined at all year levels while others implemented only one of the programs. Teachers, community health nurses and Aboriginal health workers identified that all ear health programs were beneficial to students. Reported physical health benefits included reduced ear infections, early detection of ear infections and improved hearing. Behavioural benefits included improved concentration, alertness and attention in the classroom. Barriers to implementing the programs were obtaining consent from parents/carers, student transience and attendance, time to implement and conduct the programs and human and physical resources. Evaluation methods used varied from no evaluation for the Breathe Blow Cough and tissue spearing programs to limited data collection for audiometry, otoscopy and ear toilet programs. Respondents perceived that ear health programs were effective in improving health and behavioural outcomes for children. A formal pre-post evaluation to provide objective data to confirm this is needed to inform policy around this important health issue. PMID:21138704

Doyle, June; Ristevski, Eli



Primary versus secondary contributions to particle number concentrations in the European boundary layer  

NASA Astrophysics Data System (ADS)

It is important to understand the relative contribution of primary and secondary particles to regional and global aerosol so that models can attribute aerosol radiative forcing to different sources. In large-scale models, there is considerable uncertainty associated with treatments of particle formation (nucleation) in the boundary layer (BL) and in the size distribution of emitted primary particles, leading to uncertainties in predicted cloud condensation nuclei (CCN) concentrations. Here we quantify how primary particle emissions and secondary particle formation influence size-resolved particle number concentrations in the BL using a global aerosol microphysics model and aircraft and ground site observations made during the May 2008 campaign of the European Integrated Project on Aerosol Cloud Climate Air Quality Interactions (EUCAARI). We tested four different parameterisations for BL nucleation and two assumptions for the emission size distribution of anthropogenic and wildfire carbonaceous particles. When we emit carbonaceous particles at small sizes (as recommended by the Aerosol Intercomparison project, AEROCOM), the spatial distributions of campaign-mean number concentrations of particles with diameter >50 nm (N50) and >100 nm (N100) were well captured by the model (R2?0.8) and the normalised mean bias (NMB) was also small (-18% for N50 and -1% for N100). Emission of carbonaceous particles at larger sizes, which we consider to be more realistic for low spatial resolution global models, results in equally good correlation but larger bias (R2?0.8, NMB = -52% and -29%), which could be partly but not entirely compensated by BL nucleation. Within the uncertainty of the observations and accounting for the uncertainty in the size of emitted primary particles, BL nucleation makes a statistically significant contribution to CCN-sized particles at less than a quarter of the ground sites. Our results show that a major source of uncertainty in CCN-sized particles in polluted European air is the emitted size of primary carbonaceous particles. New information is required not just from direct observations, but also to determine the "effective emission size" and composition of primary particles appropriate for different resolution models.

Reddington, C. L.; Carslaw, K. S.; Spracklen, D. V.; Frontoso, M. G.; Collins, L.; Merikanto, J.; Minikin, A.; Hamburger, T.; Coe, H.; Kulmala, M.; Aalto, P.; Flentje, H.; Plass-Dülmer, C.; Birmili, W.; Wiedensohler, A.; Wehner, B.; Tuch, T.; Sonntag, A.; O'Dowd, C. D.; Jennings, S. G.; Dupuy, R.; Baltensperger, U.; Weingartner, E.; Hansson, H.-C.; Tunved, P.; Laj, P.; Sellegri, K.; Boulon, J.; Putaud, J.-P.; Gruening, C.; Swietlicki, E.; Roldin, P.; Henzing, J. S.; Moerman, M.; Mihalopoulos, N.; Kouvarakis, G.; Ždímal, V.; Zíková, N.; Marinoni, A.; Bonasoni, P.; Duchi, R.



Germ cell apoptosis in the testes of normal stallions.  


Apoptosis in testicular germ cells has been demonstrated in many mammalian species. However, little is known about the stallion (Equus caballus) and rates of apoptosis during spermatogenesis. Morphological and biochemical features of apoptosis reported in other species were used to confirm that the TdT-mediated dUTP Nick end labeling (TUNEL) assay is an acceptable method for identification and quantification of apoptotic germ cells in histological tissue sections from stallion testis. Seminiferous tubules from eight stallions with normal testis size and semen quality were evaluated according to stage of seminiferous epithelium to determine the germ cell types and stages where apoptosis most commonly occurs. Spermatogonia and spermatocytes were the most common germ cell types labeled by the TUNEL assay. A low rate of round and elongated spermatids were labeled by the TUNEL assay. Mean numbers of TUNEL-positive germ cells per 100 Sertoli cell nuclei were highest in stages IV (15.5 +/- 1.0) and V (13.5 +/- 1.1) of the seminiferous epithelial cycle (P < 0.001). An intermediate level of apoptosis was detected in stage VI (P < 0.02). These stages (IV-VI) correspond to meiotic divisions of primary spermatocytes and mitotic proliferation of B1 and B2 spermatogonia. Establishing basal levels of germ cell apoptosis is a critical step towards understanding fertility and the role of apoptosis in regulating germ cell numbers during spermatogenesis. PMID:15159121

Heninger, Noah L; Staub, Christophe; Blanchard, Terry L; Johnson, Larry; Varner, Dickson D; Forrest, David W



Primary versus secondary contributions to particle number concentrations in the European boundary layer  

NASA Astrophysics Data System (ADS)

It is important to understand the relative contribution of primary and secondary particles to regional and global aerosol so that models can attribute aerosol radiative forcing to different sources. In large-scale models, there is considerable uncertainty associated with treatments of particle formation (nucleation) in the boundary layer (BL) and in the size distribution of emitted primary particles, leading to uncertainties in predicted cloud condensation nuclei (CCN) concentrations. Here we quantify how primary particle emissions and secondary particle formation influence size-resolved particle number concentrations in the BL using a global aerosol microphysics model and observations made during the May 2008 campaign of the European Integrated Project on Aerosol Cloud Climate Air Quality Interactions (EUCAARI). Observations are available from the DLR Falcon 20 aircraft and from 15 ground sites of the European Supersites for Atmospheric Aerosol Research (EUSAAR) and the German Ultrafine Aerosol Network (GUAN). Measurements include total and non-volatile particle number concentrations and the particle size distribution between ~3 nm and ~1 ?m. We tested four different parameterisations for BL nucleation and two assumptions for the emission size distribution of anthropogenic and wildfire carbonaceous particles. When we emit small carbonaceous particles (recommended by the Aerosol Intercomparison project, AEROCOM), the spatial distributions of campaign-mean number concentrations >50 nm (N50) and >100 nm (N100) dry diameter were well captured by the model (R2~0.9) and the normalised mean bias (NMB) was also small (-5 % for N50 and 12 % for N100). Emission of larger particles, which we consider to be more realistic for global models, results in equally good correlation but larger bias (R2~0.8, NMB = -51 % and -21 %), which could be partly but not entirely compensated by BL nucleation. The model also predicts the particle concentration frequency distribution fairly well, with an overlap of modelled and observed N50 hourly histograms of ~60 % across all sites. However, the model-observation temporal correlation on an hourly time scale is poor (R2?0.1) for this period. These comparisons show that caution is required when drawing conclusions about model realism from time or site-averaged data or frequency histograms when deterministic behaviour is not captured at individual sites. From this 1-month intensive European dataset it is not possible to determine a reliable estimate of the fraction of CCN-sized particles from primary and secondary sources, although the size of primary emitted particles is shown to be a major source of uncertainty.

Reddington, C. L.; Carslaw, K. S.; Spracklen, D. V.; Frontoso, M. G.; Collins, L.; Merikanto, J.; Minikin, A.; Hamburger, T.; Coe, H.; Kulmala, M.; Aalto, P.; Flentje, H.; Plass-Dülmer, C.; Birmili, W.; Wiedensohler, A.; Wehner, B.; Tuch, T.; Sonntag, A.; O'Dowd, C. D.; Jennings, S. G.; Dupuy, R.; Baltensperger, U.; Weingartner, E.; Hansson, H.-C.; Tunved, P.; Laj, P.; Sellegri, K.; Boulon, J.; Putaud, J.-P.; Gruening, C.; Swietlicki, E.; Roldin, P.; Henzing, J. S.; Moerman, M.; Mihalopoulos, N.; Kouvarakis, G.; Ždímal, V.; Zíková, N.; Marinoni, A.; Bonasoni, P.; Duchi, R.



Germ-like cell differentiation from induced pluripotent stem cells (iPSCs).  


Historically, our understanding of molecular genetic aspects of germ cell development has been limited. Recently, results demonstrated that the derivation of pluripotent stem cells may provide the necessary genetic system to study germ cell development. Here, we characterized an induced pluripotent stem cell (iPSC) line, which can spontaneously differentiate into embryonic bodies (EBs) after 3 days of suspension culture, expressing specific markers of three germ layers. Then, we induced the iPSCs to differentiate into germ cells by culturing adherent EBs in retinoic acid (RA) and porcine follicular fluid (PFF) differentiation medium or seminiferous tubule transplantation. Our results indicated that RA and PFF were beneficial for the derivation of germ cells and oocyte-like cells from iPSCs, and iPSCs transplantation could make a contribution to repairing the testis of infertile mice. Our study offers an approach for further study on the development and the differentiation of germ cells derived from iPSCs. PMID:23086862

Niu, Zhiwei; Hu, Yue; Chu, Zhili; Yu, Meng; Bai, Yaofu; Wang, Long; Hua, Jinlian



Analytic surface germs with minimal Pythagoras number  

Microsoft Academic Search

We determine all complete intersection surface germs whose Pythagoras number is 2, and find that they are all embedded in R3 and have the property that every positive semidefinite analytic function germ is a sum of squares of analytic function germs. In addition, we discuss completely these properties for mixed surface germs in R3. Finally, we find in higher embedding

José F. Fernando; F. Ciencias Matematicas



Microleakage and Micrographic Evaluation of Composite Restorations with Various Bases over ZOE Layer in Pulpotomized Primary Molars  

PubMed Central

Objective Zinc oxide eugenol (ZOE) under composite restorations should be covered with a suitable material in order to prevent the harmful effect of ZOE on the composite. The aim of this in vitro study was to evaluate microleakage of composite restorations in pulpotomized primary molars with different bases for covering the ZOE layer and to assess the distance between different layers. Materials and Methods Proximo-occlusal cavities were prepared in 78 extracted second primary molars. Carious lesions were removed and pulpotomy was carried out. Zinc oxide eugenol paste was placed in 2-mm thickness. The teeth were randomly divided in 6 groups and restored as follows: 1. Light-cured composite; 2. Resin-modified glass-ionomer and composite resin; 3. Glass-ionomer and composite resin; 4. Light-cured calcium hydroxide and composite resin; 5. Calcium hydroxide and composite resin; 6. Amalgam and composite resin. The restored specimens were thermocycled for 500 cycles (5°C/55°C) and microleakage was assessed by dye penetration technique. Three specimens from each group were processed for scanning electron microscope evaluation to determine the distance between the layers. The results were analyzed by Kruskal-Wallis and Dunn tests. Results Microleakage assessment revealed significant differences between the groups (P=0.04), with the amalgam group exhibiting the lowest microleakage values. In SEM micrographs no significant differences were observed in the distance between ZOE base layers (P=0.94) and base-composite layers (P=0.47); however, the amalgam group had the lowest distances. Conclusion The use of amalgam over zinc oxide eugenol layer in pulpotomized primary molars decreases microleakage.

Bargrizan, M.; Mirkarimi, M.; Rezamand, M.; Eskandarion, S.



Scientists Rewrite Germ's Genetic Code  


... this page, please enable JavaScript. Scientists Rewrite Germ's Genetic Code Aim is to redesign natural biological systems for ... researchers say. "This is the first time the genetic code has been fundamentally changed," study co-author Farren ...


In vitro male germ cell cultures of zebrafish  

Microsoft Academic Search

Transgenic modification of sperm before fertilization has the advantages of a much shorter timeline for the production of transgenic animals. A culture system using primary cultures of zebrafish male germ cells, in which the differentiation of spermatogonia to functional sperm can occur in vitro, allows us to introduce foreign DNA into the cultured sperm and to produce transgenics from the

Noriyoshi Sakai



Axon topography of layer IV spiny cells to orientation map in the cat primary visual cortex (area 18).  


Our aim was to reveal the relationship between layer IV horizontal connections and the functional architecture of the cat primary visual cortex because these connections play important roles in the first cortical stage of visual signals integration. We investigated bouton distribution of spiny neurons over an orientation preference map using in vivo optical imaging, unit recordings, and single neuron reconstructions. The radial extent of reconstructed axons (14 star pyramidal and 9 spiny stellate cells) was ~1.5 mm. In the vicinity of the parent somata (<400 ?m), boutons occupied chiefly iso-orientations, however, more distally, 7 cells projected preferentially to non-iso-orientations. Boutons of each cell were partitioned into 1-15 distinct clusters based on the mean-shift algorithm, of which 57 clusters preferred iso-orientations and 43 clusters preferred cross-orientations, each showing sharp orientation preference "tuning." However, unlike layer III/V pyramidal cells preferring chiefly iso-orientations, layer IV cells were engaged with broad orientations because each bouton cluster from the same cell could show different orientation preference. These results indicate that the circuitry of layer IV spiny cells is organized differently from that of iso-orientation dominant layer III/V cells and probably processes visual signals in a different manner from that of the superficial and deeper layers. PMID:21062952

Karube, Fuyuki; Kisvárday, Zoltán F



Mediastinal germ cell tumor complicated by visceral hemangiomatosis.  


This report describes an extremely rare combination of mediastinal germ cell tumor and visceral hemangiomatosis in a 17-year-old boy who initially presented with chest pain and dyspnea. He was treated with chemotherapy consisting of cisplatin, cyclophosphamide, bleomycin, vinblastine, and dactinomycin followed by surgery. Multiple low-density nodules developed in the spleen three weeks later, suggesting metastases from the primary tumor, but the resected specimen showed cavernous hemangiomas within the splenic parenchyma. The patient died of recurrence of germ cell tumor 19 months after the initial treatment. Postmortem examination disclosed multiple hemangiomas in the lung and liver similar to those in the spleen. PMID:9932638

Sekine, I; Kodama, T; Hasebe, T; Matsumoto, T; Nagai, K; Nishiwaki, Y




Microsoft Academic Search

This paper analyzes the propagation of a cohesive crack through a reinforcement layer and gives a solution that can be used for any specimen and loading condition. Here it faces the case of a reinforced prismatic beam loaded at three points. Reinforcement is represented by means of a free-slip bar bridging the cracked section, anchored at both sides of the

Gonzalo Ruiz


Solution Processed Lanthanum Zirconium Oxide as a Primary Barrier Layer for High Ic Coated Conductors  

SciTech Connect

High-quality lanthanum zirconium oxide (La{sub 2}Zr{sub 2}O{sub 7} or LZO) films have been deposited and processed on Ni-W substrates using a sol-gel processing approach. It has been demonstrated that crack-free coatings with thicknesses up to 100 nm can be processed in a single step, while thicker coatings (200-225 nm) were processed using a multiple coating and annealing process. Using simulated metalorganic deposition (MOD)-YBa{sub 2}Cu{sub 3}O{sub 7-:{angstrom}} (YBCO) processing conditions, the barrier properties of the sol-gel LZO coating with a thickness of 120 nm were found to be comparable to that of the standard 3-layer buffer stack deposited using physical vapor deposition. Secondary ion mass spectroscopy depth profile analysis of LZO films annealed in oxygen-18 shows that LZO effectively stops the diffusion of Ni within the first 80-100 nm. Using MOD processes, a CeO{sub 2} cap layer and superconducting YBCO layer were deposited on sol-gel LZO/Ni-W. For the first time, using such an all-solution conductor architecture, a critical current (I{sub c}) of 140 A/cm with a corresponding critical current density (J{sub c}) of 1.75 MA/cm{sup 2} has been demonstrated. Using a very thin Y{sub 2}O{sub 3} seed layer ({approx}10 nm) deposited by electron beam evaporation; improved texture quality in the LZO layers has been demonstrated. The performance of the LZO deposited on these samples was evaluated using a sputtered CeO{sub 2} cap layer and MOD YBCO layer. Critical currents of up to 255 A/cm (3.2 MA/cm{sup 2}) with 0.8-{micro}m-thick YBCO films have been demonstrated, comparable to the performance of films grown using physical vapor deposited yttria stabilized zirconia as a barrier layer. Similar experiments using an MOD-CeO{sub 2} cap layer and MOD-YBCO layer yielded critical currents of 200 A/cm (2.5 MA/cm{sup 2}) with 0.8-{micro}m-thick YBCO films.

Sathyamurthy, Srivatsan [ORNL; Paranthaman, Mariappan Parans [ORNL; Heatherly Jr, Lee [ORNL; Martin, Patrick M [ORNL; Specht, Eliot D [ORNL; Goyal, Amit [ORNL; Kodenkandath, Thomas [American Superconductor Corporation, Westborough, MA; Li, Xiaoping [American Superconductor Corporation, Westborough, MA; Rupich, Marty [American Superconductor Corporation, Westborough, MA



Measuring cell adhesion forces of primary gastrulating cells from zebrafish using atomic force microscopy  

Microsoft Academic Search

During vertebrate gastrulation, progenitor cells of different germ layers acquire specific adhesive properties that contribute to germ layer formation and separation. Wnt signals have been suggested to function in this process by modulating the different levels of adhesion between the germ layers, however, direct evidence for this is still lacking. Here we show that Wnt11, a key signal regulating gastrulation

Pierre-Henri Puech; Anna Taubenberger; Florian Ulrich; Michael Krieg; Daniel J. Muller; Carl-Philipp Heisenberg



Coherent motion induced fluctuations in the primary transition region of a plane shear layer  

NASA Astrophysics Data System (ADS)

The naturally occurring large scale motions in a single stream shear layer (that is initiated from a fully turbulent boundary layer) are made evident by the induced velocities in the entrainment region beyond the active shear layer. The distinctive attributes of these induced motions are particularly evident in the Michigan State Univerity Free Shear Flow Facility since the total test section length (3m) is nominally the same as the location of the first, fully formed, coherent motion, ca/x theta (0) = 400 (or 2.5 m). Hence, detailed studies of the induced motions can be executed. Individual coherent motions are identified by the induced velocity signatures and conditional-ensemble statistics are used to represent the irrotational field properties. Clusters of such motions exist; some of their properties are substantially different from the unconditionally averaged values.

Foss, J. F.; Davis, E. D.; Haw, R. C.; Ali, S. K.


Testicular germ cell tumours: predisposition genes and the male germ cell niche  

Microsoft Academic Search

Testicular germ cell tumours (TGCTs) of adults and adolescents are putatively derived from primordial germ cells or gonocytes. Recently reported genome-wide association studies implicate six gene loci that predispose to TGCT development. Remarkably, the functions of proteins encoded by genes within these regions bridge our understanding between the pathways involved in primordial germ cell physiology, male germ cell development and

Duncan Gilbert; Elizabeth Rapley; Janet Shipley




Technology Transfer Automated Retrieval System (TEKTRAN)

Processes are in pre-commercial stages of development, for separating corn germ prior to fermentation in a dry grind plant. Oil is currently removed from dry mill germ or wet mill germ by crushing for $35-45/ton or by hexane extraction for $20-40/ton (1). These costs, as well as the capital to bu...


iBioSeminar: Germ Cell Development  

NSDL National Science Digital Library

When an egg is fertilized, two distinct groups of cells are formed; the somatic cells which give rise to all the structures in body and will ultimately die, and the primordial germ cells which become germ line stem cells that produce sperm and egg and thus, can give rise to another generation. Hence, germ cells are responsible for the maintenance of a species.

Ruth Lehmann (New York University School of Medicine;)



Zebrafish embryo cells remain pluripotent and germ-line competent for multiple passages in culture.  


Mouse embryonic stem (ES) cell lines are routinely used to introduce targeted mutations into the genome, providing an efficient method to study gene function. Application of similar gene knockout techniques to other organisms has been unsuccessful due to the lack of germ-line competent ES cell lines from non-murine species. Previously, we reported the production of zebrafish germ-line chimeras using short-term primary embryo cell cultures. Here we demonstrate that zebrafish embryo cells, maintained for several weeks and multiple passages in culture, remain pluripotent and germ-line competent. Zebrafish germ-line chimeras were generated from passage 5 and 6 cultures initiated from blastula- and gastrula-stage embryos. In addition to the germ line, the cultured cells contributed to multiple tissues of the host embryo, including muscle, liver, gut, and fin. To facilitate the identification of germ-line chimeras, ES cells expressing the green fluorescent protein (GFP) were introduced into host embryos, and germ-line contribution was detected by the presence of GFP+ cells in the region of the gonad. The germ-line competent embryo cell cultures will be useful for the development of a gene targeting strategy that will increase the utility of the zebrafish model for studies of gene function. PMID:18248202

Fan, Lianchun; Crodian, Jennifer; Liu, Xiangyu; Aleström, Annette; Aleström, Peter; Collodi, Paul



Survival of patients with nonseminomatous germ cell cancer: a review of the IGCC classification by Cox regression and recursive partitioning  

Microsoft Academic Search

The International Germ Cell Consensus (IGCC) classification identifies good, intermediate and poor prognosis groups among patients with metastatic nonseminomatous germ cell tumours (NSGCT). It uses the risk factors primary site, presence of nonpulmonary visceral metastases and tumour markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH). The IGCC classification is easy to use and remember, but lacks flexibility.

M R van Dijk; E W Steyerberg; S P Stenning; E Dusseldorp; J D F Habbema; van Dijk



The protein encoded by the germ plasm RNA Germes associates with dynein light chains and functions in Xenopus germline development  

Microsoft Academic Search

Germ plasm plays a prominent role in germline formation in a large number of animal taxons. We previously identified a novel maternal RNA named Germes associated with Xenopus germ plasm. In the present work, we addressed possible involvement of Germes protein in germ plasm function. Expression in oocytes followed by confocal microscopy revealed that the EGFP fused to Germes, in

Lyubov A. Berekelya; Alexander A. Mikryukov; Natalia N. Luchinskaya; Maxim B. Ponomarev; Hugh R. Woodland; Alexander V. Belyavsky



Cell-type-specific sub- and suprathreshold receptive fields of layer 4 and layer 2/3 pyramids in rat primary visual cortex.  


Connectivity of cortical pyramidal neurons is layer-specific in the primary visual cortex (V1) and this is thought to be reflected in different receptive field (RF) properties of layer 4 and layer 2/3 pyramidal neurons (L4Ps and L2/3Ps, respectively). However, it remains unclear how the two cell populations convert incoming visually driven synaptic inputs into action potential (AP) outputs. Here I compared postsynaptic potentials (PSPs) and AP responses of L4Ps and L2/3Ps in the binocular portion of rat V1 by intrinsic optical imaging (IOI)-targeted whole-cell recordings followed by anatomical identification and dendritic reconstructions. L2/3Ps had about 2-fold longer dendritic branches and a higher number of branch points and endings in their apical portions. Functionally, L2/3Ps had more hyperpolarized resting potentials and lower rates of spontaneous APs (medians: 0.07 vs. 0.60 AP/s). PSP responses to optimally oriented moving bars were comparable in terms of amplitude (16.0±0.9 vs. 17.3±1.1 mV for L2/3Ps and L4Ps, respectively), reliability and size of the RF. The modulated component of subthreshold responses of L4Ps to optimal sinusoidal drifting gratings was larger and their PSP onset latency in response to bars flashed in the cell's RF center were shorter (60 vs. 86 ms). In contrast to the similarities of PSP responses to moving bars, AP responses of L2/3Ps were more sparse (medians: 0.7 vs. 2.9 APs/stimulus passage), less reliable, but sharper in terms of angular size. Based on the differences of subthreshold inputs, I conclude that L4Ps may receive mostly thalamic inputs, whereas L2/3Ps may receive both thalamic and cortical inputs from layer 4. The comparable subthreshold responses to moving bars are converted by L2/3Ps into sparser but sharper AP outputs possibly by cell-type-specific AP-generating mechanisms or differences in visually driven inhibitory inputs. PMID:21704132

Medini, P



Generation of functional neurons and glia from multipotent adult mouse germ-line stem cells  

Microsoft Academic Search

Recently, we reported the successful establishment of multipotent adult germ-line stem cells (maGSCs) from cultured adult mouse spermatogonial stem cells. Similar to embryonic stem cells, maGSCs are able to self-renew and differentiate into derivatives of all three germ layers. These properties make maGSCs a potential cell source for the treatment of neural degenerative diseases. In this study, we describe the

Katrin Streckfuss-Bömeke; Alla Vlasov; Swen Hülsmann; Dongjiao Yin; Karim Nayernia; Wolfgang Engel; Gerd Hasenfuss; Kaomei Guan



Zebrafish models of germ cell tumor.  


Germ cell tumors are neoplasms arising from pluripotent germ cells. In humans, these tumors occur in infants, children and young adults. The tumors display a wide range of histologic differentiation states which exhibit different clinical behaviors. Information about the molecular basis of germ cell tumors, and representative animal models of these neoplasms, are lacking. Germline development in zebrafish and humans is broadly conserved, making the fish a useful model to probe the connections between germ cell development and tumorigenesis. Here, we provide an overview of germline development and a brief review of germ cell tumor biology in humans and zebrafish. We also outline some methods for studying the zebrafish germline. PMID:21951524

Neumann, Joanie C; Lillard, Kate; Damoulis, Vanessa; Amatruda, James F



Experience-dependent switch in sign and mechanisms for plasticity in layer 4 of primary visual cortex  

PubMed Central

Neural circuits are extensively refined by sensory experience during postnatal development. How the maturation of recurrent cortical synapses may contribute to events regulating the postnatal refinement of neocortical microcircuits remains controversial. Here we show that in the main input layer of rat primary visual cortex, layer 4 (L4), recurrent excitatory synapses are endowed with multiple, developmentally-regulated mechanisms for induction and expression of excitatory synaptic plasticity. Maturation of L4 synapses and visual experience lead to a sharp switch in sign and mechanisms for plasticity at recurrent excitatory synapses in layer 4 at the onset of the critical period for visual cortical plasticity. The state of maturation of excitatory pyramidal neurons allows neurons to engage different mechanisms for plasticity in response to the same induction paradigm. Experience is determinant for the maturation of L4 synapses, as well as for the transition between forms of plasticity and the mechanisms they may engage. These results indicate a tight correlation between the effects of sensory drive and maturation on cortical neurons and provide a new set of cellular mechanisms engaged in the postnatal refinement of cortical circuits.

Wang, L.; Fontanini, A.; Maffei, A.



The Geochemical Earth Reference Model (GERM)  

SciTech Connect

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 are 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 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.

Staudigel, H. [Vrije Univ., Amsterdam (Netherlands); Albarede, F. [Ecole Normale Superieure, Lyon (France); Shaw, H. [Lawrence Livermore National Lab., CA (United States); McDonough, B. [Harvard Univ., Cambridge, MA (United States). Dept. of Earth and Planetary Sciences; White, W. [Cornell Univ., Ithaca, NY (United States). Dept. of Geology



Determination for dry layer resistance of sucrose under various primary drying conditions using a novel simulation program for designing pharmaceutical lyophilization cycle.  


Dry layer resistance, which is the resistance of dried cake against water vapor flow generated from sublimation, is one of the important parameters to predict maximum product temperature and drying time during primary drying in lyophilization. The purpose of this study was to develop the predictive model of dry layer resistance under various primary drying conditions using the dry layer resistance obtained from a preliminary lyophilization run. When the maximum dry layer resistance was modified under the assumption that the chamber pressure is zero, the modified dry layer resistance, which is defined as specific dry layer resistance, correlated well with the sublimation rate. From this correlation, the novel predictive model including the empirical formula of sublimation rate and specific dry layer resistance is proposed. In this model, the dry layer resistance under various conditions of shelf temperature and chamber pressure was successfully predicted based on the relationship of the sublimation rate and specific dry layer resistance of the edge and center vials obtained from the product temperature in one preliminary cycle run. It is expected that this predictive model could be a practical and useful tool to predict product temperature during primary drying. PMID:23684561

Kodama, Tatsuhiro; Sawada, Hiroyuki; Hosomi, Hiroshi; Takeuchi, Masahito; Wakiyama, Naoki; Yonemochi, Etsuo; Terada, Katsuhide



Assessment of Speech in Primary Cleft Palate by Two-layer Closure (Conservative Management).  


Treatment of the cleft palate has evolved over a long period of time. Various techniques of cleft palate repair that are practiced today are the results of principles learned through many years of modifications. The challenge in the art of modern palatoplasty is no longer successful closure of the cleft palate but an optimal speech outcome without compromising maxillofacial growth. Throughout these periods of evolution in the treatment of cleft palate, the effectiveness of various treatment protocols has been challenged by controversies concerning speech and maxillofacial growth. In this article we have evaluated the results of Pinto's modification of Wardill-Kilner palatoplasty without radical dissection of the levator veli palitini muscle on speech and post-op fistula in two different age groups in 20 patients. Preoperative and 6-month postoperative speech assessment values indicated that two-layer palatoplasty (modified Wardill-Kilner V-Y pushback technique) without an intravelar veloplasty technique was good for speech. PMID:23066454

Jain, Harsha; Rao, Dayashankara; Sharma, Shailender; Gupta, Saurabh



Delay-induced primary rhythmic behavior in a two-layer neural network.  


In this paper, we construct a two-layer feedback neural network to theoretically investigate the influence of symmetry and time delays on patterned rhythmic behaviors. Firstly, linear stability of the model is investigated by analyzing the associated transcendental characteristic equation. Next, by means of the symmetric bifurcation theory of delay differential equations coupled with representation theory of standard dihedral groups, we not only investigate the effect of synaptic delays of signal transmission on the pattern formation, but also obtain some important results about the spontaneous bifurcation of multiple branches of periodic solutions and their spatio-temporal patterns. Thirdly, based on the normal form approach and the center manifold theory, we derive the formula to determine the bifurcation direction and stability of Hopf bifurcating periodic solutions. Finally, some numerical examples and the corresponding numerical simulations are used to illustrate the effectiveness of the obtained results. PMID:20884171

Guo, Shangjiang; Yuan, Yuan



Derivation and characterization of zebrafish embryonic germ cell cultures and the effects of kit ligand a  

Microsoft Academic Search

A stem cell-mediated gene targeting approach is currently not available for zebrafish. To address this problem our lab has developed methods for the culture of pluripotent stem cells derived from early-stage zebrafish embryos. Embryonic stem (ES) cell cultures were derived from blastula-stage zebrafish embryos and primary cultures of pluripotent embryonic germ (EG) cells were initiated from primordial germ cells (PGCs).

Jesung Moon



Treatment of germ cell tumors in the pineal region  

Microsoft Academic Search

The authors retrospectively analyzed 107 patients with primary intracranial germ cell tumor (GCT), who were treated at the\\u000a Department of Neurosurgery, Yonsei Medical Center between January 1986 and January 1996. The incidence of GCT was 2.8% in\\u000a pediatric patients with intracranial tumor. Of the 107 tumors, 60 were located in the pineal region, 30 in the suprasellar\\u000a region, 16 in

Joong-Uhn Choi; Dong-Seok Kim; Sang-Sup Chung; Tae-Seung Kim



Late toxicity after treatment for testicular germ cell cancer  

Microsoft Academic Search

Summary  \\u000a Improved survival in testicular cancer has been accompanied by concern about long-term side effects of chemotherapy or radiotherapy.\\u000a Secondary malignant neoplasia represents one of the worst possible long-term complications, leading to death in patients cured\\u000a of their primary malignancy. Patients with testicular germ cell tumors appear to have a 2-fold increased risk of developing\\u000a any second cancer 25–30 years

A. Jakob; C. Kollmannsberger; L. Kanz; C. Bokemeyer



Multi-layered culture of primary human conjunctival epithelial cells producing MUC5AC.  


The purpose of our study was to establish a system for culturing normal human conjunctival epithelial (NHCE) cells under serum-free culture conditions without compromising their ability to differentiate into a mucous epithelium. To this end, small pieces of normal conjunctiva were biopsied from patients undergoing cataract surgery. Obtained NHCE cells were cultured in bronchial epithelial growth medium (BEGM) under serum free culture conditions and passage 3 cells were air-lifted. Cultured NHCE cells displayed typical epithelial morphology. Expression of cytokeratin 19 and conjunctival epithelial specific carbohydrate residue were detected. Air-lifted NHCE cells demonstrated an increase in stratification and differentiation into goblet cells up to 3weeks under air-liquid interface (ALI) culture condition. NHCE cells expressed MUC1, MUC4, MUC16, and MUC5AC mRNA, and MUC5AC production and secretion increased in a time dependent manner after culture under ALI conditions. Exposure of cells to proinflammatory cytokines (TNF-alpha or IFN-gamma) resulted in upregulation of MUC1, MUC4, MUC16, and MUC5AC gene expression. In conclusion, differentiated NHCE cells showed features of a multi-layered conjunctival epithelium, including goblet cells, and retained functional characteristics similar to those seen in vivo. This cell culture system can better facilitate investigation of conjunctival epithelial cell biology and goblet cell differentiation. PMID:17568580

Chung, So-Hyang; Lee, Joon H; Yoon, Joo-Heon; Lee, Hyung Keun; Seo, Kyoung Yul



Familial Testicular Germ Cell Tumors  

PubMed Central

In this review, we define familial testicular germ cell tumors (FTGCT) as testicular germ cell tumors (TGCT) diagnosed in at least two blood relatives, a situation which occurs in 1-2% of all cases of TGCT. Brothers and fathers of TGCT patients have an 8-10 and 4-6 fold increased risk of TGCT, respectively, and an even higher elevated risk of TGCT in twin brothers of men with TGCT has been observed, suggesting that genetic elements play an important role in these tumors. Nevertheless, previous linkage studies with multiple FTGCT families did not uncover any high-penetrance genes and it has been concluded that the combined effects of multiple common alleles, each conferring modest risk, might underlie FTGCT. In agreement with this assumption, recent candidate gene association analyses have identified the chromosome Y gr/gr deletion and mutations in the PDE11A gene as genetic modifiers of FTGCT risk. Moreover, two genomewide association studies of predominantly sporadic but also familial cases of TGCT have identified three additional susceptibility loci, KITLG, SPRY4 and BAK1. Notably, all five loci are involved in the biology of primordial germ cells, representing the cell of origin of TGCT, suggesting that the tumors arise as a result of disturbed testicular development.

Kratz, Christian P.; Mai, Phuong L.; Greene, Mark H.



Numerical study of the primary instability in a separated boundary layer transition under elevated free-stream turbulence  

NASA Astrophysics Data System (ADS)

Numerical studies of laminar-to-turbulent transition in a separation bubble subjected to two free-stream turbulence levels (FST) have been performed using Large-Eddy Simulation (LES). Separation of the laminar boundary layer occurs at a curvature change over a plate with a semi-circular leading edge at Re = 3450 based on the plate thickness and the uniform inlet velocity. A numerical trip is used to produce the targeted free-stream turbulence levels and the decay of free-stream turbulence is well predicted. A dynamic sub-grid-scale model is employed in the current study and a good agreement has been obtained between the LES results and the experimental data. Detailed analysis of the LES data has been carried out to investigate the primary instability mechanism. The flow visualisations and spectral analysis of the separated shear layer reveal that the 2D Kelvin-Helmholtz instability mode, well known to occur at low FST levels, is bypassed at higher levels leading to earlier breakdown to turbulence.

Langari, Mostafa; Yang, Zhiyin



A role for Lin28 in primordial germ-cell development and germ-cell malignancy  

Microsoft Academic Search

The rarity and inaccessibility of the earliest primordial germ cells (PGCs) in the mouse embryo thwart efforts to investigate molecular mechanisms of germ-cell specification. stella (also called Dppa3) marks the rare founder population of the germ lineage. Here we differentiate mouse embryonic stem cells carrying a stella transgenic reporter into putative PGCs in vitro. The Stella+ cells possess a transcriptional

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



Comparative study of the retinal nerve fibre layer thickness performed with optical coherence tomography and GDx scanning laser polarimetry in patients with primary open-angle glaucoma  

PubMed Central

Summary Background We compared the parameters of retinal nerve fibre layer in patients with advanced glaucoma with the use of different OCT (Optical Coherence Tomograph) devices in relation to analogical measurements performed with GDx VCC (Nerve Fiber Analyzer with Variable Corneal Compensation) scanning laser polarimetry. Material/Methods Study subjects had advanced primary open-angle glaucoma, previously treated conservatively, diagnosed and confirmed by additional examinations (visual field, ophthalmoscopy of optic nerve, gonioscopy), A total of 10 patients were enrolled (9 women and 1 man), aged 18–70 years of age. Nineteen eyes with advanced glaucomatous neuropathy were examined. 1) Performing a threshold perimetry Octopus, G2 strategy and ophthalmoscopy of optic nerve to confirm the presence of advanced primary open-angle glaucoma; 2) performing a GDx VCC scanning laser polarimetry of retinal nerve fibre layer; 3) measuring the retinal nerve fibre layer thickness with 3 different optical coherence tomographs. Results The parameters of the retinal nerve fibre layer thickness are highly correlated between the GDx and OCT Stratus and 3D OCT-1000 devices in mean retinal nerve fibre layer thickness, retinal nerve fibre layer thickness in the upper sector, and correlation of NFI (GDx) with mean retinal nerve fibre layer thickness in OCT examinations. Absolute values of the retinal nerve fibre layer thickness (measured in ?m) differ significantly between GDx and all OCT devices. Conclusions Examination with OCT devices is a sensitive diagnostic method of glaucoma, with good correlation with the results of GDx scanning laser polarimetry of the patients.

Wasyluk, Jaromir T.; Jankowska-Lech, Irmina; Terelak-Borys, Barbara; Grabska-Liberek, Iwona



Influence of estrogens and oxytocin on germ cells death in the neonatal mammalian ovary.  


During mammalian oogenesis, some processes involve proliferation and others drastic reduction of germ cells. This study reports on the role played by two hormones, estradiol monobenzoate and oxytocin, in the control of the number of germ cells in the neonatal mouse ovary. Female neonatal mice were treated with doses ranging between 0.1 and 1 microg/mouse of estradiol monobenzoate or oxytocin and sacrificed at 5 days of postnatal age. The results showed that in the animals treated with estrogen, follicular development was more advanced than that of controls. Further the number of germ cells in apoptosis was drastically reduced. In the animals treated with oxytocin, the follicular development was arrested at the stage of primary follicles. In addition, the number of apoptotic germ cells increased if compared with that of the controls. PMID:11732582

De Pol, A; Benelli, A; Arletti, R; Cavazzuti, E; Sena, P; Vaccina, F; Marzona, L



Bile salts of germ-free domestic fowl and pigs  

PubMed Central

1. The bile of germ-free domestic fowl contains taurine conjugates of 3?,7?-dihydroxy-5?-cholan-24-oic acid (chenodeoxycholic acid), 3?,7?,12?-trihydroxy-5?-cholan-24-oic acid (cholic acid) and its 5?-epimer (allocholic acid): that of germ-free pigs contains glycine and taurine conjugates of chenodeoxycholic acid, 3?,6?-dihydroxy-5?-cholan-24-oic acid (hyodeoxycholic acid), 3?,6?,7?-trihydroxy-5?-cholan-24-oic acid (hyocholic acid) and (probably) cholic acid. Keto acids were not found. 2. Allocholic acid and hyodeoxycholic acid are thus proved to be primary bile acids in intact animals. 3. The evolutionary and biochemical implications of these findings are briefly considered.

Haslewood, G. A. D.



Unique Aspects of Transcription Regulation in Male Germ Cells  

PubMed Central

Spermatogenesis is a complex and ordered differentiation process in which the spermatogonial stem cell population gives rise to primary spermatocytes that undergo two successive meiotic divisions followed by a major biochemical and structural reorganization of the haploid cells to generate mature elongate spermatids. The transcriptional regulatory programs that orchestrate this process have been intensively studied in model organisms such as Drosophila melanogaster and mouse. Genetic and biochemical approaches have identified the factors involved and revealed mechanisms of action that are unique to male germ cells. In a well-studied example, cofactors and pathways distinct from those used in somatic tissues mediate the action of CREM in male germ cells. But perhaps the most striking feature concerns the paralogs of somatically expressed transcription factors and of components of the general transcription machinery that act in distinct regulatory mechanisms in both Drosophila and murine spermatogenesis.

White-Cooper, Helen; Davidson, Irwin



Gastrointestinal Presentation of Germ Cell Malignancy  

Microsoft Academic Search

Objectives: To summarize monoinstitutional experience with gastrointestinal (GI) presentations of germ cell malignancy and to review recent medical literature on this issue.Methods: Retrospective review of 5 cases with advanced germ cell malignancy (testicular 2 and retroperitoneal 3) and involvement of the upper GI tract and a comparison with published observation.Results: In 4 patients the duodenum and in 1 patient the

C. Nord; S. D. Fossĺ; K. E. Giercksky



Infantile and adult testicular germ cell tumors  

Microsoft Academic Search

Most adult testicular germ cell tumors have a characteristic chromosomal abnormality that is an isochromosome 12p [i(12p)]. Furthermore, these tumors are characterized by a chromosome number in the triploid range and gains and losses of (parts of) specific chromosomes. Cytogenetic investigation of three cases of infantile testicular germ cell tumors, all diagnosed as yolk sac tumors, revealed highly abnormal karyotypes.

Jannie van Echten; Albertus Timmer; Anneke Y van der Veen; Willemina M Molenaar; Bauke de Jong



Correlation between peripapillary retinal nerve fiber layer thickness and fundus autofluorescence in primary open-angle glaucoma  

PubMed Central

Purpose To investigate the relationship between retinal nerve fiber layer (RNFL) thickness and retinal pigment epithelium alterations in patients with advanced glaucomatous visual field defects. Methods A consecutive, prospective series of 82 study eyes with primary open-angle glaucoma and advanced glaucomatous visual field defects were included in this study. All study participants underwent a full ophthalmic examination followed by visual field testing with standard automated perimetry as well as spectral-domain optical coherence tomography (SD-OCT) for peripapillary RNFL thickness and Optos wide-field fundus autofluorescence (FAF) images. A pattern grid with corresponding locations between functional visual field sectors and structural peripapillary RNFL thickness was aligned to the FAF images at corresponding location. Mean FAF intensity (range: 0 = black and 255 = white) of each evaluated sector (superotemporal, temporal, inferotemporal, inferonasal, nasal, superonasal) was correlated with the corresponding peripapillary RNFL thickness obtained with SD-OCT. Results Correlation analyses between sectoral RNFL thickness and standardized FAF intensity in the corresponding topographic retina segments revealed partly significant correlations with correlation coefficients ranging between 0.004 and 0.376 and were statistically significant in the temporal inferior central field (r = 0.324, P = 0.036) and the nasal field (r = 0.376, P = 0.014). Conclusion Retinal pigment epithelium abnormalities correlate with corresponding peripapillary RNFL damage, especially in the temporal inferior sector of patients with advanced glaucomatous visual field defects. A further evaluation of FAF as a potential predictive parameter for glaucomatous damage is necessary.

Reznicek, Lukas; Seidensticker, Florian; Mann, Thomas; Hubert, Irene; Buerger, Alexandra; Haritoglou, Christos; Neubauer, Aljoscha S; Kampik, Anselm; Hirneiss, Christoph; Kernt, Marcus



Expression of Axolotl DAZL RNA, a Marker of Germ Plasm: Widespread Maternal RNA and Onset of Expression in Germ Cells Approaching the Gonad  

Microsoft Academic Search

How germ cell specification occurs remains a fundamental question in embryogenesis. The embryos of several model organisms contain germ cell determinants (germ plasm) that segregate to germ cell precursors. In other animals, including mice, germ cells form in response to regulative mechanisms during development. To investigate germ cell determination in urodeles, where germ plasm has never been conclusively identified, we

Andrew D. Johnson; Rosemary F. Bachvarova; Matthew Drum; Thomas Masi



Cellular organization in germ tube tips of Gigaspora and its phylogenetic implications.  


Comparative morphology of the fine structure of fungal hyphal tips often is phylogenetically informative. In particular, morphology of the Spitzenkörper varies among higher taxa. To date no one has thoroughly characterized the hyphal tips of members of the phylum Glomeromycota to compare them with other fungi. This is partly due to difficulty growing and manipulating living hyphae of these obligate symbionts. We observed growing germ tubes of Gigaspora gigantea, G. margarita and G. rosea with a combination of light microscopy (LM) and transmission electron microscopy (TEM). For TEM, we used both traditional chemical fixation and cryo-fixation methods. Germ tubes of all species were extremely sensitive to manipulation. Healthy germ tubes often showed rapid bidirectional cytoplasmic streaming, whereas germ tubes that had been disturbed showed reduced or no cytoplasmic movement. Actively growing germ tubes contain a cluster of 10-20 spherical bodies approximately 3-8 ?m behind the apex. The bodies, which we hypothesize are lipid bodies, move rapidly in healthy germ tubes. These bodies disappear immediately after any cellular perturbation. Cells prepared with cryo-techniques had superior preservation compared to those that had been processed with traditional chemical protocols. For example, cryo-prepared samples displayed two cell-wall layers, at least three vesicle types near the tip and three distinct cytoplasmic zones were noted. We did not detect a Spitzenkörper with either LM or TEM techniques and the tip organization of Gigaspora germ tubes appeared to be similar to hyphae in zygomycetous fungi. This observation was supported by a phylogenetic analysis of microscopic characters of hyphal tips from members of five fungal phyla. Our work emphasizes the sensitive nature of cellular organization, and the need for as little manipulation as possible to observe germ tube structure accurately. PMID:23921242

Bentivenga, Stephen P; Kumar, T K Arun; Kumar, Leticia; Roberson, Robert W; McLaughlin, David J



Cyclophosphamide and Vaccine Therapy in Treating Patients With Stage II-III Breast, Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Recurrent Breast Cancer; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Breast Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Breast Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer



Posttranscriptional regulation of histone lysine methyltransferase GLP in embryonic male mouse germ cells.  


The epigenetic status of germ cells changes dynamically during development. In this study, we analyzed the dynamics of histone H3 lysine 9 dimethylation (H3K9me2), a highly conserved mark of epigenetic silencing, and the expression of two lysine methyltransferases, G9a/Ehmt2/KMT1C and GLP/Ehmt1/KMT1D, in murine male embryonic germ cells after sex determination. Our previous studies established that G9a and GLP are the primary enzymes for H3K9me2 and predominantly exist as a G9a-GLP heteromeric complex that appears to be a functional H3K9 methyltransferase in vivo. During the period from Embryonic Day (E) 13.5 to E18.5 in mice, gonadal H3K9me2 levels were substantially lower in germ cells than in cells of nongerm lineage. Immunohistochemical analysis showed that during this phase in development, GLP level, but not G9a level, was also significantly lower in male germ cells. However, GLP mRNA was present in E13 and E16 male germ cells, with levels similar to those in cells of nongerm lineage. Interestingly, GLP is upregulated in embryonic male germ cells deficient for Nanos2, which encodes a germ cell-specific RNA-binding protein. Our data suggest that GLP protein expression is posttranscriptionally regulated in murine embryonic male germ cells after sex determination and that low H3K9me2 level results from the absence of GLP (severe reduction of the G9a-GLP heteromeric complex). PMID:23284137

Deguchi, Katsuaki; Nagamatsu, Go; Miyachi, Hitoshi; Kato, Yuzuru; Morita, Sumiyo; Kimura, Hiroshi; Kitano, Satsuki; Hatada, Izuho; Saga, Yumiko; Tachibana, Makoto; Shinkai, Yoichi



Low frequency of HIF-1? overexpression in germ cell tumors of the testis.  


Cellular hypoxia is a hallmark of cancer. Hypoxia-inducible factor-1? (HIF-1?) and von Hippel-Lindau protein (pVHL) are the key mediators of cellular response to hypoxia. Little is known about their role in germ cell tumors of the testis. We therefore examined their status in a cohort of germ cell tumors of the testis. Thirty-six primary germ cell tumors of the testis (11 seminomas, 24 mixed germ cell tumors, and 1 case of pure intratubular germ cell neoplasia) were included in the study. HIF-1? and pVHL expression were studied using immunohistochemical (IHC) methods in the tumor and adjacent benign tissue. Selected cases with a low pVHL expression were further tested for genetic alterations using polymerase chain reaction. HIF-1? protein expression was not detectable in adjacent atrophic seminiferous tubules. In contrast, HIF-1? was expressed in one third of the malignancies, but in a low percentage of cells (mean, 3%; range, 0% to 20%). No difference in HIF-1? expression was observed between seminomas and nonseminomas (P=0.71). pVHL was expressed in atrophic tubular epithelium and in the Leydig cells, whereas a substantial loss of pVHL expression was observed in germ cell tumors regardless of the histologic type (mean, 45.6%; range, 0% to 100%). No genetic alterations of the VHL gene were observed in the cases with low pVHL expression. No significant correlation between HIF-1? and pVHL expression was observed (P=0.16). Germ cell tumors of the testis, regardless of the histologic type, are characterized by consistently low HIF-1? protein overexpression and a partial loss of pVHL without underlying VHL gene alterations. Further studies are necessary to clarify the functional importance of such alterations in testicular germ cell tumors. PMID:22820662

Vranic, Semir; Hes, Ondrej; Grossmann, Petr; Gatalica, Zoran



P Granule Assembly and Function in Caenorhabditis elegans Germ Cells  

PubMed Central

Germ granules are large, non–membrane-bound, ribonucleoprotein (RNP) organelles found in the germ line cytoplasm of most, if not all, animals. The term germ granule is synonymous with the perinuclear nuage in mouse and human germ cells. These large RNPs are complexed with germ line–specific cytoplasmic structures such as the mitochondrial cloud, intermitochondrial cement, and chromatoid bodies. The widespread presence of germ granules across species and the associated germ line defects when germ granules are compromised suggest that germ granules are key determinants of the identity and special properties of germ cells. The nematode Caenorhabditis elegans has been a very fruitful model system for the study of germ granules, wherein they are referred to as P granules. P granules contain a heterogeneous mixture of RNAs and proteins. To date, most of the known germ granule proteins across species, and all of the known P granule components in C elegans, are associated with RNA metabolism, which suggests that a main function of germ granules is posttranscriptional regulation. Here we review P granule structure and localization, P granule composition, the genetic pathway of P granule assembly, and the consequences in the germ line when P granule components are lost. The findings in C elegans have important implications for the germ granule function during postnatal germ cell differentiation in mammals.




Germ cells are required to maintain a stable sexual phenotype in adult zebrafish.  


Sex in zebrafish is not determined by a major chromosomal locus, but instead relies on a mechanism that is influenced by a germ cell-derived signal, as animals that lack germ cells, or specifically oocytes, develop as phenotypic males. These data suggest that during primary sex determination, an oocyte-derived signal acts on the bipotential somatic gonad to promote the female-specific program. However, it is not known if germ cells are required only during the primary sex-determining window, or if they are required throughout adult life to maintain the female sexual phenotype. Here, we show that while wild-type zebrafish do not switch sex as adults, germ cell-depleted adult females readily convert to a male phenotype. Notably, when oocytes are depleted, but germline stem cells remain, adult females sex-revert to sperm-producing males, indicating that a germ cell-derived signal acts on the somatic gonad to promote female development directly or indirectly by repressing male-specific gene expression. These results also confirm that signals from the somatic gonad in turn ensure that the sex appropriate gamete is produced. PMID:23348677

Dranow, Daniel B; Tucker, Richard P; Draper, Bruce W



GermSAGE: a comprehensive SAGE database for transcript discovery on male germ cell development  

Microsoft Academic Search

GermSAGE is a comprehensive web-based database generated by Serial Analysis of Gene Expression (SAGE) representing major stages in mouse male germ cell development, with 150000 sequence tags in each SAGE library. A total of 452095 tags derived from type A spermatogonia (Spga), pachytene sper- matocytes (Spcy) and round spermatids (Sptd) were included. GermSAGE provides web-based tools for browsing, comparing and

Tin-lap Lee; Hoi-hung Cheung; Janek Claus; Chandan Sastry; Sumeeta Singh; Loc Vu; Owen Rennert; Wai-yee Chan



Effect of diclofenac on germ cell apoptosis following testicular ischemia-reperfusion injury in a rat.  


Recent evidence suggests that enhanced cell apoptosis is responsible for germ cell loss following testicular ischemia-reperfusion (IR) injury. A nonsteroidal anti-inflammatory drug diclofenac sodium (Voltaren) is a prostaglandin-synthesis inhibitor, which is widely used in many testicular disorders. The purpose of the present study was to examine the effect of diclofenac (DIC) on germ cell apoptosis in the ischemic and contralateral testes following testicular IR in a rat. Forty rats were divided randomly into four experimental groups of ten rats each: group A (Sham)-Sham operated animals; group B (Sham-DIC)-Sham operated rats that were treated with DIC given subcutaneously at a dose of 10 mg/kg, once daily, 24, 48 and 72 h following operation; group C (IR) underwent 90 min of unilateral testicular IR; group D (IR-DIC)-rats underwent 90 min of unilateral testicular IR and were treated with DIC similarly to group B. Ninety-six hours following operation, the rats were sacrificed and testes were harvested. Johnsen's criteria and the number of germinal cell layers were used to categorize the spermatogenesis. TUNEL assay was used to determine germ cell apoptosis in both the ischemic and contralateral testes. Statistical analysis was performed using the non-parametric Kruskal-Wallis ANOVA test, with P less than 0.05 considered statistically significant. Testicular ischemia in rats led to histological damage in the ipsilateral testis. In the contralateral testis, minimal damage was observed. Germ cell apoptosis in both the ischemic and the contralateral testes increased significantly after IR. Treatment with DIC did not change histologic parameters of spermatogenesis in both the ischemic and contralateral testes, but decreased germ cell apoptosis in both testes following testicular IR. We conclude that testicular ischemia causes an increase in germ cell apoptosis in the contralateral testis. Diclofenac may be beneficial for spermatogenesis following testicular IR by decreasing germ cell apoptosis. PMID:16283337

Mogilner, Jorge G; Lurie, Michael; Coran, Arnold G; Nativ, Ofer; Shiloni, Eitan; Sukhotnik, Igor



Expression of Axdazl and Axvh in Axolotl Germ Cells, Suggest that Regulative Germ Cell Specification is a Primitive Trait Conserved in the Mammalian Lineage  

Microsoft Academic Search

How germ cells are specified in animal embryos has been a mystery for decades. Unlike most developmental processes, which are highly conserved, embryos specify germ cells in very different ways. The embryos of several prominent model organisms contain germ cell determinants (germ plasm) that segregate to germ cell precursors. In other animals, including mice, germ cells form in response to

Matthew John Drum



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

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



Germ Plasm and Germ-line Cell Determination: The Role of Mitochondria  

Microsoft Academic Search

Literature data on the structure and origin of material of the germ cell line determinants and on the presence of products of nuclear and mitochondrial genomes in the structured germ determinants (nuage) are reviewed. The personal data, obtained on spermatogenic cells of sea urchin and of other marine invertebrates, evidence the transformation of the mitochondrial matrix into the nuage material.

V. V. Isaeva; A. A. Reunov



Intracranial germ cell tumors at unusual locations.  


Germ cell tumor (GCT) is relatively uncommon in intracranial locations. They constitute ~ 0.3-0.6% of intracranial neoplasms and encompass a wide pathologic range. The majority occurs in young adults and occupies the midline locations like pineal gland followed by suprasellar compartment. These tumors are rare in the cerebral hemisphere, basal ganglia, thalamus and ventricles. Neuroimaging studies cannot differentiate GCTs from other tumors, and therefore, the diagnosis usually requires histological confirmation. Germ cell tumors can be divided into major groups including germinomas and nongerminomatous GCTs (NGGCTs). Their proper identification as well as histopathological typing is important as treatment and prognosis vary greatly between different groups. Germinomas have a superior prognosis and are more radiosensitive as compared to non-germinomatous germ cell tumors. Standard management is still controversial. In this case series we are presenting three cases of intracranial germ cell tumors arising in two unusual locations, that is intraventricular and thalamic region. Apart from the clinical, radiological, histopathological and surgical details we also discuss the various aspects of intracranial germ cell tumors. PMID:23298924

Rana, C; Krishnani, N; Kumar, R


Tensile forces govern germ-layer organization in zebrafish  

Microsoft Academic Search

1 . However, validating these hypotheses has been difficult due to the lack of appropriate tools to measure these parameters. Here we use atomic force microscopy (AFM) to quantify the adhesive and mechanical properties of individual ectoderm, mesoderm and endoderm progenitor cells from gastrulating zebrafish embryos. Combining these data with tissue self-assembly in vitro and the sorting behaviour of progenitors

M. Krieg; Y. Arboleda-Estudillo; P.-H. Puech; J. Käfer; F. Graner; D. J. Müller; C.-P. Heisenberg



Rebuilding Pluripotency from Primordial Germ Cells  

PubMed Central

Mammalian primordial germ cells (PGCs) are unipotent progenitors of the gametes. Nonetheless, they can give rise directly to pluripotent stem cells in vitro or during teratocarcinogenesis. This conversion is inconsistent, however, and has been difficult to study. Here, we delineate requirements for efficient resetting of pluripotency in culture. We demonstrate that in defined conditions, routinely 20% of PGCs become EG cells. Conversion can occur from the earliest specified PGCs. The entire process can be tracked from single cells. It is driven by leukemia inhibitory factor (LIF) and the downstream transcription factor STAT3. In contrast, LIF signaling is not required during germ cell ontogeny. We surmise that ectopic LIF/STAT3 stimulation reconstructs latent pluripotency and self-renewal. Notably, STAT3 targets are significantly upregulated in germ cell tumors, suggesting that dysregulation of this pathway may underlie teratocarcinogenesis. These findings demonstrate that EG cell formation is a robust experimental system for exploring mechanisms involved in reprogramming and cancer.

Leitch, Harry G.; Nichols, Jennifer; Humphreys, Peter; Mulas, Carla; Martello, Graziano; Lee, Caroline; Jones, Ken; Surani, M. Azim; Smith, Austin



"Life in a Germ-Free World":  

PubMed Central

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.

Kirk, Robert G. W.



Enhanced genetic integrity in mouse germ cells.  


Genetically based diseases constitute a major human health burden, and de novo germline mutations represent a source of heritable genetic alterations that can cause such disorders in offspring. The availability of transgenic rodent systems with recoverable, mutation reporter genes has been used to assess the occurrence of spontaneous point mutations in germline cells. Previous studies using the lacI mutation reporter transgenic mouse system showed that the frequency of spontaneous mutations is significantly lower in advanced male germ cells than in somatic cell types from the same individuals. Here we used this same mutation reporter transgene system to show that female germ cells also display a mutation frequency that is lower than that in corresponding somatic cells and similar to that seen in male germ cells, indicating this is a common feature of germ cells in both sexes. In addition, we showed that statistically significant differences in mutation frequencies are evident between germ cells and somatic cells in both sexes as early as mid-fetal stages in the mouse. Finally, a comparison of the mutation frequency in a general population of early type A spermatogonia with that in a population enriched for Thy-1-positive spermatogonia suggests there is heterogeneity among the early spermatogonial population such that a subset of these cells are predestined to form true spermatogonial stem cells. Taken together, these results support the disposable soma theory, which posits that genetic integrity is normally maintained more stringently in the germ line than in the soma and suggests that this is achieved by minimizing the initial occurrence of mutations in early germline cells and their subsequent gametogenic progeny relative to that in somatic cells. PMID:23153565

Murphey, Patricia; McLean, Derek J; McMahan, C Alex; Walter, Christi A; McCarrey, John R



Visual Field Defects and Normal Nerve Fiber Layer: May They Coexist in Primary Open-Angle Glaucoma?  

Microsoft Academic Search

The retinal nerve fiber layer (RNFL) is the anatomical structure most sensitive to glaucoma injury. Before a functional loss such as a visual field defect is displayed, a large number of nerve fibers can be damaged. However, there are glaucoma patients in which an apparently normal RNFL coexists with evident visual field defects. A total of 54 eyes affected with

Renato De Natale; Michele Marraffa; Roberta Morbio; Laura Tomazzoli; Luciano Bonomi



Synchronous Chaos and Broad Band Gamma Rhythm in a Minimal Multi-Layer Model of Primary Visual Cortex  

PubMed Central

Visually induced neuronal activity in V1 displays a marked gamma-band component which is modulated by stimulus properties. It has been argued that synchronized oscillations contribute to these gamma-band activity. However, analysis of Local Field Potentials (LFPs) across different experiments reveals considerable diversity in the degree of oscillatory behavior of this induced activity. Contrast-dependent power enhancements can indeed occur over a broad band in the gamma frequency range and spectral peaks may not arise at all. Furthermore, even when oscillations are observed, they undergo temporal decorrelation over very few cycles. This is not easily accounted for in previous network modeling of gamma oscillations. We argue here that interactions between cortical layers can be responsible for this fast decorrelation. We study a model of a V1 hypercolumn, embedding a simplified description of the multi-layered structure of the cortex. When the stimulus contrast is low, the induced activity is only weakly synchronous and the network resonates transiently without developing collective oscillations. When the contrast is high, on the other hand, the induced activity undergoes synchronous oscillations with an irregular spatiotemporal structure expressing a synchronous chaotic state. As a consequence the population activity undergoes fast temporal decorrelation, with concomitant rapid damping of the oscillations in LFPs autocorrelograms and peak broadening in LFPs power spectra. We show that the strength of the inter-layer coupling crucially affects this spatiotemporal structure. We predict that layer VI inactivation should induce global changes in the spectral properties of induced LFPs, reflecting their slower temporal decorrelation in the absence of inter-layer feedback. Finally, we argue that the mechanism underlying the emergence of synchronous chaos in our model is in fact very general. It stems from the fact that gamma oscillations induced by local delayed inhibition tend to develop chaos when coupled by sufficiently strong excitation.

Battaglia, Demian; Hansel, David



Turning Points in Science: Germ Theory  

NSDL National Science Digital Library

This resource guide from the Middle School Portal 2 project, written specifically for teachers, provides links to exemplary resources including background information, lessons, career information, and related national science education standards. Germ theory represents the culmination of the work of several individuals across time. Resources provided here will facilitate understanding of the early scientific community's concept of disease; the thinking that led to hypotheses relating germs to disease; the various observations and experiments that yielded information allowing for theorizing; the scientific community's reaction to and acceptance of the early investigators' findings; and the impacts of the theory on humanity.

Lefever, Mary



Principal component and cluster analysis of layer V pyramidal cells in visual and non-visual cortical areas projecting to the primary visual cortex of the mouse.  


The long-distance corticocortical connections between visual and nonvisual sensory areas that arise from pyramidal neurons located within layer V can be considered as a subpopulation of feedback connections. The purpose of the present study is to determine if layer V pyramidal neurons from visual and nonvisual sensory cortical areas that project onto the visual cortex (V1) constitute a homogeneous population of cells. Additionally, we ask whether dendritic arborization relates to the target, the sensory modality, the hierarchical level, or laterality of the source cortical area. Complete 3D reconstructions of dendritic arbors of retrogradely labeled layer V pyramidal neurons were performed for neurons of the primary auditory (A1) and somatosensory (S1) cortices and from the lateral (V2L) and medial (V2M) parts of the secondary visual cortices of both hemispheres. The morphological parameters extracted from these reconstructions were subjected to principal component analysis (PCA) and cluster analysis. The PCA showed that neurons are distributed within a continuous range of morphologies and do not form discrete groups. Nevertheless, the cluster analysis defines neuronal groups that share similar features. Each cortical area includes neurons belonging to several clusters. We suggest that layer V feedback connections within a single cortical area comprise several cell types. PMID:22426333

Laramée, M E; Rockland, K S; Prince, S; Bronchti, G; Boire, D



A note on a strong germ-Markov property  

Microsoft Academic Search

In a seminal paper on Markovian germ fields, Knight [2] proposes five distinct definitions of the infinitesimal present and shows that these alternative formulations all lead to the same class of germ-Markov processes, but that they lead to different classes of strong germ-Markov processes. The same paper asserts that every germ-Markov process is strongly Markovian relative to a certain right

David M. Malon



Transgenesis and nuclear transfer using porcine embryonic germ cells.  


Embryonic germ (EG) cells are undifferentiated stem cells isolated from cultured primordial germ cells (PGC). Porcine EG cell lines with capacities of both in vitro and in vivo differentiation have been established. Because EG cells can be cultured indefinitely in an undifferentiated state, they may be more suitable for nuclear donor cells in nuclear transfer (NT) than somatic cells that have limited lifespan in primary culture. Use of EG cells could be particularly advantageous to provide an inexhaustible source of transgenic cells for NT. In this study the efficiencies of transgenesis and NT using porcine fetal fibroblasts and EG cells were compared. The rate of development to the blastocyst stage was significantly higher in EG cell NT than somatic cell NT (94 of 518, 18.2% vs. 72 of 501, 14.4%). To investigate if EG cells can be used for transgenesis in pigs, green fluorescent protein (GFP) gene was introduced into porcine EG cells. Nuclear transfer embryos using transfected EG cells gave rise to blastocysts (29 of 137, 21.2%) expressing GFP based on observation under fluorescence microscope. The results obtained from the present study suggest that EG cell NT may have advantages over somatic cell NT, and transgenic pigs may be produced using EG cells. PMID:18154507

Ahn, Kwang Sung; Won, Ji Young; Heo, Soon Young; Kang, Jee Hyun; Yang, Hong Seok; Shim, Hosup



Ectopic expression of Cvh (Chicken Vasa homologue) mediates the reprogramming of chicken embryonic stem cells to a germ cell fate.  


When they are derived from blastodermal cells of the pre-primitive streak in vitro, the pluripotency of Chicken Embryonic Stem Cells (cESC) can be controlled by the cPouV and Nanog genes. These cESC can differentiate into derivatives of the three germ layers both in vitro and in vivo, but they only weakly colonize the gonads of host embryos. By contrast, non-cultured blastodermal cells and long-term cultured chicken primordial germ cells maintain full germline competence. This restriction in the germline potential of the cESC may result from either early germline determination in the donor embryos or it may occur as a result of in vitro culture. We are interested in understanding the genetic determinants of germline programming. The RNA binding protein Cvh (Chicken Vasa Homologue) is considered as one such determinant, although its role in germ cell physiology is still unclear. Here we show that the exogenous expression of Cvh, combined with appropriate culture conditions, induces cESC reprogramming towards a germ cell fate. Indeed, these cells express the Dazl, Tudor and Sycp3 germline markers, and they display improved germline colonization and adopt a germ cell fate when injected into recipient embryos. Thus, our results demonstrate that Vasa can drive ES cell differentiation towards the germ cell lineage, both in vitro and in vivo. PMID:19324033

Lavial, Fabrice; Acloque, Hervé; Bachelard, Elodie; Nieto, M Angela; Samarut, Jacques; Pain, Bertrand



Divergent RNA-Binding Proteins, DAZL and VASA, Induce Meiotic Progression in Human Germ Cells Derived In Vitro  

PubMed Central

Our understanding of human germ cell development is limited in large part due to inaccessibility of early human development to molecular genetic analysis. Pluripotent human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been shown to differentiate to cells of all three embryonic germ layers, as well as germ cells in vitro, and thus may provide a model for the study of the genetics and epigenetics of human germline. Here, we examined whether intrinsic germ cell translational, rather than transcriptional, factors might drive germline formation and/or differentiation from human pluripotent stem cells in vitro. We observed that, with overexpression of VASA (DDX4) and/or DAZL (Deleted in Azoospermia Like), both hESCs and iPSCs differentiated to primordial germ cells, and maturation and progression through meiosis was enhanced. These results demonstrate that evolutionarily unrelated and divergent RNA-binding proteins can promote meiotic progression of human-derived germ cells in vitro. These studies describe an in vitro model for exploring specifics of human meiosis, a process that is remarkably susceptible to errors that lead to different infertility-related diseases.

Medrano, Jose v.; Ramathal, Cyril; Nguyen, Ha N.; Simon, Carlos; Pera, Renee A. Reijo




Microsoft Academic Search

Wheat germ is one of the richest natural sources of alpha tocopherol, which possesses vitamin E activity. Wheat germ oil has a number of health benefits such as reducing plasma and liver cholesterol levels, improving physical endurance\\/fitness and delaying aging. The health benefits of wheat germ oil are attributed to its high vitamin E, polyunsaturat ed fatty acid and long

Nurhan Turgut Dunford; Jose L. Martinez


Evaluation of corn germ meal as extender in plywood adhesive  

Technology Transfer Automated Retrieval System (TEKTRAN)

This study was conducted to evaluate the potential of corn germ meal as protein extender in plywood adhesive. Partially defatted dried corn germ, containing 2.1% (dry basis, db) crude oil and 24.7% (db) crude protein, was ground to 40-mesh particle size. The corn germ meal was then substituted (on...


The Drosophila protein Wunen repels migrating germ cells  

Microsoft Academic Search

INDrosophila, germ cells migrate in embryonic development from the lumen of the developing gut towards the overlying mesoderm, where they enter the gonads1,2. The gene wunen is responsible for guiding the germ cells early in this process3. Here we report that the protein Wunen has two properties that allow it to use repulsion to guide the germ cells. Wunen can

Nian Zhang; Jiaping Zhang; Karen J. Purcell; Yan Cheng; Ken Howard



Colleges Put the Squeeze on Germs  

ERIC Educational Resources Information Center

|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 clean them,…

Sander, Libby



Modelling germ cell development in vitro  

PubMed Central

Germ cells have a critical role in mediating the generation of genetic diversity and transmitting this information across generations. Furthermore, gametogenesis is unique as a developmental process in that it generates highly-specialized haploid gametes from diploid precursor stem cells through meiosis. Despite the importance of this process, progress in elucidating the molecular mechanisms underpinning mammalian germ cell development has been retarded by the lack of an efficient and reproducible system of in vitro culture for the expansion and trans-meiotic differentiation of germline cells. The dearth of such a culture system has rendered the study of germ cell biology refractory to the application of new high-throughput technologies such as RNA interference, leaving in vivo gene-targeting approaches as the only option to determine the function of genes believed to be involved in gametogenesis. Recent reports detailing the derivation of gametes in vitro from stem cells may provide the first steps in developing new tools to solve this problem. This review considers the developments made in modelling germ cell development using stem cells, and some of the challenges that need to be overcome to make this a useful tool for studying gametogenesis and to realize any future clinical application.

Childs, Andrew J.; Saunders, Philippa T.K.; Anderson, Richard A.



Modulation of MAA-induced apoptosis in male germ cells: role of Sertoli cell P/Q-type calcium channels  

PubMed Central

Spontaneous germ cell death by apoptosis occurs during normal spermatogenesis in mammals and is thought to play a role in the physiological mechanism limiting the clonal expansion of such cell population in the male gonad. In the prepubertal rat testis, the most conspicuous dying cells are pachytene spermatocytes, which are also the primary target of the apoptosis experimentally induced by the methoxyacetic acid (MAA). Since we have recently reported that Sertoli cells, the somatic component of the seminiferous epithelium, regulate not only germ cell viability and differentiation but also their death, we have further investigated the mechanism involved in such a control. In this paper we have used the protein clusterin, produced by Sertoli cells and associated with tissue damage or injury, as indicator of germ cell apoptosis in rat seminiferous tubules treated with MAA in the presence or in the absence of omega-agatoxin, a specific inhibitor of P/Q type voltage-operated calcium channels (VOCC's). We performed both a qualitative analysis of clusterin content and germ cell apoptosis by immunofluorescence experiments and a quantitative analysis by in situ end labelling of apoptotic germ cells followed by flow cytometry. The results obtained demonstrate that Sertoli cells modulate germ cell apoptosis induced by methoxyacetic acid also throughout the P/Q-type VOCC's.

Barone, Fortunata; Aguanno, Salvatore; D'Agostino, Angela



Modulation of MAA-induced apoptosis in male germ cells: role of Sertoli cell P/Q-type calcium channels.  


Spontaneous germ cell death by apoptosis occurs during normal spermatogenesis in mammals and is thought to play a role in the physiological mechanism limiting the clonal expansion of such cell population in the male gonad. In the prepubertal rat testis, the most conspicuous dying cells are pachytene spermatocytes, which are also the primary target of the apoptosis experimentally induced by the methoxyacetic acid (MAA). Since we have recently reported that Sertoli cells, the somatic component of the seminiferous epithelium, regulate not only germ cell viability and differentiation but also their death, we have further investigated the mechanism involved in such a control. In this paper we have used the protein clusterin, produced by Sertoli cells and associated with tissue damage or injury, as indicator of germ cell apoptosis in rat seminiferous tubules treated with MAA in the presence or in the absence of omega-agatoxin, a specific inhibitor of P/Q type voltage-operated calcium channels (VOCC's). We performed both a qualitative analysis of clusterin content and germ cell apoptosis by immunofluorescence experiments and a quantitative analysis by in situ end labelling of apoptotic germ cells followed by flow cytometry. The results obtained demonstrate that Sertoli cells modulate germ cell apoptosis induced by methoxyacetic acid also throughout the P/Q-type VOCC's. PMID:15840169

Barone, Fortunata; Aguanno, Salvatore; D'Agostino, Angela



Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells.  


Foetal development of germ cells is a unique biological process orchestrated by cellular specification, migration and niche development in concert with extensive epigenetic and transcriptional programs. Many of these processes take place early in foetal life and are hence very difficult to study in humans. However, the common precursor of testicular cancers- the carcinoma in situ (CIS) cell- is thought to be an arrested foetal germ cell. Therefore studies of CIS cells may leverage information on human foetal germ cell development and, in particular, when neoplastic transformation is initiated. In this review, we will focus on current knowledge of the epigenetics of CIS cells and relate it to the epigenetic changes occurring in early developing germ cells of mice during specification, migration and colonization. We will focus on DNA methylation and some of the best studied histone modifications like H3K9me2, H3K27me3 and H3K9ac. We also show that CIS cells contain high levels of H3K27ac, which is known to mark active enhancers. Proper epigenetic reprogramming seems to be a pre-requisite of normal foetal germ cell development and we propose that alterations in these programs may be a pathogenic event in the initiation of testicular germ cell cancer. Even though only sparse information is available on epigenetic cues in human foetal germ cells, these indicate that the developmental patterns differ from the findings in mice and emphasize the need for further studies of foetal germ cell development in humans. PMID:23784842

Kristensen, Dina G; Skakkebćk, Niels E; Rajpert-De Meyts, Ewa; Almstrup, Kristian



Testicular germ cell tumor seven years after a retroperitoneal germ cell tumor.  


A 44-year-old male was diagnosed in August 1980 as having a retroperitoneal germ cell tumor (classic seminoma with anaplastic areas). After treatment with cisplatin-based chemotherapy, he reached complete clinical and pathological remission. Eighty-eight months later, in December 1987, he was diagnosed as having a testicular mixed germ cell tumor (embryonal carcinoma with anaplastic seminoma areas) after right orchiectomy. The potential mechanisms by which the latter tumor could have developed are discussed. PMID:1655464

González Quintela, A; López Bonet, E; Román, J; Aramburo, P



Spontaneous Germ Cell Apoptosis in Humans: Evidence for Ethnic Differences in the Susceptibility of Germ Cells to Programmed Cell Death  

Microsoft Academic Search

Spontaneous death of certain classes of germ cells has been shown to be a constant feature of normal spermatogenesis in a variety of mammalian species, including the human. Recent studies on various animal models have demonstrated that apoptosis is the underlying mechanism of germ cell death during normal spermatogenesis. With- drawal of gonadotropins and\\/or testosterone further accelerates the germ cell




Nodal/Cripto signaling in fetal male germ cell development: implications for testicular germ cell tumors.  


Testicular cancer is the most frequent cancer in young men aged 15-40 years and accounts for 1% of all cancer diagnosed in males. Testicular germ cell tumors (TGCT) encompass a broad group of cancers, each displaying different levels of pluripotency and differentiation as well as malignancy potential. The TGCT cell of origin is thought to be a fetal germ cell that failed to correctly differentiate during development: this is known as the ?fetal origins hypothesis?. This theory predicts that developmental pathways that control germ cell pluripotency or differentiation may be involved in the malignant transformation of these cells. Recently the Nodal/Cripto signaling pathway, known to control pluripotency and differentiation in embryonic stem (ES) cells, was implicated in regulating normal male fetal germ cell pluripotency. Although genes of this pathway are not normally expressed in germ cells during adult life, ectopic expression of this pathway was detected in several sub-groups of TGCTs. In this review, we consider the evidence for the fetal origins of TGCT and discuss the implications of Nodal/Cripto signaling in various aspects of germ cell development and cancer progression. PMID:23784832

Spiller, Cassy M; Bowles, Josephine; Koopman, Peter



NANOS3 function in human germ cell development  

PubMed Central

Human infertility is common and frequently linked to poor germ cell development. Yet, human germ cell development is poorly understood, at least in part due to the inaccessibility of germ cells to study especially during fetal development. Here, we explored the function of a highly conserved family of genes, the NANOS genes, in the differentiation of human germ cells from human embryonic stem cells. We observed that NANOS-1, -2 and -3 mRNAs and proteins were expressed in human gonads. We also noted that NANOS3 was expressed in germ cells throughout spermatogenesis and oogenesis and thus, focused further efforts on this family member. NANOS3 expression was highest in human germ cell nuclei where the protein co-localized with chromosomal DNA during mitosis/meiosis. Reduced expression of NANOS3 (via morpholinos or short hairpin RNA) resulted in a reduction in germ cell numbers and decreased expression of germ cell-intrinsic genes required for the maintenance of pluripotency and meiotic initiation and progression. These data provide the first direct experimental evidence that NANOS3 functions in human germ cell development; indeed, NANOS3 is now one of just two genes that has been directly shown to function in germ cell development across diverse species from flies, worms, frogs and mice to humans [the other is BOULE, a member of the Deleted in Azoospermia (DAZ) gene family]. Findings may contribute to our understanding of the basic biology of human germ cell development and may provide clinical insights regarding infertility.

Julaton, Vanessa T. Angeles; Reijo Pera, Renee A.



Dose intensity in germ cell cancer: continued lessons from a model neoplasm.  


Clinical trials of chemotherapy in germ cell cancer have explored the full range of dose intensity. In good risk patients, efforts have been successful in diminishing duration of treatment or number of drugs required to cure the illness reliably. In patients with poor prognosis, efforts to intensify therapy have been undertaken. It has been difficult to demonstrate improved outcome using higher doses of conventional agents in the setting of primary treatment of poor risk disease. It is more likely that improvement will come with the discovery of new active agents. High dose chemotherapy with bone marrow or peripheral blood stem cell support can cure a small portion of selected patients with multiple recurrences of germ cell cancer. The impact of earlier treatment with high dose chemotherapy as initial salvage therapy or even primary treatment is less certain. Clinical trials in these settings have not yet demonstrated a definite advantage over less toxic conventional dose therapies. PMID:8386654

Nichols, C R; Roth, B J; Broun, E R; Loehrer, P J; Williams, S D; Einhorn, L H



Epigenetic reprogramming in the porcine germ line  

PubMed Central

Background Epigenetic reprogramming is critical for genome regulation during germ line development. Genome-wide demethylation in mouse primordial germ cells (PGC) is a unique reprogramming event essential for erasing epigenetic memory and preventing the transmission of epimutations to the next generation. In addition to DNA demethylation, PGC are subject to a major reprogramming of histone marks, and many of these changes are concurrent with a cell cycle arrest in the G2 phase. There is limited information on how well conserved these events are in mammals. Here we report on the dynamic reprogramming of DNA methylation at CpGs of imprinted loci and DNA repeats, and the global changes in H3K27me3 and H3K9me2 in the developing germ line of the domestic pig. Results Our results show loss of DNA methylation in PGC colonizing the genital ridges. Analysis of IGF2-H19 regulatory region showed a gradual demethylation between E22-E42. In contrast, DMR2 of IGF2R was already demethylated in male PGC by E22. In females, IGF2R demethylation was delayed until E29-31, and was de novo methylated by E42. DNA repeats were gradually demethylated from E25 to E29-31, and became de novo methylated by E42. Analysis of histone marks showed strong H3K27me3 staining in migratory PGC between E15 and E21. In contrast, H3K9me2 signal was low in PGC by E15 and completely erased by E21. Cell cycle analysis of gonadal PGC (E22-31) showed a typical pattern of cycling cells, however, migrating PGC (E17) showed an increased proportion of cells in G2. Conclusions Our study demonstrates that epigenetic reprogramming occurs in pig migratory and gonadal PGC, and establishes the window of time for the occurrence of these events. Reprogramming of histone H3K9me2 and H3K27me3 detected between E15-E21 precedes the dynamic DNA demethylation at imprinted loci and DNA repeats between E22-E42. Our findings demonstrate that major epigenetic reprogramming in the pig germ line follows the overall dynamics shown in mice, suggesting that epigenetic reprogramming of germ cells is conserved in mammals. A better understanding of the sequential reprogramming of PGC in the pig will facilitate the derivation of embryonic germ cells in this species.



A primary analysis of microwave brightness temperature of lunar surface from Chang-E 1 multi-channel radiometer observation and inversion of regolith layer thickness  

NASA Astrophysics Data System (ADS)

In China’s first lunar exploration project, Chang-E 1 (CE-1), a multi-channel microwave radiometer was aboard the satellite, with the purpose of measuring microwave brightness temperature (Tb) from lunar surface and surveying the global distribution of lunar regolith layer thickness. In this paper, the primary 621 tracks of swath data measured by CE-1 microwave radiometer from November 2007 to February 2008 are collected and analyzed. Using the nearest neighbor interpolation to collect the Tb data under the same Sun illumination, global distributions of microwave brightness temperature from lunar surface at lunar daytime and nighttime are constructed. Based on the three-layer media modeling (the top dust-soil, regolith and underlying rock media) for microwave thermal emission of lunar surface, the CE-1 measured Tb and its dependence upon latitude, frequency and FeO + TiO2 content, etc. are discussed. The CE-1 Tb data at Apollo landing sites are especially chosen for validation and calibration on the basis of available ground measurements. Using the empirical dependence of physical temperature upon the latitude verified by the CE-1 multi-channel Tb data at Apollo landing sites, the global distribution of regolith layer thickness is further inverted from the CE-1 brightness temperature data at 3 GHz channel. Those inversions at Apollo landing sites and the characteristics of regolith layer thickness for lunar maria are well compared with the Apollo in situ measurements and the regolith thickness derived from the Earth-based radar data. Finally, the statistical distribution of regolith thickness is analyzed and discussed.

Fa, Wenzhe; Jin, Ya-Qiu



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

PubMed Central

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.

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



Glutathione S-transferase expression in the human testis and testicular germ cell neoplasia.  

PubMed Central

Glutathione S-transferase (GST) isoenzyme expression is altered in a variety of neoplasms and the enzymes are implicated in metabolism of carcinogens and resistance to drugs, including cisplatin. We have studied GST Alpha, Pi, Mu and microsomal isoenzyme expression by immunohistochemistry in normal and cryptorchid testes, intratubal germ cell neoplasia (ITGCN), seminoma and non-seminomatous germ cell tumours. In 16 stage II-IV malignant teratoma intermediate (MTI) both orchidectomy and post-treatment residual surgical masses were studied. All four isoenzymes were strongly expressed in Leydig and Sertoli cells. GST Pi was absent from normal spermatogonia but strongly expressed by the neoplastic germ cells of ITGCN and seminoma. GST Pi was strongly expressed in all elements of teratoma, irrespective of differentiation. There were no qualitative differences in expression between primary and post-chemotherapy metastases. GST Alpha expression in teratoma correlated with epithelial differentiation. GSTs may be important in normal spermatogenesis and protection of germ cells from teratogens and carcinogens. They may have a role in testicular tumour drug resistance but this role is not well defined. GST Pi is a new marker for ITGCN. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6

Klys, H. S.; Whillis, D.; Howard, G.; Harrison, D. J.



Sertoli cell modulates MAA-induced apoptosis of germ cells throughout voltage-operated calcium channels.  


Spontaneous cell death by apoptosis--occurring during normal spermatogenesis in mammals--is a prominent event, which results in the loss of up to 75% of the potential number of mature spermatozoa. In the rat testis, the most conspicuous dying cells are pachytene spermatocytes, which are also the primary target of the apoptosis experimentally induced by methoxyacetic acid (MAA). In this paper, we have used clusterin expression as an indicator of germ cell apoptosis in rat seminiferous tubules treated with MAA in the presence or in the absence of voltage-operated calcium channels (VOCCs) inhibitors. We performed both a qualitative analysis of clusterin expression by immunofluorescence experiments and a quantitative analysis of apoptosis by in situ end labeling of apoptotic germ cells followed by flow cytometry. The results obtained demonstrate that Sertoli cells, the somatic component of the seminiferous epithelium, which control male germ cell differentiation, also modulate MAA-induced apoptosis of germ cells throughout voltage-operated calcium channels. PMID:14656996

Barone, Fortunata; Aguanno, Salvatore; D'Alessio, Alessio; D'Agostino, Angela



Germ cell restricted expression of chick Nanog.  


Nanog is a pluripotency-associated factor expressed in embryonic stem cells and in the epiblast and primordial germ cells of the mouse embryo. We have identified the chick orthologue of Nanog and found that its expression is limited to primordial germ cells in the early embryo and is not found throughout the epiblast. Genomic analysis has shown that Nanog is an amniote-specific gene and is absent from anamniotes and invertebrates. Furthermore, other pluripotency associated genes that are located in close proximity to Nanog in human and mouse are absent from the chick genome. Such observations lead to a scenario of sequential addition of novel genes to a genomic region associated to pluripotency. These results have profound implications for the study of the evolution of pluripotent lineages in the embryo and of vertebrate stem cells. PMID:16921504

Cańón, Susana; Herranz, Cristina; Manzanares, Miguel



Management of Recurrent Testicular Germ Cell Tumors  

Microsoft Academic Search

Although front-line chemotherapy cures most men with testicular germ cell tumors, salvage therapy is still impor- tant in a small but significant minority. Second-line con- ventional-dose or high-dose chemotherapy with stem cell rescue may cure 25%-50% of patients. New chemothera- peutic agents, including the taxanes gemcitabine and ox- aliplatin, have added to the therapeutic armamentarium. Salvage surgical resection has an



Purification of Wheat Germ Amylase by Precipitation  

Microsoft Academic Search

?-Amylase from various sources was found to bind alginate in free solution. The alginate–enzyme complex could be precipitated with Ca2+. The enzyme activity could be recovered by dissolving the precipitate in 1 M maltose and precipitating alginate alone by addition of Ca2+. Based upon these observations, ?-amylase from wheat germ was purified with 68-fold purification and 72% recovery. The molecular

Aparna Sharma; Shweta Sharma; M. N. Gupta



Complex Maslov germs in abstract spaces  

NASA Astrophysics Data System (ADS)

For various evolution equations for an element of a Hilbert space one uses different asymptotic methods to construct approximate solutions of these equations, which are expressed in terms of points (that are time-dependent and satisfy certain equations) in a smooth manifold {\\mathscr Y} and elements of a Hilbert space {\\mathscr F}_y. In the present paper the properties of asymptotic solutions are studied under fairly general assumptions on the map associating a pair y\\in {\\mathscr Y}, f\\in {\\mathscr F}_y with an asymptotic formula. An analogue of the concept of complex Maslov germ is introduced in the abstract case and its properties are studied. An analogue of the theory of Lagrangian manifolds with complex germ is discussed. The connection between the existence of an invariant complex germ and the stability of the solution of the equation for a point in the smooth manifold {\\mathscr Y} is investigated. The results so obtained can be used for the construction and geometric interpretation of new asymptotic solutions of evolution equations in the case when some class of asymptotic solutions is already known.

Shvedov, O. Yu



Germ granules in spermatogenesis of Drosophila  

PubMed Central

Ribonucleoprotein-containing granules in the cytoplasm of germinal cells are known to be a common attribute of eukaryotic organisms. Germ granules appear to ensure the posttranscriptional regulation of germline mRNAs. Recent studies specify the participation of the germ granules in genome integrity maintenance by mechanisms involving short piRNAs. PIWI clade proteins and associated piRNAs are considered as key participants of the germline-specific piRNA pathway. Proteins of the PIWI clade, Aub and AGO3, concentrated in the germline-specific perinuclear granules called nuage, are involved in silencing of retrotransposons and other selfish repetitive elements in the Drosophila genome. In Drosophila testes, two types of perinuclear nuage granules are found: a large amount of small particles around the nuclei and significantly larger structures, the piNG-bodies. In this mini-review, we analyze the recent published data about structure and functions of Drosophila male germ granules, and especially their involvement in the piRNA silencing pathway.

Kibanov, Mikhail V.; Gvozdev, Vladimir A.; Olenina, Ludmila V.



A process for the aqueous enzymatic extraction of corn oil from dry-milled corn germ and enzymatic wet milled corn germ (E-Germ)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Previously, we reported an aqueous enzymatic oil extraction process that achieved oil yields of 80-90% using corn germ from a commercial corn wet mill. Three commercial cellulases were reported to result in similar oil yields when wet milles corn germ was used as a feedstock in this process. When ...


Lin28a regulates germ cell pool size and fertility.  


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

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



Fine-tuning evolution: germ-line epigenetics and inheritance.  


In mice, epiblast cells found both the germ-line and somatic lineages in the developing embryo. These epiblast cells carry epigenetic information from both parents that is required for development and cell function in the fetus and during post-natal life. However, germ cells must establish an epigenetic program that supports totipotency and the configuration of parent-specific epigenetic states in the gametes. To achieve this, the epigenetic information inherited by the primordial germ cells at specification is erased and new epigenetic states are established during development of the male and female germ-lines. Errors in this process can lead to transmission of epimutations through the germ-line, which have the potential to affect development and disease in the parent's progeny. This review discusses epigenetic reprogramming in the germ-line and the transmission of epigenetic information to the following generation. PMID:23633622

Stringer, Jessica M; Barrand, Sanna; Western, Patrick



Tudor and its domains: germ cell formation from a Tudor perspective  

Microsoft Academic Search

In many metazoan species, germ cell formation requires the germ plasm, a specialized cytoplasm which often contains electron dense structures. Genes required for germ cell formation in Drosophila have been isolated predominantly in screens for maternal-effect mutations. One such gene is tudor (tud); without proper tud function germ cell formation does not occur. Unlike other genes involved in Drosophila germ




Quality of corn germ oil obtained by aqueous enzymatic extraction  

Microsoft Academic Search

Aqueous enzymatic extraction of corn germ oil was investigated. By applying hydrothermal pretreatment of corn germ, it was\\u000a possible to inactivate native enzymes present in the germ and to loosen its structure. The corn was then ground and treated\\u000a with enzymes. After the oil had been released by the enzyme reaction, it was separated by centrifugation. The quality of oil

Mirjana Bocevskaa; Djerdj Karlovi?; Jovan Turkulov; Draginja Pericin



Embryonic stem cells can form germ cells in vitro  

Microsoft Academic Search

Knock-in embryonic stem (ES) cells, in which GFP or lacZ was expressed from the endogenous mouse vasa homolog (Mvh), which is specifically expressed in differentiating germ cells, were used to visualize germ cell production during in vitro differentiation. The appearance of MVH-positive germ cells depended on embryoid body formation and was greatly enhanced by the inductive effects of bone morphogenic

Yayoi Toyooka; Naoki Tsunekawa; Ryuko Akasu; Toshiaki Noce



Germ tube-specific antigens of Candida albicans cell walls  

SciTech Connect

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-specific 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.

Sundstrom, P.R.



Mixed germ cell tumor of ovary and clitoromegaly in Swyer's syndrome: a case report.  


Swyer syndrome is a type of pure gonadal dysgenesis correlating with 46 XY karyotype, primary amenorrhea, and female internal and external genitalia. It reveals a testicular differentiation abnormality.A 16-year old girl admitted to our center with primary amenorrhea and abdominal mass. In spite of the absence of normal testis, clitoromegaly was noticed. Peripheral blood karyotype analysis showed 46 XY. Histopathology of the excised gonads determined mixed germ cell tumor in right ovary and streak left gonad without gonadoblastoma in left side. In patients suffering from Swyer syndrome, high risk of gonadal neoplasia dictates early prophylactic gonadal excision to lengthen survival. PMID:22773216

Aminimoghaddam, S; Mokri, B; Mahmoodzadeh, F



Surveillance or adjuvant treatments in stage 1 testis germ-cell tumours.  


All patients with stage 1 testicular germ-cell tumours (TGCT) can expect to be permanently cured with currently available management approaches. Orchidectomy alone cures 80% of pure seminomas and 70%-75% of nonseminomatous and combined seminoma plus nonseminomatous germ-cell tumours of the testis (NSGCTT). Currently there are well-validated criteria for estimating recurrence risk in NSGCTT. The presence of vascular invasion (VI+) in the testicular primary identifies a group with a recurrence risk approaching 50%. In VI-cases, the risk is ?20%. Adjuvant chemotherapy with two cycles of bleomycin, etoposide, and cisplatin (BEP) is increasingly recommended in VI+ cases, and when offered is selected in place of surveillance by many VI- patients. In seminomatous germ-cell testicular tumours (SGCTT), there are no validated criteria for estimating recurrence risk. Concerns about second cancers complicating adjuvant radiotherapy are reducing its popularity and the absence of tumour markers, the need for frequent scans, long follow-up and evidence of poor compliance argue against surveillance. Single-dose carboplatin is well tolerated, cheap, reduces recurrence rates to <5% and also the risk of second primary TGCT. There remain concerns about long-term toxicity although evidence is accumulating to allay these. This article discusses the relevant issues affecting decision-making and choice in these intriguing, curable cancers. PMID:22987989

Cullen, M



Germ cell research: a personal perspective.  


My interest in germ cells began when I first witnessed sea urchin fertilization and embryo development during a laboratory class at Hokkaido University, Sapporo, Japan, almost 60 yr ago. Weismann's concept of germ cells that I learned during my undergraduate years became the driving force of my entire research career. During the early years, my associates and I used mainly the golden hamster and the guinea pig as model animals because their spermatozoa had large acrosomes and we could readily follow changes in the acrosomes without killing or staining spermatozoa. We later used the mouse as our model organism because we wanted to produce live offspring with known genetic backgrounds. A summary of the findings we made during those years includes the following: (1) first in vitro sperm capacitation; (2) discovery of sperm hyperactivation; (3) demonstration of the importance of Ca(2+) in sperm acrosome reaction, hyperactivation, sperm-egg fusion, and egg activation; (4) development of the sperm's fusion competence during the acrosome reaction; (5) characterization of sperm-oviduct relationships before and during fertilization; (6) use of zona-free hamster eggs to examine fertilizing ability and chromosomes of human spermatozoa; (7) development and use of intracytoplasmic sperm injection; (8) use of prespermatozoal cells for the production of offspring; (9) sperm preservation by freeze-drying and freezing whole-animal bodies; and (10) mouse cloning by somatic cell nuclear transfer. My current interests and my visions for the future include the following: (1) mass production of mature eggs and spermatozoa in vitro, (2) permanent sperm preservation at ambient temperature, (3) development of safer and more efficient assisted fertilization (reproduction) technologies, (4) development of safe and efficient methods of cloning, (5) production of artificial organs such as an artificial uterus, (6) development of safe and effective male contraceptives, and (7) prevention of cancer through germ cell research. PMID:19092115

Yanagimachi, Ryuzo



The epigenetic regulator PLZF represses L1 retrotransposition in germ and progenitor cells  

PubMed Central

Germ cells and adult stem cells maintain tissue homeostasis through a finely tuned program of responses to both physiological and stress related signals. PLZF, a member of the POK family of transcription factors, acts as an epigenetic regulator of stem cell maintenance in germ cells and in hematopoietic stem cells. We identified L1 retrotransposons as the primary targets of PLZF. PLZF-mediated DNA methylation induces silencing of the full length L1 gene and inhibit L1 retrotransposition. Furthermore, PLZF causes the formation of barrier-type boundaries by acting on inserted truncated L1 sequences in protein coding genes. Cell stress releases PLZF-mediated repression, resulting in L1 activation/retrotransposition and impaired spermatogenesis and myelopoiesis. These results reveal a novel mechanism of action by which, PLZF represses retrotransposons, safeguarding normal progenitor homeostasis.

Puszyk, William; Down, Thomas; Grimwade, David; Chomienne, Christine; Oakey, Rebecca J.; Solomon, Ellen



Vasa and the germ line lineage in a colonial urochordate.  


Germ cell sequestering in Animalia is enlightened by either, launching true germ line along epigenetic or preformistic modes of development, or by somatic embryogenesis, where no true germ line is set aside. The research on germ line-somatic tissue segregation is of special relevancy to colonial organisms like botryllid ascidians that reconstruct, on a weekly basis, completely new sets of male and female gonads in newly formed somatic tissues. By sequencing and evaluating expression patterns of BS-Vasa, the Botryllus schlosseri orthologue of Vasa, in sexually mature and asexual colonies during blastogenesis, we have demonstrated that the BS-Vasa mRNA and protein are not expressed exclusively in germ cell lineages, but appeared in cells repeatedly emerging de novo in the colony, independently of its sexual state. In addition, we recorded an immediate Vasa response to cellular stress (UV irradiation) indicating additional functions to its germ line assignments. To confirm germ lineage exclusivity, we examined the expression of three more stem cell markers (BS-Pl10, Bl-piwi and Oct4). Vasa co-expression with Pl10 and Oct4 was detected in germ line derivatives and with Bl-piwi in somatic tissues. Presumptive primordial germ cells (PGC-like cells), that are Vasa(+)/Pl10(+)/Oct4(+) and 6-12 microm in diameter, were first detected in wrapped-tail embryos, in oozooids, in sexual/asexual colonies, within a newly identified PGC niche termed as 'budlet niche', and in circulating blood borne cells, indicating epigenetic embryogenesis. Alternatively, BS-Vasa co-expression with piwi orthologue, an omnipresent bona fide stemness flag, in non germ line cell populations, may indicate germ cell neogenesis (somatic embryogenesis) in B. schlosseri. Both alternatives are not necessarily mutually exclusive. PMID:19406116

Rosner, Amalia; Moiseeva, Elizabeth; Rinkevich, Yuval; Lapidot, Ziva; Rinkevich, Baruch



Depletion of Endogenous Germ Cells in Male Pigs and Goats in Preparation for Germ Cell Transplantation  

PubMed Central

The efficiency of germ cell transplantation, the procedure of transferring germ cells from a donor male into the testes of recipient males, can be greatly increased by reduction of endogenous germ cells in recipient animals. To develop effective methods for suppression of endogenous spermatogenesis in potential pig and goat recipients, we either administered busulfan to pregnant sows or irradiated the testes of immature goats. Piglets from sows treated twice with busulfan (7.5 mg/kg) at days 98 and 108 of gestation showed reduced gonocyte numbers at 2, 4, and 8 weeks of age and reduced initiation of spermatogenesis at 16 weeks of age. For goats, groups of 3 kids at 1, 5, or 9.5 weeks of age received fractionated irradiation of the testes with 3 doses of 2 Gy on 3 consecutive days. At 2 months after irradiation, 5%–10% of seminiferous tubule cross sections contained pachytene spermatocytes, compared with 50%–100% in controls. At 3 months after irradiation, spermatozoa appeared in 20% of tubule cross sections in all treated goats and in 100% of tubules in control goats. By 6 months after irradiation, spermatogenesis had recovered in 60% of tubules in goats treated at 5 or 9.5 weeks of age but in only 29% of tubules after treatment at 1 week of age. Therefore, late gestation in utero treatment of pigs with low doses of busulfan and testicular irradiation of goats at 1 week of age will result in a reduction in the endogenous germ cell population that could facilitate donor cell colonization after germ cell transplantation.




Primordial germ cells in the primitive streak stages chick embryo as studied by scanning electron microscopy.  

PubMed Central

Chick embryo primordial germ cells (PGCs) at stages 4-8 were localised in the late hypoblast layer. PAS staining confirmed their distribution in a large arc at the anterior border of the area pellucida/area opaca. By scanning electron microscopy the PGCs were seen as spherical cells within the late hypoblast layer. Individual cells separated from this layer and collected in groups of 2-10 in shallow pockets in the hypoblast layer prior to their migration. The pockets containing PGCs were clearly visible by light and scanning electron microscopy and demarcated the germinal ridge at stages 4-8. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11

England, M A; Matsumura, G



The germ cell cycle in the guinea pig  

Microsoft Academic Search

In the literature concerned with the germ cell cycle in mammals there is a shortage of reports of studies embracing the complete cell cycle, and in many of these reports the number of stages studied seems often to be inadequate. Some investigators have confined their attention to the origin of germ cells and followed development to sexual differentiation; others have




Effects of wheat germ on a population of hyperlipidemic patients  

Microsoft Academic Search

Purpose – Reducing fat intake or inhibiting fat absorption is a useful solution for blood lipid reduction. It is shown that there are some proteins in wheat germ with pancreatic lipase inhibiting properties that have hypolipidemic effects. This paper aims to evaluate the possible beneficial effects of a daily intake of 30 g of raw wheat germ in a population

Hamid Reza Zakeri; Asal Ataie Jafari; Mohammad Rajabi; Saeed Hosseini



Germ line — soma differentiation in Ascaris : A molecular approach  

Microsoft Academic Search

Summary The early ontogenetic segregation of germ line and somatic cells in the animal kingdom is phylogenetically very old and represents probably the first step in differentiation. While this phenomenon has been shown to occur in various animal phyla, it seems to be completely msssing in the plant kingdom. In several animal species, the segregation of the germ and somatic

H. Tobler; F. Müller; E. Back; P. Aeby



Chromatin remodelling and epigenetic features of germ cells  

Microsoft Academic Search

Germ cells have the unique capacity to start a new life upon fertilization. They are generated during a sex-specific differentiation programme called gametogenesis. Maturation of germ cells is characterized by an impressive degree of cellular restructuring and gene regulation that involves remarkable genomic reorganization. These events are finely tuned, but are also susceptible to the introduction of various types of

Sarah Kimmins; Paolo Sassone-Corsi



Development: a pathway to plant female germ cells.  


Plant germ cells form late in development, but little is known about the molecular basis for germline specification in plants. Recent results have identified components of a regulatory pathway controlling female germ cell determination, including a key transcription factor and some putative signaling proteins. PMID:21683904

Wang, Yingxiang; Ma, Hong



Apoptosis of germ cells during human prenatal oogenesis  

Microsoft Academic Search

During human oogenesis two contrasting processes can be observed: germ cell proliferation and differentiation, and contemporaneous germ cell death. It is well known that apoptosis is a type of physiological cell death that occurs in proliferating and differentiating tissues. The aim of this study is to demonstrate, through ultrastructural and in- situ 39 end labelling observations in intact sections of

A. De Pol; F. Vaccina; A. Forabosco; E. Cavazzuti; L. Marzona



Pluripotential stem cells derived from migrating primordial germ cells  

Microsoft Academic Search

Pluripotent stem cells termed embryonic germ cells (EGCs) have earlier been derived from pre- and post-migrating mouse primordial germ cells (PGCs). We have recently obtained four EGC lines from migrating PGCs of 9.5 days post coitum (dpc) embryos. All lines were male with normal karyotype and showed properties that are similar to previously established EGC lines, including colony morphology, expression

Gabriela Durcova-Hills; Justin F.-X. Ainscough; Anne McLaren



Long-Term Proliferation of Primordial Germ Cells.  

National Technical Information Service (NTIS)

The invention includes a method of culturing primordial germ cells from an animal in vitro for a period of time longer than seven days. The method includes growing primordial germ cells in the presence of a fibroblast growth factor and leukemia inhibitory...

P. J. Donovan J. L. Resnick



Derivation of Putative Porcine Embryonic Germ Cells and Analysis of Their Multi-lineage Differentiation Potential.  


Embryonic germ (EG) cells are cultured pluripotent stem cells derived from the primordial germ cells (PGCs) that migrate from the dorsal mesentery of the hindgut to the developing genital ridge. In this study, the morphology of the porcine genital ridge was assessed in embryos harvested on days 22-30 of pregnancy. PGCs from embryos at these stages were cultured to obtain porcine EG cell lines, and EG-like cells were derived from PGCs from embryos harvested on days 24-28 of pregnancy. The EG-like cells expressed Oct4, Sox2, Nanog, SSEA-3, SSEA-4 and alkaline phosphatase (AP). These cells were able to form embryoid bodies (EBs) in suspension culture and differentiate into cells representative of the three germ layers as verified by a-fetoprotein (AFP), ?-smooth muscle actin (?-SMA), and Nestin expression. Spontaneous differentiation from the porcine EG-like cells of delayed passage in vitro showed that they could differentiate into epithelial-like cells, mesenchymal-like cells and neuron-like cells. In vitro directed differentiation generated osteocytes, adipocytes and a variety of neural lineage cells, as demonstrated by alizarin red staining, oil red O staining, and immunofluorescence for neuronal class ? ?-tubulin (Tuj1), glial fibrillary protein (GFAP) and galactosylceramidase (GALC), respectively. These results indicate that porcine EG-like cells have the potential for multi-lineage differentiation and are useful for basic porcine stem cell research. PMID:24053947

Cong, Yimei; Ma, Jing; Sun, Ruizhen; Wang, Jianyu; Xue, Binghua; Wang, Jiaqiang; Xie, Bingteng; Wang, Juan; Hu, Kui; Liu, Zhonghua



Immunocytochemical localization of wheat germ agglutinin in wheat  

PubMed Central

Immunocytological techniques were developed to localize the plant lectin, wheat germ agglutinin (WGA), in the tissues and cells of wheat plants. In a previous study we demonstrated with a radioimmunoassay that the lectin is present in wheat embryos and adult plants both in the roots and at the base of the stem. We have now found, using rhodamine, peroxidase, and ferritin-labeled secondary antibodies, that WGA is located in cells and tissues that establish direct contact with the soil during germination and growth of the plant In the embryo, WGA is found in the surface layer of the radicle, the first adventitious roots, the coleoptile, and the scutellum. Although found throughout the coleorhiza and epiblast, it is at its highest levels within the cells at the surface of these organs. In adult plants, WGA is located only in the caps and tips of adventitious roots. Reaction product for WGA was not visualized in embryonic or adult leaves or in other tissues of adult plants. At the subcellular level, WGA is located at the periphery of protein bodies, within electron-translucent regions of the cytoplasm, and at the cell wall-protoplast interface. Since WGA is found at potential infection sites and is known to have fungicidal properties, it may function in the defense against fungal pathogens.



RNA Expression in Male Germ Cells During Spermatogenesis (Male Germ Cell Transcriptome)  

Microsoft Academic Search

\\u000a Spermatogenesis is a key process in mammalian reproduction. This highly ordered process requires precise and well-controlled\\u000a programs governed by dynamic patterns of gene expression. Some genes are exclusive to spermatogenic cells, while others are\\u000a closely related to genes expressed in somatic cells. Although key genes in male germ cell development have been identified,\\u000a the biological mechanisms and transcripts that govern

Tin-Lap Lee; Albert Hoi-Hung Cheung; Owen M. Rennert; Wai-Yee Chan


Redo retroperitoneal lymphadenectomy for germ cell tumor.  


Redo retroperitoneal lymph node dissection (RPLND) for the treatment of germ cell tumors (GCTs) is an uncommonly performed procedure. We report on 9 patients who underwent redo RPLND at the University of Wisconsin (UW) between January 1988 and December 1990. Indications for redo RPLND include: residual retroperitoneal mass after initial RPLND and chemotherapy, normal alpha-fetoprotein (AFP) and beta subunit of human chorionic gonadotropin (B-HCG), otherwise negative metastatic workup, and evidence that the mass is resectable. Overall, 6 of 9 patients are alive with no evidence of disease at a mean follow-up of thirty-two months. Preoperative evaluation, histopathology, morbidity, and technical aspects of this procedure, which is a critical part of the management of GCT, are reviewed. PMID:8392234

Waples, M J; Messing, E M



Layer IV of the primary somatosensory cortex has the highest complexity under anesthesia and cortical complexity is modulated by specific thalamic inputs  

Microsoft Academic Search

The system complexity, as calculated from correlation dimension, embedded in each layer and its modulation by specific inputs and general excitatory state are not yet known. The aims of present study were to estimate the system complexity across the cortical layers by analyzing intracortical EEG signals using a nonlinear analytical method, and to identify how layer-related complexity varies with the

Zi-Hao Wang; Ming-Hua Chang; Jenq-Wei Yang; Jyh-Jang Sun; Hoong-Chien Lee; Bai-Chuang Shyu



Sinonasal teratocarcinosarcoma with yolk sac elements: a neoplasm of somatic or germ cell origin?  


Sinonasal teratocarcinosarcoma is an uncommon, aggressive, morphologically heterogenous tumor composed of cells derived from the 3 somatic layers. A histogenetic origin from a multipotential adult somatic stem cell with divergent differentiation has been favored over a germ cell origin. This assumption has been based on the lack of germ cell elements and, until recently, the absence of demonstrable amplification of 12p. We report a case that exhibited foci of yolk sac elements with papillary structures and intracytoplasmic periodic acid-Schiff-positive, diastase-resistant, ?-fetoprotein-positive, hyaline globules. An expanded area of undifferentiated cells, likely precursor cells, in the basal layer of the overlying mucosal epithelium transitions into and merges with the immature epithelial, neuroepithelial, and mesenchymal components. These previously unreported histomorphological features support the hypothesis that this tumor is a teratomatous tumor arising from pluripotent embryonic stem cells in the basal layer of the sinonasal epithelium. That notion is further supported by fluorescence in situ hybridization cytogenetic analysis, which showed a distinct subpopulation of the tumor cells with an extra copy of chromosome 12p13. PMID:20952296

Thomas, Jaiyeola; Adegboyega, Patrick; Iloabachie, Kenny; Mooring, John Wesley; Lian, Timothy



Regulation of CCN2 gene expression and possible roles in developing tooth germs.  


CCN proteins are extracellular and cell-associated molecules involved in several developmental processes, but their expression patterns and regulation in tooth development remain unclear. Here we first determined the expression patterns of CCN genes in mouse tooth germs. We found that at early stages CCN2 was detected in dental lamina, dental mesenchyme, and primary enamel knot, while other CCN family members were expressed broadly. By the bell stage, all members were expressed in differentiating odontoblasts and ameloblasts, but CCN1 and CCN2 transcripts were conspicuous in differentiating osteoblasts in dental follicle. Next, we asked what signalling molecules regulate CCN2 expression and what roles CCN2 may have. We found that upon surgical removal of dental epithelium CCN2 was not longer expressed in dental mesenchyme in cultured bud stage germs. Implantation of beads pre-coated with BMPs and FGFs onto E12-13 mandibular explants induced CCN2 expression in dental mesenchyme. There was a dose-dependent effect of BMP-4 on CCN2 induction; a concentration of 100ng/?l was able to induce strong CCN2 expression while a minimum concentration of 25ng/?l was needed to elicit appreciable expression. Importantly, Noggin treatment inhibited endogenous and BMP-induced CCN2 expression, verifying that CCN2 expression in developing tooth germs requires BMP signalling. Lastly, we found that rCCN2 stimulated proliferation in dental mesenchyme in a dose-dependent manner. Together, the data indicate that expression of CCN genes is spatio-temporally regulated in developing tooth germs. CCN2 expression appears to depend on epithelial and mesenchymal-derived signalling factors, and CCN2 can elicit strong proliferation in dental mesenchyme. PMID:24112732

Kanyama, Manabu; Shimo, Tsuyoshi; Sugito, Hiroki; Nagayama, Motohiko; Kuboki, Takuo; Pacifici, Maurizio; Koyama, Eiki



The making of a germ panic, then and now.  

PubMed Central

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."

Tomes, N



The making of a germ panic, then and now.  


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

Tomes, N



Inverted Impacted Primary Maxillary Incisors: A Case Report  

PubMed Central

Tooth impaction rarely occurs in primary dentition. Most of the primary teeth impactions are seen in second molars. The purpose of this article is to present a 4-year-old girl with bilateral impaction of inverted primary maxillary central incisors which trauma had displaced their tooth germ before erupting.

Seraj, B.; Ghadimi, S.; Mighani, G.; Zare, H.; Rabbani, M.



Localization of Axonally Transported 12 l-Wheat Germ Agglutinin beneath of Chick Retinal Ganglion Cells the Plasma Membrane  

Microsoft Academic Search

The distribution of 12Sl-wheat germ agglutinin (WGA) transported by axons of chick retinal ganglion cells to layer d of the optic tectum was studied by electron microscopic autoradiography. We found that 52% of the radioactivity was located in axons and axon terminals in the contralateral optic tectum 22 h after intravitreal injection of affinity-purified t2sl-WGA. Axons comprised 43% of the




Development of malignant germ cells - the genvironmental hypothesis.  


Human germ cell tumors are of interest because of their epidemiology, clinic and patho-biology. Histologically, they are subdivided into various elements, with similarities to embryogenesis. Recent insight triggered development of a higher order division into five types of human germ cell tumors. In the context of male germ cells, only three are relevant; Type I: teratomas and yolk sac tumors of neonates and infants; Type II: seminomas and nonseminomas of (predominantly) adolescents and adults; and Type III: spermatocytic seminomas of the elderly. Various animal models, both occurring spontaneous or induced, are reported, of which their relevance is still a matter of debate. Recent multidisciplinary studies have led to a significant increase in our understanding of the parameters involved in the earliest pathogenetic steps of human germ cells tumors, particularly the seminomas and nonseminomas (Type II). This paper will discuss a number of interesting insights into the normal and aberrant regulation of germ cell development, resulting in the so-called genvironmental hypothesis. This assumes a subtle interaction between environmental- and (epi)genetic parameters, resulting in clinical/phenotypical characteristics. These influence signaling pathways and thereby developmental processes, including gonadal development, germ cell proliferation, maturation and apoptosis. In the case of a disturbed physiology, either due to the germ cell itself, or the micro-environment, embryonic germ cells, during a specific window of sensitization, might be blocked in their maturation, resulting in carcinoma in situ or gonadoblastoma, the precursors of seminomas and nonseminomas. The level of testicularization of the gonad determines the histological composition of the precursor. These insights will allow a better definition of individuals at risk of developing a germ cell malignancy, and allow a better selection of scientific approaches to elucidate the corresponding pathogenesis. PMID:23784835

Looijenga, Leendert H J; Van Agthoven, Ton; Biermann, Katharina



Lipase inactivation in wheat germ by gamma irradiation  

NASA Astrophysics Data System (ADS)

An attempt was made to improve the shelf life of wheat germ by optimizing processing conditions involving ?-irradiation. Studies were carried out to investigate the effect of ?-irradiation (0-30 kGy doses) on the chemical composition of wheat germ with respect to variation in moisture, total ash, crude fat, free fatty acid, protein and lipase activity. The results demonstrate that shelf stability of wheat germ was achieved by inactivation of lipase at doses of ?-irradiation greater than 12 kGy.

Jha, Pankaj Kumar; Kudachikar, V. B.; Kumar, Sourav



The stabilization of ?-catenin leads to impaired primordial germ cell development via aberrant cell cycle progression  

Microsoft Academic Search

Primordial germ cells (PGCs) are germ cell precursors that are committed to sperm or oocytes. Dramatic proliferation during PGC development determines the number of founder spermatogonia and oocytes. Although specified to a germ lineage, PGCs produce pluripotent embryonic germ (EG) cells in vitro and testicular teratomas in vivo. Wnt\\/?-catenin signaling regulates pluripotency and differentiation in various stem cell systems, and

Tohru Kimura; Toshinobu Nakamura; Kazushige Murayama; Hiroki Umehara; Noriko Yamano; Shoko Watanabe; Makoto M. Taketo; Toru Nakano



Bazooka regulates microtubule organization and spatial restriction of germ plasm assembly in the Drosophila oocyte  

Microsoft Academic Search

Localization of the germ plasm to the posterior of the Drosophila oocyte is required for anteroposterior patterning and germ cell development during embryogenesis. While mechanisms governing the localization of individual germ plasm components have been elucidated, the process by which germ plasm assembly is restricted to the posterior pole is poorly understood. In this study, we identify a novel allele

Agata N. Becalska; Elizabeth R. Gavis



Expression of axolotl DAZL RNA, a marker of germ plasm: widespread maternal RNA and onset of expression in germ cells approaching the gonad.  


How germ cell specification occurs remains a fundamental question in embryogenesis. The embryos of several model organisms contain germ cell determinants (germ plasm) that segregate to germ cell precursors. In other animals, including mice, germ cells form in response to regulative mechanisms during development. To investigate germ cell determination in urodeles, where germ plasm has never been conclusively identified, we cloned a DAZ-like sequence from axolotls, Axdazl. Axdazl is homologous to Xdazl, a component of Xenopus germ plasm found in the vegetal pole of oocytes and eggs. Axdazl RNA is not localized in axolotl oocytes, and, furthermore, these oocytes do not contain the mitochondrial cloud that localizes Xdazl and other germ plasm components in Xenopus. Maternal Axdazl RNA is inherited in the animal cap and equatorial region of early embryos. At gastrula, neurula, and tailbud stages, Axdazl RNA is widely distributed. Axdazl first shows cell-specific expression in primordial germ cells (PGCs) approaching the gonad at stage 40, when nuage (germ plasm) appears in PGCs. These results suggest that, in axolotls, germ plasm components are insufficient to specify germ cells. PMID:11397009

Johnson, A D; Bachvarova, R F; Drum, M; Masi, T



Quantification of additional short arms of chromosome 12 in germ cell tumours using the polymerase chain reaction.  


Male germ cell tumours are characterised by the over-representation of 12p sequences, most often in the form of isochromosome i(12p). This study describes the development of a quantitative detection system for additional copies of 12p employing the polymerase chain reaction (PCR). The validity of this method was assessed on two i(12p) containing tumour cell lines in which the number of i(12p) was determined by fluorescence in situ hybridisation. Fourteen primary male germ cell tumours were analysed using the PCR-based method. While 3/8 seminomatous germ cell cancers did not contain any additional 12p, all 6 non-seminomatous tumours did and the severity of the disease correlated with the respective copy number. The ease of the PCR-based method makes it possible for the quantification of additional 12p to become a routine diagnostic and prognostic tool for testicular germ cell tumours, thereby helping to define the role of the i(12p) anomality in larger retrospective studies. PMID:9337694

Malek, N P; Casper, J; Looijenga, L H; Strohmeyer, T; Schmoll, H J; Nordheim, A; Janknecht, R



Wheat germ policosanol failed to lower plasma cholesterol in subjects with normal to mildly elevated cholesterol concentrations  

Microsoft Academic Search

Sugar cane policosanol, a mixture of long-chain primary alcohols (?67% as octacosanol), has been reported to lower plasma low-density lipoprotein (LDL)-cholesterol. We investigated the effect of wheat germ policosanol (WGP) on plasma lipid profiles in 58 adults (30 men and 28 women, aged 49 ± 11 years) with normal to mildly elevated plasma cholesterol concentrations in a double-blind, randomized, parallel

Yuguang Lin; Mike Rudrum; Reggy P. J. van der Wielen; Elke A. Trautwein; Gerald McNeill; Aafje Sierksma; Gert W. Meijer



On the stability of analytic germs under ultradifferentiable perturbations  

NASA Astrophysics Data System (ADS)

Let f be a real-analytic function germ at the origin in , whose critical locus contains a given real-analytic set X, and let Y be a germ of a closed subset at the origin. We study the stability of f under perturbations u that are flat on Y and that belong to a given Denjoy-Carleman non-quasianalytic class. We obtain a condition ensuring that f+u=f[circle, open][Phi] where [Phi] is a germ of diffeomorphism whose components belong to a (generally larger) Denjoy-Carleman class. Roughly speaking, this condition involves a Lojasiewicz-type separation property between Y and the complex zeros of a certain ideal associated with f and X. The relationship between the Denjoy-Carleman classes of u and [Phi] is controlled precisely by the inequality. This result extends, and simplifies, former work of the author on germs with isolated critical points.

Thilliez, Vincent



Female germ cell loss from radiation and chemical exposures  

SciTech Connect

Female germ cells in some mammals are extremely sensitive to killing by ionizing radiation, especially during development. Primordial oocytes in juvenile mice have an LD50 of only 6-7 rad, and the germ cell pool in squirrel monkeys is destroyed by prenatal exposure of 0.7 rad/day. Sensitivity varies greatly with species and germ cell stage. Unusually high sensitivity has not been found in macaques and may not occur in man, but this has not been established for all developmental stages. The exquisite oocyte radiosensitivity in mice apparently reflects vulnerability of the plasma membrane, not DNA, which may have implications for estimating human genetic risks. Germ cells can be killed also by chemicals. Such oocyte loss, with similarities to radiation effects, is under increasing study, including chemotherapy observations in women. More than 75 compounds have been tested in mice, with in vivo toxicity quantified by oocyte loss; certain chemicals apparently act on the membrane.

Dobson, R.L.; Felton, J.S.



Bmp7 regulates germ cell proliferation in mouse fetal gonads.  


Relatively little is known regarding the signals that regulate the proliferation and sex-specific development of germ cells during mammalian fetal gonad differentiation. Members of the bone morphogenetic protein (BMP) family have been identified as key regulators of germ cells in the Drosophila gonad. Here we show that in mice Bmp7 is expressed in gonads of both sexes and is required for germ cell proliferation during a narrow window of development between 10.5-11.5 days post coitum (dpc). The proliferation defect is more severe in male than in female embryos suggesting that there are sexually dimorphic compensatory pathways. BMP signaling appears to be an evolutionarily conserved pathway regulating embryonic germ cell proliferation in vertebrate and invertebrate species. PMID:18391523

Ross, A; Munger, S; Capel, B



Tritium effects on germ cells and fertility  

SciTech Connect

Primordial oocytes in juvenile mice show acute gamma-ray LD/sub 50/ as low as 6 rad. This provides opportunities for determining dose-response relations at low doses and chronic exposure in the intact animal - conditions of particular interest for hazard evaluation. Examined in this way, /sup 3/HOH in body water is found to kill murine oocytes exponentially with dose, the LD/sub 50/ level for chronic exposure being only (delivering 0.4 rad/day). At very low doses and dose rates, where comparisons between tritium and other radiations are of special significance for radiological protection, the RBE of tritium compared with /sup 60/Co gamma radiation reaches approximately 3. Effects on murine fertility from tritium-induced oocyte loss have been quantified by reproductive capacity measurements. Chronic low-level exposure has been examined also in three primate species - squirrel, rhesus, and bonnet monkeys. In squirrel monkeys the ovarian germ-cell supply is 99% destroyed by the time of birth from prenatal exposure to body-water levels of /sup 3/HOH (administered in maternal drinking water) of only 3, the LD/sub 50/ level being 0.5 (giving 0.1 rad/day), one fourth that in mice. Though not completely ruled out, similar high sensitivity of female germ cells has not been found in macaques; and it probably does not occur in man. The exquisite radiosensitivity of primordial oocytes in mice is apparently due to vulnerability of the plasma membrane (or something of similar geometry and location), not DNA. Evidence for this comes from tritium data as well as neutron studies. Tritium administered as /sup 3/HOH, and therefore generally distributed, is much more effective in killing murine oocytes than is tritium administered as /sup 3/H-TdR, localized in the nucleus. This situation in the mouse may have implications for estimating radiation genetic risk in the human female.

Dobson, R.L.; Kwan, T.C.; Straume, T.



Conservative management of testicular germ-cell tumors  

Microsoft Academic Search

Cure rates of germ-cell cancer have been greater than 95% for the last decade; therefore, over the past few years there has been a greater focus on 'conservative' approaches to treatment. The increased incidence of late non-germ-cell cancers in the era of radiotherapy and the incidence of subclinical testicular deficiency and metabolic syndrome in cured patients have accelerated this trend.

Tim Oliver



Pure testicular carcinoid associated with intratubular germ cell neoplasia  

PubMed Central

This case report describes for the first time a case of pure testicular carcinoid preaortic lymph node metastases in a 25 year old patient with carcinoid syndrome. The simultaneous occurrence of intratubular germ cell neoplasia in the surrounding testicular tissue was identified by OCT4 and placental-like alkaline phosphatase positivity. This confirmed that the tumour had a germ cell origin in the testis, rather than being a metastasis from an extragenital carcinoid.

Merino, J; Zuluaga, A; Gutierrez-Tejero, F; del Mar Serrano, M; Ciani, S; Nogales, F F



Heat Stress Causes Testicular Germ Cell Apoptosis in Adult Mice  

Microsoft Academic Search

An investigation was undertaken to determine whether the germ-cell lossassociatedwithexposureofthe testis to abdominal temperature occurs by apoptosis. Using an adult-mouse model of ex- perimentalunilateral cryptorchidism, it was observed that DNA frag- mentation,consistent with apoptosis, was observed on day 6 inthe cryptorchid testis, with subsequentlossof testicular weight, histologic evidence ofgerm-cell loss, and histochemical staining of apoptotic germ cells observed on day




Effects of tritiated water on germ cells in medaka embryos  

SciTech Connect

Embryos of medaka, Oryzias latipes, were exposed to tritiated water and /sup 137/Cs ..gamma.. rays continuously from the one-cell stage until hatching (10 days at 26omicronC). Germ cells in the gonads of newly hatched fry were counted in histological sections and compared with controls. The accumulated dose for 50% survival of germ cells was 195 rad for tritium ..beta.. rays and 350 rad for /sup 137/Cs ..gamma.. rays. Female progeny were produced using Yamamoto's method. The 50% survival doses for female germ cells treated in a manner similar to that described above were 140 rad for ..beta.. rays and 305 rad for ..gamma.. rays. When embryos of medaka were irradiated with ..gamma.. rays below an accumulated dose of 475 rad or treated with tritiated water at a concentration of 0.2 mCi/ml or lower, the dose response of the germ cells showed an exponential relationship. It appeared that there was no threshold or significant dose-rate effect for either ..beta.. or ..gamma.. rays on germ cell survival, and that tritium ..beta.. rays were more effective than /sup 137/Cs ..gamma.. rays in germ cell killing.

Etoh, H.; Hyodo-Taguchi, Y.



Effects of tritiated water on germ cells in medaka embryos  

SciTech Connect

Embryos of medaka, Oryzias latipes, were exposed to tritiated water and /sup 137/Cs gamma rays continuously from the one-cell stage until hatching (10 days at 26 degrees C). Germ cells in the gonads of newly hatched fry were counted in histological sections and compared with controls. The accumulated dose for 50% survival of germ cells was 195 rad for tritium beta rays and 350 rad for /sup 137/Cs gamma rays. Female progeny were produced using Yamamoto's method. The 50% survival doses for female germ cells treated in a manner similar to that described above were 140 rad for beta rays and 305 rad for gamma rays. When embryos of medaka were irradiated with gamma rays below an accumulated dose of 475 rad or treated with tritiated water at a concentration of 0.2 mCi/ml or lower, the dose response of the germ cells showed an exponential relationship. It appeared that there was no threshold or significant dose-rate effect for either beta or gamma rays on germ cell survival, and that tritium beta rays were more effective than 137Cs gamma rays in germ cell killing.

Etoh, H.; Hyodo-Taguchi, Y.



Apoptosis of germ cells during human prenatal oogenesis.  


During human oogenesis two contrasting processes can be observed: germ cell proliferation and differentiation, and contemporaneous germ cell death. It is well known that apoptosis is a type of physiological cell death that occurs in proliferating and differentiating tissues. The aim of this study is to demonstrate, through ultrastructural and in-situ 3' end labelling observations in intact sections of human fetal ovaries, that germ cell loss during fetal life is due to a phenomenon of apoptosis. We evaluated the presence of programmed cell death in female germ cells in fetal ovaries at 18-20 weeks of postconceptional age. The alterations that occur during apoptosis were detected by the electron microscope and include cytoplasmic condensation, organelle relocalization and compaction, chromatin condensation, and finally, production of membrane-enclosed particles containing intracellular material, known as apoptotic bodies, that are phagocytosed. The fragmentation of DNA, characteristic of apoptotic cells, was detected by the use of the in-situ 3' end labelling procedure on histological sections of ovaries where only some nuclei of germ cells were positively stained. The parallel use of these two methods on human ovaries of 18-20 weeks postconceptional age has allowed us to show that the numerical decrease of human female germ cells during the fetal period is due to an apoptotic phenomenon. PMID:9402287

De Pol, A; Vaccina, F; Forabosco, A; Cavazzuti, E; Marzona, L



Regulation of Sertoli cell and germ cell differentation.  


Unwanted childlessness affects approximately one in six couples worldwide. According to the World Health Organization, in nearly 40% of cases the cause can be attributed to the female, in 20% to the male, in 25% to both, and in 15% the cause remains unknown. The incidence of male factor infertility in the general population is approximately 7%. The majority of these men experience irreversible idiopathic infertility and cannot father children without some form of medical intervention. Male factor infertility, in addition, may be caused by testicular germ cell cancer, which is known to represent the most common cancer among young men in Western industrialized countries. There is growing evidence that this cancer originates from fetal germ cells exhibiting an aberrant programme of gene expression and that tumour progression may be favoured by an aberrant Sertoli cell-germ cell communication. The present monograph aims to shed more light on the regulation of Sertoli and germ cell differentiation. Involving knockout and transgenic mouse models, the authors focus on (a) male factor infertility that might be related to altered maturation of Sertoli cells, (b) male factor infertility that might be due to incorrect histone-to-protamine exchange in haploid spermatids, and (c) progression of testicular germ cell cancer that might be favoured by an aberrant Sertoli cell-germ cell communication. PMID:16281455

Brehm, R; Steger, K



Analysis of chicken primordial germ cells  

PubMed Central

Primordial germ cells (PGCs) are precursors of germline cells. Although avian PGCs have been used to produce transgenic birds, their characteristics largely remain unknown. In this study, we isolated PGCs from chicken embryos at various developmental stages and analyzed the gene expression. Using the expression of stage-specific embryonic antigen-1 (SSEA-1) as a marker of chicken PGCs, we purified PGCs from embryos by fluorescence-activated cell sorting after incubation for 2.5–8.5 days. The number of SSEA-1+ cells was almost unchanged during days 2.5–8.5 of incubation in females but continuously increased in male. Expression of several genes, including Blimp1, SOX2, and CXCR4, was observed in SSEA-1+ cells but not in SSEA-1? cells in both female and male embryos. Quantitative reverse-transcription PCR analysis revealed that the expression of CXCR4, a chemokine receptor essential for migration of PGCs from the bloodstream to the gonads, was reduced after the circulating PGC stage (day 2.5).

Motono, Makoto; Ohashi, Takuya; Iijima, Shinji



Baldness, acne and testicular germ cell tumors  

PubMed Central

Androgen levels during critical periods of testicular development may be involved in the etiology of testicular germ cell tumors (TGCT). We evaluated the roles of adolescent and early adult life correlates of androgen exposure and TGCT in a hospital-based case control study. TGCT cases (n=187) and controls (n=148), matched on age, race and state of residence, participated in the study. Unconditional logistic regression was used to estimate associations between TGCT and male pattern baldness, severe acne, markers of puberty onset and body size. Cases were significantly less likely to report hair loss than controls (OR, 0.6; 95% CI, 0.4, 1.0). Amount of hair loss, increasing age at onset and increasing rate of loss were all inversely associated with TGCT (rate of hair loss: p-trend=0.03; age at onset: p-trend=0.03; amount of hair loss: p-trend=0.01). History of severe acne was inversely associated with TGCT (OR, 0.5; 95% CI, 0.3, 0.9) and height was positively associated with TGCT (p-trend=0.02). Increased endogenous androgen levels during puberty and early adulthood may be associated with decreased risk of TGCT. Additional studies of endogenous hormone levels during puberty and early adult life are warranted, especially studies evaluating the role of androgen synthesis, metabolism and uptake.

Trabert, Britton; Sigurdson, Alice J.; Sweeney, Anne M.; Amato, Robert J.; Strom, Sara S.; McGlynn, Katherine A.



DEADSouth protein localizes to germ plasm and is required for the development of primordial germ cells in Xenopus laevis  

PubMed Central

Summary DEADSouth mRNA is a component of germ plasm in Xenopus laevis and encodes a DDX25 DEAD-box RNA helicase. To determine the intracellular localization of DEADSouth protein, we injected mRNA encoding DEADSouth tagged with mCherry fluorescent protein into fertilized eggs from transgenic Xenopus expressing EGFP fused with a mitochondrial targeting signal. The DEADSouth-mCherry fusion protein was localized to the germ plasm, a mitochondria-rich region in primordial germ cells (PGCs). DEADSouth overexpression resulted in a reduction of PGC numbers after stage 20. Conversely, DEADSouth knockdown using an antisense locked nucleic acid gapmer inhibited movement of the germ plasm from the cortex to the perinuclear region, resulting in inhibition of PGC division at stage 12 and a decrease in PGC numbers at later stages. The knockdown phenotype was rescued by intact DEADSouth mRNA, but not mutant mRNA encoding inactive DEADSouth helicase. Surprisingly, it was also rescued by mouse vasa homolog and Xenopus vasa-like gene 1 mRNAs that encode DDX4 RNA helicases. The rescue was dependent on the 3? untranslated region (3?UTR) of DEADSouth mRNA, which was used for PGC-specific expression. The 3?UTR contributed to localization of the injected mRNA to the germ plasm, resulting in effective localization of DEADSouth protein. These results demonstrate that localization of DEADSouth helicase to the germ plasm is required for proper PGC development in Xenopus laevis.

Yamaguchi, Takeshi; Taguchi, Ayaka; Watanabe, Kenji; Orii, Hidefumi



The DEAD-box protein MEL-46 is required in the germ line of the nematode Caenorhabditis elegans  

PubMed Central

Background In the hermaphrodite of the nematode Caenorhabditis elegans, the first germ cells differentiate as sperm. Later the germ line switches to the production of oocytes. This process requires the activity of a genetic regulatory network that includes among others the fem, fog and mog genes. The function of some of these genes is germline specific while others also act in somatic tissues. DEAD box proteins have been shown to be involved in the control of gene expression at different steps such as transcription and pre-mRNA processing. Results We show that the Caenorhabditis elegans gene mel-46 (maternal effect lethal) encodes a DEAD box protein that is related to the mammalian DDX20/Gemin3/DP103 genes. mel-46 is expressed throughout development and mutations in mel-46 display defects at multiple developmental stages. Here we focus on the role of mel-46 in the hermaphrodite germ line. mel-46(yt5) mutant hermaphrodites are partially penetrant sterile and fully penetrant maternal effect lethal. The germ line of mutants shows variable defects in oogenesis. Further, mel-46(yt5) suppresses the complete feminization caused by mutations in fog-2 and fem-3, two genes that are at the top and the center, respectively, of the genetic germline sex determining cascade, but not fog-1 that is at the bottom of this cascade. Conclusion The C. elegans gene mel-46 encodes a DEAD box protein that is required maternally for early embryogenesis and zygotically for postembryonic development. In the germ line, it is required for proper oogenesis. Although it interacts genetically with genes of the germline sex determination machinery its primary function appears to be in oocyte differentiation rather than sex determination.

Minasaki, Ryuji; Puoti, Alessandro; Streit, Adrian



Amniotic fluid stem cell-based models to study the effects of gene mutations and toxicants on male germ cell formation.  


Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo. Compared with model organisms including mice, there are fundamental differences in the molecular processes of human germ cell development. Therefore, an in vitro model mimicking human sperm formation would be an extremely valuable research tool. In the recent past, both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes. We here discuss the possibility to use human amniotic fluid stem (AFS) cells as a biological model. Since their discovery in 2003, AFS cells have been characterized to differentiate into cells of all three germ layers, to be genomically stable, to have a high proliferative potential and to be non-tumourigenic. In addition, AFS cells are not subject of ethical concerns. In contrast to iPS cells, AFSs cells do not need ectopic induction of pluripotency, which is often associated with only imperfectly cleared epigenetic memory of the source cells. Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency, they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity. PMID:22231297

Gundacker, Claudia; Dolznig, Helmut; Mikula, Mario; Rosner, Margit; Brandau, Oliver; Hengstschläger, Markus



Analysis of SOX2 expression in developing human testis and germ cell neoplasia  

PubMed Central

The transcriptional regulators of pluripotency, POU5F1 (OCT4), NANOG and SOX2, are highly expressed in embryonal carcinoma (EC). In contrast to OCT4 and NANOG, SOX2 has not been demonstrated in the early human germ cell lineage or carcinoma in situ (CIS), the precursor for testicular germ cell tumours (TGCTs). Here, we have analysed SOX2 expression in CIS and overt TGCTs, as well as normal second and third trimester fetal, prepubertal and adult testes by in situ hybridisation and immunohistochemistry using three different antibodies. In contrast to earlier studies, we detected SOX2 mRNA in most CIS cells. We also detected speckled nuclear SOX2 immunoreactivity in CIS cells with one primary antibody, which was not apparent with other primary antibodies. The results demonstrate SOX2 gene expression in CIS for the first time and raise the possibility of post-transcriptional regulation, most likely sumoylation as a mechanism for limiting SOX2 action in these cells.




Specification of primordial germ cells in medaka (Oryzias latipes)  

PubMed Central

Background Primordial germ cells (PGCs) give rise to gametes that are responsible for the development of a new organism in the next generation. Two modes of germ line specification have been described: the inheritance of asymmetrically-localized maternally provided cytoplasmic determinants and the induction of the PGC fate by other cell types. PGCs specification in zebrafish appears to depend on inheritance of germ plasm in which several RNA molecules such as vasa and nanos reside. Whether the specification mode of PGCs found in zebrafish is general for other fish species was brought into question upon analysis of olvas expression – the vasa homologue in another teleost, medaka (Oryzias latipes). Here, in contrast to the findings in zebrafish, the PGCs are found in a predictable position relative to a somatic structure, the embryonic shield. This finding, coupled with the fact that vasa mRNA, which is localized to the germ plasm of zebrafish but does not label a similar structure in medaka opened the possibility of fundamentally different mechanisms governing PGC specification in these two fish species. Results In this study we addressed the question concerning the mode of PGC specification in medaka using embryological experiments, analysis of RNA stability in the PGCs and electron microscopy observations. Dramatic alterations in the somatic environment, i.e. induction of a secondary axis or mesoderm formation alteration, did not affect the PGC number. Furthermore, the PGCs of medaka are capable of protecting specific RNA molecules from degradation and could therefore exhibit a specific mRNA expression pattern controlled by posttrancriptional mechanisms. Subsequent analysis of 4-cell stage medaka embryos using electron microscopy revealed germ plasm-like structures located at a region corresponding to that of zebrafish germ plasm. Conclusion Taken together, these results are consistent with the idea that in medaka the inheritance of maternally provided asymmetrically-localized cytoplasmic determinants directs cells to assume the germ line fate similar to zebrafish PGCs.

Herpin, Amaury; Rohr, Stefan; Riedel, Dietmar; Kluever, Nils; Raz, Erez; Schartl, Manfred



Maternal smoking and testicular germ cell tumors.  


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. PMID:17035387

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



Marijuana use and testicular germ cell tumors  

PubMed Central

Background Since the early 1970's the incidence of testicular germ cell tumors (TGCT) in the U.S. has been increasing, however, potential environmental exposures accounting for this rise have not been identified. A prior study reported a significant association among frequent and long-term current users of marijuana and TGCT risk. We aimed to evaluate the relationship of marijuana use and TGCT in a hospital-based case-control study conducted at The University of Texas M. D. Anderson Cancer Center. Methods TGCT cases diagnosed between January 1990 and October 1996 (n=187) and male friend controls (n=148) were enrolled in the study. All participants were between the ages of 18 and 50 at the time of cases' diagnosis and resided in Texas, Louisiana, Arkansas, or Oklahoma. Associations of marijuana use and TGCT were estimated using unconditional logistic regression, adjusting for age, race, prior cryptorchidism, cigarette smoking and alcohol intake. Results Overall, TGCT cases were more likely to be frequent marijuana users (daily or greater) than were controls [OR: 2.2, 95% CI: 1.0, 5.1]. In the histologic-specific analyses nonseminoma cases were significantly more likely than controls to be frequent users [OR: 3.1, 95% CI: 1.2, 8.2] and long-term users (10+ years) [OR: 2.4, 95% CI: 1.0, 6.1]. Discussion Our finding of an association between frequent marijuana use and TGCT, particularly among men with nonseminoma, is consistent with the findings of a previous report. Additional studies of marijuana use and TGCT are warranted, especially studies evaluating the role of endocannabinoid signaling and cannabinoid receptors in TGCT.

Trabert, Britton; Sigurdson, Alice J.; Sweeney, Anne M.; Strom, Sara S.; McGlynn, Katherine A.



Introduction to Germ Cell Development in C. elegans  

PubMed Central

A central feature of the continuum of life in sexually reproducing metazoans is the cycle of the germline from one generation to the next. This volume describes the cycle of the germline for Caenorhabditis elegans, through chapters that are focused on distinct aspects or processes in germ cell development. Topics include sequential and dependent processes such as specification of germ cells as distinct from somatic cells, sex determination, stem cell proliferative fate versus meiotic development decision, recombination/ progression through meiotic prophase, contemporaneous processes such as gametogenesis, meiotic development and apoptosis, and continuing the cycle into the next generation through fertilization and the oocyte-to-embryo-transition. Throughout germ cell development, translational control and epigenetic mechanisms play prominent roles. These different aspects of germ cell development are seamlessly integrated under optimal conditions and are modified in the different reproductive strategies that are employed by C. elegans under harsh environmental conditions. In this chapter we set the stage by providing a brief background on the C. elegans system and germ cell development, indicating processes in the cycle of the germline that are covered in each chapter.

Pazdernik, Nanette; Schedl, Tim



Mechanisms and chemical induction of aneuploidy in rodent germ cells  

SciTech Connect

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) can 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.

Mailhes, J B; Marchetti, F



Vanadium induced ultrastructural changes and apoptosis in male germ cells.  


Vanadium is a transition metal that is emitted to the atmosphere during combustion of fossil fuels. In the environment, vanadium occurs in the (V) oxidized form, but in the body it is found exclusively in the (IV) oxidized form. Vanadium tetraoxide is an inorganic chemical species in the (IV) oxidized form that has been shown to induce toxic effects in vitro and in vivo. The reproductive toxicity of vanadium in males was studied through monitoring germ cell apoptosis during spermatogenesis. We analyzed ultrastructural damage, and testosterone and progesterone concentrations following vanadium tetraoxide administered to male mice for 60 days. Spermatogenesis stages I-III and X-XII frequently showed apoptotic germ cells in control and treated animals; vanadium tetraoxide treatment induced an increase in the number of germ cell apoptosis in stages I-III and XII at 9.4 and 18.8 mg/kg, respectively. Although spermatogenesis is regulated by testosterone, in our study this hormone level was not modified by vanadium administration; thus, germ cell death was not related with testosterone concentration. At the ultrastructural level, we observed inclusion structures that varied as to location and content in the Sertoli and germ cells. PMID:15808796

Aragón, M A; Ayala, M E; Fortoul, T I; Bizarro, P; Altamirano-Lozano, M


A practical approach to immunohistochemical diagnosis of ovarian germ cell tumours and sex cord-stromal tumours.  


Immunohistochemistry can be useful in the diagnosis of ovarian germ cell tumours and sex cord-stromal tumours. A wide variety of markers are available, including many that are novel. The aim of this review is to provide a practical approach to the selection and interpretation of these markers, emphasizing an understanding of their sensitivity and specificity in the particular differential diagnosis in question. The main markers discussed include those for malignant germ cell differentiation (SALL4 and placental alkaline phosphatase), dysgerminoma (OCT4, CD117, and D2-40), yolk sac tumour (?-fetoprotein and glypican-3), embryonal carcinoma (OCT4, CD30, and SOX2), sex cord-stromal differentiation (calretinin, inhibin, SF-1, FOXL2) and steroid cell tumours (melan-A). In addition, the limited role of immunohistochemistry in determining the primary site of origin of an ovarian carcinoid tumour is discussed. PMID:23240671

Rabban, Joseph T; Zaloudek, Charles J



Mixed Germ Cell Tumor with Extensive Yolk Sac Tumor Elements in the Frontal Lobe of an Adult  

PubMed Central

Intracranial nongerminomatous germ cell tumors (NGGCTs) in unusual locations are extremely rare. Here, we report a case of a yolk sac tumor in the frontal lobe in a middle-aged patient. A 42-year-old man was admitted to our hospital for headache and nausea. Magnetic resonance imaging (MRI) showed an enhanced mass lesion with a marked cyst component. The serum alpha-fetoprotein (?FP) level was extremely high. Histological examination of specimens after subtotal removal revealed a primary mixed germ cell tumor with extensive yolk sac tumor elements, often referred to as an intracranial “yolk sac tumor.” The preoperative diagnosis of NGGCTs in unusual age and locations is extremely difficult. Clinicians should consider the possibility of NGGCTs, including yolk sac tumors, when intracranial tumors with unusual MRI findings are encountered.

Takahashi, Toshihide; Ishikawa, Eiichi; Masuda, Yosuke; Yamamoto, Tetsuya; Sato, Taiki; Shibuya, Makoto; Matsumura, Akira



Germ cell tumors with sarcomatous components: a clinicopathologic and immunohistochemical study of 46 cases.  


The clinicopathologic features of 46 patients with germ cell tumors with sarcomatous components (GCTSC) involving either the primary site or their metastases were studied. There were 43 men and 3 women aged 17 to 74 years. Twenty-three tumors arose in the mediastinum, 2 in the retroperitoneum, and 21 in the gonads. The germ cell component consisted of pure mature or immature teratoma (23 cases), teratoma mixed with other seminomatous or nonseminomatous components (17), pure seminoma (2), intratubular germ cell neoplasia (1), and yolk sac tumor (1). The SC included embryonal rhabdomyosarcoma (29), angiosarcoma (6), leiomyosarcoma (4), undifferentiated sarcoma (3), myxoid liposarcoma (1), malignant peripheral nerve sheath tumor (1), malignant "triton" tumor (1), and epithelioid hemangioendothelioma (1). Immunohistochemical studies were carried out in 34 cases with appropriate results supporting the diagnoses. Metastases containing both GCT and SC were observed in 6 cases, metastases of SC alone in 4, and metastases containing only GCT elements in 3. All patients were treated by cisplatinum-based chemotherapy plus other agents followed by surgery. Clinical follow-up was available in 40 patients (1 to 96 mo; mean=24 mo). Thirty-two of 40 patients either died of tumor (25/40; 62.5%) or were alive with advanced, progressive disease (7/40; 17.5%), and only 8/40 (20%) were alive and free of disease between 5 to 40 months (mean=18 mo). Comparison of these patients with an age-matched and stage-matched control group of patients with GCT without SC showed statistically significant differences in survival between the 2 cohorts (P

Malagón, Hugo Domínguez; Valdez, Ana María Cano; Moran, Cesar A; Suster, Saul



Ethical issues in manipulating the human germ line.  


This essay examines the arguments for and against working towards the objective of human germ line engineering for medical purposes. Germ line changes which result as a secondary consequence of other well designed and ethically acceptable manipulations of somatic cells to cure an otherwise fatal disease can be seen as acceptable. More serious objections apply to intentional germ line interventions because of the unacceptability of using a person solely as a vehicle for creating uncertain genetic change in his descendants. It is also morally unacceptable to use the promise of future benefit to experiment on fetuses or embryos when other more effective technologies exist to help parents have healthy children. Using new genetic technologies to select desirable genotypes among gametes is less problematic and affords a promising new technique for avoiding intergenerational harms. PMID:1787391

Lappé, M



Declaring the existence of human germ-cell mutagens.  


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 of recently developed genomic techniques. In preparation for this, an assessment panel of internationally recognized experts in germ-cell biology and genomics is required to consider either the current evidence now, or impending genomic evidence later, to declare whether an agent is a human germ-cell mutagen. I propose that such a panel be organized under the aegis of the World Health Organization and constructed similarly to the working groups assembled by the International Agency for Research on Cancer for the evaluation of human carcinogens. Support from prominent national and international organizations would be important. Many regulatory agencies already have procedures in place for assessing potential human germ-cell mutagens, and the time is approaching when definitive genomic data in humans will obligate such evaluations. In my view, application of an IARC-type of assessment using available evidence leads to the conclusion that ionizing radiation, cancer chemotherapy, cigarette smoking, and air pollution are "Group 1" human germ-cell mutagens. Consideration of the potential adverse health effects to the unexposed offspring of an exposed parent will usher in an entirely new realm of environmental health assessment. I suggest that the long search for human germ-cell mutagens is about to end, and a demonstration of the much-anticipated linkage between heritable disease and environmental factors is poised to begin. PMID:22351488

Demarini, David M



Germ plasm-like Dot cells maintain the wound regenerative function after in vitro expansion  

PubMed Central

Summary Wounds in fetal skin heal without scar, however the mechanism is unknown. We have identified a novel group of protein and nucleotides-positive particles in fetal and adult mouse blood and in human blood, and termed them “Dot cells”. Freshly isolated Dot cells regenerate wounds with less scarring and can be cultured without feeder layers.Because the morphology of Dot cells has never been described, in this study we describe the specific characterizations of Dot cells, including their growth pattern in vitro, and their expressions of stem cell markers using FACS analyses and immunofluorescent histology. Our data indicates that cultured Dot cells express stem cell surface markers and embryonic stem cell transcription markers, such as Oct4, Nanog and Sox-2. In addition, Dot cells express VASA, the germ plasm specific marker.To confirm if Dot cells maintain their wound regenerative activity after in vitro expansion, in vitro cultured Dot cells were transplanted to wounded mice. Dot cells from albino mice maintain their wound regenerative activities after intravenous transplantation to black-background diabetic mice. Also, Dot cells regenerate both the epithelial and dermal cells in the wounds of wild-type mice. The regenerated hair follicles, smooth muscle, and dermal tissues express transiently to VASA.Our data demonstrate that Dot cells are newly identified organisms located in the blood and bone marrow of mammals. They express germ cell, embryonic stem cell and adult stem cell markers. Dot cells maintain their regenerative function after in vitro expansion.

Kong, Wuyi; Li, Shaowei; Peter Lorenz, H.



Homotopy type of disentanglements of multi-germs  

NASA Astrophysics Data System (ADS)

For a complex analytic map f from n-space to p-space with n

germs it is known that the disentanglement is a wedge of spheres of possibly varying dimensions. In this paper we give a condition that allows us to deduce that the same is true for a large class of multi-germs.

Houston, Kevin



Status of human germ cell differentiation from pluripotent stem cells.  


Historically, the quality of life of infertile couples has been greatly diminished by the loss of opportunity to conceive. However, beginning with the advent of IVF in the late 1970s, novel clinical interventions have greatly changed the outlook for those with severe forms of infertility. Yet, in cases in which the quality and quantity of germ cells are most compromised, there are few options. In the present paper, the current status of germ cell development from stem cells is reviewed in light of potential utility for basic science and clinical applications. PMID:23445816

Pera, Renee A Reijo



Novel strong tissue specific promoter for gene expression in human germ cells  

PubMed Central

Background Tissue specific promoters may be utilized for a variety of applications, including programmed gene expression in cell types, tissues and organs of interest, for developing different cell culture models or for use in gene therapy. We report a novel, tissue-specific promoter that was identified and engineered from the native upstream regulatory region of the human gene NDUFV1 containing an endogenous retroviral sequence. Results Among seven established human cell lines and five primary cultures, this modified NDUFV1 upstream sequence (mNUS) was active only in human undifferentiated germ-derived cells (lines Tera-1 and EP2102), where it demonstrated high promoter activity (~twice greater than that of the SV40 early promoter, and comparable to the routinely used cytomegaloviral promoter). To investigate the potential applicability of the mNUS promoter for biotechnological needs, a construct carrying a recombinant cytosine deaminase (RCD) suicide gene under the control of mNUS was tested in cell lines of different tissue origin. High cytotoxic effect of RCD with a cell-death rate ~60% was observed only in germ-derived cells (Tera-1), whereas no effect was seen in a somatic, kidney-derived control cell line (HEK293). In further experiments, we tested mNUS-driven expression of a hyperactive Sleeping Beauty transposase (SB100X). The mNUS-SB100X construct mediated stable transgene insertions exclusively in germ-derived cells, thereby providing further evidence of tissue-specificity of the mNUS promoter. Conclusions We conclude that mNUS may be used as an efficient promoter for tissue-specific gene expression in human germ-derived cells in many applications. Our data also suggest that the 91 bp-long sequence located exactly upstream NDUFV1 transcriptional start site plays a crucial role in the activity of this gene promoter in vitro in the majority of tested cell types (10/12), and an important role - in the rest two cell lines.



Extragonadal germ cell tumors: a fine-needle aspiration biopsy study.  


Germ cell tumors (GCT) are neoplasms that originate predominately in the ovary and testis. Tumors of germ cell origin only very uncommonly arise in extragonadal sites. We have diagnosed ten primary malignant extragonadal GCT arising in the mediastinum, retroperitoneum, liver, and sacrococcygeal region by fine-needle aspiration biopsy (FNAB). Patient ages ranged from 1 to 54 years; the majority were males. Our series included three seminomas, three yolk sac tumors (YST), one choriocarcinoma, one embryonal carcinoma, and two mixed, poorly differentiated GCT. In aspirates, seminomatous elements are dissociated with uniform mononucleate cells having large vesicular nuclei and prominent nucleoli. A tigroid background is produced with Diff-Quik-stained smears. YST yields cohesive clusters of cells with large nuclei, vacuolated cytoplasm, and extracellular hyaline matrix (spheres or hyaline globules). Giant multinucleate tumor cells are seen in choriocarcinoma. Embryonal carcinoma yields cellular smears of hyperchromatic cells with scant cytoplasm arranged predominantly in glandular or papillary formations. Ultrastructural (four cases) and immunocytochemical (seven cases) studies of aspirated material corroborated our cytologic interpretations. Aneuploid tumor cells were found by flow cytometry in aspirated material from a YST. Subsequent histologic examinations were performed on eight, and all were confirmatory. Although extragonadal GCT are relatively uncommon, they need to be considered in FNAB material from midline mass lesions. Ancillary studies were useful in confirming their diagnosis. PMID:7621717

Collins, K A; Geisinger, K R; Wakely, P E; Olympio, G; Silverman, J F



Evolution of predetermined germ cells in vertebrate embryos: implications for macroevolution  

Microsoft Academic Search

SUMMARY The germ line is established in animal embryos with the formation of primordial germ cells (PGCs), which give rise to gametes. Therefore, the need to form PGCs can act as a developmental constraint by inhibiting the evolution of embryonic patterning mechanisms that compromise their development. Conversely, events that stabilize the PGCs may liberate these constraints. Two modes of germ

Andrew D. Johnson; Matthew Drum; Rosemary F. Bachvarova; Thomas Masi; Mary E. White; Brian I. Crotherd



Does Age Affect the Prognosis of Patients with Testicular Germ Cell Tumor?  

Microsoft Academic Search

Introduction: In this study, the effect of age on the prognosis of testicular germ cell tumors in patients over 40 was investigated. Materials and Methods: Ninety-three patients with testicular germ cell tumor who were 40 years old and over were identified in our germ cell tumor database. Patients were grouped according to their age with those between 40 and 44,

Kubilay Inci; Hasan Serkan Dogan; Bulent Akdogan; Ali Ergen; Celik Tasar; Haluk Ozen



Germ cell transplantation: a review and progress report on ICSI from spermatozoa generated in xenogeneic testes  

Microsoft Academic Search

Results from the transplantation of donor male germ cells into xenogeneic recipient seminiferous tubules indicate that donor spermatogonia are capable of differentiating to form spermatozoa morphologically characteristic of the donor species. Germ cell transplantation procedures combined with developments in freezing, culturing or enrich- ing germ cell populations have applications of paramount importance in medicine, basic sciences and animal repro- duction.

N. Sofikitis; A. Kaponis; Y. Mio; D. Makredimas; D. Giannakis; Y. Yamamoto; N. Kanakas; H. Kawamura; J. Georgiou; M. Schrader; E. Lolis; X. Giannakopoulos; D. Loutradis; V. Tarlatzis; I. Miyagawa




Technology Transfer Automated Retrieval System (TEKTRAN)

In order to identify high valued co-products from commercially processed corn germ, it was necessary to determine the affect of processing conditions on corn germ proteins. We found that significantly less protein was extracted from commercial wet- compared to dry-milled corn germ using Tris, SDS bu...



Technology Transfer Automated Retrieval System (TEKTRAN)

Methods have been proposed recently to separate germ from corn prior to fermentation to improve dry grind ethanol process economic return. Oil would be extracted from the germ and sold as a separate product. It is not clear that available methods to extract oil from this germ are economically pra...


Regulative germ cell specification in axolotl embryos: a primitive trait conserved in the mammalian lineage.  

PubMed Central

How germ cells are specified in the embryos of animals has been a mystery for decades. Unlike most developmental processes, which are highly conserved, embryos specify germ cells in very different ways. Curiously, in mouse embryos germ cells are specified by extracellular signals; they are not autonomously specified by maternal germ cell determinants (germ plasm), as are the germ cells in most animal model systems. We have developed the axolotl (Ambystoma mexicanum), a salamander, as an experimental system, because classic experiments have shown that the germ cells in this species are induced by extracellular signals in the absence of germ plasm. Here, we provide evidence that the germ cells in axolotls arise from naive mesoderm in response to simple inducing agents. In addition, by analysing the sequences of axolotl germ-cell-specific genes, we provide evidence that mice and urodele amphibians share a common mechanism of germ cell development that is ancestral to tetrapods. Our results imply that germ plasm, as found in species such as frogs and teleosts, is the result of convergent evolution. We discuss the evolutionary implications of our findings.

Johnson, Andrew D; Crother, Brian; White, Mary E; Patient, Roger; Bachvarova, Rosemary F; Drum, Matthew; Masi, Thomas




Microsoft Academic Search

From the time of the publication by Waldeyer in 1870 of his observations on the origin of germ cells in the embryo, there have been many contributions to the knowledge of this subject. Waldeyer's view that the germ cells arise from a germ­ inal epithelium in localized area of the peritoneum on the dorsal side of the coelom in vertebrates

A. Richards; J. B. Goldsmith


The relevance of spontaneous- and chemically-induced alterations in testicular germ cell apoptosis to toxicology  

Microsoft Academic Search

Elimination of germ cells via apoptosis occurs spontaneously under normal physiologic conditions and is often heightened after chemical-induced testicular injury. Though many different apoptosis-related elements have been identified in the testis, the molecular and cellular mechanisms that regulate germ cell apoptosis are not thoroughly understood. In this review, the role of germ cell apoptosis in spermatogenesis and possible key regulators

John H Richburg



Avoiding bad genes: oxidatively damaged DNA in germ line and mate choice  

Microsoft Academic Search

Summary August Weismann proposed that genetic changes in somatic cells cannot pass to germ cells and hence to next generations. Nevertheless, evidence is accumulat- ing that some environmental effects can promote herit- able changes in the DNA of germ cells, which implies that some somatic influence on germ line is possible. This influence is mostly detrimental and related to the

Alberto Velando; Roxana Torres; Carlos Alonso-Alvarez



Evidence against a germ plasm in the milkweed bug Oncopeltus fasciatus, a hemimetabolous insect  

PubMed Central

Summary Primordial germ cell (PGC) formation in holometabolous insects like Drosophila melanogaster relies on maternally synthesised germ cell determinants that are asymmetrically localised to the oocyte posterior cortex. Embryonic nuclei that inherit this “germ plasm” acquire PGC fate. In contrast, historical studies of basally branching insects (Hemimetabola) suggest that a maternal requirement for germ line genes in PGC specification may be a derived character confined principally to Holometabola. However, there have been remarkably few investigations of germ line gene expression and function in hemimetabolous insects. Here we characterise PGC formation in the milkweed bug Oncopeltus fasciatus, a member of the sister group to Holometabola, thus providing an important evolutionary comparison to members of this clade. We examine the transcript distribution of orthologues of 19 Drosophila germ cell and/or germ plasm marker genes, and show that none of them localise asymmetrically within Oncopeltus oocytes or early embryos. Using multiple molecular and cytological criteria, we provide evidence that PGCs form after cellularisation at the site of gastrulation. Functional studies of vasa and tudor reveal that these genes are not required for germ cell formation, but that vasa is required in adult males for spermatogenesis. Taken together, our results provide evidence that Oncopeltus germ cells may form in the absence of germ plasm, consistent with the hypothesis that germ plasm is a derived strategy of germ cell specification in insects.

Ewen-Campen, Ben; Jones, Tamsin E. M.; Extavour, Cassandra G.



Early orchiopexy: prepubertal intratubular germ cell neoplasia and fertility outcome  

Microsoft Academic Search

Objectives. To investigate the prepubertal prevalence of intratubular germ cell neoplasia of the unclassified type (ITGCNU) and its significance as a predictor of testicular cancer and to evaluate the effect of early orchiopexy (at younger than 2 years of age) on subsequent fertility of patients with bilateral cryptorchidism.Methods. Testicular biopsies (n = 660) from 440 prepubertal patients with cryptorchidism who

Daniel S Engeler; Paul O Hösli; Hubert John; Fridolin Bannwart; Tullio Sulser; Mahul B Amin; Philipp U Heitz; Seife Hailemariam



Musculoskeletal Differentiation of Cells Derived from Human Embryonic Germ Cells  

Microsoft Academic Search

Stem cells have the potential to significantly improve cell and tissue regeneration therapies, but little is understood about how to control their behavior. We investigated the potential differentiation capability of cells derived from human embryonic germ (EG) cells into musculoskeletal lineages by providing a three-dimensional environment with increased cell-cell contact and growth factors. Cells were clustered into pellets to mimic

Myoung Sook Kim; Nathaniel S. Hwang; Janice Lee; Tae-Kyun Kim; Kam Leong; Michael J. Shamblott; John Gearhart; Jennifer Elisseeff



p63 protects the female germ line during meiotic arrest  

Microsoft Academic Search

Meiosis in the female germ line of mammals is distinguished by a prolonged arrest in prophase of meiosis I between homologous chromosome recombination and ovulation. How DNA damage is detected in these arrested oocytes is poorly understood, but it is variably thought to involve p53, a central tumour suppressor in mammals. While the function of p53 in monitoring the genome

Eun-Kyung Suh; Annie Yang; Arminja Kettenbach; Casimir Bamberger; Ala H. Michaelis; Zhou Zhu; Julia A. Elvin; Roderick T. Bronson; Christopher P. Crum; Frank McKeon



Epigenetics of germ cells, stem cells, and early embryos.  


The International Symposium entitled "Germ Cells, Epigenetics, Reprogramming, and Embryonic Stem Cells" was organized by Norio Nakatsuji (Kyoto University) and Hiromitsu Nakauchi (University of Tokyo) in Kyoto, Japan (November 15-18, 2005). The meeting provided an overview of this important research area and highlighted recent advances. PMID:16506346

Ko, Minoru S H; McLaren, Anne



Testicular microlithiasis as a predictor of intratubular germ cell neoplasia  

Microsoft Academic Search

Sonographically detected testicular microlithiasis is an uncommon condition, which in recent years has been demonstrated with increased prevalence in patients with testicular tumors. We report a case of a 31-year old man with left testicular carcinoma and right intratubular germ cell neoplasia diagnosed by biopsy of the right testis at the time of left radical orchiectomy. In this case, preoperative

Brett L. Parra; Dennis D. Venable; Enrique Gonzalez; James A. Eastham



Germ cell tumors of the thalamus and the basal ganglia  

Microsoft Academic Search

Two cases of germ cell tumors (GCTs) of the basal ganglia are presented and 40 previously reported cases are reviewed. The incidence of GCTs of the basal ganglia and thalamus was estimated as less than 14% of all intracranial GCTs. All patients except for two (95%) were male, aged 7–19 years. The clinical course was usually slow. The major symptoms

Norihiko Tamaki; Tingkai Lin; Kunio Shirataki; Kohkichi Hosoda; Hiromitsu Kurata; Satoshi Matsumoto; Hiroshi Ito



Ultrastructure of female germ cells in Haliotis asinina Linnaeus  

Microsoft Academic Search

Germ cells in the ovary of H. asinina are divided into six stages: oogonia and five stages of oocytes. The oogonium is a scallop-shaped cell 8–10 ?m in diameter, closely adhered to a trabecula. Its nucleus exhibits small blocks of heterochromatin along the nuclear envelope and a small nucleolus. The cytoplasm contains abundant ribosomes. The stage I oocyte is a




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...


Mechanisms guiding primordial germ cell migration: strategies from different organisms  

Microsoft Academic Search

The regulated migration of cells is essential for development and tissue homeostasis, and aberrant cell migration can lead to an impaired immune response and the progression of cancer. Primordial germ cells (PGCs), precursors to sperm and eggs, have to migrate across the embryo to reach somatic gonadal precursors, where they carry out their function. Studies of model organisms have revealed

Brian E. Richardson; Ruth Lehmann



Tropics, germs, and crops: how endowments influence economic development  

Microsoft Academic Search

Does economic development depend on geographic endowments like temperate instead of tropical location, the ecological conditions shaping diseases, or an environment good for grains or certain cash crops? Or do these endowments of tropics, germs, and crops affect economic development only through institutions or policies? We test the endowment, institution, and policy views against each other using cross country evidence.

William Easterly; Ross Levine



Germ cell-less expression in zebrafish embryos.  


The gene of germ cell-less (gcl) has been shown to be important in early differentiation of germ cells in Drosophila. Although the gcl homologue genes have been identified in some organisms, there is little data on the expression pattern and functional analysis of the gcl gene in zebrafish. In this research, real-time quantitative reverse transcription-polymerase chain reaction showed that the level of gcl mRNA expression rapidly decreases from the 4-cell stage to the sphere stage at which it reaches a minimum, gradually increases from the 50%-epiboly stage, and then remains stable during the posterior stages. Results of in situ hybridization indicated that the transcripts of zebrafish gcl are evenly distributed in all blastomeres from the 2-cell stage to the blastula period, different from that of vasa, nonas1 and dead end mRNA, and condense into some clusters of cells located along the blastoderm margin from the gastrulation period. During subsequent development, the transcripts are segregated as subcellular clumps to a small number of cells that would migrate to the position of the gonad in the dorsal side. In the adult, gcl mRNA was widely expressed in developing germ cells of both ovary and testis. These data suggest that zebrafish gcl have potentially important roles in the formation of primordial germ cells. PMID:16759283

Li, Wenyan; Deng, Fengjiao; Wang, Huannan; Zhen, Yan; Xiang, Fang; Sui, Yang; Li, Jianzhen



Effects of 27 MHz Radiation on Somatic and Germ Cells.  

National Technical Information Service (NTIS)

In an effort to further understanding of the effects of radiofrequency (RF) radiation on somatic cell mitotic activity and germ cell function, cell suspensions were exposed to 27 megahertz (MHz) or 2.450MHz radiation under isothermal conditions in-vitro. ...

S. F. Cleary L. M. Liu G. Cao R. Merchant J. East R. Diegelmann J. Collins



Curing metastatic cancer: lessons from testicular germ-cell tumours  

Microsoft Academic Search

Most metastatic cancers are fatal. More than 80% of patients with metastatic testicular germ-cell tumours (TGCTs), however, can be cured using cisplatin-based combination chemotherapy. Why are TGCTs more sensitive to chemotherapeutics than most other tumour types? Answers to this question could lead to new treatments for metastatic cancers.

John R. W. Masters; Beate Köberle



Primary Malignant Melanoma of the Mediastinum: Radiologic and Pathologic Correlation in Two Case  

PubMed Central

Primary malignant melanoma of the anterior mediastinum is extremely rare, accounting for 0.1-0.5% of all primary malignant neoplasms. These tumors may be mistakenly diagnosed as lymphomas, thymic carcinomas and malignant germ-cell tumors of the mediastinum. We describe two cases of primary malignant melanomas of the anterior mediastinum and report their CT and pathology findings.

Park, Sun-Young; Chae, Eun Jin



[Infectious endocarditis caused by rare germs. Review of the literature apropos of 2 cases].  


The authors report two new cases of endocarditis secondary to exceptionnally encountered germs: one to Pasteurella pneumotropica, the other ascribed to Leptospira ictero-haemorragiae, on serologic criteria. Concerning these two cases, they propose to take a census of rare germs, from a detailed study of the literature. Among more than 5,000 cases of endocarditis published after 1944, are considered as rare germs those causing a disease in less than one p. cent of the cases. This purely "mathematical" definition enable to include 45 germs. A synthesis of all the cases reported attempts to demonstrate a few particular traits of these endocardites secondary to rare germs. PMID:3827160

Cornaert, P; Masson, P; Forzy, G; Graux, P; Camblin, J; Dutoit, A; Croccel, L



Staging of primary mediastinal tumors.  


Primary mediastinal tumors, with the exception of lymphoma, are generally rare neoplasms. The diagnosis, classification, and treatment of these tumors still cause some degree of difficulty due to their low incidence and morphologic heterogeneity. This is particularly true for thymic epithelial neoplasms, that is, thymoma and thymic carcinoma, and also applies to primary neuroendocrine carcinomas of the thymus and primary mediastinal germ cell tumors. The appropriate staging of these tumors, likewise, has been a matter of debate over the years and numerous proposals for the staging of thymic epithelial neoplasms have been put forward in the last few decades. Unfortunately, variations of such proposals have been used in some instances to stage other tumors such as thymic neuroendocrine carcinomas and germ cell tumors, which has led to the often inappropriate use of a single staging system for different types of tumors with different biological behavior. This review will provide an overview of the staging of primary mediastinal tumors with special emphasis on more recent assessments in this particular area. PMID:23232566

Weissferdt, Annikka; Moran, Cesar A



[Biphasic pulmonary blastoma with germ cell differentiation: a challenge in diagnosis and treatment].  


Serviço de Oncologia Médica. Instituto Portuguęs de Oncologia Francisco Gentil. Porto. Portugal. A 27-year-old man, smoker, presented with three months history of fever. A left pulmonary mass inseparable from the heart was identified and serum alpha-fetoprotein was 4160 ng/ml. The morphologic aspects and immunohistochemistry of the biopsy specimen, in conjunction with the clinical findings were compatible with a diagnosis of pulmonary blastoma with germ cell differentiation. The tumour was considered unresectable. The patient was submitted to two cycles of primary chemotherapy with bleomycin, etoposide and cisplatin. Despite a reduction in serum alpha-fetoprotein, the tumor did not regress. Second line chemotherapy (with paclitaxel, ifosfamide and cisplatin) was instituted, but progressive disease was identified after 2 cycles. Six months after the diagnosis cerebral metastases were found and the patient died. This case illustrates a rare situation of difficult diagnosis and treatment. PMID:22856413

Teixeira, Alexandra; Vieira, Claúdia; Sousa, Nuno; Begonha, Rosa; Afonso, Mariana; Amaro, Teresina; Maurício, Joaquina



The Role of dead-end in Germ-cell Tumor Development  

PubMed Central

Testicular germ-cell tumors occur in human males of all age groups, from infants to men over 50 years old. Most commonly, germ-cell tumors (generally known as testicular cancer) occur in young males between the ages of 15 to 35 years. The tumor tissues are usually his-tologically diverse, and testicular tumors that occur in the different age groups tend to be of specific histological subtypes. Most germ-cell tumors originate from primordial germ cells during embryonic development, although the progression and eventual detection of the disease occurs decades later in humans. Mouse strains spontaneously develop a specific subtype of testicular germ-cell tumors, the type I germ-cell tumors, and these tumors are similar to the germ-cell tumors (or teratomas) that occur in human infants. Some mouse strains, such as the 129-Ter strain, have extremely high germ-cell tumor incidences, making such strains ideal for genetic and biological studies of germ cell-tumor development. Here a brief overview of the recently identified genetic defect in the Ter strain, inactivation of the dead-end (Dnd1) gene, and the ongoing studies on Dnd1 to understand its role in germ-cell and germ cell-tumor development, are provided.




The role of a Xenopus DAZ-like gene (Xdazl) in the development of primordial germ cells  

Microsoft Academic Search

In the frog Xenopus laevis, a region of cytoplasm at the vegetal pole of oocytes and eggs, the germ plasm, is critical for the formation of primordial germ cells (PGCs). Only blastomeres that inherit the germ plasm can differentiate as PGCs. The germ plasm contains unique \\

Douglas William Houston



Tagged Mutagenesis by Efficient Minos-Based Germ Line Transposition ? †  

PubMed Central

Germ line gene transposition technology has been used to generate “libraries” of flies and worms carrying genomewide mutations. Phenotypic screening and DNA sequencing of such libraries provide functional information resulting from insertional events in target genes. There is also a great need to have a fast and efficient way to generate mouse mutants in vivo to model developmental defects and human diseases. Here we describe an optimized mammalian germ line transposition system active during early mouse spermatogenesis using the Minos transposon. Transposon-positive progeny carry on average more than 2 new transpositions, and 45 to 100% of the progeny carry an insertion in a gene. The optimized Minos-based system was tested in a small rapid dominant functional screen to identify mutated genes likely to cause measurable cardiovascular “disease” phenotypes in progeny/embryos. Importantly this system allows rapid screening for modifier genes.

de Wit, Ton; Dekker, Sylvia; Maas, Alex; Breedveld, Guido; Knoch, Tobias A.; Langeveld, An; Szumska, Dorota; Craig, Roger; Bhattacharya, Shoumo; Grosveld, Frank; Drabek, Dubravka



Germ-line engineering: a few European voices.  


We have surveyed various recent European opinions on germ-line engineering. The majority express more or less severe reservations about any interventions on the human germ-line, including therapeutic ones. However, they are divided over the pragmatic, or categorical-ethical nature of the relevant arguments. This split reflects two competing views of technology. The 'pessimistic' one is deeply concerned by the slippery slope leading from bona fide therapeutic applications of genetic engineering to eugenic practices. It insists that, if anything can defend us against these evils, it must be a set of strong, ethically-based prohibitions. The other, 'optimist' view is more confident in the discriminating powers of societal regulation. We argue for the latter view and suggest that the pragmatic arguments brought to this debate are less problematic than the ethical ones. PMID:1787393

Mauron, A; Thévoz, J M



In Search of a Germ Theory Equivalent for Chronic Disease  

PubMed Central

The fight against infectious disease advanced dramatically with the consolidation of the germ theory in the 19th century. This focus on a predominant cause of infections (ie, microbial pathogens) ultimately led to medical and public health advances (eg, immunization, pasteurization, antibiotics). However, the resulting declines in infections in the 20th century were matched by a rise in chronic, noncommunicable diseases, for which there is no single underlying etiology. The discovery of a form of low-grade systemic and chronic inflammation (“metaflammation”), linked to inducers (broadly termed “anthropogens”) associated with modern man-made environments and lifestyles, suggests an underlying basis for chronic disease that could provide a 21st-century equivalent of the germ theory.



Malignant mediastinal germ cell tumor with pure hepatoid differentiation.  


We describe a germ cell tumor of anterior mediastinal origin, with pure hepatoid differentiation and elevated serum AFP in a 41-year-old man. This is the first report of such a neoplasm analyzed by conventional stains and immunohistochemistry. Hepatocellular differentiation was proved by immunoreactivity with HepPar-1 and alpha-fetoproein (AFP), membranous expression of carcinoembryonic antigen (CEA-poly) in a canalicuar pattern, and focal expression of cytokeratin 19 in abortive ductular structures. Our investigation shows that mediastinal germ cell tumors with hepatoid components typically arise in middle-aged men; they are of pure hepatoid differentiation, as demonstrated here, or exclusively associated with yolk sac structures. PMID:12530574

Theuerkauf, Ingo; Axmann, Cristoph; Wolff, Martin; Tschubel, Klaus; Fischer, Hans-Peter



Fucose-specific adhesins on germ tubes of Candida albicans  

Microsoft Academic Search

Lectin-like adhesins of hyphal-form Candida albicans were investigated by conventional fluorescence microscopy, fluorescence microscopy with image analysis, spectrofluorimetry and flow cytometry. Labelling was done with neoglycoprotein probes consisting of sugars (fucose, mannose, glucose, galactose, lactose) covalently linked to bovine serum albumin (BSA), which itself was labelled with fluorescein. The fucose probe bound to both the yeast and germ-tube portions of

Gülhan Vardar-Ünlü; Charles McSharry; L. Julia Douglas



Reprogramming Male Germ Cells to Pluripotent Stem Cells  

Microsoft Academic Search

\\u000a Reprogramming of a differentiated cell into a cell capable of giving rise to many different cell types, a pluripotent cell,\\u000a which in turn could repopulate or repair nonfunctional or damaged tissue, would present beneficial applications in regenerative\\u000a medicine. It was shown by different groups that germ cells can be reprogrammed to pluripotent stem cells in all diploid stages\\u000a of development.

Parisa Mardanpour; Kaomei Guan; Tamara Glaeser; Jae Ho Lee; Jessica Nolte; Gerald Wulf; Gerd Hasenfuss; Wolfgang Engel; Oliver Brüstle; Karim Nayernia


miRNA and mammalian male germ cells.  


BACKGROUND Achieving the correct spatial and temporal expression of germ-cell-specific genes is fundamental to the production of viable healthy spermatozoa. Notably, post-transcriptional gene regulation resulting in the repression of protein translation is central to many embryonic processes, and is particularly active during spermatogenesis. In this review, we discuss microRNA (miRNA) regulation of target gene expression in relation to mammalian spermatogenesis, the establishment of testicular germ cell tumours (TGCT) and the potential use of miRNA manipulation for cancer therapy and fertility regulation. METHODS Journal databases such as PubMed were searched using key words, including miRNA, testis, spermatogenesis, germ cell, testicular cancer and cancer. RESULTS In the past decade, the deployment of small non-coding RNA molecules, including miRNA, by the cell, has been recognized as among the most important mechanisms of fine-tuning translational regulation in differentiating cell types. For key regulators of male gametogenesis, high levels of gene expression do not always correspond to elevated levels of protein expression. Cumulatively this indicates that enhancement and repression of post-transcriptional regulatory mechanisms are essential to the success of spermatogenesis. There is also growing evidence that this form of regulation contributes to the aetiology of both TGCT and spermatocytic tumours. CONCLUSIONS miRNA plays an essential role in regulation of genes during the process of spermatogenesis. Disruption of this regulation has the ability to contribute to the neoplastic development of germ cell tumours. However, targeted knockdown of specific miRNA molecules has the potential to form both anti-oncogenic reagents and underpin the basis for novel contraceptive technologies. PMID:21989172

McIver, S C; Roman, S D; Nixon, B; McLaughlin, E A



Role of epigenetics in the etiology of germ cell cancer.  


Embryonic development is strictly controlled by functionality of genes in which the existing networks can act both on transcription and translation regulation. Germ cell cancers (GCC) are unique because of a number of characteristics. In spite of their clinical presentation, i.e., predominantly after puberty, they arise from primordial germ cells/gonocytes that have failed appropriate maturation to either pre-spermatogonia or oogonia. GCC mimic embryonal development to a certain extent, including capacity for totipotency. This knowledge has allowed the identification of informative diagnostic markers, including OCT3/4 (POU5F1), SOX2 and SOX17. An additional marker is the overall demethylated status of the genome. Genetic mutations in GCC are rare, which is exceptional for solid cancers. Our hypothesis is that a disturbed epigenetic regulation (through combined interaction of genetic or environmental parameters; referred to as genvironment) affect embryonic germ cell development, resulting in delayed or blocked maturation, and potentially progression to GCC. In this respect, studies of patients with Disorders of Sex Development (DSD) have increased our knowledge significantly. Genvironmental influences can lead to retention of existence of embryonic germ cells, the first step in the pathogenesis of GCC, resulting into the precursor lesions gonadoblastoma or carcinoma in situ. Identification of epigenetic alterations could lead to better understanding these processes and development of specific markers for early detection, eventually leading to development of targeted treatment. This review describes an interactive model related to the role of epigenetics in GCC pathogenesis, focusing on DNA methylation, histone modifications, epigenetic memory and inheritance, as well as environmental factors. PMID:23784841

Van Der Zwan, Yvonne G; Stoop, Hans; Rossello, Fernando; White, Stefan J; Looijenga, Leendert H J



Plasma lipid lowering effects of wheat germ in hypercholesterolemic subjects  

Microsoft Academic Search

The present study was performed to investigate the possible effects of wheat germ supplementation on lipid metabolism in humans. Ten free-living adult subjects participated in the study. None was obese or diabetic. They all presented an, hypercholesterolemia (from 6.58 to 9.50 mM), associated in 6 over 10 cases to an hypertriglyceridemia (from 1.70 to 5.00 mM). The subjects were studied

Louis Cara; Patrick Borel; Martine Armand; Michele Senft; Huguette Lafont; Henri Portugal; Anne-Marie Pauli; Daniele Boulze; Christianne Lacombe; Denis Lairon



European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG)  

Microsoft Academic Search

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > _ 99% in early stages and 90%, 75-80% and 50% in

H. J. Schmoll; R. Souchon; S. Krege; P. Albers; J. Beyer; C. Kollmannsberger; S. D. Fossa; N. E. Skakkebaek; R. de Wit; K. Fizazi; J. P. Droz; G. Pizzocaro; G. Daugaard; P. H. M. de Mulder; A. Horwich; T. Oliver; R. Huddart; G. Rosti; L. Paz Ares; O. Pont; J. T. Hartmann; N. Aass; F. Algaba; M. Bamberg; I. Bodrogi; C. Bokemeyer; J. Classen; S. Clemm; S. Culine; M. de Wit; H. G. Derigs; K. P. Dieckmann; M. Flasshove; X. Garcia del Muro; A. Gerl; J. R. Germa-Lluch; M. Hartmann; A. Heidenreich; W. Hoeltl; J. Joffe; W. Jones; G. Kaiser; O. Klepp; S. Kliesch; L. Kisbenedek; K. U. Koehrmann; M. A. Kuczyk; M. P. Laguna; O. Leiva; V. Loy; M. D. Mason; G. M. Mead; R. P. Mueller; N. Nicolai; G. O. N. Oosterhof; T. Pottek; O. Rick; H. Schmidberger; F. Sedlmayer; W. Siegert; U. Studer; S. Tjulandin; H. von der Maase; P. Walz; S. Weinknecht; L. Weissbach; E. A. M. Winter; C. Wittekind



Molecular Cloning and Genomic Organization of Mouse Homologue of Drosophila germ cell-less and Its Expression in Germ Lineage Cells  

Microsoft Academic Search

Primordial germ cells (PGCs) are founder cells of all gametes. A number of genes which control PGCs development have been identified in invertebrates, whereas such genes are by and large unelucidated in mammals. Here we describe cloning, genomic structure and expression of mouse homologue of germ cell-less (gcl) gene which is required for PGCs formation in Drosophila. The mouse gcl

Tohru Kimura; Kentaro Yomogida; Naomi Iwai; Yukiko Kato; Toru Nakano



Controlled nucleation in freeze-drying: effects on pore size in the dried product layer, mass transfer resistance, and primary drying rate.  


A novel and scalable method has been developed to enable control of the ice nucleation step for the freezing process during lyophilization. This method manipulates the chamber pressure of the freeze dryer to simultaneously induce nucleation in all product vials at a desired temperature. The effects of controlled nucleation on the drying rate of various formulations including 5% (w/w) mannitol, 5% (w/w) sucrose, and a mixture of 3% (w/w) mannitol and 2% (w/w) sucrose were studied. For a 5% (w/w) mannitol, uncontrolled ice nucleation occurred randomly at product temperatures between -8.0°C and -15.9°C as the vials were cooled to -40°C. Controlled ice nucleation was achieved at product temperatures between -2.3°C and -3.7°C. The effect of nucleation control on the effective pore radius (r(e) ) of the cake was determined from the product temperature profiles using a pore diffusion model in combination with a nonlinear parameter estimation approach reported earlier. Results show that the value of r(e) for 5% (w/w) mannitol was enlarged from 13 to 27 ?m by uniformly inducing nucleation at higher temperatures. Applying the resistance parameters obtained from the pore diffusion model for 5% (w/w) mannitol, optimized cycles were theoretically generated and experimentally tested, resulting in a 41% reduction in primary drying time. PMID:21465488

Konstantinidis, Alex K; Kuu, Wei; Otten, Lori; Nail, Steven L; Sever, Robert R



Tre1, a G Protein-Coupled Receptor, Directs Transepithelial Migration of Drosophila Germ Cells  

PubMed Central

In most organisms, germ cells are formed distant from the somatic part of the gonad and thus have to migrate along and through a variety of tissues to reach the gonad. Transepithelial migration through the posterior midgut (PMG) is the first active step during Drosophila germ cell migration. Here we report the identification of a novel G protein-coupled receptor (GPCR), Tre1, that is essential for this migration step. Maternal tre1 RNA is localized to germ cells, and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos, most germ cells do not exit the PMG. The few germ cells that do leave the midgut early migrate normally to the gonad, suggesting that this gene is specifically required for transepithelial migration and that mutant germ cells are still able to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration, suggesting that Tre1 signals through Rho1. We propose that Tre1 acts in a manner similar to chemokine receptors required during transepithelial migration of leukocytes, implying an evolutionarily conserved mechanism of transepithelial migration. Recently, the chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells. Thus, germ cells may more generally use GPCR signaling to navigate the embryo toward their target.



Germ plasm in Eleutherodactylus coqui, a direct developing frog with large eggs  

PubMed Central

Background RNAs for embryo patterning and for germ cell specification are localized to the vegetal cortex of the oocyte of Xenopus laevis. In oocytes of the direct developing frog Eleutherodactylus coqui, orthologous RNAs for patterning are not localized, raising the question as to whether RNAs and other components of germ plasm are localized in this species. Methods To identify germ plasm, E. coqui embryos were stained with DiOC6(3) or examined by in situ hybridization for dazl and DEADSouth RNAs. The cDNAs for the E. coqui orthologues were cloned by RT-PCR using degenerate primers. To examine activity of the E. coqui orthologues, RNAs, made from constructs of their 3'UTRs with mCherry, were injected into X. laevis embryos. Results Both DiOC6(3) and dazl and DEADSouth in situs identified many small islands at the vegetal surface of cleaving E. coqui embryos, indicative of germ plasm. Dazl was also expressed in primordial germ cells in the genital ridge. The 3'UTRs of E. coqui dazl and DEADSouth directed primordial germ cell specific protein synthesis in X. laevis. Conclusions E. coqui utilizes germ plasm with RNAs localized to the vegetal cortex to specify primordial germ cells. The large number of germ plasm islands suggests that an increase in the amount of germ plasm was important in the evolution of the large E. coqui egg.



Management of good risk germ-cell tumours.  


Following the implementation of cisplatin-containing combined chemotherapy, patients with good-risk metastatic germ-cell cancer have an excellent prognosis. Since the 1980s, bleomycin, etoposide and cisplatin (BEP) have become the standard chemotherapy regimen for these patients. In view of both the high curative potential of BEP chemotherapy and the treatment-related side-effects, trials were carried out in patients with the greatest chance of cure to develop regimens with an improved toxicity profile while maintaining efficacy. Following the results of these trials, the standard chemotherapy in good-risk disease has been reduced from four cycles of BEP (4BEP) to three cycles of BEP (3BEP). Four cycles of etoposide and cisplatin (4EP) is an alternative treatment regimen, with similar efficacy. Studies that explored additional adjustments in the BEP regimen to further decrease toxicity have shown that the lower threshold of efficacy has been reached, and that the efficacy of the chemotherapy is compromised. Especially during the last decade, important long-term side-effects after the treatment of germ-cell cancers have been recognized. Chemotherapy in patients with germ-cell cancer increases the risk of developing cardiovascular disease and second malignant neoplasms. Whether 3BEP or 4EP is the optimal chemotherapy regimen for the future remains to be identified. Possibly differences in acute and late toxicities attributed to chemotherapy might eventually identify the best strategy. PMID:19840018

Troost, Monique M; Sternberg, Cora N; de Wit, Ronald



Sex chromosome silencing in the marsupial male germ line.  


In marsupials, dosage compensation involves silencing of the father's X-chromosome. Because no XIST orthologue has been found, how imprinted X-inactivation occurs is unknown. In eutherians, the X is subject to meiotic sex chromosome inactivation (MSCI) in the paternal germ line and persists thereafter as postmeiotic sex chromatin (PMSC). One hypothesis proposes that the paternal X is inherited by the eutherian zygote as a preinactive X and raises the possibility of a similar process in the marsupial germ line. Here we demonstrate that MSCI and PMSC occur in the opossum. Surprisingly, silencing occurs before X-Y association. After MSCI, the X and Y fuse through a dense plate without obvious synapsis. Significantly, sex chromosome silencing continues after meiosis, with the opossum PMSC sharing features of eutherian PMSC. These results reveal a common gametogenic program in two diverse clades of mammals and support the idea that male germ-line silencing may have provided an ancestral form of mammalian dosage compensation. PMID:17535928

Namekawa, Satoshi H; VandeBerg, John L; McCarrey, John R; Lee, Jeannie T



Drosophila germ-line modulation of insulin signaling and lifespan.  


Ablation of germ-line precursor cells in Caenorhabditis elegans extends lifespan by activating DAF-16, a forkhead transcription factor (FOXO) repressed by insulin/insulin-like growth factor (IGF) signaling (IIS). Signals from the gonad might thus regulate whole-organism aging by modulating IIS. To date, the details of this systemic regulation of aging by the reproductive system are not understood, and it is unknown whether such effects are evolutionarily conserved. Here we report that eliminating germ cells (GCs) in Drosophila melanogaster increases lifespan and modulates insulin signaling. Long-lived germ-line-less flies show increased production of Drosophila insulin-like peptides (dilps) and hypoglycemia but simultaneously exhibit several characteristics of IIS impedance, as indicated by up-regulation of the Drosophila FOXO (dFOXO) target genes 4E-BP and l (2)efl and the insulin/IGF-binding protein IMP-L2. These results suggest that signals from the gonad regulate lifespan and modulate insulin sensitivity in the fly and that the gonadal regulation of aging is evolutionarily conserved. PMID:18434551

Flatt, Thomas; Min, Kyung-Jin; D'Alterio, Cecilia; Villa-Cuesta, Eugenia; Cumbers, John; Lehmann, Ruth; Jones, D Leanne; Tatar, Marc



Porcine reproductive and respiratory syndrome virus replicates in testicular germ cells, alters spermatogenesis, and induces germ cell death by apoptosis.  

PubMed Central

Like other arteriviruses, porcine reproductive and respiratory syndrome virus (PRRSV) is shed in semen, a feature that is critical for the venereal transmission of this group of viruses. In spite of its epidemiological importance, little is known of the association of PRRSV or other arteriviruses with gonadal tissues. We experimentally infected a group of boars with PRRSV 12068-96, a virulent field strain. By combined use of in situ hybridization and immunohistochemistry, we detected infection by PRRSV in the testes of these boars. The PRRSV testicular replication in testis centers on two types of cells: (i) epithelial germ cells of the seminiferous tubules, primarily spermatids and spermatocytes, and (ii) macrophages, which are located in the interstitium of the testis. Histopathologically, hypospermatogenesis, formation of multinucleated giant cells (MGCs), and abundant germ cell depletion and death were observed. We obtained evidence that such germ cell death occurs by apoptosis, as determined by a characteristic histologic pattern and evidence of massive DNA fragmentation detected in situ (TUNEL [terminal deoxynucleotidyltransferase-mediated digoxigenin-UTP nick end labeling] assay). Simultaneously with these testicular alterations, we observed that there is a significant increase in the number of immature sperm cells (mainly MGCs, spermatids, and spermatocytes) in the ejaculates of the PRRSV-inoculated boars and that these cells are infected with PRRSV. Our results indicate that PRRSV may infect target cells other than macrophages, that these infected cells can be primarily responsible for the excretion of infectious PRRSV in semen, and that PRRSV induces apoptosis in these germ cells in vivo.

Sur, J H; Doster, A R; Christian, J S; Galeota, J A; Wills, R W; Zimmerman, J J; Osorio, F A



A revised timeline for biological agents: revisiting the early years of the germ theory of disease.  


An agreed upon timeline for the initial, scientifically-informed use of biological agents typically begins with the Japanese Army in Manchuria and China prior to the generalized outbreak of World War II (1932 until 1945). The process included human experimentation with multiple biological agents followed by their release in combat (e.g. the plague bacillus) targeting military personnel and civilians. Two postulates are used support these dates. First, allegations of earlier bacteriological weapon experimentation and/or use represented the accidental, small scale, and sporadic dispersion of infectious agents preceding the Germ Theory of Disease. Therefore, attempts prior to the Twentieth Century were uninformed scientifically and are not considered representative. Later, as the Germ Theory was maturing, the hypothetical timeline was derived, in part retrospectively, from reputable historical sources (the Trillat Report and The League of Nations) published immediately upon the conclusion of World War I. These documents explicitly testified to the total absence of bacteriological weapons in any form (experimentation or battlefield application) directed at human subjects-in stark contrast to the utilization of chemical agents-during the course of that war. Therefore the Japanese Army in Manchuria became time zero. Recently, evidence previously hidden from outside study has surfaced demonstrating that a small group of Turkish physicians injected typhus-contaminated serum into Armenian civilians during WWI. Although controversy persists regarding primary intent-immunization, experimentation on human subjects, or the introduction of a crude biological weapon-the discovery might suggest a revision to the accepted timeline. The primitive efforts with contaminated serum that occurred during the First World War may seem trivial, especially when compared to overall fatalities during that conflict, but they did include the informed and fatal application of microbial agents. Furthermore, the actions may have influenced certain behaviors that followed in World War II. PMID:16963192

Rutecki, Gregory W



The developmental fate of green fluorescent mouse embryonic germ cells in chimeric embryos  

Microsoft Academic Search

Primordial germ cells (PGCs), as precursors of mammalian germ lineage, have been gaining more attention as a new resource of pluripotent stem cells, which bring a great possibility to study developmental events of germ cell in vitro and at animal level. EG4 cells derived from 10.5 days post coitum (dpc) PGCs of 129\\/svJ strain mouse were established and maintained in

Xin XU; Yong Shen YU; Hsiao Chien TSUNG; Sumio SUGANO; Yuan Chang YAN



[Periodontal development after tooth germ transplantation within the framework of orthodontic treatment].  


The normal development of the periodontal structures was confirmed histologically on young beagle dogs following tooth germ transplants. In humans, clinical and radiographic examinations revealed no pathology of the periodontium following transplantation of tooth germs. The grafted teeth could be moved orthodontically in the same way as any other teeth. No precautions need to be taken. This paper describes the most common indications for transplanting the tooth germs of canines, bicuspids and molars. PMID:2792989

Eskici, A; Droschl, H; Bantleon, H; Permann, I



Evaluation of corn germ protein as an extender in plywood adhesive  

Microsoft Academic Search

This study was conducted to evaluate the potential of wet-milled corn germ protein as an extender in plywood adhesive. Partially defatted dried corn germ from wet-milling, containing 2.1% (dry basis, db) crude oil and 24.7% (db) crude protein, was ground to 40-mesh particle size to produce the meal. The predominant water- and saline-soluble proteins were extracted from the corn germ

Mila P. Hojilla-Evangelista



The Chromatoid Body: A Specialized RNA Granule of Male Germ Cells  

Microsoft Academic Search

\\u000a RNA processing and miRNA pathways have been shown to exert a central control on a wide variety of cellular functions. The\\u000a epigenetic program of male germ cells is highly specialized, including RNA processing pathways, which play an important role\\u000a in the male germ cell lineage. Male germ cells differentiate through a remarkable process of cellular restructuring. One highly\\u000a specialized structure

Ippei Nagamori; Adam Cruickshank; Paolo Sassone-Corsi


Windows for sex-specific methylation marked by DNA methyltransferase expression profiles in mouse germ cells  

Microsoft Academic Search

The acquisition of genomic methylation in the male germ line is initiated prenatally in diploid gonocytes, while DNA methylation in the female germ line is initiated postnatally in growing oocytes. We compared the temporal expression patterns of the DNA methyltransferases, DNMT1, DNMT3a, DNMT3b, and DNMT3l in the male and female germ lines. DNMT1 expression was examined by immunocytochemistry and Northerns

Sophie La Salle; Carmen Mertineit; Teruko Taketo; Peter B Moens; Timothy H Bestor; Jacquetta M Trasler



Secondary Acute Monocytic Leukemia Occurring during the Treatment of a Testicular Germ Cell Tumor  

Microsoft Academic Search

Secondary leukemia following chemotherapy or radiotherapy for mediastinal germ cell tumors is a well-described entity. It also may occur in patients with testicular germ cell tumors. We report a case of acute monocytic leukemia occurring in a 44-year-old man who received etoposide-based chemotherapy and radiotherapy for a recurrent, metastatic testicular germ cell tumor. The patient recevied 14 cycles of systemic

Norio Nonomura; Nobukazu Murosaki; Yasuyuki Kojima; Nobuyuki Kondoh; Toshinobu Seguchi; Yoshito Takeda; Yusuke Oji; Hiroyasu Ogawa; Haruo Sugiyama; Tsuneharu Miki; Äkďhďko Okuyama



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

NASA Astrophysics Data System (ADS)

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.

Ergazaki, Marida; Saltapida, Konstantina; Zogza, Vassiliki



Identifying disruptors of male germ cell development by small molecule screening in ex vivo gonad cultures  

PubMed Central

Background Germ cell development involves formation of the spermatogenic or oogenic lineages from the bipotential primordial germ cells. Signaling mechanisms in the fetal testis and ovary determine whether germ cells enter the male or female developmental pathway, respectively. These signaling processes underpin an important phase of germ cell development, disruption of which can lead to failed germ cell function resulting in infertility or the formation of germ cell tumours. Findings In this study we have developed a small molecule screening protocol combined with flow cytometry to identify signaling pathways that direct male-specific development of germ cells. Here we provide a detailed method for this screening protocol, which we have used to identify signaling pathways important for male germ cell development. Conclusion This method will be of particular use in screening inhibitors of signaling pathways, endocrine disruptors or other chemicals for their ability to disrupt testis and germ cell development, thereby providing insight into testicular dysgenesis and factors underlying poor male reproductive health.



Genetic Evidence That the Ovo Locus Is Involved in Drosophila Germ Line Sex Determination  

PubMed Central

Zygotically contributed ovo gene product is required for the survival of female germ cells in Drosophila melanogaster. Trans-allelic combinations of weak and dominant ovo mutations (ovo(D)) result in viable germ cells that appear to be partially transformed from female to male sexual identity. The ovo(D2) mutation is partially suppressed by many Sex-lethal alleles that affect the soma, while those that affect only the germ line fail to interact with ovo(D2). One of two loss-of-function ovo alleles is suppressed by a loss-of-function Sex-lethal allele. Because ovo mutations are germ line dependent, it is likely that ovo is suppressed by way of communication between the somatic and germ lines. A loss-of-function allele of ovo is epistatic to germ line dependent mutations in Sex-lethal. The germ line dependent sex determination mutation, sans fille, and ovo(D) mutations show a dominant synergistic interaction resulting in partial transformation of germ line sexual identity. The ovo locus appears to be involved in germ line sex determination and is linked in some manner to sex determination in the soma.

Oliver, B.; Pauli, D.; Mahowald, A. P.



Bilateral testicular microlithiasis with a unilateral testicular germ cell tumor: a case report.  


There is an important association between testicular microlithiasis and germ cell tumors. Ultrasound findings of 1-3 mm echogenic foci within the testicular parenchyma may be noted. Testicular microlithiasis in the general population without germ cell tumors or cryptorchidism has been estimated between 0.05 and 0.6%. However, findings of microlithiasis in concordance with germ cell tumors can be as high as 40%. We present the case report of a man with bilateral testicular microlithiasis and a unilateral germ cell tumor. Discussion of the relationship between these two conditions is also reviewed. PMID:15011989

Whitacre, Ross; Zaslau, Stanley


The germ line regulates somatic cyst cell proliferation and fate during Drosophila spermatogenesis.  


Spermatogenesis relies on the function of germ-line stem cells, as a continuous supply of differentiated spermatids is produced throughout life. In Drosophila, there must also be somatic stem cells that produce the cyst cells that accompany germ cells throughout spermatogenesis. By lineage tracing, we demonstrate the existence of such somatic stem cells and confirm that of germ-line stem cells. The somatic stem cells likely correspond to the ultrastructurally described cyst progenitor cells. The stem cells for both the germ-line and cyst lineage are anchored around the hub of non-dividing somatic cells located at the testis tip. We then address whether germ cells regulate the behavior of somatic hub cells, cyst progenitors and their daughter cyst cells by analyzing cell proliferation and fate in testes in which the germ line has been genetically ablated. Daughter cyst cells, which normally withdraw from the cell cycle, continue to proliferate in the absence of germ cells. In addition, cells from the cyst lineage switch to the hub cell fate. Male-sterile alleles of chickadee and diaphanous, which are deficient in germ cells, exhibit similar cyst cell phenotypes. We conclude that signaling from germ cells regulates the proliferation and fate of cells in the somatic cyst lineage. PMID:8756289

Gönczy, P; DiNardo, S



Cytogenetic findings in a metastasizing primary testicular chondrosarcoma.  


The first case of a primary chondrosarcoma of the testis is reported. The testicular tumor, 2.5 cm in diameter, metastasized to the retroperitoneal lymph nodes in a 24-year-old male. Histologically, the testicular tumor and the lymph node metastases revealed a well-differentiated chondrosarcoma. Cytogenetic analysis of the retroperitoneal metastases showed a complex chromosomal aberration with two copies of the isochromosome of the short arm of chromosome 12. This is a specific chromosomal anomaly in testicular germ cell tumors. Thus, the cytogenetic analysis proved the germ cell origin of tumor cells as opposed to a possible paratesticular mesenchymal histogenesis. Moreover, the triploid modal chromosomal number of tumor cells confirmed the relationship between polyploidization and a high degree of differentiation in germ cell tumors. These findings stress the clinical relevance of the cytogenetic analysis in at least a subset of cytogenetically well-characterized solid tumors. PMID:8317613

Füzesi, L; Rixen, H; Kirschner-Hermanns, R



Hematogenous extraneural metastasis of the germinomatous component of a pineal mixed germ cell tumor.  


A 23-year-old man presented with a mass in the pineal region and obstructive hydrocephalus. A neuroendoscopicbiopsy for the lesion, ventriculoperitoneal (VP)shunting, and focal irradiation were conducted as initial treatment. Histological diagnosis of the biopsy specimen was germinoma. He underwent further irradiation and two tumor resections. Histological diagnosis was mature teratoma without a germinomatous component. After serial treatments, the intracranial lesion was controlled. However,14 months after presentation, extraneural lesions were confirmed in the posterior mediastinum and retroperitoneal space. The biopsy specimen of the retroperitoneal space lesion was histologically diagnosed as germinoma. Although chemotherapy with cisplatin and etoposide was undertaken,extraneural lesions ware uncontrollable and he died. At autopsy, extraneural lesions were confirmed in the posterior mediastinum, retroperitoneal space, and right lung. Histological diagnosis of extraneural lesions was germinoma.This case was considered to be a pineal mixed germ cell tumor mainly consisting of germinoma and mature teratoma,which caused hematogenous metastasis of the germinoma component. Systemic chemotherapy and irradiation for primary lesions as an initial treatment is important to cure the primary lesion and prevent extraneural metastasis. PMID:22286191

Asanuma, Megumi; Aoyama, Tatsuro; Sakai, Keiichi; Asano, Koji; Uehara, Tsuyoshi; Hongo, Kazuhiro



Simultaneous linearization of holomorphic germs in presence of resonances  

NASA Astrophysics Data System (ADS)

Let f_{1}, ..., f_{m} be m? 2 germs of biholomorphisms of C^{n} , fixing the origin, with (df_{1})_{O} diagonalizable and such that f_{1} commutes with f_{h} for any h=2,..., m . We prove that, under certain arithmetic conditions on the eigenvalues of (df_{1})_{O} and some restrictions on their resonances, f_{1}, ..., f_{m} are simultaneously holomorphically linearizable if and only if there exists a particular complex manifold invariant under f_{1}, ..., f_{m} .

Raissy, Jasmin


Germ-line transmission of transgenes in Xenopus laevis  

PubMed Central

Adult Xenopus laevis frogs made transgenic by restriction enzyme-mediated integration were bred to test the feasibility of establishing lines of frogs that express transgenes. All of the 19 animals raised to sexual maturity generated progeny that expressed the transgene(s). The patterns and levels of expression of green fluorescent protein transgenes driven by a viral promoter, rat promoter, and four X. laevis promoters were all unaffected by passage through the germ line. These results demonstrate the ease of establishing transgenic lines in X. laevis.

Marsh-Armstrong, Nicholas; Huang, Haochu; Berry, Deborah L.; Brown, Donald D.



A Cytokinin-binding Protein from Wheat Germ  

PubMed Central

A cytokinin-binding protein has been isolated from wheat germ via ammonium sulfate precipitation, carboxymethyl Sephadex chromatography, and affinity chromatography on a column substituted with a derivative of kinetin riboside. On Sephadex G-200, the protein migrated with an apparent molecular weight of 122,000 daltons. The dissociation constant for kinetin was determined by equilibrium dialysis to be 1.2 micromolar; N6-benzylaminopurine and N6-(?2-isopentenyl)adenine were also strongly bound. Little affinity was exhibited toward either cis-zeatin or trans-zeatin. Images

Moore, F. Hardy



Differentiation of Human Embryonic Stem Cells into Embryoid Bodies Comprising the Three Embryonic Germ Layers  

Microsoft Academic Search

Background: Embryonic stem (ES) cells are lines of cells that are isolated from blastocysts. The murine ES cells were demonstrated to be true pluripotent cells as they differentiate into all embry- onic lineages. Yet, in vitro differentiation of rhesus ES cells was somewhat inconsistent and disorga- nized. The recent isolation of human ES cells calls for exploring their pluripotential nature.

Joseph Itskovitz-Eldor



Avemar (wheat germ extract) in cancer prevention and treatment.  


Many healthy foods are derived from wheat germ. The molecular composition of these products, however, greatly differs as shown by normal-phase HPLC-mass spectrometry analysis; thus, experimental data obtained by one of them is not necessarily true for the other. Avemar is a nontoxic wheat germ extract registered as a special nutriment for cancer patients in Hungary. It shows potent anticancer activity on cell lines by deeply interfering with glucose metabolism and affecting expressions of several kinases. In in vivo experimental models, Avemar is also effective by enhancing the activity of the immune system such as stimulating NK cell activity (by reducing MHC I molecule expression), enhancing TNF secretion of the macrophages, increasing ICAM 1 molecule expression on the vascular endothelial cells. All of these lead to apoptosis of tumor cells. The wide range of biological activity of Avemar probably cannot be explained by only one active ingredient. Since there are numerous experimental data and the clinical benefit repeatedly confirmed Avemar can be one of the most potent and best researched food supplements available for cancer patients. PMID:20155632

Telekes, András; Hegedus, Márta; Chae, Chang-Hoon; Vékey, Károly



Germ banks affect the inference of past demographic events.  


Continuous progress in empirical population genetics based on the whole-genome polymorphism data requires the theoretical analysis of refined models in order to interpret the evolutionary history of populations with adequate accuracy. Recent studies focus prevalently on the aspects of demography and adaptation, whereas age structure (for example, in plants via the maintenance of seed banks) has attracted less attention. Germ banking, that is, seed or egg dormancy, is a prevalent and important life-history trait in plants and invertebrates, which buffers against environmental variability and modulates species extinction in fragmented habitats. Within this study, we investigate the combined effect of germ banking and time-varying population size on the neutral coalescent and particularly derive the allele frequency spectrum under some simplifying assumptions. We then perform an ABC analysis using two simple demographic scenarios-a population expansion and an instantaneous decline. We demonstrate the appreciable influence of seed banks on the estimation of demographic parameters depending on the germination rate with biases scaled by the square of the germination rate. In the more complex case of a population bottleneck, which comprises an instantaneous decline and an expansion phase, ignoring information on the germination rate denies reliable estimates of the bottleneck parameters via the allelic spectrum. In particular, when seeds remain in the bank over several generations, recent expansions may remain invisible in the frequency spectrum, whereas ancient declines leave signatures much longer than in the absence of seed bank. PMID:23050602

Živkovi?, Daniel; Tellier, Aurélien



Bone Morphogenetic Protein 4 Mediates Human Embryonic Germ Cell Derivation  

PubMed Central

Human primordial germ cells (PGCs) have proven to be a source of pluripotent stem cells called embryonic germ cells (EGCs). Unlike embryonic stem cells, virtually little is known regarding the factors that regulate EGC survival and maintenance. In mice, the growth factor bone morphogenetic protein 4 (BMP4) has been shown to be required for maintaining mouse embryonic stem cells, and disruptions in this gene lead to defects in mouse PGC specification. Here, we sought to determine whether recombinant human BMP4 could influence EGC derivation and/or human PGC survival. We found that the addition of recombinant BMP4 increased the number of human PGCs after 1 week of culture in a dose-responsive manner. The efficiency of EGC derivation and maintenance in culture was also enhanced by the presence of recombinant BMP4 based on alkaline phosphatase and OCT4 staining. In addition, an antagonist of the BMP4 pathway, Noggin, decreased PGC proliferation and led to an increase in cystic embryoid body formation. Quantitative real-time (qRT)–polymerase chain reaction analyses and immunostaining confirmed that the constituents of the BMP4 pathway were upregulated in EGCs versus PGCs. Downstream activators of the BMP4 pathway such as ID1 and phosphorylated SMADs 1 and 5 were also expressed, suggesting a role of this growth factor in EGC pluripotency.

Hiller, Marc; Liu, Cyndi; Blumenthal, Paul D.; Gearhart, John D.



Early development and putative primordial germ cells characterization in dogs.  


Previously, three distinct populations of putative primordial germ cells (PGCs), namely gonocytes, intermediate cells and pre-spermatogonia, have been described in the human foetal testis. According to our knowledge, these PGCs have not been studied in any other species. The aim of our study was to identify similar PGC populations in canine embryos. First, we develop a protocol for canine embryo isolation. Following our protocol, 15 canine embryos at 21-25 days of pregnancy were isolated by ovaryhysterectomy surgery. Our data indicate that dramatic changes occur in canine embryo development and PGCs specification between 21 to 25 days of gestation. At that moment, only two PGC populations with distinct morphology can be identified by histological analyses. Cell population 1 presented round nuclei with prominent nucleolus and a high nuclear to cytoplasm ratio, showing gonocyte morphology. Cell population 2 was often localized at the periphery of the testicular cords and presented typical features of PGC. Both germ cell populations were positively immunostained with anti-human OCT-4 antibody. However, at day 25, all cells of population 1 reacted positively with OCT-4, whereas in population 2, fewer cells were positive for this marker. These two PGCs populations present morphological features similar to gonocytes and intermediate cells from human foetal testis. It is expected that a population of pre-spermatogonia would be observed at later stages of canine foetus development. We also showed that anti-human OCT-4 antibody can be useful to identify canine PGC in vivo. PMID:20477984

Martins, D S; Ambrósio, C E; Saraiva, N Z; Wenceslau, C V; Morini, A C; Kerkis, I; Garcia, J M; Miglino, M A



Linking genotoxic responses in Gammarus fossarum germ cells with reproduction impairment, using the Comet assay  

Microsoft Academic Search

Germ cells perform a unique and critical biological function: they pass down DNA that will be used for the development of the next generation. Thus there is an increasing need to understand how the adult exposure to genotoxicants could show negative impact on the offspring of aquatic organisms. Hence this work addresses the question of the consequences of germ cell

Emilie Lacaze; Olivier Geffard; Delphine Goyet; Sylvie Bony; Alain Devaux



Allergic Sensitization to Bovine ?-Lactoglobulin: Comparison between Germ-Free and Conventional BALB\\/c Mice  

Microsoft Academic Search

Background: The ‘hygiene hypothesis’ suggests that high hygienic standards met in western countries lead to a lack of microbial exposure, thus promoting the development of atopy by preventing the proper maturation of the immune system. Germ-free animals are deprived of the immune stimulation that occurs during postnatal gut colonization by commensal bacteria. Germ-free mice could thereby provide an attractive model

S. Hazebrouck; L. Przybylski-Nicaise; S. Ah-Leung; K. Adel-Patient; G. Corthier; J.-M. Wal; S. Rabot



Restriction enzyme analysis of the germ line limited DNA of Ascaris suum  

Microsoft Academic Search

The germ line limited DNA of Ascaris suum was isolated from sperm and testis as a satellite DNA component in Hoechst 33258 — CsCl gradients. Employing restriction enzyme analysis, we show that the germ line limited DNA is composed entirely of two families of tandemly repeated sequences, one repeat unit is 125 bp, and the other 131 bp long. The

Gtinther E. Roth; Karl B. Moritz



Partial Oxygen Pressure and Mitochondrial Permeability Transition Affect Germ Cell Apoptosis in the Human Testis  

Microsoft Academic Search

During regular spermatogenesis, a number of testicular germ cells degenerate by an apoptotic process that is under hormonal control. Oxidative and mitochondrial changes have been proposed to play a role in apoptosis of many cell types. Previously, whether human germ cell survival is controlled by oxygen or by effectors of the mitochon- drial permeability transition has not been investigated. In




Identification of genes expressed in the hermaphrodite germ line of C. elegans using SAGE  

Microsoft Academic Search

BACKGROUND: Germ cells must progress through elaborate developmental stages from an undifferentiated germ cell to a fully differentiated gamete. Some of these stages include exiting mitosis and entering meiosis, progressing through the various stages of meiotic prophase, adopting either a male (sperm) or female (oocyte) fate, and completing meiosis. Additionally, many of the factors needed to drive embryogenesis are synthesized

Xin Wang; Yongjun Zhao; Kim Wong; Peter Ehlers; Yuji Kohara; Steven J Jones; Marco A Marra; Robert A Holt; Donald G Moerman; Dave Hansen



Practical issues on the application of the GHS classification criteria for germ cell mutagens  

Microsoft Academic Search

The Globally Harmonized System of Classification and Labeling of Chemicals (GHS) requires classification of chemicals on germ cell mutagenicity. The Japanese government has conducted GHS classification on about 1400 chemicals in a 2-year project (J-GHS) for implementing GHS domestically. Prior to the classification work, the technical guidance for classification of germ cell mutagens was prepared. This guidance introduces the concept

Takeshi Morita; Makoto Hayashi; Madoka Nakajima; Noriho Tanaka; David J. Tweats; Kaoru Morikawa; Toshio Sofuni



Strange Notes from the LA Punk Underground: The Durability of Darby Crash and the Germs  

Microsoft Academic Search

This essay examines the durability of Darby Crash, lead singer of the Germs, one of Los Angeles’s earliest punk bands. Crash committed suicide in 1980, but he and the Germs continue to fascinate those familiar with their music and story. This ongoing interest is the result of numerous factors, including the Germs’ music, Crash’s disturbing worldview and charisma, and our

Peter Robert Brown



Strange Notes from the LA Punk Underground: The Durability of Darby Crash and the Germs  

Microsoft Academic Search

: This essay examines the durability of Darby Crash, lead singer of the Germs, one of Los Angeles’s earliest punk bands. Crash committed suicide in 1980, but he and the Germs continue to fascinate those familiar with their music and story. This ongoing interest is the result of numerous factors, including the Germs’ music, Crash’s disturbing worldview and charisma, and

Peter Robert Brown




Technology Transfer Automated Retrieval System (TEKTRAN)

An aqueous, enzymatic method was developed to extract corn oil from corn germ. Using commercial oven dried corn germ from wet milling, corn oil yields of 80 to 90% were achieved using two commercial enzymes in the process. Ten other commercial enzymes were evaluated and resulted in significant, bu...


Germ Cells Are Not Required to Establish the Female Pathway in Mouse Fetal Gonads  

PubMed Central

The fetal gonad is composed of a mixture of somatic cell lineages and germ cells. The fate of the gonad, male or female, is determined by a population of somatic cells that differentiate into Sertoli or granulosa cells and direct testis or ovary development. It is well established that germ cells are not required for the establishment or maintenance of Sertoli cells or testis cords in the male gonad. However, in the agametic ovary, follicles do not form suggesting that germ cells may influence granulosa cell development. Prior investigations of ovaries in which pre-meiotic germ cells were ablated during fetal life reported no histological changes during stages prior to birth. However, whether granulosa cells underwent normal molecular differentiation was not investigated. In cases where germ cell loss occurred secondary to other mutations, transdifferentiation of granulosa cells towards a Sertoli cell fate was observed, raising questions about whether germ cells play an active role in establishing or maintaining the fate of granulosa cells. We developed a group of molecular markers associated with ovarian development, and show here that the loss of pre-meiotic germ cells does not disrupt the somatic ovarian differentiation program during fetal life, or cause transdifferentiation as defined by expression of Sertoli markers. Since we do not find defects in the ovarian somatic program, the subsequent failure to form follicles at perinatal stages is likely attributable to the absence of germ cells rather than to defects in the somatic cells.

Maatouk, Danielle M.; Mork, Lindsey; Hinson, Ashley; Kobayashi, Akio; McMahon, Andrew P.; Capel, Blanche



Recent advances in the understanding of the pathology of testicular germ-cell tumors  

Microsoft Academic Search

Most testicular cancers probably arise in intratubular germ cells. This article proposes that tumorigenesis involves two steps: activation of the germ cells, which can result either in simple proliferation (intratubular atypia) or in parthenogenetic development (teratomas), and malignant transformation, either simultaneously (embryonal carcinoma) of later (tumors with restricted developmental potential). The embryonal carcinoma cells then may be able to differentiate

Ivan Damjanov




EPA Science Inventory

The induction of heritable mutations in germ cells represents a potential health concern. his paper will highlight several themes in the area of germ-cell mutagenesis and their implications in reproductive and developmental risk. dditionally, factors that influence the yield of g...


PHYSIOLOGY, ENDOCRINOLOGY, AND REPRODUCTION Isolation of Chicken Primordial Germ Cells Using Fluorescence-Activated Cell Sorting  

Microsoft Academic Search

Presently, it is difficult to undertake germ line modification of the chicken with primordial germ cells (PGC) because it has been difficult to efficiently frac- tionate the PGC from the total somatic cell population. The objective of this study was to develop a method that allows isolation of an enriched population of viable PGC from embryonic blood and embryonic gonadal

P. E. Mozdziak; J. Angerman-Stewart; B. Rushton; S. L. Pardue; J. N. Petitte


Derivation of embryonic germ cells and male gametes from embryonic stem cells  

Microsoft Academic Search

Egg and sperm cells (gametes) of the mouse are derived from a founder population of primordial germ cells that are set aside early in embryogenesis. Primordial germ cells arise from the proximal epiblast, a region of the early mouse embryo that also contributes to the first blood lineages of the embryonic yolk sac. Embryonic stem cells differentiate in vitro into

Niels Geijsen; Melissa Horoschak; Kitai Kim; Joost Gribnau; Kevin Eggan; George Q. Daley



Plzf is required in adult male germ cells for stem cell self-renewal  

Microsoft Academic Search

Adult germline stem cells are capable of self-renewal, tissue regeneration and production of large numbers of differentiated progeny. We show here that the classical mouse mutant luxoid affects adult germline stem cell self-renewal. Young homozygous luxoid mutant mice produce limited numbers of normal spermatozoa and then progressively lose their germ line after birth. Transplantation studies showed that germ cells from

F William Buaas; Andrew L Kirsh; Manju Sharma; Derek J McLean; Jamie L Morris; Michael D Griswold; Dirk G de Rooij; Robert E Braun



The Y Deletion gr\\/gr and Susceptibility to Testicular Germ Cell Tumor  

Microsoft Academic Search

Testicular germ cell tumor (TGCT) is the most common cancer in young men. Despite a considerable familial component to TGCT risk, no genetic change that confers increased risk has been substantiated to date. The human Y chromosome carries a number of genes specifically involved in male germ cell development, and deletion of the AZFc region at Yq11 is the most

Katherine L. Nathanson; Peter A. Kanetsky; Rachel Hawes; David J. Vaughn; Richard Letrero; Kathy Tucker; Michael Friedlander; Kelly-Anne Phillips; David Hogg; Michael A. S. Jewett; Radka Lohynska; Gedske Daugaard; Stéphane Richard; Agnčs Chompret; Catherine Bonaďti-Pellié; Axel Heidenreich; Edith Olah; Lajos Geczi; Istvan Bodrogi; Wilma J. Ormiston; Peter A. Daly; J. Wolter Oosterhuis; Ad J. M. Gillis; Leendert H. J. Looijenga; Parry Guilford; Sophie D. Fossĺ; Ketil Heimdal; Sergei A. Tjulandin; Ludmila Liubchenko; Hans Stoll; Walter Weber; Matthew Rudd; Robert Huddart; Gillian P. Crockford; David Forman; D. Timothy Oliver; Lawrence Einhorn; Barbara L. Weber; Joan Kramer; Mary McMaster; Mark H. Greene; Malcolm Pike; Victoria Cortessis; Chu Chen; Stephen M. Schwartz; D. Timothy Bishop; Douglas F. Easton; Michael R. Stratton; Elizabeth A. Rapley



Germ Cell Differentiation and Synaptonemal Complex Formation Are Disrupted in CPEB Knockout Mice  

Microsoft Academic Search

CPEB is a sequence-specific RNA binding protein that regulates translation during vertebrate oocyte maturation. Adult female CPEB knockout mice contained vestigial ovaries that were devoid of oocytes; ovaries from mid-gestation embryos contained oocytes that were arrested at the pachytene stage. Male CPEB null mice also contained germ cells arrested at pachytene. The germ cells from the knockout mice harbored fragmented

Joyce Tay; Joel D. Richter



Evolution of germ cell development in tetrapods: comparison of urodeles and amniotes  

Microsoft Academic Search

SUMMARY The embryonic development of germ cells in tetrapods is described, focusing on groups with the inductive mode of germ cell specification. In mammals PGCs are induced early in the gastrulation process, they are internalized with future extraembryonic mesoderm in the early posterior primitive streak, and specified soon thereafter. Strong evidence indicates that a similar process occurs in turtles and

Rosemary F. Bachvarova; Brian I. Crother; Andrew D. Johnson



The human VASA gene is specifically expressed in the germ cell lineage  

Microsoft Academic Search

To understand the origins and function of the human germ cell lineage and to identify germ cell-specific markers we have isolated a human ortholog of the Drosophila gene vasa. The gene was mapped to human chromosome 5q (near the centromere) by radiation hybrid mapping. We show by Northern analysis of fetal and adult tissues that expression of the human VASA

Diego H. Castrillon; Bradley J. Quade; T. Y. Wang; Catherine Quigley; Christopher P. Crum



The role of germs and viruses in children's theories of AIDS (or, AIDS are not Band-Aids).  


The development of knowledge of germs and viruses in relation to AIDS and flu was examined in a predominantly Mexican American sample of children aged 8-9, 10-11, and 12-13. Children progressed with age from identifying the disease agent for these diseases as a nondescript germ or something other than a germ to implicating a disease-specific germ or virus. Parallel age trends in mastery of the two diseases were observed; gender and ethnic differences were minimal. Solid command of germ and virus concepts in relation to AIDS was associated with more casually sophisticated understanding of the disease but not with more accurate knowledge of modes of HIV transmission. Grasp of flu germ/virus concepts did not contribute to greater understanding or knowledge of AIDS. Overall, children seem predisposed to construct a germ theory of an unfamiliar disease such as AIDS but need help in differentiating between one germ and another. PMID:9079578

Sigelman, C K; Alfeld-Liro, C; Lewin, C B; Derenowski, E B; Woods, T



Development and evolution of the vertebrate primary mouth.  


The vertebrate oral region represents a key interface between outer and inner environments, and its structural and functional design is among the limiting factors for survival of its owners. Both formation of the respective oral opening (primary mouth) and establishment of the food-processing apparatus (secondary mouth) require interplay between several embryonic tissues and complex embryonic rearrangements. Although many aspects of the secondary mouth formation, including development of the jaws, teeth or taste buds, are known in considerable detail, general knowledge about primary mouth formation is regrettably low. In this paper, primary mouth formation is reviewed from a comparative point of view in order to reveal its underestimated morphogenetic diversity among, and also within, particular vertebrate clades. In general, three main developmental modes were identified. The most common is characterized by primary mouth formation via a deeply invaginated ectodermal stomodeum and subsequent rupture of the bilaminar oral membrane. However, in salamander, lungfish and also in some frog species, the mouth develops alternatively via stomodeal collar formation contributed both by the ecto- and endoderm. In ray-finned fishes, on the other hand, the mouth forms via an ectoderm wedge and later horizontal detachment of the initially compressed oral epithelia with probably a mixed germ-layer derivation. A very intriguing situation can be seen in agnathan fishes: whereas lampreys develop their primary mouth in a manner similar to the most common gnathostome pattern, hagfishes seem to undergo a unique oropharyngeal morphogenesis when compared with other vertebrates. In discussing the early formative embryonic correlates of primary mouth formation likely to be responsible for evolutionary-developmental modifications of this area, we stress an essential role of four factors: first, positioning and amount of yolk tissue; closely related to, second, endoderm formation during gastrulation, which initiates the process and constrains possible evolutionary changes within this area; third, incipient structure of the stomodeal primordium at the anterior neural plate border, where the ectoderm component of the prospective primary mouth is formed; and fourth, the prime role of Pitx genes for establishment and later morphogenesis of oral region both in vertebrates and non-vertebrate chordates. PMID:22804777

Soukup, Vladimír; Horácek, Ivan; Cerny, Robert



Magical thinking about illness virulence: conceptions of germs from "safe" versus "dangerous" others.  


AIDS-related research has documented overreactions to casual contact and underreactions to sexual risk. This contradiction is explained by "magical contagion", a principle of thinking common in traditional societies, wherein contagion is considered socially discriminating, such that harmfulness depends on the nature of the relationship between source and recipient. In Study 1, 100 undergraduate participants drew germs described as their own, a stranger's, their lover's, or a disliked peer's. Lovers' germs were depicted as less threatening than disliked peers' germs. In Study 2, scenarios described contact with a flu-infected lover, stranger, or disliked peer. New undergraduate participants (N = 133) rated how likely they were to become ill and how severely. Although likelihood ratings did not differ, severity ratings followed a linear trend, effects of lover contact being least severe and contact with disliked peer most severe. Behavioral implications of the blurring of feelings about germ source with estimates of germ virulence are discussed. PMID:7789350

Nemeroff, C J



Focus Issue: From Egg to Egg--Cell Signaling in Germ Cells  

NSDL National Science Digital Library

In this Focus Issue of Science’s STKE, which complements the Science Special Issue on germ cells, we take a closer look at cell signaling in germ cells. STKE highlights the migration of germ cells with an article that describes the different mechanisms controlling primordial germ cell movement and survival in mice and flies. Another article describes a mechanism for mediating plant self-incompatibility through control of the pollen tube, to prevent inappropriate delivery of incompatible sperm to the ovule. A common feature found in each of the organisms discussed, be they animal, insect or plant, is that signals from the surrounding tissues control survival and migration of the germ cells or resulting gametes.

Elizabeth M. Adler (American Association for the Advancement of Science;Science's STKE REV); Nancy R. Gough (American Association for the Advancement of Science;Science's STKE REV)



Mouse germ cell clusters form by aggregation as well as clonal divisions  

PubMed Central

After their arrival in the fetal gonad, mammalian germ cells express E-cadherin and are found in large clusters, similar to germ cell cysts in Drosophila. In Drosophila, germ cells in cysts are connected by ring canals. Several molecular components of intercellular bridges in mammalian cells have been identified, including TEX14, a protein required for the stabilization of intercellular bridges, and several associated proteins that are components of the cytokinesis complex. This has led to the hypothesis that germ cell clusters in the mammalian gonad arise through incomplete cell divisions. We tested this hypothesis by generating chimeras between GFP-positive and GFP-negative mice. We show that germ cell clusters in the fetal gonad arise through aggregation as well as cell division. Intercellular bridges, however, are likely restricted to cells of the same genotype.

Mork, Lindsey; Tang, Hao; Batchvarov, Iordan; Capel, Blanche



Focus issue: from egg to egg--cell signaling in germ cells.  


In this Focus Issue of Science's STKE, which complements the Science Special Issue on germ cells, we take a closer look at cell signaling in germ cells. STKE highlights the migration of germ cells with an article that describes the different mechanisms controlling primordial germ cell movement and survival in mice and flies. Another article describes a mechanism for mediating plant self-incompatibility through control of the pollen tube, to prevent inappropriate delivery of incompatible sperm to the ovule. A common feature found in each of the organisms discussed, be they animal, insect or plant, is that signals from the surrounding tissues control survival and migration of the germ cells or resulting gametes. PMID:17456804

Adler, Elizabeth M; Gough, Nancy R



The mouse dead-end gene isoform ? is necessary for germ cell and embryonic viability  

PubMed Central

Inactivation of the dead-end (Dnd1) gene in the Ter mouse strain results in depletion of primordial germ cells (PGCs) so that mice become sterile. However, on the 129 mouse strain background, loss of Dnd1 also increases testicular germ cell tumor incidence in parallel to PGC depletion. We report that inactivation of Dnd1 also affects embryonic viability in the 129 strain. Mouse Dnd1 encodes two protein isoforms, DND1-isoform ? (DND1- ?) and DND1-isoform ? (DND1-?). Using isoform specific antibodies, we determined DND1-? is expressed in embryos and embryonic gonads whereas DND1-? expression is restricted to germ cells of the adult testis. Our data implicates DND1-? isoform to be necessary for germ cell viability and therefore its loss in Ter mice results in PGC depletion, germ cell tumor development and partial embryonic lethality in the 129 strain.

Bhattacharya, Chitralekha; Aggarwal, Sita; Zhu, Rui; Kumar, Madhu; Zhao, Ming; Meistrich, Marvin L.; Matin, Angabin



The Role of Germs and Viruses in Children's Theories of AIDS (or, AIDS are Not Band-Aids)  

Microsoft Academic Search

The development of knowledge of germs and viruses in relation to AIDS and flu was examined in a predominantly Mexican American sample of children aged 8-9, 10-11, and 12-13. Children progressed with age from identifying the disease agent for these diseases as a nondescript germ or something other than a germ to implicating a disease-specific germ or virus. Parallel age

Carol K. Sigelman; Corinne Alfeld-Liro; Cynthia B. Lewin; Eileen B. Derenowski; Teresa Woods



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

Microsoft Academic Search

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

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



Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice.  


Peroxisomal testis-specific 1 gene (Pxt1) is the only male germ cell-specific gene that encodes a peroxisomal protein known to date. To elucidate the role of Pxt1 in spermatogenesis, we generated transgenic mice expressing a c-MYC-PXT1 fusion protein under the control of the PGK2 promoter. Overexpression of Pxt1 resulted in induction of male germ cells' apoptosis mainly in primary spermatocytes, finally leading to male infertility. This prompted us to analyze the proapoptotic character of mouse PXT1, which harbors a BH3-like domain in the N-terminal part. In different cell lines, the overexpression of PXT1 also resulted in a dramatic increase of apoptosis, whereas the deletion of the BH3-like domain significantly reduced cell death events, thereby confirming that the domain is functional and essential for the proapoptotic activity of PXT1. Moreover, we demonstrated that PXT1 interacts with apoptosis regulator BAT3, which, if overexpressed, can protect cells from the PXT1-induced apoptosis. The PXT1-BAT3 association leads to PXT1 relocation from the cytoplasm to the nucleus. In summary, we demonstrated that PXT1 induces apoptosis via the BH3-like domain and that this process is inhibited by BAT3. PMID:21460186

Kaczmarek, Karina; Studencka, Maja; Meinhardt, Andreas; Wieczerzak, Krzysztof; Thoms, Sven; Engel, Wolfgang; Grzmil, Pawel



Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice  

PubMed Central

?Peroxisomal testis-specific 1 gene (Pxt1) is the only male germ cell–specific gene that encodes a peroxisomal protein known to date. To elucidate the role of Pxt1 in spermatogenesis, we generated transgenic mice expressing a c-MYC-PXT1 fusion protein under the control of the PGK2 promoter. Overexpression of Pxt1 resulted in induction of male germ cells’ apoptosis mainly in primary spermatocytes, finally leading to male infertility. This prompted us to analyze the proapoptotic character of mouse PXT1, which harbors a BH3-like domain in the N-terminal part. In different cell lines, the overexpression of PXT1 also resulted in a dramatic increase of apoptosis, whereas the deletion of the BH3-like domain significantly reduced cell death events, thereby confirming that the domain is functional and essential for the proapoptotic activity of PXT1. Moreover, we demonstrated that PXT1 interacts with apoptosis regulator BAT3, which, if overexpressed, can protect cells from the PXT1-induced apoptosis. The PXT1-BAT3 association leads to PXT1 relocation from the cytoplasm to the nucleus. In summary, we demonstrated that PXT1 induces apoptosis via the BH3-like domain and that this process is inhibited by BAT3.

Kaczmarek, Karina; Studencka, Maja; Meinhardt, Andreas; Wieczerzak, Krzysztof; Thoms, Sven; Engel, Wolfgang; Grzmil, Pawel



Nodal signaling regulates the entry into meiosis in fetal germ cells.  


The mechanisms regulating the entry into meiosis in mammalian germ cells remain incompletely understood. We investigated the involvement of the TGF-? family members in fetal germ cell meiosis initiation. Nodal, a member of the TGF-? family, and its target genes are precociously expressed in embryonic gonads and show sexual dimorphism in favor of the developing testis. Nodal receptor genes, Acvr2a and Acvr2b, Alk4, and Tdgf1/Cripto, were identified in male germ cells. Nodal itself, Tdgf1, and Lefty1 and Lefty2 are targets of Nodal signaling and were all found specifically expressed in male germ cells. To elucidate the role of this signaling pathway, activin-like kinases that mediate TGF-?/Nodal/activin signaling were inhibited in 11.5 d postconception testis in organotypic culture. Activin-like kinases inhibition disrupted normal male germ cell development and induced germ cell entry into meiosis such as that observed in female germ cells at the equivalent stage. Interestingly Stra8, the gatekeeper of the mitotic/meiotic switch, was induced independently of any change of either Cyp26b1 or Fgf9 expression, the two genes currently identified as testicular meiotic inhibitors. On the other hand, recombinant Nodal significantly dampened Stra8 expression and germ cell meiosis in cultured 11.5 d postconception ovaries. Our results allowed us to propose for the first time an autocrine role of Nodal during the development of germ cells and indicate that members of the TGB-? family may reinforce the male fate and prevent meiosis in embryonic germ cells. PMID:22396454

Souquet, Benoit; Tourpin, Sophie; Messiaen, Sébastien; Moison, Delphine; Habert, René; Livera, Gabriel



Identification of germ cell-specific genes in mammalian meiotic prophase  

PubMed Central

Background Mammalian germ cells undergo meiosis to produce sperm or eggs, haploid cells that are primed to meet and propagate life. Meiosis is initiated by retinoic acid and meiotic prophase is the first and most complex stage of meiosis when homologous chromosomes pair to exchange genetic information. Errors in meiosis can lead to infertility and birth defects. However, despite the importance of this process, germ cell-specific gene expression patterns during meiosis remain undefined due to difficulty in obtaining pure germ cell samples, especially in females, where prophase occurs in the embryonic ovary. Indeed, mixed signals from both germ cells and somatic cells complicate gonadal transcriptome studies. Results We developed a machine-learning method for identifying germ cell-specific patterns of gene expression in microarray data from mammalian gonads, specifically during meiotic initiation and prophase. At 10% recall, the method detected spermatocyte genes and oocyte genes with 90% and 94% precision, respectively. Our method outperformed gonadal expression levels and gonadal expression correlations in predicting germ cell-specific expression. Top-predicted spermatocyte and oocyte genes were both preferentially localized to the X chromosome and significantly enriched for essential genes. Also identified were transcription factors and microRNAs that might regulate germ cell-specific expression. Finally, we experimentally validated Rps6ka3, a top-predicted X-linked spermatocyte gene. Protein localization studies in the mouse testis revealed germ cell-specific expression of RPS6KA3, mainly detected in the cytoplasm of spermatogonia and prophase spermatocytes. Conclusions We have demonstrated that, through the use of machine-learning methods, it is possible to detect germ cell-specific expression from gonadal microarray data. Results from this study improve our understanding of the transition from germ cells to meiocytes in the mammalian gonad. Further, this approach is applicable to other tissues for which isolating cell populations remains difficult.



Beneficial Effect of Wheat Germ on Circulating Lipoproteins and Tissue LJpidsin Rats Fed a High Fat, Cholesterol-Containing Diet  

Microsoft Academic Search

Adult male rats were fed for 7 wk either a low fat diet (3% fat) or a high fat-cholesterol diet (20% fat, 0.5% cholesterol) containing 7% wheat germ or not. Body weights and food intakes were unchanged by adding wheat germ to the control low fat or high fat diets. Adding wheat germ to the high fatâ€\\



Oil separation from wet milled corn germ dispersions as part of aqueous oil extraction and aqueous enzymatic oil extraction  

Technology Transfer Automated Retrieval System (TEKTRAN)

Oil was obtained from corn germ by aqueous extraction (AE). 100 g batches of germ were mixed with a buffer solution to a mass concentration of 5 to 20% germ, preheated under 2 atm. pressure (120oC), milled in a blender and then churned in an incubator/shaker to coalesce and float oil droplets. The ...


??????????????????????- ??????????????????????????????????????????????????????? Accumulation of gamma-aminobutyric acid (GABA) in non-waxy and waxy rice germ during water soaking ????? ?????????? ?????? ??????????? ???? ?????????????? ???????? ????????????  

Microsoft Academic Search

Rice germ contains protein, vitamins, minerals, dietary fiber and gamma- aminobutyric acid (GABA). GABA has been proved to be effective for lowering the blood pressure of human being. It has neurotransmission functions and tranquilizer effects. Determination of GABA in rice germ and brown rice were investigated by using low- amylose, high-amylose and waxy rice cultivars. Percentage of germ weight showed

Patcharee Tungtrakul; Vipa Surojanametakul; Ladda Wattanasiritham


The measurement of induced genetic change in mammalian germ cells.  


In vivo methods are described to detect clastogenic and aneugenic effects of chemical agents in male and female germ cells in vivo. The knowledge of stages of germ cell development and their duration for a given test animal is essential for these experiments. Commonly, mice or rats are employed. Structural chromosome aberrations can be analyzed microscopically in mitotic cell divisions of differentiating spermatogonia, zygotes, or early embryos as well as in first meiotic cell divisions of spermatocytes and oocytes. Numerical chromosome aberrations are scorable during second meiotic divisions of spermatocytes and oocytes. The micronucleus test is applicable to early round spermatids and to first cleavage embryos, and as in somatic cells, it assesses structural as well as numerical chromosome aberrations. In contrast to the somatic micronucleus assay, the timing of cell sampling determines whether the micronuclei scored in round spermatids were formed from structural or numerical aberrations, i.e. with short treatment-sampling intervals the micronuclei are formed by exposed meiotic divisions and represent induced non-disjunction. On the -contrary, after longer intervals of 12-14 days micronuclei are formed from induced unstable structural aberrations in differentiating spermatogonia or during the last round of DNA-synthesis in early spermatocytes. Furthermore, labelling with fluorescent DNA-probes can be used to confirm these theoretical expectations. The mouse sperm-FISH assay is totally based on scoring colour spots from individual chromosomes (e.g. X, Y, and 8) hybridized with specific DNA-probes. The most animal demanding assay described here is the dominant lethal test. It is commonly performed with treated male laboratory rodents and allows the determination of the most sensitive developmental stage of spermatogenesis to a particular chemical under test. Theoretically, unstable structural chromosome aberrations in sperm will lead to foetal deaths after fertilization at around the time of implantation in the uterus wall. These can be scored as deciduomata or early dead foetuses in the uterus wall of the females at mid-pregnancy. None of the tests described in this chapter provide data for a quantitative estimate of the genetic risk to progeny from exposed germ cells. The only tests on which such calculations can be based, the heritable translocation assay and the specific locus test, are so animal and time-consuming that they can no more be performed anywhere in the world and thus are not described here. PMID:22147580

Adler, Ilse-Dore; Pacchierotti, Francesca; Russo, Antonella



miRNA regulation of Sdf1 chemokine signaling provides genetic robustness to germ cell migration  

PubMed Central

microRNAs function as genetic rheostats to control gene output. Based on their role as modulators, it has been postulated that microRNAs canalize development and provide genetic robustness. Here, we uncover a novel regulatory layer of chemokine signaling by microRNAs that confers genetic robustness on primordial-germ-cell (PGC) migration. In zebrafish, PGCs are guided to the gonad by the ligand Sdf1a, which is regulated by sequestration receptor Cxcr7b. We find that miR-430 regulates sdf1a- and cxcr7-mRNAs. Using Target Protectors, we demonstrate that miR-430-mediated regulation of endogenous sdf1a and cxcr7b (i) facilitates dynamic expression of sdf1a by clearing its mRNA from previous expression domains, (ii) modulates the levels of the decoy receptor Cxcr7b to avoid excessive depletion of Sdf1a and (iii) buffers against variation in gene dosage of chemokine signaling components to ensure accurate PGC migration. Our results indicate that losing microRNA-mediated regulation can expose otherwise buffered genetic lesions leading to developmental defects.

Staton, Alison A.; Knaut, Holger; Giraldez, Antonio J.



X-ray micro-analysis of the mineralization patterns in developing enamel in hamster tooth germs exposed to fluoride in vitro during the secretory phase of amelogenesis  

SciTech Connect

The developing enamel from three-day-old hamster first maxillary (M1) molar tooth germs exposed to fluoride (F-) in vitro was analyzed for its mineral content by means of the energy-dispersive x-ray microanalysis technique. The aim of this study was to obtain semi-quantitative data on the F(-)-induced hypermineralization patterns in the enamel and to confirm that the increase in electron density observed in micrographs of F(-)-treated enamel is indeed due to an increase in mineral content in the fluorotic enamel. The tooth germs were explanted during the early stages of secretory amelogenesis and initially cultured for 24 hr in the presence of 10 ppm F- in the culture medium. The germs were then cultured for another 24 hr without F-. In order to compare the ultrastructural results directly with the microprobe data, we used the same specimens for both investigations. The net calcium counts (measurement minus background counts) in the analyses were used as a measure of the mineral content in the enamel. The aprismatic pre-exposure enamel, deposited in vivo before the onset of culture, was the most hypermineralized region in the fluorotic enamel, i.e., it contained the highest amount of calcium measured. The degree of the F(-)-induced hypermineralization gradually decreased (but was not abolished) in the more mature regions of the enamel. The unmineralized enamel matrix secreted during the initial F- treatment in vitro mineralized during the subsequent culture without F-. The calcium content in this enamel layer was in the same order of magnitude as that recorded for the newly deposited enamel in control tooth germs cultured without F-.

Lyaruu, D.M.; Blijleven, N.; Hoeben-Schornagel, K.; Bronckers, A.L.; Woeltgens, J.H.



Evaluation of corn germ from ethanol production as an alternative fat source in dairy cow diets.  


Sixteen multiparous cows (12 Holstein and 4 Brown Swiss, 132 +/- 20 d in milk) were used in a replicated 4 x 4 Latin square design with 4-wk periods to determine the effects of feeding corn germ on dairy cow performance. Diets were formulated with increasing concentrations of corn germ (Dakota Germ, Poet Nutrition, Sioux Falls, SD) at 0, 7, 14, and 21% of the diet dry matter (DM). All diets had a 55:45 forage to concentrate ratio, where forage was 55% corn silage and 45% alfalfa hay. Dietary fat increased from 4.8% in the control diet to 8.2% at the greatest inclusion level of corn germ. The addition of corn germ resulted in a quadratic response in DM intake with numerically greater intake at 14% of diet DM. Feeding corn germ at 7 and 14% of diet DM increased milk yield and energy-corrected milk as well as fat percentage and yield. Milk protein yield tended to decrease as the concentration of corn germ increased in the diet. Dietary treatments had no effect on feed efficiency, which averaged 1.40 kg of energy-corrected milk/kg of DMI. Increasing the dietary concentration of corn germ resulted in a linear increase in milk fat concentrations of monounsaturated and polyunsaturated fatty acids at the expense of saturated fatty acids. Milk fat concentration and yield of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid were increased with increased dietary concentrations of corn germ. Although milk fat concentrations of both total trans-18:1 and cis-18:1 fatty acids increased linearly, a marked numeric increase in the concentration of trans-10 C18:1 was observed in milk from cows fed the 21% corn germ diet. A similar response was observed in plasma concentration of trans-10 C18:1. Feeding increasing concentrations of corn germ had no effect on plasma concentrations of glucose, triglyceride, or beta-hydroxybutyrate; however, the concentration of nonesterified fatty acids increased linearly, with plasma cholesterol concentration demonstrating a similar trend. Germ removed from corn grain before ethanol production provides an alternative source of fat for energy in lactating dairy cows when fed at 7 and 14% of diet DM. Our results suggest that fat from corn germ may be relatively protected with no adverse effect on DM intake, milk production, and milk composition when fed up to 14% of diet DM. PMID:19233796

Abdelqader, M M; Hippen, A R; Kalscheur, K F; Schingoethe, D J; Karges, K; Gibson, M L



Pathobiology of germ cell tumors - applying the gossip test!  


Residual mature teratoma, a frequent finding in clinical pathology since the introduction of cisplatin-based chemotherapy, put Wolter Oosterhuis on the track of germ cell tumors (GCTs). These neoplasms in the borderland between developmental biology and oncology have fascinated him ever since. He tells the story on how GCTs brought him in contact with leading investigators in the field like Ivan Damjanov, Peter Andrews, and Niels Skakkebaek. His fruitful line of research was made possible through a longstanding collaboration with Bauke de Jong and, to this day, Leendert Looijenga who joined his group as a student in 1988. Probably their most important contribution to the field of GCTs is an integrated approach to GCTs, combining epidemiology, pathology, (cyto)genetics and molecular biology, that has resulted in a pathobiology-based classification of GCTs in five types. It has clinical relevance and stimulates further research on these intriguing neoplasms and their corresponding animal models. PMID:23784840

Looijenga, Leendert H J; Oosterhuis, J Wolter



[Spinal cord compression by testicular germ cell tumor: case report].  


Malignant spinal cord compression occurs in 2.5% - 5% cancer patients. Early diagnosis and therapeutic intervention are critical for pain control and improvement of any neurological deficit. Treatment should be directed to the underlying disease together with appropriate symptom management. The case of a man with tetraparesis of 24 hours duration is presented. He had surgery five days earlier because of a testicular tumor and spinal magnetic resonance imaging (MRI) showed spinal cord compression by a soft tissue mass between C7 and D2. After confirming the diagnosis of mixed germ cell tumor, stage IIIC, the patient began chemotherapy with progressive neurological improvement. Two years after diagnosis the patient presents a slight reduction of strength in the right hand and remains without any evidence of disease. This case illustrates the importance of early diagnosis of spinal cord compression and one of the main indications for the use of chemotherapy as the treatment for an oncologic emergency. PMID:23534600

Estevinho, Fernanda; Sousa, Nuno; Rodrigues, Ângelo; Carneiro, Eduarda; Souto, Joăo; Begonha, Rosa; Maurício, Joaquina



Germ cell proliferations in the fetal horse ovary.  


During the 340 day pregnancy of the horse, the germ cells in the fetal ovary showed a meiotic prophase which began in days 60-70 and might be prolonged after day 200. Three or four successive oogonial mitotic proliferations passed into the meiotic prophase but the great majority of the oocytes first involved degenerated, and no appreciable numbers of primordial follicles were left behind. At 150 days of pregnancy and again at 197 days, oocytes in early meiotic stages filled the ovarian cortex. Primordial follicles were present, but rare. As the prophase gradually came to an end, groups of oocytes became enclosed by small 'boundary' cells which formed in the stroma. Coalescence of these groups led to the appearance of coiled and branching formations containing small and large oocytes. Many of the original groups, however, contracted and became narrow strands and these persisted until the end of pregnancy, many oocytes disappearing from them, while others eventually developed in primordial follicles. PMID:597852

Deanesly, R



The story of a largely unknown evolution - Germ theory hoax  

PubMed Central

The Piltdown Man debacle provides us with the most infamous forgery in science. However, another equally intriguing story exists concerning a document by a Bostonian called George Sleeper, which purported to be a pre-Darwin–Wallace anticipation of evolution and an equally convincing account of the germ theory published before Louis Pasteur’s famous studies on this subject. The story involves two giants in the world of evolutionary theory, Alfred Russel Wallace and E.B. Poulton. While Wallace was convinced that the Sleeper document was genuine, Poulton’s detailed investigations showed that it was a fake and a hoax. Despite this conclusion, doubts still exist about the authenticity of the Sleeper document.

Wainwright, Milton; Alharbi, Sulaiman Ali



New Monoclonal Antibody Specific for Candida albicans Germ Tube  

PubMed Central

Hydrophobic components of the germ tube of the dimorphic pathogenic fungus Candida albicans were used as immunogens to prepare monoclonal antibodies (MAbs). Among the resulting MAbs, one (MAb 16B1-F10) was shown by indirect immunofluorescence to be specific to the surface of the mycelium phase of the C. albicans and C. stellatoidea species. No labeling of any other genera and Candida species tested was observed, including C. dubliniensis, a newly described species which has many phenotypic similarities to C. albicans. This phase-specific epitope resides on a protein moiety. The molecular mass of the antigen released by Zymolyase digestion was determined by gel filtration and ranges from 25 to 166 kDa. The antigen was also shown to be highly hydrophobic. This anti-C. albicans cell wall surface-specific MAb may be a good candidate for use in tests for the rapid differentiation of the two closely related species C. albicans and C. dubliniensis.

Marot-Leblond, Agnes; Grimaud, Linda; Nail, Sandrine; Bouterige, Sandrine; Apaire-Marchais, Veronique; Sullivan, Derek J.; Robert, Raymond



The story of a largely unknown evolution - Germ theory hoax.  


The Piltdown Man debacle provides us with the most infamous forgery in science. However, another equally intriguing story exists concerning a document by a Bostonian called George Sleeper, which purported to be a pre-Darwin-Wallace anticipation of evolution and an equally convincing account of the germ theory published before Louis Pasteur's famous studies on this subject. The story involves two giants in the world of evolutionary theory, Alfred Russel Wallace and E.B. Poulton. While Wallace was convinced that the Sleeper document was genuine, Poulton's detailed investigations showed that it was a fake and a hoax. Despite this conclusion, doubts still exist about the authenticity of the Sleeper document. PMID:23961141

Wainwright, Milton; Alharbi, Sulaiman Ali



Late recurrences of germ cell malignancies: a population-based experience over three decades.  


The purpose of this study was to explore the incidence of late relapse in patients with malignant germ cell tumour (MGCT) in a population-based series, with emphasis on the mode of detection, survival, and the relevance of histological findings. The clinical records from a population-based cohort of patients with seminoma (n=1123) or non-seminoma (n=826) were evaluated for late relapses. Twenty-five patients developed a late relapse. The cumulative 10-year incidence rate was 1.3%. All 10 seminoma patients, but only eight of 15 non-seminoma patients relapsed with vital malignant tumour (P=0.02). Teratoma or necrosis was found in seven of nine primarily chemotherapy-treated non-seminoma patients with normal tumour markers at late relapse. Six of nine patients operated with limited retroperitoneal lymph node dissection as part of the primary treatment had relapsed retroperitoneally outside the original operation field. The 10-year cause-specific survival was 68% in all patients, 50% in patients relapsing with vital malignant tumour and 100% in those with teratoma/ necrosis before or after salvage chemotherapy. The 10-year incidence rate of late relapses of 1.3% might reflect the true incidence rate in a population-based cohort of MGCT patients, with cure in at least half of them. PMID:16508636

Oldenburg, J; Alfsen, G C; Waehre, H; Fossĺ, S D



Late recurrences of germ cell malignancies: a population-based experience over three decades  

PubMed Central

The purpose of this study was to explore the incidence of late relapse in patients with malignant germ cell tumour (MGCT) in a population-based series, with emphasis on the mode of detection, survival, and the relevance of histological findings. The clinical records from a population-based cohort of patients with seminoma (n=1123) or non-seminoma (n=826) were evaluated for late relapses. Twenty-five patients developed a late relapse. The cumulative 10-year incidence rate was 1.3%. All 10 seminoma patients, but only eight of 15 non-seminoma patients relapsed with vital malignant tumour (P=0.02). Teratoma or necrosis was found in seven of nine primarily chemotherapy-treated non-seminoma patients with normal tumour markers at late relapse. Six of nine patients operated with limited retroperitoneal lymph node dissection as part of the primary treatment had relapsed retroperitoneally outside the original operation field. The 10-year cause-specific survival was 68% in all patients, 50% in patients relapsing with vital malignant tumour and 100% in those with teratoma/ necrosis before or after salvage chemotherapy. The 10-year incidence rate of late relapses of 1.3% might reflect the true incidence rate in a population-based cohort of MGCT patients, with cure in at least half of them.

Oldenburg, J; Alfsen, G C; Waehre, H; Fossa, S D



Integrative characterization of germ cell-specific genes from mouse spermatocyte UniGene library  

PubMed Central

Background The primary regulator of spermatogenesis, a highly ordered and tightly regulated developmental process, is an intrinsic genetic program involving male germ cell-specific genes. Results We analyzed the mouse spermatocyte UniGene library containing 2155 gene-oriented transcript clusters. We predict that 11% of these genes are testis-specific and systematically identified 24 authentic genes specifically and abundantly expressed in the testis via in silico and in vitro approaches. Northern blot analysis disclosed various transcript characteristics, such as expression level, size and the presence of isoform. Expression analysis revealed developmentally regulated and stage-specific expression patterns in all of the genes. We further analyzed the genes at the protein and cellular levels. Transfection assays performed using GC-2 cells provided information on the cellular characteristics of the gene products. In addition, antibodies were generated against proteins encoded by some of the genes to facilitate their identification and characterization in spermatogenic cells and sperm. Our data suggest that a number of the gene products are implicated in transcriptional regulation, nuclear integrity, sperm structure and motility, and fertilization. In particular, we found for the first time that Mm.333010, predicted to contain a trypsin-like serine protease domain, is a sperm acrosomal protein. Conclusion We identify 24 authentic genes with spermatogenic cell-specific expression, and provide comprehensive information about the genes. Our findings establish a new basis for future investigation into molecular mechanisms underlying male reproduction.

Choi, Eunyoung; Lee, Jiae; Oh, Jungsu; Park, Inju; Han, Cecil; Yi, Chongil; Kim, Do Han; Cho, Byung-Nam; Eddy, Edward M; Cho, Chunghee



Germ Tube Mediated Invasion of Batrachochytrium dendrobatidis in Amphibian Skin Is Host Dependent  

PubMed Central

Batrachochytrium dendrobatidis (Bd) is the causative agent of chytridiomycosis, a fungal skin disease in amphibians and driver of worldwide amphibian declines. We focussed on the early stages of infection by Bd in 3 amphibian species with a differential susceptibility to chytridiomycosis. Skin explants of Alytes muletensis, Litoria caerulea and Xenopus leavis were exposed to Bd in an Ussing chamber for 3 to 5 days. Early interactions of Bd with amphibian skin were observed using light microscopy and transmission electron microscopy. To validate the observations in vitro, comparison was made with skin from experimentally infected frogs. Additional in vitro experiments were performed to elucidate the process of intracellular colonization in L. caerulea. Early interactions of Bd with amphibian skin are: attachment of zoospores to host skin, zoospore germination, germ tube development, penetration into skin cells, invasive growth in the host skin, resulting in the loss of host cell cytoplasm. Inoculation of A. muletensis and L. caerulea skin was followed within 24 h by endobiotic development, with sporangia located intracellularly in the skin. Evidence is provided of how intracellular colonization is established and how colonization by Bd proceeds to deeper skin layers. Older thalli develop rhizoid-like structures that spread to deeper skin layers, form a swelling inside the host cell to finally give rise to a new thallus. In X. laevis, interaction of Bd with skin was limited to an epibiotic state, with sporangia developing upon the skin. Only the superficial epidermis was affected. Epidermal cells seemed to be used as a nutrient source without development of intracellular thalli. The in vitro data agreed with the results obtained after experimental infection of the studied frog species. These data suggest that the colonization strategy of B. dendrobatidis is host dependent, with the extent of colonization most likely determined by inherent characteristics of the host epidermis.

Van Rooij, Pascale; Martel, An; D'Herde, Katharina; Brutyn, Melanie; Croubels, Siska; Ducatelle, Richard; Haesebrouck, Freddy; Pasmans, Frank



PGL proteins self associate and bind RNPs to mediate germ granule assembly in C. elegans  

PubMed Central

Germ granules are germ lineage–specific ribonucleoprotein (RNP) complexes, but how they are assembled and specifically segregated to germ lineage cells remains unclear. Here, we show that the PGL proteins PGL-1 and PGL-3 serve as the scaffold for germ granule formation in Caenorhabditis elegans. Using cultured mammalian cells, we found that PGL proteins have the ability to self-associate and recruit RNPs. Depletion of PGL proteins from early C. elegans embryos caused dispersal of other germ granule components in the cytoplasm, suggesting that PGL proteins are essential for the architecture of germ granules. Using a structure–function analysis in vivo, we found that two functional domains of PGL proteins contribute to germ granule assembly: an RGG box for recruiting RNA and RNA-binding proteins and a self-association domain for formation of globular granules. We propose that self-association of scaffold proteins that can bind to RNPs is a general mechanism by which large RNP granules are formed.

Hanazawa, Momoyo; Yonetani, Masafumi



Multiple regulatory regions control the transcription of medaka germ gene vasa.  


Numerous regulatory DNA regions and trans-acting protein factors controlling transcription have been characterized for many genes that are expressed in somatic cells. Little is known about the transcriptional control of germ genes, and no cell culture system has been explored for quantitative reporter assay of germ gene transcription in vitro. Here we report the development of such an in vitro system and the identification of regulatory regions in the medaka germ gene vasa. We established the medaka germ cell line SG3 as a suitable in vitro system for analyzing germ gene transcription. Transgenic production revealed that VAS, a 5.1-kb genomic fragment of medaka vasa, possessed regulatory regions essential for germ cell-specific transcription. Importantly, reporter assays revealed 11 positive and negative regulatory regions alternatively positioned throughout VAS including the first intron. Strikingly, the regulatory regions may act in additive, non-additive and dependent manners. We show that a 39-bp element within one regulatory region is able to interact with the nuclear factor(s) of vasa-expressing embryos and testes. These results demonstrate the complexity of transcriptional control of medaka vasa and provide important insights into opposing mechanisms underlying germ gene transcription. PMID:23232104

Li, Mingyou; Guan, Guijun; Hong, Ni; Hong, Yunhan



Germ cell and Sertoli cell interactions in human testis: evidence for stimulatory and inhibitory effects.  


In human Sertoli cell preparations obtained from healthy men (mean age 31.8 +/- 6.8 years; n = 6), we have measured the productions of lactate, 17 beta-oestradiol, transferrin and inhibin between day 4 and day 5 after plating, either in the presence or absence (hypotonic treatment of plated cells on day 2) of germ cells. The results, expressed per 10(6) of cells plated/24 h, showed that lactate production was unchanged, whether or not germ cells were present. However, if we calculated the lactate production per mg protein/24 h, the lactate output was decreased (30-60%) in the presence of germ cells. Whatever the mode of expression, Sertoli cell 17 beta-oestradiol synthesis was diminished 1.5-fold in the presence of germ cells. Conversely, the transferrin output was increased 3.2-fold in non-treated Sertoli cell preparations when compared to the hypotonic-treated plates. A similar observation was recorded for the in-vitro production of inhibin by Sertoli cells, which was enhanced 1.4-fold when germ cells were present. These results, together with a likely potentializing role of germ cells on follicle stimulating hormone control of Sertoli cell function, strongly suggest that germ cells exert both stimulatory and inhibitory effects in regulating human Sertoli cell function through either direct contact and/or via secreted factors. PMID:7868675

Foucault, P; Drosdowsky, M A; Carreau, S



Radiation-Induced Bystander Signaling from Somatic Cells to Germ Cells in Caenorhabditis elegans.  


Recently, radiation-induced bystander effects (RIBE) have been studied in mouse models in vivo, which clearly demonstrated bystander effects among somatic cells. However, there is currently no evidence for RIBE between somatic cells and germ cells in animal models in vivo. In the current study, the model animal Caenorhabditis elegans was used to investigate the bystander signaling from somatic cells to germ cells, as well as underlying mechanisms. C. elegans body size allows for precise microbeam irradiation and the abundant mutant strains for genetic dissection relative to currently adopted mouse models make it ideal for such analysis. Our results showed that irradiation of posterior pharynx bulbs and tails of C. elegans enhanced the level of germ cell apoptosis in bystander gonads. The irradiation of posterior pharynx bulbs also increased the level of DNA damage in bystander germ cells and genomic instability in the F1 progeny of irradiated worms, suggesting a potential carcinogenic risk in progeny even only somatic cells of parents are exposed to ionizing radiation (IR). It was also shown that DNA damage-induced germ cell death machinery and MAPK signaling pathways were both involved in the induction of germ cell apoptosis by microbeam induced bystander signaling, indicating a complex cooperation among multiple signaling pathways for bystander effects from somatic cells to germ cells. PMID:23931723

Guo, Xiaoying; Sun, Jie; Bian, Po; Chen, Lianyun; Zhan, Furu; Wang, Jun; Xu, An; Wang, Yugang; Hei, Tom K; Wu, Lijun



Gene expression in the axolotl germ line: Axdazl, Axvh, Axoct-4, and Axkit.  


Primordial germ cells (PGCs) in embryos of mammals and urodele amphibians are formed by induction in the absence of germ plasm. We describe expression of four germ cell-related genes through the germ cell cycle of the axolotl. The orthologs of vasa and daz-like are up-regulated in PGCs of tail bud embryos before the gonad forms and are expressed throughout the female germ cell cycle. Mammalian Oct-4 is a marker of pluripotency in embryonic cells. Axolotl Oct-4 has higher homology to Oct-4 than that found in other vertebrates. It is expressed in the equivalent of the mouse epiblast, in the posterior mesoderm of late gastrulae that gives rise to PGCs, and in diplotene growing oocytes, but not in presumptive PGCs after gastrulation. Finally, a c-kit homolog is expressed in gonadal oogonia and growing oocytes as in mice but is also not found in PGCs. The expression pattern in urodele gonadal germ cells is similar to that of other vertebrates, although the pattern in pregonadal PGCs is distinctly different from that of mice. We conclude that PGCs are restricted to the germ line later in urodeles than in mice or lack migration and proliferation programs. PMID:15517581

Bachvarova, Rosemary F; Masi, Thomas; Drum, Matthew; Parker, Nathan; Mason, Ken; Patient, Roger; Johnson, Andrew D



Endogenous Nodal signaling regulates germ cell potency during mammalian testis development.  


Germ cells, the embryonic precursors of sperm or oocytes, respond to molecular cues that regulate their sex-specific development in the fetal gonads. In males in particular, the balance between continued proliferation and cell fate commitment is crucial: defects in proliferation result in insufficient spermatogonial stem cells for fertility, but escape from commitment and prolonged pluripotency can cause testicular germ cell tumors. However, the factors that regulate this balance remain unidentified. Here, we show that signaling by the TGF? morphogen Nodal and its co-receptor Cripto is active during a crucial window of male germ cell development. The Nodal pathway is triggered when somatic signals, including FGF9, induce testicular germ cells to upregulate Cripto. Germ cells of mutant mice with compromised Nodal signaling showed premature differentiation, reduced pluripotency marker expression and a reduced ability to form embryonic germ (EG) cell colonies in vitro. Conversely, human testicular tumors showed upregulation of NODAL and CRIPTO that was proportional to invasiveness and to the number of malignant cells. Thus, Nodal signaling provides a molecular control mechanism that regulates male germ cell potency in normal development and testicular cancer. PMID:23034635

Spiller, Cassy M; Feng, Chun-Wei; Jackson, Andrew; Gillis, Ad J M; Rolland, Antoine D; Looijenga, Leendert H J; Koopman, Peter; Bowles, Josephine



DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance.  


DNA damage responses have been well characterized with regard to their cell-autonomous checkpoint functions leading to cell cycle arrest, senescence and apoptosis. In contrast, systemic responses to tissue-specific genome instability remain poorly understood. In adult Caenorhabditis elegans worms germ cells undergo mitotic and meiotic cell divisions, whereas somatic tissues are entirely post-mitotic. Consequently, DNA damage checkpoints function specifically in the germ line, whereas somatic tissues in adult C. elegans are highly radio-resistant. Some DNA repair systems such as global-genome nucleotide excision repair (GG-NER) remove lesions specifically in germ cells. Here we investigated how genome instability in germ cells affects somatic tissues in C. elegans. We show that exogenous and endogenous DNA damage in germ cells evokes elevated resistance to heat and oxidative stress. The somatic stress resistance is mediated by the ERK MAP kinase MPK-1 in germ cells that triggers the induction of putative secreted peptides associated with innate immunity. The innate immune response leads to activation of the ubiquitin-proteasome system (UPS) in somatic tissues, which confers enhanced proteostasis and systemic stress resistance. We propose that elevated systemic stress resistance promotes endurance of somatic tissues to allow delay of progeny production when germ cells are genomically compromised. PMID:23975097

Ermolaeva, Maria A; Segref, Alexandra; Dakhovnik, Alexander; Ou, Hui-Ling; Schneider, Jennifer I; Utermöhlen, Olaf; Hoppe, Thorsten; Schumacher, Björn



Control over the morphology and segregation of Zebrafish germ cell granules during embryonic development  

PubMed Central

Background Zebrafish germ cells contain granular-like structures, organized around the cell nucleus. These structures share common features with polar granules in Drosophila, germinal granules in Xenopus and chromatoid bodies in mice germ cells, such as the localization of the zebrafish Vasa, Piwi and Nanos proteins, among others. Little is known about the structure of these granules as well as their segregation in mitosis during early germ-cell development. Results Using transgenic fish expressing a fluorescently labeled novel component of Zebrafish germ cell granules termed Granulito, we followed the morphology and distribution of the granules. We show that whereas these granules initially exhibit a wide size variation, by the end of the first day of development they become a homogeneous population of medium size granules. We investigated this resizing event and demonstrated the role of microtubules and the minus-end microtubule dependent motor protein Dynein in the process. Last, we show that the function of the germ cell granule resident protein the Tudor domain containing protein-7 (Tdrd7) is required for determination of granule morphology and number. Conclusion Our results suggest that Zebrafish germ cell granules undergo a transformation process, which involves germ cell specific proteins as well as the microtubular network.

Strasser, Markus J; Mackenzie, Natalia C; Dumstrei, Karin; Nakkrasae, La-Iad; Stebler, Jurg; Raz, Erez



Sex-Specific Dynamics of Global Chromatin Changes in Fetal Mouse Germ Cells  

PubMed Central

Mammalian germ cells undergo global reprogramming of DNA methylation during their development. Global DNA demethylation occurs around the time when the primordial germ cells colonize the embryonic gonads and this coincides with dynamic changes in chromatin composition. Global de novo DNA methylation takes place with remarkably different dynamics between the two sexes, prospermatogonia attaining methylation during fetal stages and oocytes attaining methylation postnatally. Our hypothesis was that dynamic changes in chromatin composition may precede or accompany the wave of global DNA de novo methylation as well. We used immunocytochemistry to measure global DNA methylation and chromatin components in male and female mouse fetal germ cells compared to control somatic cells of the gonad. We found that global DNA methylation levels sharply increased in male germ cells at 17.5 days post coitum, but remained low in female germ cells at all fetal stages. Global changes in chromatin composition: i, preceded global DNA methylation in fetal germ cells; ii, sex specifically occurred in male but not in female germ cells; iii, affected active and repressive histone marks and iv, included histone tail and histone globular domain modifications. Our data suggest that dynamic changes of chromatin composition may provide a framework for the pattern of male-specific de novo DNA methylation in prospermatogonia.

Jin, Seung-Gi; Pfeifer, Gerd P.; Szabo, Piroska E.



The Fog-3 Gene and Regulation of Cell Fate in the Germ Line of Caenorhabditis Elegans  

PubMed Central

In the nematode Caenorhabditis elegans, germ cells normally adopt one of three fates: mitosis, spermatogenesis or oogenesis. We have identified and characterized the gene fog-3, which is required for germ cells to differentiate as sperm rather than as oocytes. Analysis of double mutants suggests that fog-3 is absolutely required for spermatogenesis and acts at the end of the regulatory hierarchy controlling sex determination for the germ line. By contrast, mutations in fog-3 do not alter the sexual identity of other tissues. We also have characterized the null phenotype of fog-1, another gene required for spermatogenesis; we demonstrate that it too controls the sexual identity of germ cells but not of other tissues. Finally, we have studied the interaction of these two fog genes with gld-1, a gene required for germ cells to undergo oogenesis rather than mitosis. On the basis of these results, we propose that germ-cell fate might be controlled by a set of inhibitory interactions among genes that specify one of three fates: mitosis, spermatogenesis or oogenesis. Such a regulatory network would link the adoption of one germ-cell fate to the suppression of the other two.

Ellis, R. E.; Kimble, J.



Electron microscopical localization of chitin in the cuticle of Halicryptus spinulosus and Priapulus caudatus (Priapulida) using gold-labelled wheat germ agglutinin: phylogenetic implications for the evolution of the cuticle within the Nemathelminthes  

Microsoft Academic Search

The ultrastructure of the cuticle of adult and larval Priapulus caudatus and Halicryptus spinulosus is investigated and new features of cuticle formation during moulting are described. For the localization of chitin by TEM\\u000a wheat germ agglutinin coupled to colloidal gold was used as a marker. Proteinaceous layers of the cuticle are revealed by\\u000a digestion with pronase. The cuticle of larval

C. Lemburg



Most regions of mouse epididymis are able to phagocytose immature germ cells.  


The role of the epididymis as a quality control organ in preventing infertile gametes entering the ejaculate has been extensively explored, and it has been suggested that a specific region of mammalian epididymis is able to phagocytose abnormal germ cells. This study examines whether the epithelium of certain zones of the mouse epididymis can act as a selection barrier by removing immature germ cells from the lumen by phagocytosis. To detect the presence of immature germ cells in the epididymis, we generated transgenic mice expressing enhanced green fluorescent protein under the deleted in azoospermia-like (mDazl) promoter to easily identify immature germ cells under fluorescence microscopy. Using this technique, we observed that during the first stage of spermatogenesis in prepuberal mice, a wave of immature germ cells is released into the epididymis and that the immature epididymis is not able to react to this abnormal situation. By contrast, when immature germ cells were artificially released into the epididymis in adult mice, a phagocytic response was observed. Phagosomes appeared inside principal cells of the epididymal epithelium and were observed to contain immature germ cells at different degradation stages in different zones of the epididymis, following the main wave of immature germ cells. In this paper, we describe how the epididymal epithelium controls sperm quality by clearing immature germ cells in response to their artificially induced massive shedding into the epididymal lumen. Our observations indicate that this phenomenon is not restricted to a given epididymis region and that phagocytic capacity is gradually acquired during epididymal development. PMID:23988666

Ramos-Ibeas, P; Pericuesta, E; Fernández-González, R; Ramírez, M A; Gutierrez-Adan, A



Local connection patterns of parvalbumin-positive inhibitory interneurons in rat primary auditory cortex.  


In the auditory cortex (AC), GABAergic neurons constitute approximately 15-25% of all neurons. GABAergic cells are present in all sensory modalities and essential for modulating sensory receptive fields. Parvalbumin (PV) positive cells represent the largest sub-group of the GABAergic population in auditory neocortex. We investigated the projection pattern of PV cells in rat primary auditory cortex (AI) with a retrograde tracer (wheat germ apo-HRP conjugated to gold [WAHG]) and immunocytochemistry for PV. All AC layers except layer I contained cells double-labeled for PV and WAHG. All co-localized PV+ cells were within 2 mm of the injection site, regardless of laminar origin. Most (ca. 90%) of the co-localized PV cells were within 500 ?m of the injection site in both dorsal-ventral and rostral-caudal dimension of the auditory core region. WAHG-only cells declined less rapidly with distance and were found up to 6 mm from the deposit sites. WAHG-only labeled cells in the medial geniculate body were in ventral division loci compatible with an injection in AI. Differences in the range and direction of the distribution pattern of co-localized PV+ cells and WAHG-only cells in AI express distinct functional convergence patterns for the two cell populations. PMID:20600741

Yuan, Kexin; Fink, Kathren L; Winer, Jeffery A; Schreiner, Christoph E



Discovery of germ cell–specific transcripts by expressed sequence tag database analysis  

Microsoft Academic Search

Objective: To identify transcripts whose expression is restricted to germ cells.Design: Expressed sequence tags (ESTs) from unfertilized egg libraries were utilized to perform in silico subtraction and identify germ cell–specific transcripts.Setting: Baylor College of Medicine, Houston, Texas.Animal(s): C57BL\\/6J\\/129SvEv hybrid.Intervention(s): Tissue harvesting from mice.Main Outcome Measure(s): Identification of germ cell–specific transcripts.Result(s): We have used the Unigene collection of mouse cDNA libraries

Aleksandar Rajkovic; Changning Yan M. S; Michal Klysik; Martin Matzuk



Identification and Genetic Analysis of Wunen, a Gene Guiding Drosophila Melanogaster Germ Cell Migration  

PubMed Central

We describe a novel genetic locus, wunen (wun), required for guidance of germ cell migration in early Drosophila development. Loss of wun function does not abolish movement but disrupts the orientation of the motion causing the germ cells to disperse even though their normal target, the somatic gonad, is well formed. We demonstrate that the product of this gene enables a signal to pass from the soma to the germ line and propose that the function of this signal is to selectively stabilize certain cytoplasmic extensions resulting in oriented movement. To characterize this guidance factor, we have mapped wun to within 100 kb of cloned DNA.

Zhang, N.; Zhang, J.; Cheng, Y.; Howard, K.



The Ter mutation in the Dead-end gene causes germ cell loss and testicular germ cell tumours  

PubMed Central

The Ter mutation causes primordial germ cell (PGC) loss on all mouse genetic backgrounds (Fig. 1a) with deficiency of PGCs1 starting at embryonic day 8. Ter is also a potent modifier of spontaneous testicular germ cell tumour (TGCT) susceptibility in the 129 family of inbred strains and increases TGCT incidence from a baseline rate of 5% in 129 to 94% in 129-Ter/Ter males2-4 (Figs. 1b & c). In 129, some of the remaining PGCs transform into undifferentiated pluripotent embryonal carcinoma (EC) cells2-6 and after birth they differentiate into various cells and tissues that compose TGCTs. Positional cloning of Ter revealed a point mutation that introduces a termination codon in the mouse ortholog (Dnd1) of the zebrafish dead-end (dnd) gene. PGC deficiency is corrected both with BACs that contain Dnd1 and with a Dnd1 encoding transgene. Dnd1 is expressed in fetal gonads during the critical period when TGCTs originate. DND1 has an RNA recognition motif (RRM) and is most similar to the apobec complementation factor (Acf), a component of the cytidine to uridine RNA editing complex. These results suggest that Ter may adversely affect essential aspects of RNA biology during PGC development. DND1 is the first protein with an RRM that is directly implicated as a heritable cause of spontaneous tumourigenesis. TGCT development of the 129-Ter strain models pediatric TGCT in humans. This work will have important implications for our understanding of the genetic control of TGCT pathogenesis and PGC biology.

Youngren, Kirsten K.; Coveney, Douglas; Peng, Xiaoning; Bhattacharya, Chitralekha; Schmidt, Laura S.; Nickerson, Michael L.; Lamb, Bruce T.; Deng, Jian Min; Behringer, Richard R.; Capel, Blanche; Rubin, Edward M.; Nadeau, Joseph H.; Matin, Angabin



Phorbol Ester Circumvents the Need for Macrophages as Well as for Mitogenic Lectins in the Stimulation of Lymphocytes With Wheat Germ Agglutinin or the Calcium lonophores A23187 or lonomycin  

Microsoft Academic Search

Numerous biochemical events precede the proliferation of primary lympho- cytes stimulated by mitogenic lectins in the presence of macrophages. Various compounds can activate parts of this response. Specifically the tumor-promot- ing phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, (TPA), can replace the requirement for macrophages, apparently by mimicking the macrophage product interleukin 1 (ILl). Wheat germ agglutinin (WGA), itself a non-mito- genic lectin, is

Charles E. Grier; Andrea M. Mastro


Putrefactive Ethanol Sources in Postmortem Tissues of Conventional and Germ-Free Mice.  

National Technical Information Service (NTIS)

Putrefaction produces high levels of ethanol (alcohol) in brain, liver, and lung of intact mice. Previously eviscerated organs produce ethanol in much lower concentrations, while no ethanol is produced in the organs of germ-free mice. These latter animals...

G. L. Davis N. W. Rantanen R. L. Leffert



Identification of Novel Long Noncoding RNA Transcripts in Male Germ Cells  

PubMed Central

Emerging evidence from these studies suggested that the male germ cell transcriptome is more complex than previously envisioned. In addition to protein-coding genes, the transcriptome also encodes a significant number of nonprotein-coding transcripts. These noncoding (nc) RNAs appear to be involved in a variety of cellular activities, ranging from simple housekeeping to complex regulatory functions. A class of ncR-NAs known as long ncRNAs (lncRNAs) were recently shown to be expressed in a developmentally regulated manner during brain and embryonic stem cell development. This protocol aims to predict and identify potential lncRNA candidates using Serial Analysis of Gene Expression (SAGE) data. We also illustrate how to validate the potential lncRNAs by expression analyses using real-time PCR and Northern Blot. Potential lncRNA candidates in male germ cells are identified using our previously established male germ cell SAGE database (GermSAGE).

Lee, Tin-Lap; Xiao, Amy; Rennert, Owen M.



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

PubMed Central

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.

Cuykendall, Tawny N.; Houston, Douglas W.



CDC Vital Signs: Making Health Care Safer -- Stop Infections from Lethal CRE Germs Now  


... 62 MB] Read the MMWR March 2013 Making Health Care Safer Stop Infections from Lethal CRE Germs Now ... CRE infections on your state's Notifiable Diseases list. Health Care CEOs/Medical Officers can Require and strictly enforce ...


A comparative morphological study of human germ cells in vitro or in situ within seminiferous tubules.  


For many infertile couples, intracytoplasmic germ cell/spermatozoon injection into unfertilized eggs may be their only hope for producing their own biological children. Thus far, success with injection of pre-spermatozoan germ cells such as round spermatids has not been as great as that of spermatozoon injection. This could be due in part to the difficulty of identifying younger (less mature) male germ cells in testicular biopsy dispersions. To improve the identification of various types of live, dispersed, human testicular cells in vitro, a comparative study of the morphological characteristics of human spermatogenic germ cells in vitro or in situ within seminiferous tubules was conducted. Live human testicular tissue was obtained from an organ-donating, brain-dead person with a high density of various germ cells. A cell suspension was obtained by enzymatic digestion, and cells were cultured for 3 days in an excessive volume (100-fold medium:cells; v:v) of HEPES-TC 199 medium at 5 degrees C and observed live with Nomarski optics (interference-contrast microscopy). For comparative purposes, testes from ten men obtained at autopsy were fixed, embedded in epoxy resin, sectioned at 20 microm, and observed unstained by Nomarski optics. This approach allowed comparison of morphological characteristics of individual germ cells seen in vitro or in situ in the human testis. In both live and fixed preparations from control men with varied daily sperm production rates, Sertoli cells have oval to pear-shaped nuclei with indented nuclear envelopes and large nucleoli, which makes their appearance distinctly different from germ cells. The size, shape, and chromatin pattern of nuclei, and the presence of meiotic metaphase figures, acrosomic vesicles/structures, tails, and/or mitochondria in the middle piece of germ cells are characteristically seen in live cells in vitro and in those cells observed in the fixed seminiferous tubules. Hence, this comparative approach allows verification of the identity of individual germ cells seen in vitro and provides a checklist of distinguishing characteristics of live human germ cells, to be used by scientists and technical staff in infertility clinics when selecting specific germ cells from a testicular aspirate or enzymatically digested biopsy. PMID:10491626

Johnson, L; Neaves, W B; Barnard, J J; Keillor, G E; Brown, S W; Yanagimachi, R



Recovering corn germ enriched in recombinant protein by wet-fractionation.  


Corn wet-fractionation processes (quick-germ fractionation and traditional wet milling) were evaluated as means of recovering fractions rich in recombinant collagen-related proteins that were targeted for expression in the germ (embryo) of transgenic corn. Transgenic corn lines accumulating a recombinant full-length human collagen type-I-alpha-1 (full-length rCIalpha1) or a 44-kDa rCIalpha1 fragment targeted for seed expression with an embryo-specific promoter were used. Factors to consider in efficient recovery processes are the distribution of the peptides among botanical parts and process recovery efficiency. Both recombinant proteins were distributed 62-64% in germ comprising about 8.6% of the dry grain mass; 34-38% in the endosperm comprising 84% of the dry grain mass; 1.7% in the pericarp comprising about 5% of the dry mass; and 1% in the tip-cap comprising 1.5-2% of the dry mass. The quick-germ method employed a short steeping period either in water or SO(2)-lactic acid solution followed by wet-milling degermination to recover a germ-rich fraction. Of the total recombinant protein expressed in germ, the quick-germ process recovered 40-43% of the total recombinant protein within 6-8% of the corn mass. The traditional corn wet-milling process produced higher purity germ but with lower recovery (24-26%) of the recombinant protein. The two quick-germ methods, using water alone or SO(2)-lactic acid steeping, did not substantially differ in rCIalpha1 recovery, and the quick-germ processes recovered germ with less leaching and proteolytic losses of the recombinant proteins than did traditional wet milling. Thus, grain fractionation enriched the recombinant proteins 6-fold higher than that of unfractionated kernels. Such enrichment may improve downstream processing efficiency and enable utilizing the protein-lean co-products to produce biofuels and biorenewable chemicals by fermenting the remaining starch-rich fractions. PMID:19726179

Paraman, Ilankovan; Fox, Steven R; Aspelund, Matthew T; Glatz, Charles E; Johnson, Lawrence A



Germ-line msh6 Mutations in Colorectal Cancer Families1  

Microsoft Academic Search

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is due primar- ily to inherited mutations in two mismatch repair genes, MSH2 and MLH1, whereas germ-line mutations in other mismatch repair genes are rare. We examined the frequency of germ-line msh6 mutations in a population-based series of 140 colorectal cancer patients, including 45 sporadic cases, 91 familial non-HNPCC cases, and 4 HNPCC cases. Among

Richard D. Kolodner; Jessica D. Tytell; James L. Schmeits; Michael F. Kane; Ruchira Das Gupta; John Weger; Siobhan Wahlberg; Edward A. Fox; David Peel; Argyrios Ziogas; Judy E. Garber; Sapna Syngal; Hoda Anton-Culver; Frederick P. Li


Determining the viability of faecal bacteria present in germ-free mice  

Microsoft Academic Search

Summary Gram-positive bacilli, originating from the diet, are present in the faeces of germ-free mice in this Unit. Although these organisms have never grown on culture and are assumed to be dead it was considered desirable to test this by non-cultural methods because some gut bacteria are difficult or impossible to grow in vitro by present techniques. Germ-free mice were

D. M. Taylor; Lesley Read; D. L. Neal



Bilateral germ-cell tumours: 22-year experience at the Institut Gustave Roussy  

Microsoft Academic Search

The aim of this study was to describe the incidence, clinical and histological characteristics, treatment and long-term follow-up of bilateral germ-cell tumours (BGCT) of the testis in order to determine in what respects they differ significantly from unilateral germ-cell tumours. In all, 31 patients with BGCT had metachronous tumours and 14 had synchronous tumours. Among the metachronous tumours, 61% occurred

Ch Theodore; M J Terrier-Lacombe; A Laplanche; G Benoit; K Fizazi; O Stamerra; P Wibault



Variations of brain histamine levels in germ-free and nephrectomized rats  

Microsoft Academic Search

The influence of nephrectomy on brain and peripheral tissue histamine and on brain norepinephrine, dopamine, serotonin, and 5-hydroxyindoleacetic acid was studied in germ-free and conventionally housed rats. The conventional controls had higher levels of histamine in the hypothalamus than the germ-free control animals, but no differences existed for histamine in whole brain minus the hypothalamus or in peripheral tissues. Nephrectomy

Linda R. Hegstrand; R. Jean Hine



No AZF deletion in 160 patients with testicular germ cell neoplasia  

Microsoft Academic Search

Testicular germ cell cancer is aetiologically linked to genital malformations and male infertility and is most probably caused by a disruption of embryonic programming and gonadal development during fetal life. In some cases, germ cell neoplasia is associ- ated with a relative reduction of Y chromosomal material (e.g. 45,X\\/46,XY) or other abnormalities of the Y chromosome. The euchromatic long arm

Lone Frydelund-Larsen; Peter H. Vogt; Henrik Leffers; Alexandra Schadwinkel; Gedske Daugaard; Niels E. Skakkebaek; Ewa Rajpert-De Meyts



Extraction of wheat germ oil by supercritical CO 2 : Oil and defatted cake characterization  

Microsoft Academic Search

In this paper the working conditions for the extraction of wheat germ oil in a supercritical CO2 pilot plant of 1-L-extraction capacity were studied. The best conditions were: pressure, 38 MPa; temperature, 55C; wheat\\u000a germ particle size, about 0.35 mm; CO2 flow rate, 1.5 L min?1. These conditions gave yields of about 92% of total oil after 3 h of

G. Panfili; L. Cinquanta; A. Fratianni; R. Cubadda



Effect of diclofenac on germ cell apoptosis following testicular ischemia-reperfusion injury in a rat  

Microsoft Academic Search

Recent evidence suggests that enhanced cell apoptosis is responsible for germ cell loss following testicular ischemia-reperfusion\\u000a (IR) injury. A nonsteroidal anti-inflammatory drug diclofenac sodium (Voltaren) is a prostaglandin-synthesis inhibitor, which\\u000a is widely used in many testicular disorders. The purpose of the present study was to examine the effect of diclofenac (DIC)\\u000a on germ cell apoptosis in the ischemic and contralateral

Jorge G. Mogilner; Michael Lurie; Arnold G. Coran; Ofer Nativ; Eitan Shiloni; Igor Sukhotnik



Effect of allopurinol on germ cell apoptosis following testicular ischemia–reperfusion injury in a rat  

Microsoft Academic Search

Recent evidence suggests that apoptosis is involved in germ cell loss following testicular ischemia-reperfusion (IR) injury.\\u000a Allopurinol (Allo) is as a free radical scavenger which prevents tissue damage caused by reperfusion and oxygenation after\\u000a ischemia; however, its effect on apoptosis in this type of injury has not been studied. To examine the effect of allopurinol\\u000a on germ cell apoptosis following

Igor Sukhotnik; Gil Meyer; Ofer Nativ; Arnold G. Coran; Katya Voskoboinik; Eitan Shiloni; Jorge G. Mogilner



Functional role of caspases in heat-induced testicular germ cell apoptosis.  


In the present study, we determined whether a pan caspase inhibitor could prevent or attenuate heat-induced germ cell apoptosis. Groups of five adult (8 wk old) C57BL/6 mice pretreated with vehicle (DMSO) or Quinoline-Val-Asp (Ome)-CH2-O-Ph (Q-VD-OPH), a new generation broad-spectrum caspase inhibitor, were exposed once to local testicular heating (43 degrees C for 15 min) and killed 6 h later. The inhibitor (40 mg/kg body weight) or vehicle was administered intraperitoneally (i.p.) 1 h before local testicular heating. Germ cell apoptosis was detected by TUNEL assay and quantitated as number of apoptotic germ cells per 100 Sertoli cells at stages XI-XII. Compared with controls (16.8 +/- 3.1), mild testicular hyperthermia within 6 h resulted in a marked activation (277.3 +/- 21.6) of germ cell apoptosis, as previously reported by us. Q-VD-OPH at this dose markedly inhibited caspase 3 activation and significantly prevented (by 67.0%) heat-induced germ cell apoptosis. Q-VD-OPH-mediated rescue of germ cells was independent of cytosolic translocation of mitochondrial cytochrome c and DIABLO. Electron microscopy further revealed normal appearance of these rescued cells. Similar protection from heat-induced germ cell apoptosis was also noted after pretreatment with minocycline, a second-generation tetracycline that effectively inhibits cytochrome c release and, in turn, caspase activation. Collectively, the present study emphasizes the role of caspases in heat-induced germ cell apoptosis. PMID:15509730

Vera, Yanira; Rodriguez, Susana; Castanares, Mark; Lue, Yanhe; Atienza, Vince; Wang, Christina; Swerdloff, Ronald S; Sinha Hikim, Amiya P



Dietary manipulation implicates lipid signaling in the regulation of germ cell maintenance in C. elegans  

Microsoft Academic Search

Reproduction in C. elegans relies on continuously proliferating germ cells which, during germline development, exit mitosis, undergo meiosis and differentiate into gametes. Supplementing the diet of C. elegans with dihommogamma-linolenic acid (20:3n-6, DGLA), a long chain omega-6 polyunsaturated fatty acid, results in sterile worms that lack germ cells. The effect is remarkably specific for DGLA, as eicosapentaenoic acid (20:5n-3, EPA)

Jennifer L. Watts; John Browse



No extension of lifespan by ablation of germ line in Drosophila  

PubMed Central

Increased reproduction is frequently associated with a reduction in longevity in a variety of organisms. Traditional explanations of this ‘cost of reproduction’ suggest that trade-offs between reproduction and longevity should be obligate. However, it is possible to uncouple the two traits in model organisms. Recently, it has been suggested that reproduction and longevity are linked by molecular signals produced by specific reproductive tissues. For example, in Caenorhabditis elegans, lifespan is extended in worms that lack a proliferating germ line, but which possess somatic gonad tissue, suggesting that these tissues are the sources of signals that mediate lifespan. In this study, we tested for evidence of such gonadal signals in Drosophila melanogaster. We ablated the germ line using two maternal effect mutations: germ cell-less and tudor. Both mutations result in flies that lack a proliferating germ line but that possess a somatic gonad. In contrast to the findings from C. elegans, we found that germ line ablated females had reduced longevity relative to controls and that the removal of the germ line led to an over-proliferation of the somatic stem cells in the germarium. Our results contrast with the widely held view that it is downstream reproductive processes such as the production and/or laying of eggs that are costly to females. In males, germ line ablation caused either no difference, or a slight extension, in longevity relative to controls. Our results indicate that early acting, upstream reproductive enabling processes are likely to be important in determining reproductive costs. In addition, we suggest that the specific roles and putative patterns of molecular signalling in the germ line and somatic tissues are not conserved between flies and worms.

Barnes, Andrew I; Boone, James M; Jacobson, Jake; Partridge, Linda; Chapman, Tracey



Fermentation and costs of fuel ethanol from corn with quick-germ process  

Microsoft Academic Search

The Quick-Germ process developed at the University of Illinois at Urbana-Champaign is a way to obtain corn oil, but with lower\\u000a capital costs than the traditional wet-milling process. Quick-Germ has the potential to increase the coproduct credits and\\u000a profitability of the existing dry-grind fuel ethanol process, but the fermentability of the corn remaining after oil recovery\\u000a has not been tested.

Frank Taylor; Andrew J. Mcaloon; James C. Craig; Ping Yang; Jenny Wahjudi; Steven R. Eckhoff



The spectrum of RB1 germ-line mutations in hereditary retinoblastoma  

Microsoft Academic Search

We have searched for germ-line RB1 mutations in 119 patients with hereditary retinoblastoma. Previous investigations by Southern blot hybridization and PCR fragment-length analysis had revealed mutations in 48 patients. Here we report on the analysis of the remaining 71 patients. By applying heteroduplex analysis, nonisotopic SSCP, and direct sequencing, we detected germ-line mutations resulting in premature termination codons or disruption

D. R. Lohmann; B. Brandt; E. Passarge



Unique germ-line organelle, nuage, functions to repress selfish genetic elements in Drosophila melanogaster  

Microsoft Academic Search

The nuage is an electron-dense perinuclear structure that is known to be a hallmark of animal germ-line cells. Although the conservation of the nuage throughout evolution accentuates its essentiality, its role(s) and the exact mechanism(s) by which it functions in the germ line still remain unknown. Here, we report a nuage component, Krimper (KRIMP), in Drosophila melanogaster and show that

A. K. Lim; Toshie Kai



Viability of Female Germ-Line Cells Homozygous for Zygotic Lethals in DROSOPHILA MELANOGASTER  

PubMed Central

We have analyzed the viability of different types of X chromosomes in homozygous clones of female germ cells. The chromosomes carried viable mutations, single-cistron zygotic-lethal and semi-lethal mutations, or small (about six chromosome band) deletions. Homozygous germ-line clones were produced by recombination in females heterozygous for an X-linked, dominant, agametic female sterile. All the zygotic-viable mutants are also viable in germ cells. Of 16 deletions tested (uncovering a total of 93 bands) only 2 (of 4 and 5 bands) are germ-cell viable. Mutations in 15 lethal complementation groups in the zeste-white region were tested. When known, the most extreme alleles at each locus were tested. Only in five loci (33%) were the mutants viable in the germ line. Similar studies of the same deletions and point-mutant lethals in epidermal cells show that 42% of the bands and 77% of the lethal alleles are viable. Thus, germ-line cells have more stringent cell-autonomous genetic requirements than do epidermal cells. The eggs recovered from clones of three of the germ-cell viable zw mutations gave embryos arrested early in embryogenesis, although genotypically identical embryos derived from heterozygous oogonia die as larvae or even hatch as adult escapers. For two genes, homozygosis of the mutations tested also caused embryonic arrest of heterozygous female embryos, and in one case, the eggs did not develop at all. Germ-line clones of one quite leaky mutation gave eggs that were indistinguishable from normal. The abundance of genes whose products are required for oogenesis, whose products are required in the oocyte, and whose activity is required during zygotic development is discussed.

Garcia-Bellido, Antonio; Robbins, Leonard G.



In vitro DNA-protective activity of roasted wheat germ and fractions thereof  

Microsoft Academic Search

An ethanolic extract of roasted wheat germ was shown to scavenge free radicals, using the DPPH-test, and to protect DNA efficiently in vitro, using the 3D-assay. The DNA-protective activity of a coffee extract was comparatively lower and strongly dependent on the concentration applied. Fractionation of the wheat germ extract by preparative HPLC demonstrated that most of the DNA protecting properties

Ulrich Krings; Lena Johansson; Holger Zorn; Ralf G. Berger



Antioxidant and free radical-scavenging activities of wheat germ protein hydrolysates (WGPH) prepared with alcalase  

Microsoft Academic Search

Wheat germ protein hydrolysates (WGPH) were obtained by enzymatic hydrolysis of defatted wheat germ protein isolates using Alcalase 2.4L FG. The degree of hydrolysis (DH) of WGPH was determined to be about 25% using pH-stat method. The molecular mass distribution of WGPH was lower than 1500Da. The antioxidant and free radical-scavenging activities of WGPH were investigated by employing several in

Kexue Zhu; Huiming Zhou; Haifeng Qian



Multiple Colorectal Adenomas, Classic Adenomatous Polyposis, and Germ-Line Mutations in MYH  

Microsoft Academic Search

background Germ-line mutations in the base-excision-repair gene MYH have been associated with recessive inheritance of multiple colorectal adenomas. Tumors from affected persons displayed excess somatic transversions of a guanine-cytosine pair to a thymine-adenine pair (G:CT:A) in the APC gene. methods We screened for germ-line MYH mutations in 152 patients with multiple (3 to 100) colo- rectal adenomas and 107 APC

Oliver M. Sieber; Lara Lipton; Michael Crabtree; Karl Heinimann; Paulo Fidalgo; Robin K. S. Phillips; Marie-Luise Bisgaard; Torben F. Orntoft; Lauri A. Aaltonen; Shirley V. Hodgson; Huw J. W. Thomas; Ian P. M. Tomlinson



Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells  

PubMed Central

Historically, our understanding of molecular genetic aspects of human germ cell development has been limited, at least in part due to inaccessibility of early stages of human development to experimentation. However, the derivation of pluripotent stem cells may provide the necessary human genetic system to study germ cell development. In this study, we compared the potential of human induced pluripotent stem cells (iPSCs), derived from adult and fetal somatic cells to form primordial and meiotic germ cells, relative to human embryonic stem cells. We found that ?5% of human iPSCs differentiated to primordial germ cells (PGCs) following induction with bone morphogenetic proteins. Furthermore, we observed that PGCs expressed green fluorescent protein from a germ cell-specific reporter and were enriched for the expression of endogenous germ cell-specific proteins and mRNAs. In response to the overexpression of intrinsic regulators, we also observed that iPSCs formed meiotic cells with extensive synaptonemal complexes and post-meiotic haploid cells with a similar pattern of ACROSIN staining as observed in human spermatids. These results indicate that human iPSCs derived from reprogramming of adult somatic cells can form germline cells. This system may provide a useful model for molecular genetic studies of human germline formation and pathology and a novel platform for clinical studies and potential therapeutical applications.

Panula, Sarita; Medrano, Jose V.; Kee, Kehkooi; Bergstrom, Rosita; Nguyen, Ha Nam; Byers, Blake; Wilson, Kitchener D.; Wu, Joseph C.; Simon, Carlos; Hovatta, Outi; Reijo Pera, Renee A.



Bisphenol A exposure modifies DNA methylation of imprint genes in mouse fetal germ cells.  


Bisphenol A (BPA) is an estrogenic environmental toxin widely used for the production of plastics. Human frequent exposure to this chemical has been proposed to be a potential public health risk. The objective of this study was to assess the effects of BPA on DNA methylation of imprinting genes in fetal mouse germ cell. Pregnant mice were treated with BPA at doses of 0, 40, 80 and 160 ?g BPA/kg body weight/day from 0.5 day post coitum. DNA methylation of imprinting genes, Igf2r, Peg3 and H19, was decreased with the increase of BPA concentration in fetal mouse germ cells (p < 0.01).The relative mRNA levels of Nobox were lower in BPA-treated group compared to control (BPA free) in female fetal germ cells, but in male fetal germ cells, a significant higher in Nobox expression was observed in BPA-treated group compared to control. Decreased mRNA expression of specific meiotic genes including Stimulated by Stra8 and Dazl were obtained in the female fetal germ cells. In conclusion, BPA exposure can affect the DNA methylation of imprinting genes in fetal mouse germ cells. PMID:22699882

Zhang, Xi-Feng; Zhang, Lian-Jun; Feng, Yan-Ni; Chen, Bo; Feng, Yan-Min; Liang, Gui-Jin; Li, Lan; Shen, Wei



METT-10, a putative methyltransferase, inhibits germ cell proliferative fate in Caenorhabditis elegans.  


Germ-line stem cells are unique because they either self-renew through mitosis or, at a certain frequency, switch to meiosis and produce gametes. The switch from proliferation to meiosis is tightly regulated, and aberrations in switching result in either too little or too much proliferation. To understand the genetic basis of this regulation, we characterized loss-of-function mutations and a novel tumorous allele of Caenorhabditis elegans mett-10, which encodes a conserved putative methyltransferase. We show that METT-10 is a nuclear protein that acts in the germ line to inhibit the specification of germ-cell proliferative fate. METT-10 also promotes vulva, somatic gonad, and embryo development and ensures meiotic development of those germ cells that do differentiate. In addition, phenotypic analysis of a mett-10 null allele reveals that METT-10 enables mitotic cell cycle progression. The finding that METT-10 functions to inhibit germ-cell proliferative fate, despite promoting mitotic cell cycle progression of those germ cells that do proliferate, separates the specification of proliferative fate from its execution. PMID:19596901

Dorsett, Maia; Westlund, Bethany; Schedl, Tim



METT-10, A Putative Methyltransferase, Inhibits Germ Cell Proliferative Fate in Caenorhabditis elegans  

PubMed Central

Germ-line stem cells are unique because they either self-renew through mitosis or, at a certain frequency, switch to meiosis and produce gametes. The switch from proliferation to meiosis is tightly regulated, and aberrations in switching result in either too little or too much proliferation. To understand the genetic basis of this regulation, we characterized loss-of-function mutations and a novel tumorous allele of Caenorhabditis elegans mett-10, which encodes a conserved putative methyltransferase. We show that METT-10 is a nuclear protein that acts in the germ line to inhibit the specification of germ-cell proliferative fate. METT-10 also promotes vulva, somatic gonad, and embryo development and ensures meiotic development of those germ cells that do differentiate. In addition, phenotypic analysis of a mett-10 null allele reveals that METT-10 enables mitotic cell cycle progression. The finding that METT-10 functions to inhibit germ-cell proliferative fate, despite promoting mitotic cell cycle progression of those germ cells that do proliferate, separates the specification of proliferative fate from its execution.

Dorsett, Maia; Westlund, Bethany; Schedl, Tim



Primordial Germ Cell-Like Cells Differentiated In Vitro from Skin-Derived Stem Cells  

PubMed Central

Background We have previously demonstrated that stem cells isolated from fetal porcine skin have the potential to form oocyte-like cells (OLCs) in vitro. However, primordial germ cells (PGCs), which must also be specified during the stem cell differentiation to give rise to these putative oocytes at more advanced stages of culture, were not systematically characterized. The current study tested the hypothesis that a morphologically distinct population of cells derived from skin stem cells prior to OLC formation corresponds to putative PGCs, which differentiate further into more mature gametes. Methodology/Principal Findings When induced to differentiate in an appropriate microenvironment, a subpopulation of morphologically distinct cells, some of which are alkaline phosphatase (AP)-positive, also express Oct4, Fragilis, Stella, Dazl, and Vasa, which are markers indicative of germ cell formation. A known differentially methylated region (DMR) within the H19 gene locus, which is demethylated in oocytes after establishment of the maternal imprint, is hypomethylated in PGC-like cells compared to undifferentiated skin-derived stem cells, suggesting that the putative germ cell population undergoes imprint erasure. Additional evidence supporting the germ cell identity of in vitro-generated PGC-like cells is that, when labeled with a Dazl-GFP reporter, these cells further differentiate into GFP-positive OLCs. Significance The ability to generate germ cell precursors from somatic stem cells may provide an in vitro model to study some of the unanswered questions surrounding early germ cell formation.

Linher, Katja; Dyce, Paul; Li, Julang



Germ cell transplantation as a potential biotechnological approach to fish reproduction.  


Although the use of germ cell transplantation has been relatively well established in mammals, the technique has only been adapted for use in fish after entering the 2000s. During the last decade, several different approaches have been developed for germ cell transplantation in fish using recipients of various ages and life stages, such as blastula-stage embryos, newly hatched larvae and sexually mature specimens. As germ cells can develop into live organisms through maturation and fertilization processes, germ cell transplantation in fish has opened up new avenues of research in reproductive biotechnology and aquaculture. For instance, the use of xenotransplantation in fish has lead to advances in the conservation of endangered species and the production of commercially valuable fish using surrogated recipients. Further, this could also facilitate the engineering of transgenic fish. However, as is the case with mammals, knowledge regarding the basic biology and physiology of germline stem cells in fish remains incomplete, imposing a considerable limitation on the application of germ cell transplantation in fish. Furthering our understanding of germline stem cells would contribute significantly to advances regarding germ cell transplantation in fish. PMID:22290474

Lacerda, S M S N; Costa, G M J; Campos-Junior, P H A; Segatelli, T M; Yazawa, R; Takeuchi, Y; Morita, T; Yoshizaki, G; França, L R



Mouse Germ Cell Development in-vivo and in-vitro  

PubMed Central

In mammalian development, primordial germ cells (PGCs) represent the initial population of cells that are committed to the germ cell lineage. PGCs segregate early in development, triggered by signals from the extra-embryonic ectoderm. They are distinguished from surrounding cells by their unique gene expression patterns. Some of the more common genes used to identify them are Blimp1, Oct3/4, Fragilis, Stella, c-Kit, Mvh, Dazl and Gcna1. These genes are involved in regulating their migration and differentiation, and in maintaining the pluripotency of these cells. Recent research has demonstrated the possibility of obtaining PGCs, and subsequently, mature germ cells from a starting population of embryonic stem cells (ESCs) in culture. This phenomenon has been investigated using a variety of methods, and ESC lines of both mouse and human origin. Embryonic stem cells can differentiate into germ cells of both the male and female phenotype and in one case has resulted in the birth of live pups from the fertilization of oocytes with ESC derived sperm. This finding leads to the prospect of using ESC derived germ cells as a treatment for sterility. This review outlines the evolvement of germ cells from ESCs in vitro in relation to in vivo events.

Saiti, Deshira; Lacham-Kaplan, Orly



Characterization and inducibility of hsp 70 proteins in the male mouse germ line  

PubMed Central

The properties and inducibility of the heat shock protein 70 (hsp 70) gene products were examined during differentiation of mouse testicular cells by one and two-dimensional gel electrophoresis and immunoblotting. Low levels of the 72- and 73-kD heat shock proteins normally found in mouse cell lines were detected in the mouse testis. A novel isoform with a relative molecular mass of 73 kD (called 73T) was also observed, in the presence or absence of heat shock. 73T was shown to be produced by germ cells since it was not detected in testes from mutant mice devoid of germ cells. Furthermore, 73T was found only in adult mouse testicular cells, not in testes from animals that lack meiotic germ cells. 73T was synthesized in enriched cell populations of both meiotic prophase and postmeiotic cells, but was not inducible by in vitro heat shock. In the adult testis, low levels of the bona fide 72-kD heat-inducible (hsp72) were induced in response to elevated temperatures. In contrast, in testes from animals in which only somatic cells and premeiotic germ cells were present, there was a substantial induction of hsp 72. It is suggested that hsp 72 is inducible in the somatic compartment and possibly in the premeiotic germ cells, but not in germ cells which have entered meiosis and which are expressing members of the hsp 70 gene family in a developmentally regulated fashion.



Toward a more precise and informative nomenclature describing fetal and neonatal male germ cells in rodents.  


The germ cell lineages are among the best characterized of all cell lineages in mammals. This characterization includes precise nomenclature that distinguishes among numerous, often subtle, changes in function or morphology as development and differentiation of germ cells proceed to form the gametes. In male rodents, there are at least 41 distinct cell types that occur during progression through the male germ cell lineage that gives rise to spermatozoa. However, there is one period during male germ cell development-that which occurs immediately following the primordial germ cell stage and prior to the spermatogonial stage-for which the system of precise and informative cell type terminology is not adequate. Often, male germ cells during this period are referred to simply as "gonocytes." However, this term is inadequate for multiple reasons, and it is suggested here that nomenclature originally proposed in the 1970s by Hilscher et al., which employs the terms M-, T1-, and T2-prospermatogonia, is preferable. In this Minireview, the history, proper utilization, and advantages of this terminology relative to that of the term gonocytes are described. PMID:23843236

McCarrey, John R



Germ cells are essential for sexual dimorphism in the medaka gonad  

PubMed Central

To further elucidate the roles of germ cells in the sex differentiation of gonads, we have used the medaka, a teleost fish, to generate mutants that lack germ cells from the onset of gonadogenesis by the morpholino-mediated knockdown of cxcr4. The resulting germ-cell-deficient medaka show female-to-male sex reversal of their secondary sex characteristics, accompanied by increased levels of androgen and reduced levels of estrogen. A failure to maintain granulosa cells or estrogen-producing cells also occurs at early stages of sex differentiation in the cxcr4 morphants, before the initiation of gonadal morphogenesis. In contrast, androgen-producing cells are unaffected in germ-cell-deficient medaka of either sex. In addition, a single tube-like gonad that expresses male-specific genes is formed in these mutants irrespective of the genetic sex. Significantly, each of these mutant phenotypes occurs in a somatic cell-autonomous manner, suggesting that gonadal somatic cells are predisposed toward male development in the absence of germ cells. This highlights the importance of germ cells in the sexual dimorphism of the gonads.

Kurokawa, Hiromi; Saito, Daisuke; Nakamura, Shuhei; Katoh-Fukui, Yuko; Ohta, Kohei; Baba, Takashi; Morohashi, Ken-ichiro; Tanaka, Minoru



Early segregation of germ and somatic lineages during gonadal regeneration in the annelid Enchytraeus japonensis.  


Although regeneration studies are useful for understanding how organs renew, little information is available about regeneration of reproductive organs and germ cells. We here describe the behavior of germ-cell precursors during regeneration of the oligochaete annelid worm Enchytraeus japonensis, which has the remarkable feature of undergoing asexual (by fission) and sexual reproduction . We first found that the gonad can regenerate from any body fragment yielded by fission during asexual reproduction. We then examined behavior of germ-cell lineage during this regenerative process, by using a homolog of the Piwi gene (Ej-piwi) as a marker. We found that in asexually growing animals, specialized cells expressing Ej-piwi are distributed widely in the body as single cells. These cells seem to serve as a reservoir of germ-cell precursors because during asexual propagation these cells migrate into the regenerating tissue, where they ultimately settle in the prospective gonads, and give rise to germ cells upon sexualization. These cells are distinct from the neoblasts, thought to be stem cells in other animals. This is the first report to directly show that the germ and somatic lineages are segregated in asexually growing animals and behave differently during regeneration. PMID:16713959

Tadokoro, Ryosuke; Sugio, Mutsumi; Kutsuna, Junko; Tochinai, Shin; Takahashi, Yoshiko



Chromosome X modulates incidence of testicular germ cell tumors in Ter mice  

PubMed Central

Germ cell tumor development in humans has been proposed to be part of testicular dysgenesis syndrome (TDS), which manifests as undescended testes, sterility, hypospadias, and, in extreme cases, as germ cell tumors. Males of the Ter mouse strain show interesting parallels to TDS because they either lack germ cells and are sterile or develop testicular germ cell tumors. We found that these defects in Ter mice are due to mutational inactivation of the Dead-end (Dnd1) gene. Here we report that chromo-some X modulates germ cell tumor development in Ter mice. We tested whether the X or the Y chromosome influences tumor incidence. We used chromosome substitution strains to generate two new mouse strains: 129-Ter/Ter that carry either a C57BL/6J (B6)-derived chromosome (Chr) X or Y. We found that Ter/Ter males with B6-Chr X, but not B6-Chr Y, showed a significant shift in propensity from testicular tumor development to sterile testes pheno-type. Thus, our studies provide unambiguous evidence that genetic factors from Chr X modulate the incidence of germ cell tumors in mice with inactivated Dnd1.

Hammond, Shirley; Zhu, Rui; Matin, Angabin; Youngren, Kirsten K.; Lam, Josephine; Anderson, Philip



A late phase of germ plasm accumulation during Drosophila oogenesis requires Lost and Rumpelstiltskin  

PubMed Central

Asymmetric mRNA localization is an effective mechanism for establishing cellular and developmental polarity. Posterior localization of oskar in the Drosophila oocyte targets the synthesis of Oskar to the posterior, where Oskar initiates the assembly of the germ plasm. In addition to harboring germline determinants, the germ plasm is required for localization and translation of the abdominal determinant nanos. Consequently, failure of oskar localization during oogenesis results in embryos lacking germ cells and abdominal segments. oskar accumulates at the oocyte posterior during mid-oogenesis through a well-studied process involving kinesin-mediated transport. Through live imaging of oskar mRNA, we have uncovered a second, mechanistically distinct phase of oskar localization that occurs during late oogenesis and results in amplification of the germ plasm. Analysis of two newly identified oskar localization factors, Rumpelstiltskin and Lost, that are required specifically for this late phase of oskar localization shows that germ plasm amplification ensures robust abdomen and germ cell formation during embryogenesis. In addition, our results indicate the importance of mechanisms for adapting mRNAs to utilize multiple localization pathways as necessitated by the dramatic changes in ovarian physiology that occur during oogenesis.

Sinsimer, Kristina S.; Jain, Roshan A.; Chatterjee, Seema; Gavis, Elizabeth R.



Morphology and function of maturation ameloblasts in kitten tooth germs.  

PubMed Central

In order to clarify the morphology and function of maturation ameloblasts, kitten tooth germs were examined using an ultrastructural tracer technique. Kitten maturation ameloblasts were divided into two cell types: a ruffle-ended type showing plasma membrane infoldings and invaginations at the distal cell surface and a smooth-ended type showing a non-invaginated, smooth distal cell surface. Both ameloblasts possessed two sets of junctional complexes at their proximal and distal ends. In either type of cell, intravenously injected horseradish peroxidase penetrated from the vascular region into the developing enamel surface through both the proximal and distal junctional complexes, although the tight junction compartment inhibited horseradish peroxidase permeation. Ruffle-ended ameloblasts further incorporated peroxidase from the distal cell surface into the cytoplasm by means of membrane invaginations and coated vesicles. Smooth-ended ameloblasts showed little intracellular peroxidase incorporation. These results show clearly that resorptive and non-resorptive maturation ameloblasts exist in kitten enamel organ and that the two cell types correspond to ruffle-ended and smooth-ended maturation ameloblasts in rat incisors. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Figs. 5-7 Fig. 8 Figs. 9-10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16

Sasaki, T



Fermented wheat germ extract (avemar) inhibits adjuvant arthritis.  


Anti-inflammatory efficacy of the fermented wheat germ extract (FWGE, Avemar) in the rat adjuvant arthritis (AA) model was examined. To Wistar rats with AA, different doses of FWGE and anti-inflammatory drugs (indomethacin, dexamethasone) as monotherapies were administered and FWGE and either diclofenac or dexamethasone were also given in combination. Besides plethysmographies of the paws, histological investigations of synovial tissues were also performed along with detection of CD4+ and CD8+ T lymphocytes. Gene expressions of COX-1 and 2 were determined by real-time polymerase chain reaction (PCR). FWGE monotherapy significantly inhibited the development of the secondary (immune-mediated) response in AA, and dexamethasone and indomethacin exerted inhibitory effects in a degree comparable to that of FWGE. Histological analysis of the affected joints confirmed the results. FWGE inhibited COX-1 and -2, while indomethacin enhanced COX-2 gene expressions. FWGE had an additive interaction with diclofenac. It is concluded that FWGE has significant anti-inflammatory efficacy confirmed by plethysmography, histology, and real-time PCR. PMID:17911450

Telekes, Andras; Resetar, Akos; Balint, Geza; Blazso, Gabor; Falkay, Gyorgy; Lapis, Karoly; Raso, Erzsebet; Szende, Bela; Ehrenfeld, Michael; Shoenfeld, Yehuda; Hidvegi, Mate



Fermented wheat germ extract - nutritional supplement or anticancer drug?  

PubMed Central

Background Fermented wheat germ extract (FWGE) is a multisubstance composition and, besides others, contains 2-methoxy benzoquinone and 2, 6-dimethoxy benzoquinone which are likely to exert some of its biological effects. FWGE interferes with anaerobic glycolysis, pentose cycle and ribonucleotide reductase. It has significant antiproliferative effects and kills tumor cells by the induction of apoptosis via the caspase-poly [ADP-ribose] polymerase-pathway. FWGE interacts synergistically with a variety of different anticancer drugs and exerted antimetastatic properties in mouse models. In addition, FWGE modulates immune response by downregulation of MHC-I complex and the induction of TNF-? and various interleukins. Data in the F-344 rat model provide evidence for a colon cancer preventing effect of FWGE. Clinical data from a randomized phase II trial in melanoma patients indicate a significant benefit for patients treated with dacarbazine in combination with FWGE in terms of progression free survival (PFS) and overall survival (OS). Similarly, data from studies in colorectal cancer suggested a benefit of FWGE treatment. Besides extension of OS and PFS, FWGE improved the quality of life in several studies. Conclusion In conclusion, available data so far, justify the use of FWGE as a non-prescription medical nutriment for cancer patients. Further randomized, controlled and large scale clinical studies are mandatory, to further clarify the value of FWGE as a drug component of future chemotherapy regimens.



Safety studies regarding a standardized extract of fermented wheat germ.  


"Avemar pulvis" is a powder consisting of an aqueous extract of fermented wheat germ, with the drying aids maltodextrin and silicon dioxide, standardized to contain approximately 200 microg/g of the natural constituent 2,6-dimethoxy-p-benzoquinone. The results of toxicological and clinical studies of this product demonstrate its safety for its intended use as a dietary supplement ingredient in the United States. Avemar pulvis has been used in Hungary since 1998 and is approved in that country, as well as in the Czech Republic, Bulgaria, and Romania, as a "medical nutriment for cancer patients." Acute and subacute toxicity studies using rodents orally administered Avemar pulvis showed that dose levels (2000 to 3000 mg/kg body weight [bw]/day) exceeding the normal recommended oral dosage (8.5 g/day or 121 mg/kg bw/day for a 70-kg individual) by up to approximately 25-fold caused no adverse effects. The test substance showed no evidence of mutagenicity or genotoxicity in vitro or in vivo. Clinical studies using Avemar pulvis as a supplement to drug therapy in cancer patients at doses of 8.5 g/day not only showed no evidence of toxicity, but also showed a reduction in the side effects of chemotherapy. Overall, it was concluded that Avemar pulvis would not be expected to cause adverse effects under the conditions of its intended use as an ingredient in dietary supplements. PMID:17564907

Heimbach, James T; Sebestyen, Gyula; Semjen, Gabor; Kennepohl, Elke


Germ-line engineering, freedom, and future generations.  


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. PMID:12718332

Cooke, Elizabeth F



Polychlorinated biphenyls and risk of testicular germ cell tumors  

PubMed Central

Exposure to endocrine disrupting chemicals, such as polychlorinated biphenyls (PCBs), may alter hormonal balance and thereby, increase risk of testicular germ cell tumors (TGCT). To study the relationship of PCBs to TGCT, pre-diagnostic serum samples from 736 cases and 913 controls in the Servicemen’s Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Adjusted odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression. PCB levels were examined in association with all TGCT and, separately, with each histologic type (seminoma, nonseminoma). Risks associated with seven functional groupings of PCBs, as well as sum of PCBs, were also examined. There were significantly decreased risks of TGCT in association with eight PCBs (PCB-118, PCB-138, PCB-153, PCB-156, PCB-163, PCB-170, PCB-180, PCB-187) and no association with the remaining three (PCB-99, PCB-101, PCB-183). The same eight congeners were significantly associated with decreased risk of nonseminoma, while five (PCB-138, PCB-153, PCB-156, PCB-163, PCB-170) were associated with decreased risk of seminoma. All functional groupings of PCBs were also associated with decreased risk of TGCT and of nonseminoma, while 3 of the 7 functional groups were associated with decreased risk of seminoma. Sum of PCBs was significantly associated with decreased risk of TGCT (ptrend=0.0008), nonseminoma (ptrend=0.001) and seminoma (ptrend=0.03). Overall, these data do not support the hypothesis that PCB exposure increases the risk of TGCT.

McGlynn, Katherine A.; Quraishi, Sabah M.; Graubard, Barry I.; Weber, Jean-Philippe; Rubertone, Mark V.; Erickson, Ralph L.



Detection of meiotic DNA breaks in mouse testicular germ cells.  


The study of location and intensity of double-strand breaks (DSBs) in mammalian systems is more challenging than in yeast because, unlike yeast, the progression through meiosis is not synchronous and only a small fraction of all testis cells are actually at the stage where DSB formation is initiated. We devised a quantitative approach that is sensitive enough to detect the position of rare DNA strand breaks in mouse germ cell-enriched testicular cell populations. The method can detect DNA breaks at any desired location in the genome but is not specific for DSBs-overhangs, nicks, or gaps with a free 3' OH group are also detected. The method was successfully used to compare testicular cells from mouse strains that possess or lack an active recombination hot spot at the H2-Ea gene. Breaks that were due to meiotic hot spot activity could be distinguished from the background of DNA breaks. This highly sensitive approach could be used to study other biological processes where rare DNA breaks are generated. PMID:19799182

Qin, Jian; Subramanian, Jaichandar; Arnheim, Norman



PHEX neutralizing agent inhibits dentin formation in mouse tooth germ.  


The mutation of phosphate-regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) can lead to human X-linked hypophosphatemic rickets which displays hypo-mineralization in bone and dentin. To study its possible roles in teeth, PHEX antibody was injected into pregnant mice on E15 to explore its roles on the formation of enamel and dentin. Mallory trichrome staining results showed that arrangements of ameloblasts and odontoblasts were irregular after PHEX antibody treatment. Differentiation of odontoblasts and the formation of dentin were inhibited. Spatiotemporal distribution of PHEX protein was observed in various stages of tooth germ. Immunohistochemical results showed positive PHEX signals appeared in the inner enamel epithelium on E16 and became stronger on E18. Ameloblasts and odontoblasts showed much higher PHEX expression on P1 and P3. Expression of PHEX in odontoblasts decreased accordingly. However, enamel formation was only slightly affected. The findings proved that a decrease in PHEX expression could suppress dentin formation. PMID:21324501

Lv, Hongbing; Fu, Sheng; Wu, Gancha; Yan, Fuhua



NANOG priming before full reprogramming may generate germ cell tumours.  


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. PMID:22071697

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



Late cardiovascular toxicity following chemotherapy for germ cell tumors.  


The introduction of cisplatin-based chemotherapy has transformed germ cell tumors (GCTs), the most common malignancy to affect young adult men, into a highly curable cancer, even in the setting of advanced disease. However, over the past decade, the success of these chemotherapy regimens in curing GCTs has been temporized by an increasing recognition of their important late toxicities, such as cardiovascular disease. The relative risk of coronary artery disease in this population is particularly elevated within the first 10 years of follow-up, when patients are still in their 30s and 40s, which are age groups often considered too young to experience cardiovascular events. Two hypotheses have been proposed to explain the association between chemotherapy and cardiovascular disease in this population. The direct hypothesis asserts that chemotherapy causes diffuse endothelial damage, including in the coronary arteries, gradually leading to cardiovascular disease. In contrast, the indirect hypothesis proposes that chemotherapy leads to an increased incidence of cardiovascular disease risk factors, such as hypertension, hyperlipidemia, and the metabolic syndrome, which in turn enhance the risk of cardiovascular disease. This article summarizes the data on the association between chemotherapy (predominantly cisplatin-based) and the development of cardiovascular disease among GCT survivors, and reviews the evidence supporting both mechanistic hypotheses. In addition, recommendations are provided for the management of GCT survivors who received cisplatin-based chemotherapy and are therefore at risk for cardiovascular toxicity. PMID:22491050

Feldman, Darren R; Schaffer, Wendy L; Steingart, Richard M



Transplantation of Genetically Engineered Primary Cells for the Analysis of Gene Function in CNS Development  

Microsoft Academic Search

Transplantation of genetically engineered primary cells into the CNS allows an analysis of gene function that is often not otherwise possible, such as with germ line mutations that result in embryonic lethality or that have pleiotropic effects. We describe the methods and use of this approach for the analysis of gene function during the development of oligodendrocytes, the myelin-forming cells

Randall D. McKinnon; George A. Zazanis



Early transcriptional response in the jejunum of germ-free piglets after oral infection with virulent rotavirus  

PubMed Central

Germ-free piglets were orally infected with virulent rotavirus to collect jejunal mucosal scrapings at 12 and 18 hours post infection (two piglets per time point). IFN-gamma mRNA expression was stimulated in the mucosa of all four infected piglets, indicating that they all responded to the rotavirus infection. RNA pools prepared from two infected piglets were used to compare whole mucosal gene expression at 12 and 18 hpi to expression in uninfected germ-free piglets (n = 3) using a porcine intestinal cDNA microarray. Microarray analysis identified 13 down-regulated and 17 up-regulated genes. Northern blot analysis of a selected group of genes confirmed the data of the microarray. Genes were functionally clustered in interferon-regulated genes, proliferation/differentiation genes, apoptosis genes, cytoskeleton genes, signal transduction genes, and enterocyte digestive, absorptive, and transport genes. Down-regulation of the transport gene cluster reflected in part the loss of rotavirus-infected enterocytes from the villous tips. Data mining suggested that several genes were regulated in lower- or mid-villus immature enterocytes and goblet cells, probably to support repair of the damaged epithelial cell layer at the villous tips. Furthermore, up-regulation was observed for IFN-? induced guanylate binding protein 2, a protein that effectively inhibited VSV and EMCV replication in vitro (Arch Virol 150:1213–1220, 2005). This protein may play a role in the small intestine’s innate defense against enteric viruses like rotavirus. Electronic supplementary material The online version of this article (doi:10.1007/s00705-008-0118-6) contains supplementary material, which is available to authorized users.

Kerstens, Hinri; de Wit, Agnes; Smits, Mari; van der Meulen, Jan; Niewold, Theo



l(3)malignant brain tumor and three novel genes are required for Drosophila germ-cell formation.  

PubMed Central

To identify genes involved in the process of germ-cell formation in Drosophila, a maternal-effect screen using the FLP/FRT-ovoD method was performed on chromosome 3R. In addition to expected mutations in the germ-cell determinant oskar and in other genes known to be involved in the process, several novel mutations caused defects in germ-cell formation. Mutations in any of three genes [l(3)malignant brain tumor, shackleton, and out of sync] affect the synchronous mitotic divisions and nuclear migration of the early embryo. The defects in nuclear migration or mitotic synchrony result in a reduction in germ-cell formation. Mutations in another gene identified in this screen, bebra, do not cause mitotic defects, but appear to act upstream of the localization of oskar. Analysis of our mutants demonstrates that two unique and independent processes must occur to form germ cells-germ-plasm formation and nuclear division/migration.

Yohn, Christopher B; Pusateri, Leslie; Barbosa, Vitor; Lehmann, Ruth



European Consensus Conference on Diagnosis and Treatment of Germ Cell Cancer: A Report of the Second Meeting of the European Germ Cell Cancer Consensus group (EGCCCG): Part I  

Microsoft Academic Search

ObjectivesThe first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands.

Susanne Krege; Jörg Beyer; Rainer Souchon; Peter Albers; Walter Albrecht; Ferran Algaba; Michael Bamberg; István Bodrogi; Carsten Bokemeyer; Eva Cavallin-Stĺhl; Johannes Classen; Christoph Clemm; Gabriella Cohn-Cedermark; Stéphane Culine; Gedske Daugaard; Pieter H. M. De Mulder; Maria De Santis; Maike de Wit; Ronald de Wit; Hans Günter Derigs; Klaus-Peter Dieckmann; Annette Dieing; Jean-Pierre Droz; Martin Fenner; Karim Fizazi; Aude Flechon; Sophie D. Fossĺ; Xavier Garcia del Muro; Thomas Gauler; Lajos Geczi; Arthur Gerl; Jose Ramon Germa-Lluch; Silke Gillessen; Jörg T. Hartmann; Michael Hartmann; Axel Heidenreich; Wolfgang Hoeltl; Alan Horwich; Robert Huddart; Michael Jewett; Johnathan Joffe; William G. Jones; László Kisbenedek; Olbjřrn Klepp; Sabine Kliesch; Kai Uwe Koehrmann; Christian Kollmannsberger; Markus Kuczyk; Pilar Laguna; Oscar Leiva Galvis; Volker Loy; Malcolm D. Mason; Graham M. Mead; Rolf Mueller; Craig Nichols; Nicola Nicolai; Tim Oliver; Dalibor Ondrus; Gosse O. N. Oosterhof; Luis Paz Ares; Giorgio Pizzocaro; Jörg Pont; Tobias Pottek; Tom Powles; Oliver Rick; Giovanni Rosti; Roberto Salvioni; Jutta Scheiderbauer; Hans-Ulrich Schmelz; Heinz Schmidberger; Hans-Joachim Schmoll; Mark Schrader; Felix Sedlmayer; Niels E. Skakkebaek; Aslam Sohaib; Sergei Tjulandin; Padraig Warde; Stefan Weinknecht; Lothar Weissbach; Christian Wittekind; Eva Winter; Lori Wood; Hans von der Maase



Time series analysis supporting the hypothesis that enhanced cosmic radiation during germ cell formation can increase breast cancer mortality in germ cell cohorts  

NASA Astrophysics Data System (ADS)

Techniques from cancer epidemiology and time series analysis were used to explore the hypothesis that cosmic radiation can induce germ cell changes leading to increases in future breast cancer mortality. A birth cohort time series for female breast cancer mortality was obtained using a model-independent, age-period-cohort analysis on age-specific mortality data for 1940-1990. The birth cohort series contained several oscillatory components, which were isolated and compared to the corresponding frequency components of a cosmic ray surrogate time series - Greenland ice-core 10Be concentrations. A technique, referred to as component wave-train alignment, was used to show that the breast cancer and cosmic ray oscillations were phase-locked approx. 25 years before the time of birth. This is consistent with the time of germ cell formation, which occurs during the fetal development stage of the preceding generation. Evidence is presented that the observable oscillations in the birth cohort series were residues of oscillations of much larger amplitude in the germ cell cohort, which were attenuated by the effect of the broad maternal age distribution. It is predicted that a minimum of 50% of breast cancer risk is associated with germ cell damage by cosmic radiation (priming event), which leads to the development of individuals with a higher risk of breast cancer. It is proposed that the priming event, by preceding other steps of carcinogenesis, works in concert with risk factor exposure during life. The priming event is consistent with epigenetic changes such as imprinting.

Juckett, D. A.; Rosenberg, Barnett


Production of chicken progeny (Gallus gallus domesticus) from interspecies germline chimeric duck (Anas domesticus) by primordial germ cell transfer.  


The present study aimed to investigate the differentiation of chicken (Gallus gallus domesticus) primordial germ cells (PGCs) in duck (Anas domesticus) gonads. Chimeric ducks were produced by transferring chicken PGCs into duck embryos. Transfer of 200 and 400 PGCs resulted in the detection of a total number of 63.0 ± 54.3 and 116.8 ± 47.1 chicken PGCs in the gonads of 7-day-old duck embryos, respectively. The chimeric rate of ducks prior to hatching was 52.9% and 90.9%, respectively. Chicken germ cells were assessed in the gonad of chimeric ducks with chicken-specific DNA probes. Chicken spermatogonia were detected in the seminiferous tubules of duck testis. Chicken oogonia, primitive and primary follicles, and chicken-derived oocytes were also found in the ovaries of chimeric ducks, indicating that chicken PGCs are able to migrate, proliferate, and differentiate in duck ovaries and participate in the progression of duck ovarian folliculogenesis. Chicken DNA was detected using PCR from the semen of chimeric ducks. A total number of 1057 chicken eggs were laid by Barred Rock hens after they were inseminated with chimeric duck semen, of which four chicken offspring hatched and one chicken embryo did not hatch. Female chimeric ducks were inseminated with chicken semen; however, no fertile eggs were obtained. In conclusion, these results demonstrated that chicken PGCs could interact with duck germinal epithelium and complete spermatogenesis and eventually give rise to functional sperm. The PGC-mediated germline chimera technology may provide a novel system for conserving endangered avian species. PMID:22190706

Liu, Chunhai; Khazanehdari, Kamal A; Baskar, Vijaya; Saleem, Shazia; Kinne, Joerg; Wernery, Ulrich; Chang, Il-Kuk



Survival of patients with nonseminomatous germ cell cancer: a review of the IGCC classification by Cox regression and recursive partitioning.  


The International Germ Cell Consensus (IGCC) classification identifies good, intermediate and poor prognosis groups among patients with metastatic nonseminomatous germ cell tumours (NSGCT). It uses the risk factors primary site, presence of nonpulmonary visceral metastases and tumour markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH). The IGCC classification is easy to use and remember, but lacks flexibility. We aimed to examine the extent of any loss in discrimination within the IGCC classification in comparison with alternative modelling by formal weighing of the risk factors. We analysed survival of 3048 NSGCT patients with Cox regression and recursive partitioning for alternative classifications. Good, intermediate and poor prognosis groups were based on predicted 5-year survival. Classifications were further refined by subgrouping within the poor prognosis group. Performance was measured primarily by a bootstrap corrected c-statistic to indicate discriminative ability for future patients. The weights of the risk factors in the alternative classifications differed slightly from the implicit weights in the IGCC classification. Discriminative ability, however, did not increase clearly (IGCC classification, c=0.732; Cox classification, c=0.730; Recursive partitioning classification, c=0.709). Three subgroups could be identified within the poor prognosis groups, resulting in classifications with five prognostic groups and slightly better discriminative ability (c=0.740). In conclusion, the IGCC classification in three prognostic groups is largely supported by Cox regression and recursive partitioning. Cox regression was the most promising tool to define a more refined classification. British Journal of Cancer (2004) 90, 1176-1183. doi:10.1038/sj.bjc.6601665 Published online 24 February 2004 PMID:15026798

van Dijk, M R; Steyerberg, E W; Stenning, S P; Dusseldorp, E; Habbema, J D F



Oestrogen receptors and small nuclear ring finger protein 4 (RNF4) in malignant ovarian germ cell tumours  

Microsoft Academic Search

The peak incidence of malignant ovarian germ cell tumours occurs soon after puberty. Thus, gonadal steroids may play a role in their development. Oestrogen receptors (ER? and ER?) and their co-regulators, including small nuclear ring finger protein 4 (SNURF\\/RNF4) mediate oestrogen actions. While ER? and SNURF are down-regulated in testicular germ cell tumours, their role in the ovarian germ cell

Jonna Salonen; Ralf Butzow; Jorma J. Palvimo; Markku Heikinheimo; Oskari Heikinheimo



A Case of Chondrosarcoma Developing in a Recurrent Retroperitoneal Mass after Chemotherapy for Testicular Germ Cell Tumor  

Microsoft Academic Search

Teratomas with malignant transformation occur in a small proportion of patients with metastatic germ cell tumors treated with platinum-based chemotherapy. Chondrosarcoma has rarely been reported as a component of the second non-germ cell malignancy. We report the case of a 37-year-old man who developed a chondrosarcoma in a recurrent retroperitoneal mass after chemotherapy for testicular germ cell tumor. Malignant transformation

Stelios F. Assimakopoulos; Angelos Koutras; Panayiota Ravazoula; Thomas Makatsoris; Theodore Petsas; Gregoris Iconomou; Vassiliki Nikolopoulou; Haralabos P. Kalofonos



Primordial germ cell deficiency in the connexin 43 knockout mouse arises from apoptosis associated with abnormal p53 activation  

Microsoft Academic Search

Connexin 43 knockout (Cx431KO) mice exhibit germ cell deficiency, but the underlying cause for the germ cell defect was unknown. Using an Oct4-GFP reporter transgene, we tracked the distribution and migration of primordial germ cells (PGCs) in the Cx431KO mouse embryo. Analysis with dye injections showed PGCs are gap-junction-communication competent, with dye coupling being markedly reduced in Cx431-deficient PGCs. Time-lapse

Richard J. B. Francis; Cecilia W. Lo



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

Microsoft Academic Search

We report molecular genetic studies of three genes involved in early germ-line proliferation in Caenorhab- ditis 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

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



fog-2, a Germ-Line-Specific Sex Determination Gene Required for Hermaphrodite Spermatogenesis in Caenorhabditis elegans  

Microsoft Academic Search

This paper describes the isolation and characterization of 16 mutations in the germ-line sex determination gene fog-2 (fog for feminization of the germ line). In the nematode Caenorhabditis elegans there are normally two sexes, self-fertilizing hermaphrodites (XX) and males (XO). Wild- type XX animals are hermaphrodite in the germ line (spermatogenesis followed by oogenesis), and female in the soma. fog-2

Tim Schedl; Judith Kimble


Effect of adding wheat bran and germ fractions on the chemical composition of high-fiber toast bread  

Microsoft Academic Search

The effect of the type of bran, level of addition, particle size and addition of wheat germ on the chemical composition of high-fiber toast bread was investigated. The bran and germ fractions were found to be high in ash, protein, fat and total dietary fiber contents. The wheat germ had a protein content of 27.88% compared with 11.35, 12.69 and

Jiwan S Sidhu; Suad N Al-Hooti; Jameela M Al-Saqer