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  1. Retinoic acid induces Sertoli cell paracrine signals for spermatogonia differentiation but cell autonomously drives spermatocyte meiosis

    PubMed Central

    Raverdeau, Mathilde; Gely-Pernot, Aurore; Féret, Betty; Dennefeld, Christine; Benoit, Gérard; Davidson, Irwin; Chambon, Pierre; Mark, Manuel; Ghyselinck, Norbert B.

    2012-01-01

    Direct evidence for a role of endogenous retinoic acid (RA), the active metabolite of vitamin A in the initial differentiation and meiotic entry of spermatogonia, and thus in the initiation of spermatogenesis is still lacking. RA is synthesized by dedicated enzymes, the retinaldehyde dehydrogenases (RALDH), and binds to and activates nuclear RA receptors (RARA, RARB, and RARG) either within the RA-synthesizing cells or in the neighboring cells. In the present study, we have used a combination of somatic genetic ablations and pharmacological approaches in vivo to show that during the first, prepubertal, spermatogenic cycle (i) RALDH-dependent synthesis of RA by Sertoli cells (SC), the supporting cells of the germ cell (GC) lineage, is indispensable to initiate differentiation of A aligned into A1 spermatogonia; (ii) RARA in SC mediates the effects of RA, possibly through activating Mafb expression, a gene whose Drosophila homolog is mandatory to GC differentiation; (iii) RA synthesized by premeiotic spermatocytes cell autonomously induces meiotic initiation through controlling the RAR-dependent expression of Stra8. Furthermore, we show that RA of SC origin is no longer necessary for the subsequent spermatogenic cycles but essential to spermiation. Altogether, our data establish that the effects of RA in vivo on spermatogonia differentiation are indirect, via SC, but direct on meiotic initiation in spermatocytes, supporting thereby the notion that, contrary to the situation in the female, RA is necessary to induce meiosis in the male. PMID:23012458

  2. High telomerase is a hallmark of undifferentiated spermatogonia and is required for maintenance of male germline stem cells.

    PubMed

    Pech, Matthew F; Garbuzov, Alina; Hasegawa, Kazuteru; Sukhwani, Meena; Zhang, Ruixuan J; Benayoun, Bérénice A; Brockman, Stephanie A; Lin, Shengda; Brunet, Anne; Orwig, Kyle E; Artandi, Steven E

    2015-12-01

    Telomerase inactivation causes loss of the male germline in worms, fish, and mice, indicating a conserved dependence on telomere maintenance in this cell lineage. Here, using telomerase reverse transcriptase (Tert) reporter mice, we found that very high telomerase expression is a hallmark of undifferentiated spermatogonia, the mitotic population where germline stem cells reside. We exploited these high telomerase levels as a basis for purifying undifferentiated spermatogonia using fluorescence-activated cell sorting. Telomerase levels in undifferentiated spermatogonia and embryonic stem cells are comparable and much greater than in somatic progenitor compartments. Within the germline, we uncovered an unanticipated gradient of telomerase activity that also enables isolation of more mature populations. Transcriptomic comparisons of Tert(High) undifferentiated spermatogonia and Tert(Low) differentiated spermatogonia by RNA sequencing reveals marked differences in cell cycle and key molecular features of each compartment. Transplantation studies show that germline stem cell activity is confined to the Tert(High) cKit(-) population. Telomere shortening in telomerase knockout strains causes depletion of undifferentiated spermatogonia and eventual loss of all germ cells after undifferentiated spermatogonia drop below a critical threshold. These data reveal that high telomerase expression is a fundamental characteristic of germline stem cells, thus explaining the broad dependence on telomerase for germline immortality in metazoans. PMID:26584619

  3. Benzo(a)pyrene Is Mutagenic in Mouse Spermatogonial Stem Cells and Dividing Spermatogonia.

    PubMed

    O'Brien, Jason M; Beal, Marc A; Yauk, Carole L; Marchetti, Francesco

    2016-08-01

    Although many environmental agents are established male germ cell mutagens, few are known to induce mutations in spermatogonial stem cells. Stem cell mutations are of great concern because they result in a permanent increase in the number of mutations carried in sperm. We investigated mutation induction during mouse spermatogenesis following exposure to benzo(a)pyrene (BaP). MutaMouse males were given 0, 12.5, 25, 50, or 100 mg/kg bw/day BaP for 28 days by oral gavage. Germ cells were collected from the cauda epididymis and seminiferous tubules 3 days after exposure and from cauda epididymis 42 and 70 days after exposure. This design enabled targeted investigation of effects on post-spermatogonia, dividing spermatogonia, and spermatogonial stem cells, respectively. BaP increased lacZ mutant frequency (MF) in cauda sperm after exposure of dividing spermatogonia (4.2-fold at highest dose, P < .01) and spermatogonial stem cells (2.1-fold at highest dose, P < .01). No significant increases in MF were detected in cauda sperm or seminiferous tubule cells collected 3 days post-exposure. Dose-response modelling suggested that the mutational response in male germ cells to BaP is sub-linear at low doses. Our results demonstrate that oral exposure to BaP causes spermatogonial stem cell mutations, that different phases of spermatogenesis exhibit varying sensitivities to BaP, with dividing spermatogonia representing a window of peak sensitivity, and that sampling spermatogenic cells from the seminiferous tubules at earlier time-points may underestimate germ cell mutagenicity. This information is critical to optimize the use of the international test guideline for transgenic rodent mutation assays for detecting germ cell mutagens. PMID:27208087

  4. Benzo(a)pyrene Is Mutagenic in Mouse Spermatogonial Stem Cells and Dividing Spermatogonia

    PubMed Central

    O’Brien, Jason M.; Beal, Marc A.; Yauk, Carole L.; Marchetti, Francesco

    2016-01-01

    Although many environmental agents are established male germ cell mutagens, few are known to induce mutations in spermatogonial stem cells. Stem cell mutations are of great concern because they result in a permanent increase in the number of mutations carried in sperm. We investigated mutation induction during mouse spermatogenesis following exposure to benzo(a)pyrene (BaP). MutaMouse males were given 0, 12.5, 25, 50, or 100 mg/kg bw/day BaP for 28 days by oral gavage. Germ cells were collected from the cauda epididymis and seminiferous tubules 3 days after exposure and from cauda epididymis 42 and 70 days after exposure. This design enabled targeted investigation of effects on post-spermatogonia, dividing spermatogonia, and spermatogonial stem cells, respectively. BaP increased lacZ mutant frequency (MF) in cauda sperm after exposure of dividing spermatogonia (4.2-fold at highest dose, P < .01) and spermatogonial stem cells (2.1-fold at highest dose, P < .01). No significant increases in MF were detected in cauda sperm or seminiferous tubule cells collected 3 days post-exposure. Dose-response modelling suggested that the mutational response in male germ cells to BaP is sub-linear at low doses. Our results demonstrate that oral exposure to BaP causes spermatogonial stem cell mutations, that different phases of spermatogenesis exhibit varying sensitivities to BaP, with dividing spermatogonia representing a window of peak sensitivity, and that sampling spermatogenic cells from the seminiferous tubules at earlier time-points may underestimate germ cell mutagenicity. This information is critical to optimize the use of the international test guideline for transgenic rodent mutation assays for detecting germ cell mutagens. PMID:27208087

  5. Retinoic Acid Receptors Control Spermatogonia Cell-Fate and Induce Expression of the SALL4A Transcription Factor.

    PubMed

    Gely-Pernot, Aurore; Raverdeau, Mathilde; Teletin, Marius; Vernet, Nadège; Féret, Betty; Klopfenstein, Muriel; Dennefeld, Christine; Davidson, Irwin; Benoit, Gérard; Mark, Manuel; Ghyselinck, Norbert B

    2015-10-01

    All-trans retinoic acid (ATRA) is instrumental to male germ cell differentiation, but its mechanism of action remains elusive. To address this question, we have analyzed the phenotypes of mice lacking, in spermatogonia, all rexinoid receptors (RXRA, RXRB and RXRG) or all ATRA receptors (RARA, RARB and RARG). We demonstrate that the combined ablation of RXRA and RXRB in spermatogonia recapitulates the set of defects observed both upon ablation of RAR in spermatogonia. We also show that ATRA activates RAR and RXR bound to a conserved regulatory region to increase expression of the SALL4A transcription factor in spermatogonia. Our results reveal that this major pluripotency gene is a target of ATRA signaling and that RAR/RXR heterodimers are the functional units driving its expression in spermatogonia. They add to the mechanisms through which ATRA promote expression of the KIT tyrosine kinase receptor to trigger a critical step in spermatogonia differentiation. Importantly, they indicate also that meiosis eventually occurs in the absence of a RAR/RXR pathway within germ cells and suggest that instructing this process is either ATRA-independent or requires an ATRA signal originating from Sertoli cells. PMID:26427057

  6. Retinoic Acid Receptors Control Spermatogonia Cell-Fate and Induce Expression of the SALL4A Transcription Factor

    PubMed Central

    Gely-Pernot, Aurore; Raverdeau, Mathilde; Teletin, Marius; Vernet, Nadège; Féret, Betty; Klopfenstein, Muriel; Dennefeld, Christine; Davidson, Irwin; Benoit, Gérard; Mark, Manuel; Ghyselinck, Norbert B.

    2015-01-01

    All-trans retinoic acid (ATRA) is instrumental to male germ cell differentiation, but its mechanism of action remains elusive. To address this question, we have analyzed the phenotypes of mice lacking, in spermatogonia, all rexinoid receptors (RXRA, RXRB and RXRG) or all ATRA receptors (RARA, RARB and RARG). We demonstrate that the combined ablation of RXRA and RXRB in spermatogonia recapitulates the set of defects observed both upon ablation of RAR in spermatogonia. We also show that ATRA activates RAR and RXR bound to a conserved regulatory region to increase expression of the SALL4A transcription factor in spermatogonia. Our results reveal that this major pluripotency gene is a target of ATRA signaling and that RAR/RXR heterodimers are the functional units driving its expression in spermatogonia. They add to the mechanisms through which ATRA promote expression of the KIT tyrosine kinase receptor to trigger a critical step in spermatogonia differentiation. Importantly, they indicate also that meiosis eventually occurs in the absence of a RAR/RXR pathway within germ cells and suggest that instructing this process is either ATRA-independent or requires an ATRA signal originating from Sertoli cells. PMID:26427057

  7. Quantitative detection of human spermatogonia for optimization of spermatogonial stem cell culture

    PubMed Central

    Zheng, Y.; Thomas, A.; Schmidt, C.M.; Dann, C.T.

    2014-01-01

    STUDY QUESTION Can human spermatogonia be detected in long-term primary testicular cell cultures using validated, germ cell-specific markers of spermatogonia? SUMMARY ANSWER Germ cell-specific markers of spermatogonia/spermatogonial stem cells (SSCs) are detected in early (1–2 weeks) but not late (> 6 weeks) primary testicular cell cultures; somatic cell markers are detected in late primary testicular cell cultures. WHAT IS KNOWN ALREADY The development of conditions for human SSC culture is critically dependent on the ability to define cell types unequivocally and to quantify spermatogonia/SSCs. Growth by somatic cells presents a major challenge in the establishment of SSC cultures and therefore markers that define spermatogonia/SSCs, but are not also expressed by testicular somatic cells, are essential for accurate characterization of SSC cultures. STUDY DESIGN, SIZE, DURATION Testicular tissue from eight organ donors with normal spermatogenesis was used for assay validation and establishing primary testicular cell cultures. PARTICIPANTS/MATERIALS, SETTING, METHODS Immunofluorescence analysis of normal human testicular tissue was used to validate antibodies (UTF1, SALL4, DAZL and VIM) and then the antibodies were used to demonstrate that primary testicular cells cultured in vitro for 1–2 weeks were composed of somatic cells and rare germ cells. Primary testicular cell cultures were further characterized by comparing to testicular somatic cell cultures using quantitative reverse transcriptase PCR (UTF1, FGFR3, ZBTB16, GPR125, DAZL, GATA4 and VIM) and flow cytometry (CD9 and SSEA4). MAIN RESULTS AND THE ROLE OF CHANCE UTF1, FGFR3, DAZL and ZBTB16 qRT–PCR and SSEA4 flow cytometry were validated for the sensitive, quantitative and specific detection of germ cells. In contrast, GPR125 mRNA and CD9 were found to be not specific to germ cells because they were also expressed in testicular somatic cell cultures. While the germ cell-specific markers were detected in

  8. Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia

    PubMed Central

    Di Fiore, Maria Maddalena; Santillo, Alessandra; Falvo, Sara; Longobardi, Salvatore; Chieffi Baccari, Gabriella

    2016-01-01

    A bulk of evidence suggests that d-aspartate (d-Asp) regulates steroidogenesis and spermatogenesis in vertebrate testes. This review article focuses on intracellular signaling mechanisms elicited by d-Asp possibly via binding to the N-methyl-d-aspartate receptor (NMDAR) in both Leydig cells, and spermatogonia. In Leydig cells, the amino acid upregulates androgen production by eliciting the adenylate cyclase-cAMP and/or mitogen-activated protein kinase (MAPK) pathways. d-Asp treatment enhances gene and protein expression of enzymes involved in the steroidogenic cascade. d-Asp also directly affects spermatogonial mitotic activity. In spermatogonial GC-1 cells, d-Asp induces phosphorylation of MAPK and AKT serine-threonine kinase proteins, and stimulates expression of proliferating cell nuclear antigen (PCNA) and aurora kinase B (AURKB). Further stimulation of spermatogonial GC-1 cell proliferation might come from estradiol/estrogen receptor β (ESR2) interaction. d-Asp modulates androgen and estrogen levels as well as the expression of their receptors in the rat epididymis by acting on mRNA levels of Srd5a1 and Cyp19a1 enzymes, hence suggesting involvement in spermatozoa maturation. PMID:27428949

  9. Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia.

    PubMed

    Di Fiore, Maria Maddalena; Santillo, Alessandra; Falvo, Sara; Longobardi, Salvatore; Chieffi Baccari, Gabriella

    2016-01-01

    A bulk of evidence suggests that d-aspartate (d-Asp) regulates steroidogenesis and spermatogenesis in vertebrate testes. This review article focuses on intracellular signaling mechanisms elicited by d-Asp possibly via binding to the N-methyl-d-aspartate receptor (NMDAR) in both Leydig cells, and spermatogonia. In Leydig cells, the amino acid upregulates androgen production by eliciting the adenylate cyclase-cAMP and/or mitogen-activated protein kinase (MAPK) pathways. d-Asp treatment enhances gene and protein expression of enzymes involved in the steroidogenic cascade. d-Asp also directly affects spermatogonial mitotic activity. In spermatogonial GC-1 cells, d-Asp induces phosphorylation of MAPK and AKT serine-threonine kinase proteins, and stimulates expression of proliferating cell nuclear antigen (PCNA) and aurora kinase B (AURKB). Further stimulation of spermatogonial GC-1 cell proliferation might come from estradiol/estrogen receptor β (ESR2) interaction. d-Asp modulates androgen and estrogen levels as well as the expression of their receptors in the rat epididymis by acting on mRNA levels of Srd5a1 and Cyp19a1 enzymes, hence suggesting involvement in spermatozoa maturation. PMID:27428949

  10. Conservation of spermatogonial stem cell marker expression in undifferentiated felid spermatogonia.

    PubMed

    Vansandt, Lindsey M; Livesay, Janelle L; Dickson, Melissa Joy; Li, Lei; Pukazhenthi, Budhan S; Keefer, Carol L

    2016-09-01

    Spermatogonial stem cells (SSCs) are distinct in their ability to self-renew, transmit genetic information, and persist throughout the life of an individual. These characteristics make SSCs a useful tool for addressing diverse challenges such as efficient transgenic production in nonrodent, biomedical animal models, or preservation of the male genome for species in which survival of frozen-thawed sperm is low. A requisite first step to access this technology in felids is the establishment of molecular markers. This study was designed to evaluate, in the domestic cat (Felis catus), the expression both in situ and following enrichment in vitro of six genes (GFRA1, GPR125, ZBTB16, POU5F1, THY1, and UCHL1) that had been previously identified as SSC markers in other species. Antibodies for surface markers glial cell line-derived neurotrophic factor family receptor alpha 1, G protein-coupled receptor 125, and thymus cell antigen 1 could not be validated, whereas Western blot analysis of prepubertal, peripubertal, and adult cat testis confirmed protein expression for the intracellular markers ubiquitin carboxy-terminal hydrolase 1, zinc finger and BTB domain-containing protein 16, and POU domain, class 5, transcription factor 1. Colocalization of the markers by immunohistochemistry revealed that several cells within the subpopulation adjacent to the basement membrane of the seminiferous tubules and identified morphologically as spermatogonia, expressed all three intracellular markers. Studies performed on cheetah (Acinonyx jubatus) and Amur leopard (Panthera pardus orientalis) testis exhibited a conserved expression pattern in protein molecular weights, relative abundance, and localization of positive cells within the testis. The expression of the three intracellular SSC marker proteins in domestic and wild cat testes confirms conservation of these markers in felids. Enrichment of marker transcripts after differential plating was also observed. These markers will

  11. Classification of several types of maturational arrest of spermatogonia according to Sertoli cell morphology: an approach to aetiology.

    PubMed

    Nistal, M; De Mora, J C; Paniagua, R

    1998-12-01

    Bilateral testicular biopsies and clinical histories from 34 adult men with maturational arrest of spermatogonia were examined. According to the morphology of Sertoli cell nuclei, five testicular types of spermatogonial maturational arrest were established. In type I lesion, Sertoli cells resembled the immature Sertoli cells of infant testes. These cells had a round, regularly outlined, dark nucleus with a small nucleolus. The seminiferous tubules showed no apparent lumen and a poorly developed lamina propria lacking in elastic fibres. This lesion was found in patients exhibiting a eunuchoid phenotype, with small tests and low serum levels of gonadotrophins and testosterone (hypogonadotrophic hypogonadism). Type II lesion showed morphologically normal, mature, adult Sertoli cells which had a pale, irregularly outlined nucleus, many often triangle-shaped, with a large, centrally located nucleolus. The seminiferous tubules were reduced in diameter and showed a few spermatocytes and spermatids. This lesion was found in patients with varicocoele, epididymitis, testicular trauma or idiopathic infertility. Serum FSH levels were normal or increased while LH and testosterone levels were normal. In type III lesion, Sertoli cells resembled the involuting Sertoli cells found in the testes of aging men, and displayed very infolded nuclei, with abundant dense chromatin patches and a large nucleolus. The seminiferous tubules showed a slightly dilated lumen and a normal tubular wall. The most relevant clinical findings in patients with this lesion were alcoholism, varicocoele, falciform cell anaemia, epididymitis and germ cell tumour. Serum follicle stimulating hormone (FSH) levels were normal or increased while luteinizing hormone (LH) and testosterone levels were normal. Type IV lesion Sertoli cells presented with a de-differentiated appearance. These cells had a small, round euchromatic nucleus with a small nucleolus and vacuolated cytoplasm. The seminiferous tubules were

  12. Improving the Efficacy of Cryopreservation of Spermatogonia Stem Cells by Antioxidant Supplements.

    PubMed

    Aliakbari, Fereshte; Gilani, Mohamad Ali Sedighi; Amidi, Fardin; Baazm, Maryam; Korouji, Morteza; Izadyar, Fariborz; Yazdekhasti, Hosein; Abbasi, Mehdi

    2016-04-01

    Cryopreservation of spermatogonial stem cells (SSCs) is an applicable method for young males seeking fertility preservation before starting a treatment. It increases reactive oxygen species (ROS) formation and oxidative stress, which damages cellular structures. In this study, we added two antioxidants, catalase and α-tocopherol (α-TCP), to the basic freezing medium to evaluate their effects on the efficiency of SSCs. SSCs were isolated from testes of 3- to 6-day-old male mice using enzymatic digestion. The enrichment of isolated cells was evaluated by flow cytometry and Stra8 antibody. Catalase (40 μg/mL), or α-TCP (200 μg/mL) was added to the basic freezing medium. The cell viability was evaluated by the methylthiazoltetrazolium (MTT) assay. After thawing, cells were cultured for 1 month, and the expression pattern of specific genes of SSCs and the ability of the cells to restore spermatogenesis were used to determine the efficiency of the cryopreservation method. The survival rate of the frozen cells in the presence of catalase or α-TCP was significantly higher than the control group (p < 0.05). The number of colonies and their diameter measured after 1 month were significantly higher in the antioxidant groups than in the control group (p < 0.05). Gene expression and resumption of spermatogenesis also followed the same pattern. Thus, adding antioxidants to the basic freezing medium can be helpful in increasing the quality and viability of SSCs after cryopreservation. This new approach to stem cells cryopreservation can also be a promising strategy for fertility preservation in patients who suffer from malignancy. PMID:27055629

  13. Induction of reciprocal translocations in rhesus monkey stem-cell spermatogonia: effects of low doses and low dose rates

    SciTech Connect

    van Buul, P.P.; Richardson, J.F. Jr.; Goudzwaard, J.H.

    1986-01-01

    The induction of reciprocal translocation in rhesus monkey spermatogonial stem cells was studied following exposure to low doses of acute X rays (0.25 Gy, 300 mGy/min) or to low-dose-rate X rays (1 Gy, 2 mGy/min) and gamma rays (1 Gy, 0.2 mGy/min). The results obtained at 0.25 Gy of X rays fitted exactly the linear extrapolation down from the 0.5 and 1.0 Gy points obtained earlier. Extension of X-ray exposure reduced the yield of translocations similar to that in the mouse by about 50%. The reduction to 40% of translocation rate after chronic gamma exposure was clearly less than the value of about 80% reported for the mouse over the same range of dose rates. Differential cell killing with ensuing differential elimination of aberration-carrying cells is the most likely explanation for the differences between mouse and monkey.

  14. Conditions for Long-Term Culture of Cattle Undifferentiated Spermatogonia.

    PubMed

    Oatley, Melissa J; Kaucher, Amy V; Yang, Qi-En; Waqas, Muhammad Salman; Oatley, Jon M

    2016-07-01

    Continual and robust spermatogenesis relies on the actions of an undifferentiated spermatogonial population that contains stem cells. A remarkable feature of spermatogonial stem cells (SSCs) is the capacity to regenerate spermatogenesis following isolation from a donor testis and transplantation into a permissive recipient testis. This capacity has enormous potential as a tool for enhancing the reproductive capacity of livestock, which can improve production efficiency. Because SSCs are a rare subset of the undifferentiated spermatogonial population, a period of in vitro amplification in number following isolation from donor testicular tissue is essential. Here, we describe methodology for isolation of a cell fraction from prepubertal bull testes that is enriched for undifferentiated spermatogonia and long-term maintenance of the cells in both the feeder cell coculture and the feeder-free format. To achieve this method, we derived bovine fetal fibroblasts (BFF) to serve as feeders for optimizing medium conditions that promote maintenance of bovine undifferentiated spermatogonia for at least 2 mo. In addition, we devised a feeder-free system with BFF-conditioned medium that sustained bovine undifferentiated spermatogonia for at least 1 mo in vitro. The methodologies described could be optimized to provide platforms for exponential expansion of bovine SSCs that will provide the numbers needed for transplantation into recipient testes. PMID:27251094

  15. Distinct purinergic signaling pathways in prepubescent mouse spermatogonia.

    PubMed

    Fleck, David; Mundt, Nadine; Bruentgens, Felicitas; Geilenkirchen, Petra; Machado, Patricia A; Veitinger, Thomas; Veitinger, Sophie; Lipartowski, Susanne M; Engelhardt, Corinna H; Oldiges, Marco; Spehr, Jennifer; Spehr, Marc

    2016-09-01

    Spermatogenesis ranks among the most complex, yet least understood, developmental processes. The physiological principles that control male germ cell development in mammals are notoriously difficult to unravel, given the intricate anatomy and complex endo- and paracrinology of the testis. Accordingly, we lack a conceptual understanding of the basic signaling mechanisms within the testis, which control the seminiferous epithelial cycle and thus govern spermatogenesis. Here, we address paracrine signal transduction in undifferentiated male germ cells from an electrophysiological perspective. We identify distinct purinergic signaling pathways in prepubescent mouse spermatogonia, both in vitro and in situ. ATP-a dynamic, widespread, and evolutionary conserved mediator of cell to cell communication in various developmental contexts-activates at least two different spermatogonial purinoceptor isoforms. Both receptors operate within nonoverlapping stimulus concentration ranges, display distinct response kinetics and, in the juvenile seminiferous cord, are uniquely expressed in spermatogonia. We further find that spermatogonia express Ca(2+)-activated large-conductance K(+) channels that appear to function as a safeguard against prolonged ATP-dependent depolarization. Quantitative purine measurements additionally suggest testicular ATP-induced ATP release, a mechanism that could increase the paracrine radius of initially localized signaling events. Moreover, we establish a novel seminiferous tubule slice preparation that allows targeted electrophysiological recordings from identified testicular cell types in an intact epithelial environment. This unique approach not only confirms our in vitro findings, but also supports the notion of purinergic signaling during the early stages of spermatogenesis. PMID:27574293

  16. Data on in vivo phenotypes of GFRα1-positive spermatogonia stimulated by interstitial GDNF signals in mouse testes.

    PubMed

    Uchida, Aya; Kanai, Yoshiakira

    2016-09-01

    This article contains the data related to the research article "in vivo dynamics of GFRα1-positive spermatogonia stimulated by GDNF signals using a bead transplantation assay" (Uchida et al., 2016) [1]. A novel transplantation assay of growth factor-soaked beads into the mammalian testicular interstitium was developed, in order to examine the effects of various soluble factors on in vivo dynamics of the spermatogonia including spermatogonial stem cells (SSC). Here we provide the image data of GFRα1-positive stem/progenitor spermatogonia in mouse seminiferous tubules near the beads soaked in GDNF (glial cell-derived neurotrophic factor), one of the SSC niche factors. The data provide various phenotypes of GFRα1-positive spermatogonia induced by bead-derived GDNF signals, which are useful to understand the active state of GFRα1-positive stem/progenitor spermatogonia in vivo. PMID:27547806

  17. In vivo dynamics of GFRα1-positive spermatogonia stimulated by GDNF signals using a bead transplantation assay.

    PubMed

    Uchida, Aya; Kishi, Kasane; Aiyama, Yoshimi; Miura, Kento; Takase, Hinako M; Suzuki, Hitomi; Kanai-Azuma, Masami; Iwamori, Tokuko; Kurohmaru, Masamichi; Tsunekawa, Naoki; Kanai, Yoshiakira

    2016-08-01

    In mouse testes, spermatogonial stem cells (SSCs), a subpopulation of GFRα1 (GDNF family receptor-α1)-positive spermatogonia, are widely distributed along the convoluted seminiferous tubules. The proliferation and differentiation of the SSCs are regulated in part by local expression of GDNF (glial cell-derived neurotorphic factor), one of major niche factors for SSCs. However, the in vivo dynamics of the GDNF-stimulated GFRα1-positive spermatogonia remains unclear. Here, we developed a simple method for transplanting DiI-labeled and GDNF-soaked beads into the mouse testicular interstitium. By using this method, we examined the dynamics of GFRα1-positive spermatogonia in the tubular walls close to the transplanted GDNF-soaked beads. The bead-derived GDNF signals were able to induce the stratified aggregate formation of GFRα1-positive undifferentiated spermatogonia by day 3 post-transplantation. Each aggregate consisted of tightly compacted Asingle and marginal Apaired-Aaligned GFRα1-positive spermatogonia and was surrounded by Aaligned GFRα1-negative spermatogonia at more advanced stages. These data not only provide in vivo evidence for the inductive roles of GDNF in forming a rapid aggregation of GFRα1-positive spermatogonia but also indicate the usefulness of this in vivo assay system of various growth factors for the stem/progenitor spermatogonia in mammalian spermatogenesis. PMID:27255992

  18. Lung Cancer Stem Cell Lose Their Stemness Default State after Exposure to Microgravity

    PubMed Central

    Pisanu, Maria Elena; Noto, Alessia; De Vitis, Claudia; Masiello, Maria Grazia; Coluccia, Pierpaolo; Proietti, Sara; Giovagnoli, Maria Rosaria; Ricci, Alberto; Giarnieri, Enrico; Cucina, Alessandra; Ciliberto, Gennaro; Bizzarri, Mariano; Mancini, Rita

    2014-01-01

    Microgravity influences cell differentiation by modifying the morphogenetic field in which stem cells are embedded. Preliminary data showed indeed that stem cells are committed to selective differentiation when exposed to real or simulated microgravity. Our study provides evidence that a similar event occurs when cancer stem cells (CSCs) are cultured in microgravity. In the same time, a significant increase in apoptosis was recorded: those data point out that microgravity rescues CSCs from their relative quiescent state, inducing CSCs to lose their stemness features, as documented by the decrease in ALDH and the downregulation of both Nanog and Oct-4 genes. Those traits were stably acquired and preserved by CSCs when cells were placed again on a 1 g field. Studies conducted in microgravity on CSCs may improve our understanding of the fundamental role exerted by biophysical forces in cancer cell growth and function. PMID:25276790

  19. AZFc deletions do not affect the function of human spermatogonia in vitro

    PubMed Central

    Nickkholgh, B.; Korver, C.M.; van Daalen, S.K.M.; van Pelt, A.M.M.; Repping, S.

    2015-01-01

    Azoospermic factor c (AZFc) deletions are the underlying cause in 10% of azoo- or severe oligozoospermia. Through extensive molecular analysis the precise genetic content of the AZFc region and the origin of its deletion have been determined. However, little is known about the effect of AZFc deletions on the functionality of germ cells at various developmental steps. The presence of normal, fertilization-competent sperm in the ejaculate and/or testis of the majority of men with AZFc deletions suggests that the process of differentiation from spermatogonial stem cells (SSCs) to mature spermatozoa can take place in the absence of the AZFc region. To determine the functionality of AZFc-deleted spermatogonia, we compared in vitro propagated spermatogonia from six men with complete AZFc deletions with spermatogonia from three normozoospermic controls. We found that spermatogonia of AZFc-deleted men behave similar to controls during culture. Short-term (18 days) and long-term (48 days) culture of AZFc-deleted spermatogonia showed the same characteristics as non-deleted spermatogonia. This similarity was revealed by the same number of passages, the same germ cell clusters formation and similar level of genes expression of spermatogonial markers including ubiquitin carboxyl-terminal esterase L1 (UCHL1), zinc finger and BTB domain containing 16 (ZBTB16) and glial cell line-derived neurotrophic factor family receptor alpha 1 (GFRA1), as well as germ cell differentiation markers including signal transducer and activator of transcription 3 (STAT3), spermatogenesis and oogenesis specific basic helix-loophelix 2 (SOHLH2), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) and synaptonemal complex protein 3 (SYCP3). The only exception was melanoma antigen family A4 (MAGEA4) which showed significantly lower expression in AZFc-deleted samples than controls in short-term culture while in long-term culture it was hardly detected in both AZFc-deleted and control

  20. A Simple Method for Labeling Human Embryonic Stem Cells Destined to Lose Undifferentiated Potency.

    PubMed

    Kumagai, Ayako; Suga, Mika; Yanagihara, Kana; Itoh, Yumi; Takemori, Hiroshi; Furue, Miho K

    2016-03-01

    Mitochondrial oxidative phosphorylation is a major source of cellular ATP. Its usage as an energy source varies, not only according to the extracellular environment, but also during development and differentiation, as indicated by the reported changes in the flux ratio of glycolysis to oxidative phosphorylation during embryonic stem (ES) cell differentiation. The fluorescent probe JC-1 allows visualization of changes in the mitochondrial membrane potential produced by oxidative phosphorylation. Strong JC-1 signals were localized in the differentiated cells located at the edge of H9 ES colonies that expressed vimentin, an early differentiation maker. The JC-1 signals were further intensified when individual adjacent colonies were in contact with each other. Time-lapse analyses revealed that JC-1-labeled H9 cells under an overconfluent condition were highly differentiated after subculture, suggesting that monitoring oxidative phosphorylation in live cells might facilitate the prediction of induced pluripotent stem cells, as well as ES cells, that are destined to lose their undifferentiated potency. PMID:26819254

  1. HEB-deficient T-cell precursors lose T-cell potential and adopt an alternative pathway of differentiation.

    PubMed

    Braunstein, Marsela; Anderson, Michele K

    2011-03-01

    Early thymocytes possess multilineage potential, which is progressively restricted as cells transit through the double-negative stages of T-cell development. DN1 cells retain the ability to become natural killer cells, dendritic cells, B cells, and myeloid cells as well as T cells, but these options are lost by the DN3 stage. The Notch1 signaling pathway is indispensable for initiation of the T-cell lineage and inhibitory for the B-cell lineage, but the regulatory mechanisms by which the T-cell fate is locked in are largely undefined. Previously, we discovered that the E-protein transcription factor HEBAlt promoted T-cell specification. Here, we report that HEB(-/-) T-cell precursors have compromised Notch1 function and lose T-cell potential. Moreover, reconstituting HEB(-/-) precursors with Notch1 activity enforced fidelity to the T-cell fate. However, instead of becoming B cells, HEB(-/-) DN3 cells adopted a DN1-like phenotype and could be induced to differentiate into thymic NK cells. HEB(-/-) DN1-like cells retained GATA3 and Id2 expression but had lower levels of the Bcl11b gene, a Notch target gene. Therefore, our studies have revealed a new set of interactions between HEB, Notch1, and GATA3 that regulate the T-cell fate choice in developing thymocytes. PMID:21189289

  2. Bleomycin, unlike other male-mouse mutagens, is most effective in spermatogonia, inducing primarily deletions.

    PubMed

    Russell, L B; Hunsicker, P R; Kerley, M K; Johnson, D K; Shelby, M D

    2000-08-21

    Dominant-lethal tests [P.D. Sudman, J.C. Rutledge, J.B. Bishop, W.M. Generoso, Bleomycin: female-specific dominant lethal effects in mice, Mutat. Res. 296 (1992) 205-217] had suggested that Bleomycin sulfate (Blenoxane), BLM, might be a female-specific mutagen. While confirming that BLM is indeed a powerful inducer of dominant-lethal mutations in females that fails to induce such mutations in postspermatogonial stages of males, we have shown in a specific-locus test that BLM is, in fact, mutagenic in males. This mutagenicity, however, is restricted to spermatogonia (stem-cell and differentiating stages), for which the specific-locus mutation rate differed significantly (P<0.008) from the historical control rate. In treated groups, dominant mutations, also, originated only in spermatogonia. With regard to mutation frequencies, this germ-cell-stage pattern is different from that for radiation and for any other chemical studied to date, except ethylnitrosourea (ENU). However, the nature of the spermatogonial specific-locus mutations differentiates BLM from ENU as well, because BLM induced primarily (or, perhaps, exclusively) multilocus deletions. Heretofore, no chemical that induced specific-locus mutations in spermatogonia did not also induce specific-locus as well as dominant-lethal mutations in postspermatogonial stages, making the dominant lethal test, up till now, predictive of male mutagenicity in general. The BLM results now demonstrate that there are chemicals that can induce specific-locus mutations in spermatogonia without testing positive in postspermatogonial stages. Thus, BLM, while not female-specific, is unique, (a) in its germ-cell-stage specificity in males, and (b) in inducing a type of mutation (deletions) that is atypical for the responding germ-cell stages (spermatogonia). PMID:10946246

  3. Expression of c-kit receptor and its autophosphorylation in immature rat type A spermatogonia.

    PubMed

    Dym, M; Jia, M C; Dirami, G; Price, J M; Rabin, S J; Mocchetti, I; Ravindranath, N

    1995-01-01

    The objective of this study was to examine the expression and activation of the c-kit receptor, a specific receptor for kit ligand (stem cell factor, steel factor), in rat type A spermatogonia. Testes were obtained from 9-day-old rats, decapsulated, and then subjected to sequential enzymatic digestion. The mixture of testicular cell types was then separated by sedimentation velocity at unit gravity. The isolated type A spermatogonia were characterized by light and electron microscopy. They exhibited spherical nuclei containing several nucleoli and associated chromatin clumps and organelles generally in a perinuclear location similar to that found in the in vivo 9-day-old testis. The synthesis of the c-kit receptor by the spermatogonia was established by hybridization of total RNA with a specific cDNA for mouse c-kit receptor. Two mRNA transcripts migrating at 4.8 kb and 12 kb were observed. Localization of the c-kit receptor in the isolated cells was determined by immunocytochemistry using an antibody to c-kit protein. Specific staining for c-kit receptor was observed in the cytoplasm of the isolated type A spermatogonia. Furthermore, the presence of the c-kit receptor protein in the spermatogonia was confirmed by Western blot analysis using the same antibody. The antibody recognized the c-kit receptor at approximately 160 kDa. In an attempt to determine whether this receptor has a functional significance, we examined the effect of kit ligand on the phosphorylation of the c-kit receptor. The c-kit receptor appeared to be constitutively autophosphorylated on tyrosine at low basal levels, and upon stimulation with kit ligand, the amount of phosphorylated protein increased significantly. These observations indicate that kit ligand induces autophosphorylation of the c-kit receptor, which may lead to the activation of other cellular target proteins responsible for spermatogonial proliferation and/or differentiation. PMID:7536046

  4. Successful cryopreservation of spermatogonia in critically endangered Manchurian trout (Brachymystax lenok).

    PubMed

    Lee, Seungki; Yoshizaki, Goro

    2016-04-01

    Because of the lack of cryopreservation techniques for fish eggs and embryos, cryopreservation of fish spermatogonia and subsequent generation of eggs and sperm would be an exit strategy for the long-term preservation of genetic resources. This study aimed to optimize cryoprotectants, cooling rates, and thawing temperatures for slow freezing of spermatogonia from endangered Manchurian trout (Brachymystax lenok). Whole testes were frozen with a cryomedium containing 1.3 M methanol, 0.2 M trehalose, and 10% egg yolk at a cooling rate of -1 °C/min and then stored in liquid nitrogen for 2 days. After thawing at 30 °C in a water bath, testicular cells from thawed testes were intraperitoneally transplanted into allogeneic triploid hatchlings. Transplanted spermatogonia migrated toward and were incorporated into recipient gonads, where they underwent gametogenesis. Transplantation efficiency did not significantly differ between frozen and fresh testes, demonstrating that Manchurian trout spermatogonia can be successfully cryopreserved in liquid nitrogen. PMID:26827783

  5. Isolation, identification and enrichment of type a spermatogonia from the testis of chinese cross-bred buffaloes (swamp × river).

    PubMed

    Ahmad, S; Xiao, Y; Han, L; Hua, H; Riaz, H; Liang, A; Yang, L-G

    2013-06-01

    The proportion of type A spermatogonia in the isolated testis cells is a prerequisite for conducting experiments and the manipulation of these germ cells. Thus, this study was designed to examine the wide range of strategies for the isolation, identification and enrichment of type A spermatogonia in pre-pubertal buffalo calves (3-6 months). Histological findings revealed the presence of maximum number of type A spermatogonia at 5 months, which was further confirmed by DBA immunohistochemistry. In a newly modified strategy for the isolation of testis tissues, mincing followed by trituration and two rounds of digestion with collagenase, hyaluronidase and DNase yielded more than 95% testis cell population. Differential plating with laminin, poly-l-lysine and gelatin significantly (p < 0.05) affected the purity of type A spermatogonia. Among these extracellular matrix (ECMs) molecules, laminin and gelatin performed well and reached at a purity of 39.38 ± 1.21% and 32.15 ± 1.60%, respectively. In addition, combination of laminin and gelatin followed by Percoll centrifugation performed the best and yielded >90% type A spermatogonial purity. Moreover, viability of the cells was not affected (p > 0.05) irrespective of different enrichment methods. In conclusion, type A spermatogonia isolation and enrichment system was developed using different ECM molecules in buffaloes, which will aid in solving wide range of problems especially fertility-related problems and transgenic animal production in buffaloes. PMID:22928737

  6. Production of donor-derived offspring by allogeneic transplantation of spermatogonia in the yellowtail (Seriola quinqueradiata).

    PubMed

    Morita, Tetsuro; Kumakura, Naoki; Morishima, Kagayaki; Mitsuboshi, Toru; Ishida, Masashi; Hara, Takashi; Kudo, Satomi; Miwa, Misako; Ihara, Shoko; Higuchi, Kentaro; Takeuchi, Yutaka; Yoshizaki, Goro

    2012-06-01

    Although the yellowtail (Seriola quinqueradiata) is the fish most commonly farmed in Japan, breeding of this species has not yet started. This is primarily due to the lack of sufficiently sophisticated methods for manipulating gametogenesis, which makes it difficult to collect gametes from specific dams and sires. If it were possible to produce large numbers of surrogate fish by transplanting germ cells isolated from donor individuals harboring desirable genetic traits, then the probability of acquiring gametes carrying the donor-derived haplotype would increase, and breeding programs involving this species might increase as a result. As a first step, we established a method for the allogeneic transplantation of yellowtail spermatogonia and the production of donor-derived offspring. Donor cells were collected from immature (10-month-old) yellowtail males with testes containing abundant type A spermatogonia, labeled with PKH26 fluorescent dye, and transferred into the peritoneal cavities of 8-day-old larvae. Fluorescence observation at 28 days post-transplantation revealed that PKH26-labeled cells were incorporated into recipients' gonads. To assess whether donor-derived spermatogonia could differentiate into functional gametes in the allogeneic recipient gonads, gametes collected from nine male and four female adult recipients were fertilized with wild-type eggs and milt. Analysis of microsatellite DNA markers confirmed that some of the first filial (F(1)) offspring were derived from donor fish, with the average contribution of donor-derived F(1) offspring being 66% and the maximum reaching 99%. These findings confirmed that our method was effective for transplanting yellowtail spermatogonia into allogeneic larvae to produce donor-derived offspring. PMID:22460666

  7. Adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer.

    PubMed

    Jamieson, Nigel B; Brown, Duncan J F; Michael Wallace, A; McMillan, Donald C

    The aim of the present study was to examine the relationship between adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer (NSCLC). Measurement of anthropometry, acute phase proteins, interleukin-6, leptin (total and free) and adiponectin were carried out on healthy subjects (n = 13) and non-small cell lung cancer patients with weight loss (n = 20). The groups were age and sex matched. Compared with the controls the cancer group had a lower BMI (p < 0.01), mid-upper arm circumference (p < 0.001), triceps skinfold thickness (p < 0.05) and circulating concentrations of albumin (p < 0.001), haemoglobin (p < 0.05), free and total leptin (p < 0.05) and adiponectin (p < 0.01). In contrast, the cancer group had elevated circulating concentrations of interleukin-6 and C-reactive protein concentrations (p < 0.001). In the cancer group circulating adiponectin concentrations were significantly inversely correlated with both free (rs = -0.675, p = 0.001) and total leptin concentrations (rs = -0.690, p = 0.001). However, neither weight loss, interleukin-6 or C-reactive protein concentrations were correlated with either adiponectin, free or total leptin concentrations in the cancer group. These results suggest that adipokine production is normal and is unlikely to play a major role in the abnormal fat metabolism in weight-losing cancer patients. PMID:15242698

  8. Epithelia suspended in collagen gels can lose polarity and express characteristics of migrating mesenchymal cells.

    PubMed

    Greenburg, G; Hay, E D

    1982-10-01

    This study of epithelial-mesenchymal transformation and epithelial cell polarity in vitro reveals that environmental conditions can have a profound effect on the epithelial phenotype, cell shape, and polarity as expressed by the presence of apical and basal surfaces. A number of different adult and embryonic epithelia were suspended within native collagen gels. Under these conditions, cells elongate, detach from the explants, and migrate as individual cells within the three-dimensional lattice, a previously unknown property of well-differentiated epithelia. Epithelial cells from adult and embryonic anterior lens were studied in detail. Elongated cells derived from the apical surface develop pseudopodia and filopodia characteristic of migratory cells and acquire a morphology and ultrastructure virtually indistinguishable from that of mesenchymal cells in vivo. It is concluded from these experiments that the three-dimensional collagen gel can promote dissociation, migration, and acquisition of secretory organelles by differentiated epithelial cells, and can abolish the apical-basal cell polarity characteristic of the original epithelium. PMID:7142291

  9. Depletion of the spermatogonia from the seminiferous epithelium of the rhesus monkey after X irradiation

    SciTech Connect

    van Alphen, M.M.; van de Kant, H.J.; de Rooij, D.G.

    1988-03-01

    In unirradiated testes large differences were found in the total number of spermatogonia among different monkeys, but the number of spermatogonia in the right and the left testes of the same monkey appeared to be rather similar. During the first 11 days after irradiation with 0.5 to 4.0 Gy of X rays the number of Apale spermatogonia (Ap) decreased to about 13% of the control level, while the number of Adark spermatogonia (Ad) did not change significantly. A significant decrease in the number of Ad spermatogonia was seen at Day 14 together with a significant increase in the number of Ap spermatogonia. It was concluded that the resting Ad spermatogonia are activated into proliferating Ap spermatogonia. After Day 16 the number of both Ap and Ad spermatogonia decreased to low levels. Apparently the new Ap spermatogonia were formed by lethally irradiated Ad spermatogonia and degenerated while attempting to divide. The activation of the Ad spermatogonia was found to take place throughout the cycle of the seminiferous epithelium. Serum FSH, LH, and testosterone levels were measured before and after irradiation. Serum FSH levels already had increased during the first week after irradiation to 160% of the control level. Serum LH levels increased between 18 and 25 days after irradiation. Serum testosterone levels did not change at all. The results found in the rhesus monkey are in line with those found in humans, but due to the presence of Ad spermatogonia they differ from those obtained in non-primates.

  10. Aging Stem Cells Lose the Capability to Distribute Damaged Proteins Asymmetrically.

    PubMed

    Mendelsohn, Andrew R; Larrick, James W

    2015-12-01

    Understanding the interplay between reversible epigenetic changes and potentially more difficult to reverse accumulation of damaged macromolecules is a central challenge in developing treatments for aging-associated dysfunction. One hypothesis is that epigenetic drift leads to subtle losses of homeostatic maintenance mechanisms, that in turn, lead to the accumulation of damaged macromolecules, which then further degrade homeostasis. A key mechanism of maintaining optimal cell function is asymmetrical division, whereby cellular damage is segregated away from cells that need to undergo further proliferation, such as stem cells. Such asymmetrical distribution of damaged macromolecules has been observed during cell division in many organisms, from yeast to human embryonic stem cells, and depends on diffusion barriers (DBs) in the membrane of the endoplasmic reticulum (ER). In a recent study, these results have been extended to neural stem cells (NSCs), in which the ability of the ER DB to promote asymmetrical distribution of damaged proteins deteriorates with age. NSC function declines with age as proliferative capacity is reduced. The loss of asymmetric protein distribution correlates with the loss of NSC proliferative capacity. Ectopic expression of progerin, an altered form of lamin A, is associated with the premature aging disorder, Hutchinson-Gilford progeria syndrome (HGPS). Progerin's expression also increases with normal aging due to mis-splicing, weakening the ER DB. Recent work suggests that many cell signaling pathway changes associated with HGPS are replicated during normal aging in cultured cells. Moreover, the detrimental changes associated with progerin expression in HGPS are partially reversible experimentally after treatment with statins, a farnesyltransferase inhibitor, a isoprenylcysteine carboxyl methyltransferase inhibitor, or sulforaphane. It will be of great interest if these compounds can also reverse the aging-associated permeability of the ER

  11. Wnt some lose some: transcriptional governance of stem cells by Wnt/β-catenin signaling

    PubMed Central

    Lien, Wen-Hui; Fuchs, Elaine

    2014-01-01

    In mammals, Wnt/β-catenin signaling features prominently in stem cells and cancers, but how and for what purposes have been matters of much debate. In this review, we summarize our current knowledge of Wnt/β-catenin signaling and its downstream transcriptional regulators in normal and malignant stem cells. We centered this review largely on three types of stem cells—embryonic stem cells, hair follicle stem cells, and intestinal epithelial stem cells—in which the roles of Wnt/β-catenin have been extensively studied. Using these models, we unravel how many controversial issues surrounding Wnt signaling have been resolved by dissecting the diversity of its downstream circuitry and effectors, often leading to opposite outcomes of Wnt/β-catenin-mediated regulation and differences rooted in stage- and context-dependent effects. PMID:25030692

  12. Neural stem cells exposed to BrdU lose their global DNA methylation and undergo astrocytic differentiation

    PubMed Central

    Schneider, Leonid; d’Adda di Fagagna, Fabrizio

    2012-01-01

    Bromodeoxyuridine (5-bromo-2′-deoxyuridine, BrdU) is a halogenated nucleotide of low toxicity commonly used to monitor DNA replication. It is considered a valuable tool for in vitro and in vivo studies, including the detection of the small population of neural stem cells (NSC) in the mammalian brain. Here, we show that NSC grown in self-renewing conditions in vitro, when exposed to BrdU, lose the expression of stem cell markers like Nestin, Sox2 and Pax6 and undergo glial differentiation, strongly up-regulating the astrocytic marker GFAP. The onset of GFAP expression in BrdU exposed NSC was paralleled by a reduced expression of key DNA methyltransferases (DNMT) and a rapid loss of global DNA CpG methylation, as we determined by our specially developed analytic assay. Remarkably, a known DNA demethylating compound, 5-aza-2′-deoxycytidine (Decitabine), had similar effect on demethylation and differentiation of NSC. Since our key findings apply also to NSC derived from murine forebrain, our observations strongly suggest more caution in BrdU uses in stem cells research. We also propose that BrdU and its related substances may also open new opportunities for differentiation therapy in oncology. PMID:22379135

  13. Neural stem cells exposed to BrdU lose their global DNA methylation and undergo astrocytic differentiation.

    PubMed

    Schneider, Leonid; d'Adda di Fagagna, Fabrizio

    2012-07-01

    Bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU) is a halogenated nucleotide of low toxicity commonly used to monitor DNA replication. It is considered a valuable tool for in vitro and in vivo studies, including the detection of the small population of neural stem cells (NSC) in the mammalian brain. Here, we show that NSC grown in self-renewing conditions in vitro, when exposed to BrdU, lose the expression of stem cell markers like Nestin, Sox2 and Pax6 and undergo glial differentiation, strongly up-regulating the astrocytic marker GFAP. The onset of GFAP expression in BrdU exposed NSC was paralleled by a reduced expression of key DNA methyltransferases (DNMT) and a rapid loss of global DNA CpG methylation, as we determined by our specially developed analytic assay. Remarkably, a known DNA demethylating compound, 5-aza-2'-deoxycytidine (Decitabine), had similar effect on demethylation and differentiation of NSC. Since our key findings apply also to NSC derived from murine forebrain, our observations strongly suggest more caution in BrdU uses in stem cells research. We also propose that BrdU and its related substances may also open new opportunities for differentiation therapy in oncology. PMID:22379135

  14. Genes Involved in Post-Transcriptional Regulation Are Overrepresented in Stem/Progenitor Spermatogonia of Cryptorchid Mouse Testes

    PubMed Central

    Orwig, Kyle E.; Ryu, Buom-Yong; Master, Stephen R.; Phillips, Bart T.; Mack, Matthias; Avarbock, Mary R.; Chodosh, Lewis; Brinster, Ralph L.

    2014-01-01

    Gene expression and consequent biological activity of adult tissue stem cells are regulated by signals emanating from the local microenvironment (niche). To gain insights into the molecular regulation of spermatogonial stem cells (SSCs), gene expression was characterized from SSCs isolated from their cognate niches of cryptorchid (stem cell-enriched), wild-type, and busulfan-treated (stem cell-depleted) mouse testes. Quantitative assessment of stem cell activity in each testis model was determined using an in vivo functional assay and correlated with gene expression using Affymetrix MGU74Av2 microarrays and the ChipStat algorithm optimized to detect gene expression from rare cells in complex tissues. We identified 389 stem/progenitor spermatogonia candidate genes, which exhibited significant overlap with genes expressed by embryonic, hematopoietic, and neural stem cells; enriched spermatogonia; and cultured SSCs identified in previous studies. Candidate cell surface markers identified by the microarray may facilitate the isolation and enrichment of stem and/or progenitor spermatogonia. Flow cytometric analyses confirmed the expression of chemokine receptor 2 (Ccr2) and Cd14 on a subpopulation cryptorchid testis cells (α6-integrin+, side scatterlo) enriched for SSCs. These cell surface molecules may mark progenitor spermatogonia but not SSCs because Ccr2+ and Cd14+ fractions failed to produce spermatogenesis upon transplantation to recipient testes. Functional annotation of candidate genes and subsequent immunohistochemistry revealed that proteins involved in post-transcriptional regulation are overrepresented in cryptorchid testes that are enriched for SSCs. Comparative analyses indicated that this is a recurrent biological theme among stem cells. PMID:18203673

  15. Protein-losing enteropathy

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/007338.htm Protein-losing enteropathy To use the sharing features on this page, please enable JavaScript. Protein-losing enteropathy is an abnormal loss of protein ...

  16. Paracrine Wnt/β-catenin signaling mediates proliferation of undifferentiated spermatogonia in the adult mouse testis

    PubMed Central

    Takase, Hinako M.; Nusse, Roeland

    2016-01-01

    Spermatogonial stem cells (SSCs) fuel the production of male germ cells but the mechanisms behind SSC self-renewal, proliferation, and differentiation are still poorly understood. Using the Wnt target gene Axin2 and genetic lineage-tracing experiments, we found that undifferentiated spermatogonia, comprising SSCs and transit amplifying progenitor cells, respond to Wnt/β-catenin signals. Genetic elimination of β-catenin indicates that Wnt/β-catenin signaling promotes the proliferation of these cells. Signaling is likely initiated by Wnt6, which is uniquely expressed by neighboring Sertoli cells, the only somatic cells in the seminiferous tubule that support germ cells and act as a niche for SSCs. Therefore, unlike other stem cell systems where Wnt/β-catenin signaling is implicated in self-renewal, the Wnt pathway in the testis specifically contributes to the proliferation of SSCs and progenitor cells. PMID:26929341

  17. The regulatory repertoire of PLZF and SALL4 in undifferentiated spermatogonia.

    PubMed

    Lovelace, Dawn L; Gao, Zhen; Mutoji, Kazadi; Song, Yuntao Charlie; Ruan, Jianhua; Hermann, Brian P

    2016-06-01

    Spermatogonial stem cells (SSCs) maintain spermatogenesis throughout adulthood through balanced self-renewal and differentiation, yet the regulatory logic of these fate decisions is poorly understood. The transcription factors Sal-like 4 (SALL4) and promyelocytic leukemia zinc finger (PLZF; also known as ZBTB16) are known to be required for normal SSC function, but their targets are largely unknown. ChIP-seq in mouse THY1(+) spermatogonia identified 4176 PLZF-bound and 2696 SALL4-bound genes, including 1149 and 515 that were unique to each factor, respectively, and 1295 that were bound by both factors. PLZF and SALL4 preferentially bound gene promoters and introns, respectively. Motif analyses identified putative PLZF and SALL4 binding sequences, but rarely both at shared sites, indicating significant non-autonomous binding in any given cell. Indeed, the majority of PLZF/SALL4 shared sites contained only PLZF motifs. SALL4 also bound gene introns at sites containing motifs for the differentiation factor DMRT1. Moreover, mRNA levels for both unique and shared target genes involved in both SSC self-renewal and differentiation were suppressed following SALL4 or PLZF knockdown. Together, these data reveal the full profile of PLZF and SALL4 regulatory targets in undifferentiated spermatogonia, including SSCs, which will help elucidate mechanisms controlling the earliest cell fate decisions in spermatogenesis. PMID:27068105

  18. In vitro differentiation of rat spermatogonia into round spermatids in tissue culture

    PubMed Central

    Reda, A.; Hou, M.; Winton, T.R.; Chapin, R.E.; Söder, O.; Stukenborg, J.-B.

    2016-01-01

    STUDY QUESTION Do the organ culture conditions, previously defined for in vitro murine male germ cell differentiation, also result in differentiation of rat spermatogonia into post-meiotic germ cells exhibiting specific markers for haploid germ cells? SUMMARY ANSWER We demonstrated the differentiation of rat spermatogonia into post-meiotic cells in vitro, with emphasis on exhibiting, protein markers described for round spermatids. WHAT IS KNOWN ALREADY Full spermatogenesis in vitro from immature germ cells using an organ culture technique in mice was first reported 5 years ago. However, no studies reporting the differentiation of rat spermatogonia into post-meiotic germ cells exhibiting the characteristic protein expression profile or into functional sperm have been reported. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Organ culture of testicular fragments of 5 days postpartum (dpp) neonatal rats was performed for up to 52 days. Evaluation of microscopic morphology, testosterone levels, mRNA and protein expression as measured by RT-qPCR and immunostaining were conducted to monitor germ cell differentiation in vitro. Potential effects of melatonin, Glutamax® medium, retinoic acid and the presence of epidydimal fat tissue on the spermatogenic process were evaluated. A minimum of three biological replicates were performed for all experiments presented in this study. One-way ANOVA, ANOVA on ranks and student's t-test were applied to perform the statistical analysis. MAIN RESULTS AND THE ROLE OF CHANCE Male germ cells, present in testicular tissue pieces grown from 5 dpp rats, exhibited positive protein expression for Acrosin and Crem (cAMP (cyclic adenosine mono phosphate) response element modulator) after 52 days of culture in vitro. Intra-testicular testosterone production could be observed after 3 days of culture, while when epididymal fat tissue was added, spontaneous contractility of cultured seminiferous tubules could be observed after 21 days. However, no

  19. A G-quadruplex DNA structure resolvase, RHAU, is essential for spermatogonia differentiation

    PubMed Central

    Gao, X; Ma, W; Nie, J; Zhang, C; Zhang, J; Yao, G; Han, J; Xu, J; Hu, B; Du, Y; Shi, Q; Yang, Z; Huang, X; Zhang, Y

    2015-01-01

    G-quadruplex (G4) DNA and G4 DNA resolvase are involved in a variety of biological processes. To understand the biological function of G4 DNA structures and their resolvases in spermatogenesis, we investigated the distribution of G4 structures in mouse testis and identified their alterations during spermatogenesis. Meanwhile, we studied the function of RNA helicase associated with AU-rich element (RHAU), a G4 DNA resolvase, in spermatogenesis with a germ-cell-specific knockout mouse model. The results showed that the ablation of RHAU in germ cells caused the increase of G4 structures and thus resulted in the decrease of spermatogonial differentiation. c-kit, a spermatogonia differentiation-related gene, contains two G4 DNA motifs on its promoter. We found its expression was significantly downregulated in RHAU conditional knockout testis. A further analysis demonstrated that RHAU directly bound to the G4 structures to activate c-kit expression. We concluded that RHAU regulates spermatogonia differentiation by promoting c-kit expression via directly binding to the G4 DNA motifs c-kit promoter. PMID:25611385

  20. [Protein-losing enteropathy].

    PubMed

    Amiot, A

    2015-07-01

    Protein-losing enteropathy is a rare syndrome of gastrointestinal protein loss. The primary causes can be classified into lymphatic leakage due to increased interstitial pressure and increased leakage of protein-rich fluids due to erosive or non-erosive gastrointestinal disorders. The diagnosis of protein-losing enteropathy should be considered in patients with chronic diarrhea and peripheral oedema. The diagnosis of protein-losing enteropathy is most commonly based on the determination of fecal alpha-1 antitrypsin clearance. Most protein-losing enteropathy cases are the result of either lymphatic obstruction or a variety of gastrointestinal disorders and cardiac diseases, while primary intestinal lymphangiectasia (Waldmann's disease) is less common. Treatment of protein-losing enteropathy targets the underlying disease but also includes dietary modification, such as high-protein and low-fat diet along with medium-chain triglyceride supplementation. PMID:25618488

  1. Losing weight after pregnancy

    MedlinePlus

    ... below the minimum number of calories you need. Breastfeeding If you are breastfeeding, you will want to lose weight slowly. Weight ... not affect your milk supply or your health. Breastfeeding makes your body burn calories. It helps you ...

  2. NIH Loses a Friend

    MedlinePlus

    ... page please turn Javascript on. NIH Loses a Friend Past Issues / Fall 2009 Table of Contents Donald ... changingthefaceofmedicine/ . Sincerely, Donald West King, M.D., Chairman Friends of the National Library of Medicine Let Us ...

  3. Conservation of avian germplasm by xenogeneic transplantation of spermatogonia from sexually mature donors.

    PubMed

    Pereira, Ricardo J G; Napolitano, Angelo; Garcia-Pereira, Fernando L; Baldo, Caroline F; Suhr, Steven T; King, Louis E; Cibelli, Jose B; Karcher, Darrin M; McNiel, Elizabeth A; Perez, Gloria I

    2013-03-01

    Approximately 12.5% of all 9,920 extant bird species in the world are threatened with extinction, and yet conservation efforts through natural breeding of captive species continue to encounter difficulties. However, sperm cryopreservation and artificial insemination offer potential benefits over natural breeding, but their applicability is still limited in nondomestic species. In this study, we aimed to exploit the potential of germ cell xenotransplantation as an alternative tool for preserving germplasm of endangered birds. The study was designed to investigate whether transfer of either spermatogonia-enriched cell fraction (SEF) or crude testicular cell fraction (CTF) from adult Japanese quails (as a model for wild species) would result in recolonization of gamma-irradiated gonads of adult recipient chickens. One month after transplantation, 75% of recipients injected with SEF and 25% of recipients injected with CTF resumed spermatogenesis. However, it took more than 3 months for 33% of the negative controls to resume marginal production of sperm. Some SEF recipients produced more spermatozoa bearing head morphology compared with donor controls. DNA analysis using quail-specific primers did not detect donor's DNA in these recipients' semen. However, 6 months after xenotransplantation, presence of quail germ cells was demonstrated by polymerase chain reaction and by immunohistochemistry in 1 rooster injected with SEF. These findings indicate that spermatogonia from adult quails were capable of colonizing immunocompetent testis of adult chickens but failed to produce sufficient sperm. Despite this limitation, the present approach represents a potential conservation tool that may be used to rescue germ cells of endangered adult male birds. PMID:23025754

  4. Losing Libraries, Saving Libraries

    ERIC Educational Resources Information Center

    Miller, Rebecca

    2010-01-01

    This summer, as public libraries continued to get budget hit after budget hit across the country, several readers asked for a comprehensive picture of the ravages of the recession on library service. In partnership with 2010 Movers & Shakers Laura Solomon and Mandy Knapp, Ohio librarians who bought the Losing Libraries domain name, "LJ" launched…

  5. Inter-relationships between single carbon units' metabolism and resting energy expenditure in weight-losing patients with small cell lung cancer. Effects of methionine supply and chemotherapy.

    PubMed

    Sengeløv, H; Hansen, O P; Simonsen, L; Bülow, J; Nielsen, O J; Ovesen, L

    1994-01-01

    The one-carbon unit metabolism was investigated in 8 weight-losing patients with small cell carcinoma of the lung (SCLC). At diagnosis, 6 of the 8 patients had elevated formiminoglutamic acid (FIGLU) excretion after a histidine load, suggesting a lack of one-carbon units. In accordance, a significant decrease of FIGLU excretion was observed in the patients after oral administration of DL-methionine for 4 days. The elevated FIGLU excretion was positively correlated to weight loss prior to diagnosis and negatively correlated to serum albumin at time of diagnosis. After 3 months of combination chemotherapy, FIGLU excretion was reduced in all patients except 1, who had progressive disease. Despite the elevated FIGLU excretions, all patients had normal blood folate levels. The resting energy expenditure (REE) was recorded in 7 patients, and a significant, positive correlation was observed between pretreatment FIGLU excretion and REE, although the REE measured in this group of patients was within the normal range. These data demonstrate an increased demand of "active" one-carbon units in energy consumption in a group of weight-losing cancer patients. The one-carbon unit deficit was reconditioned by oral administration of the one-carbon unit donor DL-methionine. PMID:7833132

  6. The cancer stem cell phenotype: You can't win until you learn how to lose it

    PubMed Central

    Lopez-Bertoni, Hernando; Laterra, John

    2015-01-01

    Cancer stem cells and their relatively differentiated progenitors coexist in dynamic equilibrium and are subject to bidirectional conversion. We recently showed that reprogramming transcription factors induce glioblastoma cells to become stem-like and tumor propagating via a mechanism involving changes in global DNA methylation and downregulation of miRNAs.

  7. Enrichment of Undifferentiated Type A Spermatogonia from Goat Testis Using Discontinuous Percoll Density Gradient and Differential Plating

    PubMed Central

    Heidari, Banafsheh; Gifani, Minoo; Shirazi, Abolfazl; Zarnani, Amir-Hassan; Baradaran, Behzad; Naderi, Mohammad Mehdi; Behzadi, Bahareh; Borjian-Boroujeni, Sara; Sarvari, Ali; Lakpour, Niknam; Akhondi, Mohammad Mehdi

    2014-01-01

    Background The well documented source for adult multipotent stem cells is Spermatogonial Stem Cells (SSCs). They are the foundation of spermatogenesis in the testis throughout adult life by balancing self-renewal and differentiation. The aim of this study was to assess the effect of percoll density gradient and differential plating on enrichment of undifferentiated type A spermatogonia in dissociated cellular suspension of goat testes. Additionally, we evaluated the separated fractions of the gradients in percoll and samples in differential plating at different times for cell number, viability and purification rate of goat SSCs in culture. Methods Testicular cells were successfully isolated from one month old goat testis using two-step enzymatic digestion and followed by two purification protocols, differential plating with different times of culture (3, 4, 5, and 6 hr) and discontinuous percoll density with different gradients (20, 28, 30, and 32%). The difference of percentage of undifferentiated SSCs (PGP9.5 positive) in each method was compared using ANOVA and comparison between the highest percentage of corresponding value between two methods was carried out by t-test using Sigma Stat (ver. 3.5). Results The highest PGP9.5 (94.6±0.4) and the lowest c-Kit positive (25.1±0.7) in Percoll method was significantly (p ≤ 0.001) achieved in 32% percoll gradient. While the corresponding rates in differential plating method for the highest PGP9.5 positive cells (81.3±1.1) and lowest c-Kit (17.1±1.4) was achieved after 5 hr culturing (p < 0.001). The enrichment of undifferentiated type A spermatogonia using Percoll was more efficient than differential plating method (p < 0.001). Conclusion Percoll density gradient and differential plating were efficient and fast methods for enrichment of type A spermatogonial stem cells from goat testes. PMID:24834311

  8. Eating Well and Losing Weight

    MedlinePlus

    ... Smoking - Eating Well and Losing Weight • Tools & Resources Sodium & High Blood Pressure Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 All About Heart Rate (Pulse) ...

  9. Human spermatogonial stem cells: a possible origin for spermatocytic seminoma

    PubMed Central

    Waheeb, Reham; Hofmann, Marie-Claude

    2011-01-01

    In mammals, spermatogenesis is maintained throughout life by a small subpopulation of type A spermatogonia called spermatogonial stem cells (SSCs). In rodents, SSCs, or Asingle spermatogonia, form the self-renewing population. SSCs can also divide into Apaired (Apr) spermatogonia that are predestined to differentiate. Apaired spermatogonia produce chains of Aaligned (Aal) spermatogonia that divide to form A1 to A4, then type B spermatogonia. Type B spermatogonia will divide into primary spermatocytes that undergo meiosis. In human, there are only two different types of A spermatogonia, the Adark and Apale spermatogonia. The Adark spermatogonia are considered reserve stem cells, whereas the Apale spermatogonia are the self-renewing stem cells. There is only one generation of type B spermatogonia before differentiation into spermatocytes, which makes human spermatogenesis less efficient than in rodents. Although the biology of human SSCs is not well known, a panel of phenotypic markers has recently emerged that is remarkably similar to the list of markers expressed in mice. One such marker, the orphan receptor GPR125, is a plasma membrane protein that can be used to isolate human SSCs. Human SSCs proliferate in culture in response to growth factors such as GDNF, which is essential for SSC self-renewal in mice and triggers the same signaling pathways in both species. Therefore, despite differences in the spermatogonial differentiation scheme, both species use the same genes and proteins to maintain the pool of self-renewing SSCs within their niche. Spermatocytic seminomas are mainly found in the testes of older men, and they rarely metastasize. It is believed that these tumors originate from a postnatal germ cell. Because these lesions can express markers specific for meiotic prophase, they might originate form a primary spermatocyte. However, morphological appearance and overall immunohistochemical profile of these tumors indicate that the cell of origin could also

  10. Protein-losing nephropathy in small animals.

    PubMed

    Littman, Meryl P

    2011-01-01

    Genetic and acquired defects of glomerular permselectivity may lead to proteinuria and protein-losing nephropathy (PLN). Morbidity and mortality from complications of PLN may be severe even before progression to azotemia and renal failure. Leakage of plasma proteins into the glomerular filtrate can damage tubular cells and the function of the entire nephron. Detection, localization, and treatment of proteinuria are important to decrease the clinical signs and complications of PLN and the likelihood of progression to renal failure. Thorough diagnostic work-ups help to identify subsets of glomerular disease and their response to specific treatment protocols. PMID:21251510

  11. The Effect of Dose Rate on the Frequency of Specific-Locus Mutations Induced in Mouse Spermatogonia is Restricted to Larger Lesions; a Retrospective Analysis of Historical Data

    SciTech Connect

    Russell, Liane B; Hunsicker, Patricia R

    2012-01-01

    A series of 19 large-scale germ-cell mutagenesis experiments conducted several decades ago led to the conclusion that low-LET radiation delivered to mouse spermatogonia at dose rates of 0.8 R/min and below induced only about one-third as many specific-locus mutations as did single, acute exposures at 24 R/min and above. A two-hit origin of the mutations was deemed unlikely in view of the then prevailing evidence for the small size of genetic lesions in spermatogonia. Instead, the dose-rate effect was hypothesized to be the result of a repair system that exists in spermatogonia, but not in more mature male reproductive cells. More recent genetic and molecular studies on the marker genes have identified the phenotypes associated with specific states of the mutant chromosomes, and it is now possible retrospectively to classify individual past mutations as "large lesions" or "other lesions". The mutation-frequency difference between high and low dose rates is restricted to the large lesion mutations, for which the dose-curve slopes differ by a factor exceeding 3.4. For other lesion mutations, there is essentially no difference between the slopes for protracted and acute irradiations; induced other lesions frequencies per unit dose remain similar for dose rates ranging over more than 7 orders of magnitude. For large lesions, these values rise sharply at dose rates >0.8 R/min, though they remain similar within the whole range of protracted doses, failing to provide evidence for a threshold dose rate. The downward bend at high doses that had been noted for X-ray-induced specific-locus mutations as a whole and ascribed to a positive correlation between spermatogonial death and mutation load is now found to be restricted to large lesion mutations. There is a marked difference between the mutation spectra (distributions among the seven loci) for large lesions and other lesions. Within each class, however, the spectra are similar for acute and protracted irradiation.

  12. Losing and Saving and Losing Physics in Texas

    NASA Astrophysics Data System (ADS)

    Marder, Michael

    2015-03-01

    Texas has the second-largest population of the states, and played even a larger role in education reform movements of the past 15 years than its size would indicate. In the Fall of 2011, physicists across the country were surprised to learn that six university physics programs in Texas were threatened with closure because of small graduation numbers. Five of them ultimately closed. Many of the faculty at the institutions losing programs came together and formed a consortium that eventually made it possible to continue offering physics,by unconventional means, to their undergraduates. In the Spring of 2013 came an even larger change. Physics had been part of the recommended high school graduation plan in Texas. As part of a bill making sweeping changes to high school graduation requirements and accountability, the physics requirement was removed. Physics may partly be falling victim to the national focus on STEM, which suggests that the various disciplines of science are interchangeable and not individually important. None of the changes in Texas are hard to imagine coming to other states as well.

  13. How Did Mars Lose Its Atmosphere?

    NASA Video Gallery

    Though it doesn't look like a nice place to live now, Mars may have had an atmosphere more like ours on Earth! But how did it lose it? One way a planet can lose its atmosphere is through a process ...

  14. You Can Lose What You Never Had

    ERIC Educational Resources Information Center

    Cobb, Cam

    2016-01-01

    An often-used idiom states: "you can't lose what you never had." Yet contrary to this expression, it "is" possible to lose what you never had--at least when special education support is concerned. In Ontario, as in other jurisdictions, special education exists as a codified system. An ever-changing nexus of discourses and…

  15. Peripheral blood cells from weight-losing cancer patients control the hepatic acute phase response by a primarily interleukin-6 dependent mechanism.

    PubMed

    O'Riordain, M G; Falconer, J S; Maingay, J; Fearon, K C; Ross, J A

    1999-10-01

    Cancer cachexia is associated with an elevated hepatic acute phase protein response, poor outcome and elevated cytokine production from peripheral blood mononuclear cells (PBMC). This study investigates the mechanism by which PBMC can induce a hepatic acute phase response. Supernatants from the peripheral blood cells of cancer patients induced significantly higher C-reactive protein (CRP) from hepatocytes (198+/-21 ng ml-1) than did supernatants from healthy controls (64+/-20, p<0.005). CRP production in vitro correlated with IL-6 production by PBMC from patients with pancreatic cancer (r=0.76, p<0.0001). This C-reactive protein production was reduced by 84% using neutralising antibody to IL-6 (p<0.001). There was a significant negative correlation between PBMC-induced hepatocyte C-reactive protein production and survival (r=-0.45, p<0.01). PBMC from cancer patients induce the hepatic acute phase response via a primarily IL-6-dependent mechanism. PMID:10493968

  16. Will Titan lose its veil?

    NASA Astrophysics Data System (ADS)

    Dimitrov, V.

    2007-08-01

    . If the real stock (CH4)real (CH4)crit=1.65.1020 kg, than Titan will lose its veil inevitably (scenario of the "mosaic history"), otherwise (CH4)real (CH4)crit the veil survives down to Titan's dying day ("continuous history"). References [1] H. B. Niemann and 17-co-authors, Nature, 438, 779, (2005). [2] V. Dimitrov, Prog. React. Kin. Mech. 30, N4, 227, (2006).

  17. NRG1 and KITL Signal Downstream of Retinoic Acid in the Germline to Support Soma-Free Syncytial Growth of Differentiating Spermatogonia

    PubMed Central

    Chapman, Karen M.; Medrano, Gerardo A.; Chaudhary, Jaideep; Hamra, F. Kent

    2015-01-01

    Defined culture systems supporting spermatogonial differentiation will provide experimental platforms to study spermatogenesis. However, germline-intrinsic signaling mechanisms sufficient to support spermatogonial differentiation without somatic cells remain largely undefined. Here, we analyzed EGF superfamily receptor and ligand diversity in rat testis cells, and delineated germline-intrinsic signaling via an ERBB3 co-transducer, ERBB2, as essential for retinoic acid-induced syncytial growth by differentiating spermatogonia. Like the ERBB2/3 agonist NRG1, we found KIT Ligand (KITL) robustly supported spermatogonial differentiation without serum or somatic cells. ERBB2 inhibitors failed to disrupt KITL-dependent spermatogonial development, and, KITL prevented ERBB3-deficient spermatogonial degeneration upon differentiation. Thus, we report NRG1 and KITL activate alternative pathways downstream of retinoic acid signaling in the germline that are essential for stem cells to undergo pre-meiotic steps of spermatogenesis in culture. Robust serum/soma-free spermatogonial differentiation opens new doors to study mammalian germ cell biology in culture, which will facilitate the discovery of spermatogenic factors that can drive meiotic progression in vitro. PMID:26500786

  18. Order Lunch Early, Lose Weight Later?

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160190.html Order Lunch Early, Lose Weight Later? Study found those ... a new study suggests. Researchers examined the lunch orders of 690 employees using a corporate cafeteria and ...

  19. Medical Mystery: Losing the sense of smell

    MedlinePlus

    ... Hearing Disorders Medical Mystery: Losing the sense of smell Past Issues / Fall 2008 Table of Contents For ... a teenager that took away her sense of smell. Photo courtesy of Malone University Imagine, if you ...

  20. 'Doctor, how can I lose weight?'.

    PubMed

    Bright-See, E

    1983-11-01

    Millions of Canadians are trying to lose weight. According to the Metropolitan Life Insurance Company's recently released height and weight tables, some of them don't need to lose weight from a health standpoint. For those who would benefit from weight loss, a good program includes a balanced, low fat, high fiber diet; exercise; behavior modification and moral support. Few of the popular books and self-help groups offer all these essential components. PMID:21283478

  1. Bubble-fusion professor loses faculty post

    NASA Astrophysics Data System (ADS)

    Gwynne, Peter

    2008-10-01

    Purdue University in the US has announced that Rusi Taleyarkhan - who was found guilty of scientific misconduct by the university in July - will lose his title of Al Bement Jr Professor of Nuclear Engineering and will not be able to advise graduate students for at least three years. Purdue has also denied an appeal from the researcher about the misconduct verdict.

  2. Transcription and imprinting dynamics in developing postnatal male germline stem cells

    PubMed Central

    Hammoud, Saher Sue; Low, Diana H.P.; Yi, Chongil; Lee, Chee Leng; Oatley, Jon M.; Payne, Christopher J.; Carrell, Douglas T.; Guccione, Ernesto; Cairns, Bradley R.

    2015-01-01

    Postnatal spermatogonial stem cells (SSCs) progress through proliferative and developmental stages to populate the testicular niche prior to productive spermatogenesis. To better understand, we conducted extensive genomic profiling at multiple postnatal stages on subpopulations enriched for particular markers (THY1, KIT, OCT4, ID4, or GFRa1). Overall, our profiles suggest three broad populations of spermatogonia in juveniles: (1) epithelial-like spermatogonia (THY1+; high OCT4, ID4, and GFRa1), (2) more abundant mesenchymal-like spermatogonia (THY1+; moderate OCT4 and ID4; high mesenchymal markers), and (3) (in older juveniles) abundant spermatogonia committing to gametogenesis (high KIT+). Epithelial-like spermatogonia displayed the expected imprinting patterns, but, surprisingly, mesenchymal-like spermatogonia lacked imprinting specifically at paternally imprinted loci but fully restored imprinting prior to puberty. Furthermore, mesenchymal-like spermatogonia also displayed developmentally linked DNA demethylation at meiotic genes and also at certain monoallelic neural genes (e.g., protocadherins and olfactory receptors). We also reveal novel candidate receptor–ligand networks involving SSCs and the developing niche. Taken together, neonates/juveniles contain heterogeneous epithelial-like or mesenchymal-like spermatogonial populations, with the latter displaying extensive DNA methylation/chromatin dynamics. We speculate that this plasticity helps SSCs proliferate and migrate within the developing seminiferous tubule, with proper niche interaction and membrane attachment reverting mesenchymal-like spermatogonial subtype cells back to an epithelial-like state with normal imprinting profiles. PMID:26545815

  3. Transcription and imprinting dynamics in developing postnatal male germline stem cells.

    PubMed

    Hammoud, Saher Sue; Low, Diana H P; Yi, Chongil; Lee, Chee Leng; Oatley, Jon M; Payne, Christopher J; Carrell, Douglas T; Guccione, Ernesto; Cairns, Bradley R

    2015-11-01

    Postnatal spermatogonial stem cells (SSCs) progress through proliferative and developmental stages to populate the testicular niche prior to productive spermatogenesis. To better understand, we conducted extensive genomic profiling at multiple postnatal stages on subpopulations enriched for particular markers (THY1, KIT, OCT4, ID4, or GFRa1). Overall, our profiles suggest three broad populations of spermatogonia in juveniles: (1) epithelial-like spermatogonia (THY1(+); high OCT4, ID4, and GFRa1), (2) more abundant mesenchymal-like spermatogonia (THY1(+); moderate OCT4 and ID4; high mesenchymal markers), and (3) (in older juveniles) abundant spermatogonia committing to gametogenesis (high KIT(+)). Epithelial-like spermatogonia displayed the expected imprinting patterns, but, surprisingly, mesenchymal-like spermatogonia lacked imprinting specifically at paternally imprinted loci but fully restored imprinting prior to puberty. Furthermore, mesenchymal-like spermatogonia also displayed developmentally linked DNA demethylation at meiotic genes and also at certain monoallelic neural genes (e.g., protocadherins and olfactory receptors). We also reveal novel candidate receptor-ligand networks involving SSCs and the developing niche. Taken together, neonates/juveniles contain heterogeneous epithelial-like or mesenchymal-like spermatogonial populations, with the latter displaying extensive DNA methylation/chromatin dynamics. We speculate that this plasticity helps SSCs proliferate and migrate within the developing seminiferous tubule, with proper niche interaction and membrane attachment reverting mesenchymal-like spermatogonial subtype cells back to an epithelial-like state with normal imprinting profiles. PMID:26545815

  4. Sleep Loses Out for Many Hooked on Video Games

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159434.html Sleep Loses Out for Many Hooked on Video Games ... Bloodborne," "Fallout" and "Call of Duty" worth losing sleep over? For plenty of gamers, the answer is ...

  5. Sleep Loses Out for Many Hooked on Video Games

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_159434.html Sleep Loses Out for Many Hooked on Video Games ... Bloodborne," "Fallout" and "Call of Duty" worth losing sleep over? For plenty of gamers, the answer is ...

  6. The "Biggest Loser" Expounds on the Benefits of Losing Pounds

    MedlinePlus

    ... Bar Home Current Issue Past Issues Special Section The "Biggest Loser" Expounds on the Benefits of Losing Pounds Past Issues / Winter 2008 ... 186 pounds, going from 361 to 175 pounds. The Twins on Losing Weight Bill: "The only way ...

  7. The Persistence of Gaining and Losing Streams

    NASA Astrophysics Data System (ADS)

    McNamara, J. P.; Frye, A.

    2012-12-01

    Streams are commonly classified as "gaining" or "losing", according to their relationships with groundwater. However, the gaining and losing nature of a stream can vary in space and time. Understanding the spatial and temporal persistence of gaining and losing reaches is essential for understanding controls on stream health. This is particularly important during low flow conditions. Hydrologic models are typically designed to simulate high flows, and are challenged by low flow. This problem will become more important as hydrologists are asked to forecast the increasing occurrence of low flows as a consequence of climate change. Low flow discharges have been a focus of research as they are occurring earlier in the summer and have longer durations throughout the fall. A concern is how low flow will affect water resources and its users in the region when demand is at its highest. As low flow discharges continue to persist, debate over these rights will continue as well. This study we used chloride as a chemical tracer to monitor gains and losses of stream discharge of small watershed in Southwestern, Idaho. Six conductivity probes were spaced evenly 200m apart along a control reach 1200m in total length. Tracers were performed at least once a month at this site throughout the winter and spring and even more often during the summer dry down to understand the temporal changes occurring. Spatial variations were observed by performing basin wide tracers over a stream length of ~9km during the spring and late summer. Results show that stream baseflow is dependent on the winter snowpack and spring rains in order to recharge the deep groundwater systems and to create a hydrologic connection between the stream and local hillslopes. As a result, when winter snowpack's and spring rains are mild, this connectivity is cut off much sooner producing low flow conditions much earlier in the summer.

  8. Male ironman triathletes lose skeletal muscle mass.

    PubMed

    Knechtle, Beat; Baumann, Barbara; Wirth, Andrea; Knechtle, Patrizia; Rosemann, Thomas

    2010-01-01

    We investigated whether male triathletes in an Ironman triathlon lose body mass in the form of fat mass or skeletal muscle mass in a field study at the Ironman Switzerland in 27 male Caucasian non-professional Ironman triathletes. Pre- and post-race body mass, fat mass and skeletal muscle mass were determined. In addition, total body water, hematological and urinary parameters were measured in order to quantify hydration status. Body mass decreased by 1.8 kg (p< 0.05), skeletal muscle decreased by 1.0 kg (p< 0.05) whereas fat mass showed no changes. Urinary specific gravity, plasma urea and plasma volume increased (p< 0.05). Pre- to post-race change (Delta) in body mass was not associated with ? skeletal muscle mass. Additionally, there was no association between Delta plasma urea and Delta skeletal muscle mass; Delta plasma volume was not associated with Delta total body water (p< 0.05). We concluded that male triathletes in an Ironman triathlon lose 1.8 kg of body mass and 1 kg of skeletal muscle mass, presumably due to a depletion of intramyocellular stored glycogen and lipids. PMID:20199992

  9. Comparison of sister chromatid exchange induction in murine germinal and somatic cells by gamma radiation exposure in vivo

    SciTech Connect

    Morales-Ramirez, P.; Mendiola-Cruz, M.T.; Vallarino-Kelly, T.; Rodriguez-Reyes, R.

    1994-12-31

    Sister chromatid exchange (SCE) induction by gamma rays was determined in speratogonia irradiated before or after BrdU incorporation. Furthermore, the comparison of responses obtained in spermatogonia, bone marrow and salivary gland cells was carried out in the cells irradiated after BrdU incorporation, a condition which permits a higher SCE induction. Results indicate that gamma ray exposure of spermatogonia could induce a significant increase in SCE frequency with doses as low as 0.27 Gy, either before or after BrdU incorporation. However, the increase caused by radiation exposure after BrdU incorporation in spermatogonia was nearly three times lower than that obtained in both bone marrow and salivary gland cells. These data suggest that spermatogonia are either more efficient in repairing the gamma ray-induced lesions involved in SCE production or that these cells are less prone to the induction of such lesions. 53 refs., 2 figs., 3 tabs.

  10. Maintenance of potential spermatogonial stem cells in vitro by GDNF treatment in a chondrichthyan model (Scyliorhinus canicula L.).

    PubMed

    Gautier, Aude; Bosseboeuf, Adrien; Auvray, Pierrick; Sourdaine, Pascal

    2014-10-01

    Previous work in dogfish, Scyliorhinus canicula, has identified the testicular germinative area as the spermatogonial stem cell niche. In the present study, an in vitro co-culture system of spermatogonia and somatic cells from the germinative area was developed. Long-term maintenance of spermatogonia has been successful, and addition of GDNF has promoted the development of clones of spermatogonia expressing stem cell characteristics such as alkaline phosphatase activity and has allowed maintenance of self-renewal in spermatogonia for at least 5 mo under culture conditions, notably by decreasing cell apoptosis. Furthermore, clones of spermatogonia expressed the receptor of GDNF, GFRalpha1, which is consistent with the effect of GDNF on cells despite the lack of identification of a GDNF sequence in the dogfish's transcriptome. However, a sequence homologous to artemin has been identified, and in silico analysis supports the hypothesis that artemin could replace GDNF in the germinative area in dogfish. This study, as the first report on long-term in vitro maintenance of spermatogonia in a chondrichthyan species, suggests that the GFRalpha1 signaling function in self-renewal of spermatogonial stem cells is probably conserved in gnathostomes. PMID:25143357

  11. Antimutagenic properties of selected radioprotective drug mixtures with regard to X-ray-induced reciprocal translocations in mouse spermatogonia.

    PubMed

    Benova, D K

    1986-01-01

    The radioprotective drugs AET, serotonin, and ATP were tested for antimutagenic activity against induction by 4.0 Gy X-rays of reciprocal translocations in mouse spermatogonia. Single drugs administered in doses of 8, 24 and 360 mg/kg b.wt., respectively, had no effect on translocation yields recorded in diakinesis-metaphase I spermatocytes. Two-drug mixtures afforded insignificant protection. Three-drug mixtures, however, were found to reduce radiation damage considerably, and the extent of protection was dependent in part on the amount of ATP. The best effect was obtained with formulations of serotonin-AET-ATP at the following doses, respectively: 8 + 24 + 360 mg/kg, 16 + 24 + 336 mg/kg, and 16 + 32 + 264 mg/kg. Less effective were the serotonin-AET-ATP formulations: 16 + 32 + 120 mg/kg, and 8 + 24 + 480 mg/kg. Treatment with drugs omitting radiation exposure was observed to raise, though insignificantly, the level of spontaneous translocation frequency. PMID:3941667

  12. Is the Fungus Magnaporthe Losing DNA Methylation?

    PubMed Central

    Ikeda, Ken-ichi; Van Vu, Ba; Kadotani, Naoki; Tanaka, Masaki; Murata, Toshiki; Shiina, Kohta; Chuma, Izumi; Tosa, Yukio; Nakayashiki, Hitoshi

    2013-01-01

    The long terminal repeat retrotransposon, Magnaporthe gypsy-like element (MAGGY), has been shown to be targeted for cytosine methylation in a subset of Magnaporthe oryzae field isolates. Analysis of the F1 progeny from a genetic cross between methylation-proficient (Br48) and methylation-deficient (GFSI1-7-2) isolates revealed that methylation of the MAGGY element was governed by a single dominant gene. Positional cloning followed by gene disruption and complementation experiments revealed that the responsible gene was the DNA methyltransferase, MoDMT1, an ortholog of Neurospora crassa Dim-2. A survey of MAGGY methylation in 60 Magnaporthe field isolates revealed that 42 isolates from rice, common millet, wheat, finger millet, and buffelgrass were methylation proficient while 18 isolates from foxtail millet, green bristlegrass, Japanese panicgrass, torpedo grass, Guinea grass, and crabgrass were methylation deficient. Phenotypic analyses showed that MoDMT1 plays no major role in development and pathogenicity of the fungus. Quantitative polymerase chain reaction analysis showed that the average copy number of genomic MAGGY elements was not significantly different between methylation-deficient and -proficient field isolates even though the levels of MAGGY transcript were generally higher in the former group. MoDMT1 gene sequences in the methylation-deficient isolates suggested that at least three independent mutations were responsible for the loss of MoDMT1 function. Overall, our data suggest that MoDMT1 is not essential for the natural life cycle of the fungus and raise the possibility that the genus Magnaporthe may be losing the mechanism of DNA methylation on the evolutionary time scale. PMID:23979580

  13. 21 CFR 182.1745 - Sodium carboxymethylcellu-lose.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium carboxymethylcellu-lose. 182.1745 Section... GRAS Food Substances § 182.1745 Sodium carboxymethylcellu-lose. (a) Product. Sodium carboxy-methylcellulose is the sodium salt of carboxymethylcellulose not less than 99.5 percent on a dry-weight...

  14. 21 CFR 182.1745 - Sodium carboxymethylcellu-lose.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium carboxymethylcellu-lose. 182.1745 Section... (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food Substances § 182.1745 Sodium carboxymethylcellu-lose. (a) Product. Sodium carboxy-methylcellulose is the sodium salt of carboxymethylcellulose...

  15. 21 CFR 182.1745 - Sodium carboxymethylcellu-lose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium carboxymethylcellu-lose. 182.1745 Section... GRAS Food Substances § 182.1745 Sodium carboxymethylcellu-lose. (a) Product. Sodium carboxy-methylcellulose is the sodium salt of carboxymethylcellulose not less than 99.5 percent on a dry-weight...

  16. 21 CFR 182.1745 - Sodium carboxymethylcellu-lose.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium carboxymethylcellu-lose. 182.1745 Section... GRAS Food Substances § 182.1745 Sodium carboxymethylcellu-lose. (a) Product. Sodium carboxy-methylcellulose is the sodium salt of carboxymethylcellulose not less than 99.5 percent on a dry-weight...

  17. Reduction of spermatogonia and testosterone in rat testes flown on Space Lab-3

    NASA Technical Reports Server (NTRS)

    Philpott, Delbert E.; Stevenson, J.; Black, S.; Sapp, W.; Williams, C.

    1986-01-01

    The effects of space flight on rat testes were investigated. The weight, spermatogonial cell count, and testosterone levels in six rats flown on Space Lab-3 were measured. It is observed that compared to ground control rats the average weight loss was 7.1 percent and the spermatogonial cell count decreased by 7.5 percent. The data reveal that the testosterone level for large control rats was 9.13 ng/ml and 0.31 ng/ml for flight rats; and 2.54 ng/ml and 0.233 ng/ml for smaller control and flight rats, respectively. It is noted that spermatogenesis and testosterone production are reduced during spaceflight.

  18. Study of the potential spermatogonial stem cell compartment in dogfish testis, Scyliorhinus canicula L.

    PubMed

    Loppion, Geraldine; Crespel, Amélie; Martinez, Anne-Sophie; Auvray, Pierrïck; Sourdaine, Pascal

    2008-06-01

    In the lesser-spotted dogfish (Scyliorhinus canicula), spermatogenesis takes place within spermatocysts made up of Sertoli cells associated with stage-synchronized germ cells. As shown in testicular cross sections, cysts radiate in maturational order from the germinative area, where they are formed, to the opposite margin of the testis, where spermiation occurs. In the germinative zone, which is located in a specific area between the tunica albuginea of the testis and the dorsal testicular vessel, individual large spermatogonia are surrounded by elongated somatic cells. The aim of this study has been to define whether these spermatogonia share characteristics with spermatogonial stem cells described in vertebrate and non-vertebrate species. We have studied their ultrastructure and their mitotic activity by 5'-bromo-2'-deoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) immunodetection. Additionally, immunodetection of c-Kit receptor, a marker of differentiating spermatogonia in rodents, and of alpha- and beta-spectrins, as constituents of the spectrosome and the fusome, has been performed. Ultrastructurally, nuclei of stage I spermatogonia present the same mottled aspect in dogfish as undifferentiated spermatogonia nuclei in rodents. Moreover, intercellular bridges are not observed in dogfish spermatogonia, although they are present in stage II spermatogonia. BrdU and PCNA immunodetection underlines their low mitotic activity. The presence of a spectrosome-like structure, a cytological marker of the germline stem cells in Drosophila, has been observed. Our results constitute the first step in the study of spermatogonial stem cells and their niche in the dogfish. PMID:18340468

  19. Antimutagenic properties of WR 2721 and of a radioprotective mixture, ATP-AET-serotonin, with regard to X ray induced reciprocal translocations in mouse spermatogonia

    SciTech Connect

    Benova, D.

    1987-01-01

    Pretreatment by intraperitoneal administration of WR 2721 at 400 mg/kg body weight in mice receiving 4.0 Gy X rays was found to have an appreciable antimutagenic effect with regard to reciprocal translocation induction in spermatogonia. The effectiveness of the product tested proved superior to that of a radioprotective mixture of ATP-AET-serotonin given at optimal dose ratio--360, 24, and 8 mg/kg body weight, respectively. The RF (Reduction Factor) was 2.4 for WR 2721 and 1.8 for the mixture. The effect observed indicated WR 2721 to have potential capabilities for reducing the genetic risk of radiation in male individuals.

  20. Antimutagenic properties of WR 2721 and of a radioprotective mixture, ATP-AET-serotonin, with regard to X ray induced reciprocal translocations in mouse spermatogonia.

    PubMed

    Benova, D

    1987-01-01

    Pretreatment by intraperitoneal administration of WR 2721 at 400 mg/kg body weight in mice receiving 4.0 Gy X rays was found to have an appreciable antimutagenic effect with regard to reciprocal translocation induction in spermatogonia. The effectiveness of the product tested proved superior to that of a radioprotective mixture of ATP-AET-serotonin given at optimal dose ratio--360, 24, and 8 mg/kg body weight, respectively. The RF (Reduction Factor) was 2.4 for WR 2721 and 1.8 for the mixture. The effect observed indicated WR 2721 to have potential capabilities for reducing the genetic risk of radiation in male individuals. PMID:3027009

  1. Eliminating malignant contamination from therapeutic human spermatogonial stem cells

    PubMed Central

    Dovey, Serena L.; Valli, Hanna; Hermann, Brian P.; Sukhwani, Meena; Donohue, Julia; Castro, Carlos A.; Chu, Tianjiao; Sanfilippo, Joseph S.; Orwig, Kyle E.

    2013-01-01

    Spermatogonial stem cell (SSC) transplantation has been shown to restore fertility in several species and may have application for treating some cases of male infertility (e.g., secondary to gonadotoxic therapy for cancer). To ensure safety of this fertility preservation strategy, methods are needed to isolate and enrich SSCs from human testis cell suspensions and also remove malignant contamination. We used flow cytometry to characterize cell surface antigen expression on human testicular cells and leukemic cells (MOLT-4 and TF-1a). We demonstrated via FACS that EpCAM is expressed by human spermatogonia but not MOLT-4 cells. In contrast, HLA-ABC and CD49e marked >95% of MOLT-4 cells but were not expressed on human spermatogonia. A multiparameter sort of MOLT-4–contaminated human testicular cell suspensions was performed to isolate EpCAM+/HLA-ABC–/CD49e– (putative spermatogonia) and EpCAM–/HLA-ABC+/CD49e+ (putative MOLT-4) cell fractions. The EpCAM+/HLA-ABC–/CD49e– fraction was enriched for spermatogonial colonizing activity and did not form tumors following human-to–nude mouse xenotransplantation. The EpCAM–/HLA-ABC+/CD49e+ fraction produced tumors following xenotransplantation. This approach could be generalized with slight modification to also remove contaminating TF-1a leukemia cells. Thus, FACS provides a method to isolate and enrich human spermatogonia and remove malignant contamination by exploiting differences in cell surface antigen expression. PMID:23549087

  2. 'I want to lose weight': Early risk for disordered eating?

    PubMed

    Gusella, Joanne; Goodwin, Jacqueline; van Roosmalen, Erica

    2008-02-01

    The present study examined the risk of disordered eating and its relation to attempts to lose weight by surveying a Maritime Canadian sample of 247 girls and boys in grades 6, 7 and 8. Current attempts to lose weight were highest in grade 8 girls (41% of girls and 9% of boys) compared with grade 6 (14% of girls and 24% of boys) and grade 7 (21% of girls and 13% of boys) children. Of those trying to lose weight, 71.4% were in the average range for weight and height, 12.2% were overweight and 16.3% were obese. The Children's version of the Eating Attitudes Test (ChEAT) was used to assess eating attitudes and behaviours, and the Rosenberg Self-Esteem Scale was used as a measure of self-esteem. The results showed that 8.5% of the children fell in the high-risk group for disordered eating (ChEAT score 20 or higher). Those in the high-risk group were significantly more likely to fear being overweight (90%), to have tried to lose weight in the past (81%), to be currently trying to lose weight (76%), and to have engaged in binge eating (38%) and self-induced vomiting (24%). The best predictor of membership in the high-risk group for girls was current attempts at weight loss and having lower self-esteem. Only two boys fell in the high-risk group. Body mass index and current weight category (underweight, average, overweight and obese) could not explain the differences between the low- and high-risk groups. Knowing that a child is trying to lose weight can aid in identifying youth at risk for disordered eating, and can provide an opportunity for preventive education. PMID:19183713

  3. Mass-losing red giants in open clusters

    NASA Technical Reports Server (NTRS)

    Jura, M.

    1987-01-01

    Mass-losing stars in open clusters with main-sequence turn-offs at intermediate mass have been searched for by using the IRAS data base. The absence of many strong 60 micron sources in open clusters implies that intermediate-mass stars lose much of their mass during an intense wind phase of rather short duration. For stars of about seven solar masses, this phase, if it exists at all, lasts for not much more than 100,000 yr. For stars of about four solar masses, the intense wind phase appears to last considerably less than 10 million yr; it may well last for less than a million yr.

  4. Meaning-Making through Narrative: On Not Losing the Plot

    ERIC Educational Resources Information Center

    Martin, Terry

    2009-01-01

    This article explores the process of meaning-making from within the "narrative" mode and in particular considers the difficulty or even impossibility, in certain kinds of organisational and social situations, of constructing viable narratives. This experience is sometimes referred to as "losing the plot", hence the subtitle of the article. When…

  5. Learning to Lose: Weight Loss Classes and Personal Transformation

    ERIC Educational Resources Information Center

    Jarvis, Christine

    2012-01-01

    Adult learning takes place not only in educational organisations, but through participation in leisure and special interest groups. Commercially operated weight management organisations recruit large numbers of adults to their classes to learn how to eat healthily and lose weight. They publish readers' "real life" success stories in their…

  6. Nothing to lose: why early career scientists make ideal entrepreneurs.

    PubMed

    Thon, Jonathan N

    2014-12-01

    An entrepreneurial movement within science strives to invert the classical trajectory of academic research careers by positioning trainees at the apex of burgeoning industries. Young scientists today have nothing to lose and everything to gain by pursuing this 'third road', and academic institutes and established companies only stand to benefit from supporting this emerging movement of discovery research with economic purpose. PMID:25458606

  7. We're Losing Our Minds: Rethinking American Higher Education

    ERIC Educational Resources Information Center

    Keeling, Richard P.; Hersh, Richard H.

    2011-01-01

    America is being held back by the quality and quantity of learning in college. This is a true educational emergency! Many college graduates cannot think critically, write effectively, solve problems, understand complex issues, or meet employers' expectations. We are losing our minds--and endangering our social, economic, and scientific leadership.…

  8. 5 CFR 531.241 - Retaining and losing GM status.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... retained rate under 5 CFR part 536. (A retained grade is not considered in determining whether a GM employee has been reduced in grade. See 5 CFR 536.205.) ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Retaining and losing GM status....

  9. They Snooze, You Lose: The Educator's Guide to Successful Presentations

    ERIC Educational Resources Information Center

    Burmark, Lynell

    2011-01-01

    In today's increasingly visual world, the art of giving presentations is a much-needed talent. "They Snooze, You Lose", provides a comprehensive guide made especially for teachers and administrators who want to become presentation "stars" in their classrooms, at board meetings, or any time they are in front of an audience. This book describes how…

  10. Glycerol dynamics in weight-losing cancer patients.

    PubMed

    Edén, E; Edström, S; Bennegárd, K; Lindmark, L; Lundholm, K

    1985-02-01

    This study was designed to show whether weight-losing cancer patients have an elevated glycerol turnover. Four groups of patients were examined: weight-losing cancer patients, weight-losing patients without cancer, cancer patients without weight loss, and weight-stable and well-nourished hospitalized control patients. Glycerol was infused intravenously at three different rates (200, 400, and 800 mumol/hr/kg body weight) after an overnight fast. This allowed measurement of clearance and plasma glycerol turnover. Weight-losing cancer patients (group 1) had an almost threefold higher glycerol turnover per kilogram of body weight compared with malnourished and well-nourished noncancer patients. However, both malnourished cancer and noncancer patients had an elevated glycerol turnover compared with well-nourished patients when glycerol turnover was related to whole body lipids. The results how that progressive clinical cancer is associated with an elevated plasma glycerol turnover, probably indicating an increased whole body lipolysis. This may explain the loss of body fat during the development of cancer cachexia. PMID:4038560

  11. The ambivalence of losing weight after bariatric surgery

    PubMed Central

    Warholm, Christine; Øien, Aud Marie; Råheim, Målfrid

    2014-01-01

    This study is grounded in a phenomenological lifeworld perspective. It aims at providing rich descriptions of lived experience of the process of losing weight after obesity surgery. Two women participated in in-depth interviews four times each during the first postoperative year. Based on the women’s experiences, a meaning structure—the ambivalence of losing weight after obesity surgery—was identified across the women’s processes of change. This consisted of five core themes: movement and activity—freedom but new demands and old restraints; eating habits and digestion—the complexity of change; appearance—smaller, but looser; social relations—stability and change; and being oneself—vulnerability and self-assurance. These core themes changed over time in terms of dominance. The experience of ambivalence is discussed according to a phenomenological perspective of the body as lived experience. PMID:24480033

  12. FACS and MACS sorting strategies to isolate and enrich human spermatogonial stem cells

    PubMed Central

    Valli, Hanna; Sukhwani, Meena; Dovey, Serena L.; Peters, Karen A.; Donohue, Julia; Castro, Carlos A.; Chu, Tianjiao; Marshall, Gary R.; Orwig, Kyle E.

    2014-01-01

    Objective Determine the molecular characteristics of human spermatogonia and optimize methods to enrich spermatogonial stem cells (SSCs). Design Laboratory study using human tissues Setting Research institute Patient(s)/Animal(s) Normal adult human testicular tissue. Interventions Human testicular tissue was fixed or digested with enzymes to produce a cell suspension. Human testis cells were fractionated by FACS and MACS. Main Outcome Measure(s) Immunostaining for selected markers, human-to-nude mouse xenotransplantation assay. Results Immunohistochemistry co-staining revealed the relative expression patterns of SALL4, UTF1, ZBTB16, UCHL1 and ENO2 in human undifferentiated spermatogonia as well as the extent of overlap with the differentiation marker, KIT. Whole mount analyses revealed that human undifferentiated spermatogonia (UCHL1+) were typically arranged in clones of 1–4 cells while differentiated spermatogonia (KIT+) were typically arranged in clones of 8 or more cells. The ratio of undifferentiated to differentiated spermatogonia is greater in humans than in rodents. SSC colonizing activity was enriched in the THY1dim and ITGA6+ fractions of human testes sorted by FACS. ITGA6 was effective for sorting human SSCs by MACS; THY1 and EPCAM were not. Conclusions Human spermatogonial differentiation correlates with increased clone size and onset of KIT expression, similar to rodents. The undifferentiated to differentiated developmental dynamics in human spermatogonia is different than rodents. THY1, ITGA6 and EPCAM can be used to enrich human SSC colonizing activity by FACS, but only ITGA6 is amenable to high throughput sorting by MACS. PMID:24890267

  13. Losing a valued member of the medical practice team.

    PubMed

    Hills, Laura

    2014-01-01

    Losing a valued member of your staff can be disruptive, painful, and costly to your medical practice. And despite your best intentions and impeccable employee management policies and skills, things will happen beyond your control, and people move on. Being prepared for that possibility will help you minimize and contain the damage and move your practice forward. This article suggests 15 strategies that you can use to mitigate the effects of losing a valued employee. These include strategies to protect your practice's interests and several that will smooth the transition for your remaining staff. This article also describes 10 ways that losing a valued employee can impact a practice. It offers 10 additional strategies to help you cope with the death of an employee, one of the most difficult challenges a practice manager may ever face. This article further suggests several easy-to-implement practice management techniques that will help you soften the blow of employee turnover. It offers a sample farewell letter to announce an employee's departure from your practice and suggests six knowledge transfer questions to ask before the employee leaves. Finally, this article provides a comprehensive list of more than 30 thoughtful, eye-opening, and revealing questions that you can ask in an employee exit interview or exit survey. PMID:25807601

  14. Isolation and Characterization of Pluripotent Human Spermatogonial Stem Cell-Derived Cells

    PubMed Central

    Kossack, Nina; Meneses, Juanito; Shefi, Shai; Nguyen, Ha Nam; Chavez, Shawn; Nicholas, Cory; Gromoll, Joerg; Turek, Paul J; Reijo-Pera, Renee A

    2009-01-01

    Several reports have documented the derivation of pluripotent cells (multipotent germline stem cells) from spermatogonial stem cells obtained from the adult mouse testis. These spermatogonia-derived stem cells express embryonic stem cell markers and differentiate to the three primary germ layers, as well as the germline. Data indicate that derivation may involve reprogramming of endogenous spermatogonia in culture. Here, we report the derivation of human multipotent germline stem cells (hMGSCs) from a testis biopsy. The cells express distinct markers of pluripotency, form embryoid bodies that contain derivatives of all three germ layers, maintain a normal XY karyotype, are hypomethylated at the H19 locus, and express high levels of telomerase. Teratoma assays indicate the presence of human cells 8 weeks post-transplantation but limited teratoma formation. Thus, these data suggest the potential to derive pluripotent cells from human testis biopsies but indicate a need for novel strategies to optimize hMGSC culture conditions and reprogramming. PMID:18927477

  15. Age at which the long-cycling spermatogonial stem-cell population is established in the mouse

    SciTech Connect

    Oakberg, E.F.

    1981-01-01

    The long-cycling A/sub 5/ spermatogonia are the cells of primary importance in estimating the reproductive and genetic hazards of radiation, chemicals, and pollutants in mammals. This addresses the following questions: (1) when do the long-cycling cells appear; (2) are they present at birth; and (3) from which cells do they arise. (ACR)

  16. Cool and luminous transients from mass-losing binary stars

    NASA Astrophysics Data System (ADS)

    Pejcha, Ondřej; Metzger, Brian D.; Tomida, Kengo

    2016-02-01

    We study transients produced by equatorial disc-like outflows from catastrophically mass-losing binary stars with an asymptotic velocity and energy deposition rate near the inner edge which are proportional to the binary escape velocity vesc. As a test case, we present the first smoothed-particle radiation-hydrodynamics calculations of the mass loss from the outer Lagrange point with realistic equation of state and opacities. The resulting spiral stream becomes unbound for binary mass ratios 0.06 ≲ q ≲ 0.8. For synchronous binaries with non-degenerate components, the spiral-stream arms merge at a radius of ˜10a, where a is the binary semi-major axis, and the accompanying shock thermalizes about 10 per cent of the kinetic power of the outflow. The mass-losing binary outflows produce luminosities reaching up to ˜106 L⊙ and effective temperatures spanning 500 ≲ Teff ≲ 6000 K, which is compatible with many of the class of recently discovered red transients such as V838 Mon and V1309 Sco. Dust readily forms in the outflow, potentially in a catastrophic global cooling transition. The appearance of the transient is viewing angle-dependent due to vastly different optical depths parallel and perpendicular to the binary plane. We predict a correlation between the peak luminosity and the outflow velocity, which is roughly obeyed by the known red transients. Outflows from mass-losing binaries can produce luminous (105 L⊙) and cool (Teff ≲ 1500 K) transients lasting a year or longer, as has potentially been detected by Spitzer surveys of nearby galaxies.

  17. 42 CFR 136a.34 - Care and treatment of people losing eligibility.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Care and treatment of people losing eligibility. 136a.34 Section 136a.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES....34 Care and treatment of people losing eligibility. (a) Individuals who lose their eligibility...

  18. 42 CFR 136a.34 - Care and treatment of people losing eligibility.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Care and treatment of people losing eligibility. 136a.34 Section 136a.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES....34 Care and treatment of people losing eligibility. (a) Individuals who lose their eligibility...

  19. 42 CFR 136a.34 - Care and treatment of people losing eligibility.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Care and treatment of people losing eligibility. 136a.34 Section 136a.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES....34 Care and treatment of people losing eligibility. (a) Individuals who lose their eligibility...

  20. 42 CFR 136a.34 - Care and treatment of people losing eligibility.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Care and treatment of people losing eligibility. 136a.34 Section 136a.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES....34 Care and treatment of people losing eligibility. (a) Individuals who lose their eligibility...

  1. 42 CFR 136a.34 - Care and treatment of people losing eligibility.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Care and treatment of people losing eligibility. 136a.34 Section 136a.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES....34 Care and treatment of people losing eligibility. (a) Individuals who lose their eligibility...

  2. Seven reasons you are losing patients to the competition.

    PubMed

    Chism, Marlene

    2015-01-01

    Patients who choose elective procedures such as laser treatments, plastic surgery, Botox, fillers, bioidentical hormone therapy, or alternative medicine will leave your practice if their experience is anything less than favorable. This is true even if they get the results they were seeking. It is up to the office manager to create the right environment and engagement from the staff to ensure sustainability. This article offers seven reasons practices lose patients to the competition, and what to do to course-correct. PMID:26062331

  3. Losing the Dark: A Planetarium PSA about Light Pollution

    NASA Astrophysics Data System (ADS)

    Petersen, Carolyn Collins; Walker, Constance

    2015-03-01

    Losing the Dark is a six-minute PSA video created for fulldome theaters by Loch Ness Productions, the International Dark Sky Association Education Committee headed by Dr. Constance Walker of the National Optical Astronomy Observatories, Dome3, Adler Planetarium, and Babak Tafreshi (The World at Night). It explains light pollution, its effects, and ways to implement ``wise lighting`` practices to mitigate light pollution. The show is also made in flat-screen HD format for classical planetariums, non-dome theaters, and for presentatons by IDA speakers.

  4. Targeting the Gdnf Gene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development

    PubMed Central

    Chen, Liang-Yu; Willis, William D.; Eddy, Edward M.

    2016-01-01

    Spermatogonial stem cells (SSCs) are a subpopulation of undifferentiated spermatogonia located in a niche at the base of the seminiferous epithelium delimited by Sertoli cells and peritubular myoid (PM) cells. SSCs self-renew or differentiate into spermatogonia that proliferate to give rise to spermatocytes and maintain spermatogenesis. Glial cell line-derived neurotrophic factor (GDNF) is essential for this process. Sertoli cells produce GDNF and other growth factors and are commonly thought to be responsible for regulating SSC development, but limited attention has been paid to the role of PM cells in this process. A conditional knockout (cKO) of the androgen receptor gene in PM cells resulted in male infertility. We found that testosterone (T) induces GDNF expression in mouse PM cells in vitro and neonatal spermatogonia (including SSCs) co-cultured with T-treated PM cells were able to colonize testes of germ cell-depleted mice after transplantation. This strongly suggested that T-regulated production of GDNF by PM cells is required for spermatogonial development, but PM cells might produce other factors in vitro that are responsible. In this study, we tested the hypothesis that production of GDNF by PM cells is essential for spermatogonial development by generating mice with a cKO of the Gdnf gene in PM cells. The cKO males sired up to two litters but became infertile due to collapse of spermatogenesis and loss of undifferentiated spermatogonia. These studies show for the first time, to our knowledge, that the production of GDNF by PM cells is essential for undifferentiated spermatogonial cell development in vivo. PMID:26831079

  5. Targeting the Gdnf Gene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development.

    PubMed

    Chen, Liang-Yu; Willis, William D; Eddy, Edward M

    2016-02-16

    Spermatogonial stem cells (SSCs) are a subpopulation of undifferentiated spermatogonia located in a niche at the base of the seminiferous epithelium delimited by Sertoli cells and peritubular myoid (PM) cells. SSCs self-renew or differentiate into spermatogonia that proliferate to give rise to spermatocytes and maintain spermatogenesis. Glial cell line-derived neurotrophic factor (GDNF) is essential for this process. Sertoli cells produce GDNF and other growth factors and are commonly thought to be responsible for regulating SSC development, but limited attention has been paid to the role of PM cells in this process. A conditional knockout (cKO) of the androgen receptor gene in PM cells resulted in male infertility. We found that testosterone (T) induces GDNF expression in mouse PM cells in vitro and neonatal spermatogonia (including SSCs) co-cultured with T-treated PM cells were able to colonize testes of germ cell-depleted mice after transplantation. This strongly suggested that T-regulated production of GDNF by PM cells is required for spermatogonial development, but PM cells might produce other factors in vitro that are responsible. In this study, we tested the hypothesis that production of GDNF by PM cells is essential for spermatogonial development by generating mice with a cKO of the Gdnf gene in PM cells. The cKO males sired up to two litters but became infertile due to collapse of spermatogenesis and loss of undifferentiated spermatogonia. These studies show for the first time, to our knowledge, that the production of GDNF by PM cells is essential for undifferentiated spermatogonial cell development in vivo. PMID:26831079

  6. Cool and Luminous Transients from Mass-Losing Binary Stars

    NASA Astrophysics Data System (ADS)

    Pejcha, Ondrej; Metzger, Brian D.; Tomida, Kengo

    2016-01-01

    We study transients produced by equatorial disk-like outflows from catastrophically mass-losing binary stars with an asymptotic velocity and energy deposition rate near the inner edge which are proportional to the binary escape velocity. As a test case, we present the first smoothed-particle radiation-hydrodynamics calculations of the mass loss from the outer Lagrange point with realistic equation of state and opacities. The mass-losing binary outflows produce luminosities reaching up to 106 L⊙ and the effective temperatures are between 500 and 6000 K, which is compatible with those of many of the class of recently-discovered red transients such as V838 Mon and V1309 Sco. Dust readily forms in the outflow, potentially in a catastrophic global cooling transition. The appearance of the transient is viewing angle-dependent due to vastly different optical depths parallel and perpendicular to the binary plane. We predict a correlation between the peak luminosity and the outflow velocity, which is roughly obeyed by the known red transients.

  7. Honeybee society destruction by losing control of self-reproduction

    NASA Astrophysics Data System (ADS)

    Zhang, Peipei; Su, Beibei; He, Da-Ren

    2004-03-01

    Recently the mechanism of the damage caused by invasion of Apis mellifera capensis honeybee into the normal A. M. Scutellata colonies became interesting for scientists due to the fact that the mechanism may resemble those of cancer vicious hyperplasia, spreading of some epidemic, and turbulence of society induced by some bad society groups. For the mechanism, we suggest a new guess, which means that the losing control of self-reproduction disturbs and throws information structure of the society into confuse. We also simulate the damage process with a cellular automata based on the idea. The simulation shows that the process is equivalent to a non-equilibrium percolation phase transition. This discussion remind us that the management and monitor on the information network between society members may be a more effective way for avoiding the overflow of the destructor sub-colonies.

  8. ``Losing the Dark:'' A Planetarium PSA about Light Pollution

    NASA Astrophysics Data System (ADS)

    Productions, L. N.; Walker, D. C.

    2013-04-01

    Losing the Dark is a PSA video being created for fulldome theaters by Loch Ness Productions under the direction of the International Dark Sky Association Education Committee headed by Dr. Constance Walker of the National Optical Astronomy Observatories. It explains the problems with light pollution, its effects on life, and three ways in which people can implement “wise lighting” practices to mitigate light pollution. The show is also being produced in a flat-screen HD format for use in classical planetarium and non-dome theaters, for presentations by IDA speakers when addressing planning boards, etc. and will be posted on the IDA and other web sites. The final length is six minutes for both versions. Funding has been provided by The International Planetarium Society and the International Dark-Sky Association.

  9. WHO in retreat: is it losing its influence?

    PubMed Central

    Godlee, F.

    1994-01-01

    WHO says it has three main functions: to set normative standards; to provide technical advice and assistance on medical matters; and to advocate changes in health policy. During its 46 year history the first two functions have been a constant and uncontroversial backbone through which WHO has earned its reputation for scientific excellence. The third function, advocacy, came to the fore with the launch of Health for All in 1977, after which WHO took a key role in influencing international health policy. WHO's friends and critics alike now say that the organisation is losing its influence and retreating into its technical and biomedical shell. This article maps the changes in WHO's approach over the past 46 years and considers whether fears about its loss of influence are justified. Images p1492-a p1492-b p1493-a p1494-a FIG 1 PMID:7804058

  10. [CO-CULTURE OF BOAR SPERMATOGONIAL CELLS WITH SERTOLI CELLS].

    PubMed

    Savchenkova, I P; Vasil'eva, S A

    2016-01-01

    In the present study, we developed in vitro culture conditions using co-culture of boar spermatogonial cells with Sertoli cells. Testes from 60-day-old crossbred boar were used. A spermatogonia-enriched culture was achieved by enzymatic digestion method and purification by density gradient centrifugation using a discontinuous Percoll gradient and differentiated adherence technique. Lipid drops were detected in isolated Sertoli cells by Oil Red O staining. We have found that the cultivation of boar spermatogonia in the presence of Sertoli cells (up to 35 days) leads to their differentiation as well as in vivo in testis. Association of cells in groups, formation of chains and suspension clusters of the spermatogenic cells were observed on the 10th day. Spermatogonial cellular colonies were noted at the same time. These cellular colonies were analyzed for the expression of genes: Nanog and Plzf in RT PCR. The expression of the Nanog gene in the experimental cellular clones obtained by short-term culture of spermatogonial cells in the presence of Sertoli cells was 200 times higher than the expression of this gene in the freshly isolated spermatogonial cells expression was found in freshly isolated germ cells and in cellular clones derived in vitro. We have found that, in the case of longer cultivation of these cells on Sertoli cells, in vitro process of differentiation of germ cells and formation of single mobile boar spermatozoa occurs at 30-33 days. Cellular population is heterogeneous at this stage. Spermatogenic differentiation in vitro without Sertoli cells stays on the 7th day of cultivation. The results show that co-culture of boar spermatogonia-enriched cells with Sertoli cells can induce their differentiation into spermatozoa in vitro and facilitate obtaining of porcine germ cell culture. PMID:27228660

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

    PubMed Central

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

    2014-01-01

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

  12. Mass-losing M supergiants in the solar neighborhood

    NASA Technical Reports Server (NTRS)

    Jura, M.; Kleinmann, S. G.

    1990-01-01

    A list of the 21 mass-losing red supergiants (20 M type, one G type; L greater than 100,000 solar luminosities) within 2.5 kpc of the sun is compiled. These supergiants are highly evolved descendants of main-sequence stars with initial masses larger than 20 solar masses. The surface density is between about 1 and 2/sq kpc. As found previously, these stars are much less concentrated toward the Galactic center than W-R stars, which are also highly evolved massive stars. Although with considerable uncertainty, it is estimated that the mass return by the M supergiants is somewhere between 0.00001 and 0.00003 solar mass/sq kpc yr. In the hemisphere facing the Galactic center there is much less mass loss from M supergiants than from W-R stars, but, in the anticenter direction, the M supergiants return more mass than do the W-R stars. The duration of the M supergiant phase appears to be between 200,000 and 400,000 yr. During this phase, a star of initially at least 20 solar masses returns perhaps 3-10 solar masses into the interstellar medium.

  13. Everolimus for Primary Intestinal Lymphangiectasia With Protein-Losing Enteropathy.

    PubMed

    Ozeki, Michio; Hori, Tomohiro; Kanda, Kaori; Kawamoto, Norio; Ibuka, Takashi; Miyazaki, Tatsuhiko; Fukao, Toshiyuki

    2016-03-01

    Primary intestinal lymphangiectasia (PIL), also known as Waldmann's disease, is an exudative enteropathy resulting from morphologic abnormalities in the intestinal lymphatics. In this article, we describe a 12-year-old boy with PIL that led to protein-losing enteropathy characterized by diarrhea, hypoalbuminemia associated with edema (serum albumin level: 1.0 g/dL), and hypogammaglobulinemia (serum IgG level: 144 mg/dL). Severe hypoalbuminemia, electrolyte abnormalities, and tetany persisted despite a low-fat diet and propranolol. Everolimus (1.6 mg/m(2)/day) was added to his treatment as an antiangiogenic agent. With everolimus treatment, the patient's diarrhea resolved and replacement therapy for hypoproteinemia was less frequent. Hematologic and scintigraphy findings also improved (serum albumin level: 2.5 g/dL). There were no adverse reactions during the 12-month follow-up. To the best of our knowledge, this is the first report of everolimus use in a patient with PIL. PMID:26908672

  14. Losing track of time through delayed body representations

    PubMed Central

    Fritz, Thomas H.; Steixner, Agnes; Boettger, Joachim; Villringer, Arno

    2015-01-01

    The ability to keep track of time is perceived as crucial in most human societies. However, to lose track of time may also serve an important social role, associated with recreational purpose. To this end a number of social technologies are employed, some of which may relate to a manipulation of time perception through a modulation of body representation. Here, we investigated an influence of real-time or delayed videos of own-body representations on time perception in an experimental setup with virtual mirrors. Seventy participants were asked to either stay in the installation until they thought that a defined time (90 s) had passed, or they were encouraged to stay in the installation as long as they wanted and after exiting were asked to estimate the duration of their stay. Results show that a modulation of body representation by time-delayed representations of the mirror-video displays influenced time perception. Furthermore, these time-delayed conditions were associated with a greater sense of arousal and intoxication. We suggest that feeding in references to the immediate past into working memory could be the underlying mental mechanism mediating the observed modulation of time perception. We argue that such an influence on time perception would probably not only be achieved visually, but might also work with acoustic references to the immediate past (e.g., with music). PMID:25918507

  15. Losing track of time through delayed body representations.

    PubMed

    Fritz, Thomas H; Steixner, Agnes; Boettger, Joachim; Villringer, Arno

    2015-01-01

    The ability to keep track of time is perceived as crucial in most human societies. However, to lose track of time may also serve an important social role, associated with recreational purpose. To this end a number of social technologies are employed, some of which may relate to a manipulation of time perception through a modulation of body representation. Here, we investigated an influence of real-time or delayed videos of own-body representations on time perception in an experimental setup with virtual mirrors. Seventy participants were asked to either stay in the installation until they thought that a defined time (90 s) had passed, or they were encouraged to stay in the installation as long as they wanted and after exiting were asked to estimate the duration of their stay. Results show that a modulation of body representation by time-delayed representations of the mirror-video displays influenced time perception. Furthermore, these time-delayed conditions were associated with a greater sense of arousal and intoxication. We suggest that feeding in references to the immediate past into working memory could be the underlying mental mechanism mediating the observed modulation of time perception. We argue that such an influence on time perception would probably not only be achieved visually, but might also work with acoustic references to the immediate past (e.g., with music). PMID:25918507

  16. Retinoblastoma Protein (RB1) Controls Fate Determination in Stem Cells and Progenitors of the Mouse Male Germline1

    PubMed Central

    Yang, Qi-En; Gwost, Ivy; Oatley, Melissa J.; Oatley, Jon M.

    2013-01-01

    ABSTRACT Continual spermatogenesis is the cornerstone of male fertility and relies on the actions of an undifferentiated spermatogonial population comprised of stem cells and progenitors. A foundational spermatogonial stem cell (SSC) pool is established during postnatal development that serves as a self-renewing reservoir from which progenitor spermatogonia arise that transiently amplify in number before committing to terminal differentiation. At present, the underlying molecular mechanisms governing these actions are undefined. Using conditional mutant mouse models, we investigated whether function of the undifferentiated spermatogonial population during postnatal life is influenced by the tumor suppressor protein RB1. Spermatogenesis initiates in mice with conditional inactivation of Rb1 in prospermatogonial precursors, but the germline is progressively lost upon aging due to impaired renewal of the undifferentiated spermatogonial population. In contrast, continual spermatogenesis is sustained following Rb1 inactivation in progenitor spermatogonia, but some cells transform into a carcinoma in situ-like state. Furthermore, knockdown of Rb1 abundance within primary cultures of wild-type undifferentiated spermatogonia impairs maintenance of the SSC pool, and some cells are invasive of the basement membrane after transplant into recipient testes, indicating acquisition of tumorigenic properties. Collectively, these findings indicate that RB1 plays an essential role in establishment of a self-renewing SSC pool and commitment to the spermatogenic lineage within progenitor spermatogonia. PMID:24089198

  17. Towards a no-lose theorem for naturalness

    NASA Astrophysics Data System (ADS)

    Curtin, David; Saraswat, Prashant

    2016-03-01

    We derive a phenomenological no-lose theorem for naturalness up to the TeV scale, which applies when quantum corrections to the Higgs mass from top quarks are canceled by perturbative beyond Standard Model (BSM) particles (top partners) of similar multiplicity due to to some symmetry. Null results from LHC searches already seem to disfavor such partners if they are colored. Any partners with SM charges and ˜TeV masses will be exhaustively probed by the LHC and a future 100 TeV collider. Therefore, we focus on neutral top partners. While these arise in twin Higgs theories, we analyze neutral top partners as model-independently as possible using effective field theory and simplified model methods. We classify all perturbative neutral top partner structures in order to compute their irreducible low-energy signatures at proposed future lepton and hadron colliders, as well as the irreducible tunings suffered in each scenario. Central to our theorem is the assumption that SM-charged BSM states appear in the UV completion of neutral naturalness, which is the case in all known examples. Direct production at the 100 TeV collider then allows this scale to be probed at the ˜10 TeV level. We find that proposed future colliders probe any such scenario of naturalness with tuning of 10% or better. This provides very strong model-independent motivation for both new lepton and hadron colliders, which in tandem act as discovery machines for general naturalness. We put our results in context by discussing other possibilities for naturalness, including "swarms" of top partners, inherently nonperturbative or exotic physics, or theories without SM-charged states in the UV completion. Realizing a concrete scenario which avoids our arguments while still lacking experimental signatures remains an open model-building challenge.

  18. Physically Active Rats Lose More Weight during Calorie Restriction

    PubMed Central

    Smyers, Mark E.; Bachir, Kailey Z.; Britton, Steven L.; Koch, Lauren G.; Novak, Colleen M.

    2014-01-01

    Daily physical activity shows substantial inter-individual variation, and low physical activity is associated with obesity and weight gain. Elevated physical activity is also associated with high intrinsic aerobic capacity, which confers considerable metabolic health benefits. Rats artificially selected for high intrinsic aerobic capacity (high-capacity runners, HCR) are more physically active than their low-capacity counterparts (low-capacity runners, LCR). To test the hypothesis that physical activity counters metabolic thriftiness, we measured physical activity and weight loss during three weeks of 50% calorie restriction (CR) in the HCR and LCR rat lines. At baseline, HCR ate more and were more active than LCR; this was seen in male rats, where LCR are considerably heavier than HCR, as well as in a set of female rats where body weight did not differ between the lines, demonstrating that this effect is consistent across sex and not secondary to body weight. We show for the first time that HCR lose more weight than LCR relative to baseline. Physical activity levels declined throughout CR, and this was more pronounced in HCR than in LCR, yet some aspects of activity remained elevated in HCR relative to LCR even during CR. This is consistent with the idea that low physical activity contributes to metabolic thriftiness during food restriction, allowing LCR to defend body mass, particularly lean mass. This has implications for physical activity during diet-induced weight loss, the genetic underpinnings of individual differences in weight loss during a diet, and the potential evolutionary opposition between metabolic thriftiness and aerobic capacity. PMID:25449411

  19. Physically active rats lose more weight during calorie restriction.

    PubMed

    Smyers, Mark E; Bachir, Kailey Z; Britton, Steven L; Koch, Lauren G; Novak, Colleen M

    2015-02-01

    Daily physical activity shows substantial inter-individual variation, and low physical activity is associated with obesity and weight gain. Elevated physical activity is also associated with high intrinsic aerobic capacity, which confers considerable metabolic health benefits. Rats artificially selected for high intrinsic aerobic capacity (high-capacity runners, HCR) are more physically active than their low-capacity counterparts (low-capacity runners, LCR). To test the hypothesis that physical activity counters metabolic thriftiness, we measured physical activity and weight loss during three weeks of 50% calorie restriction (CR) in the HCR and LCR rat lines. At baseline, HCR ate more and were more active than LCR; this was seen in male rats, where LCR are considerably heavier than HCR, as well as in a set of female rats where body weight did not differ between the lines, demonstrating that this effect is consistent across sex and not secondary to body weight. We show for the first time that HCR lose more weight than LCR relative to baseline. Physical activity levels declined throughout CR, and this was more pronounced in HCR than in LCR, yet some aspects of activity remained elevated in HCR relative to LCR even during CR. This is consistent with the idea that low physical activity contributes to metabolic thriftiness during food restriction, allowing LCR to defend body mass, particularly lean mass. This has implications for physical activity during diet-induced weight loss, the genetic underpinnings of individual differences in weight loss during a diet, and the potential evolutionary opposition between metabolic thriftiness and aerobic capacity. PMID:25449411

  20. 20 CFR 408.232 - When do you lose your foreign resident status?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false When do you lose your foreign resident status... CERTAIN WORLD WAR II VETERANS SVB Qualification and Entitlement Residence Outside the United States § 408.232 When do you lose your foreign resident status? (a) General rule. We consider you to have lost...

  1. 25 CFR 115.808 - Could trust fund investments made by OTFM lose money?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Could trust fund investments made by OTFM lose money? 115.808 Section 115.808 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES... § 115.808 Could trust fund investments made by OTFM lose money? The value of trust fund investments...

  2. 25 CFR 115.808 - Could trust fund investments made by OTFM lose money?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Could trust fund investments made by OTFM lose money? 115.808 Section 115.808 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES... § 115.808 Could trust fund investments made by OTFM lose money? The value of trust fund investments...

  3. 25 CFR 115.808 - Could trust fund investments made by OTFM lose money?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Could trust fund investments made by OTFM lose money? 115.808 Section 115.808 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES... § 115.808 Could trust fund investments made by OTFM lose money? The value of trust fund investments...

  4. 25 CFR 115.808 - Could trust fund investments made by OTFM lose money?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Could trust fund investments made by OTFM lose money? 115.808 Section 115.808 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES... § 115.808 Could trust fund investments made by OTFM lose money? The value of trust fund investments...

  5. 25 CFR 115.808 - Could trust fund investments made by OTFM lose money?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Could trust fund investments made by OTFM lose money? 115.808 Section 115.808 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES... § 115.808 Could trust fund investments made by OTFM lose money? The value of trust fund investments...

  6. Pluripotent cell derivation from male germline cells by suppression of Dmrt1 and Trp53.

    PubMed

    Tanaka, Takashi; Kanatsu-Shinohara, Mito; Hirose, Michiko; Ogura, Atsuo; Shinohara, Takashi

    2015-01-01

    Diploid germ cells are thought to have pluripotency potential. We recently described a method to derive pluripotent stem cells (PSCs) from cultured spermatogonial stem cells (SSCs) by depleting Trp53 and Dmrt1, both of which are known suppressors of teratomas. In this study, we used this technique to analyze the effect of this protocol in deriving PSCs from the male germline at different developmental stages. We collected primordial germ cells (PGCs), gonocytes and spermatogonia, and the cells were transduced with lentiviruses expressing short hairpin RNA against Dmrt1 and/or Trp53. We found that PGCs are highly susceptible to reprogramming induction and that only Trp53 depletion was sufficient to induce pluripotency. In contrast, gonocytes and spermatogonia were resistant to reprogramming by double knockdown of Dmrt1 and Trp53. PSCs derived from PGCs contributed to chimeras produced by blastocyst injection, but some of the embryos showed placenta-only phenotypes suggestive of epigenetic abnormalities of PGC-derived PSCs. These results show that PGCs and gonocytes/spermatogonia have distinct reprogramming potential and also suggest that fresh and cultured SSCs do not necessarily have the same properties. PMID:26227109

  7. Immunological changes following protein losing enteropathy after surgery total cavopulmonary connection (TCPC) by cytomics

    NASA Astrophysics Data System (ADS)

    Bocsi, József; Lenz, Dominik; Mittag, Anja; Sauer, Ursula; Wild, Lena; Hess, John; Schranz, Dietmar; Hambsch, Jörg; Schneider, Peter; Tárnok, Attila

    2008-02-01

    Complex immunophenotyping single-cell analysis are essential for systems biology and cytomics. The application of cytomics in immunology and cardiac research and diagnostics is very broad, ranging from the better understanding of the cardiovascular cell biology to the identification of heart function and immune consequences after surgery. TCPC or Fontan-type circulation is an accepted palliative surgery for patients with a functionally univentricular heart. Protein-losing enteropathy (PLE), the enteric loss of proteins, is a potential late complication after TCPC surgery. PLE etiology is poorly understood, but immunological factors seem to play a role. This study was aimed to gain insight into immune phenotype alterations following post-TCPC PLE. Patients were studied during routine follow-up up to 5yrs after surgery, blood samples of TCPC patients without (n=21, age 6.8+/-2.6 years at surgery; mean+/-SD) and with manifest PLE (n=12, age 12.8+/- 4.5 years at sampling) and age matched healthy children (control, n=22, age 8.6+/-2.5 years) were collected. Routine laboratory, immune phenotype and serological parameters were determined. Following PLE the immune phenotype dramatically changed with signs of acute inflammation (increased neutrophil and monocyte count, CRP, IL-8). In contrast, lymphocyte count (NK-cells, αβTCR +CD4 +, αβTCR +CD8 + cells) decreased (p<0.001). The residual T-cells had elevated CD25 and CD69 expression. In PLE-patients unique cell populations with CD3 +αβ/γδTCR - and αβTCR +CD4 -8 - phenotype were present in increased frequencies. Our studies show dramatically altered leukocyte phenotype after PLE in TCPC patients. These alterations resemble to changes in autoimmune diseases. We conclude that autoimmune processes may play a role in etiology and pathophysiology of PLE.

  8. Sexually dimorphic expression of Dmrt1 and γH2AX in germ stem cells during gonadal development in Xenopus laevis.

    PubMed

    Fujitani, Kazuko; Otomo, Asako; Wada, Mikako; Takamatsu, Nobuhiko; Ito, Michihiko

    2016-04-01

    In many animals, primordial germ cells (PGCs) migrate into developing gonads. There, they proliferate and differentiate into female and male germ stem cells (GSCs), oogonia and spermatogonia, respectively. Few studies have focused on the molecular mechanisms underlying the development of GSC sex determination. Here, we investigated the expression of the transcription factor Dmrt1 and a phosphorylated form of the histone variant H2AX (γH2AX) during gonadal development in Xenopus laevis. During early sexual differentiation, Dmrt1 was expressed in the GSCs of the ZW (female) and ZZ (male) gonads as well as somatic cells of the ZZ gonads. Notably, the PGCs and primary GSCs contained large, unstructured nuclei, whereas condensed, rounder nuclei appeared only in primary oogonia during tadpole development. After metamorphosis, Dmrt1 showed its expression in secondary spermatogonia, but not in secondary oogonia. Like Dmrt1, γH2AX was expressed in the nuclei of primary GSCs in early developing gonads. However, after metamorphosis, γH2AX expression continued in primary and secondary spermatogonia, but was barely detected in the condensed nuclei of primary oogonia. Taken together, these observations indicate that spermatogonia tend to retain PGC characteristics, compared to oogonia, which undergo substantial changes during gonadal differentiation in X. laevis. Our findings suggest that Dmrt1 and γH2AX may contribute to the maintenance of stem cell identity by controlling gene expression and epigenetic changes, respectively. PMID:27239441

  9. Stress reticulocytes lose transferrin receptors by an extrinsic process involving spleen and macrophages.

    PubMed

    Rhodes, Melissa M; Koury, Stephen T; Kopsombut, Prapaporn; Alford, Catherine E; Price, James O; Koury, Mark J

    2016-09-01

    As they mature into erythrocytes during normal erythropoiesis, reticulocytes lose surface transferrin receptors before or concurrently with reticulin. Exosome release accounts for most of the loss of transferrin receptors from reticulocytes. During erythropoietic stress, reticulocytes are released early from hematopoietic tissues and have increased reticulin staining and transferrin receptors. Flow cytometry of dually stained erythrocytes of mice recovering from phlebotomy demonstrated delayed loss of reticulin and transferrin receptors during in vitro maturation compared to in vivo maturation, indicating that an in vivo process extrinsic to the reticulocytes facilitates their maturation. Splenectomy or macrophage depletion by liposomal clodronate inhibited in vivo maturation of reticulocytes and increased the numbers of reticulin-negative, transferrin receptor-positive cells during and after recovery from phlebotomy. This reticulin-negative, transferrin receptor-positive population was rarely found in normal mice. Transmission electron microscopy demonstrated that the reticulin-negative, transferrin receptor-positive cells were elongated and discoid erythrocytes, but they had intracellular and surface structures that appeared to be partially degraded organelles. The results indicate that maturation of circulating stress reticulocytes is enhanced by an extrinsic process that occurs in the spleen and involves macrophage activity. Complete loss of reticulin with incomplete loss of surface transferrin receptors in this process produces a reticulin-negative, transferrin receptor-positive erythrocyte population that has potential utility for detecting prior erythropoietic stresses including bleeding, hemolysis and erythropoietin administration, even after recovery has been completed. Am. J. Hematol. 91:875-882, 2016. © 2016 Wiley Periodicals, Inc. PMID:27194638

  10. Microarray-Based Analysis of Cell-Cycle Gene Expression During Spermatogenesis in the Mouse1

    PubMed Central

    Roy Choudhury, Dipanwita; Small, Chris; Wang, Yufeng; Mueller, Paul R.; Rebel, Vivienne I.; Griswold, Michael D.; McCarrey, John R.

    2010-01-01

    Mammalian spermatogenesis is a continuum of cellular differentiation in a lineage that features three principal stages: 1) a mitotically active stage in spermatogonia, 2) a meiotic stage in spermatocytes, and 3) a postreplicative stage in spermatids. We used a microarray-based approach to identify changes in expression of cell-cycle genes that distinguish 1) mitotic type A spermatogonia from meiotic pachytene spermatocytes and 2) pachytene spermatocytes from postreplicative round spermatids. We detected expression of 550 genes related to cell-cycle function in one or more of these cell types. Although a majority of these genes were expressed during all three stages of spermatogenesis, we observed dramatic changes in levels of individual transcripts between mitotic spermatogonia and meiotic spermatocytes and between meiotic spermatocytes and postreplicative spermatids. Our results suggest that distinct cell-cycle gene regulatory networks or subnetworks are associated with each phase of the cell cycle in each spermatogenic cell type. In addition, we observed expression of different members of certain cell-cycle gene families in each of the three spermatogenic cell types investigated. Finally, we report expression of 221 cell-cycle genes that have not previously been annotated as part of the cell cycle network expressed during spermatogenesis, including eight novel genes that appear to be testis-specific. PMID:20631398

  11. Testicular structure and germ cells morphology in salamanders

    PubMed Central

    Uribe, Mari Carmen; Mejía-Roa, Víctor

    2014-01-01

    Testes of salamanders or urodeles are paired elongated organs that are attached to the dorsal wall of the body by a mesorchium. The testes are composed of one or several lobes. Each lobe is morphologically and functionally a similar testicular unit. The lobes of the testis are joined by cords covered by a single peritoneal epithelium and subjacent connective tissue. The cords contain spermatogonia. Spermatogonia associate with Sertoli cells to form spermatocysts or cysts. The spermatogenic cells in a cyst undergo their development through spermatogenesis synchronously. The distribution of cysts displays the cephalo-caudal gradient in respect to the stage of spermatogenesis. The formation of cysts at cephalic end of the testis causes their migration along the lobules to the caudal end. Consequently, the disposition in cephalo-caudal regions of spermatogenesis can be observed in longitudinal sections of the testis. The germ cells are spermatogonia, diploid cells with mitotic activity; primary and second spermatocytes characterized by meiotic divisions that develop haploid spermatids; during spermiogenesis the spermatids differentiate to spermatozoa. During spermiation the cysts open and spermatozoa leave the testicular lobules. After spermiation occurs the development of Leydig cells into glandular tissue. This glandular tissue regressed at the end of the reproductive cycle. PMID:26413406

  12. INTERDISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Aggregation Behaviors of a Two-Species System with Lose-Lose Interactions

    NASA Astrophysics Data System (ADS)

    Song, Mei-Xia; Lin, Zhen-Quan; Li, Xiao-Dong; Ke, Jian-Hong

    2010-06-01

    We propose an aggregation evolution model of two-species (A- and B-species) aggregates to study the prevalent aggregation phenomena in social and economic systems. In this model, A- and B-species aggregates perform self-exchange-driven growths with the exchange rate kernels K (k,l) = Kkl and L(k,l) = Lkl, respectively, and the two species aggregates perform self-birth processes with the rate kernels J1(k) = J1k and J2(k) = J2k, and meanwhile the interaction between the aggregates of different species A and B causes a lose-lose scheme with the rate kernel H(k,l) = Hkl. Based on the mean-field theory, we investigated the evolution behaviors of the two species aggregates to study the competitions among above three aggregate evolution schemes on the distinct initial monomer concentrations A0 and B0 of the two species. The results show that the evolution behaviors of A- and B-species are crucially dominated by the competition between the two self-birth processes, and the initial monomer concentrations A0 and B0 play important roles, while the lose-lose scheme play important roles in some special cases.

  13. Protein-losing enteropathy in a dog with lymphangiectasia, lymphoplasmacytic enteritis and pancreatic exocrine insufficiency.

    PubMed

    Rodríguez-Alarcón, C A; Beristaín-Ruiz, D M; Pérez-Casio, F; Rivera, R; Ochoa, G; Martín-Orozco, U

    2012-01-01

    This is a report of seven-year-old male Akita mixed dog, with protein-losing enteropathy (PLE). He had a history of chronic vomiting and diarrhea with anorexia/hyporexia. Previously he suffered acute abdomen about eight months prior to this visit. Our dog showed uncommon combination of diseases that could cause PLE since it was affected by inflammatory bowel disease (IBD), intestinal lymphangiectasia (IL), and exocrine pancreatic insufficiency (EPI). The dog had most of the abnormalities found in IL, as well as hypoalbuminemia, hyperglobulinemia, lymphopenia, hypocalcemia, and hypercholesterolemia. During endoscopy exam, we found changes characteristic of IL such as irregular small white spots. We took biopsies from stomach, duodenum, and cecum. These biopsies showed infiltration by lymphocytes and plasmatic cells in the lamina propria also, the duodenal biopsies showed moderate dilation of the lymphatic vessels. The patient had 2.1 µg/mL of TLI, this result was compatible with EPI. We assume that the first pathology in this animal was IBD, which caused chronic pancreatitis (CP) that in turn progressed to EPI. It is also possible that IL was secondary to IBD. We have reported for the first time the correlation of IBD and EPI in dogs. This should change our approach to treating chronic diarrhea in dogs. Therefore, we propose that dogs diagnosed with EPI should also be subjected to endoscopy and intestinal biopsy. Similarly, to rule out secondary EPI, TLI should be measured routinely in dogs with IBD. PMID:23106499

  14. EDITORIAL: Advanced fractions? or use it or lose it

    NASA Astrophysics Data System (ADS)

    Dobson, Ken

    1997-09-01

    kind of mixture of skill, knowledge and understanding required for successful mathematical operations is use it or lose it. We went `decimal' a long time ago, and the ideas of pence as 12ths of a shilling and shillings as 20ths of a pound are positively mediaeval for everyone under 40 or so. Remember farthings? In those days fractions were everywhere. Nowadays they are somewhat esoteric for the average citizen - and physicist. Yet fractions are vital in advanced mathematics, e.g. involving the differentiation and integration of polynomial fractions, as Peter Gill pointed out. This is why he was teaching simple fractions to his students, and possibly why their competence at these was such a good indicator of success in their end-of-year mathematics exam. What can we conclude from all this? I suggest two things. First, that fractions as illustrated above might well be considered as advanced mathematics, a fit and intriguing topic for an A-level course. Ordinary citizens should be taught - very thoroughly - to understand and use that useful kind of fraction based on dividing things into 100 parts, called percentages. Secondly, and more fundamentally, we should learn from this example to take a hard look at what we teach and what we need to teach, removing or adapting those things that exist in syllabuses and the National Curriculum for reasons of purely historical inertia. I hope that the IoP Working Party on Mathematics and Physics, due to report in the autumn, has looked hard at issues like this. And, of course, anyone interested in this topic is cordially invited to the Education Group's 16 - 19 Day Conference, which this year is about this vexed question of what mathematics physics learners need - and how they get it. At IoP Headquarters on Saturday, 15 November 1997. Details from Catherine Wilson.

  15. Spermatogonial stem cells in the testis of an endangered bovid: Indian black buck (Antilope cervicapra L.).

    PubMed

    Goel, Sandeep; Reddy, Niranjan; Mahla, Ranjeet Singh; Suman, Sanjay Kumar; Pawar, Rahul Mohanchandra

    2011-07-01

    Numerous wild bovids are facing threat of extinction owing to the loss of habitat and various other reasons. Spermatogonial stem cells (SSCs) represent the only germline stem cells in adult body that are capable of self-renewal and that can undergo differentiation to produce haploid germ cells. SSCs can, therefore, serve as a useful resource for preservation of germplasm of threatened and endangered mammals. The Indian black buck (Antilope cervicapra L.) is a small Indian antelope that is listed as endangered by the Indian Wildlife Protection Act, 1972. Immunohistochemical analysis of testes tissues of black buck revealed the presence of spermatogonia that were specifically stained by lectin-Dolichos biflorus agglutinin (DBA). The expression of pluripotent cell-specific markers, NANOG and stage-specific embryonic antigen-1 (SSEA-1), was detected in spermatogonia. Interestingly, the expression of POU5F1 (OCT3/4) was absent from spermatogonia, however, it was detected in differentiating cells such as spermatocytes and round spermatids but not in elongated spermatids. The expression of NANOG protein was also present in spermatocytes but absent in round and elongated spermatids. Using the testis transplantation assay, stem cell potential of black buck spermatogonia was confirmed as indicated by the presence of colonized DBA-stained cells in the basal membrane of seminiferous tubules of xenotransplanted mice testis. The findings from this study suggest the presence of SSCs in the testis of an endangered bovid for the first time and open new possibility to explore the use of SSCs in conservation. PMID:21719218

  16. Altered protein prenylation in Sertoli cells is associated with adult infertility resulting from childhood mumps infection.

    PubMed

    Wang, Xiu-Xing; Ying, Pu; Diao, Fan; Wang, Qiang; Ye, Dan; Jiang, Chen; Shen, Ning; Xu, Na; Chen, Wei-Bo; Lai, Shan-Shan; Jiang, Shan; Miao, Xiao-Li; Feng, Jin; Tao, Wei-Wei; Zhao, Ning-Wei; Yao, Bing; Xu, Zhi-Peng; Sun, Hai-Xiang; Li, Jian-Min; Sha, Jia-Hao; Huang, Xing-Xu; Shi, Qing-Hua; Tang, Hong; Gao, Xiang; Li, Chao-Jun

    2013-07-29

    Mumps commonly affects children 5-9 yr of age, and can lead to permanent adult sterility in certain cases. However, the etiology of this long-term effect remains unclear. Mumps infection results in progressive degeneration of the seminiferous epithelium and, occasionally, Sertoli cell-only syndrome. Thus, the remaining Sertoli cells may be critical to spermatogenesis recovery after orchitis healing. Here, we report that the protein farnesylation/geranylgeranylation balance is critical for patients' fertility. The expression of geranylgeranyl diphosphate synthase 1 (GGPPS) was decreased due to elevated promoter methylation in the testes of infertile patients with mumps infection history. When we deleted GGPPS in mouse Sertoli cells, these cells remained intact, whereas the adjacent spermatogonia significantly decreased after the fifth postnatal day. The proinflammatory MAPK and NF-κB signaling pathways were constitutively activated in GGPPS(-/-) Sertoli cells due to the enhanced farnesylation of H-Ras. GGPPS(-/-) Sertoli cells secreted an array of cytokines to stimulate spermatogonia apoptosis, and chemokines to induce macrophage invasion into the seminiferous tubules. Invaded macrophages further blocked spermatogonia development, resulting in a long-term effect through to adulthood. Notably, this defect could be rescued by GGPP administration in EMCV-challenged mice. Our results suggest a novel mechanism by which mumps infection during childhood results in adult sterility. PMID:23825187

  17. Surviving the tornado of mental illness: psychiatric survivors' experiences of getting, losing, and keeping housing.

    PubMed

    Forchuk, Cheryl; Ward-Griffin, Catherine; Csiernik, Rick; Turner, Katherine

    2006-04-01

    This qualitative study explored experiences of psychiatric consumer-survivors related to housing. Nine focus groups involving 90 people were conducted in urban and rural areas in South-Western Ontario. A set of open-ended questions was used. Many participants described a devastating experience of losing much of what was important to them and going through a long arduous process to rebuild their lives. Group discussions were audiotaped and transcribed. Individual and team analyses of the transcripts revealed that psychiatric survivors experienced three levels of upheaval, loss, and destruction, similar to the effects of a tornado: losing ground, struggling to survive, and gaining stability. Within each of these levels, five major themes were identified: living in fear, losing control of basic human rights, attempting to hold onto and create relationships, identifying supports and seeking services, and obtaining personal space and place. A caring community response, including adequate housing, income support, and community care, can help people rebuild their lives. PMID:16603754

  18. Relaxin affects cell organization and early and late stages of spermatogenesis in a coculture of rat testicular cells.

    PubMed

    Pimenta, M T; Francisco, R A R; Silva, R P; Porto, C S; Lazari, M F M

    2015-07-01

    Relaxin and its receptor RXFP1 are co-expressed in Sertoli cells, and relaxin can stimulate proliferation of Sertoli cells. In this study, we investigated a role of relaxin in spermatogenesis, using a short-term culture of testicular cells of the rat that allowed differentiation of spermatogonia to spermatids. Sertoli, germ, and peritubular myoid cells were the predominant cell types in the culture. Sertoli and germ cells expressed RXFP1. Cultures were incubated without (control) or with 0.5% fetal bovine serum (FBS) or 100 ng/mL H2 relaxin (RLN) for 2 days. Cell organization, number, and differentiation were analyzed after 2 (D2), 5 (D5) or 8 (D8) days of culturing. Although the proportion of germ cells decayed from D2 to D5, the relative contribution of HC, 1C, 2C, and 4C germ cell populations remained constant in the control group during the whole culture. RLN did not affect the proportion of germ cell populations compared with control, but increased gene and/or protein expression of the undifferentiated and differentiated spermatogonia markers PLZF and c-KIT, and of the post-meiotic marker Odf2 in D5. RLN favored organization of cells in tubule-like structures, the arrangement of myoid cells around the tubules, arrangement of c-KIT-positive spermatogonia at the basal region of the tubules, and expression of the cell junction protein β-catenin close to the plasma membrane region. Knockdown of relaxin with small interfering RNA (siRNA) reduced expression of β-catenin at the cell junctions, and shifted its expression to the nucleus. We propose that relaxin may affect spermatogenesis by modulating spermatogonial self renewal and favoring cell contact. PMID:26041439

  19. Your money or your self-esteem: threatened egotism promotes costly entrapment in losing endeavors.

    PubMed

    Zhang, Liqing; Baumeister, Roy F

    2006-07-01

    The present research explored egotism-maintaining favorable views of the self-as a motivation underlying entrapment in losing endeavors. Four studies suggested that threatened selfesteem would cause decision makers to invest and lose more money in a previously chosen course of action. Ego-threatened participants consistently lost more money than nonthreatened participants across diverse entrapping situations regardless of whether the outcome was ostensibly determined by luck (Experiments 1 and 4), ability (Experiment 2), or interpersonal competition (Experiment 3). Thus, pursuing favorable views of the self could be costly to decision makers' financial well-being and may produce self-defeating behaviors. PMID:16738022

  20. Cell proliferation in the seminiferous and epididymal epithelia of Sus domesticus.

    PubMed

    Bernal-Mañas, C M; Beltrán-Frutos, E; Ferrer, C; Seco-Rovira, V; Pinart, E; Briz, M D; Bonet, S; Canteras, M; Pastor, L M

    2014-03-15

    It is important to understand the proliferative activity of the different structures of the male reproductive apparatus in livestock species, such as Sus domesticus, to ensure reproductive efficiency. The main aims of this study were (a) to evaluate the proliferative activity of the spermatogonia in the different stages of the seminiferous cycle and (b) to study the cell proliferation in the epididymal epithelium in each region, identifying the different cells involved. For this, the testes and epididymis of three healthy, sexually mature Sus domesticus boars were used. The organs were processed for light microscopy, and immunohistochemical techniques were used to detect proliferating cell nuclear antigen. The cells immunostaining positively and negatively for proliferating cell nuclear antigen were counted and several parameters and indexes were calculated to evaluate the proliferation in both epithelia, taking into account the stage of the seminiferous epithelium cycle, and, in the case of the epididymal epithelium, the different regions and cells are the same. Finally, a contrast analysis of equality between pairs of means was carried out followed by a least significant differences test, in which differences were considered significant at P < 0.05. In the seminiferous epithelium, the greatest total number of spermatogonia and proliferating spermatogonia was observed in the postmeiotic stages (mainly VII and VIII). The proliferation index of the spermatogonia increased from the meiotic to postmeiotic stages. As regards the epididymal epithelium, the total proliferation index was higher in the caput. In each region, the clear and principal cells showed the highest proliferation index with respect to the total number of cells counted, whereas the proliferation index of each cell with respect to the same type was higher in the clear cells, followed by the narrow and principal cells. In conclusion, the proliferative activity of spermatogonia in the seminiferous

  1. Dose-response studies on the spermatogonial stem cells of the rhesus monkey (Macaca mulatta) after X irradiation

    SciTech Connect

    van Alphen, M.M.; van de Kant, H.J.; Davids, J.A.; Warmer, C.J.; Bootsma, A.L.; de Rooij, D.G. )

    1989-09-01

    Studies of the dose response of the spermatogonial stem cells in the rhesus monkey were performed at intervals of 130 and 160 days after graded doses of X irradiation. The D0 of the spermatogonial stem cells was established using the total numbers of the type A spermatogonia that were present at 130 and 160 days after irradiation and was found to be 1.07 Gy; the 95% confidence interval was 0.90-1.34 Gy.

  2. Propagation of bovine spermatogonial stem cells in vitro.

    PubMed

    Aponte, Pedro M; Soda, Takeshi; Teerds, Katja J; Mizrak, S Canan; van de Kant, Henk J G; de Rooij, Dirk G

    2008-11-01

    The access to sufficient numbers of spermatogonial stem cells (SSCs) is a prerequisite for the study of their regulation and further biomanipulation. A specialized medium and several growth factors were tested to study the in vitro behavior of bovine type A spermatogonia, a cell population that includes the SSCs and can be specifically stained for the lectin Dolichos biflorus agglutinin. During short-term culture (2 weeks), colonies appeared, the morphology of which varied with the specific growth factor(s) added. Whenever the stem cell medium was used, round structures reminiscent of sectioned seminiferous tubules appeared in the core of the colonies. Remarkably, these round structures always contained type A spermatogonia. When leukemia inhibitory factor (LIF), epidermal growth factor (EGF), or fibroblast growth factor 2 (FGF2) were added, specific effects on the numbers and arrangement of somatic cells were observed. However, the number of type A spermatogonia was significantly higher in cultures to which glial cell line-derived neurotrophic factor (GDNF) was added and highest when GDNF, LIF, EGF, and FGF2 were all present. The latter suggests that a proper stimulation of the somatic cells is necessary for optimal stimulation of the germ cells in culture. Somatic cells present in the colonies included Sertoli cells, peritubular myoid cells, and a few Leydig cells. A transplantation experiment, using nude mice, showed the presence of SSCs among the cultured cells and in addition strongly suggested a more than 10 000-fold increase in the number of SSCs after 30 days of culture. These results demonstrate that bovine SSC self-renew in our specialized bovine culture system and that this system can be used for the propagation of these cells. PMID:18663014

  3. 2007 Presidential Address: Fear of Losing Control--Power, Perfectionism, and the Psychology of Women

    ERIC Educational Resources Information Center

    Chrisler, Joan C.

    2008-01-01

    Anecdotal evidence and popular culture suggest that fear of losing control of oneself is common among North American women, yet there is little in the way of data or theory to show why so many women fear loss of control or how to help them to leave that fear behind. In this article a commonly accepted definition of self-regulation is examined…

  4. Losing Perspective: The Recent Debate Over Welfare and Poverty. Working Paper 2081-02.

    ERIC Educational Resources Information Center

    Levy, Frank S.; Michel, Richard C.

    Charles Murray's book, "Losing Ground: American Social Policy, 1950-1980," proposes the abolition of benefit programs for all working-aged persons for the following reasons: (1) it is logically impossible for the government to aid the poor by creating incentives for people to become poor; (2) since the mid-1960s the United States has so…

  5. Influence of breast feeding on the clinical features of salt-losing congenital adrenal hyperplasia

    PubMed Central

    Curtis, Joseph A; Bailey, John D

    1983-01-01

    Feeding habits before diagnosis were reviewed in 32 infants with salt-losing congenital adrenal hyperplasia who were admitted to hospital in adrenal crisis. Most breast-fed babies failed to thrive, seldom vomited, and despite severe salt wasting, presented at a later age than their formula-fed counterparts. PMID:6830279

  6. Why Some Hope Scholarship Recipients Retain the Scholarship and Others Lose It

    ERIC Educational Resources Information Center

    Trant, Eleanore C.; Crabtree, Katelyn E.; Ciancio, Dennis J.; Hart, Leslie A.; Watson, Tiffany B.; Williams, Robert L.

    2015-01-01

    The study we report here examined parental, pre-course, and in-course predictors of students' probability of retaining (n = 136) or losing the HOPE scholarship (n = 41). The study was conducted in a multi-section, entry-level course (n = 203) for the Teacher-Education Program at a large state university in the southeastern U.S. Logistic regression…

  7. Evaluation of the "Lose Your Excuse" Public Service Advertising Campaign for Tweens to Save Energy

    ERIC Educational Resources Information Center

    Bertrand, Jane T.; Goldman, Patty; Zhivan, Natalia; Agyeman, Yaw; Barber, Erin

    2011-01-01

    This study evaluates the 2008-2009 "Lose your Excuse" public service advertising (PSA) campaign on energy efficiency targeting 8- to 12-year-olds, intended to increase knowledge, foster proactive attitudes, and change energy usage behaviors. Baseline and two follow-up surveys were conducted with online samples representative of the national…

  8. Children Who Lose Their Parents to HIV/AIDS: Agency Guidelines for Adoptive and Kinship Placement.

    ERIC Educational Resources Information Center

    Merkel-Holguin, Lisa

    Across the United States and world, children who lose their parents to HIV/AIDS are one of the fasted emerging groups affected by this epidemic. Increasingly, child welfare and family service agencies are helping infected parents to secure legal and permanent care arrangements for their children. These guidelines address the issues of placing…

  9. 20 CFR 663.565 - May an eligible training provider lose its eligibility?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... of title I of WIA or the WIA regulations, including 29 CFR part 37, may be removed from the list in... training to appeal a denial of eligibility under this subpart according to the requirements of 20 CFR 667... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false May an eligible training provider lose...

  10. Factors associated with BMI, weight perceptions and trying to lose weight in African-American smokers.

    PubMed Central

    Lee, Rebecca E.; Harris, Kari Jo; Catley, Delwyn; Shostrom, Valerie; Choi, Simon; Mayo, Matthew S.; Okuyemi, Kola; Kaur, Harsohena; Ahluwalia, Jasjit S.

    2005-01-01

    This study examined sociodemographic, behavioral and psychosocial factors associated with BMI, weight perceptions and trying to lose weight among African-American smokers (N=600, M=44.2 years, 70% female). Sixty-eight percent of the sample were overweight or obese (sample BMI M=28.0, SD=6.7). Three separate, simultaneous multivariable regression models were used to determine which factors were associated with BMI, weight perceptions and trying to lose weight. Poorer health, female gender and high-school education or higher were significantly associated with higher BMIs (p<0.05). Being female (OR=5.8, 95% CI=3.6-9.3) and having a higher BMI (OR=0.6, 95% CI=0.5-0.6) was associated with perception of overweight and smoking more cigarettes per day (OR=1.0, 95% CI=1.0-1.1), and perceiving oneself as overweight (OR=14.1, 95% CI=8.2-24.2) was associated with trying to lose weight. Participants somewhat underestimated their BMI in their weight perceptions. Those who perceived themselves as overweight were more likely to be trying to lose weight; therefore, increasing participant awareness of actual BMI status may lead to improved weight-control efforts in African-American smokers. Several expected associations with outcomes were not found, suggesting that BMI and weight constructs are not well-understood in this population. PMID:15719872

  11. A Professor's Controversial Analysis of Why Black Students Are "Losing the Race."

    ERIC Educational Resources Information Center

    Reisberg, Leo

    2000-01-01

    Reports on the controversial stands taken by John H. McWhorter, a black University of Berkeley associate professor, in his book "Losing the Race: Self-Sabotage in Black America." The book opposes affirmative action and suggests that black academic achievement lags because of a mindset endemic to black culture that discourages learning, while…

  12. 20 CFR 663.565 - May an eligible training provider lose its eligibility?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... subsequently violated any provision of title I of WIA or the WIA regulations, including 29 CFR part 37, may be... according to the requirements of 20 CFR 667.640(b). ... 20 Employees' Benefits 4 2012-04-01 2012-04-01 false May an eligible training provider lose...

  13. 20 CFR 663.565 - May an eligible training provider lose its eligibility?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... subsequently violated any provision of title I of WIA or the WIA regulations, including 29 CFR part 37, may be... according to the requirements of 20 CFR 667.640(b). ... 20 Employees' Benefits 4 2014-04-01 2014-04-01 false May an eligible training provider lose...

  14. Living with clipped wings—Patients’ experience of losing a leg

    PubMed Central

    Norlyk, Annelise; Martinsen, Bente; Kjaer-Petersen, Klaus

    2013-01-01

    This study explores the lived experience of losing a leg as described by the patients themselves post-discharge. Studies have documented that regardless of aetiology patients are faced with severe physical as well as psychosocial challenges post-amputation. However, only few studies explore in-depth the patients’ perspective on the various challenges following the loss of a leg. The study uses the phenomenological approach of Reflective Lifeworld Research (RLR). Data were collected from 24 in-depth interviews with 12 Danish patients. Data analysis was performed according to the guidelines given in RLR. The essential meaning of losing a leg is a radical and existential upheaval, which restricts patients’ lifestyle and irretrievably alters their lifeworld. Life after the operation is associated with despair, and a painful sense of loss, but also with the hope of regaining personal independence. The consequences of losing a leg gradually materialize as the patients realize how the loss of mobility limits their freedom. Patients experience the professional help as primarily directed towards physical care and rehabilitation. The findings show that the loss of a leg and, subsequently, the restricted mobility carry with them an existential dimension which refers to limitation of action space and loss of freedom experienced as an exclusion from life. Our findings demonstrate a need for complementary care and stress the importance of an increased awareness of the psychosocial and existential consequences of losing a limb. PMID:24128661

  15. Winning or Losing against an Opposite-Sex Peer on a Gender-Based Competitive Task.

    ERIC Educational Resources Information Center

    Gilbert, Stefanie; Thompson, J. Kevin

    1999-01-01

    Explored the effects on college students' mood and body image of a negative versus positive outcome in an opposite-sex, competitive peer interaction. Used one gender-neutral and one gender stereotypical task. There were no gender differences in reactions to winning or losing gender-neutral competitions, except marginally for depression. The…

  16. Lose to Win: A Goal-Oriented Group for Overweight Children.

    ERIC Educational Resources Information Center

    Marin, Roselyn

    1985-01-01

    Describes the Lose to Win Program, a weight loss program for third, fourth and fifth grade students. The program included nutrition education, exercise, and improving the self concept, and involved the use of rewards, and support of parents and school staff. (JAC)

  17. A Longitudinal Study of Body Image and Strategies to Lose Weight and Increase Muscles among Children

    ERIC Educational Resources Information Center

    McCabe, M. P.; Ricciardelli, L. A.

    2005-01-01

    A longitudinal study was used to examine age differences in the role of body mass index (BMI) and sociocultural pressures in predicting changes in body image and strategies to both lose weight and increase muscles among 443 children aged between 8 and 12 years (207 boys, 236 girls) over a 16-month period. The strongest predictors of body image and…

  18. Communicative Acts in Coach-Athlete Interactions: When Losing Competitions and when Making Mistakes in Training

    ERIC Educational Resources Information Center

    Sagar, Sam S.; Jowett, Sophia

    2012-01-01

    Athletes' perceptions of coaches' communicative acts of interaction in two key interpersonal situations were examined, and their impact on the athletes: (a) when athletes lose competitions; and, (b) when athletes make mistakes in training. Athletes (N = 324, M age = 20.11) completed an open-ended survey. Data were deductively and inductively…

  19. Who Gains, Who Loses?: The Fiscal Impact of the Milwaukee Parental Choice Program

    ERIC Educational Resources Information Center

    Costrell, Robert M.

    2009-01-01

    Do school vouchers save the taxpayer money, or do they add to taxpayer burdens? Which groups of taxpayers are most affected, and do they gain or lose? What is the financial impact on public school districts? Usually, these questions are debated in the abstract. Now it is possible to get more concrete answers from the nation's longest-running…

  20. Assets and Depreciation: Or, Only an Accountant Would Claim Books Lose Value.

    ERIC Educational Resources Information Center

    Snyder, Herbert

    1998-01-01

    Examines the purpose for using historical costs in library financial records. Discusses the difference between spending money and losing resources. Describes how financial record systems operate and the ways in which accounting treats classes of expenditures. Uses the example of a bookmobile. (AEF)

  1. Losing Ground: A Critique. Institute for Research on Poverty Special Report Series #38.

    ERIC Educational Resources Information Center

    McLanahan, Sara; And Others

    Five papers which criticize Charles Murray's book, "Losing Ground: American Social Policy 1950-1980" are presented in this report. In general, the papers dispute Murray's thesis that the poor did not benefit from social policies but were, instead, substantially harmed by these programs. The papers (and their authors) are: (1) "Charles Murray and…

  2. Osteoclasts Lose Innate Inflammatory Reactivity to Metal and Polymer Implant Debris Compared to Monocytes/Macrophages

    PubMed Central

    Yadav, Jessica; Samelko, Lauryn; Gilvar, Phil; McAllister, Kyron; Hallab, Nadim James

    2013-01-01

    Long-term aseptic failures of joint replacements are generally attributed to implant debris-induced inflammation and osteolysis. This response is largely mediated by immune and bone cells (monocytes/macrophages and osteoclasts, respectively), that in the presence of implant debris (e.g. metal particles and ions), release pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6. The relative degree to which implant debris can illicit inflammatory response(s) from osteoclasts vs monocytes/macrophages is unknown, i.e. are osteoclasts a viable target for anti-inflammatory therapy for implant debris? We investigated relative monocyte versus osteoclast inflammatory responses in a side-by-side comparison using implant debris from the perspective of both danger signaling (IL-1β) and pathogenic recognition (TNF-α) reactivity (Challenge Agents: Cobalt-alloy, Titanium-alloy, and PMMA particles, 0.9-1.8um-dia ECD and Cobalt, and Nickel-ions 0.01-0.1mM, all with and without LPS priming). Human monocytes/macrophages reacted to implant debris with >100 fold greater production of cytokines compared to osteoclast-like cells. Particulate Co-alloy challenge induced >1000 pg/ml of IL-1β and TNF-α, in monocytes and <50pg/mL IL-1β and TNF-α in osteoclasts. Cobalt ions induced >3000pg/mL IL-1β and TNF-α in monocytes/macrophages and <50pg/mL IL-1β and TNF-α in osteoclasts. The paracrine effect of supernatants from debris-treated monocytes/macrophages was capable of inducing greater osteoclastogenesis (TRAP+, p<0.06) and inflammation than direct debris challenge on osteoclasts. Our results indicate that as monocytes/macrophages differentiate into osteoclasts, they largely lose their innate immune reactivity to implant debris and thus may not be as relevant a therapeutic target as monocytes/macrophages for mitigating debris-induced inflammation. PMID:24198853

  3. Losing it.

    PubMed

    Coutu, Diane L

    2004-04-01

    "It's worse than I thought.... She's completely lost her mind," says Harry Beecham, the CEO of blue chip management consultancy Pierce and Company. The perplexed executive was in a hotel suite with his wife in Amsterdam, the latest stop on his regular trek to dozens of Pierce offices worldwide. In his hand was a sheaf of paper--the same message sent over and over again by his star employee and protégée Katharina Waldburg. The end of the world is coming, she warned. "Someone is going to die." Harry wouldn't have expected this sort of behavior from Katharina. After graduating with distinction from Oxford, she made a name for herself by single-handedly building Pierce's organizational behavior practice. At 27, she's poised to become the youngest partner ever elected at the firm. But Harry can't ignore the faxes in his hand. Or the stream-of-consciousness e-mails Katharina's been sending to one of the directors in Pierce's Berlin office--mostly gibberish but potentially disastrous to Katharina's reputation if they ever got out. Harry also can't dismiss reports from Roland Fuoroli, manager of the Berlin office, of a vicious verbal exchange Katharina had with him, or of an "over the top" lunch date Katharina had with one of Pierce's clients in which she was explaining the alphabet's role in the creation of the universe. Harry is planning to talk to Katharina when he gets to Berlin. What should he say? And will it be too late? Four commentators offer their advice in this fictional case study. They are Kay Redfield Jamison, a professor of psychiatry and a coauthor of Manic-Depressive Illness; David E. Meen, a former director at McKinsey & Company; Norman Pearlstine, the editor in chief at Time Incorporated; and Richard Primus, an assistant law professor at the University of Michigan. PMID:15077365

  4. Losing ground.

    PubMed

    Carter, D

    1993-01-01

    A recent research effort by the Nepalese Topological Survey Branch and the Department of Soil Science and the University of British Columbia, Canada, found with the use of the geographic information system (GIS) that forest cover has expanded, but soil fertility is decreasing at a rapid rate in Nepal. These findings conflict with media allegations which allege forest destruction from farmers' wood-cutting practices and responsibility for flooding in Bangladesh. The research was conducted in the Jhikhu Khola watershed in the Middle Mountains, which is Nepal's most populous region that is intensively used in subsistence farming and grazing. Migration adds to the existing problems of soil erosion, sedimentation, deforestation, and loss in soil fertility. The soil is prone to erosion. Data were collected through the GIS system by aerial photos, field surveys, and soil analysis. Hydrometric stations to measure the sedimentation process were established in 7 places and farmers monitored the climate, water loss and gain, and sediment movement. Interviews were also conducted among the farm population on demographics, livestock, fodder and fuel consumption, crop yields and practices, and fertilizer use. Researchers aimed both to identify the causes of soil degradation and to estimate the productivity, profitability, and sustainability of different land uses and farming systems. Another finding was that, in Jhikhu Khola, the deforestation of the 1960s has been abated by reforestation efforts in the 1980s. This has contributed to a 10% expansion of forest cover, and increase of sloping terrace by 9%, and a decline in grazing land by 9% and shrub land by 6%. Calculations for the year 2000 showed that the fuelwood surplus would drop to 6% from 73% and food surplus of 25% would become a 27% deficit. The 40% deficiency in animal feed would increase to 54%. Although reforestation has added to forest cover, pine tree cultivation occurred on moderate elevations where grazing and food production are possible, while higher altitudes on steep slopes were untouched. Workshops are conducted in the villages and efforts are being made to promote the exchange of information between departments. The ultimate solution is to increase agricultural production for profit. PMID:12318008

  5. Losing Ground

    ERIC Educational Resources Information Center

    Eckholm, Erik

    1976-01-01

    Past unsound agricultural practices coupled with drought and high winds eroded away topsoil in the Great Plains. Because of technology and food surpluses productivity returned to the deteriorated lands. Ecosystem overstress could become devastating especially in poor countries as food surpluses and energy decline and populations soar. (MR)

  6. Impact of streambed heterogeneity on hyporheic exchange fluxes under losing and gaining stream flow conditions

    NASA Astrophysics Data System (ADS)

    Fox, Aryeh; Laube, Gerrit; Schmidt, Christian; Fleckenstein, Jan H.; Arnon, Shai

    2015-04-01

    Biogeochemical processes in streams are affected by water exchange between the surface and subsurface environments (e.g. hyporheic exchange). It has previously been shown that hyporheic exchange is strongly affected by the local morphology of the streambed and the flow conditions, including overlying water velocity and losing or gaining fluxes. The objectives of this work were to evaluate how the streambed heterogeneity is affecting hyporheic exchange. In addition, we tested how losing or gaining flow conditions are affecting the hyporheic exchange fluxes and the spatial distribution of the flow paths within the streambed. Experiments measuring the combined effect of streambed heterogeneity and losing and gaining flow conditions on hyporheic exchange were conducted in a laboratory flume system (640 cm long and 30 cm wide). The flow in the flume is fully controlled including gaining or losing fluxes, and it was packed with heterogeneous sediments. An estimate of the solute exchange between the stream and the sediment was obtained from the analysis of a salt tracer (NaCl) injection into the overlying water, which then was monitored by an electrical conductivity meter. In addition, dye injections into the overlying water were used to visualize the effect of sediment heterogeneity on the flow paths in the streambed. Experimental results showed that increasing losing and gaining fluxes resulted in a similar decline in the hyporheic exchange flux as previously observed for a homogenous streambed. However the location in which the hyporheic exchange takes place is different and is strongly influenced by the sediment heterogeneity. The spatial distribution of hyporheic exchange within the streambed will be discussed in light of the distribution of the local, horizontal and vertical hydraulic conductivities.

  7. Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults.

    PubMed

    Ewen, Katherine A; Olesen, Inge A; Winge, Sofia B; Nielsen, Ana R; Nielsen, John E; Graem, Niels; Juul, Anders; Rajpert-De Meyts, Ewa

    2013-01-01

    Observations in patients with an activating mutation of fibroblast growth factor receptor 3 (FGFR3) suggest a role for FGFR3 signalling in promoting proliferation or survival of germ cells. In this study, we aimed to identify the FGFR3 subtype and the ontogeny of expression during human testis development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3 expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis development, expression of FGFR3 did not directly correlate with proliferation markers. In preinvasive CIS cells and in TGCTs, including classical seminoma and embryonal carcinoma, FGFR3IIIc was detected only in a small number of cells, with a heterogeneous expression pattern. FGFR3 is an excellent marker for human pre-/spermatogonia throughout development. Signalling through this receptor is likely associated with spermatogonial survival rather than proliferation. FGFR3 is not expressed in gonocytes and may not be essential to the aetiology of TGCTs stemming from CIS. PMID:23784824

  8. Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading

    PubMed Central

    Farr, Joshua; Cheng, An-Lin; Johnson, Mark L.; Bonewald, Lynda F.

    2016-01-01

    As the β-catenin pathway has been shown to be involved in mechanotransduction, we sought to determine if haploinsufficiency would affect skeletal response to unloading. It has previously been shown that deletion of both alleles of β-catenin in bone cells results in a fragile skeleton highly susceptible to fracture, but deletion of one allele using Dmp1-Cre (Ctnnb1+/loxP; Dmp1-Cre, cKO HET) has little effect on the 2 mo old skeleton. We found that under normal housing conditions, trabecular bone volume was significantly less in 5 mo old male cKO HET mice compared to controls (Ctrl/HET:Tb. BV/TV = 13.96±2.71/8.92±0.95%, Tb.N. = 4.88±0.51/3.95±0.44/mm, Tb. Sp. = 0.20±0.02/0.26±0.03mm, a 36%, 19% and 30% change respectively) but not in females suggesting an age and gender related effect. Before performing suspension experiments and to control for the environmental effects, animals with the same tail attachment and housing conditions, but not suspended (NS), were compared to normally housed (NH) animals. Attachment and housing resulted in weight loss in both genders and phenotypes. Cortical bone loss was observed in the cKO HET males (NH/NS, Ct BV/TV: 90.45±0.72/89.12±0.56%) and both diaphyseal (0.19±0.01/0.17±0.01mm) and metaphyseal (0.10±0.01/0.08±0.01mm) thickness, but not in female cKO HET mice suggesting that male cKO HET mice are susceptible to attachment and housing conditions. These results with transgenic mice emphasizes the importance of proper controls when attributing skeletal responses to unloading. With suspension, cKO HET male mice did not lose bone unlike female cKO HET mice that had greater trabecular bone loss than controls (Ctrl 9%:cKO HET 21% decrease Tb. N; Ctrl 12%:cKO HET 27% increase Tb. Sp.). Suspended and non-suspended mice lost weight compared to normally housed animals. Taken together, the data suggest a protective effect of β-catenin against the effects of stress in males and partial protection against unloading in females

  9. Losing the Dark: Public Outreach about Light Pollution and Its Mitigation

    NASA Astrophysics Data System (ADS)

    Collins Petersen, Carolyn; Petersen, Mark C.; Walker, Constance E.; Kardel, W. Scott; International Dark Sky Association Education Committee

    2015-01-01

    Losing the Dark is a PSA video available for public outreach through fulldome theaters as well as conventional venues (classroom, lecture hall, YouTube, Vimeo). It was created by Loch Ness Productions for the International Dark Sky Association. It explains problems caused by light pollution, which targets astronomy, health, and the environment. Losing the Dark also suggests ways people can implement "wise lighting" practices to help mitigate light pollution. The video is available free of charge for outreach professionals in planetarium facilities (both fulldome and classical), science centers, classroom, and other outreach venues, and has been translated into 13 languages. It is available via download, USB key (at cost), and through online venues. This paper summarizes the program's outreach to more than a thousand fulldome theaters, nearly 100,000 views via four sites on Youtube and Vimeo,a number of presentations at other museum and classroom facilities, and shares some preliminary metrics and commentary from users.

  10. I feel good whether my friends win or my foes lose: Brain mechanisms underlying feeling similarity

    PubMed Central

    Aue, Tatjana

    2014-01-01

    People say they enjoy both seeing a preferred social group succeed and seeing an adversary social group fail. At the same time, they state they dislike seeing a preferred social group fail and seeing an adversary social group succeed. The current magnetic resonance imaging study investigated whether—and if so, how—such similarities in reported feeling states are reflected in neural activities. American football fans anticipated success and failure situations for their favorite or their adversary teams. The data support the idea that feeling similarities and divergences expressed in verbal reports carry with them significant neural similarities and differences, respectively. Desired (favorite team likely to win and adversary team likely to lose) rather than undesired (favorite team likely to lose and adversary team likely to win) outcomes were associated with heightened activity in the supramarginal gyrus, posterior cingulate cortex, insula, and cerebellum. Precuneus activity additionally distinguished anticipated desirable outcomes for favorite versus adversary teams. PMID:24912072

  11. Thoracic Duct Decompression for Protein-Losing Enteropathy in Failing Fontan Circulation.

    PubMed

    António, Marta; Gordo, Andreia; Pereira, Conceição; Pinto, Fátima; Fragata, Isabel; Fragata, José

    2016-06-01

    An infrequent but devastating late complication of Fontan circulation is protein-losing enteropathy (PLE), which results from unbalanced lymphatic homeostasis. Surgical decompression of the thoracic duct by redirecting its drainage to the pulmonary venous atrium has been introduced recently as a possible treatment. This report describes a single-institution experience with this innovative procedure in 2 patients with failing Fontan circulation with PLE refractory to optimized medical therapy. PMID:27211948

  12. Oxygen consumption along bed forms under losing and gaining streamflow conditions

    NASA Astrophysics Data System (ADS)

    De Falco, Natalie; Arnon, Shai; Boano, Fulvio

    2016-04-01

    Recent studies have demonstrated that bed forms are the most significant geomorphological structure that drives hyporheic exchange and biogeochemical processes in stream networks. Other studies also demonstrated that due to the hyporheic flow patterns within bed form, biogeochemical processes do not occur uniformly along and within the bed forms. The objective of this work was to systematically evaluate how losing or gaining flow conditions affect oxygen consumption by biofilm along sandy bed forms. We measured the effects of losing and gaining flow conditions on oxygen consumption by combining modeling and experiments in a novel laboratory flume system that enable the control of losing and gaining fluxes. Oxygen consumption was measured after growing a benthic biofilm fed with Sodium Benzoate (as a carbon source) and measuring the distribution of oxygen in the streambed with microelectrodes. The experimental results were analyzed using a novel code that calculates vertical profiles of reaction rates in the presence of hyporheic water fluxes. These experimental observations and modeling revealed that oxygen distribution varied along the bed forms. The zone of oxygen consumption (i.e. depth of penetration) was the largest at the upstream side of the bed form and the smallest in the lee side (at the lowest part of the bed form), regardless of the flow conditions. Also, the zone of oxygen consumption was the largest under losing conditions, the smallest under gaining conditions, and in-between under neutral conditions. The distribution of oxygen consumption rates determined with our new model will be also discussed. Our preliminary results enable us to show the importance of the coupling between flow conditions and oxygen consumption along bed forms and are expected to improve our understanding of nutrient cycling in streams.

  13. Seizures Associated With Hypocalcemia in a Yorkshire Terrier With Protein-Losing Enteropathy.

    PubMed

    Whitehead, Jim; Quimby, Jessica; Bayliss, Danielle

    2015-01-01

    A 7 yr old, male, castrated, Yorkshire terrier was presented on emergency for an acute onset of seizure activity. The owner also reported that the dog had previously exhibited other symptoms, including intermittent vomiting, diarrhea, and anorexia for several yr. The initial workup revealed a marked decrease in ionized calcium and total protein. Further diagnostics revealed decreases in magnesium, 25 hydroxyvitamin D, albumin, and globulins, and an increased parathyroid hormone level. Intestinal biopsies revealed inflammatory bowel disease and lymphangiectasia. The dog received intravenous calcium gluconate for treatment of hypocalcemia followed by oral calcium and vitamin D supplementation. Seizure activity ceased once calcium levels approached the normal range. Medical and dietary therapy for lymphangiectasia and inflammatory bowel disease consisted of prednisone, rutin, and a low-fat diet. Decreased serum total ionized calcium levels have been reported previously in dogs with protein-losing enteropathies. Typically, the hypocalcemia is not associated with clinical signs. Severe clinical signs of hypocalcemia are rarely reported in dogs with protein-losing enteropathy, but seizures, facial twitching, and tremors can occur. When presented with a dog with a history of seizure activity, panhypoproteinemia, and hypocalcemia, protein-losing enteropathy should be included on the list of differential diagnoses. PMID:26535456

  14. Winning and Losing Tree Species of Reassembly in Minnesota’s Mixed and Broadleaf Forests

    PubMed Central

    Hanberry, Brice B.; Palik, Brian J.; He, Hong S.

    2013-01-01

    We examined reassembly of winning and losing tree species, species traits including shade and fire tolerance, and associated disturbance filters and forest ecosystem types due to rapid forest change in the Great Lakes region since 1850. We identified winning and losing species by changes in composition, distribution, and site factors between historical and current surveys in Minnesota’s mixed and broadleaf forests. In the Laurentian Mixed Forest, shade-intolerant aspen replaced shade-intolerant tamarack as the most dominant tree species. Fire-tolerant white pine and jack pine decreased, whereas shade-tolerant ashes, maples, and white cedar increased. In the Eastern Broadleaf Forest, fire-tolerant white oaks and red oaks decreased, while shade-tolerant ashes, American basswood, and maples increased. Tamarack, pines, and oaks have become restricted to sites with either wetter or sandier and drier soils due to increases in aspen and shade-tolerant, fire-sensitive species on mesic sites. The proportion of shade-tolerant species increased in both regions, but selective harvest reduced the applicability of functional groups alone to specify winners and losers. Harvest and existing forestry practices supported aspen dominance in mixed forests, although without aspen forestry and with fire suppression, mixed forests will transition to a greater composition of shade-tolerant species, converging to forests similar to broadleaf forests. A functional group framework provided a perspective of winning and losing species and traits, selective filters, and forest ecosystems that can be generalized to other regions, regardless of species identity. PMID:23613911

  15. Trying to lose weight among non-overweight university students from 22 low, middle and emerging economy countries.

    PubMed

    Peltzer, Karl; Pengpid, Supa

    2015-01-01

    The aim of this study was to assess the prevalence of trying to lose weight among non-overweight in university students and its sociodemographic and behavioural factors from 22 low and middle income and emerging economy countries. In a cross-sectional survey we took anthropometric measurements and used a self-administered questionnaire among 15997 undergraduate university students (mean age 20.8, Standard deviation=2.8, age range of 16-30 years) from 22 universities in 22 countries. Body mass index (BMI) was used for weight status. Results indicate that 27.1% non-overweight students were trying to lose weight, 34.6% among women and 16.5% among men. Among underweight or normal weight students, 19.0% perceived themselves to be overweight, 11.3% were dieting to lose weight, and 53.5% considered to lose weight of high importance. Multivariate logistic regression found that being female, coming from a low income country, the perception of being overweight, high importance of losing weight, dieting to lose weight, trying to eat fibre, and avoiding foods with fat and cholesterol were associated with trying to lose weight in non-overweight university students. The study found a high prevalence of weight control practices and several specific risk factors were identified that can be utilized in interventions to target unhealthy weight control measures. PMID:25740756

  16. Photo-generated carriers lose energy during extraction from polymer-fullerene solar cells

    PubMed Central

    Melianas, Armantas; Etzold, Fabian; Savenije, Tom J.; Laquai, Frédéric; Inganäs, Olle; Kemerink, Martijn

    2015-01-01

    In photovoltaic devices, the photo-generated charge carriers are typically assumed to be in thermal equilibrium with the lattice. In conventional materials, this assumption is experimentally justified as carrier thermalization completes before any significant carrier transport has occurred. Here, we demonstrate by unifying time-resolved optical and electrical experiments and Monte Carlo simulations over an exceptionally wide dynamic range that in the case of organic photovoltaic devices, this assumption is invalid. As the photo-generated carriers are transported to the electrodes, a substantial amount of their energy is lost by continuous thermalization in the disorder broadened density of states. Since thermalization occurs downward in energy, carrier motion is boosted by this process, leading to a time-dependent carrier mobility as confirmed by direct experiments. We identify the time and distance scales relevant for carrier extraction and show that the photo-generated carriers are extracted from the operating device before reaching thermal equilibrium. PMID:26537357

  17. Photo-generated carriers lose energy during extraction from polymer-fullerene solar cells.

    PubMed

    Melianas, Armantas; Etzold, Fabian; Savenije, Tom J; Laquai, Frédéric; Inganäs, Olle; Kemerink, Martijn

    2015-01-01

    In photovoltaic devices, the photo-generated charge carriers are typically assumed to be in thermal equilibrium with the lattice. In conventional materials, this assumption is experimentally justified as carrier thermalization completes before any significant carrier transport has occurred. Here, we demonstrate by unifying time-resolved optical and electrical experiments and Monte Carlo simulations over an exceptionally wide dynamic range that in the case of organic photovoltaic devices, this assumption is invalid. As the photo-generated carriers are transported to the electrodes, a substantial amount of their energy is lost by continuous thermalization in the disorder broadened density of states. Since thermalization occurs downward in energy, carrier motion is boosted by this process, leading to a time-dependent carrier mobility as confirmed by direct experiments. We identify the time and distance scales relevant for carrier extraction and show that the photo-generated carriers are extracted from the operating device before reaching thermal equilibrium. PMID:26537357

  18. Protein-losing enteropathy associated with refractory systemic lupus erythematosus with a good response to rituximab.

    PubMed

    Sansinanea, Pierina; Carrica, Sebastián Augusto; Marcos, Josefina; García, Mercedes Argentina

    2016-01-01

    A case is presented of a protein-losing enteropathy (PLE) as the initial manifestation of systemic lupus erythematosus (SLE) in a 17 year-old female patient, who presented with ascites, edema and hypoalbuminemia. The diagnosis of SLE was based on the presence of: malar rash, oral ulcers, thrombocytopenia, antinuclear antibodies, IgM anticardiolipin antibody, and lupus anticoagulant. Renal and liver diseases were ruled out. The PLE diagnosis was confirmed with fecal alpha 1-antitrypsin clearance. The PLE was refractory to different lines of immunosuppressive agents like glucocorticoids, cyclophosphamide, azathioprine, and cyclosporine, showing a satisfactory and sustained response with rituximab, allowing steroid sparing and long term remission. PMID:25818375

  19. Mass-losing peculiar red giants - The comparison between theory and observations

    NASA Technical Reports Server (NTRS)

    Jura, M.

    1989-01-01

    The mass loss from evolved red giants is considered. It seems that red giants on the Asymptotic Giant Branch (AGB) are losing between 0.0003 and 0.0006 solar mass/sq kpc yr in the solar neighborhood. If all the main sequence stars between 1 and 5 solar masses ultimately evolve into white dwarfs with masses of 0.7 solar mass, the predicted mass loss rate in the solar neighborhood from these stars is 0.0008 solar mass/sq kpc yr. Although there are still uncertainties, it appears that there is no strong disagreement between theory and observation.

  20. Late post liver transplant protein losing enteropathy: Rare complication of incisional hernia

    PubMed Central

    Evans, Jonathan D; Perera, M Thamara PR; Pal, CY; Neuberger, James; Mirza, Darius F

    2013-01-01

    Development of oedema and hypoproteinaemia in a liver transplant recipient may be the first signs of graft dysfunction and should prompt a full assessment. We report the novel case of a patient who, years after liver transplantation developed a functional blind loop in an incisional hernia, which manifested as oedema and hypoproteinaemia secondary to protein losing enteropathy. After numerous investigations, the diagnosis was made by flurodeoxyglucose positron emmision tomography (FDG-PET) imaging. Surgical repair of the incisional hernia was followed several months later by resolution of the protein loss, and confirmed at a post operative FDG-PET scan at one year. PMID:23885154

  1. Carbon dust particle size distributions around mass-losing AGB stars

    NASA Astrophysics Data System (ADS)

    Jura, M.

    1997-03-01

    Solids of presolar SiC and interstellar carbon have qualitatively similar relative size distribution for particles with radii, a, in the range 0.35 μm0.35 μm are produced by interacting binary systems rather than single mass-losing stars.

  2. Protein-losing nephropathy associated with Borrelia burgdorferi seropositivity in a soft-coated wheaten terrier: Response to therapy

    PubMed Central

    Horney, Barbara S.; Stojanovic, Vladimir

    2013-01-01

    A soft-coated wheaten terrier was examined for lameness with subsequent identification of protein-losing nephropathy, hypoalbuminemia, hyperglobulinemia, and seroconversion to Borrelia burgdorferi. Following doxycycline therapy, the urine protein loss decreased significantly and serum albumin concentration remained close to or within the reference interval for over 3 years, contrary to the reported poor prognosis for renal disease associated with B. burgdorferi or protein-losing nephropathy of soft-coated wheaten terriers. PMID:24082169

  3. How Do Massive Asymptotic Giant Branch Stars Lose All Their Mass?

    NASA Astrophysics Data System (ADS)

    de Vries, B. L.; Blommaert, J. A. D. L.; Waters, L. B. F. M.; Waelkens, C.; Min, M.; Lombaert, R.; Van Winckel, H.

    2015-08-01

    Recent studies have made it increasingly clear that oxygen-rich and massive (≥5 M⊙) asymptotic giant branch (AGB) stars go through only one, short, superwind. Although the superwind was originally introduced for the star to lose enough mass to reach that of a white dwarf, evidence is now building that the superwind lasts too short a time for it to be sufficiently efficient. The integrated mass lost during the whole superwind is not enough to remove the remaining H-rich envelope and terminate the AGB. Studies presented at the conference have shown, from methods based on both gas and dust, that the superwind lasts only ≲1200 years. The analysis of solid-state spectral bands of crystalline olivine (Mg2-2xFe2xSiO4) in the spectra of massive OH/IR stars is a powerful way to determine the extent of the superwind. De Vries, Blommaert, Waters et al. (2014) show that the temperature indicated by the observed 69μm band of crystalline olivine can only be reproduced by models with a geometrically compact superwind (RSW ≲ 2500 AU = 1400 R*). The way by which a star loses its remaining mass after the superwind is unknown. During the conference this problem was discussed and the most likely hypothesis would be a short but very strong phase after the superwind. This hyperwind would have a mass-loss rate of ≳10-3 M⊙/yr.

  4. Application of integral pumping tests to investigate the influence of a losing stream on groundwater quality

    NASA Astrophysics Data System (ADS)

    Leschik, S.; Musolff, A.; Krieg, R.; Martienssen, M.; Bayer-Raich, M.; Reinstorf, F.; Strauch, G.; Schirmer, M.

    2009-06-01

    Losing streams that are influenced by wastewater treatment plant effluents and combined sewer overflows (CSO's) can be a source of groundwater contamination. Released micropollutants such as pharmaceuticals, endocrine disrupters and other ecotoxicologically relevant substances as well as inorganic wastewater constituents can reach the groundwater, where they may deteriorate groundwater quality. This paper presents a method to quantify exfiltration mass flow rates Mex of wastewater constituents from losing streams by the operation of integral pumping tests (IPT's) up- and downstream of a target section. Due to the large sampled water volume during IPT's the results are more reliable than those from conventional point sampling. We applied the method at a test site in Leipzig (Germany). Wastewater constituents K+ and NO3- showed Mex values of 1241 to 4315 and 749 to 924 mg m-1stream d-1, respectively, while Cl- (16.8 to 47.3 g m-1stream d-1) and SO42- (20.3 to 32.2 g m-1stream d-1) revealed the highest observed Mex values at the test site. The micropollutants caffeine and technical-nonylphenol were dominated by elimination processes in the groundwater between upstream and downstream wells. Additional concentration measurements in the stream and a connected sewer at the test site were performed to identify relevant processes that influence the concentrations at the IPT wells.

  5. Application of integral pumping tests to investigate the influence of a losing stream on groundwater quality

    NASA Astrophysics Data System (ADS)

    Leschik, S.; Musolff, A.; Krieg, R.; Martienssen, M.; Bayer-Raich, M.; Reinstorf, F.; Strauch, G.; Schirmer, M.

    2009-10-01

    Losing streams that are influenced by wastewater treatment plant effluents and combined sewer overflows (CSOs) can be a source of groundwater contamination. Released micropollutants such as pharmaceuticals, endocrine disrupters and other ecotoxicologically relevant substances as well as inorganic wastewater constituents can reach the groundwater, where they may deteriorate groundwater quality. This paper presents a method to quantify exfiltration mass flow rates per stream length unit Mex of wastewater constituents from losing streams by the operation of integral pumping tests (IPTs) up- and downstream of a target section. Due to the large sampled water volume during IPTs the results are more reliable than those from conventional point sampling. We applied the method at a test site in Leipzig (Germany). Wastewater constituents K+ and NO3- showed Mex values of 1241 to 4315 and 749 to 924 mg mstream-1 d-1, respectively, while Cl- (16.8 to 47.3 g mstream-1 d-1) and SO42- (20.3 to 32.2 g mstream-1 d-1) revealed the highest observed Mex values at the test site. The micropollutants caffeine and technical-nonylphenol were dominated by elimination processes in the groundwater between upstream and downstream wells. Additional concentration measurements in the stream and a connected sewer at the test site were performed to identify relevant processes that influence the concentrations at the IPT wells.

  6. Changes in the morphology and protein expression of germ cells and Sertoli cells in plateau pikas testes during non-breeding season.

    PubMed

    Liu, Ming; Cao, Guangming; Zhang, Yanming; Qu, Jiapeng; Li, Wei; Wan, Xinrong; Li, Yu-Xia; Zhang, Zhibin; Wang, Yan-Ling; Gao, Fei

    2016-01-01

    Plateau pikas are seasonally breeding small herbivores that inhabit the meadow ecosystem of the Qinghai-Tibetan Plateau. Testis regression in plateau pikas begins in early June, and the male pikas are completely infertile, with a dramatically reduced testis size, in late July. In this study, a decreased germ cell number in the testes was first noted in early June. By late June, only Sertoli cells and a small number of spermatogonia remained. Interestingly, large gonocyte-like germ cells were observed in early July. In late July, the number of gonocyte-like cells per tubule increased significantly, and most of the Sertoli cell nuclei moved to and clustered in the center of the seminiferous tubules. The gonocyte-like germ cells and Sertoli cells began to express AP-2γ and anti-Mullerian hormone (AMH) proteins, which were detected in the germ cells and Sertoli cells of juvenile pikas but not in adult testes. Simultaneously, LC3 puncta dramatically increased in the seminiferous tubules of the pikas' testes during the non-breeding season. Our study found that spermatogonia and Sertoli cells in non-breeding adult pikas morphologically resembled those in juvenile pikas and expressed specific markers, indicating that de-differentiation-like transitions may occur during this process. PMID:26939551

  7. Changes in the morphology and protein expression of germ cells and Sertoli cells in plateau pikas testes during non-breeding season

    PubMed Central

    Liu, Ming; Cao, Guangming; Zhang, Yanming; Qu, Jiapeng; Li, Wei; Wan, Xinrong; Li, Yu-xia; Zhang, Zhibin; Wang, Yan-ling; Gao, Fei

    2016-01-01

    Plateau pikas are seasonally breeding small herbivores that inhabit the meadow ecosystem of the Qinghai-Tibetan Plateau. Testis regression in plateau pikas begins in early June, and the male pikas are completely infertile, with a dramatically reduced testis size, in late July. In this study, a decreased germ cell number in the testes was first noted in early June. By late June, only Sertoli cells and a small number of spermatogonia remained. Interestingly, large gonocyte-like germ cells were observed in early July. In late July, the number of gonocyte-like cells per tubule increased significantly, and most of the Sertoli cell nuclei moved to and clustered in the center of the seminiferous tubules. The gonocyte-like germ cells and Sertoli cells began to express AP-2γ and anti-Mullerian hormone (AMH) proteins, which were detected in the germ cells and Sertoli cells of juvenile pikas but not in adult testes. Simultaneously, LC3 puncta dramatically increased in the seminiferous tubules of the pikas’ testes during the non-breeding season. Our study found that spermatogonia and Sertoli cells in non-breeding adult pikas morphologically resembled those in juvenile pikas and expressed specific markers, indicating that de-differentiation-like transitions may occur during this process. PMID:26939551

  8. Application of Integral Pumping Tests to estimate the influence of losing streams on groundwater quality

    NASA Astrophysics Data System (ADS)

    Leschik, S.; Musolff, A.; Reinstorf, F.; Strauch, G.; Schirmer, M.

    2009-05-01

    Urban streams receive effluents of wastewater treatment plants and untreated wastewater during combined sewer overflow events. In the case of losing streams substances, which originate from wastewater, can reach the groundwater and deteriorate its quality. The estimation of mass flow rates Mex from losing streams to the groundwater is important to support groundwater management strategies, but is a challenging task. Variable inflow of wastewater with time-dependent concentrations of wastewater constituents causes a variable water composition in urban streams. Heterogeneities in the structure of the streambed and the connected aquifer lead, in combination with this variable water composition, to heterogeneous concentration patterns of wastewater constituents in the vicinity of urban streams. Groundwater investigation methods based on conventional point sampling may yield unreliable results under these conditions. Integral Pumping Tests (IPT) can overcome the problem of heterogeneous concentrations in an aquifer by increasing the sampled volume. Long-time pumping (several days) and simultaneous sampling yields reliable average concentrations Cav and mass flow rates Mcp for virtual control planes perpendicular to the natural flow direction. We applied the IPT method in order to estimate Mex of a stream section in Leipzig (Germany). The investigated stream is strongly influenced by combined sewer overflow events. Four pumping wells were installed up- and downstream of the stream section and operated for a period of five days. The study was focused on four inorganic (potassium, chloride, nitrate and sulfate) and two organic (caffeine and technical-nonylphenol) wastewater constituents with different transport properties. The obtained concentration-time series were used in combination with a numerical flow model to estimate Mcp of the respective wells. The difference of the Mcp's between up- and downstream wells yields Mex of wastewater constituents that increase

  9. Comparison of game-related statistics in men's international championships between winning and losing teams according to margin of victory.

    PubMed

    Saavedra, Jose M; Escalantel, Yolanda; Madera, Joaquin; Mansilla, Mirella; García-Hermoso, Antonio

    2014-09-01

    The aims of this study were (i) to compare water polo game-related statistics by game outcome (winning and losing teams) and margins of victory (close games, unbalanced games, and very unbalanced games), and (ii) to identify characteristics that mark the differences in performances for each group of margin of victory. The game-related statistics of the 308 men's matches played in seven International Championships (Olympic Games, World and European Championships) were analysed. A cluster analysis established three groups (close games, unbalanced games, and very unbalanced games) according to the margin of victory. Differences between game outcomes (winning or losing teams) and margins of victory (close, unbalanced, and very unbalanced games) were determined using the chi-squared statistic, also calculating the effect sizes of the differences. A discriminant analysis was then performed applying the sample-splitting method according to game outcome (winning and losing teams) by margin of victory. It was found that the game-related statistics differentiate the winning from the losing teams in each final score group, with 7 (offensive and defensive) variables differentiating winners from losers in close games, 16 in unbalanced games, and 11 in very unbalanced games. In all three types of game, the game-related statistics were shown to discriminate performance (85% or more), with two variables being discriminatory by game outcome (winning or losing teams) in all three cases: shots and goalkeeper-blocked shots. PMID:25420372

  10. Comparison of game-related statistics in men's international championships between winning and losing teams according to margin of victory.

    PubMed

    Saavedra, Jose M; Escalantel, Yolanda; Madera, Joaquin; Mansilla, Mirella; García-Hermoso, Antonio

    2014-09-01

    The aims of this study were (i) to compare water polo game-related statistics by game outcome (winning and losing teams) and margins of victory (close games, unbalanced games, and very unbalanced games), and (ii) to identify characteristics that mark the differences in performances for each group of margin of victory. The game-related statistics of the 308 men's matches played in seven International Championships (Olympic Games, World and European Championships) were analysed. A cluster analysis established three groups (close games, unbalanced games, and very unbalanced games) according to the margin of victory. Differences between game outcomes (winning or losing teams) and margins of victory (close, unbalanced, and very unbalanced games) were determined using the chi-squared statistic, also calculating the effect sizes of the differences. A discriminant analysis was then performed applying the sample-splitting method according to game outcome (winning and losing teams) by margin of victory. It was found that the game-related statistics differentiate the winning from the losing teams in each final score group, with 7 (offensive and defensive) variables differentiating winners from losers in close games, 16 in unbalanced games, and 11 in very unbalanced games. In all three types of game, the game-related statistics were shown to discriminate performance (85% or more), with two variables being discriminatory by game outcome (winning or losing teams) in all three cases: shots and goalkeeper-blocked shots. PMID:25507356

  11. The risk of losing 10 years of life put in perspective: views of college student smokers.

    PubMed

    Chuang, Shu-Hui; Huang, Song-Lih

    2015-03-01

    Health messages have limited effects on young smokers. The health effects typically have long latent periods, and the appreciation of risk depends on the meaning given to longevity. This study aims to understand how college student smokers interpreted the risks of losing 10 years of life because of smoking. In-depth semistructured interviews were conducted with 23 male smokers from a relatively low-achieving college in southern Taiwan. The participants had vague ideas about the future; were not expecting a successful life, thought life was stressful and boring; and expressed that there was no need to live too long. Many believed that removing the stress and having a composed lifestyle was the way to becoming healthy, which could be achieved only by people with economic success. They would quit had they been rich. Empowerment to help young smokers gain control over their life events may be the key to tobacco control. PMID:23695539

  12. Disseminated mycobacterium avium complex as protein-losing enteropathy in a non-HIV patient.

    PubMed

    Konjeti, Venkata Rajesh; Paluri, Sravanthi

    2014-01-01

    Disseminated mycobacterium avium complex (MAC) causing protein-losing enteropathy (PLE) due to intestinal lymphangiectasia (IL) in a non-HIV immunocompromised state is extremely rare. We present a case of 56-year-old male who was evaluated for worsening dyspnea and found to have right-sided chylous pleural effusion as well as worsening abdominal and retroperitoneal lymphadenopathy. He had a history of psoriasis for which hewas on etanercept and alefacept which were stopped two years prior to the presentation. The evaluation revealed a MAC infection in his lymph nodes--a low CD4 count but negative for HIV. He was started on MAC therapy. He subsequently developed noninfectious diarrhea, Hypoalbuminemia, recurrentpleural effusions, ascites, and Pneumocystis jiroveci pneumonia (PJP). Despite appropriate antibiotics and management--including total parental nutrition (TPN) with a medium-chain triglyceride enriched low fat diet--the patient's clinical condition deteriorated rapidly resulting in death. PMID:25672059

  13. Sociocultural influences on strategies to lose weight, gain weight, and increase muscles among ten cultural groups.

    PubMed

    McCabe, Marita P; Busija, Lucy; Fuller-Tyszkiewicz, Matthew; Ricciardelli, Lina; Mellor, David; Mussap, Alexander

    2015-01-01

    This study determined how sociocultural messages to change one's body are perceived by adolescents from different cultural groups. In total, 4904 adolescents, including Australian, Chilean, Chinese, Indo-Fijian, Indigenous Fijian, Greek, Malaysian, Chinese Malaysian, Tongans in New Zealand, and Tongans in Tonga, were surveyed about messages from family, peers, and the media to lose weight, gain weight, and increase muscles. Groups were best differentiated by family pressure to gain weight. Girls were more likely to receive the messages from multiple sociocultural sources whereas boys were more likely to receive the messages from the family. Some participants in a cultural group indicated higher, and others lower, levels of these sociocultural messages. These findings highlight the differences in sociocultural messages across cultural groups, but also that adolescents receive contrasting messages within a cultural group. These results demonstrate the difficulty in representing a particular message as being characteristic of each cultural group. PMID:25497878

  14. Evaluation of the "Lose Your Excuse" public service advertising campaign for tweens to save energy.

    PubMed

    Bertrand, Jane T; Goldman, Patty; Zhivan, Natalia; Agyeman, Yaw; Barber, Erin

    2011-10-01

    This study evaluates the 2008-2009 "Lose your Excuse" public service advertising (PSA) campaign on energy efficiency targeting 8- to 12-year-olds, intended to increase knowledge, foster proactive attitudes, and change energy usage behaviors. Baseline and two follow-up surveys were conducted with online samples representative of the national population of households with kids with online access. Almost half (47%) of the tweens recognized at least one ad from the campaign. Ad recognition was positively associated with knowledge, proactive attitudes, and energy-saving behavior. Propensity score analysis confirmed a small but measurable and statistically significant effect on energy-saving behavior. The discussion section compares these results to public health campaigns in terms of ghost awareness, reach, and effect size. PMID:22167204

  15. Coal slurry lobby loses again: but believes time is on its side

    SciTech Connect

    Madison, C.

    1980-10-11

    Time favors the Slurry Transport Association's attempts to overcome railroad and railroad-union opposition and gain legislative support for coal-slurry pipelines. The long-standing support for railroads in Congress has so far successfully blocked the efforts of a coalition of slurry lobbyists to develop an alternative method of coal transport. Pipeline sponsors seek eminent domainright to cross railroad rights-of-way, but the railroads feel they cannot afford to lose even 20 percent of their profitable coal freight. At issue is whether coal should guarantee a monopoly to the railroads at the expense of national energy needs, policies which mandate coal substitution for oil and gas, and coal exports. Union lobbyists impress legislators with the impact of pipelines on employees even though Congress recently deregulated the railroads. (DCK)

  16. Integrated Hydrogeological Investigation on the Vulnerability of a Pumping Station at a Losing Stream

    NASA Astrophysics Data System (ADS)

    Ngueleu Kamangou, Stephane; Vogt, Tobias; Cirpka, Olaf

    2010-05-01

    River restoration usually includes alteration of the river channel morphology. Thereby the interaction between river and groundwater can be modified. For the design of a river restoration project - especially in the vicinity of a groundwater pumping well for drinking water production - this impact must be predicted. But a good prediction requires a proper understanding of the existing situation. Numerical models help to improve the strategy of a successful river restoration project. The main objective of this study was to investigate the vulnerability of a pumping station located at losing river in northeast Switzerland. Besides the effect that river restoration could create, a particular attention was placed on the effect of a beaver dam in a side channel close to the pumping station. Analysis of field measurements coupled with numerical modeling of the pumping station area improved the understanding of the interactions in the river corridor between the river, side channels and the alluvial aquifer.

  17. Do stars that lose mass expand or contract? A semianalytical approach

    NASA Technical Reports Server (NTRS)

    Heisler, J.; Alcock, C.

    1986-01-01

    Semianalytic methods are used to determine whether a star of polytropic index n expands or contracts following an insentropic loss of mass. It is found that most stars shrink, including radiative stars which can be approximated by polytropes of index roughly three. However, stars that have a ratio of specific heats gamma only slightly larger than 1 + 1/n do expand if the perturbation of the core density is sufficiently large. For stars that shrink, the fractional change in the radius is not a linear function of the fractional change in mass. Using Lane's theorem, it is shown that a star with gamma = 4/3 cannot lose mass isentropically, although the radius increases if the core density is reduced.

  18. Cortical topography of event-related potentials to winning and losing in a video tennis game.

    PubMed

    Ivanitsky, A M; Kurnitskaya, I V; Sobotka, S

    1986-07-01

    The event-related potentials (ERP) in frontal and posterior associative cortex in right and left hemispheres were studied in two different outcomes of a television tennis game. These outcomes were 'win' and 'loss' of the ball, the first serving as a model of positive, the second as a model of negative emotional reactions. The ERPs consisted of 4 waves: P300, N600, P800, N1000. The most characteristic interhemispheric difference for 'win' was an increase of N600 in the left posterior associative cortex, and for 'loss', a decrease of P800 in the right frontal area. Thus, the positive and negative emotional reactions have specific spatio-temporal cortical organizations. The topography of ERP related to positive and negative emotions was disturbed in depressive patients. The patients revealed a larger negativity of the right posterior associative cortex and the left frontal cortex waves both at winning and losing the ball. PMID:3733492

  19. Differential gauging and tracer tests resolve seepage fluxes in a strongly-losing stream

    NASA Astrophysics Data System (ADS)

    Ruehl, C.; Fisher, A. T.; Hatch, C.; Huertos, M. Los; Stemler, G.; Shennan, C.

    2006-10-01

    SummaryThe Pajaro River, central coastal California, consistently loses 0.2-0.4 m 3/s of discharge along an 11.42-km experimental reach late in the water year, when discharge is ⩽4.5 m 3/s. Channel loss occurs throughout this reach, but is greatest in magnitude near the bottom of the reach. Water isotopic data and other observations suggest that channel loss results mainly from streambed seepage, as opposed to evapotranspiration. If it occurs throughout the year, the channel loss along this short stream reach could contribute 6-13 × 10 6 m 3 of annual aquifer recharge, or ˜20-40% of current sustainable basin yield. We performed a series of tracer injections along this reach to determine if hydrologic exchange occurs within this strongly-losing stream. We found that during periods of high channel loss, there were also comparable storage exchange fluxes and lateral inflow of tracer-free water. Within upper and lower parts of the experimental reach, storage exchange fluxes are about 10 times greater than lateral inflow. The former are associated with the movement of water between the main channel and surface or subsurface storage zones. In this system, it is likely that the latter are primarily associated with spatially- or temporally-long subsurface flow paths within the shallow streambed, as opposed to inflow of ground water from deeper in the basin. Along both upper and lower parts of the experimental reach, lateral inflow tends to increase as channel discharge decreases. In contrast, storage exchange fluxes increase with decreasing discharge along the upper parts of the reach, but decrease with decreasing discharge along the lower parts. Gauging and tracer test results suggest that subsurface storage exchange and loss may occur simultaneously, and that the lateral inflow of tracer-free water can be caused by long-scale subsurface flow as well as ground water making its first appearance in the channel.

  20. Thermal regime of dune-covered sediments under gaining and losing water bodies

    NASA Astrophysics Data System (ADS)

    Cardenas, M. Bayani; Wilson, John L.

    2007-12-01

    We investigate the effects of current-bed form induced flow and heat transport through permeable-bottom sediments overlain by a marine or terrestrial water column that is gaining or losing deep groundwater. Heat transport is forced by the diel variation of temperature in the water column. The investigation utilizes sequentially coupled simulations of turbulent flow in the water column, and Darcy flow and heat transport in the sediments. The simulations address the question when, where, and by how much are diel water column temperature variations transmitted into sediments subjected to ambient-groundwater discharge? This is crucial information for detecting, observing, and predicting temperature-sensitive biogeochemical and ecological processes in the bottom sediments. When the groundwater gain or loss is small, it has no appreciable effect on temperatures in the sediments, which are controlled by heat conduction and current-bed form induced heat advection. As losing discharge increases, the temperature signal from the water column penetrates deeper into the sediments, with the largest temperature variations found under a downwelling zone along the stoss side of the bed form and damped temperature variations found near a narrow upwelling zone below the crest. Similar patterns are observed under gaining conditions, but with temperature variations penetrating to shallower depths; the interfacial exchange zone is diminished by upward movement of deep groundwater. Large gains or losses of deep groundwater prevent the formation of an interfacial exchange zone making heat transport almost vertically one-dimensional. The sensitivity of the sediment-thermal regime to hydrodynamic conditions increases with increasing water column current (Reynolds number) and with sediment permeability.

  1. Isolation and Identification of Prepubertal Buffalo (Bubalus bubalis) Spermatogonial Stem Cells.

    PubMed

    Feng, Wanyou; Chen, Shibei; Do, Dagiang; Liu, Qinyou; Deng, Yanfei; Lei, Xiaocan; Luo, Chan; Huang, Ben; Shi, Deshun

    2016-10-01

    Isolation and culture of spermatogonial stem cells (SSCs) are attractive for production of genetic modified offspring. In the present study, buffalo spermatogonial stem-like cells were isolated, cultured and expression pattern of different germ cell marker genes were determined. To recover spermatogonia, testes from age 3 to 7 months of buffalo were decapsulated, and seminiferous tubules were enzymatically dissociated. Two types of cells, immature sertoli cell and type A spermatogonia were observed in buffalo testes in this stage. Germ cell marker genes, OCT3/4 (Pou5f1), THY-1, c-kit, PGP9.5 (UCHL-1) and Dolichos biflorus agglutinin, were determined to be expressed both in mRNA and protein level by reverse transcription polymerase chain reaction and immunostaining in buffalo testes and buffalo spermatogonial stem-like cells, respectively. In the following, when the isolated buffalo buffalo spermatogonial stem-like cells were cultured in the medium supplemented 2.5% fetal bovine serum and 40 ng/mL glial cell-derived neurotrophic factor medium, SSCs proliferation efficiency and colony number were significantly improved than those of other groups (p<0.05). These findings may help in isolation and establishing long term in vitro culture system for buffalo spermatogonial stem-like cells, and accelerating the generation of genetic modified buffaloes. PMID:26954139

  2. Gaining, losing, and dry stream reaches at Bear Creek Valley, Oak Ridge, Tennessee, March and September 1994

    SciTech Connect

    Robinson, J.A.; Mitchell, R.L. III

    1996-12-31

    A study was conducted, to delineate stream reaches that were gaining flow, losing flow, or that were dry in the upper reaches of Bear Creek Valley near the Y-12 Plant in Oak Ridge, Tennessee. The study included a review of maps and discharge data from a seepage investigation conducted at Bear Creek Valley; preparation of tables showing site identification and discharge and stream reaches that were gaining flow, losing flow, or that were dry; and preparation of maps showing measurement site locations and discharge measurements, and gaining, losing, and dry stream reaches. This report will aid in developing a better understanding of ground-water and surface-water interactions in the upper reaches of Bear Creek.

  3. A point-by-point analysis of performance in a fencing match: psychological processes associated with winning and losing streaks.

    PubMed

    Doron, Julie; Gaudreau, Patrick

    2014-02-01

    This study aimed to revisit the complex nature of serial dependency of performance during a match, examining the prospective associations between psychological processes and subsequent performance at the within-person level of analysis, and explore whether psychological processes are associated with the likelihood of winning series of points. A process-oriented sequential approach was used with 16 elite fencers during a simulated competition. Multilevel regression analyses revealed that serial dependency of performance fluctuates within a match. Results of a Bayesian multilevel structural equation model showed that prior performance subsequently influenced psychological processes. Although psychological processes did not predict performance in the subsequent point, successive winnings were associated with higher perceived control and task-oriented coping and lower negative affectivity compared with both losing streaks and nonstreaks. Overall, serial dependencies of performance are nonstationary during a match whereas psychological processes significantly differ in episodes of winning after winning versus losing after losing. PMID:24501140

  4. NANOG promoter methylation and expression correlation during normal and malignant human germ cell development

    PubMed Central

    Nettersheim, Daniel; Bierman, Katharina; Gillis, Ad JM; Steger, Klaus; Looijenga, Leendert HJ

    2011-01-01

    Testicular germ cell tumors are the most frequent malignant tumors in young Caucasian males, with increasing incidence. The actual model of tumorigenesis is based on the theory that a block in maturation of fetal germ cells lead to formation of the intratubular germ cell neoplasia unclassified. Early fetal germ cells and undifferentiated germ cell tumors express pluripotency markers such as the transcription factor NANOG. It has been demonstrated that epigenetic modifications, such as promoter DNA methylation, are able to silence gene expression in normal and cancer cells. Here we show that OCT3/4-SOX2 mediated expression of NANOG can be silenced by methylation of promoter CpG-sites. We found that global methylation of DNA decreased from fetal spermatogonia to mature sperm. In contrast, CpGs in the NANOG promoter were found hypomethylated in spermatogonia and hypermethylated in sperm. This selective repression might reflect the cells need to suppress pluripotency in order to prevent malignant transformation. Finally, methylation of CpGs in the NANOG promoter in germ cell tumors and derived cell lines correlated to differentiation state. PMID:20930529

  5. The actin-binding protein profilin is required for germline stem cell maintenance and germ cell enclosure by somatic cyst cells

    PubMed Central

    Shields, Alicia R.; Spence, Allyson C.; Yamashita, Yukiko M.; Davies, Erin L.; Fuller, Margaret T.

    2014-01-01

    Specialized microenvironments, or niches, provide signaling cues that regulate stem cell behavior. In the Drosophila testis, the JAK-STAT signaling pathway regulates germline stem cell (GSC) attachment to the apical hub and somatic cyst stem cell (CySC) identity. Here, we demonstrate that chickadee, the Drosophila gene that encodes profilin, is required cell autonomously to maintain GSCs, possibly facilitating localization or maintenance of E-cadherin to the GSC-hub cell interface. Germline specific overexpression of Adenomatous Polyposis Coli 2 (APC2) rescued GSC loss in chic hypomorphs, suggesting an additive role of APC2 and F-actin in maintaining the adherens junctions that anchor GSCs to the niche. In addition, loss of chic function in the soma resulted in failure of somatic cyst cells to maintain germ cell enclosure and overproliferation of transit-amplifying spermatogonia. PMID:24346697

  6. A case of protein supplement effect in protein-losing enteropathy.

    PubMed

    Lee, Hyun Jeong; Rha, Mi Yong; Cho, Young Yun; Kim, Eun Ran; Chang, Dong Kyung

    2012-07-01

    The objective of this article is to report improvement of nutritional status by protein supplements in the patient with protein-losing enteropathy. The patient was a female whose age was 25 and underwent medical treatment of Crohn's disease, an inflammatory bowl disease, after diagnosis of cryptogenic multifocal ulcerous enteritis. The weight was 33.3 kg (68% of IBW) in the severe underweight and suffered from ascites and subcutaneous edema with hypoalbuminemia (1.3 g/dL) at the time of hospitalization. The patient consumed food restrictively due to abdominal discomfort. Despite various attempts of oral feeding, the levels of calorie and protein intake fell into 40-50% of the required amount, which was 800-900 kcal/d (24-27 kcal/kg/d) for calorie and 34 g/d (1 g/kg/d) for protein. It was planned to supplement the patient with caloric supplementation (40-50 kcal/kg) and protein supplementation (2.5 g/kg) to increase body weight and improve hypoproteinemia. It was also planned to increase the level of protein intake slowly to target 55 g/d in about 2 weeks starting from 10 g/d and monitored kidney load with high protein supplementation. The weight loss was 1.0 kg when the patient was discharged from the hospital (hospitalization periods of 4 weeks), however, serum albumin was improved from 1.3 g/dL to 2.5 g/dL and there was no abdominal discomfort. She kept supplement of protein at 55 g/d for 5 months after the discharge from the hospital and kept it at 35 g/d for about 2 months and then 25 g/d. The body weight increased gradually from 32.3 kg (65% of IBW) to 44.0 kg (89% of IBW) by 36% for the period of F/u and serum albumin was kept above 2.8 g/dL without intravenous injection of albumin. The performance status was improved from 4 points of 'very tired' to 2 points of 'a little tired' out of 5-point scale measurement and the use of diuretic stopped from the time of 4th month after the discharge from the hospital owing to improvement in edema and ascites. During

  7. Adaptive reduction in thermogenesis and resistance to lose fat in obese men.

    PubMed

    Tremblay, Angelo; Chaput, Jean-Philippe

    2009-08-01

    Adaptive thermogenesis is defined as a greater than predicted change in energy expenditure in response to changes in energy balance. This issue is particularly relevant in the context of a weight-reducing programme in which diminished thermogenesis can be sufficient to compensate for a prescribed decrease in daily energy intake. In the present pilot study, we investigated the adaptive reduction in thermogenesis in resting state that appears to favour resistance to further weight loss. Eight obese men (mean BMI: 33.4 kg/m2, mean age: 38 years) participated in this repeated-measures, within-subject, clinical intervention. They were subjected to a weight-loss programme that consisted of a supervised diet (-2930 kJ/d) and exercise clinical intervention. The phases investigated were as follows: (i) baseline, (ii) after 5 (SE 1) kg loss of body weight (phase 1), (iii) after 10 (SE 1) kg weight loss (phase 2) and (iv) at resistance to further weight loss (plateau). At each phase of the weight-reducing programme, body weight and composition as well as RMR were measured. A regression equation was established in a control population of the same age to predict RMR in obese men at each phase of the weight-loss programme. We observed that body weight and fat mass (FM) were significantly reduced (P < 0.05), while fat-free mass remained unchanged throughout the programme. In phase 1, measured RMR had fallen by 418 kJ/d, more than predicted (P < 0.05), and this difference reached 706 kJ/d at plateau (P < 0.05 v. phase 1). A positive association (r 0.64, P < 0.05) was observed between the reduction in thermogenesis and the degree of FM depletion at plateau. The adaptive reduction in thermogenesis at plateau was substantial and represented 30.9% of the compensation in energy balance that led to resistance to further lose body weight. In conclusion, these results show that adaptive reduction in thermogenesis may contribute to the occurrence of resistance to lose fat in obese men

  8. 40 CFR 266.355 - How could you lose the transportation and disposal conditional exemption for your waste and what...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false How could you lose the transportation and disposal conditional exemption for your waste and what actions must you take? 266.355 Section 266.355 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF...

  9. 40 CFR 266.355 - How could you lose the transportation and disposal conditional exemption for your waste and what...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false How could you lose the transportation....355 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED... may endanger human health or the environment, you must also immediately notify us orally within...

  10. Associations of Trying to Lose Weight, Weight Control Behaviors, and Current Cigarette Use among US High School Students

    ERIC Educational Resources Information Center

    Johnson, Jonetta L.; Eaton, Danice K.; Pederson, Linda L.; Lowry, Richard

    2009-01-01

    Background: Approximately one-quarter of high school students currently use cigarettes. Previous research has suggested some youth use smoking as a method for losing weight. The purpose of this study was to describe the association of current cigarette use with specific healthy and unhealthy weight control practices among 9th-12th grade students…

  11. 25 CFR 115.430 - Will your account lose its supervised status when you reach the age of 18?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... reach the age of 18? 115.430 Section 115.430 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... Will your account lose its supervised status when you reach the age of 18? Your account will no longer be supervised when you reach the age of 18 unless statutory language or a tribal resolution...

  12. 25 CFR 115.430 - Will your account lose its supervised status when you reach the age of 18?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... reach the age of 18? 115.430 Section 115.430 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... Will your account lose its supervised status when you reach the age of 18? Your account will no longer be supervised when you reach the age of 18 unless statutory language or a tribal resolution...

  13. The Experience of Receiving and Then Losing a Scholarship: A Tracer Study of Secondary School Scholarship Recipients in Uganda

    ERIC Educational Resources Information Center

    Watson, Cathy; Chapman, David W.; Okurut, Charles Opolot

    2014-01-01

    This study reports findings of a tracer that investigated differences in the profile and subsequent experiences of scholarship recipients in Uganda who were able to complete the lower secondary school cycle (O level) without interruption (N = 174) and those that dropped out before completing their O-level cycle (N = 51), thereby losing their…

  14. Losing Chlordimeform Use in Cotton Production. Its Effects on the Economy and Pest Resistance. Agricultural Economic Report Number 587.

    ERIC Educational Resources Information Center

    Osteen, Craig; Suguiyama, Luis

    This report examines the economic implications of losing chlordimeform use on cotton and considers chlordimeform's role in managing the resistance of bollworms and tobacco budworms to synthetic pyrethroids. It estimates changes in prices, production, acreage, consumer expenditures, aggregate producer returns, regional crop effects, and returns to…

  15. Successful therapy for protein-losing enteropathy caused by chronic neuronopathic Gaucher disease

    PubMed Central

    Mhanni, A.A.; Kozenko, M.; Hartley, J.N.; Deneau, M.; El-Matary, W.; Rockman-Greenberg, C.

    2015-01-01

    Gaucher disease (OMIM #230800) is caused by β-glucosidase deficiency and primarily involves the mononuclear phagocyte system (also called Reticuloendothelial System or Macrophage System). The disease is classified into three main phenotypes based on the presence or absence of neurological manifestations: non-neuronopathic (type 1), acute neuronopathic (type 2) and chronic neuronopathic (type 3). Typical manifestations include hepatosplenomegaly, skeletal deformities, hematological abnormalities, interstitial lung fibrosis and neurodegeneration in neuronopathic cases. Mesenteric lymphadenopathy with resultant protein losing enteropathy (PLE) has only been rarely described. Mesenteric lymphadenopathy may lead to intestinal lymphatic obstruction and secondary lymphangiectasia resulting in chronic diarrhea, abdominal pain and weight loss. Fecal protein loss with secondary hypoalbuminemia can be significant. We report a male with Chronic Neuronopathic Gaucher disease (GD) (homozygous for c.1448T > C (NM_000157.3) GBA mutation) who at 16 years of age developed intractable abdominal pain, diarrhea and weight loss. This was caused by PLE secondary to intestinal lymphangiectasia caused by calcified mesenteric lymphadenopathy despite prior long term enzyme replacement therapy (ERT) and/or substrate reduction therapy (SRT). His older similarly affected sister who had been receiving treatment with ERT and/or SRT remains stable on these treatments with no evidence of mesenteric lymphadenopathy. Medical management with total parenteral nutrition, daily medium chain triglyceride-oil (MCT) supplementation, low dose oral budesonide, continued oral SRT and an increased dose of parenteral ERT has stabilized his condition with resolution of the gastrointestinal symptoms and appropriate weight gain. PMID:27014572

  16. Gaining pounds by losing pounds: preferences for lifestyle interventions to reduce obesity.

    PubMed

    Ryan, Mandy; Yi, Deokhee; Avenell, Alison; Douglas, Flora; Aucott, Lorna; van Teijlingen, Edwin; Vale, Luke

    2015-04-01

    While there is evidence that weight-loss interventions reduce morbidity, indications of their acceptability are limited. Understanding preferences for lifestyle interventions will help policymakers design interventions. We used a discrete choice experiment to investigate preferences for lifestyle interventions to reduce adult obesity. Attributes focused on: the components of the programme; weight change; short-term and longer-term health gains; time spent on the intervention and financial costs incurred. Data were collected through a web-based questionnaire, with 504 UK adults responding. Despite evidence that dietary interventions are the most effective way to lose weight, respondents preferred lifestyle interventions involving physical activity. While the evidence suggests that behaviour change support improves effectiveness of interventions, its value to participants was limited. A general preference to maintain current lifestyles, together with the sensitivity of take up to financial costs, suggests financial incentives could be used to help maximise uptake of healthy lifestyle interventions. An important target group for change, men, required more compensation to take up healthier lifestyles. Those of normal weight, who will increase in weight over time if they do not change their lifestyle, required the highest compensation. Policymakers face challenges in inducing people to change their behaviour and adopt healthy lifestyles. PMID:25348049

  17. Protein-losing enteropathy cured by resection of adenomatous goiter: report of a case.

    PubMed

    Takada, Jun; Araki, Hiroshi; Kubota, Masaya; Ibuka, Takashi; Shiraki, Makoto; Shimizu, Masahito; Moriwaki, Hisataka

    2015-06-01

    A 51-year-old Japanese woman presented to our hospital with systemic edema and general fatigue. Her serum albumin level was very low (1.5 g/dL). Technetium-99 m-human serum albumin ((99m)Tc-HSA) scintigraphy showed albumin leakage from the upper small bowel. Magnetic resonance lymphangiography showed dilated lymphatic vessels in the chest, whereas double-balloon enteroscopy (DBE) showed white villi and chyle leakage in the deeper part of the duodenal mucosa. A duodenal mucosa biopsy specimen revealed lymphangiectasia. She was diagnosed with protein-losing enteropathy (PLE). Treatment with a fat-restricted diet and tranexamic acid--previously reported to be effective against PLE--was attempted, but was ineffective. A thyroid tumor was simultaneously detected in her left neck, and was found to extend to the mediastinum on computed tomography. The tumor (size, >5 cm) was resected, and a pathological diagnosis of adenomatous goiter was made. The patient's serum albumin level increased to normal levels within 1 month postoperatively. After 6 months, (99m)Tc-HSA scintigraphy showed no albumin leakage from the gastrointestinal tract, and disappearance of white villi and chyle leakage on DBE. No lymphangiectasia was noted in the biopsy specimen. Adenomatous goiter was thus considered the cause of the PLE, possibly through lymph flow obstruction in the mediastinum. PMID:25845937

  18. Tactical metrics that discriminate winning, drawing and losing teams in UEFA Euro 2012®.

    PubMed

    Winter, Christian; Pfeiffer, Mark

    2016-01-01

    The objectives of this article are twofold: first, an innovative approach to notational analysis in football is outlined. By considering the important theoretical requirements for the analysis of sports games (like the interaction between two parties, the procedural sequence of action or the significance of tactical behaviour) the meaning of the introduced parameters, called tactical metrics, is illustrated. In a second step, the validity of this approach is tested using matches of the Union of European Football Associations (UEFA) Euro 2012® to investigate a connection between these metrics and success. The results show that 11 tactical metrics model tactical behaviour in 4 different dimensions (game speed, transition play after ball recovery, transition play after ball loss and offence efficiency (OE)). Discriminant analysis based on the factor values leads to a correct classification of 64.8% identifying winners, losers and drawers. This successful discrimination reveals a connection between match success and the presented metrics. Especially, the transition play after losing the ball and the OE seem to be factors connected directly with the result of a match, since those were important values for a successful discrimination. Furthermore, the procedural description of tactical behaviour provides the opportunity to conduct meaningful recommendations for the training and coaching process. PMID:26508419

  19. Congenital protein losing enteropathy: an inborn error of lipid metabolism due to DGAT1 mutations.

    PubMed

    Stephen, Joshi; Vilboux, Thierry; Haberman, Yael; Pri-Chen, Hadass; Pode-Shakked, Ben; Mazaheri, Sina; Marek-Yagel, Dina; Barel, Ortal; Di Segni, Ayelet; Eyal, Eran; Hout-Siloni, Goni; Lahad, Avishay; Shalem, Tzippora; Rechavi, Gideon; Malicdan, May Christine V; Weiss, Batia; Gahl, William A; Anikster, Yair

    2016-08-01

    Protein-losing enteropathy (PLE) is a clinical disorder of protein loss from the gastrointestinal system that results in hypoproteinemia and malnutrition. This condition is associated with a wide range of gastrointestinal disorders. Recently, a unique syndrome of congenital PLE associated with biallelic mutations in the DGAT1 gene has been reported in a single family. We hypothesize that mutations in this gene are responsible for undiagnosed cases of PLE in infancy. Here we investigated three children in two families presenting with severe diarrhea, hypoalbuminemia and PLE, using clinical studies, homozygosity mapping, and exome sequencing. In one family, homozygosity mapping using SNP arrays revealed the DGAT1 gene as the best candidate gene for the proband. Sequencing of all the exons including flanking regions and promoter regions of the gene identified a novel homozygous missense variant, p.(Leu295Pro), in the highly conserved membrane-bound O-acyl transferase (MBOAT) domain of the DGAT1 protein. Expression studies verified reduced amounts of DGAT1 in patient fibroblasts. In a second family, exome sequencing identified a previously reported splice site mutation in intron 8. These cases of DGAT1 deficiency extend the molecular and phenotypic spectrum of PLE, suggesting a re-evaluation of the use of DGAT1 inhibitors for metabolic disorders including obesity and diabetes. PMID:26883093

  20. Prefrontal neurons represent winning and losing during competitive video shooting games between monkeys.

    PubMed

    Hosokawa, Takayuki; Watanabe, Masataka

    2012-05-30

    Humans and animals must work to support their survival and reproductive needs. Because resources are limited in the natural environment, competition is inevitable, and competing successfully is vitally important. However, the neuronal mechanisms of competitive behavior are poorly studied. We examined whether neurons in the lateral prefrontal cortex (LPFC) showed response sensitivity related to a competitive game. In this study, monkeys played a video shooting game, either competing with another monkey or the computer, or playing alone without a rival. Monkeys performed more quickly and more accurately in the competitive than in the noncompetitive games, indicating that they were more motivated in the competitive than in the noncompetitive games. LPFC neurons showed differential activity between the competitive and noncompetitive games showing winning- and losing-related activity. Furthermore, activities of prefrontal neurons differed depending on whether the competition was between monkeys or between the monkey and the computer. These results indicate that LPFC neurons may play an important role in monitoring the outcome of competition and enabling animals to adapt their behavior to increase their chances of obtaining a reward in a socially interactive environment. PMID:22649245

  1. Losing an only child: the one-child policy and elderly care in China.

    PubMed

    Song, Yu

    2014-05-01

    China has had the one-child policy for more than 30 years. It reduced China's population growth within a short period of time and promoted economic development. However, it has also led to difficulties, and this paper focuses on those which pertain to ageing and losing one's only child. Approximately one million families have lost their only child in China. They suffer mentally and physically, and sometimes face social stigma and economic loss. What worries them most, however, is elderly care, which has become a severe crisis for the families who have lost their only children. This article draws upon several qualitative studies and 12 cases reported by the Chinese media in 2012 and 2013, and existing laws and policies for supporting those who have lost only children. It also analyses the current elderly care situation facing these families. The Chinese government has recognized the predicament and provides some help, which is increasing but is still not always adequate. To both sustain China's economic development and limit population growth, it is essential for the government to reform the one-child policy and provide a comprehensive support system for the families who have lost their only children, including financial relief and elderly care, and work to reduce stigma against these families. PMID:24908462

  2. Cholestasis and protein-losing enteropathy secondary to hyperthyroidism in a 6-year-old girl.

    PubMed

    Gargouri, Lamia; Charfi, Manel; Maalej, Bayen; Majdoub, Imen; Safi, Faiza; Fourati, Hela; Hentati, Yosr; Daoud, Emna; Mnif, Zeineb; Abid, Mohamed; Mahfoudh, Abdelmajid

    2014-09-01

    Hepatic dysfunctions are not infrequent in patients with hyperthyroidism. These disorders may be related to the effects of the excess thyroid hormone secretion, to the uses of antithyroid drugs, or to the presence of concomitant hepatic diseases. Our aim is to describe the clinical and biochemical features of liver dysfunction related to thyrotoxicosis. We report here a case of a 6-year-old girl who was admitted for jaundice and pruritus as a result of the development of hyperthyroidism due to Graves' disease. On physical examination at admission, she was found to have jaundice and hepatomegaly. Laboratory data show cholestasis and protein-losing enteropathy. Investigations exclude other causes of hepatic disorder. One month after the initiation of antithyroid drug, the patient became euthyroid with improvement in jaundice and pruritus and normalization of hepatic tests and alpha antitrypsine clearance. In conclusion, the diagnosis of hyperthyroidism may be delayed in patients in whom the primary manifestations were pruritus and jaundice. The physician should suspect thyrotoxicosis prior to hepatitis or skin manifestations. PMID:24825088

  3. Use of vertical electrical resistivity profiles to characterize the riverbed of losing-disconnected rivers

    NASA Astrophysics Data System (ADS)

    Lamontagne, Sebastien; Davis, Aaron; Crosbie, Russell; Taylor, Andrew; Munday, Tim

    2014-05-01

    There are few field techniques available to estimate infiltration rates from losing-disconnected rivers, where infiltration rates are often constrained by the presence of clay layers with a low hydraulic conductivity. It is hypothesized that, in this environment, the bulk of the infiltration would occur in 'hotspots' where the clay layer is thin or absent. Infiltration was estimated over a 2 km section of Billabong Creek (Murray-Darling Basin, Australia) using vertical electrical sounding (VES) resistivity to characterize the continuity and thickness of the riverbed clay layer. Both a towed in-river survey over the whole study reach and three fixed array measurements at the shoreline at selected areas were used. Using locations with measured high and low resistivity, the resistivity profiles were constrained by coring the riverbed to measure vertical variations in riverbed texture, porewater content and porewater salinity. The VES showed that the clay layer was continuous along the study reach and varied in thickness between 1 m and >4 m. Using a simple steady-state model, infiltration rates along the study reach were estimated to vary between 1700 and 7800 m3 km-1 year-1, with an average of 3400 m3 km-1 year-1. This methodology can provide independent estimates of infiltration rates at a scale suitable for the calibration of regional groundwater models.

  4. Protein-losing enteropathy in a patient with familial adenomatous polyposis and advanced colon cancer.

    PubMed

    Miyamoto, Yoshihiko; Muguruma, Naoki; Kimura, Tetsuo; Okamoto, Koichi; Sogabe, Masahiro; Miyamoto, Hiroshi; Kohno, Seiya; Nakasono, Masahiko; Hayashi, Hiroshige; Bando, Yoshimi; Takayama, Tetsuji

    2016-06-01

    A 29-year-old female visited a hospital because of increasingly severe lower leg edema. She was diagnosed as having multiple polyps in the stomach and colon by gastroscopy and sigmoidoscopy as well as multiple liver tumors by abdominal CT. She was referred to our hospital for further examination. Total colonoscopy revealed a type 2 tumor in the transverse colon and more than 200 polyps distributed throughout the colorectum. Biopsies of the tumor and polyps showed histological characteristics of adenocarcinoma and tubulovillous adenoma, respectively. Thus, she was diagnosed as having metastatic colon cancer derived from familial adenomatous polyposis (FAP). Laboratory tests showed a marked hypoalbuminemia of 1.1 g/dl. The fecal alpha-1 anti-trypsin test showed abnormal clearance (62.1 ml/day), and scintigraphy using 99mTc-human serum albumin revealed protein loss in the whole colon. Multiple ligation probe amplification analysis of the APC gene identified a germline duplication of exons 11-13. Direct sequencing of the reverse transcription PCR products of APC mRNA revealed a deletion of 25 base pairs and a tandem duplication of exons 11-13. This case was considered to be protein-losing enteropathy resulting from numerous colonic tubulovillous adenomas and advanced colon cancer in a FAP patient with unusual mutational events in APC. PMID:27170298

  5. A prospect theory explanation of the disposition to trade losing investments for less than market price.

    PubMed

    Johnstone, D J

    2002-06-01

    Investors have a proven general reluctance to realize losses. The theory of "mental accounting" suggests that losses are easier to accept when mentally integrated with either preceding losses or with compensatory gains. Mental integration is made easier when a failed asset is exchanged against a new, apparently profitable, acquisition. The alternative is to sell the existing asset on the open market before re-investing the proceeds as desired. This is emotionally less appealing than "rolling over" a losing investment into a new venture by way of an asset trade. The psychological benefits of exchanging rather than selling a failed asset come at a cost. It is typical of trade-in arrangements, e.g., where one trades an old car against a new one, that the effective sale price of the existing asset is less than current market value. Acceptance of this low price adds to the investor's total monetary loss on the existing asset but is essential to an overall package deal apart from which that asset would often remain belatedly unsold. PMID:12090518

  6. Losing jobs and lighting up: Employment experiences and smoking in the Great Recession

    PubMed Central

    Golden, Shelley D.; Perreira, Krista M.

    2015-01-01

    The Great Recession produced the highest rates of unemployment observed in decades, in part due to particularly high rates of people losing work involuntarily. The impact of these job losses on health is unknown, due to the length of time required for most disease development, concerns about reverse causation, and limited data that covers this time period. We examine associations between job loss, employment status and smoking, the leading preventable cause of death, among 13,571 individuals participating in the 2001-2011 waves of the U.S.-based Panel Study of Income Dynamics. Results indicate that recent involuntary job loss is associated with an average 1.1 percentage point increase in smoking probability. This risk is strongest when people have returned to work, and appears reversed when they leave the labor market altogether. Although some job loss is associated with changes in household income and psychological distress levels, we find no evidence that these changes explain smoking behavior modifications. Smoking prevention programs and policies targeted at displaced workers or the newly employed may alleviate some negative health effects produced by joblessness during the Great Recession. PMID:26079992

  7. Can't wait to lose weight? Characterizing temporal discounting parameters for weight-loss.

    PubMed

    Lim, Seung-Lark; Bruce, Amanda S

    2015-02-01

    Obesity is often related to steeper temporal discounting, that is, higher decision impulsivity for immediate rewards over delayed rewards. However, previous studies have measured temporal discounting parameters through monetary rewards. The aim of this study was to develop a temporal discounting measure based on weight-loss rewards, which may help to understand decision-making mechanisms more closely related to body weight regulation. After having their heights and weights measured, healthy young adults completed the Monetary Choice Questionnaire (MCQ), and an adapted version of the MCQ, with weight-loss as a reward. Participants also completed self-reports that measure obesity-related cognitive variables. For 42 participants who expressed a desire to lose weight, weight-loss rewards were discounted over time and had a positive correlation with temporal discounting for monetary rewards. Higher temporal discounting for weight loss rewards (i.e., preference for immediate weight loss) showed correlations with beliefs that obesity is under obese persons' control and largely due to lack of willpower, while temporal discounting parameters for monetary rewards did not. Taken together, our weight loss temporal discounting measure demonstrated both convergent and divergent validity, which can be utilized for future obesity research and interventions. PMID:25450897

  8. Losing jobs and lighting up: Employment experiences and smoking in the Great Recession.

    PubMed

    Golden, Shelley D; Perreira, Krista M

    2015-08-01

    The Great Recession produced the highest rates of unemployment observed in decades, in part due to particularly high rates of people losing work involuntarily. The impact of these job losses on health is unknown, due to the length of time required for most disease development, concerns about reverse causation, and limited data that covers this time period. We examine associations between job loss, employment status and smoking, the leading preventable cause of death, among 13,571 individuals participating in the 2001-2011 waves of the U.S.-based Panel Study of Income Dynamics. Results indicate that recent involuntary job loss is associated with an average 1.1 percentage point increase in smoking probability. This risk is strongest when people have returned to work, and appears reversed when they leave the labor market altogether. Although some job loss is associated with changes in household income and psychological distress levels, we find no evidence that these changes explain smoking behavior modifications. Smoking prevention programs and policies targeted at displaced workers or the newly employed may alleviate some negative health effects produced by joblessness during the Great Recession. PMID:26079992

  9. No Time To Lose - High Throughput Screening To Assess Nanomaterial Safety

    PubMed Central

    Damoiseaux, R; George, S; Li, M; Pokhrel, S; Ji, Z; France, B; Xia, T; Suarez, E; Rallo, R; Mädler, L; Cohen, Y; Hoek, EMV; Nel, A

    2014-01-01

    Nanomaterials hold great promise for medical, technological and economical benefits. Knowledge concerning the toxicological properties of these novel materials is typically lacking. At the same time, it is becoming evident that some nanomaterials could have a toxic potential in humans and the environment. Animal based systems lack the needed capacity to cope with the abundance of novel nanomaterials being produced, and thus we have to employ in vitro methods with high throughput to manage the rush logistically and use high content readouts wherever needed in order to gain more depth of information. Towards this end, high throughput screening (HTS) and high content screening (HCS) approaches can be used to speed up the safety analysis on a scale that commensurate with the rate of expansion of new materials and new properties. The insights gained from HTS/HCS should aid in our understanding of the tenets of nanomaterial hazard at biological level as well as asset the development of safe-by-design approaches. This review aims to provide a comprehensive introduction to the HTS/HCS methodology employed for safety assessment of engineered nanomaterials (ENMs), including data analysis and prediction of potentially hazardous material properties. Given the current pace of nanomaterial development, HTS/HCS is a potentially effective means of keeping up with the rapid progress in this field – we have literally no time to lose. PMID:21301704

  10. Cytochrome c oxidase loses catalytic activity and structural integrity during the aging process in Drosophila melanogaster

    SciTech Connect

    Ren, Jian-Ching; Rebrin, Igor; Klichko, Vladimir; Orr, William C.; Sohal, Rajindar S.

    2010-10-08

    Research highlights: {yields} Cytochrome c oxidase loses catalytic activity during the aging process. {yields} Abundance of seven nuclear-encoded subunits of cytochrome c oxidase decreased with age in Drosophila. {yields} Cytochrome c oxidase is specific intra-mitochondrial site of age-related deterioration. -- Abstract: The hypothesis, that structural deterioration of cytochrome c oxidase (CcO) is a causal factor in the age-related decline in mitochondrial respiratory activity and an increase in H{sub 2}O{sub 2} generation, was tested in Drosophila melanogaster. CcO activity and the levels of seven different nuclear DNA-encoded CcO subunits were determined at three different stages of adult life, namely, young-, middle-, and old-age. CcO activity declined progressively with age by 33%. Western blot analysis, using antibodies specific to Drosophila CcO subunits IV, Va, Vb, VIb, VIc, VIIc, and VIII, indicated that the abundance these polypeptides decreased, ranging from 11% to 40%, during aging. These and previous results suggest that CcO is a specific intra-mitochondrial site of age-related deterioration, which may have a broad impact on mitochondrial physiology.

  11. Who Is Counseled to Lose Weight? Survey Results and Anthropometric Data from 3149 Lower Socioeconomic Women

    PubMed Central

    Breitkopf, Carmen Radecki; Egginton, Jason S.; Naessens, James M.; Montori, Victor M.; Jatoi, Aminah

    2013-01-01

    Objective Because obesity is a grave public health concern, this study examined the percentage of disadvantaged women who recalled ever receiving weight loss advice from a healthcare provider and factors associated with such advice. Design This study was part of 5-clinic, cervical cancer prevention trial. Patients not immediately post-partum completed a Spanish/English survey; height and weight were also obtained. Results Of the 3149 respondents (response rate 83%), 2138 (68%) were overweight or obese (body mass index (BMI) >/= 25); 94% reported a household income of <$35,000/year; 69% were Hispanic; 10% non-Hispanic black; and 40% completed the survey in Spanish. Only one-third reported ever having been told to lose weight. Based on BMI, these rates were 15% in the 25–29.9 range (overweight); 34% within 30–34.9; 57% within 35–39.9; and 73% >/= 40. In univariate analyses, among overweight women, diabetes or English-speaking was associated with weight loss advice. In multivariate analyses, being older, more educated, and diabetic were associated with such advice. 48% of non-Hispanic whites, 31% of non-Hispanic blacks, and 29% of Hispanic had a home scale. Conclusions Among disadvantaged women, obesity alone does not determine who recalls weight loss advice. Language barriers and lack of a home scale merit further study to address obesity. PMID:21744160

  12. Successful therapy for protein-losing enteropathy caused by chronic neuronopathic Gaucher disease.

    PubMed

    Mhanni, A A; Kozenko, M; Hartley, J N; Deneau, M; El-Matary, W; Rockman-Greenberg, C

    2016-03-01

    Gaucher disease (OMIM #230800) is caused by β-glucosidase deficiency and primarily involves the mononuclear phagocyte system (also called Reticuloendothelial System or Macrophage System). The disease is classified into three main phenotypes based on the presence or absence of neurological manifestations: non-neuronopathic (type 1), acute neuronopathic (type 2) and chronic neuronopathic (type 3). Typical manifestations include hepatosplenomegaly, skeletal deformities, hematological abnormalities, interstitial lung fibrosis and neurodegeneration in neuronopathic cases. Mesenteric lymphadenopathy with resultant protein losing enteropathy (PLE) has only been rarely described. Mesenteric lymphadenopathy may lead to intestinal lymphatic obstruction and secondary lymphangiectasia resulting in chronic diarrhea, abdominal pain and weight loss. Fecal protein loss with secondary hypoalbuminemia can be significant. We report a male with Chronic Neuronopathic Gaucher disease (GD) (homozygous for c.1448T > C (NM_000157.3) GBA mutation) who at 16 years of age developed intractable abdominal pain, diarrhea and weight loss. This was caused by PLE secondary to intestinal lymphangiectasia caused by calcified mesenteric lymphadenopathy despite prior long term enzyme replacement therapy (ERT) and/or substrate reduction therapy (SRT). His older similarly affected sister who had been receiving treatment with ERT and/or SRT remains stable on these treatments with no evidence of mesenteric lymphadenopathy. Medical management with total parenteral nutrition, daily medium chain triglyceride-oil (MCT) supplementation, low dose oral budesonide, continued oral SRT and an increased dose of parenteral ERT has stabilized his condition with resolution of the gastrointestinal symptoms and appropriate weight gain. PMID:27014572

  13. Stream-aquifer interactions and hyporheic exchange in gaining and losing sinuous streams

    NASA Astrophysics Data System (ADS)

    Cardenas, M. Bayani

    2009-06-01

    The irregular planform morphology of rivers leads to formation of hyporheic zones along its banks. This study investigates how hyporheic exchange in stream banks, whose planform is idealized as sinusoidal, is affected by net gains from and net losses of water to the adjacent aquifer. These effects are studied via numerical modeling of groundwater flow adjacent to sinuous channels across a broad range of sinuosity and gain/loss magnitude. Hyporheic zone areas and fluxes both decrease exponentially with increasing magnitude of net gain or loss relative to the case where the stream has no net flux of water (neutral). Residence time through the hyporheic zone also decreases with gain/loss magnitude. The hyporheic zones become constrained near the apex of bends, indicating that these areas could be hot spots for mixing and biogeochemical processing. Hyporheic zones in channels with smaller sinuosity are more prone to hyporheic flux and area reduction while very sinuous channels are able to maintain a hyporheic zone even under largely losing or gaining conditions. Equations fitted to the suite of simulation results allow for prediction of hyporheic flux, area, and residence time on the basis of aquifer hydraulic conductivity, channel sinuosity, and the ratio of along-valley and across-valley mean head gradients.

  14. Assessment of testicular function after acute and chronic irradiation: Further evidence for an influence of late spermatids on Sertoli cell function in the adult rat

    SciTech Connect

    Pineau, C.; Velez de la Calle, J.F.; Pinon-Lataillade, G.; Jegou, B.

    1989-06-01

    To study cell to cell communications within the testis of adult Sprague-Dawley rats, we used acute whole body neutron plus gamma-irradiation over 7-121 days postirradiation and chronic whole body gamma-irradiation over 14-84 days of irradiation and 7-86 days postirradiation. Neither irradiation protocol had an effect on the body weight of the animals. Neutron plus gamma-rays induced dramatic damages to spermatogonia, preleptotene spermatocytes, spermatozoa, and, to a lesser extent, pachytene spermatocytes. In contrast, gamma-rays induced a selective destruction of spermatogonia. Subsequently, in both experiments a maturation-depletion process led to a marked decrease in all germ cell types. A complete or near complete recovery of the different germ cell types and spermatozoa took place during the two postirradiation periods. Under both irradiation protocols Sertoli cells number was unchanged. Androgen-binding protein and FSH levels were normal in spite of the disappearance of most germ cells from spermatogonia to early spermatids. However, the decline of androgen-binding protein as well as the rise of FSH and their subsequent recovery were highly correlated to the number of late spermatids and spermatozoa. Moreover, it appeared that spermatocytes may also interfere with the production of inhibin (Exp B). With neither irradiation was Leydig cell function altered, except in Exp B in which elevated LH levels were temporarily observed. Correlation analysis suggested a relationship between preleptotene spermatocytes and Leydig cell function. In conclusion, this study establishes that chronic gamma-irradiation is particularly useful in the study of intratesticular paracrine regulation in vivo and provides further support to the concept that late spermatids play a major role in controlling some aspects of Sertoli cell function in the adult rat.

  15. Loss of Gata4 in Sertoli cells impairs the spermatogonial stem cell niche and causes germ cell exhaustion by attenuating chemokine signaling

    PubMed Central

    Chen, Su-Ren; Tang, Ji-Xin; Cheng, Jin-Mei; Li, Jian; Jin, Cheng; Li, Xiao-Yu; Deng, Shou-Long; Zhang, Yan; Wang, Xiu-Xia; Liu, Yi-Xun

    2015-01-01

    Sertoli cells, the primary somatic cell in the seminiferous epithelium, provide the spermatogonial stem cell (SSC) microenvironment (niche) through physical support and the expression of paracrine factors. However, the regulatory mechanisms within the SSC niche, which is primarily controlled by Sertoli cells, remain largely unknown. GATA4 is a Sertoli cell marker, involved in genital ridge initiation, sex determination and differentiation during the embryonic stage. Here, we showed that neonatal mice with a targeted disruption of Gata4 in Sertoli cells (Gata4flox/flox; Amh-Cre; hereafter termed Gata4 cKO) displayed a loss of the establishment and maintenance of the SSC pool and apoptosis of both gonocyte-derived differentiating spermatogonia and meiotic spermatocytes. Thus, progressive germ cell depletion and a Sertoli-cell-only syndrome were observed as early as the first wave of murine spermatogenesis. Transplantation of germ cells from postnatal day 5 (P5) Gata4 cKO mice into KitW/W-v recipient seminiferous tubules restored spermatogenesis. In addition, microarray analyses of P5 Gata4 cKO mouse testes showed alterations in chemokine signaling factors, including Cxcl12, Ccl3, Cxcr4 (CXCL12 receptor), Ccr1 (CCL3 receptor), Ccl9, Xcl1 and Ccrl2. Deletion of Gata4 in Sertoli cells markedly attenuated Sertoli cell chemotaxis, which guides SSCs or prospermatogonia to the stem cell niche. Finally, we showed that GATA4 transcriptionally regulated Cxcl12 and Ccl9, and the addition of CXCL12 and CCL9 to an in vitro testis tissue culture system increased the number of PLZF+ undifferentiated spermatogonia within Gata4 cKO testes. Together, these results reveal a novel role for GATA4 in controlling the SSC niche via the transcriptional regulation of chemokine signaling shortly after birth. PMID:26473289

  16. Crowding in the City: Losing and Winning Competitors of an Invasive Bird

    PubMed Central

    Hernández-Brito, Dailos; Carrete, Martina; Popa-Lisseanu, Ana G.; Ibáñez, Carlos; Tella, José L.

    2014-01-01

    Invasive species can take advantage of resources unexploited by natives (opportunism hypothesis) or they can exploit the same resources but more aggressively or efficiently (competition hypothesis), thus impacting native species. However, invasive species tend to exploit anthropogenic habitats that are inefficiently used by natives such as urban environments. Focusing on the ring-necked parakeet (Psittacula krameri), one of the most invasive birds worldwide, we combined observations of interspecific aggressions, species-specific cavity-nest preferences and the spatial distribution of the native cavity-nesting vertebrate community to determine the invasion process as well as its potential impacts on native species in a Mediterranean city. Our results support the competition hypothesis, suggesting that ring-necked parakeets are outcompeting native species sharing nest-site preferences. Parakeets initiated and won most interspecific aggressions, which were directed towards competitors but also towards predators. This behaviour could explain the spatial arrangement of natives, with most bird species breeding close to parakeets possibly to take advantage of their effective antipredatory behaviour. However, temporal and spatial patterns of segregation suggest that a threatened bat species is negatively affected by parakeets. This demonstrates that common species gain benefits and threatened ones (in this study, a bat and possibly a falcon) lose nest sites due to invaders. Therefore, the conservation status of the native species that pay the costs of competition with invaders should be considered. This scenario of winners and losers may, however, shift towards more losers if the ring-necked parakeet population continues to grow, thus requiring close monitoring and control/eradication programs to avoid further impacts. PMID:24945439

  17. Crowding in the city: losing and winning competitors of an invasive bird.

    PubMed

    Hernández-Brito, Dailos; Carrete, Martina; Popa-Lisseanu, Ana G; Ibáñez, Carlos; Tella, José L

    2014-01-01

    Invasive species can take advantage of resources unexploited by natives (opportunism hypothesis) or they can exploit the same resources but more aggressively or efficiently (competition hypothesis), thus impacting native species. However, invasive species tend to exploit anthropogenic habitats that are inefficiently used by natives such as urban environments. Focusing on the ring-necked parakeet (Psittacula krameri), one of the most invasive birds worldwide, we combined observations of interspecific aggressions, species-specific cavity-nest preferences and the spatial distribution of the native cavity-nesting vertebrate community to determine the invasion process as well as its potential impacts on native species in a Mediterranean city. Our results support the competition hypothesis, suggesting that ring-necked parakeets are outcompeting native species sharing nest-site preferences. Parakeets initiated and won most interspecific aggressions, which were directed towards competitors but also towards predators. This behaviour could explain the spatial arrangement of natives, with most bird species breeding close to parakeets possibly to take advantage of their effective antipredatory behaviour. However, temporal and spatial patterns of segregation suggest that a threatened bat species is negatively affected by parakeets. This demonstrates that common species gain benefits and threatened ones (in this study, a bat and possibly a falcon) lose nest sites due to invaders. Therefore, the conservation status of the native species that pay the costs of competition with invaders should be considered. This scenario of winners and losers may, however, shift towards more losers if the ring-necked parakeet population continues to grow, thus requiring close monitoring and control/eradication programs to avoid further impacts. PMID:24945439

  18. Nitrate dynamics within the Pajaro River, a nutrient-rich, losing stream

    USGS Publications Warehouse

    Ruehl, C.R.; Fisher, A.T.; Los, Huertos M.; Wankel, Scott D.; Wheat, C.G.; Kendall, C.; Hatch, C.E.; Shennan, C.

    2007-01-01

    The major ion chemistry of water from an 11.42-km reach of the Pajaro River, a losing stream in central coastal California, shows a consistent pattern of higher concentrations during the 2nd (dry) half of the water year. Most solutes are conserved during flow along the reach, but [NO 3-] decreases by ???30% and is accompanied by net loss of channel discharge and extensive surface-subsurface exchange. The corresponding net NO3- uptake length is 37 ?? 13 km (42 ?? 12 km when normalized to the conservative solute Cl-), and the areal NO3- uptake rate is 0.5 ??mol m -2 s-1. The observed reduction in [NO3-] along the reach results from one or more internal sinks, not dilution by ground water, hill-slope water, or other water inputs. Observed reductions in [NO3-] and channel discharge along the experimental reach result in a net loss of 200-400 kg/d of NO3--N, ???50% of the input load. High-resolution (temporal and spatial) sampling indicates that most of the NO3- loss occurs along the lower part of the reach, where there is the greatest seepage loss and surface-subsurface exchange of water. Stable isotopes of NO 3-, total dissolved P concentrations, and streambed chemical profiles suggest that denitrification is the most significant NO 3- sink along the reach. Denitrification efficiency, as expressed through downstream enrichment in 15N-NO3-, varies considerably during the water year. When discharge is greater (typically earlier in the water year), denitrification is least efficient and downstream enrichment in 15N-NO3- is greatest. When discharge is lower, denitrification in the streambed appears to occur with greater efficiency, resulting in lower downstream enrichment in 15N-NO3-. ?? 2007 by The North American Benthological Society.

  19. Altered insulin response to glucose in weight-losing cancer patients.

    PubMed

    Rofe, A M; Bourgeois, C S; Coyle, P; Taylor, A; Abdi, E A

    1994-01-01

    Cancer cachexia and the underlying metabolic disturbances are due in part to either altered insulin release and action. Glucose intolerance in cancer patients is frequently observed but the nature of the insulin response is not usually described. The aim of this study was to investigate the insulin response in fasted, weigh-losing cancer patients following an oral glucose load (75 g). All cancer patients (n = 35) showed glucose intolerance. Three types of response were identified; those with an increased insulin: glucose ratio (I:G) at 60 min, (average 12.3, n = 13), those with a normal I:G (average 7.2 n = 7) and those with a decrease I:G (average 4.2, n = 15). Fasting plasma glucose concentrations were normal in all groups prior to the glucose tolerance test. However, patients with the lowest I:G also had the lowest fasting plasma insulin concentrations, the lowest plasma albumin concentrations and the highest plasma triglyceride concentrations. Those patients with an abnormal insulin response (either high or low I:G) had significantly greater weight loss (16% for low I:G group, 13% for the high I:G) compared to the normal responders (8%). Plasma fatty acid concentrations were increased in all cancer patients and decreased appropriately after glucose administration, indicating that lipolysis remained sensitive to the action of insulin. It is concluded that weight loss in cancer is associated with glucose intolerance and an abnormal insulin response, and that this response is indicative of either insulin resistance (high I:G) or decreased pancreatic function (low I:G). These findings suggest a role for insulin replacement therapy in the latter group of patients. PMID:8010722

  20. The impact of losing a child on the clinical presentation of complicated grief

    PubMed Central

    Zetumer, Samuel; Young, Ilanit; Shear, M. Katherine; Skritskaya, Natalia; Lebowitz, Barry; Simon, Naomi; Reynolds, Charles; Mauro, Christine; Zisook, Sidney

    2014-01-01

    Background It is unclear whether bereaved parents with Complicated Grief (CG) struggle with their grief differently than others with CG. This study addressed this question by comparing CG severity, CG-related symptoms, thoughts and behaviors, and comorbid psychiatric diagnoses of bereaved parents with CG to the diagnoses and symptoms of others with CG. Methods Baseline data from 345 participants enrolled in the Healing Emotions After Loss (HEAL) study, a multi-site CG treatment study, were used to compare parents with CG (n = 75) to others with CG (n = 275). Data from the parent group was then used to compare parents with CG who had lost a younger child (n = 24) to parents with CG who had lost an older child (n = 34). Demographic and loss-related data were also gathered and used to control for confounders between groups. Results Parents with CG demonstrated slightly higher levels of CG (p = .025), caregiver self-blame (p = .007), and suicidality (p = .025) than non-parents with CG. Parents who had lost younger children were more likely to have had a wish to be dead since the loss than parents who had lost older children (p = .041). Limitations All data were gathered from a treatment research study, limiting the of these results. No corrections were made for multiple comparisons. The comparison of parents who lost younger children to parents who lost older children was limited by a small sample size. Conclusions Even in the context of CG, the relationship to the deceased may have a bearing on the degree and severity of grief symptoms and associated features. Bereaved parents with CG reported more intense CG, self-blame, and suicidality than other bereaved groups with CG, though this finding requires confirmation. The heightened levels of suicidal ideation experienced by parents with CG, especially after losing a younger child, suggest the value of routinely screening for suicidal thoughts and behaviors in this group. PMID:25217759

  1. Tropical nature reserves are losing their buffer zones, but leakage is not to blame.

    PubMed

    Lui, Gillian V; Coomes, David A

    2016-05-01

    Tropical forests provide important ecosystem services to humanity, yet are threatened by habitat loss resulting from deforestation and land-use change. Although reserves are considered the cornerstones of conservation efforts in the tropics, their efficacy remains equivocal. One question that remains unresolved is whether leakage - the unanticipated displacement of deforestation from inside reserves into the unrestricted zones just beyond a reserve's administrative boundary - is common around tropical forest reserves, or whether the zones are acting as buffers between the protected area and the outside world. To resolve this question, we used the Landsat-derived Global Forest Change dataset to estimate deforestation rates between 2000 and 2012 inside and outside of 60 nature reserves spread across the tropics. Deforestation rates inside reserves (within 5km of the administrative boundary) were generally lower than those immediately outside the reserves (i.e. in buffer zones 0-10km from the boundary), suggesting that reserves are effective at protecting forests. We hypothesised that leakage would result in greater deforestation rates in reserve buffer zones than in the broader reserve landscapes, but such a pattern was observed in only five African sites, suggesting that leakage does not often occur on the edge of established reserves. However, roughly 80% of reserves experienced deforestation rates that increased gradually from their interiors to the outer periphery of their buffer zones. Thus, while leakage may not be a pervasive phenomenon around tropical reserves worldwide, tropical reserves are often losing their buffer zones, resulting in increased isolation that could have ramifications for ecosystem services provisioning and tropical conservation strategies. PMID:26632993

  2. From fan to fat? Vicarious losing increases unhealthy eating, but self-affirmation is an effective remedy.

    PubMed

    Cornil, Yann; Chandon, Pierre

    2013-10-01

    Using archival and experimental data, we showed that vicarious defeats experienced by fans when their favorite football team loses lead them to consume less healthy food. On the Mondays following a Sunday National Football League (NFL) game, saturated-fat and food-calorie intake increase significantly in cities with losing teams, decrease in cities with winning teams, and remain at their usual levels in comparable cities without an NFL team or with an NFL team that did not play. These effects are greater in cities with the most committed fans, when the opponents are more evenly matched, and when the defeats are narrow. We found similar results when measuring the actual or intended food consumption of French soccer fans who had previously been asked to write about or watch highlights from victories or defeats of soccer teams. However, these unhealthy consequences of vicarious defeats disappear when supporters spontaneously self-affirm or are given the opportunity to do so. PMID:23925307

  3. Oral disodium cromoglycate and ketotifen for a patient with eosinophilic gastroenteritis, food allergy and protein-losing enteropathy.

    PubMed

    Suzuki, Junzo; Kawasaki, Yukihiko; Nozawa, Ruriko; Isome, Masato; Suzuki, Shigeo; Takahashi, Ai; Suzuki, Hitoshi

    2003-09-01

    We present a case report of a 10 years old boy with protein-losing enteropathy and eosinophilic gastroenteritis who had positive histamine release tests, increased allergen-specific IgE antibodies to some food items, and low levels of total serum protein and albumin. Upper gastrointestinal endoscopy revealed a number of polyps and diffuse gastritis. Biopsy specimens of the stomach and duodenum showed widespread eosinophilia and neutrophilia. Although a restricted diet was recommended, a diet which excluded foods with positive results to both histamine release test and allergen-specific IgE antibodies was poorly tolerated, and the patient rejected systemic administration of corticosteroids. Thus, we initiated an oral disodium cromoglycate (DSCG) and ketotifen therapy. After oral DSCG and ketotifen administration, the patient's condition improved gradually. Therefore, oral DSCG and ketotifen therapy might be considered as treatment option in patients with eosinophilic gastroenteritis and protein-losing enteropathy caused by food allergy. PMID:15032404

  4. Germ cell toxicity: significance in genetic and fertility effects of radiation and chemicals

    SciTech Connect

    Oakberg, E.F.

    1983-01-01

    The response of the male and female to radiation and chemicals is different. Any loss of oocytes in the female cannot be replaced, and if severe enough, will result in a shortening of the reproductive span. In the male, a temporary sterile period may be induced owing to destruction of the differentiating spermatogonia, but the stem cells are the most resistant spermatogonial type, are capable of repopulating the seminiferous epithelium, and fertility usually returns. The response of both the male and female changes with development of the embryonic to the adult gonad, and with differentiation and maturation in the adult. The primordial germ cells, early oocytes, and differentiating spermatogonia of the adult male are unusually sensitive to the cytotoxic action of noxious agents, but each agent elicits a specific response owing to the intricate biochemical and physiological changes associated with development and maturation of the gametes. The relationship of germ cell killing to fertility is direct, and long-term fertility effects can be predicted from histological analysis of the gonads. The relationship to genetic effects, on the other hand, is indirect, and acts primarily by limiting the cell stages available for testing, by affecting the distribution of mitotically active stem cells among the different stages of the mitotic cycle, and thereby, changing both the type and frequency of genetic effects observed. 100 references, 38 figures, 7 tables.

  5. Dietary Conjugated Linoleic Acid (CLA) increases milk yield without losing body weight in lactating sows.

    PubMed

    Lee, Sung-Hoon; Joo, Young-Kuk; Lee, Jin-Woo; Ha, Young-Joo; Yeo, Joon-Mo; Kim, Wan-Young

    2014-01-01

    This study was conducted to evaluate the effects of dietary conjugated linoleic acid (CLA) on the performance of lactating sows and piglets as well as the immunity of piglets suckling from sows fed CLA. Eighteen multiparous Duroc sows with an average body weight (BW) of 232.0 ± 6.38 kg were randomly selected and assigned to two dietary treatments (n = 9 for each treatment), control (no CLA addition) and 1% CLA supplementation. For the control diet, CLA was replaced with soybean oil. Experimental diets were fed to sows during a 28-day lactation period. Litter size for each sow was standardized to nine piglets by cross-fostering within 24 hours after birth. Sow milk and blood samples were taken from sows and piglets after 21 and 27 days of lactation, respectively. Loss of BW was significantly (p < 0.05) higher in sows fed control diet compared to sows fed CLA diet. Piglet weights at weaning and weight gain during suckling were significantly (p < 0.05) higher in sows fed CLA compared to sows fed control diet. Serum non-esterified fatty acid (NEFA) and urea nitrogen concentrations were significantly (p < 0.05) lower in sows fed CLA than in sows fed soybean oil. IgG concentrations of the groups supplemented with CLA increased by 49% in sow serum (p < 0.0001), 23% in milk (p < 0.05), and 35% in piglet serum (p < 0.05) compared with the control group. Sows fed CLA showed an increase of 10% in milk yield compared with sows fed soybean oil (p < 0.05), even though there was no difference in daily feed intake between the treatments. Milk fat content was significantly (p < 0.05) lower in sows fed CLA than in sows fed soybean oil. Solid-not-fat yield was significantly (p < 0.05) higher in sows supplemented with CLA than in sows fed control diet and also protein-to-fat ratio in milk was significantly (p < 0.05) higher in sows fed CLA compared with the control group. The results show that CLA supplementation to sows increased milk yield without losing BW during

  6. Are urban safety-net hospitals losing low-risk Medicaid maternity patients?

    PubMed Central

    Gaskin, D J; Hadley, J; Freeman, V G

    2001-01-01

    patient volumes to subsidize care for uninsured and underinsured patients. If safety-net hospitals continue to lose their low-risk Medicaid patients, their ability to finance care for the medically indigent will be impaired. Increased hospital competition may improve access to hospital care for low-risk Medicaid patients, but policymakers should be cognizant of the potential reduction in access to hospital care for uninsured and underinsured patients. Public policymakers should ensure that safety-net hospitals have sufficient financial resources to care for these patients by subsidizing their care directly. PMID:11324742

  7. Aggression and Related Behavioral Traits: The Impact of Winning and Losing and the Role of Hormones

    PubMed Central

    Chang, Ching; Li, Cheng-Yu; Earley, Ryan L.; Hsu, Yuying

    2012-01-01

    A suite of correlated behaviors reflecting between-individual consistency in behavior across multiple situations is termed a “behavioral syndrome.” Researchers have suggested that a cause for the correlation between different behaviors might lie in the neuroendocrine system. In this study, we examined the relationships between aggressiveness (a fish's readiness to perform gill display to its mirror image) and each of boldness (the readiness to emerge from a shelter), exploratory tendency (the readiness to approach a novel shelter), and learning performance (the probability of entering the correct reservoir in a T-maze test) in a mangrove rivulus, Kryptolebias marmoratus. We explored the possibility that the relationships between them arise because these behaviors are all modulated by cortisol and testosterone. We also tested the stability of the relationships between these behaviors shortly after using a winning or losing experience to alter individuals’ aggressiveness. The results were that aggressiveness correlated positively with boldness and the tendency to explore, and that these three behavioral traits were all positively correlated with pre-experience testosterone levels. Aggressiveness and boldness also positively correlated with pre-experience cortisol levels; exploratory tendency did not. The relationship between aggressiveness and boldness appeared to be stronger than that between either of them and exploratory tendency. These results suggest that testosterone and cortisol play important roles in mediating the correlations between these behavioral traits. Learning performance was not significantly correlated with the other behavioral traits or with levels of testosterone or cortisol. Recent experience in contests influenced individuals’ aggressiveness, tendency to explore, and learning performance but not their boldness; individuals that received a winning experience were quicker to display to their mirror image and performed better in the

  8. Losing Neutrality: The Neural Basis of Impaired Emotional Control without Sleep.

    PubMed

    Simon, Eti Ben; Oren, Noga; Sharon, Haggai; Kirschner, Adi; Goldway, Noam; Okon-Singer, Hadas; Tauman, Rivi; Deweese, Menton M; Keil, Andreas; Hendler, Talma

    2015-09-23

    Sleep deprivation has been shown recently to alter emotional processing possibly associated with reduced frontal regulation. Such impairments can ultimately fail adaptive attempts to regulate emotional processing (also known as cognitive control of emotion), although this hypothesis has not been examined directly. Therefore, we explored the influence of sleep deprivation on the human brain using two different cognitive-emotional tasks, recorded using fMRI and EEG. Both tasks involved irrelevant emotional and neutral distractors presented during a competing cognitive challenge, thus creating a continuous demand for regulating emotional processing. Results reveal that, although participants showed enhanced limbic and electrophysiological reactions to emotional distractors regardless of their sleep state, they were specifically unable to ignore neutral distracting information after sleep deprivation. As a consequence, sleep deprivation resulted in similar processing of neutral and negative distractors, thus disabling accurate emotional discrimination. As expected, these findings were further associated with a decrease in prefrontal connectivity patterns in both EEG and fMRI signals, reflecting a profound decline in cognitive control of emotion. Notably, such a decline was associated with lower REM sleep amounts, supporting a role for REM sleep in overnight emotional processing. Altogether, our findings suggest that losing sleep alters emotional reactivity by lowering the threshold for emotional activation, leading to a maladaptive loss of emotional neutrality. Significance statement: Sleep loss is known as a robust modulator of emotional reactivity, leading to increased anxiety and stress elicited by seemingly minor triggers. In this work, we aimed to portray the neural basis of these emotional impairments and their possible association with frontal regulation of emotional processing, also known as cognitive control of emotion. Using specifically suited EEG and f

  9. A Novel Transcriptional Factor Nkapl Is a Germ Cell-Specific Suppressor of Notch Signaling and Is Indispensable for Spermatogenesis

    PubMed Central

    Okuda, Hidenobu; Kiuchi, Hiroshi; Takao, Tetsuya; Miyagawa, Yasushi; Tsujimura, Akira; Nonomura, Norio; Miyata, Haruhiko; Okabe, Masaru; Ikawa, Masahito; Kawakami, Yoshitaka; Goshima, Naoki; Wada, Morimasa; Tanaka, Hiromitsu

    2015-01-01

    Spermatogenesis is an elaborately regulated system dedicated to the continuous production of spermatozoa via the genesis of spermatogonia. In this process, a variety of genes are expressed that are relevant to the differentiation of germ cells at each stage. Although Notch signaling plays a critical role in germ cell development in Drosophila and Caenorhabditis elegans, its function and importance for spermatogenesis in mammals is controversial. We report that Nkapl is a novel germ cell-specific transcriptional suppressor in Notch signaling. It is also associated with several molecules of the Notch corepressor complex such as CIR, HDAC3, and CSL. It was expressed robustly in spermatogonia and early spermatocytes after the age of 3 weeks. Nkapl-deleted mice showed complete arrest at the level of pachytene spermatocytes. In addition, apoptosis was observed in this cell type. Overexpression of NKAPL in germline stem cells demonstrated that Nkapl induced changes in spermatogonial stem cell (SSC) markers and the reduction of differentiation factors through the Notch signaling pathway, whereas testes with Nkapl deleted showed inverse changes in those markers and factors. Therefore, Nkapl is indispensable because aberrantly elevated Notch signaling has negative effects on spermatogenesis, affecting SSC maintenance and differentiation factors. Notch signaling should be properly regulated through the transcriptional factor Nkapl. PMID:25875095

  10. D-Aspartate Induces Proliferative Pathways in Spermatogonial GC-1 Cells.

    PubMed

    Santillo, Alessandra; Falvo, Sara; Chieffi, Paolo; Di Fiore, Maria Maddalena; Senese, Rosalba; Chieffi Baccari, Gabriella

    2016-02-01

    D-aspartate (D-Asp) is an endogenous amino acid present in vertebrate tissues, with particularly high levels in the testis. In vivo studies indicate that D-Asp indirectly stimulates spermatogenesis through the hypothalamic-pituitary-gonadal axis. Moreover, in vitro studies have demonstrated that D-Asp up-regulates testosterone production in Leydig cells by enhancing expression of the steroidogenic acute regulatory protein. In this study, a cell line derived from immortalized type-B mouse spermatogonia retaining markers of mitotic germ cells (GC-1) was employed to explore more direct involvement of D-Asp in spermatogenesis. Activity and protein expression of markers of cell proliferation were determined at intervals during incubation in D-Asp-containing medium. D-Asp induced phosphorylation of ERK and Akt proteins, stimulated expression of PCNA and Aurora B, and enhanced mRNA synthesis and protein expression of P450 aromatase and protein expression of Estrogen Receptor β (ERβ). These results are the first demonstration of a direct effect of D-Asp on spermatogonial mitotic activity. Considering that spermatogonia express the NR1 subunit of the N-Methyl-D-Aspartic Acid receptor (NMDAR), we suggest that their response to D-Asp depends on NMDAR-mediated activation of the ERK and Akt pathways and is further enhanced by activation of the P450 aromatase/ERβ pathway. PMID:26189884

  11. A Sertoli Cell-Specific Knockout of Connexin43 Prevents Initiation of Spermatogenesis

    PubMed Central

    Brehm, Ralph; Zeiler, Martina; Rüttinger, Christina; Herde, Katja; Kibschull, Mark; Winterhager, Elke; Willecke, Klaus; Guillou, Florian; Lécureuil, Charlotte; Steger, Klaus; Konrad, Lutz; Biermann, Katharina; Failing, Klaus; Bergmann, Martin

    2007-01-01

    The predominant testicular gap junctional protein connexin43 (cx43) is located between neighboring Sertoli cells (SCs) and between SCs and germ cells. It is assumed to be involved in testicular development, cell differentiation, initiation, and maintenance of spermatogenesis with alterations of its expression being correlated with various testicular disorders. Because total disruption of the cx43 gene leads to perinatal death, we generated a conditional cx43 knockout (KO) mouse using the Cre/loxP recombination system, which lacks the cx43 gene solely in SCs (SCCx43KO), to evaluate the SC-specific functions of cx43 on spermatogenesis in vivo. Adult SCCx43KO−/− mice showed normal testis descent and development of the urogenital tract, but testis size and weight were drastically lower compared with heterozygous and wild-type littermates. Histological analysis and quantitation of mRNA expression of germ cell-specific marker genes revealed a significant reduction in the number of spermatogonia but increased SC numbers/tubule with only a few tubules left showing normal spermatogenesis. Thus, SC-specific deletion of cx43 mostly resulted in an arrest of spermatogenesis at the level of spermatogonia or SC-only syndrome and in intratubular SC clusters. Our data demonstrate for the first time that cx43 expression in SCs is an absolute requirement for normal testicular development and spermatogenesis. PMID:17591950

  12. Redox Processes and Arsenic Release in the Streambed of a Semi-arid Losing Stream

    NASA Astrophysics Data System (ADS)

    Andersen, M. S.; Rau, G. C.; McCallum, A. M.; Acworth, I.

    2011-12-01

    The water quality of groundwater recharge is a function of rainfall chemistry, soil processes and land use. It is less obvious that the mechanism of groundwater recharge itself can influence the resulting groundwater quality, but it has been shown that slow infiltration into thick unsaturated zones generally lead to oxic groundwater (Appelo and Postma, 2005). This is due to the relatively long residence time in the unsaturated zone where reactive organic matter from the soil can be exhausted in the presence of excess atmospheric oxygen. On the other hand, in shallow unsaturated zones some of the reactive organic matter tends to survive the short residence time in the unsaturated zone. Upon reaching the saturated zone this organic matter will reduce the limited amount of dissolved oxygen and start reducing other dissolved or solid electron acceptors (e.g. NO3-, SO42-, Fe(OH)3(s)). Consequently, it is to be expected that recharge from streams, where no unsaturated zone is present, in general should lead to anoxic groundwater. This could be beneficial for attenuating nitrate, but could lead to problems with high levels of dissolved iron or mobility of problematic trace elements such as arsenic. To explore these processes a field investigation was done in the ephemeral Maules Creek in NSW, Australia. A transect of groundwater and streambed piezometers were installed adjacent to a losing section of the creek. Water samples were collected from surface water, streambed pore waters and groundwater piezometers and analysed for water quality parameters (DO, pH, EC), major ions, trace elements, redox sensitive species (NO3-, Fe2+, Mn2+ and H2S) and dissolved organic carbon (DOC). The distribution of radioisotopes and dissolved species below the stream channel delineates a zone of the streambed-aquifer continuum containing water of a recent surface water origin. Measurable concentrations of reduced species (Fe2+, Mn2+ and NH4+), elevated levels of DOC and the lack of oxygen

  13. Congenital chloride-losing diarrhea in a Mexican child with the novel homozygous SLC26A3 mutation G393W

    PubMed Central

    Reimold, Fabian R.; Balasubramanian, Savithri; Doroquez, David B.; Shmukler, Boris E.; Zsengeller, Zsuzsanna K.; Saslowsky, David; Thiagarajah, Jay R.; Stillman, Isaac E.; Lencer, Wayne I.; Wu, Bai-Lin; Villalpando-Carrion, Salvador; Alper, Seth L.

    2015-01-01

    Congenital chloride diarrhea is an autosomal recessive disease caused by mutations in the intestinal lumenal membrane Cl−/HCO−3 exchanger, SLC26A3. We report here the novel SLC26A3 mutation G393W in a Mexican child, the first such report in a patient from Central America. SLC26A3 G393W expression in Xenopus oocytes exhibits a mild hypomorphic phenotype, with normal surface expression and moderately reduced anion transport function. However, expression of HA-SLC26A3 in HEK-293 cells reveals intracellular retention and greatly decreased steady-state levels of the mutant polypeptide, in contrast to peripheral membrane expression of the wildtype protein. Whereas wildtype HA-SLC26A3 is apically localized in polarized monolayers of filter-grown MDCK cells and Caco2 cells, mutant HA-SLC26A3 G393W exhibits decreased total polypeptide abundance, with reduced or absent surface expression and sparse punctate (or absent) intracellular distribution. The WT protein is similarly localized in LLC-PK1 cells, but the mutant fails to accumulate to detectable levels. We conclude that the chloride-losing diarrhea phenotype associated with homozygous expression of SLC26A3 G393W likely reflects lack of apical surface expression in enterocytes, secondary to combined abnormalities in polypeptide trafficking and stability. Future progress in development of general or target-specific folding chaperonins and correctors may hold promise for pharmacological rescue of this and similar genetic defects in membrane protein targeting. PMID:26157392

  14. In Vitro Ectopic Behavior of Porcine Spermatogonial Germ Cells and Testicular Somatic Cells.

    PubMed

    Lee, Kyung Hoon; Lee, Won Young; Do, Jung Tae; Park, Chan Kyu; Kim, Nam Hyung; Kim, Jin Hoi; Chung, Hak Jae; Kim, Dong Woon; Song, Hyuk

    2016-08-01

    Embryonic body-like colony formation is a unique pattern in male germ cell cultures, including spermatogonial stem cells. However, detailed information of the colony formation has not yet been sufficiently reported in male germ cell culture. To elucidate the formation of germ cell-derived colony (GDC), glial cell-derived neurotrophic factor receptor alpha-1 (GFRα-1)-positive pig germ cells were isolated using an immunomagnetic cell isolation method and labeled with red- or green-fluorescent dye. In GDC culture, red-fluorescent-labeled germ cells were evenly distributed in the wells from day 1 to 4, and they clustered together at the time of GDC formation on day 6. Interestingly, feeder cells migrated to the site of colony formation as spermatogonia carriers. Furthermore, when freshly prepared green-labeled GFRα-1-positive germ cells were added, mixed-fluorescent dye (red and green) colonies were observed. On bromodeoxyuridine (BrdU) treatment, 58% ± 3.13% of germ cells were positive to protein gene product 9.5 but negative to BrdU cells. Immunocytochemistry and reverse transcription-polymerase chain reaction results showed that cultured GDC cells were positive to stem cell- and pig germ cell-specific marker genes. In conclusion, in vitro formation of GDCs is mainly dependent on the aggregation of single germ cells as well as on the slow proliferation of germ cells. PMID:27328332

  15. Characterization of the testicular cell types present in the rat by in vivo 31P magnetic resonance spectroscopy

    SciTech Connect

    van der Grond, J.; Van Pelt, A.M.; van Echteld, C.J.; Dijkstra, G.; Grootegoed, J.A.; de Rooij, D.G.; Mali, W.P. )

    1991-07-01

    Testes of vitamin A-deficient Wistar rats before and after vitamin A replacement, of rats irradiated in utero, and of control rats were investigated by in vivo 31P magnetic resonance (MR) spectroscopy. The testicular phosphomonoester/ATP (PM/ATP) ratio ranged from 0.79 {plus minus} 0.05 for testes that contained only interstitial tissue and Sertoli cells to 1.64 {plus minus} 0.04 for testes in which spermatocytes were the most advanced cell types present. When new generations of spermatids entered the seminiferous epithelium, this ratio decreased. The testicular phosphodiester/ATP (PD/ATP) ratio amounted to 0.16 {plus minus} 0.06 for testes in which Sertoli cells, spermatogonia, or spermatocytes were the most advanced cell type present. When new generations of spermatids entered the seminiferous epithelium, the PD/ATP ratio rapidly increased and finally reached a value of 0.71 {plus minus} 0.06 for fully developed testes. Taken together, specific patterns of the PM/ATP ratio, the PD/ATP ratio, and pH were obtained that were correlated to the presence of spermatogonia, spermatocytes, round spermatids, and elongated spermatids or to the absence of spermatogenic cells. Hence, a good impression of the status of the seminiferous epithelium in the rat can be obtained by in vivo 31P MR spectroscopy.

  16. SKAP, an outer kinetochore protein, is required for mouse germ cell development

    PubMed Central

    Grey, Corinne; Espeut, Julien; Ametsitsi, Rachel; Kumar, Rajeev; Luksza, Malgorzata; Brun, Christine; Verlhac, Marie-Hélene; Suja, José Angél; de Massy, Bernard

    2016-01-01

    In sexually reproducing organisms, accurate gametogenesis is crucial for the transmission of genetic material from one generation to the next. This requires the faithful segregation of chromosomes during mitotic and meiotic divisions. One of the main players in this process is the kinetochore, a large multi-protein complex that forms at the interface of centromeres and microtubules. Here, we analyzed the expression profile and function of small kinetochore-associated protein (SKAP) in the mouse. We found that two distinct SKAP isoforms are specifically expressed in the germline: a smaller isoform, which is detected in spermatogonia and spermatocytes and localized in the outer mitotic and meiotic kinetochores from metaphase to telophase, and a larger isoform, which is expressed in the cytoplasm of elongating spermatids. We generated SKAP-deficient mice and found that testis size and sperm production were severely reduced in mutant males. This phenotype was partially caused by defects during spermatogonia proliferation before entry into meiosis. We conclude that mouse SKAP, while being dispensable for somatic cell divisions, has an important role in the successful outcome of male gametogenesis. In germ cells, analogous to what has been suggested in studies using immortalized cells, SKAP most likely stabilizes the interaction between kinetochores and microtubules, where it might be needed as an extra safeguard to ensure the correct segregation of mitotic and meiotic chromosomes. PMID:26667018

  17. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    SciTech Connect

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E.

    2015-08-01

    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

  18. Iatrogenic Cushing's Disease in a Boy after Misdiagnosis of Salt-Losing Virilizing Adrenal Hyperplasia: Impaired Metyrapone Response with Failure of Catch-Up Growth

    ERIC Educational Resources Information Center

    Mendilaharzu, Hernan; And Others

    1973-01-01

    A boy misdiagnosed as having the sodium-losing form of virilizing adrenal hyperplasia was treated with large doses of glucocorticoids and mineralocorticoids from the newborn period until he was more than 4 years of age. (Author)

  19. Use it or lose it: how neurogenesis keeps the brain fit for learning.

    PubMed

    Shors, T J; Anderson, M L; Curlik, D M; Nokia, M S

    2012-02-14

    The presence of new neurons in the adult hippocampus indicates that this structure incorporates new neurons into its circuitry and uses them for some function related to learning and/or related thought processes. Their generation depends on a variety of factors ranging from age to aerobic exercise to sexual behavior to alcohol consumption. However, most of the cells will die unless the animal engages in some kind of effortful learning experience when the cells are about one week of age. If learning does occur, the new cells become incorporated into brain circuits used for learning. In turn, some processes of learning and mental activity appear to depend on their presence. In this review, we discuss the now rather extensive literature showing that new neurons are kept alive by effortful learning, a process that involves concentration in the present moment of experience over some extended period of time. As these thought processes occur, endogenous patterns of rhythmic electrophysiological activity engage the new cells with cell networks that already exist in the hippocampus and at efferent locations. Concurrent and synchronous activity provides a mechanism whereby the new neurons become integrated with the other neurons. This integration allows the present experience to become integrated with memories from the recent past in order to learn and predict when events will occur in the near future. In this way, neurogenesis and learning interact to maintain a fit brain. PMID:21536076

  20. Use it or lose it: How neurogenesis keeps the brain fit for learning

    PubMed Central

    Shors, T.J; Anderson, LM; Curlik, D. M.; Nokia, SM

    2011-01-01

    The presence of new neurons in the adult hippocampus indicates that this structure incorporates new neurons into its circuitry and uses them for some function related to learning and/or related thought processes. Their generation depends on a variety of factors ranging from age to aerobic exercise to sexual behavior to alcohol consumption. However, most of the cells will die unless the animal engages in some kind of effortful learning experience when the cells are about one week of age. If learning does occur, the new cells become incorporated into brain circuits used for learning. In turn, some processes of learning and mental activity appear to depend on their presence. In this review, we discuss the now rather extensive literature showing that new neurons are kept alive by effortful learning, a process that involves concentration in the present moment of experience over some extended period of time. As these thought processes occur, endogenous patterns of rhythmic electrophysiological activity engage the new cells with cell networks that already exist in the hippocampus and at efferent locations. Concurrent and synchronous activity provides a mechanism whereby the new neurons become integrated with the other neurons. This integration allows the present experience to become integrated with memories from the recent past in order to learn and predict when events will occur in the near future. In this way, neurogenesis and learning interact to maintain a fit brain. PMID:21536076

  1. Establishment and applications of male germ cell and Sertoli cell lines.

    PubMed

    Wang, Hong; Wen, Liping; Yuan, Qingqing; Sun, Min; Niu, Minghui; He, Zuping

    2016-08-01

    Within the seminiferous tubules there are two major cell types, namely male germ cells and Sertoli cells. Recent studies have demonstrated that male germ cells and Sertoli cells can have significant applications in treating male infertility and other diseases. However, primary male germ cells are hard to proliferate in vitro and the number of spermatogonial stem cells is scarce. Therefore, methods that promote the expansion of these cell populations are essential for their use from the bench to the bed side. Notably, a number of cell lines for rodent spermatogonia, spermatocytes and Sertoli cells have been developed, and significantly we have successfully established a human spermatogonial stem cell line with an unlimited proliferation potential and no tumor formation. This newly developed cell line could provide an abundant source of cells for uncovering molecular mechanisms underlying human spermatogenesis and for their utilization in the field of reproductive and regenerative medicine. In this review, we discuss the methods for establishing spermatogonial, spermatocyte and Sertoli cell lines using various kinds of approaches, including spontaneity, transgenic animals with oncogenes, simian virus 40 (SV40) large T antigen, the gene coding for a temperature-sensitive mutant of p53, telomerase reverse gene (Tert), and the specific promoter-based selection strategy. We further highlight the essential applications of these cell lines in basic research and translation medicine. PMID:27069011

  2. Energy losing rate and open-circuit voltage analysis of organic solar cells based on detailed photocurrent simulation

    SciTech Connect

    Yu Junsheng; Huang Jiang; Zhang Lei; Jiang Yadong

    2009-09-15

    The J-V characteristics and photovoltaic response of indium tin oxide/pentacene (d nm)/C{sub 60} (40 nm)/BCP (10 nm)/Ag (100 nm) devices have been systematically analyzed. By fitting the J-V characteristics of the fabricated devices, photocurrent densities J{sub ph} were obtained. Meanwhile, we proposed a modified optical transfer matrix theory to satisfy the reasonable trend between P{sub 0}R{sub 0} and film thickness of pentacene layers. Then, we revealed that an accurate rate of energy loss can be defined as E{sub loss}=1-betaJ{sub e}/P{sub 0}R{sub 0}. Also, the relationship between open-circuit voltage V{sub OC}, compensation voltage V{sub 0} and initial polaron-pair bounding energy E{sub B} was determined based on the detailed study and simulation of device photocurrent.

  3. A long non-coding RNA interacts with Gfra1 and maintains survival of mouse spermatogonial stem cells

    PubMed Central

    Li, L; Wang, M; Wang, M; Wu, X; Geng, L; Xue, Y; Wei, X; Jia, Y; Wu, X

    2016-01-01

    Spermatogonial stem cells (SSCs) are unique male germline stem cells that support spermatogenesis and male fertility. Long non-coding RNAs (lncRNA) have been identified as key regulators of stem cell fate; however, their role in SSCs has not been explored. Here, we report that a novel spermatogonia-specific lncRNA (lncRNA033862) is essential for the survival of murine SSCs. LncRNA033862 is expressed in early spermatogonia including SSC and was among 805 lncRNAs identified by global expression profiling as responsive to glial cell-derived neurotrophic factor (GDNF), a growth factor required for SSC self-renewal and survival. LncRNA033862 is an antisense transcript of the GDNF receptor alpha1 (Gfra1) that lacks protein coding potential and regulates Gfra1 expression levels by interacting with Gfra1 chromatin. Importantly, lncRNA033862 knockdown severely impairs SSC survival and their capacity to repopulate recipient testes in a transplantation assay. Collectively, our data provide the first evidence that long non-coding RNAs (lncRNAs) regulate SSC fate. PMID:26962690

  4. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    SciTech Connect

    Kheradmand, Arash; Dezfoulian, Omid; Alirezaei, Masoud; Rasoulian, Bahram

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  5. Expression of low density lipoprotein receptor-related protein 4 (Lrp4) gene in the mouse germ cells.

    PubMed

    Yamaguchi, Yasuka L; Tanaka, Satomi S; Kasa, Miyuki; Yasuda, Kunio; Tam, Patrick P L; Matsui, Yasuhisa

    2006-08-01

    The low density lipoprotein receptor-related protein 4 gene (Lrp4) was identified by subtractive screening of cDNAs of the migratory primordial germ cells (PGCs) of E8.5-9.5 embryo and E3.5 blastocysts. Lrp4 is expressed in PGCs in the hindgut and the dorsal mesentery of E9.5 embryos, and in germ cells in the genital ridges of male and female E10.5-13.5 embryos. Lrp4 is also expressed in spermatogonia of the neonatal and adult testes and in the immature oocytes and follicular cells of the adult ovary. The absence of Lrp4 expression in the blastocyst, embryonic stem cells and embryonic germ cells suggests the Lrp4 is a molecular marker that distinguishes the germ cells from embryo-derived pluripotent stem cells. PMID:16434236

  6. Detection of phase specificity of in vivo germ cell mutagens in an in vitro germ cell system.

    PubMed

    Habas, Khaled; Anderson, Diana; Brinkworth, Martin

    2016-04-15

    In vivo tests for male reproductive genotoxicity are time consuming, resource-intensive and their use should be minimised according to the principles of the 3Rs. Accordingly, we investigated the effects in vitro, of a variety of known, phase-specific germ cell mutagens, i.e., pre-meiotic, meiotic, and post-meiotic genotoxins, on rat spermatogenic cell types separated using Staput unit-gravity velocity sedimentation, evaluating DNA damage using the Comet assay. N-ethyl-N-nitrosourea (ENU), N-methyl-N-nitrosourea (MNU) (spermatogenic phase), 6-mercaptopurine (6-MP) and 5-bromo-2'-deoxy-uridine (5-BrdU) (meiotic phase), methyl methanesulphonate (MMS) and ethyl methanesulphonate (EMS) (post-meiotic phase) were selected for use as they are potent male rodent, germ cell mutagens in vivo. DNA damage was detected directly using the Comet assay and indirectly using the TUNEL assay. Treatment of the isolated cells with ENU and MNU produced the greatest concentration-related increase in DNA damage in spermatogonia. Spermatocytes were most sensitive to 6-MP and 5-BrdU while spermatids were particularly susceptible to MMS and EMS. Increases were found when measuring both Olive tail moment (OTM) and% tail DNA, but the greatest changes were in OTM. Parallel results were found with the TUNEL assay, which showed highly significant, concentration dependent effects of all these genotoxins on spermatogonia, spermatocytes and spermatids in the same way as for DNA damage. The specific effects of these chemicals on different germ cell types matches those produced in vivo. This approach therefore shows potential for use in the detection of male germ cell genotoxicity and could contribute to the reduction of the use of animals in such toxicity assays. PMID:27059372

  7. Elucidating human male germ cell development by studying germ cell cancer.

    PubMed

    Nettersheim, Daniel; Jostes, Sina; Schneider, Simon; Schorle, Hubert

    2016-10-01

    Human germ cell development is regulated in a spatio-temporal manner by complex regulatory networks. Here, we summarize results obtained in germ cell tumors and respective cell lines and try to pinpoint similarities to normal germ cell development. This comparison allows speculating about the critical and error-prone mechanisms, which when disturbed, lead to the development of germ cell tumors. Short after specification, primordial germ cells express markers of pluripotency, which, in humans, persists up to the stage of fetal/infantile spermatogonia. Aside from the rare spermatocytic tumors, virtually all seminomas and embryonal carcinomas express markers of pluripotency and show signs of pluripotency or totipotency. Therefore, it appears that proper handling of the pluripotency program appears to be the most critical step in germ cell development in terms of tumor biology. Furthermore, data from mice reveal that germline cells display an epigenetic signature, which is highly similar to pluripotent cells. This signature (poised histone code, DNA hypomethylation) is required for the rapid induction of toti- and pluripotency upon fertilization. We propose that adult spermatogonial cells, when exposed to endocrine disruptors or epigenetic active substances, are prone to reinitiate the pluripotency program, giving rise to a germ cell tumor. The fact that pluripotent cells can be derived from adult murine and human testicular cells further corroborates this idea. PMID:27512122

  8. Cytotoxic effects of benzene on mouse germ cells determined by flow cytometry

    SciTech Connect

    Spano, M.; Pacchierotti, F.; Ucelli, R.; Amendola, R.; Bartoleschi, C. )

    1989-01-01

    Flow cytometric (FCM) DNA content measurements were performed on testicular monocellular suspensions obtained from mice exposed per os to 0, 1, 2, 4, 6, and 7 ml/kg body weight of benzene in order to investigate its cytotoxic action on gem cells. The effects of benzene were measured 7, 14, 21, 28, and 70 d after treatment. Benzene had no effect on testis weight, but FCM analysis showed the relative percentages of some cell subpopulations (tetraploid and haploid cells) to be different from the control pattern, indicating the occurrence of some cytotoxic damage to differentiating spermatogonia. These data demonstrate that spermatogenesis is sensitive to benzene single exposures as evidenced by an altered cell ratio of testicular cell types.

  9. Differential response of mouse male germ-cell stages to radiation-induced specific-locus and dominant mutations.

    PubMed Central

    Russell, W L; Bangham, J W; Russell, L B

    1998-01-01

    In an attempt to provide a systematic assessment of the frequency and nature of mutations induced in successive stages of spermato- and spermiogenesis, X-irradiated male mice were re-mated at weekly intervals, and large samples of progeny, observed from birth onward, were scored and genetically tested for recessive mutations at seven specific loci and for externally recognizable dominant mutations. Productivity findings provided a rough measure of induced dominant-lethal frequencies. A qualitative assessment of specific-locus mutations (which include deletions and other rearrangements) was made on the basis of homozygosity test results, as well as from information derived from more recent complementation studies and molecular analyses. Both recessive and dominant visibles revealed clear distinctions between spermatogonia and postspermatogonial stages. In addition, differences for both of these endpoints, as well as for presumed dominant lethals, were found among various postspermatogonial stages. It may be concluded that radiation produces its maximum rates of genetic damage in germ-cell stages ranging from midpachytene spermatocytes through early spermatids, a pattern unlike any of those that have been defined for chemicals; further, the frequency peaks for radiation are lower and broader. The difference between post-stem-cell stages overall and stem-cell spermatogonia was smaller than is generally found with chemicals, not only with respect to the frequency but also the nature of mutations. PMID:9560376

  10. Gaining myocytes or losing fibroblasts: Challenges in cardiac fibroblast reprogramming for infarct repair.

    PubMed

    Nagalingam, Raghu S; Safi, Hamza A; Czubryt, Michael P

    2016-04-01

    Unlike most somatic tissues, the heart possesses a very limited inherent ability to repair itself following damage. Attempts to therapeutically salvage the myocardium after infarction, either by sparing surviving myocytes or by injection of exogenous cells of varied provenance, have met with limited success. Cardiac fibroblasts are numerous, resistant to hypoxia, and amenable to phenotype reprogramming to cardiomyocytes - a potential panacea to an intractable problem. However, the long-term effects of mass conversion of fibroblasts are as-yet unknown. Since fibroblasts play key roles in normal cardiac function, treating these cells as a ready source of replacements for myocytes may have the effect of swapping one problem for another. This review briefly examines the roles of cardiac fibroblasts, recaps the strides made so far in their reprogramming to cardiomyocytes both in vitro and in vivo, and discusses the potential ramifications of large-scale cellular identity swapping. While such therapy offers great promise, the potential repercussions require consideration and careful study. PMID:26640115

  11. Effects of Consecutive Basketball Games on the Game-Related Statistics that Discriminate Winner and Losing Teams

    PubMed Central

    Ibáñez, Sergio J.; García, Javier; Feu, Sebastian; Lorenzo, Alberto; Sampaio, Jaime

    2009-01-01

    The aim of the present study was to identify the game-related statistics that discriminated basketball winning and losing teams in each of the three consecutive games played in a condensed tournament format. The data were obtained from the Spanish Basketball Federation and included game-related statistics from the Under-20 league (2005-2006 and 2006-2007 seasons). A total of 223 games were analyzed with the following game-related statistics: two and three-point field goal (made and missed), free-throws (made and missed), offensive and defensive rebounds, assists, steals, turnovers, blocks (made and received), fouls committed, ball possessions and offensive rating. Results showed that winning teams in this competition had better values in all game-related statistics, with the exception of three point field goals made, free-throws missed and turnovers (p ≥ 0.05). The main effect of game number was only identified in turnovers, with a statistical significant decrease between the second and third game. No interaction was found in the analysed variables. A discriminant analysis allowed identifying the two-point field goals made, the defensive rebounds and the assists as discriminators between winning and losing teams in all three games. Additionally to these, only the three-point field goals made contributed to discriminate teams in game three, suggesting a moderate effect of fatigue. Coaches may benefit from being aware of this variation in game determinant related statistics and, also, from using offensive and defensive strategies in the third game, allowing to explore or hide the three point field-goals performance. Key points Overall team performances along the three consecutive games were very similar, not confirming an accumulated fatigue effect. The results from the three-point field goals in the third game suggested that winning teams were able to shoot better from longer distances and this could be the result of exhibiting higher conditioning status and

  12. Effects of Consecutive Basketball Games on the Game-Related Statistics that Discriminate Winner and Losing Teams.

    PubMed

    Ibáñez, Sergio J; García, Javier; Feu, Sebastian; Lorenzo, Alberto; Sampaio, Jaime

    2009-01-01

    The aim of the present study was to identify the game-related statistics that discriminated basketball winning and losing teams in each of the three consecutive games played in a condensed tournament format. The data were obtained from the Spanish Basketball Federation and included game-related statistics from the Under-20 league (2005-2006 and 2006-2007 seasons). A total of 223 games were analyzed with the following game-related statistics: two and three-point field goal (made and missed), free-throws (made and missed), offensive and defensive rebounds, assists, steals, turnovers, blocks (made and received), fouls committed, ball possessions and offensive rating. Results showed that winning teams in this competition had better values in all game-related statistics, with the exception of three point field goals made, free-throws missed and turnovers (p ≥ 0.05). The main effect of game number was only identified in turnovers, with a statistical significant decrease between the second and third game. No interaction was found in the analysed variables. A discriminant analysis allowed identifying the two-point field goals made, the defensive rebounds and the assists as discriminators between winning and losing teams in all three games. Additionally to these, only the three-point field goals made contributed to discriminate teams in game three, suggesting a moderate effect of fatigue. Coaches may benefit from being aware of this variation in game determinant related statistics and, also, from using offensive and defensive strategies in the third game, allowing to explore or hide the three point field-goals performance. Key pointsOverall team performances along the three consecutive games were very similar, not confirming an accumulated fatigue effect.The results from the three-point field goals in the third game suggested that winning teams were able to shoot better from longer distances and this could be the result of exhibiting higher conditioning status and/or the

  13. Major gastrointestinal manifestations in lupus patients in Asia: lupus enteritis, intestinal pseudo-obstruction, and protein-losing gastroenteropathy.

    PubMed

    Chng, H H; Tan, B E; Teh, C L; Lian, T Y

    2010-10-01

    Gastrointestinal (GI) symptoms are common in patients with systemic lupus erythematosus (SLE) and may be due to the disease itself, side-effects of medications, or non-SLE causes. However, GI manifestations of lupus attract far less attention than the other major organ involvements, are infrequently reviewed and rarely documented in published lupus databases or cohort studies including those from countries in Asia. According to three reports from two countries in Asia, the cumulative prevalence of SLE GI manifestations range from 3.8% to 18%. In this review, we focus on three major GI manifestations in patients from Asian countries: lupus enteritis, intestinal pseudo-obstruction, and protein-losing gastroenteropathy, for which early recognition improves outcome and reduces morbidity and mortality. PMID:20947549

  14. Protein-Losing Gastroenteropathy Associated With Sjögren's Syndrome: First Known Case Reported Outside of Asia.

    PubMed

    Gupta, Amit; Cohen, Natalie L; McCarthy, Sean; McHugh, Jonathan B; Kwon, Richard

    2015-04-01

    Protein-losing gastroenteropathy (PLGE) is a rare extraglandular manifestation of Sjögren's syndrome, reported in fewer than 10 cases. We report a 58-year-old white woman with Sjögren's syndrome, type 1 renal tubular acidosis, and PLGE, who presented with cachexia and 100-pound weight loss. The diagnosis was made based on hypoalbuminemia in the absence of significant proteinuria, low levels of fat soluble vitamins, low transferrin, and an elevated alpha-1 antitrypsin (A1AT) fecal clearance, supported by imaging and endoscopy, with biopsy showing lymphocytic infiltration. She was successfully treated with cyclophosphamide and prednisone. To our knowledge, this is the first such case outside of Asia. PMID:26157958

  15. Sjögren's syndrome associated with protein losing gastroenteropathy manifested by intestinal lymphangiectasia successfully treated with prednisolone and hydroxychloroquine.

    PubMed

    Liao, C-Y; Chien, S-T; Wang, C-C; Chen, I-H; Chiu, H-W; Liu, M-Y; Lin, C-H; Ben, R-J; Tsai, M-K

    2015-12-01

    Protein-losing gastroenteropathy (PLGE), a rare manifestation of primary Sjögren's syndrome (SS), is characterized by profound edema and severe hypoalbuminemia secondary to excessive serum protein loss from the gastrointestinal tract and is clinically indistinguishable from nephrotic syndrome. We report a case of a 30-year-old Taiwanese woman with PLGE-associated SS. In addition to a positive Schirmer's test, she had eye-dryness, thirst, and high levels of anti-SSA antibodies, fulfilling SS criteria. PLGE diagnosis was highly appropriate given the clinical profile of hypoalbuminemia, hypercholesterolemia, pleural effusion, and ascites, with absent cardiac, hepatic, or renal disease. We were unable to perform technetium-99 m-labeled human serum albumin scintigraphy ((99m)Tc-HAS). However, the patient's edema and albumin level improved dramatically in response to a 3-month regime of oral prednisolone followed by oral hydroxychloroquine. PMID:26169478

  16. If not dieting, how to lose weight? Tips and tricks for a better global and cardiovascular health.

    PubMed

    Leclerc, Jacinthe; Bonneville, Nadine; Auclair, Audrey; Bastien, Marjorie; Leblanc, Marie-Eve; Poirier, Paul

    2015-03-01

    Weight loss is a popular topic and may be of serious concern for many patients. Even with the abundant literature on obesity and cardiometabolic risk, it is always challenging to demystify and reinforce the determinants of safe approaches to lose weight. Measures of central obesity are essential to characterize the patient's adiposity distribution and should be part of the routine medical examination. Beyond this, screening for fasting lipids and glucose are important for the assessment of the cardiometabolic risk which may lead to increased cardiovascular morbidity and mortality. Differences in adiposity as well as in weight loss exist between sexes and should be taken into consideration. Rather than avoiding some food or following certain type of diet, any planned weight loss interventions should promote lifestyle and environmental modifications with healthy eating and appropriate physical activity. With clear objectives, this appears to be the best way in order to achieve weight loss goals permanently. PMID:25539643

  17. Suicidal Ideation in Underweight Adults Who Attempt to Lose Weight: Korea National Health and Nutrition Examination Survey, 2007-2012

    PubMed Central

    Lee, Jungkwon

    2015-01-01

    Background Being underweight has been related to health risks. However, little is known about the relationship between suicidal ideation and attempting to lose weight. This study was conducted to examine if there is an association between suicidal ideation and attempting to lose weight among underweight adults. Methods A cross-sectional study of 1,122 underweight adults (range, 19 to 69 years) was conducted based on the Korea National Health and Nutrition Examination Survey, 2007-2012. We examined suicidal ideation, doctor-diagnosed depression, depressive mood, stress, physical activity, health-related behavior, comorbidity, and socioeconomic status by weight loss attempts. Logistic regression analysis was performed to examine the association between suicidal ideation and weight loss attempts. The following covariates were controlled for: age, sex, physical activity, alcohol problem, marital status, education, income, occupation, self-perception of body image, chronic disease, and body mass index. Results There were 101 subjects in the weight loss attempt group and 1,021 in the non-attempt group. The attempt group had a higher risk of suicidal ideation (odds ratio [OR], 2.47; 95% confidence interval [CI], 1.35 to 4.53) and depressive symptoms (OR, 2.17; 95% CI, 1.19 to 3.98). After depressive symptoms were added to the covariates, the risk of suicidal ideation was also significant (OR 2.11, 95% CI: 1.03 to 4.35). The two groups did not significantly differ in doctor-diagnosed depression and stress. Conclusion Weight loss attempts were associated with suicidal ideation in underweight Korean adults. PMID:25802689

  18. Dieting to lose weight and occurrence of neural tube defects in offspring of Mexican-American women.

    PubMed

    Suarez, Lucina; Felkner, Marilyn; Brender, Jean D; Canfield, Mark A

    2012-05-01

    Lowered maternal weight gain and reduction in early pregnancy have been associated with risk of neural tube defects (NTDs) in offspring. We examined the association of self-reported maternal dieting behaviors on the occurrence of NTDs. We conducted a population based case-control study among Mexican-American women who were residents of the 14 Texas counties bordering Mexico. Case women had an NTD-affected pregnancy identified at birth or prenatally and had deliveries during the years 1995-2000. Control women were those who delivered live born infants without an apparent congenital malformation, randomly selected and frequency-matched to cases by year and facility. One hundred eighty-four case women and 225 control women were asked in person about the use of nutritional supplements, dieting to lose weight, and type of weight reduction supplements used during the 3 months before conception. Women who reported being on a diet to lose weight during the 3 months before conception had an NTD odds ratio (OR) of 1.9 (95% confidence interval (CI) = 1.1, 3.3) compared with those not reporting being on a diet. Neither consuming vitamin drinks (OR = 1.2) nor using diet pills (OR = 1.6) during the 3 months before conception had ORs that were different from the null, when compared to women not reporting those behaviors. The risk effect for dieting did not differ markedly among normal or underweight (OR = 2.0, 95% CI = 0.7, 5.6), overweight (OR = 1.9, 95% CI = 0.7, 5.0), or obese women (OR = 1.5, 95% CI = 0.6, 4.0). No effect was seen among dieting women who were consuming at least 1.0 mg/day of folate (OR = 1.1, CI = 0.3, 4.5). Maternal dieting prior to conception may increase the risk of NTDs in offspring. PMID:21512779

  19. Plasticity and epistasis strongly affect bacterial fitness after losing multiple metabolic genes.

    PubMed

    D'Souza, Glen; Waschina, Silvio; Kaleta, Christoph; Kost, Christian

    2015-05-01

    Many bacterial lineages lack seemingly essential metabolic genes. Previous work suggested selective benefits could drive the loss of biosynthetic functions from bacterial genomes when the corresponding metabolites are sufficiently available in the environment. However, the factors that govern this "genome streamlining" remain poorly understood. Here we determine the effect of plasticity and epistasis on the fitness of Escherichia coli genotypes from whose genome biosynthetic genes for one, two, or three different amino acids have been deleted. Competitive fitness experiments between auxotrophic mutants and prototrophic wild-type cells in one of two carbon environments revealed that plasticity and epistasis strongly affected the mutants' fitness individually and interactively. Positive and negative epistatic interactions were prevalent, yet on average cancelled each other out. Moreover, epistasis correlated negatively with the expected effects of combined auxotrophy-causing mutations, thus producing a pattern of diminishing returns. Moreover, computationally analyzing 1,432 eubacterial metabolic networks revealed that most pairs of auxotrophies co-occurred significantly more often than expected by chance, suggesting epistatic interactions and/or environmental factors favored these combinations. Our results demonstrate that both the genetic background and environmental conditions determine the adaptive value of a loss-of-biochemical-function mutation and that fitness gains decelerate, as more biochemical functions are lost. PMID:25765095

  20. Canine Distemper Viruses Expressing a Hemagglutinin without N-Glycans Lose Virulence but Retain Immunosuppression▿

    PubMed Central

    Sawatsky, Bevan; von Messling, Veronika

    2010-01-01

    Paramyxovirus glycoproteins are posttranslationally modified by the addition of N-linked glycans, which are often necessary for correct folding, processing, and cell surface expression. To establish the contribution of N glycosylation to morbillivirus attachment (H) protein function and overall virulence, we first determined the use of the potential N-glycosylation sites in the canine distemper virus (CDV) H proteins. Biochemical characterization revealed that the three sites conserved in all strains were N glycosylated, whereas only two of the up to five additional sites present in wild-type strains are used. A wild-type virus with an H protein reproducing the vaccine strain N-glycosylation pattern remained lethal in ferrets but with a prolonged course of disease. In contrast, introduction of the vaccine H protein in the wild-type context resulted in complete attenuation. To further characterize the role of N glycosylation in CDV pathogenesis, the N-glycosylation sites of wild-type H proteins were successively deleted, including a nonstandard site, to ultimately generate a nonglycosylated H protein. Despite reduced expression levels, this protein remained fully functional. Recombinant viruses expressing N-glycan-deficient H proteins no longer caused disease, even though their immunosuppressive capacities were retained, indicating that reduced N glycosylation contributes to attenuation without affecting immunosuppression. PMID:20042514

  1. Membrane trafficking and organelle biogenesis in Giardia lamblia: use it or lose it.

    PubMed

    Faso, Carmen; Hehl, Adrian B

    2011-04-01

    The secretory transport capacity of Giardia trophozoites is perfectly adapted to the changing environment in the small intestine of the host and is able to deploy essential protective surface coats as well as molecules which act on epithelia. These lumen-dwelling parasites take up nutrients by bulk endocytosis through peripheral vesicles or by receptor-mediated transport. The environmentally-resistant cyst form is quiescent but poised for activation following stomach passage. Its versatility and fidelity notwithstanding, the giardial trafficking systems appear to be the product of a general secondary reduction process geared towards minimization of all components and machineries identified to date. Since membrane transport is directly linked to organelle biogenesis and maintenance, less complexity also means loss of organelle structures and functions. A case in point is the Golgi apparatus which is missing as a steady-state organelle system. Only a few basic Golgi functions have been experimentally demonstrated in trophozoites undergoing encystation. Similarly, mitochondrial remnants have reached a terminally minimized state and appear to be functionally restricted to essential iron-sulfur protein maturation processes. Giardia's minimized organization combined with its genetic tractability provides unique opportunities to study basic principles of secretory transport in an uncluttered cellular environment. Not surprisingly, Giardia is gaining increasing attention as a model for the investigation of gene regulation, organelle biogenesis, and export of simple but highly protective cell wall biopolymers, a hallmark of all perorally transmitted protozoan and metazoan parasites. PMID:21296082

  2. Development of interspecies testicular germ-cell transplantation in flatfish.

    PubMed

    Pacchiarini, Tiziana; Sarasquete, Carmen; Cabrita, Elsa

    2014-06-01

    Interspecific testicular germ cell (TGC) transplantation was investigated in two commercial flatfish species. Testes from donor species (Senegalese sole) were evaluated using classical histological techniques (haematoxylin-eosin staining and haematoxylin-light green-orange G-acid fuchsine staining), in situ hybridisation and immunohistochemical analysis. Both Ssvasa1-2 mRNAs and SsVasa protein allowed the characterisation of TGCs, confirming the usefulness of the vasa gene in the detection of Senegalese sole TGCs. Xenogenic transplants were carried out using TGCs from one-year-old Senegalese sole into turbot larvae. Propidium iodide-SYBR-14 and 4',6'-diamidino-2-phenylindole (DAPI) staining showed that 87.98% of the extracted testicular cells were viable for microinjection and that 15.63% of the total recovered cells were spermatogonia. The vasa gene was characterised in turbot recipients using cDNA cloning. Smvasa mRNA was confirmed as a germ cell-specific molecular marker in this species. Smvasa expression analysis during turbot ontogeny was carried out before Senegalese sole TGC transplants into turbot larvae. Turbot larvae at 18 days after hatching (DAH) proved to be susceptible to manipulation procedures. High survival rates (83.75±15.90-100%) were obtained for turbot larvae at 27, 34 and 42 DAH. These data highlight the huge potential of this species for transplantation studies. Quantitative PCR was employed to detect Senegalese sole vasa mRNAs (Ssvasa1-2) in the recipient turbot larvae. The Ssvasa mRNAs showed a significant increase in relative expression in 42-DAH microinjected larvae three weeks after treatment, showing the proliferation of Senegalese sole spermatogonia in transplanted turbot larvae. PMID:23735683

  3. Losing the sugar coating: potential impact of perineuronal net abnormalities on interneurons in schizophrenia.

    PubMed

    Berretta, Sabina; Pantazopoulos, Harry; Markota, Matej; Brown, Christopher; Batzianouli, Eleni T

    2015-09-01

    Perineuronal nets (PNNs) were shown to be markedly altered in subjects with schizophrenia. In particular, decreases of PNNs have been detected in the amygdala, entorhinal cortex and prefrontal cortex. The formation of these specialized extracellular matrix (ECM) aggregates during postnatal development, their functions, and association with distinct populations of GABAergic interneurons, bear great relevance to the pathophysiology of schizophrenia. PNNs gradually mature in an experience-dependent manner during late stages of postnatal development, overlapping with the prodromal period/age of onset of schizophrenia. Throughout adulthood, PNNs regulate neuronal properties, including synaptic remodeling, cell membrane compartmentalization and subsequent regulation of glutamate receptors and calcium channels, and susceptibility to oxidative stress. With the present paper, we discuss evidence for PNN abnormalities in schizophrenia, the potential functional impact of such abnormalities on inhibitory circuits and, in turn, cognitive and emotion processing. We integrate these considerations with results from recent genetic studies showing genetic susceptibility for schizophrenia associated with genes encoding for PNN components, matrix-regulating molecules and immune system factors. Notably, the composition of PNNs is regulated dynamically in response to factors such as fear, reward, stress, and immune response. This regulation occurs through families of matrix metalloproteinases that cleave ECM components, altering their functions and affecting plasticity. Several metalloproteinases have been proposed as vulnerability factors for schizophrenia. We speculate that the physiological process of PNN remodeling may be disrupted in schizophrenia as a result of interactions between matrix remodeling processes and immune system dysregulation. In turn, these mechanisms may contribute to the dysfunction of GABAergic neurons. PMID:25601362

  4. Effect of Removal of Spermatogonial Stem Cells (SSCs) from In Vitro Culture on Gene Expression of Niche Factors in Bovine

    PubMed Central

    Akbarinejad, Vahid; Tajik, Parviz; Movahedin, Mansoureh; Youssefi, Reza

    2016-01-01

    Background: Niche cells, regulating Spermatogonial Stem Cells (SSCs) fate are believed to have a reciprocal communication with SSCs. The present study was conducted to evaluate the effect of SSC elimination on the gene expression of Glial cell line-Derived Neurotrophic Factor (GDNF), Fibroblast Growth Factor 2 (FGF2) and Kit Ligand (KITLG), which are the main growth factors regulating SSCs development and secreted by niche cells, primarily Sertoli cells. Methods: Following isolation, bovine testicular cells were cultured for 12 days on extracellular matrix-coated plates. In the germ cell-removed group, the SSCs were removed from the in vitro culture using differential plating; however, in the control group, no intervention in the culture was performed. Colony formation of SSCs was evaluated using an inverted microscope. The gene expression of growth factors and spermatogonia markers were assessed using quantitative real time PCR. Results: SSCs colonies were developed in the control group but they were rarely observed in the germ cell-removed group; moreover, the expression of spermatogonia markers was detected in the control group while it was not observed in the germ cell-removed group, substantiating the success of SSCs removal. The expression of Gdnf and Fgf2 was greater in the germ cell-removed than control group (p<0.05), whereas the expression of Kitlg was lower in the germ cell-removed than control group (p< 0.05). Conclusion: In conclusion, the results revealed that niche cells respond to SSCs removal by upregulation of GDNF and FGF2, and downregulation of KITLG in order to stimulate self-renewal and arrest differentiation. PMID:27563426

  5. Immunolocalization of the telomerase-1 component in cells of the regenerating tail, testis, and intestine of lizards.

    PubMed

    Alibardi, Lorenzo

    2015-07-01

    Using an antibody against a lizard telomerase-1 component the presence of telomerase has been detected in regenerating lizard tails where numerous cells are proliferating. Immunoblots showed telomerase positive bands at 75-80 kDa in normal tissues and at 50, 75, and 90 kDa in those regenerating. Immunofluorescence and ultrastructural immunolocalization showed telomerase-immunoreactivity in sparCe (few/diluted) mesenchymal cells of the blastema, early regenerating muscles, perichondrium of the cartilaginous tube, ependyma of the spinal cord, and in the regenerating epidermis. Clusters of gold particles were detected in condensing chromosomes of few mesenchymal and epithelial cells in the regenerating tail, but a low to undetectable labeling in interphase cells. Telomerase-immunoreactivity was intense in the nucleus and sparCe (few/diluted) in the cytoplasm of spermatogonia and spermatocytes and drastically decreased in early spermatids where some nuclear labeling remains. Some intense immunoreactivity was seen in few cells near the basal membrane of intestinal enterocytes or in leukocytes (likely lymphocytes) of the intestine mucosa. In spermatogonia, spermatids and in enterocytes part of the nuclear labeling formed cluster of gold particles in dense areas identified as Cajal Bodies, suggesting that telomerase is a marker for these stem cells. This therefore suggests that also the sparCe (few/diluted) telomerase positive cells detected in the regenerating tail may represent sparCe (few/diluted) stem cells localized in regenerating tissues where transit amplifying cells are instead preponderant to allow for tail growth. This observation supports previous studies indicating that few stem cells are present in the stump after tail amputation and give rise to transit amplifying cells for tail regeneration. PMID:25712511

  6. Identification of 5-bromo-2'-deoxyuridine-labeled cells during mouse spermatogenesis by heat-induced antigen retrieval in lectin staining and immunohistochemistry.

    PubMed

    Wakayama, Tomohiko; Nakata, Hiroki; Kumchantuek, Tewarat; Gewaily, Mahmoud Saad; Iseki, Shoichi

    2015-03-01

    DNA replication occurs during S-phase in spermatogonia and preleptotene spermatocytes during spermatogenesis. 5-Bromo-2'-deoxyuridine (BrdU) is incorporated into synthesized DNA and is detectable in the nucleus by immunohistochemistry (IHC). To identify BrdU-labeled spermatogenic cells, the spermatogenic stages must be determined by visualizing acrosomes and detecting cell type-specific marker molecules in the seminiferous tubules. However, the antibody reaction with BrdU routinely requires denaturation of the DNA, which is achieved by pretreating tissue sections with hydrochloric acid; however, this commonly interferes with further histochemical approaches. Therefore, we examined optimal methods for pretreating paraffin sections of the mouse testis to detect incorporated BrdU by an antibody and, at the same time, visualize acrosomes with peanut agglutinin (PNA) or detect several marker molecules with antibodies. We found that the use of heat-induced antigen retrieval (HIAR), which consisted of heating at 95C in 20 mM Tris-HCl buffer (pH 9.0) for 15 min, was superior to the use of 2 N hydrochloric acid for 90 min at room temperature in terms of the quality of subsequent PNA-lectin histochemistry with double IHC for BrdU and an appropriate stage marker protein. With this method, we identified BrdU-labeled spermatogenic cells during mouse spermatogenesis as A1 spermatogonia through to preleptotene spermatocytes. PMID:25479790

  7. Light and electron microscopic analyses of Vasa expression in adult germ cells of the fish medaka.

    PubMed

    Yuan, Yongming; Li, Mingyou; Hong, Yunhan

    2014-07-15

    Germ cells of diverse animal species have a unique membrane-less organelle called germ plasm (GP). GP is usually associated with mitochondria and contains RNA binding proteins and mRNAs of germ genes such as vasa. GP has been described as the mitochondrial cloud (MC), intermitochondrial cement (IC) and chromatoid body (CB). The mechanism underlying varying GP structures has remained incompletely understood. Here we report the analysis of GP through light and electron microscopy by using Vasa as a marker in adult male germ cells of the fish medaka (Oryzias latipes). Immunofluorescence light microscopy revealed germ cell-specific Vasa expression. Vasa is the most abundant in mitotic germ cells (oogonia and spermatogonia) and reduced in meiotic germ cells. Vasa in round spermatids exist as a spherical structure reminiscent of CB. Nanogold immunoelectron microscopy revealed subcellular Vasa redistribution in male germ cells. Vasa in spermatogonia concentrates in small areas of the cytoplasm and is surrounded by mitochondria, which is reminiscent of MC. Vasa is intermixed with mitochondria to form IC in primary spermatocytes, appears as the free cement (FC) via separation from mitochondria in secondary spermatocyte and becomes condensed in CB at the caudal pole of round spermatids. During spermatid morphogenesis, Vasa redistributes and forms a second CB that is a ring-like structure surrounding the dense fiber of the flagellum in the midpiece. These structures resemble those described for GP in various species. Thus, Vasa identifies GP and adopts varying structures via dynamic reorganization at different stages of germ cell development. PMID:24814190

  8. 40 CFR 266.240 - How could you lose the conditional exemption for your LLMW and what action must you take?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false How could you lose the conditional exemption for your LLMW and what action must you take? 266.240 Section 266.240 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF SPECIFIC HAZARDOUS WASTES AND SPECIFIC TYPES...

  9. 40 CFR 266.240 - How could you lose the conditional exemption for your LLMW and what action must you take?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false How could you lose the conditional exemption for your LLMW and what action must you take? 266.240 Section 266.240 Protection of Environment... environment, you must also immediately notify us orally within 24 hours and follow up with a...

  10. Nonrandom Germline Transmission of Mouse Spermatogonial Stem Cells.

    PubMed

    Kanatsu-Shinohara, Mito; Naoki, Honda; Shinohara, Takashi

    2016-08-01

    Genes are thought to be transmitted to offspring by random fertilization of a small number of oocytes with numerous spermatozoa. Here we analyzed the dynamics of male germline transmission by genetic marking and transplantation of spermatogonial stem cells (SSCs). We found that offspring deriving from a small number of specific SSCs appear within a limited time. Interestingly, the same SSC clones reappear later with an average functional lifespan of ∼124.4 days. Cyclic offspring production from SSCs was not caused by changes in SSC self-renewal activity because lineage-tracing analyses suggested that all SSCs actively proliferated. Selection appears to occur during the differentiating spermatogonia stage, when extensive apoptosis was observed. The pattern of germline transmission could be predicted using a mathematical model in which SSCs repeat cycles of transient spermatogenic burst and refractory periods. Thus, spermatogenesis is a regulated process whereby specific SSC clones are repeatedly recruited for fertilization with long-term cycles. PMID:27505415

  11. Barriers to Lose Weight from the Perspective of Children with Overweight/Obesity and Their Parents: A Sociocultural Approach

    PubMed Central

    Rodríguez-Ventura, Ana Lilia; Pelaez-Ballestas, Ingris; Sámano-Sámano, Reyna; Jimenez-Gutierrez, Carlos; Aguilar-Salinas, Carlos

    2014-01-01

    Introduction. There are not enough studies about the barriers to lose weight from the perspective of children and their parents. Methods. Children and adolescents diagnosed with overweight/obesity in the Department of Endocrinology and their parents were invited to participate in a series of focus group discussions (FGD). Twenty-nine children 10–16 years old and 22 parents participated in 7 focus groups; 2 mothers and 2 adolescents participated in depth interviews. All interviews were recorded, transcribed, and analyzed through grounded theory. Results. Parents went to the hospital only when their children presented any obesity complication; for them, overweight was not a health problem. Parents referred to lack of time to supervise about a healthy diet and exercise; besides, the same parents, relatives, friends, and the mass media encourage the consumption of junk food. Children accepted eating a lot, not doing exercise, skipping meals, and not understanding overweight consequences. Both, parents and children, demanded support to do the time recommended for exercise inside the schools. They also suggested getting information from schools and mass media (TV) about overweight consequences, exercise, and healthy food by health workers; they recommended prohibiting announcements about junk food and its sale. Conclusions. The barriers detected were lack of perception of being overweight, its identification as a disease and its consequences, lack of time to supervise a healthy lifestyle, and a big social influence to eat junk food. PMID:25371816

  12. The experience of Japanese adolescents and young adults after losing siblings to childhood cancer: three types of narratives.

    PubMed

    Kamibeppu, Kiyoko; Sato, Iori; Hoshi, Yasutaka

    2015-01-01

    The aim of this study was to describe Japanese adolescents' and young adults' experiences after losing siblings to childhood cancer. A conceptual framework of the transition and analysis based on narrative method were adopted from qualitative data from 6 Japanese adolescents and young adults who had lost their siblings to childhood cancer. It was revealed that the participants' psychological experience after the sibling's death was directed by their perceptions of their mothers' responses to bereavement. We also found that the psychological distance between participants and their mothers could be an important factor in enabling transition into mourning and in orienting the lost sibling in their mind. The stories obtained from these 6 participants were categorized into the following 3 types of narratives: "Mother in another world and the sibling who became a god," "Return of the loving mother and the sibling as savior," and "The poor mother and the sibling who needs my help to carry on her legacy." This typology will serve as a framework for grief care and future research. PMID:25413258

  13. Recovery of graft steatosis and protein-losing enteropathy after biliary diversion in a PFIC 1 liver transplanted child.

    PubMed

    Nicastro, Emanuele; Stephenne, Xavier; Smets, Françoise; Fusaro, Fabio; de Magnée, Catherine; Reding, Raymond; Sokal, Etienne M

    2012-08-01

    PFIC 1 is a genetic disorder characterized by hepatic and gastrointestinal disease, often requiring LT during childhood. Extrahepatic symptoms, such as diarrhea and malabsorption, do not improve or may be aggravated after LT, as graft steatosis or steatohepatitis as consequences of the interaction between transplanted liver and native bowel. We describe a patient with PFIC 1 who presented with cholestasis in infancy, who developed intractable pruritus and liver fibrosis. The child underwent living donor LT at 3.6 yr of age, and he early developed severe refractory diarrhea, secondary malabsorption with protein-losing enteropathy, and an early fatty liver disease trough graft steatohepatitis. As the response to cholestyramine was unsatisfactory, we decided to perform an EBD by using the jejunal loop used for the cholangiojejunostomy. Diarrhea resolved rapidly after surgery. He remained well after six months following biliary diversion, with normal stool output and no protein loss. We documented a dramatic improvement of graft steatosis at histology as well as normalization of liver function test. EBD can be considered a valuable treatment option to avoid organ disfunction and loss in PFIC 1 transplanted patients who develop graft steatohepatitis. PMID:21672103

  14. Scared to lose control? General and health locus of control in females with a phobia of vomiting.

    PubMed

    Davidson, Angela L; Boyle, Christopher; Lauchlan, Fraser

    2008-01-01

    The term emetophobia (i.e., a fear of vomiting) exists as rather an elusive predicament, often eluding conventional treatment. The present study involved 149 participants, consisting of 51 emetophobics, 48 phobic controls (i.e. those who suffered from a different phobia), and 50 nonphobic controls. Participants were administered the Rotter (1966) Locus of Control Scale and the Health Locus of Control Scale by B.S. Wallston, Wallston, Kaplan, and Maides (1976). Significant differences were found among the three groups; specifically, that emetophobics had a significantly higher internal Locus of Control Scale score with regard to both general and health-related issues than did the two control groups. It is suggested that vomiting phobics may have a fear of losing control, and that their vomiting phobia is reflective of this alternative, underlying problem. More research is required to explore the association between emetophobia and issues surrounding control; however, the current study suggests that it may be helpful for therapists to consider this aspect when treating a patient with vomiting phobia. PMID:18161045

  15. Losing the battle but winning the war: uncertain outcomes reverse the usual effect of winning on testosterone.

    PubMed

    Zilioli, Samuele; Mehta, Pranjal H; Watson, Neil V

    2014-12-01

    The biosocial model of status predicts a competition effect (or winner-loser effect), whereby winning a competition should cause a rise in testosterone relative to losing. However, its applicability to women and the role of contextual factors, such as a decisive versus close match, have been overlooked. In two studies of female competition, we tested whether the winner-loser effect generalizes to dominance contests that model unstable social hierarchies, namely in close competitions wherein the winner-loser distinction is unsettled (Study 1) and in competitions in which the outcome is uncertain (Study 2). In both studies we found evidence for a reverse winner-loser effect whereby losers experienced a net increase in testosterone compared to winners. Moreover, the rise in testosterone was stronger in those competitors who reported being more surprised by the loss (Study 2). These results represent some of the first empirical evidence for the reverse effect of what is predicted by the biosocial model of status. We interpret these findings in terms of the dominance motivation that testosterone might subserve within unstable status hierarchies. PMID:25148788

  16. Dilemmas in the process of weight reduction: Exploring how women experience training as a means of losing weight

    PubMed Central

    Groven, Karen Synne; Engelsrud, Gunn

    2010-01-01

    Patients diagnosed with obesity are usually offered group-based behavior interventions which include dietary advice and exercise programs. In particular, high-intensity training—combining weight lifting with aerobic exercising—has been proven effective for losing weight. Moreover, recent studies have shown that persons participating in high-intensity training are more likely to maintain their weight loss compared to persons with lower levels of physical activity. However, most of the research in the field has made use of quantitative methods focusing on the measurable effect of such interventions. Therefore, the aim of this study was to show how the training is experienced from a first-person perspective, namely the patients themselves. Our hope was to shed some new light on the process of weight loss that concerns more than the measurable “impacts” of the training. A qualitative approach was used based on interviews with five women selected from a primary healthcare clinic in Norway. Our results show that experiences of training are connected to the participants' general experience of being overweight. Both relationships to other people and earlier experiences are important for how the training is carried out and perceived. Five themes were identified supporting this line of argument: (1) the gaze of others; (2) a common ground; (3) dependence of close-follow up; (4) bodily discomfort as painful; and (5) aiming for results—an ambivalent experience. The results highlight the importance of finding the proper context and support for each patient's needs. PMID:20640017

  17. Who is counseled to lose weight? Survey results and anthropometric data from 3,149 lower socioeconomic women.

    PubMed

    Breitkopf, Carmen Radecki; Egginton, Jason S; Naessens, James M; Montori, Victor M; Jatoi, Aminah

    2012-02-01

    Because obesity is a grave public health concern, this study examined the percentage of disadvantaged women who recalled ever having received weight loss advice from a healthcare provider and factors associated with such advice. This study was part of a 5-clinic, cervical cancer prevention trial. Patients not immediately post-partum completed a Spanish/English survey; height and weight were also obtained. Of the 3,149 respondents (response rate 83%), 2,138 (68%) were overweight or obese (body mass index (BMI) ≥ 25); 94% reported a household income of <$35,000/year; 69% were Hispanic; 10% non-Hispanic black; and 40% completed the survey in Spanish. Only one-third reported ever having been told to lose weight. Based on BMI, these rates were 15% in the 25-29.9 range (overweight); 34% within 30-34.9; 57% within 35-39.9; and 73% ≥ 40. In univariate analyses, among overweight women, diabetes or English-speaking was associated with weight loss advice. In multivariate analyses, being older, more educated, and diabetic were associated with such advice. 48% of non-Hispanic whites, 31% of non-Hispanic blacks, and 29% of Hispanic had a home scale. Among disadvantaged women, obesity alone does not determine who recalls weight loss advice. Language barriers and lack of a home scale merit further study to address obesity. PMID:21744160

  18. Mixed germ cell-sex cord stromal tumor of the testis with an intratubular component: a problem in differential diagnosis.

    PubMed

    Roth, Lawrence M; Cheng, Liang

    2016-05-01

    The origin of mixed germ cell-sex cord stromal tumor (MGC-SCST) of the testis is uncertain, and a controversy exists as to whether the germ cells in these tumors are neoplastic. Although intratubular components of the common and several uncommon forms of testicular germ cell tumors have been described, to our knowledge, intratubular MGC-SCST has not previously been reported in detail. In a study of 13 cases of testicular MGC-SCST, we observed entrapped seminiferous tubules in 7 cases and an intratubular component in 2, both of which were associated with extensive entrapped tubules. Intratubular MGC-SCST is distinguished from entrapped tubules by the occurrence of germ cells resembling spermatogonia in the adluminal compartment and the absence of tubular lumens. By way of contrast, the adluminal compartment of entrapped tubules is composed entirely of immature Sertoli cells, and lumen formation is observed in favorably oriented tubules. Although the germ cells in our cases of MGC-SCST do not show histologic features of malignancy, the observation of spermatogonia-like cells in the adluminal compartment of the tubule, sometimes with concomitant germ cell proliferation, and the infiltrative pattern of the germ cells in the extratubular component support their neoplastic nature. The intratubular component tends to be more centrally located than the adjacent entrapped seminiferous tubules suggesting that it originates from the latter. The tubules of intratubular MGC-SCST are not expanded except in the advanced stage and are approximately the same size as entrapped seminiferous tubules but are considerably smaller than those of the uninvolved testis that shows active spermatogenesis. PMID:27067782

  19. Repopulation of the seminiferous epithelium of the rhesus monkey after X irradiation

    SciTech Connect

    van Alphen, M.M.; van de Kant, H.J.; de Rooij, D.G.

    1988-03-01

    Repopulation of the seminiferous epithelium became evident from Day 75 postirradiation onward after doses of 0.5, 1.0, and 2.0 Gy of X rays. Cell counts in cross sections of seminiferous tubules revealed that during this repopulation the numbers of Apale (Ap) spermatogonia, Adark (Ad) spermatogonia, and B spermatogonia increased simultaneously. After 0.5 Gy the number of spermatogonia increased from approximately 10% of the control level at Day 44 to 90% at Day 200. After 1.0 and 2.0 Gy the numbers of spermatogonia increased from less than 5% at Day 44 to 70% at Days 200 and 370. The number of Ad and B spermatogonia, which are considered to be resting and differentiating spermatogonia, respectively, already had increased when the number of proliferating Ap spermatogonia was still very low. This early inactivation and differentiation of a large part of the population of Ap spermatogonia slows down repopulation of the seminiferous epithelium of the primates. By studying repopulating colonies in whole mounts of seminiferous tubules various types of colonies were found. In colonies consisting of only A spermatogonia, 40% of the A spermatogonia were found to be of the Ad type, which indicates that even before the colony had differentiated, 40% of the A spermatogonia were inactivated into Ad. Differentiating colonies were also found in which one or two generations of germ cells were missing. In some of those colonies it was found that the Ap spermatogonia did not form any B spermatogonia during one or two cycles of the seminiferous epithelium, while in other colonies all Ap spermatogonia present had differentiated into B spermatogonia. This indicates that the differentiation of Ap into B spermatogonia is a stochastic process.

  20. Losing Baby Weight

    MedlinePlus

    ... cravings for unhealthy snacks. Proteins Meat, pork, poultry, fish, eggs and beans contain important nutrients like protein ... trim away visible fat for a healthier meal. Fish like salmon, herring, sardines or fresh-water trout ...

  1. On the Losing End

    ERIC Educational Resources Information Center

    Nealy, Michelle J.

    2008-01-01

    How well a particular industry fares during any given time has an impact on countless other industries and consumers. Case in point--rising gas prices are affecting everything from airfares to the price of getting a pizza delivered. This article describes a similar situation that is happening with the wave of home foreclosures as the subprime…

  2. Losing weight after pregnancy

    MedlinePlus

    ... behavioral guidelines for post-partum weight control. BMC Pregnancy and Childbirth . 2014;14. Accessed Nov. 24, 2014. Mottola MF. Exercise prescription for overweight and obese women: pregnancy and ...

  3. Lose the Recipe

    ERIC Educational Resources Information Center

    Owens, Theresa A.; Martin, Chanda

    2011-01-01

    When learning about plants, elementary students are typically given set directions on how to plant seeds and make their plants grow. To enable their class of first-grade students to build their own knowledge and encourage constructivism, the authors decided to take this set of prescribe activities and make them more inquiry-based. In traditional…

  4. Losing Sleep over Tuition

    ERIC Educational Resources Information Center

    Fogg, Piper

    2009-01-01

    With two children already in college and three more in the wings, the Nwanguma family knows about sacrifice. The annual tuition bill for Prince George's Community College typically comes to between $3,500 and $4,000 for the oldest son, Chuka. To afford it, Chuma Nwanguma, a Nigerian immigrant, often works overtime in addition to his regular night…

  5. NIH Loses a Friend

    MedlinePlus

    ... work as pathology researchers. They made a tremendous team, providing NIH with outstanding competence, integrity, and vision for over 50 years. She held the most important leadership posts in recent NIH history. Dr. Ruth Kirschstein ...

  6. Match intensity and pacing strategies in rugby league: an examination of whole-game and interchanged players, and winning and losing teams.

    PubMed

    Black, Georgia M; Gabbett, Tim J

    2014-06-01

    There is currently limited information on whether pacing occurs during rugby league match play. In addition, to date no research has investigated whether pacing strategies differ between winning and losing teams. This study investigated the pacing strategies of whole-game and interchanged rugby league players. Furthermore, we investigated the pacing strategies of winning and losing teams. Fifty-two rugby league players, from a sample of 11 teams competing in a semi-elite competition, underwent global positioning system analysis. Performances were divided into match quartiles for whole-game and interchanged players. Total distance, including low- and high-speed distances, and repeated high-intensity effort bouts were recorded. The total distance and low-speed distance covered across all quartiles of the match, but specifically quartiles 1 and 8, were greater for interchanged players than whole-game players. The match outcome differentially affected the pacing strategies of whole-game and interchanged players. Whole-game players from winning teams set a higher pacing strategy than whole-game players from losing teams (effect size [ES] = 1.03 ± 0.77, 96%, very likely), whereas interchanged players from losing teams demonstrated a greater "end-spurt" than interchanged players from winning teams (ES = 0.60 ± 0.52, 96%, very likely). The pacing strategies of interchanged players were higher than whole-game players, irrespective of playing position. The results of this study suggest that pacing strategies differ between interchanged and whole-game rugby league players. Furthermore, our results demonstrate a different pacing strategy between winning and losing teams. These findings suggest that physical preparation for rugby league matches, and recovery from these matches, should be individualized for whole-game and interchanged players. Finally, performing physically intense training on a regular basis is likely to develop the physical and mental qualities required to

  7. Skp1-Cullin-F-box (SCF)-type ubiquitin ligase FBXW7 negatively regulates spermatogonial stem cell self-renewal

    PubMed Central

    Kanatsu-Shinohara, Mito; Onoyama, Ichiro; Nakayama, Keiichi I.; Shinohara, Takashi

    2014-01-01

    Spermatogonial stem cells (SSCs) undergo self-renewal divisions to support spermatogenesis throughout life. Although several positive regulators of SSC self-renewal have been discovered, little is known about the negative regulators. Here, we report that F-box and WD-40 domain protein 7 (FBXW7), a component of the Skp1-Cullin-F-box–type ubiquitin ligase, is a negative regulator of SSC self-renewal. FBXW7 is expressed in undifferentiated spermatogonia in a cell cycle-dependent manner. Although peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1), essential for spermatogenesis, is thought to destroy FBXW7, Pin1 depletion decreased FBXW7 expression. Spermatogonial transplantation showed that Fbxw7 overexpression compromised SSC activity whereas Fbxw7 deficiency enhanced SSC colonization and caused accumulation of undifferentiated spermatogonia, suggesting that the level of FBXW7 is critical for self-renewal and differentiation. Screening of putative FBXW7 targets revealed that Fbxw7 deficiency up-regulated myelocytomatosis oncogene (MYC) and cyclin E1 (CCNE1). Although depletion of Myc/Mycn or Ccne1/Ccne2 compromised SSC activity, overexpression of Myc, but not Ccne1, increased colonization of SSCs. These results suggest that FBXW7 regulates SSC self-renewal in a negative manner by degradation of MYC. PMID:24879440

  8. Losing the battle but winning the war: game theoretic analysis of the competition between motoneurons innervating a skeletal muscle.

    PubMed

    Nowik, Irit; Zamir, Shmuel; Segev, Idan

    2012-01-01

    The fibers in a skeletal muscle are divided into groups called "muscle units" whereby each muscle unit is innervated by a single neuron. It was found that neurons with low activation thresholds have smaller muscle units than neurons with higher activation thresholds. This results in a fixed recruitment order of muscle units, from smallest to largest, called the "size principle." It is thought that the size principle results from a competitive process-taking place after birth-between the neurons innervating the muscle. The underlying mechanism of the competition was not understood. Moreover, the results in the majority of experiments that manipulated the activity during the competition period seemed to contradict the size principle. Experiments at the isolated muscle fibers showed that the competition is governed by a Hebbian-like rule, whereby neurons with low activation thresholds have a competitive advantage at any single muscle fiber. Thus neurons with low activation thresholds are expected to have larger muscle units in contradiction to what is seen empirically. This state of affairs was termed "paradoxical." In the present study we developed a new game theoretic framework to analyze such competitive biological processes. In this game, neurons are the players competing to innervate a maximal number of muscle fibers. We showed that in order to innervate more muscle fibers, it is advantageous to win (as the neurons with higher activation thresholds do) later competitions. This both explains the size principle and resolves the seemingly paradoxical experimental data. Our model establishes that the competition at each muscle fiber may indeed be Hebbian and that the size principle still emerges from these competitions as an overall property of the system. Thus, the less active neurons "lose the battle but win the war." Our model provides experimentally testable predictions. The new game-theoretic approach may be applied to competitions in other biological systems

  9. Market Imitation and Win-Stay Lose-Shift Strategies Emerge as Unintended Patterns in Market Direction Guesses

    PubMed Central

    Segura, Carlota; Duch, Jordi; Perelló, Josep

    2016-01-01

    Decisions made in our everyday lives are based on a wide variety of information so it is generally very difficult to assess what are the strategies that guide us. Stock market provides a rich environment to study how people make decisions since responding to market uncertainty needs a constant update of these strategies. For this purpose, we run a lab-in-the-field experiment where volunteers are given a controlled set of financial information -based on real data from worldwide financial indices- and they are required to guess whether the market price would go “up” or “down” in each situation. From the data collected we explore basic statistical traits, behavioural biases and emerging strategies. In particular, we detect unintended patterns of behavior through consistent actions, which can be interpreted as Market Imitation and Win-Stay Lose-Shift emerging strategies, with Market Imitation being the most dominant. We also observe that these strategies are affected by external factors: the expert advice, the lack of information or an information overload reinforce the use of these intuitive strategies, while the probability to follow them significantly decreases when subjects spends more time to make a decision. The cohort analysis shows that women and children are more prone to use such strategies although their performance is not undermined. Our results are of interest for better handling clients expectations of trading companies, to avoid behavioural anomalies in financial analysts decisions and to improve not only the design of markets but also the trading digital interfaces where information is set down. Strategies and behavioural biases observed can also be translated into new agent based modelling or stochastic price dynamics to better understand financial bubbles or the effects of asymmetric risk perception to price drops. PMID:27532219

  10. Comparison of total and cardiovascular death rates in the same city during a losing versus winning super bowl championship.

    PubMed

    Kloner, Robert A; McDonald, Scott; Leeka, Justin; Poole, W Kenneth

    2009-06-15

    The purpose of this study was to determine whether there were changes in death rates when a local football team participated in the Super Bowl. Los Angeles (LA) played in the Super Bowl twice: on January 20, 1980 (LA Rams vs Pittsburgh Steelers, which LA lost), and on January 22, 1984 (LA Raiders vs Washington Redskins, which LA won). Data from LA County were analyzed for all-cause and circulatory death rates for the Super Bowl and the following 14 days when LA played (Super Bowl-related days) and control days (from January 15 to the end of February for 1980 to 1983 and 1984 to 1988). The Super Bowl-related days during LA's losing 1980 game were associated with higher daily death rates in LA County (per 100,000 population) for all deaths (2.4482 vs 2.0968 for control days, p <0.0001), circulatory deaths (1.3024 vs 1.0665 for control days, p <0.0001), deaths from ischemic heart disease (0.8551 vs 0.7143 for control days, p <0.0001), and deaths from acute myocardial infarctions (0.2710 vs 0.2322 for control days, p = 0.0213). In contrast, the Super Bowl-related days during the winning 1984 game were associated with a lower rate of all-cause death (2.1870 vs 2.3205 for control days, p = 0.0302). In conclusion, the emotional stress of loss and/or the intensity of a game played by a sports team in a highly publicized rivalry such as the Super Bowl can trigger total and cardiovascular deaths. PMID:19539070

  11. Market Imitation and Win-Stay Lose-Shift Strategies Emerge as Unintended Patterns in Market Direction Guesses.

    PubMed

    Gutiérrez-Roig, Mario; Segura, Carlota; Duch, Jordi; Perelló, Josep

    2016-01-01

    Decisions made in our everyday lives are based on a wide variety of information so it is generally very difficult to assess what are the strategies that guide us. Stock market provides a rich environment to study how people make decisions since responding to market uncertainty needs a constant update of these strategies. For this purpose, we run a lab-in-the-field experiment where volunteers are given a controlled set of financial information -based on real data from worldwide financial indices- and they are required to guess whether the market price would go "up" or "down" in each situation. From the data collected we explore basic statistical traits, behavioural biases and emerging strategies. In particular, we detect unintended patterns of behavior through consistent actions, which can be interpreted as Market Imitation and Win-Stay Lose-Shift emerging strategies, with Market Imitation being the most dominant. We also observe that these strategies are affected by external factors: the expert advice, the lack of information or an information overload reinforce the use of these intuitive strategies, while the probability to follow them significantly decreases when subjects spends more time to make a decision. The cohort analysis shows that women and children are more prone to use such strategies although their performance is not undermined. Our results are of interest for better handling clients expectations of trading companies, to avoid behavioural anomalies in financial analysts decisions and to improve not only the design of markets but also the trading digital interfaces where information is set down. Strategies and behavioural biases observed can also be translated into new agent based modelling or stochastic price dynamics to better understand financial bubbles or the effects of asymmetric risk perception to price drops. PMID:27532219

  12. Measurement of canine gastric vascular permeability to plasma proteins in the normal and protein-losing states

    SciTech Connect

    Wood, J.G.; Davenport, H.W.

    1982-04-01

    An isolated segment of the greater curvature of a dog's stomach was perfused at constant flow through a single cannulated artery with donor blood containing 131I-albumin, 125I-fibrinogen, and papaverine. Perfusion pressure was 30-50 mmHg, and venous pressure was set at 15 mmHg. Venous blood was collected in 1-min samples for 60 min. Filtration of fluid and loss of labeled proteins were calculated as the difference between measured arterial inflow and venous outflow. Permeability-surface area products (PS) were calculated for the proteins, and reflection coefficients (sigma) were calculated from solute flux and filtration. Intraarterial infusion of histamine (1.6-1.9 microgram . ml-1) increased filtration and PS and decreased sigma for albumin but not fibrinogen. When protein-losing was established by topical irrigation with 10 mM dithiothreitol in neutral solution, filtration and PS increased, and sigma for albumin but not fibrinogen decreased. Irrigation of the mucosa with 10 mM salicylic acid in 100 mN HCl caused bleeding that was quantitated by addition of 51Cr-erythrocytes to perfusing blood. Filtration and PS increased, and sigma for albumin but not fibrinogen decreased. Hematocrit of blood lost remained low during extensive mucosal damage. Effects of histamine infusion were attenuated or abolished by cimetidine (4 mg . kg-1 loading, 1.4 mg . kg-1 . h-1 continuous infusion) or by pyrilamine maleate (5 mg . kg-1 bolus injection at beginning of irrigation, repeated at 40-50 min). Pyrilamine attenuated or abolished effects of topical dithiothreitol or salicylic acid. We conclude that during protein loss caused by dithiothreitol or salicylic acid, histamine released within the mucosa causes increased vascular permeability for plasma proteins.

  13. Genomic Landscape of Developing Male Germ Cells

    PubMed Central

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

    2010-01-01

    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.† PMID:19306351

  14. Expression of Genes Related to Germ Cell Lineage and Pluripotency in Single Cells and Colonies of Human Adult Germ Stem Cells.

    PubMed

    Conrad, Sabine; Azizi, Hossein; Hatami, Maryam; Kubista, Mikael; Bonin, Michael; Hennenlotter, Jörg; Sievert, Karl-Dietrich; Skutella, Thomas

    2016-01-01

    The aim of this study was to elucidate the molecular status of single human adult germ stem cells (haGSCs) and haGSC colonies, which spontaneously developed from the CD49f MACS and matrix- (collagen-/laminin+ binding-) selected fraction of enriched spermatogonia. Single-cell transcriptional profiling by Fluidigm BioMark system of a long-term cultured haGSCs cluster in comparison to human embryonic stem cells (hESCs) and human fibroblasts (hFibs) revealed that haGSCs showed a characteristic germ- and pluripotency-associated gene expression profile with some similarities to hESCs and with a significant distinction from somatic hFibs. Genome-wide comparisons with microarray analysis confirmed that different haGSC colonies exhibited gene expression heterogeneity with more or less pluripotency. The results of this study confirm that haGSCs are adult stem cells with a specific molecular gene expression profile in vitro, related but not identical to true pluripotent stem cells. Under ES-cell conditions haGSC colonies could be selected and maintained in a partial pluripotent state at the molecular level, which may be related to their cell plasticity and potential to differentiate into cells of all germ layers. PMID:26649052

  15. Expression of Genes Related to Germ Cell Lineage and Pluripotency in Single Cells and Colonies of Human Adult Germ Stem Cells

    PubMed Central

    Conrad, Sabine; Azizi, Hossein; Hatami, Maryam; Kubista, Mikael; Bonin, Michael; Hennenlotter, Jörg; Sievert, Karl-Dietrich; Skutella, Thomas

    2016-01-01

    The aim of this study was to elucidate the molecular status of single human adult germ stem cells (haGSCs) and haGSC colonies, which spontaneously developed from the CD49f MACS and matrix- (collagen−/laminin+ binding-) selected fraction of enriched spermatogonia. Single-cell transcriptional profiling by Fluidigm BioMark system of a long-term cultured haGSCs cluster in comparison to human embryonic stem cells (hESCs) and human fibroblasts (hFibs) revealed that haGSCs showed a characteristic germ- and pluripotency-associated gene expression profile with some similarities to hESCs and with a significant distinction from somatic hFibs. Genome-wide comparisons with microarray analysis confirmed that different haGSC colonies exhibited gene expression heterogeneity with more or less pluripotency. The results of this study confirm that haGSCs are adult stem cells with a specific molecular gene expression profile in vitro, related but not identical to true pluripotent stem cells. Under ES-cell conditions haGSC colonies could be selected and maintained in a partial pluripotent state at the molecular level, which may be related to their cell plasticity and potential to differentiate into cells of all germ layers. PMID:26649052

  16. Expression of cubilin in mouse testes and Leydig cells.

    PubMed

    Oh, Y S; Seo, J T; Ahn, H S; Gye, M C

    2016-04-01

    Cubilin (cubn) is a receptor for vitamins and various protein ligands. Cubn lacks a transmembrane domain but anchors to apical membranes by forming complexes with Amnionless or Megalin. In an effort to better understand the uptake of nutrients in testis, we analysed cubn expression in the developing mice testes. In testes, cubn mRNA increased from birth to adulthood. In the inter-stitium and isolated seminiferous tubules, neonatal increase in cubn mRNA until 14 days post-partum (pp) was followed by a marked increase at puberty (28 days pp). Cubn was found in the gonocytes, spermatogonia, spermatocytes and spermatids in the developing testes. In adult testes, strong Cubn immunoreactivity was found in the elongating spermatids, suggesting the role of Cubn in endocytosis during early spermiogenesis. In Sertoli cells and peritubular cells, Cubn immunoreactivity was weak throughout the testis development. In the inter-stitium, Cubn immunoreactivity was found in foetal Leydig cells, was weak to negligible in the stem cells and progenitor Leydig cells and was strong in immature and adult Leydig cells, demonstrating a positive association between Cubn and steroidogenic activity of Leydig cells. Collectively, these results suggest that Cubn may participate in the endocytotic uptake of nutrients in germ cells and somatic cells, supporting the spermatogenesis and steroidogenesis in mouse testes. PMID:26148765

  17. Reconstruction of a seminiferous tubule-like structure in a 3 dimensional culture system of re-aggregated mouse neonatal testicular cells within a collagen matrix.

    PubMed

    Zhang, Jidong; Hatakeyama, Jun; Eto, Ko; Abe, Shin-Ichi

    2014-09-01

    Male gonad development is initiated by the aggregation of pre-Sertoli cells (SCs), which surround germ cells to form cords. Several attempts to reconstruct testes from dissociated testicular cells have been made; however, only very limited morphogenesis beyond seminiferous cord formation has been achieved. Therefore, we aimed to reconstruct seminiferous tubules using a 3-dimensional (D) re-aggregate culture of testicular cells, which were dissociated from 6-dpp neonatal mice, inside a collagen matrix. We performed a short-term culture (for 3 days) and a long-term culture (up to 3 wks). The addition of KnockOut Serum Replacement (KSR) promoted (1) the enlargement of SC re-aggregates; (2) the attachment of peritubular myoid (PTM) cells around the SC re-aggregates; (3) the sorting of germ cells inside, and Leydig cells outside, seminiferous cord-like structures; (4) the alignment of SC polarity inside a seminiferous cord-like structure relative to the basement membrane; (5) the differentiation of SCs (the expression of the androgen receptor); (6) the formation of a blood-testis-barrier between the SCs; (7) SC elongation and lumen formation; and (8) the proliferation of SCs and spermatogonia, as well as the differentiation of spermatogonia into primary spermatocytes. Eventually, KSR promoted the formation of seminiferous tubule-like structures, which accompanied germ cell differentiation. However, these morphogenetic events did not occur in the absence of KSR. This in vitro system presents an excellent model with which to identify the possible factors that induce these events and to analyze the mechanisms that underlie cellular interactions during testicular morphogenesis and germ cell differentiation. PMID:24717811

  18. Spermatogonial Nature of the Germ Cell Component of Canine Testicular Mixed Germ Cell-Sex Cord Stromal Tumours.

    PubMed

    Mizukami, S; Murakami, T; Tanaka, T; Machida, N; Nomura, K; Yoshida, T; Shibutani, M

    2016-07-01

    The present study has characterized the germ cell component of canine testicular mixed germ cell-sex cord stromal tumours (MGSCTs) by examining the histological nature and histochemical and immunohistochemical features using gonocytic and spermatogonial cellular markers, c-Kit, placental alkaline phosphatase (PLAP), protein gene product 9.5 (PGP9.5), Sal-like protein 4 (SALL4), and the periodic acid-Schiff (PAS) reaction. Histologically, all 45 examples of MGSCTs were classified as spermatocytic seminomas (SSs) and Sertoli cell tumours in combination. The germ cell component of all MGSCTs was negative by PAS staining. Immunohistochemically, PLAP immunoreactivity was lacking in the germ cell component of all MGSCTs, which is not consistent with a gonocytic origin. The germ cell component was positive for PGP9.5 and SALL4 in all MGSCTs and positive for c-Kit in 53% of MGSCTs, which is consistent with the phenotype of spermatogonia. Furthermore, the germ cell component in 71% of MGSCTs had moderate immunoreactivity for SALL4, which is suggestive of a spermatogonial phenotype. Conversely, 29% of cases had a minor population of germ cells showing strong SALL4 immunoreactivity, suggesting a phenotype similar to prespermatogonia. The results suggest that the germ cell component of canine MGSCTs is morphologically classified as SS, with the majority of cases showing the spermatogonial phenotype and some cases containing a small population of prespermatogonia. PMID:27241073

  19. Periodic retinoic acid–STRA8 signaling intersects with periodic germ-cell competencies to regulate spermatogenesis

    PubMed Central

    Endo, Tsutomu; Romer, Katherine A.; Anderson, Ericka L.; Baltus, Andrew E.; de Rooij, Dirk G.; Page, David C.

    2015-01-01

    Mammalian spermatogenesis—the transformation of stem cells into millions of haploid spermatozoa—is elaborately organized in time and space. We explored the underlying regulatory mechanisms by genetically and chemically perturbing spermatogenesis in vivo, focusing on spermatogonial differentiation, which begins a series of amplifying divisions, and meiotic initiation, which ends these divisions. We first found that, in mice lacking the retinoic acid (RA) target gene Stimulated by retinoic acid gene 8 (Stra8), undifferentiated spermatogonia accumulated in unusually high numbers as early as 10 d after birth, whereas differentiating spermatogonia were depleted. We thus conclude that Stra8, previously shown to be required for meiotic initiation, also promotes (but is not strictly required for) spermatogonial differentiation. Second, we found that injection of RA into wild-type adult males induced, independently, precocious spermatogonial differentiation and precocious meiotic initiation; thus, RA acts instructively on germ cells at both transitions. Third, the competencies of germ cells to undergo spermatogonial differentiation or meiotic initiation in response to RA were found to be distinct, periodic, and limited to particular seminiferous stages. Competencies for both transitions begin while RA levels are low, so that the germ cells respond as soon as RA levels rise. Together with other findings, our results demonstrate that periodic RA–STRA8 signaling intersects with periodic germ-cell competencies to regulate two distinct, cell-type-specific responses: spermatogonial differentiation and meiotic initiation. This simple mechanism, with one signal both starting and ending the amplifying divisions, contributes to the prodigious output of spermatozoa and to the elaborate organization of spermatogenesis. PMID:25902548

  20. The Mouse Cohesin-Associated Protein PDS5B Is Expressed in Testicular Cells and Is Associated with the Meiotic Chromosome Axes.

    PubMed

    Fukuda, Tomoyuki; Hoog, Christer

    2010-01-01

    During the first meiotic prophase, the cohesin complex is localized to the chromosome axis and contributes to chromosome organization, pairing, synapsis, and recombination. The PDS5 protein, an accessory factor of the cohesin complex, is known to be a component of meiotic chromosome cores in fungi and to be implicated in meiotic chromosome structure and function. We found by immunoblotting experiments that a mammalian PDS5 protein, PDS5B, is abundantly expressed in mouse testis compared to other tissues. Immunofluorescence labeling experiments revealed that PDS5B is highly expressed in spermatogonia and that most PDS5B is depleted from chromatin as cells enter meiosis. During the first meiotic prophase, PDS5B associates with the axial cores of chromosomes. The axial association of PDS5B was observed also in the absence of synaptonemal complex proteins, such as SYCP1 and SYCP3, suggesting that PDS5B is an integral part of the chromosome axis as defined by the cohesin complex. These results suggest that PDS5B modulates cohesin functions in spermatocytes as well as in spermatogonia, contributing to meiotic chromosome structure and function. PMID:24710098

  1. The Mouse Cohesin-Associated Protein PDS5B Is Expressed in Testicular Cells and Is Associated with the Meiotic Chromosome Axes

    PubMed Central

    Fukuda, Tomoyuki; Hoog, Christer

    2010-01-01

    During the first meiotic prophase, the cohesin complex is localized to the chromosome axis and contributes to chromosome organization, pairing, synapsis, and recombination. The PDS5 protein, an accessory factor of the cohesin complex, is known to be a component of meiotic chromosome cores in fungi and to be implicated in meiotic chromosome structure and function. We found by immunoblotting experiments that a mammalian PDS5 protein, PDS5B, is abundantly expressed in mouse testis compared to other tissues. Immunofluorescence labeling experiments revealed that PDS5B is highly expressed in spermatogonia and that most PDS5B is depleted from chromatin as cells enter meiosis. During the first meiotic prophase, PDS5B associates with the axial cores of chromosomes. The axial association of PDS5B was observed also in the absence of synaptonemal complex proteins, such as SYCP1 and SYCP3, suggesting that PDS5B is an integral part of the chromosome axis as defined by the cohesin complex. These results suggest that PDS5B modulates cohesin functions in spermatocytes as well as in spermatogonia, contributing to meiotic chromosome structure and function. PMID:24710098

  2. Inherited or Behavior? What Causal Beliefs about Obesity Are Associated with Weight Perceptions and Decisions to Lose Weight in a US Sample?

    PubMed Central

    Fleary, Sasha A.

    2014-01-01

    Objectives. To identify the extent to which (1) beliefs about obesity and obesity-related behaviors distinguish individuals based on weight perception (WP) and (2) beliefs about obesity predict perceived health status and WP and how these in turn predict decisions to try to lose weight. Method. 7456 noninstitutionalized US adults (Mage = 54.13, SDage = 16.93; 61.2% female; 75.9% White) completed the 2007 Health Information National Trends Survey. Multinomial logistic regressions and structural equation modeling were used to accomplish study objectives. Results. Age, gender, information-seeking, health status, belief that obesity is inherited, and knowledge of fruits and vegetables recommendations distinguished participants based on WP. Beliefs about obesity predicted health status, WP, and trying to lose weight in the general model. The models varied based on gender, race/ethnicity, education, and weight misperception. Conclusion. This study supports the role of beliefs about obesity, WP, and health perceptions in individuals' decisions and actions regarding weight management. This study increases our understanding of gender, race/ethnicity, education, and weight misperceptions differences in decisions to lose weight. This knowledge may lead to targeted interventions, rather than “one size fits all” interventions, to promote health and prevent obesity.

  3. In it together: Mother talk of weight concerns moderates negative outcomes of encouragement to lose weight on daughter body dissatisfaction and disordered eating.

    PubMed

    Hillard, Erin E; Gondoli, Dawn M; Corning, Alexandra F; Morrissey, Rebecca A

    2016-03-01

    Mothers' influence on their daughters is important for understanding girls' disordered eating and body dissatisfaction. Direct maternal encouragement of daughters to lose weight is linked to daughters' development of bulimic symptoms, and additional findings indicate that daughters whose mothers merely talk about dieting and body dissatisfaction are more likely to be diagnosed with an eating disorder. The current study extends such research by examining the interactive contributions of maternal encouragement to lose weight and maternal dieting discussions to the prediction of early adolescent daughters' body dissatisfaction and disordered eating over the middle school period. Participants were 89 adolescent girls who were in the 6th grade at Time 1. Regression analyses were conducted to examine interactive effects of mother encouragement to diet and talk of weight concerns on daughter body dissatisfaction, drive for thinness, and dieting behavior. Results suggest an interactive effect in which mothers' dieting talk may act as a buffer against the negative effects of direct encouragement to lose weight. PMID:26551484

  4. Large and forgotten in rural Australia: assessment, attitudes and possible approaches to losing weight in young adult males

    PubMed Central

    2014-01-01

    Background Young Adult Males (YAMs) in rural Australia are poorly studied with respect to overweight and obesity. Firstly, we explored the feasibility of recruiting 17–25 year old YAMs to obtain baseline data on overweight and obesity rates, socio-demographics, nutrition, exercise and mobile phone usage. Secondly, we explored the views of YAMs with a waist measurement over 94 cm about using mobile phone text messages to promote weight loss and incentives to promote healthy lifestyles. Methods A two-staged, mixed-methods approach was used to study obesity and overweight issues in Dubbo, a regional city in New South Wales, Australia. In Phase I, socio-demographic, health behaviour and mobile phone usage data were collected using a questionnaire and anthropometric data collected by direct measurement. In Phase II, YAMs’ views were explored by focus group discussion using a semi-structured questionnaire. Results Phase I (145 participants): mean Body Mass Index (BMI) 25.06 ± 5.01; mean waist circumference 87.4 ± 15.4 cm. In total, 39.3% were obese (12.4%) or overweight (26.9%) and 24.1% had an increased risk of metabolic complications associated with obesity. 135 (93.1%) owned a mobile phone and sent on average 17 ± 25 text messages per day and received 18 ± 24. Phase II (30 participants): YAMs acknowledged that overweight and obesity was a growing societal concern with many health related implications, but didn’t feel this was something that affected them personally at this stage of their lives. Motivation was therefore an issue. YAMs admitted that they would only be concerned about losing weight if something drastic occurred in their lives. Text messages would encourage and motivate them to adopt a healthy lifestyle if they were individually tailored. Gym memberships, not cash payments, seem to be the most favoured incentive. Conclusion There is a clear need for an effective health promotion strategy for the almost 40% overweight or obese

  5. Losing fat, gaining treatments: the use of biomedicine as a cure for folk illnesses in the Andes

    PubMed Central

    2014-01-01

    Background This article explores how people in the Andes incorporate beliefs from both biomedical and ethnomedical systems in treating folk illnesses that often involve spiritual beings. The article focuses on the kharisiri—one who is believed to steal fat and blood from unsuspecting humans to make exchanges with the devil. The kharisiri in turn is rewarded with good fortune. Victims of kharisiris, however, fall ill and may die if untreated. Historically, kharisiri victims relied on ethnomedicine for treatment, but it appears biomedical pills are now perceived by some as an effective treatment. By drawing on participants’ attitudes towards biomedicine, and how people in the Andes conceptualize health, this article theorizes as to why biomedical pills are sought to treat kharisiri attacks but not for other folk illnesses. Methods Fieldwork was conducted in Arequipa and Yunguyo among market vendors, who make up a significant portion of Peru’s working population. This type of work increases the risk of different illnesses due to work conditions like exposure to extreme temperatures, long-distance travel, and social dynamics. Biomedical and ethnomedical products are often sold in and around marketplaces, making vendors a compelling group for exploring issues relating to treatment systems. Qualitative data was collected in 2011 with a follow-up visit in 2013. Participant observation, informal conversations, and unstructured interviews with 29 participants informed the study. Results Participants unanimously reported that biomedical pills are not capable of treating folk illnesses such as susto and mal de ojo. Several participants reported that pharmaceutical pills can cure kharisiri victims. Conclusions In comparison to other folk illnesses that involve spiritual beings, those who fall ill from a kharisiri attack lose physical elements (fat and blood) rather than their soul (ánimo) or becoming ill due to a misbalance in reciprocal relations—either with humans

  6. Physicians' use of the 5As in counseling obese patients: is the quality of counseling associated with patients' motivation and intention to lose weight?

    PubMed Central

    2010-01-01

    Background Physicians are encouraged to counsel obese patients to lose weight, but studies measuring the quality of physicians' counseling are rare. We sought to describe the quality of physicians' obesity counseling and to determine associations between the quality of counseling and obese patients' motivation and intentions to lose weight, key predictors of behavior change. Methods We conducted post-visit surveys with obese patients to assess physician's use of 5As counseling techniques and the overall patient-centeredness of the physician.. Patients also reported on their motivation to lose weight and their intentions to eat healthier and exercise. One-way ANOVAs were used to describe mean differences in number of counseling practices across levels of self-rated intention and motivation. Logistic regression analyses were conducted to assess associations between number of 5As counseling practices used and patient intention and motivation. Results 137 patients of 23 physicians were included in the analysis. While 85% of the patients were counseled about obesity, physicians used only a mean of 5.3 (SD = 4.6) of 18 possible 5As counseling practices. Patients with higher levels of motivation and intentions reported receiving more 5As counseling techniques than those with lower levels. Each additional counseling practice was associated with higher odds of being motivated to lose weight (OR 1.31, CI 1.11-1.55), intending to eat better (OR 1.23, CI 1.06-1.44), and intending to exercise regularly (OR 1.14, CI 1.00-1.31). Patient centeredness of the physician was also positively associated with intentions to eat better (OR 2.96, CI 1.03-8.47) and exercise (OR 26.07, CI 3.70-83.93). Conclusions Quality of physician counseling (as measured using the 5As counseling framework and patient-centeredness scales) was associated with motivation to lose weight and intentions to change behavior. Future studies should determine whether higher quality obesity counseling leads to

  7. Differentiation of human umbilical cord mesenchymal stem cells into germ-like cells in mouse seminiferous tubules

    PubMed Central

    CHEN, HUI; TANG, QIU-LING; WU, XIAO-YING; XIE, LI-CHUN; LIN, LI-MIN; HO, GU-YU; MA, LIAN

    2015-01-01

    Our previous study demonstrated that human umbilical cord mesenchymal stem cells (HUMSCs) were capable of differentiation into germ cells in vitro. To assess this potential in vivo, HUMSCs were microinjected into the lumen of seminiferous tubules of immunocompetent mice, which were treated with busulfan to destroy endogenous spermatogenesis. Bromodeoxyuridine labeling studies demonstrated that HUMSCs survived in the tubule for at least 120 days, exhibited a round cell shape typical of proliferating or differentiating germ cells, migrated to the basement of the tubule, where proliferating spermatogonia reside and returned to the luminal compartment, where differentiating spermatids and spermatozoa reside. The migration pattern resembled that of germ cell development in vivo. Immunohistochemical and colocalization studies revealed that transplanted HUMSCs expressed the germ cell markers octamer-binding transcription factor 4, α6 integrin, C-kit and VASA, confirming the germ cell differentiation. In addition, it was observed that tubules transplanted with HUMSCs exhibited marked improvement in the histological features damaged by the chemotherapeutic busulfan, as judged by morphology and quantitative histology. Taken together, these data demonstrated the capacity of HUMSCs to form germ cells in the testes and to repair testicular tissue. These findings suggest a potential utility of HUMSCs to treat the infertility and testicular insufficiency caused by cancer therapeutics. PMID:25815600

  8. Losing the Quality Battle in Australian Education for Librarianship: A Decade on. (An Update on the Original Article by Ross Harvey, "Losing the Quality Battle in Australian Education for Librarianship". "The Australian Library Journal", 50 No. 1, 2001: 15-22.)

    ERIC Educational Resources Information Center

    Harvey, Ross

    2011-01-01

    The Editor of "ALJ" has invited me to comment on my 2001 article "Losing the quality battle in Australian education for librarianship" (Harvey 2001). The article was prompted by a period I spent as a visiting professor in the Department of Information Studies at UCLA (the University of California Los Angeles) and was written while I was there.…

  9. Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl(-) channel disruption.

    PubMed

    Bösl, M R; Stein, V; Hübner, C; Zdebik, A A; Jordt, S E; Mukhopadhyay, A K; Davidoff, M S; Holstein, A F; Jentsch, T J

    2001-03-15

    The functions of some CLC Cl(-) channels are evident from human diseases that result from their mutations, but the role of the broadly expressed ClC-2 Cl(-) channel is less clear. Several important functions have been attributed to ClC-2, but contrary to these expectations ClC-2-deficient mice lacked overt abnormalities except for a severe degeneration of the retina and the testes, which led to selective male infertility. Seminiferous tubules did not develop lumina and germ cells failed to complete meiosis. Beginning around puberty there was a massive death of primary spermatocytes and later also of spermatogonia. Tubules were filled with abnormal Sertoli cells, which normally express ClC-2 in patches adjacent to germ cells. In the retina, photoreceptors lacked normal outer segments and degenerated between days P10 and P30. The current across the retinal pigment epithelium was severely reduced at P36. Thus, ClC-2 disruption entails the death of two cell types which depend on supporting cells that form the blood-testes and blood-retina barriers. We propose that ClC-2 is crucial for controlling the ionic environment of these cells. PMID:11250895

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

    PubMed Central

    Jung, Dajung; Kee, Kehkooi

    2015-01-01

    Understanding the mechanisms of human germ cell biology is important for developing infertility treatments. However, little is known about the mechanisms that regulate human gametogenesis due to the difficulties in collecting samples, especially germ cells during fetal development. In contrast to the mitotic arrest of spermatogonia stem cells in the fetal testis, female germ cells proceed into meiosis and began folliculogenesis in fetal ovaries. Regulations of these developmental events, including the initiation of meiosis and the endowment of primordial follicles, remain an enigma. Studying the molecular mechanisms of female germ cell biology in the human ovary has been mostly limited to spatiotemporal characterizations of genes or proteins. Recent efforts in utilizing in vitro differentiation system of stem cells to derive germ cells have allowed researchers to begin studying molecular mechanisms during human germ cell development. Meanwhile, the possibility of isolating female germline stem cells in adult ovaries also excites researchers and generates many debates. This review will mainly focus on presenting and discussing recent in vivo and in vitro studies on female germ cell biology in human. The topics will highlight the progress made in understanding the three main stages of germ cell developments: namely, primordial germ cell formation, meiotic initiation, and folliculogenesis. PMID:25652637

  11. Mutation of mitochondria genome: trigger of somatic cell transforming to cancer cell.

    PubMed

    Jianping, Du

    2010-01-01

    Nearly 80 years ago, scientist Otto Warburg originated a hypothesis that the cause of cancer is primarily a defect in energy metabolism. Following studies showed that mitochondria impact carcinogenesis to remodel somatic cells to cancer cells through modifying the genome, through maintenance the tumorigenic phenotype, and through apoptosis. And the Endosymbiotic Theory explains the origin of mitochondria and eukaryotes, on the other hands, the mitochondria also can fall back. Compared to chromosome genomes, the mitochondria genomes were not restricted by introns so they were mutated(fall back) easy. The result is that mitochondria lose function and internal environment of somatic cell become acid and evoked chromosome genomes to mutate, in the end somatic cells become cancer cells. It is the trigger of somatic cell transforming to cancer cell that mitochondria genome happen mutation and lose function. PMID:20181100

  12. Biology and identity of fish spermatogonial stem cell.

    PubMed

    Lacerda, Samyra Maria dos Santos Nassif; Costa, Guilherme Mattos Jardim; de França, Luiz Renato

    2014-10-01

    Although present at relatively low number in the testis, spermatogonial stem cells (SSCs) are crucial for the establishment and maintenance of spermatogenesis in eukaryotes and, until recently, those cells were investigated in fish using morphological criteria. The isolation and characterization of these cells in fish have been so far limited by the lack of specific molecular markers, hampering the high SSCs biotechnological potential for aquaculture. However, some highly conserved vertebrate molecular markers, such as Gfra1 and Pou5f1/Oct4, are now available representing important candidates for studies evaluating the regulation of SSCs in fish and even functional investigations using germ cells transplantation. A technique already used to demonstrate that, different from mammals, fish germ stem cells (spermatogonia and oogonia) present high sexual plasticity that is determined by the somatic microenvironment. As relatively well established in mammals, and demonstrated in zebrafish and dogfish, this somatic environment is very important for the preferential location and regulation of SSCs. Importantly, a long-term in vitro culture system for SSCs has been now established for some fish species. Therefore, besides the aforementioned possibilities, such culture system would allow the development of strategies to in vitro investigate key regulatory and functional aspects of germline stem cells (ex: self-renewal and/or differentiation) or to amplify SSCs of rare, endangered, or commercially valuable fish species, representing an important tool for transgenesis and the development of new biotechnologies in fish production. PMID:24967950

  13. Germ cell DNA quantification shortly after IR laser radiation.

    PubMed

    Bermúdez, D; Carrasco, F; Diaz, F; Perez-de-Vargas, I

    1991-01-01

    The immediate effect of IR laser radiation on rat germ cells was studied by cytophotometric quantification of the nuclear DNA content in testicular sections. Two different levels of radiation were studied: one according to clinical application (28.05 J/cm2) and another known to increase the germ cell number (46.80 J/cm2). The laser beam induced changes in the germ cell DNA content depending on the cell type, the cell cycle phase and the doses of radiation energy applied. Following irradiation at both doses the percentage of spermatogonia showing a 4c DNA content was increased, while the percentage of these with a 2c DNA content was decreased. Likewise, the percentages of primary spermatocytes with a DNA content equal to 4c (at 28.05 J/cm2), between 2c and 4c (at 46.80 J/cm2) and higher than 4c (at both doses) were increased. No change in the mean spermatid DNA content was observed. Nevertheless, at 46.80 J/cm2 the percentages of elongated spermatids with a c or 2c DNA content differed from the controls. Data show that, even at laser radiation doses used in therapy, the germ cell DNA content is increased shortly after IR laser radiation. PMID:1772145

  14. Ectopic expression of single transcription factors directs differentiation of a medaka spermatogonial cell line.

    PubMed

    Thoma, Eva C; Wagner, Toni U; Weber, Isabell P; Herpin, Amaury; Fischer, Andreas; Schartl, Manfred

    2011-08-01

    The capability to form all cell types of the body is a unique feature of stem cells. However, many questions remain concerning the mechanisms regulating differentiation potential. The derivation of spermatogonial cell lines (SGs) from mouse and human, which can differentiate across germ-layer borders, suggested male germ cells as a potential stem cell source in addition to embryonic stem cells. Here, we present a differentiation system using an SG of the vertebrate model organism Oryzias latipes (medaka). We report differentiation of this cell line into 4 different ectodermal and mesodermal somatic cell types. In addition to differentiation into adipocytes by retinoic acid treatment, we demonstrate for the first time that directed differentiation of an SG can be induced by ectopic expression of single transcription factors, completely independent of culture conditions. Transient transfection with mitf-m, a transcription factor that has been shown to induce differentiation into melanocytes in medaka embryonic stem cells, resulted in the formation of the same cell type in spermatogonia. Similarly, the formation of neuron-like cells and matrix-depositing osteoblasts was induced by ectopic expression of mash1 and cbfa1, respectively. Interestingly, we found that the expression of all mentioned fate-inducing transcription factors leads to recapitulation of the temporal pattern of marker gene expression known from in vivo studies. PMID:21090990

  15. The Social Amoeba Polysphondylium pallidum Loses Encystation and Sporulation, but Can Still Erect Fruiting Bodies in the Absence of Cellulose

    PubMed Central

    Du, Qingyou; Schaap, Pauline

    2014-01-01

    Amoebas and other freely moving protists differentiate into walled cysts when exposed to stress. As cysts, amoeba pathogens are resistant to biocides, preventing treatment and eradication. Lack of gene modification procedures has left the mechanisms of encystation largely unexplored. Genetically tractable Dictyostelium discoideum amoebas require cellulose synthase for formation of multicellular fructifications with cellulose-rich stalk and spore cells. Amoebas of its distant relative Polysphondylium pallidum (Ppal), can additionally encyst individually in response to stress. Ppal has two cellulose synthase genes, DcsA and DcsB, which we deleted individually and in combination. Dcsa- mutants formed fruiting bodies with normal stalks, but their spore and cyst walls lacked cellulose, which obliterated stress-resistance of spores and rendered cysts entirely non-viable. A dcsa-/dcsb- mutant made no walled spores, stalk cells or cysts, although simple fruiting structures were formed with a droplet of amoeboid cells resting on an sheathed column of decaying cells. DcsB is expressed in prestalk and stalk cells, while DcsA is additionally expressed in spores and cysts. We conclude that cellulose is essential for encystation and that cellulose synthase may be a suitable target for drugs to prevent encystation and render amoeba pathogens susceptible to conventional antibiotics. PMID:25113829

  16. Probabilistic risk assessment of the Space Shuttle. Phase 3: A study of the potential of losing the vehicle during nominal operation. Volume 2: Integrated loss of vehicle model

    NASA Technical Reports Server (NTRS)

    Fragola, Joseph R.; Maggio, Gaspare; Frank, Michael V.; Gerez, Luis; Mcfadden, Richard H.; Collins, Erin P.; Ballesio, Jorge; Appignani, Peter L.; Karns, James J.

    1995-01-01

    The application of the probabilistic risk assessment methodology to a Space Shuttle environment, particularly to the potential of losing the Shuttle during nominal operation is addressed. The different related concerns are identified and combined to determine overall program risks. A fault tree model is used to allocate system probabilities to the subsystem level. The loss of the vehicle due to failure to contain energetic gas and debris, to maintain proper propulsion and configuration is analyzed, along with the loss due to Orbiter, external tank failure, and landing failure or error.

  17. The use of low-calorie sweeteners is associated with self-reported prior intent to lose weight in a representative sample of US adults

    PubMed Central

    Drewnowski, A; Rehm, C D

    2016-01-01

    Background: Low-calorie sweeteners (LCSs) are said to be a risk factor for obesity and diabetes. Reverse causality may be an alternative explanation. Methods: Data on LCS use, from a single 24-h dietary recall, for a representative sample of 22 231 adults were obtained from 5 cycles of the National Health and Nutrition Examination Survey (1999–2008 NHANES). Retrospective data on intent to lose or maintain weight during the prior 12-months and 10-year weight history were obtained from the weight history questionnaire. Objectively measured heights and weights were obtained from the examination. Primary analyses evaluated the association between intent to lose/maintain weight and use of LCSs and specific LCS product types using survey-weighted generalized linear models. We further evaluated whether body mass index (BMI) may mediate the association between weight loss intent and use of LCSs. The association between 10-year weight history and current LCS use was evaluated using restricted cubic splines. Results: In cross-sectional analyses, LCS use was associated with a higher prevalence of obesity and diabetes. Adults who tried to lose weight during the previous 12 months were more likely to consume LCS beverages (prevalence ratio=1.64, 95% confidence interval (CI) 1.54–1.75), tabletop LCS (prevalence ratio=1.68, 95% CI 1.47–1.91) and LCS foods (prevalence ratio=1.93, 95% CI 1.60–2.33) as compared with those who did not. In mediation analyses, BMI only partially mediated the association between weight control history and the use of LCS beverages, tabletop LCS, but not LCS foods. Current LCS use was further associated with a history of prior weight change (for example, weight loss and gain). Conclusions: LCS use was associated with self-reported intent to lose weight during the previous 12 months. This association was only partially mediated by differences in BMI. Any inference of causality between attempts at weight control and LCS use is tempered by the

  18. Id4 Marks Spermatogonial Stem Cells in the Mouse Testis

    PubMed Central

    Sun, Feng; Xu, Qing; Zhao, Danfeng; Degui Chen, Charlie

    2015-01-01

    Mammalian spermatogenesis is a classic adult stems cell–dependent process, supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs). However, the identification of SSCs and elucidation of their behaviors in undisturbed testis has long been a big challenge. Here, we generated a knock-in mouse model, Id4-2A-CreERT2-2A-tdTomato, which allowed us to mark Id4-expressing (Id4+) cells at different time points in situ and track their behaviors across distinct developmental stages during steady-state and regenerating spermatogenesis. We found that Id4+ cells continue to produce spermatogonia, spermatocytes and sperm in mouse testis, showing they are capable of self-renewal and have differentiation potential. Consistent with these findings, ablation of Id4+ cells in mice results in a loss of spermatogenesis. Furthermore, developmental fate mapping reveals that Id4+ SSCs originate from neonate Id4+ gonocytes. Therefore, our results indicate that Id4 marks spermatogonial stem cells in the mouse testis. PMID:26621350

  19. DMRT1 Is Required for Mouse Spermatogonial Stem Cell Maintenance and Replenishment.

    PubMed

    Zhang, Teng; Oatley, Jon; Bardwell, Vivian J; Zarkower, David

    2016-09-01

    Male mammals produce sperm for most of postnatal life and therefore require a robust germ line stem cell system, with precise balance between self-renewal and differentiation. Prior work established doublesex- and mab-3-related transcription factor 1 (Dmrt1) as a conserved transcriptional regulator of male sexual differentiation. Here we investigate the role of Dmrt1 in mouse spermatogonial stem cell (SSC) homeostasis. We find that Dmrt1 maintains SSCs during steady state spermatogenesis, where it regulates expression of Plzf, another transcription factor required for SSC maintenance. We also find that Dmrt1 is required for recovery of spermatogenesis after germ cell depletion. Committed progenitor cells expressing Ngn3 normally do not contribute to SSCs marked by the Id4-Gfp transgene, but do so when spermatogonia are chemically depleted using busulfan. Removal of Dmrt1 from Ngn3-positive germ cells blocks the replenishment of Id4-GFP-positive SSCs and recovery of spermatogenesis after busulfan treatment. Our data therefore reveal that Dmrt1 supports SSC maintenance in two ways: allowing SSCs to remain in the stem cell pool under normal conditions; and enabling progenitor cells to help restore the stem cell pool after germ cell depletion. PMID:27583450

  20. Mouse testis cell sorting according to DNA and mitochondrial changes during spermatogenesis

    SciTech Connect

    Petit, J.M.; Ratinaud, M.H.; Cordelli, E.; Spano, M.; Julien, R.

    1995-04-01

    Flow cytometry can measure variations in DNA content and chromatin structure as well as dramatic changes in the mitochondria of germ cells during maturation from spermatogonia to elongated spermatids. Using 10-N nonyl acridine orange (NAO), an inner mitochondrial membrane dye, it is easy to follow mitochondria rearrangements. Mouse testis cells stained with the DNA fluorescent probe propidium iodide (PI) and analyzed by flow cytometry can be discriminated on the basis of their ploidy levels into five main regions corresponding to elongated spermatids, round spermatids, diploid, S-phase, and tetraploid cells. The simultaneous use of PI and NAO demonstrated the presence of cells having low and high mitochondrial content in the haploid, diploid, and tetraploid compartments. Eleven sorting windows were selected from the bivariate analysis (PI/NAO) and the corresponding cells were identified by microscopic observation. Cells were also discriminated by two parameter analysis of DNA content vs. cell diameter. The definition of seven different regions allowed us to determine NAO or rhodamine 123 (Rh 123) uptakes in each compartment. We observed that the ratio (Rh 123/NAO) dramatically changed according to the progression of cell differentiation which occurs during spermatogenesis. 45 refs., 5 figs., 2 tabs.

  1. Immunotherapy in Cancer: A Combat between Tumors and the Immune System; You Win Some, You Lose Some

    PubMed Central

    Madorsky Rowdo, Florencia Paula; Baron, Antonela; Urrutia, Mariela; Mordoh, José

    2015-01-01

    Cancer immunotherapy has emerged as a treatment modality, mainly as the result of discoveries in the immune response regulation, including mechanisms that turn off immune responses. Immunogenic cutaneous melanoma is a canonical model for therapeutic immunotherapy studies. “Passive” immunotherapy with monoclonal antibodies (mAbs) has outpaced “active” immunotherapy with anti-tumor vaccines, and mAbs that antagonize the off responses have been recently introduced in clinical practice. Despite these recent successes, many unresolved practical and theoretical questions remain. Notably unknown are the identity of the lymphocytes that eliminate tumor cells, which white cells enter into tumors, through which endothelium, in what order, and how they perform their task. The parameters of size and location that could be used to determine in which tumors the immune response may be sufficient to eradicate the tumor are yet unknown. Immunotherapy has been so far more efficient to treat solid and hematologic tumors located outside the central nervous system, than primary brain tumors and brain metastases. In contrast to recent advances with mAbs, anti-tumor vaccine development has been lagging behind. The multiplicity of antigens that must be targeted to achieve significant clinical response is partially responsible for this lag, especially in melanoma, one of the most mutated tumors. Further hampering vaccination results is the fact that tumor elimination by the immune system is the result of a race between tumors with different growth rates and the relatively slow development of the adaptive immune response. The enhancement of the native arm of the immune response or the administration of targeted chemotherapy to slow tumor development, are approaches that should be studied. Finally, criteria used to analyze patient response to immunotherapeutic treatments must be perfected, and the patient populations that could benefit the most from this approach must be better

  2. Judgments of Nonverbal Behaviour by Children with High-Functioning Autism Spectrum Disorder: Can they Detect Signs of Winning and Losing from Brief Video Clips?

    PubMed

    Ryan, Christian; Furley, Philip; Mulhall, Kathleen

    2016-09-01

    Typically developing children are able to judge who is winning or losing from very short clips of video footage of behaviour between active match play across a number of sports. Inferences from "thin slices" (short video clips) allow participants to make complex judgments about the meaning of posture, gesture and body language. This study extends the use of the thin slice research paradigm to children with high-functioning autism spectrum disorder (ASD). We tested 38 children with ASD, in two age groups: 15 participants aged 5-8 years and 23 participants aged 9-13 years. We found that the children with ASD had a rate of accuracy similar to that of typically developing peers tested in a previous study. PMID:27306454

  3. High-temperature Solar Cell Development

    NASA Technical Reports Server (NTRS)

    Landis, Geoffrey A.; Merritt, Danielle; Raffaelle, Ryne P.; Scheiman, David

    2005-01-01

    The vast majority of space probes to date have relied upon photovoltaic power generation. If future missions designed to probe environments close to the sun (Figure 1) will be able to use such power generation, solar cells that can function at high temperatures, under high light intensity, and high radiation conditions must be developed. The significant problem is that solar cells lose performance at high temperatures.

  4. Severe Salt-Losing Syndrome and Hyperkalemia Induced by Adult Nephron-Specific Knockout of the Epithelial Sodium Channel α-Subunit.

    PubMed

    Perrier, Romain; Boscardin, Emilie; Malsure, Sumedha; Sergi, Chloé; Maillard, Marc P; Loffing, Johannes; Loffing-Cueni, Dominique; Sørensen, Mads Vaarby; Koesters, Robert; Rossier, Bernard C; Frateschi, Simona; Hummler, Edith

    2016-08-01

    Systemic pseudohypoaldosteronism type 1 (PHA-1) is a severe salt-losing syndrome caused by loss-of-function mutations of the amiloride-sensitive epithelial sodium channel (ENaC) and characterized by neonatal life-threatening hypovolemia and hyperkalemia. The very high plasma aldosterone levels detected under hypovolemic or hyperkalemic challenge can lead to increased or decreased sodium reabsorption, respectively, through the Na(+)/Cl(-) cotransporter (NCC). However, the role of ENaC deficiency remains incompletely defined, because constitutive inactivation of individual ENaC subunits is neonatally lethal in mice. We generated adult inducible nephron-specific αENaC-knockout mice (Scnn1a(Pax8/LC1)) that exhibit hyperkalemia and body weight loss when kept on a regular-salt diet, thus mimicking PHA-1. Compared with control mice fed a regular-salt diet, knockout mice fed a regular-salt diet exhibited downregulated expression and phosphorylation of NCC protein, despite high plasma aldosterone levels. In knockout mice fed a high-sodium and reduced-potassium diet (rescue diet), although plasma aldosterone levels remained significantly increased, NCC expression returned to control levels, and body weight, plasma and urinary electrolyte concentrations, and excretion normalized. Finally, shift to a regular diet after the rescue diet reinstated the symptoms of severe PHA-1 syndrome and significantly reduced NCC phosphorylation. In conclusion, lack of ENaC-mediated sodium transport along the nephron cannot be compensated for by other sodium channels and/or transporters, only by a high-sodium and reduced-potassium diet. We further conclude that hyperkalemia becomes the determining factor in regulating NCC activity, regardless of sodium loss, in the ENaC-mediated salt-losing PHA-1 phenotype. PMID:26701978

  5. Protein synthesis and degradation are essential to regulate germline stem cell homeostasis in Drosophila testes.

    PubMed

    Yu, Jun; Lan, Xiang; Chen, Xia; Yu, Chao; Xu, Yiwen; Liu, Yujuan; Xu, Lingna; Fan, Heng-Yu; Tong, Chao

    2016-08-15

    The homeostasis of self-renewal and differentiation in stem cells is controlled by intrinsic signals and their niche. We conducted a large-scale RNA interference (RNAi) screen in Drosophila testes and identified 221 genes required for germline stem cell (GSC) maintenance or differentiation. Knockdown of these genes in transit-amplifying spermatogonia and cyst cells further revealed various phenotypes. Complex analysis uncovered that many of the identified genes are involved in key steps of protein synthesis and degradation. A group of genes that are required for mRNA splicing and protein translation contributes to both GSC self-renewal and early germ cell differentiation. Loss of genes in the protein degradation pathway in cyst cells leads to testis tumors consisting of overproliferated germ cells. Importantly, in the Cullin 4-RING E3 ubiquitin ligase (CRL4) complex, we identified multiple proteins that are crucial to GSC self-renewal: pic/DDB1, a CRL4 linker protein, is not only required for GSC self-renewal in flies but also for maintenance of spermatogonial stem cells (SSCs) in mice. PMID:27471256

  6. Three-dimensional reconstruction of a rat stage V Sertoli cell: III. A study of specific cellular relationships.

    PubMed

    Russell, L D; Tallon-Doran, M; Weber, J E; Wong, V; Peterson, R N

    1983-06-01

    Specific Sertoli--Sertoli and Sertoli--germ-cell contacts and/or junctions were investigated employing micrographs used to reconstruct serially a model of a rat stage V Sertoli cell. The Sertoli--Sertoli junctional contact areas occurred in a belt-like arrangement near the base of the Sertoli cell. This configuration is consistent with their proposed function as a sealing element limiting the passage of materials toward the tubular lumen. Sertoli ectoplasmic specializations also formed a continuous belt, or band, around the reconstructed cell at the junctional contact area. Eighteen Sertoli--Sertoli tubulobulbar complexes were found; some (12 in number) invaginated the reconstructed cell, while others (6) emanated from it. Of 37 round germ cells that were sectioned in their entirety and adjoined the reconstructed cell, 23 displayed desmosome-gap junctions with either the reconstructed cell or an adjoining cell. Since there were multiple junctions connecting some germ cells to Sertoli cells, the total number of junctions was much greater (35). Desmosome-gap junctions of the Sertoli cell were numerous connecting pachytene spermatocytes, less numerous connecting type B spermatogonia, and even less numerous connecting step 5 spermatids; and none was seen joining Sertoli cells with elongate spermatids. Most desmosome-gap junctions join germ cells to the body of the Sertoli cell at its basal aspect. Their numbers and position indicate that they play a role in the maintenance of the integrity of the seminiferous epithelium and may provide a route for cell-to-cell communication. Ectoplasmic specializations of the reconstructed cell were seen facing only 3 of 37 round germ cells, and 7 ectoplasmic specializations from adjoining Sertoli cells faced these germ cells, all of which were step 5 spermatids. That there were no ectoplasmic specializations facing pachytene cells indicates that ectoplasmic specializations are not acquired as these cells pass through Sertoli

  7. Slowing them down will make them lose: a role for attine ant crop fungus in defending pupae against infections?

    PubMed

    Armitage, Sophie A O; Fernández-Marín, Hermógenes; Boomsma, Jacobus J; Wcislo, William T

    2016-09-01

    Fungus-growing ants (Attini) have evolved an obligate dependency upon a basidiomycete fungus that they cultivate as their food. Less well known is that the crop fungus is also used by many attine species to cover their eggs, larvae and pupae. The adaptive functional significance of this brood covering is poorly understood. One hypothesis to account for this behaviour is that it is part of the pathogen protection portfolio when many thousands of sister workers live in close proximity and larvae and pupae are not protected by cells, as in bees and wasps, and are immobile. We performed behavioural observations on brood covering in the leaf-cutting ant Acromyrmex echinatior, and we experimentally manipulated mycelial cover on pupae and exposed them to the entomopathogenic fungus Metarhizium brunneum to test for a role in pathogen resistance. Our results show that active mycelial brood covering by workers is a behaviourally plastic trait that varies temporally, and across life stages and castes. The presence of a fungal cover on the pupae reduced the rate at which conidia appeared and the percentage of pupal surface that produced pathogen spores, compared to pupae that had fungal cover experimentally removed or naturally had no mycelial cover. Infected pupae with mycelium had higher survival rates than infected pupae without the cover, although this depended upon the time at which adult sister workers were allowed to interact with pupae. Finally, workers employed higher rates of metapleural gland grooming to infected pupae without mycelium than to infected pupae with mycelium. Our results imply that mycelial brood covering may play a significant role in suppressing the growth and subsequent spread of disease, thus adding a novel layer of protection to their defence portfolio. PMID:27136600

  8. Cell Division Drives Epithelial Cell Rearrangements during Gastrulation in Chick.

    PubMed

    Firmino, Joao; Rocancourt, Didier; Saadaoui, Mehdi; Moreau, Chloe; Gros, Jerome

    2016-02-01

    During early embryonic development, cells are organized as cohesive epithelial sheets that are continuously growing and remodeled without losing their integrity, giving rise to a wide array of tissue shapes. Here, using live imaging in chick embryo, we investigate how epithelial cells rearrange during gastrulation. We find that cell division is a major rearrangement driver that powers dramatic epithelial cell intercalation events. We show that these cell division-mediated intercalations, which represent the majority of epithelial rearrangements within the early embryo, are absolutely necessary for the spatial patterning of gastrulation movements. Furthermore, we demonstrate that these intercalation events result from overall low cortical actomyosin accumulation within the epithelial cells of the embryo, which enables dividing cells to remodel junctions in their vicinity. These findings uncover a role for cell division as coordinator of epithelial growth and remodeling that might underlie various developmental, homeostatic, or pathological processes in amniotes. PMID:26859350

  9. Development of germ cell neoplasia in situ in chinchilla rabbits.

    PubMed

    Vigueras-Villaseñor, Rosa María; Montelongo Solís, Paola; Chávez-Saldaña, Margarita; Gutiérrez-Pérez, Oscar; Cortés Trujillo, Lucero; Rojas-Castañeda, Julio César

    2016-05-01

    The present study was designed to describe the development of germ cell neoplasia in situ in Chinchilla rabbit by administration of estradiol. The study was performed in rabbits distributed into two groups: control and 17 β-estradiol. The determination of histological alterations and POU5F1 and c-kit proteins employed as biomarkers for the diagnosis of this neoplasia was carried out. Testicular descent and complete spermatogenesis were observed in the control group. The protein biomarkers were negative. However, in the rabbits treated with estradiol, the testes remained undescended with the gonocytes undifferentiated to spermatogonia. There were histological lesions owing to germ cell neoplasia in situ and positive to POU5F1 and c-kit proteins. These findings indicate that the chinchilla rabbit is an ideal model to study this neoplasia in which the histological characteristics and biomarkers of the disease could be clearly observed. Using this model we suggested that the persisting gonocytes could be responsible for the development of germ cell neoplasia in situ. PMID:26617392

  10. Germ cell differentiation in the marmoset (Callithrix jacchus) during fetal and neonatal life closely parallels that in the human

    PubMed Central

    Mitchell, R.T.; Cowan, G.; Morris, K.D.; Anderson, R.A.; Fraser, H.M.; Mckenzie, K.J.; Wallace, W.H.B.; Kelnar, C.J.H.; Saunders, P.T.K.; Sharpe, R.M.

    2008-01-01

    BACKGROUND Testicular germ cell tumours (TGCT) are thought to originate from fetal germ cells that fail to differentiate normally, but no animal model for these events has been described. We evaluated the marmoset (Callithrix jacchus) as a model by comparing perinatal germ cell differentiation with that in humans. METHODS Immunohistochemical profiling was used to investigate germ cell differentiation (OCT4, NANOG, AP-2γ, MAGE-A4, VASA, NANOS-1) and proliferation (Ki67) in fetal and neonatal marmoset testes in comparison with the human and, to a lesser extent, the rat. RESULTS In marmosets and humans, differentiation of gonocytes into spermatogonia is associated with the gradual loss of pluripotency markers such as OCT4 and NANOG, and the expression of germ cell-specific proteins such as VASA. This differentiation occurs asynchronously within individual cords during fetal and early postnatal life. This contrasts with rapid and synchronous germ cell differentiation within and between cords in the rat. Similarly, germ cell proliferation in the marmoset and human occurs throughout perinatal life, in contrast to rats in which proliferation ceases during this period. CONCLUSIONS The marmoset provides a good model for normal human germ cell differentiation and proliferation. The perinatal marmoset may be a useful model in which to establish factors that lead to failure of normal germ cell differentiation and the origins of TGCT. PMID:18694875

  11. Are testicular mast cells involved in the regulation of germ cells in man?

    PubMed

    Windschüttl, S; Nettersheim, D; Schlatt, S; Huber, A; Welter, H; Schwarzer, J U; Köhn, F M; Schorle, H; Mayerhofer, A

    2014-07-01

    Protease activated receptor-2 (PAR-2) is the receptor for the prototype mast cell product tryptase. PAR-2 expression by cells of the human germinal epithelium was reported, but the exact cellular sites of testicular expression remained unknown. That became of interest, because mast cells, expressing tryptase, were found in the walls of seminiferous tubules of patients suffering from sub- and infertility. This location suggested that mast cells via tryptase might be able to influence PAR-2-expressing cells in the germinal epithelium. To explore these points, we used testicular paraffin-embedded sections for immunohistochemistry. PAR-2-positive cells were mostly basally located cells of the seminiferous epithelium, namely spermatogonia. Some stained for the receptor for GDNF (GFRalpha-1), and possibly represent spermatogonial stem cells (SSCs). As true human SSCs could not be examined, we turned to TCam-2 seminoma cells, expressing PAR-2 and stem cell markers, including GFRalpha-1. TCam-2 cells robustly responded to stimulation with a specific PAR-2 agonist (SLIGKV) by increased intracellular Ca(2+) levels. Recombinant tryptase and trypsin, but not a control peptide (VKGILS) evoked this response, implying functional PAR-2. Video imaging and caspase 3/7 assays showed that SLIGKV and tryptase prevented spontaneous apoptosis and increased proliferation of TCam-2 cells. The expression of the marker of pluripotency OCT3/4 was unchanged upon activation of PAR-2, suggesting that the stem cell-like character is not changed. Furthermore, human germ cell cancers were examined. A subset of seminoma and carcinoma in situ samples expressed PAR-2, indicating that yet unknown subgroups exist. Collectively, the descriptive data obtained in human testicular sections, in germ cell cancers and the functional results in TCam-2 cells imply a trophic role of mast cell-derived tryptase for human germ cells. This may be relevant for subtypes of human germ cell cancers, and possibly SSCs. It

  12. RBE and genetic susceptibility of mouse and rat spermatogonial stem cells to protons, heavy charged particles and 1.5 MeV neutrons

    NASA Astrophysics Data System (ADS)

    Vaglenov, A.; Fedorenko, B.; Kaltenboeck, B.

    The main purpose of the present study is to provide data on RBE and genetic susceptibility in the mouse and the rat when exposed to protons, HZE particles and neutrons. Genetic damage from exposure to 50 MeV and 9 GeV protons, 4 GeV/nucleon helium ions, 4 GeV/nucleon carbon ions and 1.5 MeV neutrons was studied in adult (CBA × C57Bl/6J) F1 mice. Damage from 9 GeV protons and 4 GeV helium ions was studied in adult Wistar rats. The incidence of reciprocal translocations (RT) induced in the spermatogonial stem cells of each species was recorded. RBE values were derived by comparing linear regression coefficients from dose-responses within the same dose-range for each of the radiation types tested and 60Co γ-rays or by means of a direct nonparametric method. RT yields measured after mouse and rat spermatogonial irradiation with protons, heavy charged particles and neutrons fit the linear model of the dose-response relationship. Relative to 60Co γ-rays, RBE values are as follows for mouse spermatogonia: 0.9 for 50 MeV protons; 1.3 for 9 GeV protons; 0.7 for 4 GeV helium ions; and 1.3 for 4 GeV carbon ions. For rat spermatogonia, values were: 1.7 for 9 GeV protons and 1.3 for helium ions. Compared to mice irradiated using the same experimental design, rats were more susceptible to high-LET radiations, with susceptibility assessed by genetic damage to their spermatogonial stem cells. The RBE of 1.5 MeV neutron is about 6.6.

  13. Cells producing insulin-like androgenic gland hormone of the giant freshwater prawn, Macrobrachium rosenbergii, proliferate following bilateral eyestalk-ablation.

    PubMed

    Phoungpetchara, Ittipon; Tinikul, Yotsawan; Poljaroen, Jaruwan; Chotwiwatthanakun, Charoonroj; Vanichviriyakit, Rapeepun; Sroyraya, Morakot; Hanna, Peter J; Sobhon, Prasert

    2011-06-01

    We found that the androgenic gland (AG) of Macrobrachium rosenbergii possesses three cell types. Type I cells are small polygonal shaped-cells (13.4 μm in diameter), stain strongly with hematoxylin-eosin (H&E), have abundant multilayered rough endoplasmic reticulum (rER), and nuclei containing mostly heterochromatin. Type II cells are slightly larger (18.6 μm in diameter), stain lightly with H&E, have rER with dilated cisternae, and nuclei containing mostly euchromatin. Type III cells (previously undescribed) are similar in size and shape to type I cells, but the cytoplasm is unstained and they have a high amount of smooth endoplasmic reticulum (sER) and mitochondria with tubular cristae. Bilateral eyestalk-ablation resulted in AG hypertrophy with a proliferation and predominance of type I cells as determined by bromodeoxyuridine (BrdU) assays. Expression of insulin-like androgenic gland hormone (Mr-IAG), determined by immunohistochemistry, was weak in type I cells, strong in type II cells of both the intact and eyestalk-ablated, and negative in type III cells. It was also detected in spermatogonia, nurse cells, and epithelium lining of the spermatic duct. The function of Mr-IAG in these tissues is yet to be elucidated but the distribution implies a strong role in male reproduction. PMID:21477831

  14. What Do You Lose When You Lose Your Language?

    ERIC Educational Resources Information Center

    Fishman, Joshua

    This paper addresses the impact of language loss on culture and the need for developing effective strategies for language restoration. Culture is expressed through language; when language is lost, those things that represent a way of life, a way of valuing, and human reality are also lost. However, if you talk to members of a particular culture…

  15. The Dynamical Mechanisms of the Cell Cycle Size Checkpoint

    NASA Astrophysics Data System (ADS)

    Feng, Shi-Fu; Yan, Jie; Liu, Zeng-Rong; Yang, Ling

    2012-10-01

    Cell division must be tightly coupled to cell growth in order to maintain cell size, whereas the mechanisms of how initialization of mitosis is regulated by cell size remain to be elucidated. We develop a mathematical model of the cell cycle, which incorporates cell growth to investigate the dynamical properties of the size checkpoint in embryos of Xenopus laevis. We show that the size checkpoint is naturally raised from a saddle-node bifurcation, and in a mutant case, the cell loses its size control ability due to the loss of this saddle-node point.

  16. Reduced germ cell apoptosis during spermatogenesis in the teratospermic domestic cat.

    PubMed

    Jewgenow, Katarina; Neubauer, Katrin; Blottner, Steffen; Schön, Jennifer; Wildt, David E; Pukazhenthi, Budhan S

    2009-01-01

    Teratospermia (>60% morphologically abnormal sperm/ejaculate) is associated with increased sperm output in the domestic cat. The objective of this study was to determine whether increased sperm production in teratospermic donors was associated with disturbances in germ cell apoptosis, the usual mechanism for sperm cell elimination. Apoptosis was measured by evaluating DNA fragmentation, expression of Caspase-3, and anti-apoptosis repressor with caspase recruitment domain (ARC) in the testes of normospermic compared with teratospermic cats. Testes (n = 6 males/group) were obtained by bilateral castration and immediately fixed in Bouin solution. Results revealed that greater than 97% of cells labeled as DNA fragmented were tubular regardless of male type. Fewer (P < .05) apoptotic spermatogenic cells per tubule (0.52 +/- 0.11 cells/tubule, x +/- SEM) and per 100 Sertoli cells (3.79 cells/100 Sertoli cells) were observed in teratospermic compared with normospermic (1.25 +/- 0.36 cells/tubule and 6.44 cells/100 Sertoli cells) cats. Among the spermatogenic cells, fewer (P < .03) spermatocytes were positively labeled in teratospermic (0.3 +/- 0.07/tubule) compared with normospermic (0.83 +/- 0.28/tubule) counterparts. Neither donor type differed in Caspase-3 or ARC expression activity. However, each factor was both cell- and stage-specific in expression. Specifically, Caspase-3 was located in Sertoli cells, A-spermatogonia, and round spermatids at stage V. The ARC was found in primary spermatocytes at each stage of the spermatogenic cycle. These results demonstrate that the high incidence of morphologically abnormal sperm in teratospermic male cats is accompanied by a reduced elimination of defective spermatogenic cells via apoptosis. PMID:19201698

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  18. Loss of Sertoli-germ cell adhesion determines the rapid germ cell elimination during the seasonal regression of the seminiferous epithelium of the large hairy armadillo Chaetophractus villosus.

    PubMed

    Luaces, Juan Pablo; Rossi, Luis Francisco; Sciurano, Roberta Beatriz; Rebuzzini, Paola; Merico, Valeria; Zuccotti, Maurizio; Merani, Maria Susana; Garagna, Silvia

    2014-03-01

    The armadillo Chaetophractus villosus is a seasonal breeder whose seminiferous epithelium undergoes rapid regression with massive germ cell loss, leaving the tubules with only Sertoli cells and spermatogonia. Here, we addressed the question of whether this regression entails 1) the disassembly of cell junctions (immunolocalization of nectin-3, Cadm1, N-cadherin, and beta-catenin, and transmission electron microscopy [TEM]); 2) apoptosis (immunolocalization of cytochrome c and caspase 3; TUNEL assay); and 3) the involvement of Sertoli cells in germ cell phagocytosis (TEM). We showed a dramatic reduction in the extension of vimentin filaments associated with desmosomelike junctions at the interface between Sertoli and germ cells, and an increased diffusion of the immunosignals of nectin-3, Cadm1, N-cadherin, and beta-catenin. Together, these results suggest loss of Sertoli-germ cell adhesion, which in turn might determine postmeiotic cell sloughing at the beginning of epithelium regression. Then, loss of Sertoli-germ cell adhesion triggers cell death. Cytochrome c is released from mitochondria, but although postmeiotic cells were negative for late apoptotic markers, at advanced regression spermatocytes were positive for all apoptotic markers. Transmission electron microscopy analysis showed cytoplasmic engulfment of cell debris and lipid droplets within Sertoli cells, a sign of their phagocytic activity, which contributes to the elimination of the residual meiocytes still present in the latest regression phases. These findings are novel and add new players to the mechanisms of seminiferous epithelium regression occurring in seasonal breeders, and they introduce the armadillo as an interesting model for studying seasonal spermatogenesis. PMID:24451984

  19. Cost savings of anti-TNF therapy using a test-based strategy versus an empirical dose escalation in Crohn's disease patients who lose response to infliximab

    PubMed Central

    Roblin, Xavier; Attar, Alain; Lamure, Michel; Savarieau, Bernard; Brunel, Pierre; Duru, Gérard; Peyrin-Biroulet, Laurent

    2015-01-01

    Background The use of pharmacokinetics is associated with cost savings in anti-tumor necrosis factor (anti-TNF) therapy, but the long-term cost savings in a large cohort of Crohn's disease (CD) patients are unknown. Aim The goal of this study was to compare the cost of anti-TNF therapy in two cohorts of CD patients losing response to infliximab, one using a test-based strategy and one an empirical dose escalation. Methods We used a selected mathematical model to describe the trajectories of CD patients based on a discrete event system. This design allowed us to track over a given period a double cohort of patients who moved randomly and asynchronously from one state to another, while keeping all the information on their entire trajectory. Both cohorts were modeled using state diagram parameters where transition probabilities from one state to another are derived from literature data. Costs were estimated based on the French health care system. Results Cost savings among the 10,000 CD patients using a test-based strategy were €131,300,293 at 5 years. At 5 years the mean cost saving was €13,130 per patient. The direct cost of the test had no impact on the results until the cost per test reached €2,000. Conclusions A test-based strategy leads to major cost savings related to anti-TNF therapy in CD. PMID:27123185

  20. Psychological and social consequences of losing a child in a natural or human-made disaster: a review of the evidence.

    PubMed

    Xu, Yao; Herrman, Helen; Tsutsumi, Atsuro; Fisher, Jane

    2013-12-01

    Exposure to natural and human-made disasters is associated with long-term health consequences, including for mental health. Parents who have lost children, particularly their only children, in any circumstances are also at increased risk of developing mental health problems. The aim of this study was to review the available evidence about the psychological and social consequences for parents who had faced these circumstances simultaneously through losing children in a disaster. Systematic searching of the English and Chinese language literatures about the psychological and social functioning of bereaved parents after disasters revealed that a small number of studies met inclusion criteria. The results showed that bereaved parents had more mental health problems than bereaved spouses and non-bereaved parents, and mothers appeared to be more vulnerable to mental health problems than fathers. Potential protective factors for bereaved parents' mental health included having psychological interventions, having adequate social support, seeing their children's bodies and having a subsequent baby. Although the literature was modest and methodologically diverse, there was a consistent finding that parents who have lost children in disasters were at high risk of suffering mental health problems, especially bereaved mothers. As there was little evidence, further studies are needed to understand the best advice and interventions to offer bereaved parents and provide enhanced mental health care of such bereaved populations after disasters. PMID:23857912

  1. RNA interference of a heat shock protein, Hsp70, loses its protection role in indirect chilling injury to the beet armyworm, Spodoptera exigua.

    PubMed

    Choi, Bong-Gee; Hepat, Rahul; Kim, Yonggyun

    2014-02-01

    The beet armyworm, Spodoptera exigua, is freeze-susceptible, in which glycerol plays a crucial role in depressing supercooling point (SCP) to avoid the freezing injury. This study focused on a non-freezing injury classified into indirect chilling injury of S. exigua after a prolonged exposure to low temperatures much above SCPs. Exposure to 0 and 5°C for longer than 2weeks was lethal to all the immature stages. Among immature stages, eggs were the most susceptible to the low temperature treatments and pupae were the next susceptible. Among larvae, the third instar (L3) appeared to be more tolerant than the fifth instar (L5). The temperature treatment at 15°C allowed both L3 and L5 to exhibit a feeding behavior and induced little non-freezing injury, suggesting a minimal temperature threshold for optimal overwintering conditions of S. exigua. Three heat shock protein genes (Hsp70, Hsp74, Hsp83) were expressed in the larvae at the low temperature treatments. Only Hsp70 was inducible to the low temperatures in both L3 and L5 stages. RNA interference of Hsp70 expression led to significantly lose the survival rates of the treated larvae in the conditions inducing the non-freezing injury. These results suggest that Hsp70 plays a role in protecting S. exigua from the indirect chilling injury. PMID:24309290

  2. Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2alpha may signal skeletal muscle atrophy in weight-losing cancer patients.

    PubMed

    Eley, H L; Skipworth, R J E; Deans, D A C; Fearon, K C H; Tisdale, M J

    2008-01-29

    Previous studies suggest that the activation (autophosphorylation) of dsRNA-dependent protein kinase (PKR) can stimulate protein degradation, and depress protein synthesis in skeletal muscle through phosphorylation of the translation initiation factor 2 (eIF2) on the alpha-subunit. To understand whether these mediators are important in muscle wasting in cancer patients, levels of the phospho forms of PKR and eIF2alpha have been determined in rectus abdominus muscle of weight losing patients with oesophago-gastric cancer, in comparison with healthy controls. Levels of both phospho PKR and phospho eIF2alpha were significantly enhanced in muscle of cancer patients with weight loss irrespective of the amount and there was a linear relationship between phosphorylation of PKR and phosphorylation of eIF2alpha (correlation coefficient 0.76, P=0.005). This suggests that phosphorylation of PKR led to phosphorylation of eIF2alpha. Myosin levels decreased as the weight loss increased, and there was a linear relationship between myosin expression and the extent of phosphorylation of eIF2alpha (correlation coefficient 0.77, P=0.004). These results suggest that phosphorylation of PKR may be an important initiator of muscle wasting in cancer patients. PMID:18087277

  3. Radiosensitivity of testicular cells in the fetal mouse

    SciTech Connect

    Vergouwen, R.P.F.A.; Roepers-Gajadien, H.L.; Rooij, D.G. de; Huiskamp, R.; Bas, R.J.; Davids, J.A.G.

    1995-01-01

    The effects of prenatal X irradiation on postnatal development of the CBA/P mouse testis was studied. At days 14, 15 and 18 post coitus pregnant female mice were exposed to single doses of X rays ranging from 0.25-1.5 Gy. Higher doses resulted in extensive loss of fetal mice. In the male offspring, at days 3 and 31 post partum, the numbers of gonocytes, type A spermatogonia and Sertoli cells per testis were determined using the disector method. Furthermore, after irradiation at day 15 post coitus, the numbers of Leydig cells, mesenchymal cells, macrophages, myoid cells, lymphatic endothelial cells, endothelial cells and perivascular cells per testis were also determined at days 3 and 31 post partum. At day 3 post partum, the number of germ cells was decreased after irradiation at days 14 and 15 post coitus. A D{sub o} value of 0.7 Gy was determined for the radiosensitivity of the gonocytes at day 14 post coitus. A D{sub o} value of 0.8 Gy was determined for the gonocytes at day 15 post coitus which, however, seems to be less accurate. No accurate D{sub o} value could be determined for the gonocytes at day 18 post coitus. At day 31 post partum, the repopulation of the seminiferous epithelium as well as testis weights and tubular diameters were more affected by irradiation with increasing age of the mice at the time of irradiation. The percentage of tubular cross sections showing spermatids decreased with increasing dose after irradiation at days 15 and 18 post coitus, but not after irradiation at day 14 post coitus. Furthermore, in tubular cross sections showing spermatids, exposure of testes to 1.25 and 1.5 Gy at day 18 post coitus resulted in significantly lower numbers of spermatids per cross section when compared to those testes exposed to the same doses at day 15 post coitus. 30 refs., 7 figs., 1 tab.

  4. Use it or lose it

    NASA Astrophysics Data System (ADS)

    Hatheway, Alson E.

    2014-11-01

    Brutus to Cassius in Julius Caesar: "There is a tide in the affairs of men which taken at the flood leads on to fortune. Omitted, all the voyage of their life is bound in shallows and in miseries." - W. Shakespeare

  5. When Directors Lose Their Way

    ERIC Educational Resources Information Center

    Carter, Margie

    2011-01-01

    Directors of early childhood programs are an amazing lot! There's so much dedication, such hard work and creative problem solving. But then that inevitable undertow of deadlines, crises, and illness begins to suck directors down. With crisis management becoming a way of life, they don't even recognize their vital signs slipping away. The author…

  6. Why Should I Lose Weight?

    MedlinePlus

    ... and nuts. • Cook foods in healthier ways like baking, boiling, broiling, grilling, roasting or stewing. Don’t fry foods in oil. • Read food labels and avoid foods ... Reduction Fitness + ...

  7. How to Lose Your Charter

    ERIC Educational Resources Information Center

    Wilkens, Christian P.

    2013-01-01

    In this scholarly commentary, the author examines the major reasons U.S. charter schools have closed since 1992. The commentary provides examples of charter school failures in high-frequency areas, such as financial and organizational mismanagement, and academic underperformance; it further identifies two subcategories of academic risk:…

  8. Losing Sleep over Student Success?

    ERIC Educational Resources Information Center

    Cordova, France A.

    2006-01-01

    Over the past year, a number of journals have reprised many of the questions plaguing higher education--providing a full year's worth of sleepless nights. While each of these issues justifies considerable dialogue and attention, the one issue on which parents, students, the public, and educators can agree is the importance--and the challenge--of…

  9. Autoimmune Regulator (AIRE) Is Expressed in Spermatogenic Cells, and It Altered the Expression of Several Nucleic-Acid-Binding and Cytoskeletal Proteins in Germ Cell 1 Spermatogonial (GC1-spg) Cells.

    PubMed

    Radhakrishnan, Karthika; Bhagya, Kongattu P; Kumar, Anil Tr; Devi, Anandavalli N; Sengottaiyan, Jeeva; Kumar, Pradeep G

    2016-08-01

    Autoimmune regulator (AIRE) is a gene associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE is expressed heavily in the thymic epithelial cells and is involved in maintaining self-tolerance through regulating the expression of tissue-specific antigens. The testes are the most predominant extrathymic location where a heavy expression of AIRE is reported. Homozygous Aire-deficient male mice were infertile, possibly due to impaired spermatogenesis, deregulated germ cell apoptosis, or autoimmunity. We report that AIRE is expressed in the testes of neonatal, adolescent, and adult mice. AIRE expression was detected in glial cell derived neurotrophic factor receptor alpha (GFRα)(+) (spermatogonia), GFRα(-)/synaptonemal complex protein (SCP3)(+) (meiotic), and GFRα(-)/Phosphoglycerate kinase 2 (PGK2)(+) (postmeiotic) germ cells in mouse testes. GC1-spg, a germ-cell-derived cell line, did not express AIRE. Retinoic acid induced AIRE expression in GC1-spg cells. Ectopic expression of AIRE in GC1-spg cells using label-free LC-MS/MS identified a total of 371 proteins that were differentially expressed. 100 proteins were up-regulated, and 271 proteins were down-regulated. Data are available via ProteomeXchange with identifier PXD002511. Functional analysis of the differentially expressed proteins showed increased levels of various nucleic-acid-binding proteins and transcription factors and a decreased level of various cytoskeletal and structural proteins in the AIRE overexpressing cells as compared with the empty vector-transfected controls. The transcripts of a select set of the up-regulated proteins were also elevated. However, there was no corresponding decrease in the mRNA levels of the down-regulated set of proteins. Molecular function network analysis indicated that AIRE influenced gene expression in GC1-spg cells by acting at multiple levels, including transcription, translation, RNA processing, protein transport, protein

  10. Generation of In-vitro Spermatogonial Stem Cells following Genetic Manipulation of Primordial Germ-like Cells

    PubMed Central

    Mazaheri, Zohreh; Movahedin, Mansoureh; Rahbarizadeh, Fatemeh; Amanpour, Saied

    2012-01-01

    Research about potential use of stem cells for the development of germ line cells in vitro had been challenged. In the present study, we reported a novel protocol consisting of cocktail growth factor addition for germ cell differentiation followed by transfection. The cells were purificated based on the expression on the cell surface of a protein. This protein is not present in normal cells of mice and does not interfere with cellular function. This cell surface marker is efficiently recognized by monoclonal antibodies. Bone marrow mesenchymal stem cells derived primordial germ like cells were differentiated to spermatogonial stem like cells by inducer cocktail including Retinoic acid (RA)+Leukemia inhibitory factor (LIF)+Basic fibroblast growth factor (bFgF). Co-culture system was used as a feeder under differentiated cells. A 400 bp fragment of spermatogonia-specific Stra-8 locus was enough to direct gene expression to the germ line stem cells. Stra8-CD4HAglo construct was used for purification of premeiotic differentiated cells. Expression of pluripotency (Pou5F1, Nanog, c-Myc) and specific germ cell (Mvh, Piwil2, Stra-8) genes in each stage were analyzed. The purified cells expressed the known molecular markers of PGC-like cells such as Mvh, Piwil2 & Stra-8. The outcomes of qPCR showed that ratio pluripotency of genes expression in selective group significantly decreased (p≤0.05) in the initial differentiation process. This results showed that ratio of Pou5F1, Nanog, c-Myc, Mvh, Piwil2 & Stra-8 expression to purified PGC-like cells were 0.41, 0.204, 1.1, 0.003, 0.184 and 2.276, respectively. Treatment of cells with RA affected up regulation of Stra-8. Although, c-Myc gene as an oncogenic gene had significantly increased (p≤0.05) at the end of differentiation stage compared to initial phase of study, this level of expression could not be tumorgenic. qPCR results of the differentiation stage showed higher expression of Stra-8 in co-culture+ cocktail and co

  11. Synthesis of milk specific fatty acids and proteins by dispersed goat mammary-gland epithelial cells.

    PubMed Central

    Hansen, H O; Tornehave, D; Knudsen, J

    1986-01-01

    The method now described for preparation of dispersed lactating goat mammary-gland cells gives a high yield of morphologically and functionally normal mammary cells. The cells synthesize specific goat milk fatty acids in the right proportions, and they respond to hormones by increased protein synthesis. The cells can be frozen and thawed without losing the above properties, which makes them an excellent tool for metabolic and hormonal studies. Images Fig. 1. Fig. 2. PMID:3800930

  12. GermlncRNA: a unique catalogue of long non-coding RNAs and associated regulations in male germ cell development.

    PubMed

    Luk, Alfred Chun-Shui; Gao, Huayan; Xiao, Sizhe; Liao, Jinyue; Wang, Daxi; Tu, Jiajie; Rennert, Owen M; Chan, Wai-Yee; Lee, Tin-Lap

    2015-01-01

    Spermatogenic failure is a major cause of male infertility, which affects millions of couples worldwide. Recent discovery of long non-coding RNAs (lncRNAs) as critical regulators in normal and disease development provides new clues for delineating the molecular regulation in male germ cell development. However, few functional lncRNAs have been characterized to date. A major limitation in studying lncRNA in male germ cell development is the absence of germ cell-specific lncRNA annotation. Current lncRNA annotations are assembled by transcriptome data from heterogeneous tissue sources; specific germ cell transcript information of various developmental stages is therefore under-represented, which may lead to biased prediction or fail to identity important germ cell-specific lncRNAs. GermlncRNA provides the first comprehensive web-based and open-access lncRNA catalogue for three key male germ cell stages, including type A spermatogonia, pachytene spermatocytes and round spermatids. This information has been developed by integrating male germ transcriptome resources derived from RNA-Seq, tiling microarray and GermSAGE. Characterizations on lncRNA-associated regulatory features, potential coding gene and microRNA targets are also provided. Search results from GermlncRNA can be exported to Galaxy for downstream analysis or downloaded locally. Taken together, GermlncRNA offers a new avenue to better understand the role of lncRNAs and associated targets during spermatogenesis. Database URL: http://germlncrna.cbiit.cuhk.edu.hk/ PMID:25982314

  13. GermlncRNA: a unique catalogue of long non-coding RNAs and associated regulations in male germ cell development

    PubMed Central

    Luk, Alfred Chun-Shui; Gao, Huayan; Xiao, Sizhe; Liao, Jinyue; Wang, Daxi; Tu, Jiajie; Rennert, Owen M.; Chan, Wai-Yee; Lee, Tin-Lap

    2015-01-01

    Spermatogenic failure is a major cause of male infertility, which affects millions of couples worldwide. Recent discovery of long non-coding RNAs (lncRNAs) as critical regulators in normal and disease development provides new clues for delineating the molecular regulation in male germ cell development. However, few functional lncRNAs have been characterized to date. A major limitation in studying lncRNA in male germ cell development is the absence of germ cell-specific lncRNA annotation. Current lncRNA annotations are assembled by transcriptome data from heterogeneous tissue sources; specific germ cell transcript information of various developmental stages is therefore under-represented, which may lead to biased prediction or fail to identity important germ cell-specific lncRNAs. GermlncRNA provides the first comprehensive web-based and open-access lncRNA catalogue for three key male germ cell stages, including type A spermatogonia, pachytene spermatocytes and round spermatids. This information has been developed by integrating male germ transcriptome resources derived from RNA-Seq, tiling microarray and GermSAGE. Characterizations on lncRNA-associated regulatory features, potential coding gene and microRNA targets are also provided. Search results from GermlncRNA can be exported to Galaxy for downstream analysis or downloaded locally. Taken together, GermlncRNA offers a new avenue to better understand the role of lncRNAs and associated targets during spermatogenesis. Database URL: http://germlncrna.cbiit.cuhk.edu.hk/ PMID:25982314

  14. Evaluation of the Cell Population of the Seminiferous Epithelium and Spermatic Indexes of the Bat Sturnira lilium (Chiroptera: Phyllostomidae)

    PubMed Central

    Morais, Danielle B.; Barros, Mirlaine S.; Paula, Tarcízio A. R.; Freitas, Mariella B. D.; Gomes, Marcos L. M.; Matta, Sérgio L. P.

    2014-01-01

    Due to the scarcity of information about patterns of spermatogenesis in bats, this study aimed to provide information on the testicular activity of the bat Sturnira lilium along the annual seasons. Thus, a series of morphometrical and stereological analyses were made using the testes of adult S. lilium in order to achieve a better understanding of the sperm production dynamics. Light and transmission electron microscopy analyses were performed in testicular fragments of animals captured during dry and rainy seasons. The testes followed the pattern of organization described for other mammals, and there were no morphological differences between organs collected either in dry or in rainy seasons. Each tubular cross-section in stage 1 was made of 0.5 type-A spermatogonia, 4.4 primary spermatocytes in preleptotene/leptotene, 3.7 in zygotene, 11.9 in pachytene, 35.6 round spermatids and 8.5 Sertoli cells. The mitotic and meiotic indexes were 15.4 and 2.9 cells, respectively, while the spermatogenesis yield was 68.7 cells. The testicular sperm reserves was 37.61×106 cells, and daily sperm production per gram of testis averaged 209.68×106 cells, both highest averages occurring in the rainy season. S. lilium male bats have a continuous reproductive pattern, high spermatogenesis yield and low support capacity by the Sertoli cells. PMID:25003782

  15. Boule Is Present in Fish and Bisexually Expressed in Adult and Embryonic Germ Cells of Medaka

    PubMed Central

    Xu, Hongyan; Li, Zhendong; Li, Mingyou; Wang, Li; Hong, Yunhan

    2009-01-01

    Background The DAZ family genes boule, daz and dazl encode RNA binding proteins essential for fertility of diverse animals including human. dazl has bisexual expression in both mitotic and meiotic germ cells, whereas daz has male premeiotic expression, and boule is largely a unisexual meiotic regulator. Although boule has been proposed as the ancestor for dazl/daz by gene duplication, it has been identified only in invertebrates and mammals. It has, however, remained unclear when and how the DAZ family has evolved in vertebrates. Methodology and Principal Findings This study was aimed at identifying and characterizing the DAZ family genes in fish as the basal vertebrate. We show that boule and dazl coexist in medaka and stickleback. Similar to the medaka dazl (Odazl), the medaka boule (Obol) is maternally supplied and segregates with primordial germ cells. Surprisingly, Obol is expressed in adult germ cells at pre-meiotic and meiotic stages of spermatogenesis and oogenesis. However, the maximal meiotic Obol expression in spermatocytes contrasts with the predominant pre-meiotic Odazl expression in spermatogonia, and the diffuse cytoplasmic Obol distribution in early oocytes contrasts with the Odazl concentration in the Balbinani's body. Conclusions The identification of fish boule and dazl genes provides direct evidence for the early gene duplication during vertebrate evolution. Our finding that Obol exhibits bisexual expression in both embryonic and adult germ cells considerably extends the diversity of boule expression patterns and offers a new insight into the evolutions of DAZ family members, expression patterns and functions in animal fertility. PMID:19564913

  16. Altered hepatic gluconeogenesis during L-alanine infusion in weight-losing lung cancer patients as observed by phosphorus magnetic resonance spectroscopy and turnover measurements.

    PubMed

    Leij-Halfwerk, S; van den Berg, J W; Sijens, P E; Wilson, J H; Oudkerk, M; Dagnelie, P C

    2000-02-01

    .86, respectively; P < 0.001). In addition, changes in PMEs during alanine infusion in lung cancer patients were inversely correlated with the degree of weight loss (r = -0.54; P < 0.05). This study demonstrates the presence of major alterations in the pathway of hepatic gluconeogenesis in weight-losing lung cancer patients, as shown by elevated glucose flux before and during L-alanine infusion, and by the increased PME and PDE levels, which reflect accumulation of gluconeogenic intermediates in these patients. Weight-stable lung cancer patients show accelerated increases in PME and PDE levels during L-alanine infusion, suggesting enhanced induction of the gluconeogenic pathway. Our results suggest altered gluconeogenic enzyme activities and elevated alanine uptake within the livers of weight-losing/weight-stable lung cancer patients. PMID:10676645

  17. Niche signaling promotes stem cell survival in the Drosophila testis via the Jak-STAT target DIAP1

    PubMed Central

    Hasan, Salman; Hétié, Phylis; Matunis, Erika L.

    2015-01-01

    Tissue-specific stem cells are thought to resist environmental insults better than their differentiating progeny, but this resistance varies from one tissue to another, and the underlying mechanisms are not well-understood. Here, we use the Drosophila testis as a model system to study the regulation of cell death within an intact niche. This niche contains sperm-producing germline stem cells (GSCs) and accompanying somatic cyst stem cells (or CySCs). Although many signals are known to promote stem cell self-renewal in this tissue, including the highly conserved JAK-STAT pathway, the response of these stem cells to potential death-inducing signals, and factors promoting stem cell survival, have not been characterized. Here we find that both GSCs and CySCs resist cell death better than their differentiating progeny, under normal laboratory conditions and in response to potential death-inducing stimuli such as irradiation or starvation. To ask what might be promoting stem cell survival, we characterized the role of the anti-apoptotic gene Drosophila inhibitor of apoptosis 1 (diap1) in testis stem cells. DIAP1 protein is enriched in the GSCs and CySCs and is a Jak-STAT target. diap1 is necessary for survival of both GSCs and CySCs, and ectopic up-regulation of DIAP1 in somatic cyst cells is sufficient to non-autonomously rescue stress-induced cell death in adjacent differentiating germ cells (spermatogonia). Altogether, our results show that niche signals can promote stem cell survival by up-regulation of highly conserved anti-apoptotic proteins, and suggest that this strategy may underlie the ability of stem cells to resist death more generally. PMID:25941003

  18. Regulatory T cells: stability revisited

    PubMed Central

    Bailey-Bucktrout, Samantha L.; Bluestone, Jeffrey A.

    2011-01-01

    Breakdown in self-tolerance is due, in part, to a loss of regulatory T (Treg) cells. Recently, a controversy has surfaced about whether Treg cells are overwhelmingly stable, or if they can be reprogrammed in inflammatory and autoimmune environments. Those in the instability “camp” have shown that a fraction of Treg cells lose Foxp3 and acquire effector arm activities. Instability is coupled with IL-2 insufficiency and the inflammatory milieu that promote reprogramming. Here, we highlight the basic tenets of each viewpoint and discuss technical, biological and environmental differences in the models that may help yield a unifying hypothesis. Also considered is how Treg cell instability could link to development of autoimmune disease and the implications for Treg cell-based cellular therapy trials. PMID:21620768

  19. FGF2 stimulates SDF-1 expression through the Erm transcription factor in Sertoli cells.

    PubMed

    Yoon, Kyung-Ae; Chae, Young-Mi; Cho, Je-Yoel

    2009-07-01

    Ets-related molecule (Erm) is a member of the Ets transcription factor family. Erm is known to be an important factor for the self-renewal of Spermatogonial stem cells (SSCs) and the maintenance of spermatogenesis. We investigated the molecular mechanism of Erm regulation on SDF-1 in TM4 Sertoli cells. Erm and Sdf-1 levels were up-regulated after FGF2 treatment in TM4 cells, whereas these levels were significantly decreased by FGF2 in ST2 bone marrow stromal cells. Knockdown of Erm by siRNA in the presence of FGF2 decreased the Sdf-1 levels in TM4 cells. The expression levels of Erm were similar and Erm overexpression increased the Sdf-1 in both TM4 and ST2 cells. FGFR subtype analysis revealed that FGFR4 was expressed in TM4 cells but not in ST2 cells. A blocking experiment also confirmed that FGFR4 is partly responsible for the up-regulation of Erm and SDF-1 induced by FGF2 stimulation in TM4 cells. FGF2 and ERM increased the activity of Sdf-1 gene promoter region in a dose-dependent manner. EMSA revealed that ERM strongly binds to the -846 to -851 nucleotide region of the potential Ets binding site (EBS) in the Sdf-1 promoter. In addition, CXCR4, the SDF-1 receptor, was expressed in spermatogonia and Sertoli cells in the seminiferous tubules of the mouse testis. Our results indicate that ERM directly regulates Sdf-1 gene expression by interacting with its cis-acting element in response to FGF2 stimulation in TM4 cells. PMID:19301256

  20. Electron wavepacket dynamics in highly quasi-degenerate coupled electronic states: A theory for chemistry where the notion of adiabatic potential energy surface loses the sense

    NASA Astrophysics Data System (ADS)

    Yonehara, Takehiro; Takatsuka, Kazuo

    2012-12-01

    We develop a theory and the method of its application for chemical dynamics in systems, in which the adiabatic potential energy hyper-surfaces (PES) are densely quasi-degenerate to each other in a wide range of molecular geometry. Such adiabatic electronic states tend to couple each other through strong nonadiabatic interactions. Technically, therefore, it is often extremely hard to accurately single out the individual PES in those systems. Moreover, due to the mutual nonadiabatic couplings that may spread wide in space and due to the energy-time uncertainty relation, the notion of the isolated and well-defined potential energy surface should lose the sense. On the other hand, such dense electronic states should offer a very interesting molecular field in which chemical reactions to proceed in characteristic manners. However, to treat these systems, the standard theoretical framework of chemical reaction dynamics, which starts from the Born-Oppenheimer approximation and ends up with quantum nuclear wavepacket dynamics, is not very useful. We here explore this problem with our developed nonadiabatic electron wavepacket theory, which we call the phase-space averaging and natural branching (PSANB) method [T. Yonehara and K. Takatsuka, J. Chem. Phys. 129, 134109 (2008)], 10.1063/1.2987302, or branching-path representation, in which the packets are propagated in time along the non-Born-Oppenheimer branching paths. In this paper, after outlining the basic theory, we examine using a one-dimensional model how well the PSANB method works with such densely quasi-degenerate nonadiabatic systems. To do so, we compare the performance of PSANB with the full quantum mechanical results and those given by the fewest switches surface hopping (FSSH) method, which is known to be one of the most reliable and flexible methods to date. It turns out that the PSANB electron wavepacket approach actually yields very good results with far fewer initial sampling paths. Then we apply the

  1. Taste thresholds in patients with small-cell lung cancer.

    PubMed

    Ovesen, L; Hannibal, J; Sørensen, M

    1991-01-01

    Recognition thresholds for the four basic tastes (salt, sour, sweet and bitter) were tested by the forced-choice technique in 27 patients with small-cell lung cancer, and 22 weight-matched control patients with non-malignant diseases. No significant differences in threshold concentrations could be demonstrated. When patients who were losing weight were compared with weight-stable patients, significantly lower taste thresholds for bitter substances were found in weight losing groups in both cancer and control patients. Small-cell lung cancer patients who responded to therapy had obtained an increased threshold for bitter taste at the time of reevaluation than at the time of diagnosis, an effect that may be explained by the chemotherapeutic regimen. The results suggest that in patients with small-cell lung cancer it is not the cancer disease per se but the weight loss that often accompanies it that causes an increased taste sensitivity for bitter substances. PMID:1847701

  2. Characterization of Ovine Dermal Papilla Cell Aggregation

    PubMed Central

    Sari, Agnes Rosarina Prita; Rufaut, Nicholas Wolfgang; Jones, Leslie Norman; Sinclair, Rodney Daniel

    2016-01-01

    Context: The dermal papilla (DP) is a condensation of mesenchymal cells at the proximal end of the hair follicle, which determines hair shaft size and regulates matrix cell proliferation and differentiation. DP cells have the ability to regenerate new hair follicles. These cells tend to aggregate both in vitro and in vivo. This tendency is associated with the ability of papilla cells to induce hair growth. However, human papilla cells lose their hair-inducing activity in later passage number. Ovine DP cells are different from human DP cells since they do not lose their aggregative behavior or hair-inducing activity in culture. Nonetheless, our understanding of ovine DP cells is still limited. Aim: The aim of this study was to observe the expression of established DP markers in ovine cells and their association with aggregation. Subjects and Methods: Ovine DP cells from three different sheep were compared. Histochemistry, immunoflourescence, and polymerase chain reaction experiments were done to analyze the DP markers. Results: We found that ovine DP aggregates expressed all the 16 markers evaluated, including alkaline phosphatase and versican. Expression of the versican V0 and V3 isoforms, neural cell adhesion molecule, and corin was increased significantly with aggregation, while hey-1 expression was significantly decreased. Conclusions: Overall, the stable expression of numerous markers suggests that aggregating ovine DP cells have a similar phenotype to papillae in vivo. The stability of their molecular phenotype is consistent with their robust aggregative behavior and retained follicle-inducing activity after prolonged culture. Their phenotypic stability in culture contrasts with DP cells from other species, and suggests that a better understanding of ovine DP cells might provide opportunities to improve the hair-inducing activity and therapeutic potential of human cells. PMID:27625564

  3. Successful xenogeneic germ cell transplantation from Jundia catfish (Rhamdia quelen) into adult Nile tilapia (Oreochromis niloticus) testes.

    PubMed

    Silva, M A; Costa, G M J; Lacerda, S M S N; Brandão-Dias, P F P; Kalapothakis, E; Silva Júnior, A F; Alvarenga, E R; França, L R

    2016-05-01

    Fish germ cell transplantation presents several important potential applications for aquaculture, including the preservation of germplasm from endangered fish species with high genetic and commercial values. Using this technique in studies developed in our laboratory with adult male Nile tilapias (Oreochromis niloticus), all the necessary procedures were successfully established, allowing the production of functional sperm and healthy progeny approximately 2months after allogeneic transplantation. In the present study, we evaluated the viability of the adult Nile tilapia testis to generate sperm after xenogeneic transplant of germ cells from sexually mature Jundia catfish (Rhamdia quelen) that belong to a different taxonomic order. Therefore, in order to investigate at different time-periods post-transplantation, the presence and development of donor PKH26 labeled catfish germ cells were followed in the tilapia seminiferous tubules. From 7 to 20days post-transplantation, only PKH26 labeled spermatogonia were observed, whereas spermatocytes at different stages of development were found at 70days. Germ cell transplantation success and progression of spermatogenesis were indicated by the presence of labeled PKH26 spermatids and sperm on days 90 and 120 post-transplantation, respectively. Confirming the presence of the catfish genetic material in the tilapia testis, all recipient tilapias evaluated (n=8) showed the genetic markers evaluated. Therefore, we demonstrated for the first time that the adult Nile tilapia testis offers the functional conditions for development of spermatogenesis with sperm production from a fish species belonging to a different order, which provides an important new venue for aquaculture advancement. PMID:26972155

  4. The role of fibroblast growth factor receptor 2 (FGFR2) in differentiation of bovine spermatogonial stem cells (SCC)

    PubMed Central

    Akbarinejad, Vahid; Tajik, Parviz; Movahedin, Mansoureh; Youssefi, Reza

    2016-01-01

    The receptors 1 and 2 of fibroblast growth factor (FGFR1 and FGFR2, respectively) have been observed in all types of testicular cells. Culture on extracellular matrix (ECM) has been observed to lead to initiation of differentiation in spermatogonial stem cells (SSCs). The present study was carried out to investigate whether FGFR1 and FGFR2 play a role in SSCs differentiation. Following isolation, bovine testicular cells were cultured on ECM-coated or uncoated (control) plates for 12 days. The gene expression of THY1, cKIT, FGFR1 and FGFR2 was evaluated using quantitative real-time polymerase chain reaction (PCR). Results related to the gene expression of markers of with undifferentiated (THY1) and differentiated (cKIT) spermatogonia implicated stimulation of self-renewal and differentiation in cells cultured on ECM-coated and uncoated plates, respectively (p < 0.05). Concomitantly, the expression of FGFR2 increased during culture in the ECM group (p < 0.05), whereas it did not change in the control group (p > 0.05). As a result, the gene expression of FGFR2 was greater in the ECM than control group (p < 0.05). Nevertheless, FGFR1 expression did not change during culture in the control and ECM groups (p > 0.05). In conclusion, the present study revealed the potential role of FGFR2 in differentiation of SSCs during culture on ECM. PMID:27482360

  5. The role of fibroblast growth factor receptor 2 (FGFR2) in differentiation of bovine spermatogonial stem cells (SCC).

    PubMed

    Akbarinejad, Vahid; Tajik, Parviz; Movahedin, Mansoureh; Youssefi, Reza

    2016-01-01

    The receptors 1 and 2 of fibroblast growth factor (FGFR1 and FGFR2, respectively) have been observed in all types of testicular cells. Culture on extracellular matrix (ECM) has been observed to lead to initiation of differentiation in spermatogonial stem cells (SSCs). The present study was carried out to investigate whether FGFR1 and FGFR2 play a role in SSCs differentiation. Following isolation, bovine testicular cells were cultured on ECM-coated or uncoated (control) plates for 12 days. The gene expression of THY1, cKIT, FGFR1 and FGFR2 was evaluated using quantitative real-time polymerase chain reaction (PCR). Results related to the gene expression of markers of with undifferentiated (THY1) and differentiated (cKIT) spermatogonia implicated stimulation of self-renewal and differentiation in cells cultured on ECM-coated and uncoated plates, respectively (p < 0.05). Concomitantly, the expression of FGFR2 increased during culture in the ECM group (p < 0.05), whereas it did not change in the control group (p > 0.05). As a result, the gene expression of FGFR2 was greater in the ECM than control group (p < 0.05). Nevertheless, FGFR1 expression did not change during culture in the control and ECM groups (p > 0.05). In conclusion, the present study revealed the potential role of FGFR2 in differentiation of SSCs during culture on ECM. PMID:27482360

  6. Spermatogenesis in Platynereis massiliensis (Polychaeta: Nereidae)

    NASA Astrophysics Data System (ADS)

    Lücht, Joachim; Pfannenstiel, Hans-Dieter

    1989-03-01

    Stage 1 of spermatogenesis in the protandrous polychaete Platynereis massiliensis is represented by clusters of about 60 spermatogonia which appear in the coelomic cavity. There are no testes in P. massiliensis. The origin of the spermatogonial clusters is not known. Subclusters of approximately 20 primary spermatocytes each represent stage 2. The appearance of synaptonemal figures in the spermatocyte nuclei marks the beginning of stage 3. Cells tend to lose their tight packing during stage 3 but interdigitate with cellular processes. Then very small subclusters of 4 to 8 spermatocytes appear. Meiosis is completed during stage 4, giving rise to secondary spermatocytes and then to spermatid tetrads. Spermatogonia and primary spermatocytes are interconnected by structurally specialized fusomes while secondary spermatocytes and spermatids, which are also in cytoplasmic continuity, show rather simple cell bridges. Synthesis of acrosomal material starts during stage 2. During spermiogenesis the proacrosomal vesicles of Golgi origin travel from the posterior part of the cell to its anterior part to form the acrosome proper. Acrosome formation, nuclear condensation, shaping of the long and slender sperm nucleus, and development of the sperm tail are the main events during spermiogenesis. Sperm morphology is briefly discussed wity respect to its phylogenetic bearings.

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

    PubMed Central

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

    2014-01-01

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

  8. TAF4b is required for mouse spermatogonial stem cell development

    PubMed Central

    Lovasco, Lindsay A.; Gustafson, Eric A.; Seymour, Kimberly A.; de Rooij, Dirk G.; Freiman, Richard N.

    2014-01-01

    Long-term mammalian spermatogenesis requires proper development of spermatogonial stem cells (SSCs) that replenish the testis with germ cell progenitors during adult life. TAF4b is a gonadal-enriched component of the general transcription factor complex, TFIID, which is required for the maintenance of spermatogenesis in the mouse. Successful germ cell transplantation assays into adult TAF4b-deficient host testes suggested that TAF4b performs an essential germ cell autonomous function in SSC establishment and/or maintenance. To elucidate the SSC function of TAF4b, we characterized the initial gonocyte pool and rounds of spermatogenic differentiation in the context of the Taf4b-deficient mouse testis. Here we demonstrate a significant reduction in the late embryonic gonocyte pool and a deficient expansion of this pool soon after birth. Resulting from this reduction of germ cell progenitors is a developmental delay in meiosis initiation, as compared to age-matched controls. While GFRα1+ spermatogonia are appropriately present as Asingle and Apaired in wild type testes, TAF4b-deficient testes display an increased proportion of long and clustered chains of GFRα1+ cells. In the absence of TAF4b, seminiferous tubules in the adult testis either lack germ cells altogether or are found to have missing generations of spermatogenic progenitor cells. Together these data indicate that TAF4b-deficient spermatogenic progenitor cells display a tendency for differentiation at the expense of self-renewal and a renewing pool of SSCs fail to establish during the critical window of SSC development. PMID:25727968

  9. Signaling molecules and pathways regulating the fate of spermatogonial stem cells

    PubMed Central

    He, Zuping; Kokkinaki, Maria; Dym, Martin

    2009-01-01

    Spermatogenesis is the process that involves the division and differentiation of spermatogonial stem cells (SSCs) into mature spermatozoa. SSCs are a subpopulation of type A spermatogonia resting on the basement membrane in the mammalian testis. Self-renewal and differentiation of SSCs are the foundation of normal spermatogenesis, and thus a better understanding of molecular mechanisms and signaling pathways in the SSCs is of paramount importance for the regulation of spermatogenesis and may eventually lead to novel targets for male contraception as well as for gene therapy of male infertility and testicular cancer. Uncovering the molecular mechanisms is also of great interest to a better understanding of SSC aging and for developing novel therapeutic strategies for degenerative diseases in view of the recent work demonstrating the pluripotent potential of the SSC. Progress has recently been made in elucidating the signaling molecules and pathways that determine cell fate decisions of SSCs. In this review, we first address the morphological features, phenotypic characteristics, and the potential of SSCs. And then we focus on the recent advances in defining the key signaling molecules and crucial signaling pathways regulating self-renewal and differentiation of SSCs. The association of aberrant expression of signaling molecules and cascades with abnormal spermatogenesis and testicular cancer are also discussed. Finally we point out potential future directions to pursue in research on signaling pathways of SSCs. PMID:19263492

  10. Proteomic analysis of the spermatogonial stem cell compartment in dogfish Scyliorhinus canicula L.

    PubMed

    Loppion, Géraldine; Lavigne, Régis; Pineau, Charles; Auvray, Pierrïck; Sourdaine, Pascal

    2010-06-01

    In the dogfish (Scyliorhinus canicula L.) the testicular germinative zone (GZ), composed of large isolated spermatogonia surrounded by elongating pre-Sertoli cells, is located between the albuginea and the ventrolateral intratesticular vessel. During the spermatogenic wave, cysts radiate in maturational order forming distinct testicular zones. In this study, soluble proteins of the GZ and of the zone containing cysts with spermatocytes were separated by two-dimensional electrophoresis. Gel images were matched and then evaluated for GZ-specific proteins. From the1400 protein spots identified, 680 were found to be apparently specific to this zone. Using MALDI-TOF/TOF mass spectrometry, de novo sequences were obtained for 33 proteins out of the 169 selected for identification by mass spectrometry, but only 16 of these 169 proteins were identified. One of them, proteasome subunit alpha-6, was analyzed further by immunohistochemistry. This study demonstrates the utility of the dogfish as a model for proteome analysis of the spermatogonial stem cell niche, even if it remains restricted by the lack of genomic data available on Elasmobranchs. PMID:20435534

  11. Effects of X-irradiation on mouse testicular cells and sperm chromatin structure

    SciTech Connect

    Sailer, B.L.; Jost, L.K.; Erickson, K.R.; Tajiran, M.A.; Evenson, D.P.

    1995-07-01

    The testicular regions of male mice were exposed to x-ray doses ranging from 0 to 400 rads. Forty days after exposure the mice were killed and the testes and cauda epididymal sperm removed surgically. Flow cytometric measurements of acridine orange stained testicular samples indicated a repopulation of testicular samples indicated a repopulation of testicular cell types following x-ray killing of stem cells. Cauda epididymal sperm were analyzed by the sperm chromatin structure assay (SCSA), a flow cytometric measurement of the susceptibility of the sperm nuclear DNA to in situ acid denaturation. The SCSA detected increased susceptibility to DNA denaturation in situ after 12.5 rads of x-ray exposure, with significant increases following 25 rads. Abnormal sperm head morphology was not significantly increased until the testes were exposed to 60 rads of x-rays. These data suggest that the SCSA is currently the most sensitive, noninvasive method of detecting x-ray damage to testicular stem spermatogonia. 47 refs., 5 figs.

  12. Spermatogonial stem cells specific marker identification in channel catfish, Ictalurus punctatus and blue catfish, I. furcatus.

    PubMed

    Shang, Mei; Su, Baofeng; Lipke, Elizabeth A; Perera, Dayan A; Li, Chao; Qin, Zhenkui; Li, Yun; Dunn, David A; Cek, Sehriban; Peatman, Eric; Dunham, Rex A

    2015-12-01

    Testicular germ cells of channel catfish, Ictalurus punctatus, and blue catfish, I. furcatus were separated into four layers with Percoll density gradient centrifugation, containing different cell types (40% in the first layer were spermatogonial stem cells, SSCs). Expression of seventeen genes was analyzed for cells from different layers by real-time quantitative PCR. Pfkfb4, Urod, Plzf, Integrin6, IntegrinV, Thy1 and Cdh1 genes showed the same expression change pattern in both channel and blue catfish as these genes were down-regulated in the spermatocytes and even more so in spermatids. Plzf and Integrin6 had especially high expression in SSCs and can be used as SSCs specific markers. Sox2 gene was up-regulated in spermatocytes and even more highly up-regulated in spermatids, which indicated it could be a spermatid marker. In contrast to channel catfish, Id4, Smad5 and Prdm14 gene expressions were strongly down-regulated in spermatocyte cells, but up-regulated in spermatid cells in blue catfish. Smad5 gene was down-regulated in spermatocytes, but up-regulated in both spermatogonia and spermatids, allowing identification as a marker for spermatocytes in blue catfish. Oct4, Id4, Gfrα2, Pum2 and Prdm14 genes showed different expression patterns in the testicular germ cells of channel and blue catfish. This may be a partial explanation to the differing responses of channel catfish and blue catfish to induced spawning technologies. The SSCs specific markers can be used for further SSCs labeling, which can increase the SSCs sorting efficiency and be applied in various studies involving SSCs and other germ cells. PMID:26251285

  13. Degradation of bulk diffusion length in CZ silicon solar cells

    SciTech Connect

    Reiss, J.H.; King, R.R.; Mitchell, K.W.

    1995-08-01

    Commercially-produced, unencapsulated, CZ silicon solar cells can lose 3 to 4% of their initial efficiency after exposure to light. After this initial, rapid ( < 30 min.) decrease, the cell power output remains stable. The cell performance recovers in a matter of hours in the dark at room temperature, and degrades again under light exposure. The different conditions under which CZ silicon cells degrade, and the reverse process, annealing, are characterized with the methods of spectral response and current-voltage (I-V) measurements. Iron impurities are a possible cause of this effect.

  14. Microbead-based biomimetic synthetic neighbors enhance survival and function of rat pancreatic β-cells

    NASA Astrophysics Data System (ADS)

    Li, Wei; Lee, Samuel; Ma, Minglin; Kim, Soo Min; Guye, Patrick; Pancoast, James R.; Anderson, Daniel G.; Weiss, Ron; Lee, Richard T.; Hammond, Paula T.

    2013-10-01

    Diabetes is caused by the loss or dysfunction of insulin-secreting β-cells in the pancreas. β-cells reduce their mass and lose insulin-producing ability in vitro, likely due to insufficient cell-cell and cell-extracellular matrix (ECM) interactions as β-cells lose their native microenvironment. Herein, we built an ex-vivo cell microenvironment by culturing primary β-cells in direct contact with `synthetic neighbors', cell-sized soft polymer microbeads that were modified with cell-cell signaling factors as well as components from pancreatic-tissue-specific ECMs. This biomimetic 3D microenvironment was able to promote native cell-cell and cell-ECM interactions. We obtained sustained maintenance of β-cell function in vitro enhanced cell viability from the few days usually observed in 2D culture to periods exceeding three weeks, with enhanced β-cell stability and insulin production. Our approach can be extended to create a general 3D culture platform for other cell types.

  15. Communication is key: Reducing DEK1 activity reveals a link between cell-cell contacts and epidermal cell differentiation status.

    PubMed

    Galletti, Roberta; Ingram, Gwyneth C

    2015-01-01

    Plant epidermis development requires not only the initial acquisition of tissue identity, but also the ability to differentiate specific cell types over time and to maintain these differentiated states throughout the plant life. To set-up and maintain differentiation, plants activate specific transcriptional programs. Interfering with these programs can prevent differentiation and/or force differentiated cells to lose their identity and re-enter a proliferative state. We have recently shown that the Arabidopsis Defective Kernel 1 (DEK1) protein is required both for the differentiation of epidermal cells and for the maintenance of their fully differentiated state. Defects in DEK1 activity lead to a deregulation of the expression of epidermis-specific differentiation-promoting HD-ZIP IV transcription factors. Here we propose a working model in which DEK1, by maintaining cell-cell contacts, and thus communication between neighboring cells, influences HD-ZIP IV gene expression and epidermis differentiation. PMID:27064205

  16. Crystal Violet Assay for Determining Viability of Cultured Cells.

    PubMed

    Feoktistova, Maria; Geserick, Peter; Leverkus, Martin

    2016-01-01

    Adherent cells detach from cell culture plates during cell death. This characteristic can be used for the indirect quantification of cell death and to determine differences in proliferation upon stimulation with death-inducing agents. One simple method to detect maintained adherence of cells is the staining of attached cells with crystal violet dye, which binds to proteins and DNA. Cells that undergo cell death lose their adherence and are subsequently lost from the population of cells, reducing the amount of crystal violet staining in a culture. This protocol describes a quick and reliable screening method that is suitable for the examination of the impact of chemotherapeutics or other compounds on cell survival and growth inhibition. However, characterization of the cause of reduced crystal violet staining requires additional methods detailed elsewhere. PMID:27037069

  17. Phenotypic and Molecular Characterization of Domestic Cat (Felis catus) Spermatogonial Stem Cells.

    PubMed

    Powell, Robin H; Galiguis, Jason; Biancardi, Monica N; Pope, C Earle; Leibo, Stanley P; Wang, Guoshun; Gómez, Martha C

    2016-07-01

    In many mammalian species, surface markers have been used to obtain enriched populations of spermatogonial stem cells (SSCs) for assisted reproduction and other applications; however, little is known about the expression patterns of feline SSCs. In this study, we assessed expression of the SSC surface markers commonly used in other species, KIT, ITGA6, CD9, GFRalpha1, ADGRA3, and THY1, in addition to the less frequently used pluripotent markers TRA-1-60, TRA-1-81, SSEA-1, and SSEA-4 in SSCs of both prepubertal and adult domestic cats (Felis catus). To further characterize cat SSCs, we sorted cells using SSC-specific markers and evaluated the expression of the pluripotent transcription factors NANOG, POU5F1, and SOX2 and the proto-oncogene MYC within these populations. We concluded that SSC surface markers used in other mammalian species were not specific for identifying cat SSCs. However, the pluripotent markers we evaluated were more specific to cat spermatogonia, and the presence of SSEA-1 and SSEA-4 in fewer and primarily individual cells suggests that these two markers may be used for enrichment of cat SSCs. The expression of pluripotent transcription factors at mRNA level by single-stained cells positive for SSEA-4 and by dual-stained cells positive for both GFRalpha1 and SSEA-4 reflects the undifferentiated stage of cat SSCs. The absence of transcription factors in double-stained cells positive for only one marker implies the loss of the stem cell-like identity with the loss of either GFRalpha1 or SSEA-4. Further investigation is warranted to elucidate the biological characteristics of these spermatogonial subpopulations. PMID:27281702

  18. Properly substituted analogues of BIX-01294 lose inhibition of G9a histone methyltransferase and gain selective anti-DNA methyltransferase 3A activity.

    PubMed

    Rotili, Dante; Tarantino, Domenico; Marrocco, Biagina; Gros, Christina; Masson, Véronique; Poughon, Valérie; Ausseil, Fréderic; Chang, Yanqi; Labella, Donatella; Cosconati, Sandro; Di Maro, Salvatore; Novellino, Ettore; Schnekenburger, Michael; Grandjenette, Cindy; Bouvy, Celine; Diederich, Marc; Cheng, Xiaodong; Arimondo, Paola B; Mai, Antonello

    2014-01-01

    Chemical manipulations performed on the histone H3 lysine 9 methyltransferases (G9a/GLP) inhibitor BIX-01294 afforded novel desmethoxyquinazolines able to inhibit the DNA methyltransferase DNMT3A at low micromolar levels without any significant inhibition of DNMT1 and G9a. In KG-1 cells such compounds, when tested at sub-toxic doses, induced the luciferase re-expression in a stable construct controlled by a cytomegalovirus (CMV) promoter silenced by methylation (CMV-luc assay). Finally, in human lymphoma U-937 and RAJI cells, the N-(1-benzylpiperidin-4-yl)-2-(4-phenylpiperazin-1-yl)quinazolin-4-amine induced the highest proliferation arrest and cell death induction starting from 10 µM, in agreement with its DNMT3A inhibitory potency. PMID:24810902

  19. The Controversy, Challenges, and Potential Benefits of Putative Female Germline Stem Cells Research in Mammals

    PubMed Central

    Pan, Zezheng; Sun, Mengli; Liang, Xia; Li, Jia; Zhou, Fangyue; Zhong, Zhisheng; Zheng, Yuehui

    2016-01-01

    The conventional view is that female mammals lose their ability to generate new germ cells after birth. However, in recent years, researchers have successfully isolated and cultured a type of germ cell from postnatal ovaries in a variety of mammalian species that have the abilities of self-proliferation and differentiation into oocytes, and this finding indicates that putative germline stem cells maybe exist in the postnatal mammalian ovaries. Herein, we review the research history and discovery of putative female germline stem cells, the concept that putative germline stem cells exist in the postnatal mammalian ovary, and the research progress, challenge, and application of putative germline stem cells in recent years. PMID:26788065

  20. The Controversy, Challenges, and Potential Benefits of Putative Female Germline Stem Cells Research in Mammals.

    PubMed

    Pan, Zezheng; Sun, Mengli; Liang, Xia; Li, Jia; Zhou, Fangyue; Zhong, Zhisheng; Zheng, Yuehui

    2016-01-01

    The conventional view is that female mammals lose their ability to generate new germ cells after birth. However, in recent years, researchers have successfully isolated and cultured a type of germ cell from postnatal ovaries in a variety of mammalian species that have the abilities of self-proliferation and differentiation into oocytes, and this finding indicates that putative germline stem cells maybe exist in the postnatal mammalian ovaries. Herein, we review the research history and discovery of putative female germline stem cells, the concept that putative germline stem cells exist in the postnatal mammalian ovary, and the research progress, challenge, and application of putative germline stem cells in recent years. PMID:26788065

  1. [Functional morphology of the adrenal cortex and incretory kidney structures in the salt-losing form of adrenogenital syndrome in children].

    PubMed

    Tsibel', B N; Padalko, N L

    1986-01-01

    The adrenals and kidney incretory structures (the juxtaglomerular apparatuses and renomedullary interstitial cells) were studied in 12 cases of a desalinization form of the adrenogenital syndrome in children who died at the age of 1-6 mos of acute water-electrolytic disturbances in order to assess function of the structures involved in the regulation of the water-salt equilibrium. The adrenals and kidneys from 7 children of the same age who died of mechanical asphyxia, were taken as controls. The depth of adrenocortical zones, volumes of nuclei and nucleoli in different cortical zones were determined; the juxtaglomerular index, cell count (including vacuolized cells), the area of the juxtaglomerular apparatus and mesangium were determined in the juxtaglomerular apparatus. The amount of cell lipid granules (the interstitial-cellular index), the mean granule volume and the total granule volume were counted in renomedullary interstitial cells. The results were statistically processed, and a paired correlation analysis of all the studied parameters was performed. In the desalinization form of the adrenogenital syndrome morphometric investigation of the glomerular and fascicular zones revealed compensatory processes, not of hyperplastic nature but mainly of hypertrophic nature; morphological and morphometric characteristics of the kidney incretory structures indicated tension of the renin-angiotensin system and probably a decrease in prostaglandin synthesis in salt and water loss. In the control group parameters of structures related to the regulation of the water-salt equilibrium, especially in the adrenal cortex, showed good correlation. In the desalinization form of the adrenogenital syndrome some other relationships between these structures developed. PMID:3809126

  2. The interplay of effector and regulatory T cells in cancer.

    PubMed

    Roychoudhuri, Rahul; Eil, Robert L; Restifo, Nicholas P

    2015-04-01

    Regulatory T (Treg) cells suppress effector T (Teff) cells and prevent immune-mediated rejection of cancer. Much less appreciated are mechanisms by which Teff cells antagonize Treg cells. Herein, we consider how complex reciprocal interactions between Teff and Treg cells shape their population dynamics within tumors. Under states of tolerance, including during tumor escape, suppressed Teff cells support Treg cell populations through antigen-dependent provision of interleukin (IL)-2. During immune activation, Teff cells can lose this supportive capacity and directly antagonize Treg cell populations to neutralize their immunosuppressive function. While this latter state is rarely achieved spontaneously within tumors, we propose that therapeutic induction of immune activation has the potential to stably disrupt immunosuppressive population states resulting in durable cancer regression. PMID:25728990

  3. Formation of a Neurosensory Organ by Epithelial Cell Slithering.

    PubMed

    Kuo, Christin S; Krasnow, Mark A

    2015-10-01

    Epithelial cells are normally stably anchored, maintaining their relative positions and association with the basement membrane. Developmental rearrangements occur through cell intercalation, and cells can delaminate during epithelial-mesenchymal transitions and metastasis. We mapped the formation of lung neuroepithelial bodies (NEBs), innervated clusters of neuroendocrine/neurosensory cells within the bronchial epithelium, revealing a targeted mode of cell migration that we named "slithering," in which cells transiently lose epithelial character but remain associated with the membrane while traversing neighboring epithelial cells to reach cluster sites. Immunostaining, lineage tracing, clonal analysis, and live imaging showed that NEB progenitors, initially distributed randomly, downregulate adhesion and polarity proteins, crawling over and between neighboring cells to converge at diametrically opposed positions at bronchial branchpoints, where they reestablish epithelial structure and express neuroendocrine genes. There is little accompanying progenitor proliferation or apoptosis. Activation of the slithering program may explain why lung cancers arising from neuroendocrine cells are highly metastatic. PMID:26435104

  4. Functional Differences between GDNF-Dependent and FGF2-Dependent Mouse Spermatogonial Stem Cell Self-Renewal

    PubMed Central

    Takashima, Seiji; Kanatsu-Shinohara, Mito; Tanaka, Takashi; Morimoto, Hiroko; Inoue, Kimiko; Ogonuki, Narumi; Jijiwa, Mayumi; Takahashi, Masahide; Ogura, Atsuo; Shinohara, Takashi

    2015-01-01

    Summary Spermatogonial stem cells (SSCs) are required for spermatogenesis. Earlier studies showed that glial cell line-derived neurotrophic factor (GDNF) was indispensable for SSC self-renewal by binding to the GFRA1/RET receptor. Mice with mutations in these molecules showed impaired spermatogenesis, which was attributed to SSC depletion. Here we show that SSCs undergo GDNF-independent self-renewal. A small number of spermatogonia formed colonies when testis fragments from a Ret mutant mouse strain were transplanted into heterologous recipients. Moreover, fibroblast growth factor 2 (FGF2) supplementation enabled in vitro SSC expansion without GDNF. Although GDNF-mediated self-renewal signaling required both AKT and MAP2K1/2, the latter was dispensable in FGF2-mediated self-renewal. FGF2-depleted testes exhibited increased levels of GDNF and were enriched for SSCs, suggesting that the balance between FGF2 and GDNF levels influences SSC self-renewal in vivo. Our results show that SSCs exhibit at least two modes of self-renewal and suggest complexity of SSC regulation in vivo. PMID:25684228

  5. Ionomycin Treatment Renders NK Cells Hyporesponsive.

    PubMed

    Romera-Cárdenas, Gema; Thomas, L Michael; Lopez-Cobo, Sheila; García-Cuesta, Eva M; Long, Eric O; Reyburn, Hugh T

    2016-01-01

    Natural killer cells are cytotoxic lymphocytes important in immune responses to cancer and multiple pathogens. However, chronic activation of NK cells can induce a hyporesponsive state. The molecular basis of the mechanisms underlying the generation and maintenance of this hyporesponsive condition are unknown, thus an easy and reproducible mechanism able to induce hyporesponsiveness on human NK cells would be very useful to gain understanding of this process. Human NK cells treated with ionomycin lose their ability to degranulate and secrete IFN-γ in response to a variety of stimuli, but IL-2 stimulation can compensate these defects. Apart from reductions in the expression of CD11a/CD18, no great changes were observed in the activating and inhibitory receptors expressed by these NK cells, however their transcriptional signature is different to that described for other hyporesponsive lymphocytes. PMID:27007115

  6. Ionomycin Treatment Renders NK Cells Hyporesponsive

    PubMed Central

    Romera-Cárdenas, Gema; Thomas, L. Michael; Lopez-Cobo, Sheila; García-Cuesta, Eva M.; Long, Eric O.; Reyburn, Hugh T.

    2016-01-01

    Natural killer cells are cytotoxic lymphocytes important in immune responses to cancer and multiple pathogens. However, chronic activation of NK cells can induce a hyporesponsive state. The molecular basis of the mechanisms underlying the generation and maintenance of this hyporesponsive condition are unknown, thus an easy and reproducible mechanism able to induce hyporesponsiveness on human NK cells would be very useful to gain understanding of this process. Human NK cells treated with ionomycin lose their ability to degranulate and secrete IFN-γ in response to a variety of stimuli, but IL-2 stimulation can compensate these defects. Apart from reductions in the expression of CD11a/CD18, no great changes were observed in the activating and inhibitory receptors expressed by these NK cells, however their transcriptional signature is different to that described for other hyporesponsive lymphocytes. PMID:27007115

  7. Expansion and long-term culture of human spermatogonial stem cells via the activation of SMAD3 and AKT pathways.

    PubMed

    Guo, Ying; Liu, Linhong; Sun, Min; Hai, Yanan; Li, Zheng; He, Zuping

    2015-08-01

    Spermatogonial stem cells (SSCs) can differentiate into spermatids, reflecting that they could be used in reproductive medicine for treating male infertility. SSCs are able to become embryonic stem-like cells with the potentials of differentiating into numerous cell types of the three germ layers and they can transdifferentiate to mature and functional cells of other lineages, highlighting significant applications of human SSCs for treating human diseases. However, human SSCs are very rare and a long-term culture system of human SSCs has not yet established. This aim of study was to isolate, identify and culture human SSCs for a long period. We isolated GPR125-positive spermatogonia with high purity and viability from adult human testicular tissues utilizing the two-step enzymatic digestion and magnetic-activated cell sorting with antibody against GPR125. These freshly isolated cells expressed a number of markers for SSCs, including GPR125, PLZF, GFRA1, RET, THY1, UCHL1 and MAGEA4, but not the hallmarks for spermatocytes and spermatozoa, e.g. SYCP1, SYCP3, PRM1, and TNP1. The isolated human SSCs could be cultured for two months with a significant increase of cell number with the defined medium containing growth factors and hydrogel. Notably, the expression of numerous SSC markers was maintained during the cultivation of human SSCs. Furthermore, SMAD3 and AKT phosphorylation was enhanced during the culture of human SSCs. Collectively, these results suggest that human SSCs can be cultivated for a long period and expanded whilst retaining an undifferentiated status via the activation of SMAD3 and AKT pathways. This study could provide sufficient cells of SSCs for their basic research and clinic applications in reproductive and regenerative medicine. PMID:26088866

  8. RasGAP Shields Akt from Deactivating Phosphatases in Fibroblast Growth Factor Signaling but Loses This Ability Once Cleaved by Caspase-3.

    PubMed

    Cailliau, Katia; Lescuyer, Arlette; Burnol, Anne-Françoise; Cuesta-Marbán, Álvaro; Widmann, Christian; Browaeys-Poly, Edith

    2015-08-01

    Fibroblast growth factor receptors (FGFRs) are involved in proliferative and differentiation physiological responses. Deregulation of FGFR-mediated signaling involving the Ras/PI3K/Akt and the Ras/Raf/ERK MAPK pathways is causally involved in the development of several cancers. The caspase-3/p120 RasGAP module is a stress sensor switch. Under mild stress conditions, RasGAP is cleaved by caspase-3 at position 455. The resulting N-terminal fragment, called fragment N, stimulates anti-death signaling. When caspase-3 activity further increases, fragment N is cleaved at position 157. This generates a fragment, called N2, that no longer protects cells. Here, we investigated in Xenopus oocytes the impact of RasGAP and its fragments on FGF1-mediated signaling during G2/M cell cycle transition. RasGAP used its N-terminal Src homology 2 domain to bind FGFR once stimulated by FGF1, and this was necessary for the recruitment of Akt to the FGFR complex. Fragment N, which did not associate with the FGFR complex, favored FGF1-induced ERK stimulation, leading to accelerated G2/M transition. In contrast, fragment N2 bound the FGFR, and this inhibited mTORC2-dependent Akt Ser-473 phosphorylation and ERK2 phosphorylation but not phosphorylation of Akt on Thr-308. This also blocked cell cycle progression. Inhibition of Akt Ser-473 phosphorylation and entry into G2/M was relieved by PHLPP phosphatase inhibition. Hence, full-length RasGAP favors Akt activity by shielding it from deactivating phosphatases. This shielding was abrogated by fragment N2. These results highlight the role played by RasGAP in FGFR signaling and how graded stress intensities, by generating different RasGAP fragments, can positively or negatively impact this signaling. PMID:26109071

  9. Antigenotoxic effect of Chamomilla recutita (L.) Rauschert essential oil in mouse spermatogonial cells, and determination of its antioxidant capacity in vitro.

    PubMed

    Hernández-Ceruelos, Alejandra; Madrigal-Santillán, Eduardo; Morales-González, José Antonio; Chamorro-Cevallos, Germán; Cassani-Galindo, Martha; Madrigal-Bujaidar, Eduardo

    2010-01-01

    Chamomilla recutita (L.) Rauschert (Asteraceae), popularly known as chamomile, is a plant used in traditional medicine for various therapeutic purposes. Chamomile essential oil (CEO) is particularly known to inhibit the genotoxic damage produced by mutagens in mice somatic cells. The aim of this research was to determine the inhibitory potential of CEO on the genotoxic damage produced by daunorubicin (DAU) in mice germ cells. We evaluated the effect of 5, 50, and 500 mg/kg of essential oil on the rate of sister chromatid exchange (SCE) induced in spermatogonia by 10 mg/kg of the mutagen. We found no genotoxicity of CEO, but detected an inhibition of SCE after the damage induced by DAU; from the lowest to the highest dose of CEO we found an inhibition of 47.5%, 61.9%, and 93.5%, respectively. As a possible mechanism of action, the antioxidant capacity of CEO was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging method and ferric thiocyanate assays. In the first test we observed a moderate scavenging potential of the oil; nevertheless, the second assay showed an antioxidant capacity similar to that observed with vitamin E. In conclusion, we found that CEO is an efficient chemoprotective agent against the damage induced by DAU in the precursor cells of the germinal line of mice, and that its antioxidant capacity may induce this effect. PMID:21152302

  10. Antigenotoxic Effect of Chamomilla recutita (L.) Rauschert Essential Oil in Mouse Spermatogonial Cells, and Determination of Its Antioxidant Capacity in Vitro

    PubMed Central

    Hernández-Ceruelos, Alejandra; Madrigal-Santillán, Eduardo; Morales-González, José Antonio; Chamorro-Cevallos, Germán; Cassani-Galindo, Martha; Madrigal-Bujaidar, Eduardo

    2010-01-01

    Chamomilla recutita (L.) Rauschert (Asteraceae), popularly known as chamomile, is a plant used in traditional medicine for various therapeutic purposes. Chamomile essential oil (CEO) is particularly known to inhibit the genotoxic damage produced by mutagens in mice somatic cells. The aim of this research was to determine the inhibitory potential of CEO on the genotoxic damage produced by daunorubicin (DAU) in mice germ cells. We evaluated the effect of 5, 50, and 500 mg/kg of essential oil on the rate of sister chromatid exchange (SCE) induced in spermatogonia by 10 mg/kg of the mutagen. We found no genotoxicity of CEO, but detected an inhibition of SCE after the damage induced by DAU; from the lowest to the highest dose of CEO we found an inhibition of 47.5%, 61.9%, and 93.5%, respectively. As a possible mechanism of action, the antioxidant capacity of CEO was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging method and ferric thiocyanate assays. In the first test we observed a moderate scavenging potential of the oil; nevertheless, the second assay showed an antioxidant capacity similar to that observed with vitamin E. In conclusion, we found that CEO is an efficient chemoprotective agent against the damage induced by DAU in the precursor cells of the germinal line of mice, and that its antioxidant capacity may induce this effect. PMID:21152302

  11. Evaluating the role of silver nanoparticles on acrosomal reaction and spermatogenic cells in rat

    PubMed Central

    Miresmaeili, Sayyed Mohsen; Halvaei, Iman; Fesahat, Farzaneh; Fallah, Asghar; Nikonahad, Narges; Taherinejad, Mohaddeseh

    2013-01-01

    Background: Nanoparticles have wide range of application while there are some reports regarding their probable effects on male reproductive system and spermatozoa. Objective: The aim of this study was to evaluate the effect of different doses of silver nanoparticles (AgNPs) (70nm) on acrosome of rat spermatozoa and number of spermatogenic cells. Materials and Methods: In this experimental study, in experimental group, 32 male wistar rats (8 rats/group) received oral feeding AgNPs every 12 hr in one spermatogenesis period (48 days) by means of gavages in 25, 50 , 100 and 200 mg/kg concentration (experimental groups 1-4, respectively). The control group (8 rats) was treated on schedule with distilled water. Spermatozoa were stained by triple staining protocol for acrosome reaction. Histological evaluation on testis sections was performed using tissue processing and hematoxylin-eosin (H&E) staining. Results: There was significant difference between the control group and the experimental group 1 for acrosome reaction (11.00±0.00 and 24.25±3.68, respectively, p=0.01). There was only significant reduction in spermatogonia cells in experimental group 4. Experimental groups 2, 3 and 4 showed a significant reduction in the number of primary spermatocytes and spermatids as well as spermatozoa. But there were no significant differences between different groups for Sertoli cell number and seminiferous tubule diameter. Conclusion: It seems that Ag NPs have acute and significant effects on spermatogenesis and number of spermatogenic cells and also on acrosome reaction in sperm cells. More experimental investigations are necessary to elucidate better conclusion regarding the safety of nanoparticles on male reproduction system. PMID:24639775

  12. Bactericidal Dendritic Polycation Cloaked with Stealth Material via Lipase-Sensitive Intersegment Acquires Neutral Surface Charge without Losing Membrane-Disruptive Activity.

    PubMed

    Xu, Lulu; He, Chen; Hui, Liwei; Xie, Yuntao; Li, Jia-Min; He, Wei-Dong; Yang, Lihua

    2015-12-23

    Net cationicity of membrane-disruptive antimicrobials is necessary for their activity but may elicit immune attack when administered intravenously. By cloaking a dendritic polycation (G2) with poly(caprolactone-b-ethylene glycol) (PCL-b-PEG), we obtain a nanoparticle antimicrobial, G2-g-(PCL-b-PEG), which exhibits neutral surface charge but kills >99.9% of inoculated bacterial cells at ≤8 μg/mL. The observed activity may be attributed PCL's responsive degradation by bacterial lipase and the consequent exposure of the membrane-disruptive, bactericidal G2 core. Moreover, G2-g-(PCL-b-PEG) exhibits good colloidal stability in the presence of serum and insignificant hemolytic toxicity even at ≥2048 μg/mL. suggesting good blood compatibility required for intravenous administration. PMID:26632646

  13. Hair cell recovery in mitotically blocked cultures of the bullfrog saccule

    NASA Technical Reports Server (NTRS)

    Baird, R. A.; Burton, M. D.; Fashena, D. S.; Naeger, R. A.

    2000-01-01

    Hair cells in many nonmammalian vertebrates are regenerated by the mitotic division of supporting cell progenitors and the differentiation of the resulting progeny into new hair cells and supporting cells. Recent studies have shown that nonmitotic hair cell recovery after aminoglycoside-induced damage can also occur in the vestibular organs. Using hair cell and supporting cell immunocytochemical markers, we have used confocal and electron microscopy to examine the fate of damaged hair cells and the origin of immature hair cells after gentamicin treatment in mitotically blocked cultures of the bullfrog saccule. Extruding and fragmenting hair cells, which undergo apoptotic cell death, are replaced by scar formations. After losing their bundles, sublethally damaged hair cells remain in the sensory epithelium for prolonged periods, acquiring supporting cell-like morphology and immunoreactivity. These modes of damage appear to be mutually exclusive, implying that sublethally damaged hair cells repair their bundles. Transitional cells, coexpressing hair cell and supporting cell markers, are seen near scar formations created by the expansion of neighboring supporting cells. Most of these cells have morphology and immunoreactivity similar to that of sublethally damaged hair cells. Ultrastructural analysis also reveals that most immature hair cells had autophagic vacuoles, implying that they originated from damaged hair cells rather than supporting cells. Some transitional cells are supporting cells participating in scar formations. Supporting cells also decrease in number during hair cell recovery, supporting the conclusion that some supporting cells undergo phenotypic conversion into hair cells without an intervening mitotic event.

  14. Comparison of Diverse Differential Plating Methods to Enrich Bovine Spermatogonial Cells.

    PubMed

    Giassetti, M I; Goissis, M D; de Barros, Fro; Bruno, A H; Assumpção, Meoa; Visintin, J A

    2016-02-01

    Spermatogonial stem cells (SSC) have important applications in domestic animal reproduction and advanced biotechnologies. Because differential plating is one of the most common methods used for SSC enrichment, the goal of this study was to compare three differential plating methods for the enrichment of bovine SSC. To achieve this goal, testicular parenchyma from pre-pubertal calves was minced and single cells were obtained after two enzymatic digestions. We compared three coating methods for differential plating: laminin (20 ng/ml), BSA (0.05 mg/ml) and PBS. Cells were incubated at 37°C, 5% CO2 in air for 15 min onto laminin-coated dishes or 2 h onto BSA- or PBS-coated dishes. Cell viability was assessed by trypan blue exclusion method. Recovered cells were analysed for the expression of SSC molecular markers by quantitative RT-PCR (GFRA1, CXCR4, ITGA6, THY1) and flow cytometry (GFRA1, CXCR4 and ITGA6). Cells at time 0, adherent cells on laminin and non-adherent cells from BSA and PBS groups had the same cell viability (p = 0.0655). GFRA1, CXCR4 and THY1 relative gene expression was higher (p = 0.0402, p = 0.0007, p = 0.0117, respectively) for non-adherent cells selected in PBS group. Flow cytometry analysis revealed that the presence of GFRA-positive (GFRA+) cells was higher in non-adherent cells from BSA and PBS groups (p < 0.001). However, laminin-adherent cells had higher number of ITGA6+ cells (p < 0.001) and lower presence of CXCR4+ cells (p = 0.0012). In conclusion, differential plating is an effective method for the enrichment of bovine undifferentiated spermatogonia and higher expression of SSC markers is obtained without laminin or BSA coating. PMID:26576932

  15. Gonads in Histiostoma mites (Acariformes: Astigmata): structure and development.

    PubMed

    Witaliński, Wojciech; Rożej-Pabijan, Elżbieta; Podkowa, Dagmara

    2014-07-01

    The development of male and female gonads in arrhenotokous and thelytokous species of Histiostoma was studied using transmission electron microscopy (TEM). All instars were examined: larvae, protonymphs, facultative heteromorphic deutonymphs (=hypopi), tritonymphs, and adults. In testis primordium, spermatogonia surrounding a testicular central cell (TCC) with a gradually enlarging, branched nucleus are present already at the larval stage. Spermatogonia and the TCC are connected via narrow, tubular intercellular bridges revealing that the TCC is a germline cell. Spermatocytes appear at the protonymphal stage. At the heteromorphic deutonymph stage, the testis primordium is similar to that of the protonymph, but in the tritonymph it is much larger and composed as in the adult: spermatids as well as sperm cells are present. The latter are congregated ventrally in the testis at the entrance of the deferent duct. In the larval ovary, an eccentrically located ovarian nutritive cell (ONC) is surrounded by oogonia which are connected with the ONC via tubular intercellular bridges. In later stages, the ovary grows and oocytes appear in the protonymph. Meiotic synaptonemal complexes in oocytes occur from the tritonymph stage. At about the time of the final molting, tubular intercellular bridges transform into peculiar diaphragm-crossed bridges known only in Histiostoma mites. In the adult female, growing oocytes at the end of previtellogenesis lose intercellular bridges and move ventro-laterally to the ovarian periphery towards the oviduct entrance. Vitellogenesis occurs in oviducts. Germinal cells in both the testis and ovary are embedded in a few somatic stroma cells which may be well discernible already in the larval ovary; in the testis, somatic stroma cells are evident not earlier than the end of the tritonymphal stage. The ovary has a thin wall of flat somatic cells, whereas the testis is covered by a basal lamina only. The obtained results suggest that gonads in

  16. BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties.

    PubMed

    Rendl, Michael; Polak, Lisa; Fuchs, Elaine

    2008-02-15

    Hair follicle (HF) formation is initiated when epithelial stem cells receive cues from specialized mesenchymal dermal papilla (DP) cells. In culture, DP cells lose their HF-inducing properties, but during hair growth in vivo, they reside within the HF bulb and instruct surrounding epithelial progenitors to orchestrate the complex hair differentiation program. To gain insights into the molecular program that maintains DP cell fate, we previously purified DP cells and four neighboring populations and defined their cell-type-specific molecular signatures. Here, we exploit this information to show that the bulb microenvironment is rich in bone morphogenetic proteins (BMPs) that act on DP cells to maintain key signature features in vitro and hair-inducing activity in vivo. By employing a novel in vitro/in vivo hybrid knockout assay, we ablate BMP receptor 1a in purified DP cells. When DPs cannot receive BMP signals, they lose signature characteristics in vitro and fail to generate HFs when engrafted with epithelial stem cells in vivo. These results reveal that BMP signaling, in addition to its key role in epithelial stem cell maintenance and progenitor cell differentiation, is essential for DP cell function, and suggest that it is a critical feature of the complex epithelial-mesenchymal cross-talk necessary to make hair. PMID:18281466

  17. RNA binding protein Musashi-1 directly targets Msi2 and Erh during early testis germ cell development and interacts with IPO5 upon translocation to the nucleus.

    PubMed

    Sutherland, Jessie M; Sobinoff, Alexander P; Fraser, Barbara A; Redgrove, Kate A; Davidson, Tara-Lynne; Siddall, Nicole A; Koopman, Peter; Hime, Gary R; McLaughlin, Eileen A

    2015-07-01

    Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the process of gamete development, male germ cells experience extended periods of inactive transcription despite requirements for continued growth and differentiation. Spermatogenesis therefore provides an ideal model to study the effects of posttranscriptional control on gene regulation. During spermatogenesis posttranscriptional regulation is orchestrated by abundantly expressed RNA-binding proteins. One such group of RNA-binding proteins is the Musashi family, previously identified as a critical regulator of testis germ cell development and meiosis in Drosophila and also shown to be vital to sperm development and reproductive potential in the mouse. We focus in depth on the role and function of the vertebrate Musashi ortholog Musashi-1 (MSI1). Through detailed expression studies and utilizing our novel transgenic Msi1 testis-specific overexpression model, we have identified 2 unique RNA-binding targets of MSI1 in spermatogonia, Msi2 and Erh, and have demonstrated a role for MSI1 in translational regulation. We have also provided evidence to suggest that nuclear import protein, IPO5, facilitates the nuclear translocation of MSI1 to the transcriptionally silenced XY chromatin domain in meiotic pachytene spermatocytes, resulting in the release of MSI1 RNA-binding targets. This firmly establishes MSI1 as a master regulator of posttranscriptional control during early spermatogenesis and highlights the significance of the subcellular localization of RNA binding proteins in relation to their function. PMID:25782991

  18. Umbilical Cord Derived Mesenchymal Stem Cells Useful in Insulin Production - Another Opportunity in Cell Therapy

    PubMed Central

    Sarang, Shabari; Viswanathan, Chandra

    2016-01-01

    Background and Objectives Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder resulting out of T cell mediated destruction of pancreatic beta cells. Immunomodulatory properties of mesenchymal stem cells may help to regenerate beta cells and/or prevent further destruction of remnant, unaffected beta cells in diabetes. We have assessed the ability of umbilical cord derived MSCs (UCMSCs) to differentiate into functional islet cells in vitro. Methods and Results We have isolated UCMSCs and allowed sequential exposure of various inducing agents and growth factors. We characterized these cells for confirmation of the presence of islet cell markers and their functionality. The spindle shaped undifferentiated UCMSCs, change their morphology to become triangular in shape. These cells then come together to form the islet like structures which then grow in size and mature over time. These cells express pancreatic and duodenal homeobox −1 (PDX-1), neurogenin 3 (Ngn-3), glucose transporter 2 (Glut 2) and other pancreatic cell markers like glucagon, somatostatin and pancreatic polypeptide and lose expression of MSC markers like CD73 and CD105. They were functionally active as demonstrated by release of physiological insulin and C-peptide in response to elevated glucose concentrations. Conclusions Pancreatic islet like cells with desired functionality can thus be obtained in reasonable numbers from undifferentiated UCMSCs invitro. This could help in establishing a “very definitive source” of islet like cells for cell therapy. UCMSCs could thus be a game changer in treatment of diabetes. PMID:27426087

  19. Attenuation of Cell Mechanosensitivity in Colon Cancer Cells during In Vitro Metastasis

    PubMed Central

    Tang, Xin; Wen, Qi; Kuhlenschmidt, Theresa B.; Kuhlenschmidt, Mark S.; Janmey, Paul A.; Saif, Taher A.

    2012-01-01

    Human colon carcinoma (HCT-8) cells show a stable transition from low to high metastatic state when cultured on appropriately soft substrates (21 kPa). Initially epithelial (E) in nature, the HCT-8 cells become rounded (R) after seven days of culture on soft substrate. R cells show a number of metastatic hallmarks [1]. Here, we use gradient stiffness substrates, a bio-MEMS force sensor, and Coulter counter assays to study mechanosensitivity and adhesion of E and R cells. We find that HCT-8 cells lose mechanosensitivity as they undergo E-to-R transition. HCT-8 R cells' stiffness, spread area, proliferation and migration become insensitive to substrate stiffness in contrast to their epithelial counterpart. They are softer, proliferative and migratory on all substrates. R cells show negligible cell-cell homotypic adhesion, as well as non-specific cell-substrate adhesion. Consequently they show the same spread area on all substrates in contrast to E cells. Taken together, these results indicate that R cells acquire autonomy and anchorage independence, and are thus potentially more invasive than E cells. To the best of our knowledge, this is the first report of quantitative data relating changes in cancer cell adhesion and stiffness during the expression of an in vitro metastasis-like phenotype. PMID:23226284

  20. Plant cell in the process of the adaptation to simulated microgravity

    NASA Astrophysics Data System (ADS)

    Kordyum, E. L.

    Analysis of structural-and-functional rearrangements in the organelles of meristematic, differentiating and differentiated cells of pea root under microgravity demonstrated certain consistencies in their manifestation, namely: a) heterogeneity of the organelles in a cell population with respect to the degree of the rearrangements; b) coincidence of a spatial succession in development; c) increased reactivity under changes in functional load during cell growth and differentiation; d) enhanced activity when a cell loses its specific functions (replacement of functions). It is assumed that microgravity does not prevent the development of certain adaptative reactions of organisms at the cellular level.

  1. Identification of proteins sensitive to thermal stress in human neuroblastoma and glioma cell lines.

    PubMed

    Xu, Guilian; Stevens, Stanley M; Kobeissy, Firas; Kobiessy, Firas; Brown, Hilda; McClung, Scott; Gold, Mark S; Borchelt, David R

    2012-01-01

    Heat-shock is an acute insult to the mammalian proteome. The sudden elevation in temperature has far-reaching effects on protein metabolism, leads to a rapid inhibition of most protein synthesis, and the induction of protein chaperones. Using heat-shock in cells of neuronal (SH-SY5Y) and glial (CCF-STTG1) lineage, in conjunction with detergent extraction and sedimentation followed by LC-MS/MS proteomic approaches, we sought to identify human proteins that lose solubility upon heat-shock. The two cell lines showed largely overlapping profiles of proteins detected by LC-MS/MS. We identified 58 proteins in detergent insoluble fractions as losing solubility in after heat shock; 10 were common between the 2 cell lines. A subset of the proteins identified by LC-MS/MS was validated by immunoblotting of similarly prepared fractions. Ultimately, we were able to definitively identify 3 proteins as putatively metastable neural proteins; FEN1, CDK1, and TDP-43. We also determined that after heat-shock these cells accumulate insoluble polyubiquitin chains largely linked via lysine 48 (K-48) residues. Collectively, this study identifies human neural proteins that lose solubility upon heat-shock. These proteins may represent components of the human proteome that are vulnerable to misfolding in settings of proteostasis stress. PMID:23145051

  2. N-Cadherin-Mediated Signaling Regulates Cell Phenotype for Nucleus Pulposus Cells of the Intervertebral Disc

    PubMed Central

    Hwang, Priscilla Y.; Jing, Liufang; Michael, Keith W.; Richardson, William J.; Chen, Jun; Setton, Lori A.

    2015-01-01

    Juvenile nucleus pulposus (NP) cells of the intervertebral disc (IVD) are large, vacuolated cells that form cell clusters with strong cell–cell interactions. With maturation and aging, NP cells lose their ability to form these cell clusters, with aging-associated changes in NP cell phenotype, morphology, and proteoglycan synthesis that may contribute to IVD degeneration. Therefore, it is important to understand the mechanisms governing juvenile NP cell cluster behavior towards the goal of revealing factors that can promote juvenile, healthy NP cell phenotypes. N-cadherin has been identified as a cell–cell adhesion marker that is present in juvenile NP cells, but disappears with age. The goal of this study was to reveal the importance of N-cadherin in regulating cell–cell interactions in juvenile NP cell cluster formation and test for a regulatory role in maintaining a juvenile NP phenotype in vitro. Juvenile porcine IVD cells, of notochordal origin, were promoted to form cell clusters in vitro, and analyzed for preservation of the juvenile NP phenotype. Additionally, cadherin-blocking experiments were performed to prevent cluster formation in order to study the importance of cluster formation in NP cell signaling. Findings reveal N-cadherin-mediated cell–cell contacts promote cell clustering behavior and regulate NP cell matrix production and preservation of NP-specific markers. Inhibition of N-cadherin-mediated contacts resulted in loss of all features of the juvenile NP cell. These results establish a regulatory role for N-cadherin in juvenile NP cells, and suggest that preservation of the N-cadherin mediated cell–cell contact is important for preserving juvenile NP cell phenotype and morphology. PMID:25848407

  3. Primordial germ cell migration in the yellowtail kingfish (Seriola lalandi) and identification of stromal cell-derived factor 1.

    PubMed

    Fernández, J A; Bubner, E J; Takeuchi, Y; Yoshizaki, G; Wang, T; Cummins, S F; Elizur, A

    2015-03-01

    Primordial germ cells (PGCs) are progenitors of the germ cell lineage, giving rise to either spermatogonia or oogonia after the completion of gonadal differentiation. Currently, there is little information on the mechanism of PGCs migration leading to the formation of the primordial gonad in perciform fish. Yellowtail kingfish (Seriola lalandi) (YTK) (order Perciforms) inhabit tropical and temperate waters in the southern hemisphere. Fundamental details into the molecular basis of larval development in this species can be easily studied in Australia, as they are commercially cultured and readily available. In this study, histological analysis of YTK larvae revealed critical time points for the migration of PGCs to the genital ridge, resulting in the subsequent development of the primordial gonad. In YTK larvae at 3, 5, 7 and 10 days post hatch (DPH), PGCs were not yet enclosed by somatic cells, indicating the primordial gonad had not yet started to form. While at 15, 18 and 20 DPH PGCs had already settled at the genital ridge and started to become enclosed by somatic cells indicating the primordial gonad had started to develop. A higher number of PGCs were observed in the larvae at 15 and 18 DPH indicating PGCs proliferation, which corresponds with them becoming enclosed by the somatic cells. Directional migration of PGCs toward the genital ridge is a critical event in the subsequent development of a gonad. In zebrafish, mouse and chicken, stromal-cell derived factor (SDF1) signalling is one of the key molecules for PGC migration. We subsequently isolated from YTK the SDF1 (Slal-SDF1) gene, which encodes for a 98-residue precursor protein with a signal peptide at the N-terminus. There is spatial conservation between fish species of four cysteine residues at positions C9, C11, C34 and C49, expected to form disulphide bonds and stabilize the SDF structure. In YTK, Slal-SDF1 gene expression analyses shows that this gene is expressed in larvae from 1 to 22 DPH and

  4. Three RNA Binding Proteins Form a Complex to Promote Differentiation of Germline Stem Cell Lineage in Drosophila

    PubMed Central

    Zhao, Shaowei; Geng, Qing; Gao, Yu; Li, Xin; Zhang, Yang; Wang, Zhaohui

    2014-01-01

    In regenerative tissues, one of the strategies to protect stem cells from genetic aberrations, potentially caused by frequent cell division, is to transiently expand the stem cell daughters before further differentiation. However, failure to exit the transit amplification may lead to overgrowth, and the molecular mechanism governing this regulation remains vague. In a Drosophila mutagenesis screen for factors involved in the regulation of germline stem cell (GSC) lineage, we isolated a mutation in the gene CG32364, which encodes a putative RNA-binding protein (RBP) and is designated as tumorous testis (tut). In tut mutant, spermatogonia fail to differentiate and over-amplify, a phenotype similar to that in mei-P26 mutant. Mei-P26 is a TRIM-NHL tumor suppressor homolog required for the differentiation of GSC lineage. We found that Tut binds preferentially a long isoform of mei-P26 3′UTR, and is essential for the translational repression of mei-P26 reporter. Bam and Bgcn are both RBPs that have also been shown to repress mei-P26 expression. Our genetic analyses indicate that tut, bam, or bgcn is required to repress mei-P26 and to promote the differentiation of GSCs. Biochemically, we demonstrate that Tut, Bam, and Bgcn can form a physical complex in which Bam holds Tut on its N-terminus and Bgcn on its C-terminus. Our in vivo and in vitro evidence illustrate that Tut acts with Bam, Bgcn to accurately coordinate proliferation and differentiation in Drosophila germline stem cell lineage. PMID:25412508

  5. Neonatal bisphenol A exposure induces meiotic arrest and apoptosis of spermatogenic cells

    PubMed Central

    Xie, Meina; Bu, Pengli; Li, Fengjie; Lan, Shijian; Wu, Hongjuan; Yuan, Lu; Wang, Ying

    2016-01-01

    Bisphenol A (BPA) is a widely used industrial plasticizer, which is ubiquitously present in the environment and organisms. As an endocrine disruptor, BPA has caused significant concerns regarding its interference with reproductive function. However, little is known about the impact of BPA exposure on early testicular development. The aim of the present study was to investigate the influence of neonatal BPA exposure on the first wave of spermatogenesis. Newborn male mice were subcutaneously injected with BPA (0.01, 0.1 and 5 mg/kg body weight) daily from postnatal day (PND) 1 to 21. Histological analysis of testes at PND 22 revealed that BPA-treated testes contained mostly spermatogonia and spermatocytes with markedly less round spermatids, indicating signs of meiotic arrest. Terminal dUTP nick-end labeling (TUNEL) assay showed that BPA treatment significantly increased the number of apoptotic germ cells per tubule, which corroborated the observation of meiotic arrest. In addition, BPA caused abnormal proliferation of germ cells as revealed by Proliferating Cell Nuclear Antigen (PCNA) immunohistochemical staining. Mechanistically, BPA-treated testes displayed a complete lack of BOULE expression, which is a conserved key regulator for spermatogenesis. Moreover, BPA significantly increased the expression of estrogen receptor (ER) α and β in the developing testis. The present study demonstrated that neonatal BPA exposure disrupted meiosis progression during the first wave of spermatogenesis, which may be, at least in part, due to inhibition of BOULE expression and/or up-regulation of ERα/β expression in BPA-exposed developing testis. PMID:26863571

  6. AZT, rodent somatic and germ cell mutagenicity and reproductive toxicity tests

    SciTech Connect

    Shelby, M.D.; Russell, L.B.; Generoso, W.

    1995-11-01

    AZT (3`-axido-3`-deoxythymidine, Zidovudine) is the most widely used therapeutic agent in the treatment of Acquired Immune Deficiency Syndrome (AIDS). Use of AZT has not been limited to HIV-seropositive individuals or to those with symptoms of AIDS. It has also been used as a chemoprophylactic agent in people accidentally exposed to HIV-contaminated body fluids, and to HIV-seropositive pregnant women to prevent infection of the fetus. Because of these latter uses, it is particularly important to determine whether long-term health effects might be associated with AZT exposure. Tests have been conducted to determine the in vivo genetic toxicity of AZT in mice. Dominant-lethal and morphological-specific-locus tests were conducted in males using 2 daily initraperitoneal injections of 750 mg/kg. The dominant-lethal test was negative for all germ cell stages from differentiating spermatogonia to mature sperm. Likewise, no evidence of the induction of specific locus mutations was observed in either spermatogonial stem cells or poststem-cell stages. Further, tests for effects on male and female reproduction and in utero development indicate a lack of effects. These results, along with preliminary clinical reports that birth outcomes are normal in newborns exposed to AZT in utero, are encouraging with regard to the risks to offspring of parents exposed to AZT, either prior to or during pregnancy. However, positive results in mouse bone marrow micronucleus tests and one report on the induction of chromosomal aberrations in the lymphocytes of AIDS patients on AZT therapy indicate that further studies are needed on the potential of AZT to adversely affect the long-term health of exposed individuals.

  7. Germ cell mutagenesis in medaka fish after exposures to high-energy cosmic ray nuclei: A human model

    NASA Astrophysics Data System (ADS)

    Shimada, Atsuko; Shima, Akihiro; Nojima, Kumie; Seino, Yo; Setlow, Richard B.

    2005-04-01

    Astronauts beyond the Earth's orbit are exposed to high-energy cosmic-ray nuclei with high values of linear energy transfer (LET), resulting in much more biological damage than from x-rays or -rays and may result in mutations and cancer induction. The relative biological effectiveness of these nuclei depends on the LET, rising to as high as 50 at LET values of 100-200 keV/µm. An endpoint of concern is germ cell mutations passed on to offspring, arising from exposure to these nuclei. A vertebrate model for germ cell mutation is Medaka fish (Oryzias latipes). We exposed wild type males to doses of 1 GeV per nucleon Fe nuclei or to 290 MeV per nucleon C nuclei. They were mated to females with recessive mutations at five-color loci. The transparent embryos from >100 days of mating (representing exposed sperm, spermatids, or spermatogonia) were observed so as to detect dominant lethal mutations and total color mutations, even though the embryos might not hatch. The relative number of mutant embryos as a function of dose were compared with those induced by -rays. The relative biological effectiveness values for dominant lethal mutations and total color mutations for exposed sperm and spermatids were 1.3-2.1 for exposure to C nuclei and 1.5-3.0 for exposure to Fe nuclei. (The spermatogonial data were uncertain.) These low values, and the negligible number of viable mutations, compared with those for mutations in somatic cells and for neoplastic transformation, indicate that germ cell mutations arising from exposures to cosmic ray nuclei are not a significant hazard to astronauts. astronaut hazards | linear energy transfer | relative biological effect

  8. Stochastic Particle Barcoding for Single-Cell Tracking and Multiparametric Analysis

    PubMed Central

    Castellarnau, Marc; Szeto, Gregory L.; Su, Hao-Wei; Tokatlian, Talar; Love, J. Christopher; Irvine, Darrell J.; Voldman, Joel

    2014-01-01

    This study presents stochastic particle barcoding (SPB), a method for tracking cell identity across bioanalytical platforms. In this approach, single cells or small collections of cells are co-encapsulated within an enzymatically-degradable hydrogel block along with a random collection of fluorescent beads, whose number, color, and position encode the identity of the cell, enabling samples to be transferred in bulk between single-cell assay platforms without losing the identity of individual cells. The application of SPB was demonstrated for transferring cells from a subnanoliter protein secretion/phenotyping array platform into a microtiter plate, with re-identification accuracies in the plate assay of 96±2%. Encapsulated cells were recovered by digesting the hydrogel, allowing subsequent genotyping and phenotyping of cell lysates. Finally, a model scaling was developed to illustrate how different parameters affect the accuracy of SPB and to motivate scaling of the method to 1,000's of unique blocks. PMID:25180800

  9. Molecular Cloning of Spergen-4, Encoding a Spermatogenic Cell-Specific Protein Associated with Sperm Flagella and the Acrosome Region in Rat Spermatozoa.

    PubMed

    Howida, Ali; Salaheldeen, Elsaid; Iida, Hiroshi

    2016-04-01

    We used a differential display in combination with complementary DNA (cDNA) cloning approach to isolate a novel rat gene LOC690919 with an open reading frame of 1227-length nucleotides encoding a protein of 409 amino acids. This gene was designated as Spergen-4 (a spermatogenic cell-specific gene-4). Spergen-4 mRNA was highly expressed in testis, and its expression was detected in rat testis starting at three weeks of postnatal development and persisting up to adulthood. Mouse and human orthologs, which lack N-terminal 77 amino acid residues of rat Spegen-4, were found in the database. Immunofluorescence microscopy and immunoblot analysis demonstrated that Spergen-4 was not expressed in spermatogonia, spermatocytes, and round spermatids, but was restrictedly detected at sperm head, cytoplasm, and developing flagella of elongated spermatids in rat testis. In mature spermatozoa, Spergen-4 was detected at the acrosome region as well as the principal piece of flagella. Spergen-4 immunosignal disappeared from sperm heads on acrosome reaction induced by progesterone. These data suggest that Spergen-4 integrated into elongated spermatids during spermiogenesis serves as a constituent for acrosome region and flagella of rat spermatozoa. PMID:27032685

  10. Losing Control: Conducting Studies with Comparison Groups

    ERIC Educational Resources Information Center

    Norton, Jan

    2006-01-01

    Studies in education often report the differences between participants' and non-participants' test scores, course grades, retention, and other criteria. When participants' average performance is higher, it can be difficult to attribute the improvements to participation. Comparing participants and non-participants on other measures can strengthen…

  11. Volunteer Losing Balance Wearing Inverted Glasses

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Brad McLain for the Space Biology Museum Network puts a volunteer back on balance as he tries to adjust to a world inverted by a special pair of glasses. This helps illustrate how dependent the human vestibular system is on visual cues. A volunteer is The activity was part of the Space Research and You education event held by NASA's Office of Biological and Physical Research on June 25, 2002, in Arlington, VA, to highlight the research that will be conducted on STS-107.

  12. Losing Your Gut Feelings. Intuition in Depression.

    PubMed

    Remmers, Carina; Michalak, Johannes

    2016-01-01

    Whereas in basic research, intuition has become a topic of great interest, clinical research and depression research in specific have not applied to the topic of intuition, yet. This is astonishing because a well-known phenomenon during depression is that patients have difficulties to judge and decide. In contrast to healthy individuals who take most daily life decisions intuitively (Kahneman, 2011), depressed individuals seem to have difficulties to come to fast and adaptive decisions. The current article pursues three goals. First, our aim is to establish the hypothesis that intuition is impaired in depression against the background of influential theoretical accounts as well as empirical evidence from basic and clinical research. The second aim of the current paper is to provide explanations for recent findings on the depression-intuition interplay and to present directions for future research that may help to broaden our understanding of decision difficulties in depression. Third, we seek to propose ideas on how therapeutic interventions can support depressed individuals in taking better decisions. Even though our knowledge regarding this topic is still limited, we will tentatively launch the idea that an important first step may be to enhance patients' access to intuitions. Overall, this paper seeks to introduce the topic of intuition to clinical research on depression and to hereby set the stage for upcoming theory and practice. PMID:27602015

  13. Bottle bill loses, nuclear power gains

    SciTech Connect

    Not Available

    1987-11-01

    The November 3, 1987 elections saw a number of environmental-related referenda defeated for what was seen as economic reasons. Maine voters decided 59 to 41 percent against a proposal which would have closed down the Maine Yankee Nuclear Power Plant. In the District of Columbia, a litter reducing bill that would have required a 5 to 20 cent deposit on cans and bottles was defeated by 55 to 45 percent. Finally, in California, Indian Wells voters supported a project to build a one billion dollar resort in the nearby desert.

  14. Losing Your Gut Feelings. Intuition in Depression

    PubMed Central

    Remmers, Carina; Michalak, Johannes

    2016-01-01

    Whereas in basic research, intuition has become a topic of great interest, clinical research and depression research in specific have not applied to the topic of intuition, yet. This is astonishing because a well-known phenomenon during depression is that patients have difficulties to judge and decide. In contrast to healthy individuals who take most daily life decisions intuitively (Kahneman, 2011), depressed individuals seem to have difficulties to come to fast and adaptive decisions. The current article pursues three goals. First, our aim is to establish the hypothesis that intuition is impaired in depression against the background of influential theoretical accounts as well as empirical evidence from basic and clinical research. The second aim of the current paper is to provide explanations for recent findings on the depression-intuition interplay and to present directions for future research that may help to broaden our understanding of decision difficulties in depression. Third, we seek to propose ideas on how therapeutic interventions can support depressed individuals in taking better decisions. Even though our knowledge regarding this topic is still limited, we will tentatively launch the idea that an important first step may be to enhance patients’ access to intuitions. Overall, this paper seeks to introduce the topic of intuition to clinical research on depression and to hereby set the stage for upcoming theory and practice. PMID:27602015

  15. Losing the beat: deficits in temporal coordination

    PubMed Central

    Palmer, Caroline; Lidji, Pascale; Peretz, Isabelle

    2014-01-01

    Tapping or clapping to an auditory beat, an easy task for most individuals, reveals precise temporal synchronization with auditory patterns such as music, even in the presence of temporal fluctuations. Most models of beat-tracking rely on the theoretical concept of pulse: a perceived regular beat generated by an internal oscillation that forms the foundation of entrainment abilities. Although tapping to the beat is a natural sensorimotor activity for most individuals, not everyone can track an auditory beat. Recently, the case of Mathieu was documented (Phillips-Silver et al. 2011 Neuropsychologia 49, 961–969. (doi:10.1016/j.neuropsychologia.2011.02.002)). Mathieu presented himself as having difficulty following a beat and exhibited synchronization failures. We examined beat-tracking in normal control participants, Mathieu, and a second beat-deaf individual, who tapped with an auditory metronome in which unpredictable perturbations were introduced to disrupt entrainment. Both beat-deaf cases exhibited failures in error correction in response to the perturbation task while exhibiting normal spontaneous motor tempi (in the absence of an auditory stimulus), supporting a deficit specific to perception–action coupling. A damped harmonic oscillator model was applied to the temporal adaptation responses; the model's parameters of relaxation time and endogenous frequency accounted for differences between the beat-deaf cases as well as the control group individuals. PMID:25385783

  16. Losing one's memory in early Alzheimer's disease.

    PubMed

    Parsons-Suhl, Karen; Johnson, Mary E; McCann, Judy J; Solberg, Shirley

    2008-01-01

    A Heideggerian hermeneutical phenomenological research method was used to investigate the experience of memory loss in twelve individuals with early Alzheimer's disease or mild cognitive impairment. Data analysis proceeded as described by Diekelmann, Allen, and Tanner (1989), and incorporated the methods of Benner (1994), Thomas and Pollio (2002), and van Manen (1990). Three constitutive patterns with relational themes were identified. The first pattern, experiencing breakdown, consisted of two themes: awakening to breakdown and living with forgetting. The second pattern, temporality, consisted of three themes: being in the nothing, forgetting the past, and looking ahead. The third pattern, managing forgetting, consisted of the themes: remembering with cues, writing things down, recognizing what made remembering better or worse, and using laughter. The finding show that early Alzheimer's disease is more than an illness of cognitive losses and that forgetting is significant in light of the meaning that it has within everyday life. PMID:18174533

  17. Stay lean without dieting: Lose Sam68.

    PubMed

    Huot, Marc-Étienne; Richard, Stéphane

    2012-10-01

    Alternative splicing is well known to be tissue-specific. Although several genes have been shown to undergo alternative splicing in adipocytes, little is known about the mechanism that regulates alternative splicing during adipogenesis. We recently reported that Sam68(-/-) mice exhibit a lean phenotype and are protected against diet-induced obesity. Our genome-wide exon array analysis in white adipose tissue (WAT) from wild-type and Sam68(-/-) mice revealed that Sam68 deficiency leads to an abnormal splicing of the mTOR gene. This has been shown to reduce the overall mTOR protein content and activity during in vitro adipose differentiation. In Sam68(-/-) mice, this situation leads to an increased energy expenditure, decreased adipogenesis and WAT formation. PMID:23700540

  18. States Hurt as Stimulus Loses Steam

    ERIC Educational Resources Information Center

    Cavanagh, Sean; Hollingsworth, Heather

    2011-01-01

    States are finally arriving at the "funding cliff"--the point where about $100 billion in federal economic-stimulus aid for education runs out. The loss seems certain to compound severe budget woes and could mean thousands of school layoffs and the elimination of popular programs and services in districts across the country. The bulk of that…

  19. Children Losing Health Coverage. Special Report. Revised.

    ERIC Educational Resources Information Center

    Klein, Rachel

    Although the State Children's Health Insurance Program (SCHIP), in operation for 5 years, has made rapid progress in reducing the number of children in the United States without health insurance coverage, pending reductions in federal funding, the expected reversion of SCHIP funds back to the U.S. Treasury, and growing state budget crises will…

  20. Pluto loses its status as a planet

    NASA Astrophysics Data System (ADS)

    Zielinski, Sarah; Kumar, Mohi

    2006-08-01

    Astronomers nave accepted a definition for 'planet' that excludes Pluto, instead relegating that object and at least two others to the status of 'dwarf planet,' in a series of votes taken on 24 August at the International Astronomical Union (IAU) 2006 General Assembly in Prague, Czech Republic.Michael Brown, the California Institute of Technology astronomer who discovered the newly classified dwarf planet 2003 UB313, said, "If you started from scratch, and you looked at the solar system as you were flying in from outer space, you would very quickly realize that there are eight really large objects in the solar system and you would put those into one category and use one word to describe them…All of the other objects in the solar system are much smaller, and they belong to these vast populations of other objects."

  1. Nevada may lose nuclear waste funds

    SciTech Connect

    Marshall, E.

    1988-06-24

    The people of Nevada are concerned that a cut in DOE funding for a nuclear waste repository at Yucca Mountain, Nevada will result in cuts in the state monitoring program, e.g. dropping a seismic monitoring network and a sophisticated drilling program. Economic and social impact studies will be curtailed. Even though a provision to curtail local research forbids duplication of DOE`s work and would limit the ability of Nevada to go out and collect its own data, Nevada State University at Las Vegas would receive a nice plum, a top-of-the-line supercomputer known as the ETA-10 costing almost $30 million financed by DOE.

  2. Losing ground: physician income, 1995-2003.

    PubMed

    Tu, Ha T; Ginsburg, Paul B

    2006-06-01

    Between 1995 and 2003, average physician net income from the practice of medicine declined about 7 percent after adjusting for inflation, according to a national study from the Center for Studying Health System Change (HSC). The decline in physicians' real income stands in sharp contrast to the wage trends for other professionals who saw about a 7 percent increase after adjusting for inflation during the same period. Among different types of physicians, primary care physicians fared the worst with a 10.2 percent decline in real income between 1995 and 2003, while surgeons' real income declined by 8.2 percent. But medical specialists' real income essentially remained unchanged. Physicians reported working slightly fewer hours overall but spent more time on direct patient care. Flat or declining fees from both public and private payers appear to be a major factor underlying declining real incomes for physicians. The downward trend in real incomes since the mid-1990s likely is an important reason for growing physician unwillingness to undertake pro bono work, including charity care and volunteering to serve on hospital committees. PMID:16791996

  3. The Golden State Loses Its Luster

    ERIC Educational Resources Information Center

    Dessoff, Alan

    2010-01-01

    From the glamour and glitz of Hollywood to the technological hub of Silicon Valley, from the majestic Redwoods to the surfers off the Malibu beaches, California is a state of contrasts in many ways, including its politics. The contrasts extend to its public education system, from the renowned University of California system, which employs more…

  4. [Driving ability: how not to lose control?].

    PubMed

    Vetsch, Melissa; Gantcheva, Neil; Favrat, Bernard; Perron, Noëlle Junod

    2014-09-24

    Any primary care doctor should be able to decide on the fitness to drive of a given patient. The issue of an older driver, patients addicted to alcohol or drugs, under current psychotropic drug treatment, or diabetic, is discussed in the light of legal provisions and current recommendations. This article also discusses aspects associated with neurological, cardiac and orthopedic issues. PMID:25369694

  5. Local Control: Use It or Lose It.

    ERIC Educational Resources Information Center

    California School Boards Association, Sacramento.

    Two California laws have increased the autonomy of local school districts. As of January 1982, virtually all provisions of the California Education Code can be waived at the request of local school boards with the approval of the state board of education. Under Article 2 of Assembly Bill 777, Chapter 100, programs that may be waived include state…

  6. Losing the beat: deficits in temporal coordination.

    PubMed

    Palmer, Caroline; Lidji, Pascale; Peretz, Isabelle

    2014-12-19

    Tapping or clapping to an auditory beat, an easy task for most individuals, reveals precise temporal synchronization with auditory patterns such as music, even in the presence of temporal fluctuations. Most models of beat-tracking rely on the theoretical concept of pulse: a perceived regular beat generated by an internal oscillation that forms the foundation of entrainment abilities. Although tapping to the beat is a natural sensorimotor activity for most individuals, not everyone can track an auditory beat. Recently, the case of Mathieu was documented (Phillips-Silver et al. 2011 Neuropsychologia 49, 961-969. (doi:10.1016/j.neuropsychologia.2011.02.002)). Mathieu presented himself as having difficulty following a beat and exhibited synchronization failures. We examined beat-tracking in normal control participants, Mathieu, and a second beat-deaf individual, who tapped with an auditory metronome in which unpredictable perturbations were introduced to disrupt entrainment. Both beat-deaf cases exhibited failures in error correction in response to the perturbation task while exhibiting normal spontaneous motor tempi (in the absence of an auditory stimulus), supporting a deficit specific to perception-action coupling. A damped harmonic oscillator model was applied to the temporal adaptation responses; the model's parameters of relaxation time and endogenous frequency accounted for differences between the beat-deaf cases as well as the control group individuals. PMID:25385783

  7. Losing Ground: School Segregation in Massachuestts

    ERIC Educational Resources Information Center

    Ayscue, Jennifer B.; Greenberg, Alyssa

    2013-01-01

    Though once a leader in school integration, Massachusetts has regressed over the last two decades as its students of color have experienced intensifying school segregation. This report investigates trends in school segregation in Massachusetts by examining concentration, exposure, and evenness measures by both race and class. First, the report…

  8. "Losing Touch": Teachers on Teaching and Learning

    ERIC Educational Resources Information Center

    Brownhill, Suzanne; Wilhelm, Kay; Watson, Alan

    2006-01-01

    Teachers recruited to a cohort study in 1978 were interviewed to elicit their views on issues surrounding the education system and teaching profession. Qualitative data were derived from a semi-structured interview and quantitative data included a self-report measure of temperament and character. The findings highlight a "mismatch" between the…

  9. Medical Mystery: Losing the sense of smell

    MedlinePlus

    ... depressing and dangerous. Thomas recalls being in her kitchen with her back to the stove, unaware that ... was happening until her sons burst into the kitchen yelling, "What's burning?" Our sense of smell is ...

  10. School Boards -- Losing Power or Influence

    ERIC Educational Resources Information Center

    Wynia, Bob

    1973-01-01

    The authority of school boards is being eroded by teacher militancy, administrative professionalism, and technology. Boards are performing a legal rather than a deliberative function. Court decisions regarding due process are forcing important adjustments in board power. (Author/WM)

  11. How not to lose the top job.

    PubMed

    Goldsmith, Marshall

    2009-01-01

    If you're on the way to becoming CEO, take care. Many anointed successors find their path to the corner office unexpectedly blocked. The obstacle is usually a mismanaged relationship with any of six kinds of stakeholders: the current chief executive, the successor's peers, his or her direct reports, customers, analysts and shareholders, and the board of directors. Succession isn't an entirely rational process, explains veteran executive coach Goldsmith. Personal issues, egos, and emotions influence succession decisions just as much as business logic. Look at what happened in 1978 to Lee Iacocca, considered by many the obvious candidate to become head of Ford. Iacocca didn't just fail to get the job--he was fired. In explaining why, Henry Ford II famously remarked, "Sometimes you just don't like somebody." To secure their promotion, prospective heirs must strengthen relationships with the stakeholders whose commitment they'll need to succeed as CEO. That involves striking a delicate balance in a number of areas. For instance, candidates must project readiness to lead while supporting the current CEO, showing respect for peers, and demonstrating that they can make tough decisions without alienating their reports. It's also critical for them to determine if they've made past missteps that call for a change in personal style or relationship-building approach. The current CEO can provide invaluable guidance on areas ripe for improvement, as well as many other issues, such as which customers aspiring successors need to get to know or what the concerns of individual board members might be. Building better relationships with stakeholders takes time and effort, and treading so carefully may be wearying. But executives who do it before they become CEO stand a much better chance of making it across the finish line and in the end will become much more effective leaders. PMID:19227410

  12. Never Lose Sight of Your Site.

    ERIC Educational Resources Information Center

    Young, Terry

    1998-01-01

    Discusses the use of bookmarks, or favorite places, and compares procedures for using them on the two main browsers, Internet Explorer and Netscape Navigator. Describes how to organize favorite Web sites using folders, how to share bookmarks between browsers, and checking for Web page updates and link changes. (LRW)

  13. How Can I Lose Weight Safely?

    MedlinePlus

    ... Muscle burns more calories than fat. So adding strength training to your exercise routine can help you reach ... good, well-balanced fitness routine includes aerobic workouts, strength training, and flexibility exercises. Forgive yourself. So you were ...

  14. Three-dimensional chemotaxis-driven aggregation of tumor cells

    PubMed Central

    Puliafito, Alberto; De Simone, Alessandro; Seano, Giorgio; Gagliardi, Paolo Armando; Di Blasio, Laura; Chianale, Federica; Gamba, Andrea; Primo, Luca; Celani, Antonio

    2015-01-01

    One of the most important steps in tumor progression involves the transformation from a differentiated epithelial phenotype to an aggressive, highly motile phenotype, where tumor cells invade neighboring tissues. Invasion can occur either by isolated mesenchymal cells or by aggregates that migrate collectively and do not lose completely the epithelial phenotype. Here, we show that, in a three-dimensional cancer cell culture, collective migration of cells eventually leads to aggregation in large clusters. We present quantitative measurements of cluster velocity, coalescence rates, and proliferation rates. These results cannot be explained in terms of random aggregation. Instead, a model of chemotaxis-driven aggregation – mediated by a diffusible attractant – is able to capture several quantitative aspects of our results. Experimental assays of chemotaxis towards culture conditioned media confirm this hypothesis. Theoretical and numerical results further suggest an important role for chemotactic-driven aggregation in spreading and survival of tumor cells. PMID:26471876

  15. Three-dimensional chemotaxis-driven aggregation of tumor cells.

    PubMed

    Puliafito, Alberto; De Simone, Alessandro; Seano, Giorgio; Gagliardi, Paolo Armando; Di Blasio, Laura; Chianale, Federica; Gamba, Andrea; Primo, Luca; Celani, Antonio

    2015-01-01

    One of the most important steps in tumor progression involves the transformation from a differentiated epithelial phenotype to an aggressive, highly motile phenotype, where tumor cells invade neighboring tissues. Invasion can occur either by isolated mesenchymal cells or by aggregates that migrate collectively and do not lose completely the epithelial phenotype. Here, we show that, in a three-dimensional cancer cell culture, collective migration of cells eventually leads to aggregation in large clusters. We present quantitative measurements of cluster velocity, coalescence rates, and proliferation rates. These results cannot be explained in terms of random aggregation. Instead, a model of chemotaxis-driven aggregation - mediated by a diffusible attractant - is able to capture several quantitative aspects of our results. Experimental assays of chemotaxis towards culture conditioned media confirm this hypothesis. Theoretical and numerical results further suggest an important role for chemotactic-driven aggregation in spreading and survival of tumor cells. PMID:26471876

  16. Ex-vivo assessment of chronic toxicity of low levels of cadmium on testicular meiotic cells

    SciTech Connect

    Geoffroy-Siraudin, Cendrine; Perrard, Marie-Hélène; Ghalamoun-Slaimi, Rahma; Ali, Sazan; Chaspoul, Florence; Lanteaume, André; Achard, Vincent; Gallice, Philippe; Durand, Philippe; and others

    2012-08-01

    Using a validated model of culture of rat seminiferous tubules, we assessed the effects of 0.1, 1 and 10 μg/L cadmium (Cd) on spermatogenic cells over a 2‐week culture period. With concentrations of 1 and 10 μg/L in the culture medium, the Cd concentration in the cells, determined by ICP-MS, increased with concentration in the medium and the day of culture. Flow cytometric analysis enabled us to evaluate changes in the number of Sertoli cells and germ cells during the culture period. The number of Sertoli cells did not appear to be affected by Cd. By contrast, spermatogonia and meiotic cells were decreased by 1 and 10 μg/L Cd in a time and dose dependent manner. Stage distribution of the meiotic prophase I and qualitative study of the synaptonemal complexes (SC) at the pachytene stage were performed by immunocytochemistry with an anti SCP3 antibody. Cd caused a time-and-dose-dependent increase of total abnormalities, of fragmented SC and of asynapsis from concentration of 0.1 μg/L. Additionally, we observed a new SC abnormality, the “motheaten” SC. This abnormality is frequently associated with asynapsis and SC widening which increased with both the Cd concentration and the duration of exposure. This abnormality suggests that Cd disrupts the structure and function of proteins involved in pairing and/or meiotic recombination. These results show that Cd induces dose-and-time-dependent alterations of the meiotic process of spermatogenesis ex-vivo, and that the lowest metal concentration, which induces an adverse effect, may vary with the cell parameter studied. -- Highlights: ► Cadmium induces ex-vivo severe time- and dose-dependent germ cell abnormalities. ► Cadmium at very low concentration (0.1 µg/l) induces synaptonemal complex abnormalities. ► The lowest concentration inducing adverse effect varied with the cell parameter studied. ► Cadmium alters proteins involved in pairing and recombination. ► Cadmium leads to achiasmate univalents and

  17. Effect of vitamin C on growth of caprine spermatogonial stem cells in vitro.

    PubMed

    Wang, Juhua; Cao, Hongguo; Xue, Xiuheng; Fan, Caiyun; Fang, Fugui; Zhou, Jie; Zhang, Yunhai; Zhang, Xiaorong

    2014-03-01

    The genetic manipulation of spermatogonial stem cells (SSCs) can be used for the production of transgenic animals in a wide range of species. However, this technology is limited by the absence of an ideal culture system in which SSCs can be maintained and proliferated, especially in domestic animals like the goat. The aim of this study therefore was to investigate whether the addition of vitamin C (Vc) in cell culture influences the growth of caprine SSCs. Various concentrations of Vc (0, 5, 10, 25, 40, and 50 μg/mL(-1)) were added to SSC culture media, and their effect on morphology and alkaline phosphatase activity was studied. The number of caprine SSC colonies and area covered by them were measured at 10 days of culture. The expression of various germ cell and somatic cell markers such as VASA, integrins, Oct-4, GATA-4, α-SMA, vimentin, and Thy-1 was studied to identify the proliferated cells using immunostaining analyses. Further, the intracellular reactive oxygen species (ROS) level was measured at the 3rd, 6th, and 9th day after culture, and expression of Bax, Bcl-2, and P53, factors involved in the regulation of apoptosis, were analyzed on the 7th day after culture using reverse transcription polymerase chain reaction and quantitative real-time polymerase chain reaction. The results showed that the SSCs formed compact colonies and had unclear borders in the different Vc-supplemented groups at 10 days, and there were no major morphologic differences between the groups. The number and area of colonies were both the highest in the 40 μg/mL(-1) Vc group. Differential expression of markers for germ cells, undifferentiated spermatogonia, and testis somatic cells was observed. Cultured germ cell clumps were found to have alkaline phosphatase activity regardless of the Vc dose. The number of Thy-1- and Oct-4-positive cells was the most in the 40 μg/mL(-1) Vc group. Moreover, the level of ROS was dependent on the Vc dose and culture time. The Vc dose 40

  18. Hepatoma SK Hep-1 Cells Exhibit Characteristics of Oncogenic Mesenchymal Stem Cells with Highly Metastatic Capacity

    PubMed Central

    Zhang, Yanling; Zhang, Yanhong; Tschudy-Seney, Benjamin; Ramsamooj, Rajen; Wan, Yu-Jui Yvonne; Theise, Neil D.; Zern, Mark A.; Duan, Yuyou

    2014-01-01

    Background SK Hep-1 cells (SK cells) derived from a patient with liver adenocarcinoma have been considered a human hepatoma cell line with mesenchymal origin characteristics, however, SK cells do not express liver genes and exhibit liver function, thus, we hypothesized whether mesenchymal cells might contribute to human liver primary cancers. Here, we characterized SK cells and its tumourigenicity. Methods and Principal Findings We found that classical mesenchymal stem cell (MSC) markers were presented on SK cells, but endothelial marker CD31, hematopoietic markers CD34 and CD45 were negative. SK cells are capable of differentiate into adipocytes and osteoblasts as adipose-derived MSC (Ad-MSC) and bone marrow-derived MSC (BM-MSC) do. Importantly, a single SK cell exhibited a substantial tumourigenicity and metastatic capacity in immunodefficient mice. Metastasis not only occurred in circulating organs such as lung, liver, and kidneys, but also in muscle, outer abdomen, and skin. SK cells presented greater in vitro invasive capacity than those of Ad-MSC and BM-MSC. The xenograft cells from subcutaneous and metastatic tumors exhibited a similar tumourigenicity and metastatic capacity, and showed the same relatively homogenous population with MSC characteristics when compared to parental SK cells. SK cells could unlimitedly expand in vitro without losing MSC characteristics, its tumuorigenicity and metastatic capacity, indicating that SK cells are oncogenic MSC with enhanced self-renewal capacity. We believe that this is the first report that human MSC appear to be transformed into cancer stem cells (CSC), and that their derivatives also function as CSCs. Conclusion Our findings demonstrate that SK cells represent a transformation mechanism of normal MSC into an enhanced self-renewal CSC with metastasis capacity, SK cells and their xenografts represent a same relative homogeneity of CSC with substantial metastatic capacity. Thus, it represents a novel mechanism of

  19. [Structure of cytosolic membrane and chemical composition of red blood cells during the early period of wound damage according to scanning probe microscopy].

    PubMed

    Belousova, O D; Gaĭdash, A A; Tolmachev, I A; Ivchenko, E V; Golubok, A O; Levichev, V V; Mukhin, I S; Zhukov, M V; Belousov, I S; Tkachuk, I V

    2013-01-01

    With the help of scanning electronic and atomic force microscopy structure of red blood cell membranes of the system blood-groove and microcirculatory channels is studied. It is established, that in early stages of skin wounds in a peripheral blood circulation appear compressed red blood cells, losing water. As a result the basic mechanism of destruction of red blood cell membranes are interlayered shifts and stratification. In red blood cells of microvasculature, on the contrary, red blood cells in state of vacuolar degeneration are indentified. It creates preconditions for hydration and bullous deformations of membranes. Porous structures of membranes of both types erythrocytes are exposed to expansion. PMID:23805624

  20. Lumican induces human corneal epithelial cell migration and integrin expression via ERK 1/2 signaling

    SciTech Connect

    Seomun, Young; Joo, Choun-Ki

    2008-07-18

    Lumican is a major proteoglycans of the human cornea. Lumican knock-out mice have been shown to lose corneal transparency and to display delayed wound healing. The purpose of this study was to define the role of lumican in corneal epithelial cell migration. Over-expression of lumican in human corneal epithelial (HCE-T) cells increased both cell migration and proliferation, and increased levels of integrins {alpha}2 and {beta}1. ERK 1/2 was also activated in lumican over-expressed cells. When we treated HCE-T cells with the ERK-specific inhibitor U0126, cell migration and the expression of integrin {beta}1 were completely blocked. These data provide evidence that lumican stimulates cell migration in the corneal epithelium by activating ERK 1/2, and point to a novel signaling pathway implicated in corneal epithelial cell migration.

  1. Educational clinical case series for pediatric allergy and immunology: allergic proctocolitis, food protein-induced enterocolitis syndrome and allergic eosinophilic gastroenteritis with protein-losing gastroenteropathy as manifestations of non-IgE-mediated cow's milk allergy.

    PubMed

    Maloney, Jennifer; Nowak-Wegrzyn, Anna

    2007-06-01

    Cow's milk protein allergy is the most common food allergy in infants and young children. It is estimated that up to 50% of pediatric cow's milk allergy is non-IgE-mediated. Allergic proctocolitis is a benign disorder manifesting with blood-streaked stools in otherwise healthy-appearing infants who are breast- or formula-fed. Symptoms resolve within 48-72 h following elimination of dietary cow's milk protein. Most infants tolerate cow's milk by their first birthday. Food protein-induced enterocolitis syndrome presents in young formula-fed infants with chronic emesis, diarrhea, and failure to thrive. Reintroduction of cow's milk protein following a period of avoidance results in profuse, repetitive emesis within 2-3 h following ingestion; 20% of acute exposures may be associated with hypovolemic shock. Treatment of acute reactions is with vigorous hydration. Most children become tolerant with age; attempts of re-introduction of milk must be done under physician supervision and with secure i.v. access. Allergic eosinophilic gastroenteritis affects infants as well as older children and adolescents. Abdominal pain, emesis, diarrhea, failure to thrive, or weight loss are the most common symptoms. A subset of patients may develop protein-losing enteropathy. Fifty percent of affected children are atopic and have evidence of food-specific IgE antibody but skin prick tests and serum food-IgE levels correlate with response to elimination diet poorly. Elemental diet based on the amino-acid formula leads to resolutions of gastrointestinal eosinophilic inflammation typically within 6 wk. PMID:17584315

  2. Cell surface morphology in epithelial malignancy and its precursor lesions.

    PubMed

    Kenemans, P; Davina, J H; de Haan, R W; van der Zanden, P; Vooys, G P; Stolk, J G; Stadhouders, A M

    1981-01-01

    The cell surface organization of cancer cells is of potentially great significance, as it may not only allow (early) diagnosis, but as it may also harbour markers for refined prognosis (degree of oncogenetic and metastatic potential), and targets for selective cancer (chemo- and immuno) therapy. With these aspects in mind, the present review deals with SEM work done on (pre-) malignant cells, both in vivo and in vitro, and in animal models. Attention, however, is focused on human cancer cells. Cancer cells in vitro may lose many of their original malignant characteristics, and show adaptations to culture conditions. Many other factors have been shown to influence cell surface morphology, such as cell cycle, cell contacts, and preparations technique. Cancer cells differ in their surface morphology from normal cells, and have an extra ordinary amount of surface activity. Human malignant epithelial cells show abundant long. pleomorphic microvilli, especially those present in effusions. In squamous epithelium (bladder, cervix) microridge system present on normal superficial cells are progressively replaced by microvilli which increase in number and degree of pleomorphism during experimental and clinical oncogenesis. The question of whether or not the appearance of long. Pleomorphic microvilli reflects an irreversible alteration of the epithelium, and thus provides an early marker of irreversible neoplastic transformation is considered and assessed on the basis of our work with (pre-) malignant cells of the human uterine cervix. Although SEM has contributed significantly to the description of oncogenesis, up to now it has no early diagnostic, prognostic or therapeutic significance. PMID:7199203

  3. Cell-cell contact and matrix adhesion promote αSMA expression during TGFβ1-induced epithelial-myofibroblast transition via Notch and MRTF-A

    PubMed Central

    O’Connor, Joseph W.; Mistry, Krunal; Detweiler, Dayne; Wang, Clayton; Gomez, Esther W.

    2016-01-01

    During epithelial-mesenchymal transition (EMT) epithelial cells lose cell-cell adhesion, exhibit morphological changes, and upregulate the expression of cytoskeletal proteins. Previous studies have demonstrated that complete disruption of cell-cell contact can promote transforming growth factor (TGF)-β1-induced EMT and the expression of the myofibroblast marker alpha smooth muscle actin (αSMA). Furthermore, increased cell spreading mediates TGFβ1-induced αSMA expression during EMT. Here, we sought to examine how the presence of partial cell-cell contacts impacts EMT. A microfabrication approach was employed to decouple the effects of cell-cell contact and cell-matrix adhesion in TGFβ1-induced EMT. When cell spreading is controlled, the presence of partial cell-cell contacts enhances expression of αSMA. Moreover, cell spreading and intercellular contacts together control the subcellular localization of activated Notch1 and myocardin related transcription factor (MRTF)-A. Knockdown of Notch1 or MRTF-A as well as pharmacological inhibition of these pathways abates the cell-cell contact mediated expression of αSMA. These data suggest that the interplay between cell-matrix adhesion and intercellular adhesion is an important determinant for some aspects of TGFβ1-induced EMT. PMID:27194451

  4. Cell-cell contact and matrix adhesion promote αSMA expression during TGFβ1-induced epithelial-myofibroblast transition via Notch and MRTF-A.

    PubMed

    O'Connor, Joseph W; Mistry, Krunal; Detweiler, Dayne; Wang, Clayton; Gomez, Esther W

    2016-01-01

    During epithelial-mesenchymal transition (EMT) epithelial cells lose cell-cell adhesion, exhibit morphological changes, and upregulate the expression of cytoskeletal proteins. Previous studies have demonstrated that complete disruption of cell-cell contact can promote transforming growth factor (TGF)-β1-induced EMT and the expression of the myofibroblast marker alpha smooth muscle actin (αSMA). Furthermore, increased cell spreading mediates TGFβ1-induced αSMA expression during EMT. Here, we sought to examine how the presence of partial cell-cell contacts impacts EMT. A microfabrication approach was employed to decouple the effects of cell-cell contact and cell-matrix adhesion in TGFβ1-induced EMT. When cell spreading is controlled, the presence of partial cell-cell contacts enhances expression of αSMA. Moreover, cell spreading and intercellular contacts together control the subcellular localization of activated Notch1 and myocardin related transcription factor (MRTF)-A. Knockdown of Notch1 or MRTF-A as well as pharmacological inhibition of these pathways abates the cell-cell contact mediated expression of αSMA. These data suggest that the interplay between cell-matrix adhesion and intercellular adhesion is an important determinant for some aspects of TGFβ1-induced EMT. PMID:27194451

  5. On the road toward a hot carrier solar cell

    NASA Astrophysics Data System (ADS)

    Taylor, P. C.; Fields, J. D.; Collins, R. T.

    2015-09-01

    We suggest a new paradigm for solar cells that uses a nanostructured crystalline collector (silicon) in an amorphous absorber matrix (hydrogenated amorphous silicon). Previously amorphous absorbers have received no serious consideration because of their low carrier mobilities. Specifically, we demonstrate that carriers generated in the amorphous region are transported out of this region before losing their energy to heat. This result establishes the possibility of using a wide range of nanostructured amorphous matrices to dramatically increase the efficiencies of solar cells. The use of an amorphous absorber provides a highly desirable and flexible approach to producing low-cost, hot carrier solar cells. Since amorphous materials can be grown over a much wider composition space than crystalline materials, this surprising result greatly broadens the absorbing materials that can be used to dramatically increase the efficiencies of solar cells.

  6. The development of cat testicular sperm cryopreservation protocols: Effects of tissue fragments or sperm cell suspension.

    PubMed

    Chatdarong, Kaywalee; Thuwanut, Paweena; Morrell, Jane M

    2016-01-15

    In endangered animals that have been found dead or sterilized for medical reasons, testis is the ultimate source of haploid DNA or sperm. Thus, preservation of testicular sperm may be performed to rescue their genetics. The aim of this study was to evaluate protocols for testicular sperm freezing: as tissue fragments or cell suspension in domestic cats as a model. A pair of testes from each cat (n = 9) were cut into eight equal pieces. Four randomly selected pieces were cryopreserved as: (1) tissue pieces using two-step freezing; (2) tissue pieces using a slow passive cooling device (CoolCell); (3) sperm suspension after single-layer centrifugation (SLC) through colloids; and (4) sperm suspension without being processed through SLC. A testicular piece from each cat served as fresh control. Testicular sperm membrane and DNA integrity were evaluated before, and after, the cryopreservation process. In addition, spermatogenic cell types (testicular sperm, spermatogonia, spermatocyte, and spermatid) present in the suspension samples were counted before and after SLC. The results found that testicular sperm membrane integrity in the suspension after SLC process was higher than that in the fragment form neither using the two-step nor CoolCell freezing, both before and after freezing (before freezing: 92.3 ± 3.4 vs. 81 ± 4.5 and 80.0 ± 7.0; after freezing: 84.5 ± 4.6 vs. 71.2 ± 12 and 76.2 ± 4.6; P ≤ 0.05). Testicular sperm DNA integrity was, however, not different among groups. Furthermore, the samples processed through the SLC had higher ration of sperm cells: other spermatogenic cells than those were not processed through the SLC (88.9 ± 3.8 vs. 30 ± 7.9; P ≤ 0.05). In summary, testicular sperm cryopreserved as a minced suspension is considered suitable in terms of preventing sperm membrane integrity, and SLC is considered a selection tool for enriching haploid sperm cells from castrated or postmortem cats. PMID:26498389

  7. β-cell dedifferentiation in diabetes is important, but what is it?

    PubMed Central

    Weir, Gordon C; Aguayo-Mazzucato, Cristina; Bonner-Weir, Susan

    2013-01-01

    This commentary discusses the concept of β-cell dedifferentiation in diabetes, which is important but not well defined. A broad interpretation is that a state of differentiation has been lost, which means changes in gene expression as well as in structural and functional elements. Thus, a fully mature healthy β cell will have its unique differentiation characteristics, but maturing cells and old β cells will have different patterns of gene expression and might therefore be considered as dedifferentiated. The meaning of dedifferentiation is now being debated because β cells in the diabetic state lose components of their differentiated state, which results in severe dysfunction of insulin secretion. The major cause of this change is thought to be glucose toxicity (glucotoxicity) and that lowering glucose levels with treatment results in some restoration of function. An issue to be discussed is whether dedifferentiated β cells return to a multipotent precursor cell phenotype or whether they follow a different pathway of dedifferentiation. PMID:24356710

  8. Alphavirus adsorption to mosquito cells as viewed by freeze fracture immunolabeling

    SciTech Connect

    Kononchik, Joseph P.; Vancini, Ricardo; Brown, Dennis T.

    2011-07-05

    Sindbis Virus (SV), the prototype alphavirus in the family togaviridae, infects both mammalian and insect cells. The ability of SV to infect cells possessing significantly different biochemical environments suggests that there may be a common mode of entry into each cell type. Previous studies show that up to 4 h post infection cells are permeable to small ions and alpha sarcin suggesting that the plasma membrane is compromised as infection takes place. Thin-section electron microscopy has also shown SV to bind to the plasma membrane and lose its electron dense core through a pore like structure developed upon interaction of the virus with the cell surface. Using freeze-fracture replicas, thin-sections and antibody labeling the data presented herein show virus associated with intramembrane particles on mosquito cells. These data suggest that the intramembrane particles associated with SV may be part of the pore structure consisting of virus proteins and cell receptor.

  9. A Microfluidic Bioreactor for Toxicity Testing of Stem Cell Derived 3D Cardiac Bodies.

    PubMed

    Christoffersson, Jonas; Bergström, Gunnar; Schwanke, Kristin; Kempf, Henning; Zweigerdt, Robert; Mandenius, Carl-Fredrik

    2016-01-01

    Modeling tissues and organs using conventional 2D cell cultures is problematic as the cells rapidly lose their in vivo phenotype. In microfluidic bioreactors the cells reside in microstructures that are continuously perfused with cell culture medium to provide a dynamic environment mimicking the cells natural habitat. These micro scale bioreactors are sometimes referred to as organs-on-chips and are developed in order to improve and extend cell culture experiments. Here, we describe the two manufacturing techniques photolithography and soft lithography that are used in order to easily produce microfluidic bioreactors. The use of these bioreactors is exemplified by a toxicity assessment on 3D clustered human pluripotent stem cells (hPSC)-derived cardiomyocytes by beating frequency imaging. PMID:27052611

  10. Downregulation of miR-320a/383-sponge-like long non-coding RNA NLC1-C (narcolepsy candidate-region 1 genes) is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation

    PubMed Central

    Lü, M; Tian, H; Cao, Y-x; He, X; Chen, L; Song, X; Ping, P; Huang, H; Sun, F

    2015-01-01

    Long non-coding RNAs (lncRNAs), which are extensively transcribed from the genome, have been proposed to be key regulators of diverse biological processes. However, little is known about the role of lncRNAs in regulating spermatogenesis in human males. Here, using microarray technology, we show altered expression of lncRNAs in the testes of infertile men with maturation arrest (MA) or hypospermatogenesis (Hypo), with 757 and 2370 differentially down-regulated and 475 and 163 up-regulated lncRNAs in MA and Hypo, respectively. These findings were confirmed by quantitative real-time PCR (qRT-PCR) assays on select lncRNAs, including HOTTIP, imsrna320, imsrna292 and NLC1-C (narcolepsy candidate-region 1 genes). Interestingly, NLC1-C, also known as long intergenic non-protein-coding RNA162 (LINC00162), was down-regulated in the cytoplasm and accumulated in the nucleus of spermatogonia and primary spermatocytes in the testes of infertile men with mixed patterns of MA compared with normal control. The accumulation of NLC1-C in the nucleus repressed miR-320a and miR-383 transcript and promoted testicular embryonal carcinoma cell proliferation by binding to Nucleolin. Here, we define a novel mechanism by which lncRNAs modulate miRNA expression at the transcriptional level by binding to RNA-binding proteins to regulate human spermatogenesis. PMID:26539909

  11. Downregulation of miR-320a/383-sponge-like long non-coding RNA NLC1-C (narcolepsy candidate-region 1 genes) is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation.

    PubMed

    Lü, M; Tian, H; Cao, Y-X; He, X; Chen, L; Song, X; Ping, P; Huang, H; Sun, F

    2015-01-01

    Long non-coding RNAs (lncRNAs), which are extensively transcribed from the genome, have been proposed to be key regulators of diverse biological processes. However, little is known about the role of lncRNAs in regulating spermatogenesis in human males. Here, using microarray technology, we show altered expression of lncRNAs in the testes of infertile men with maturation arrest (MA) or hypospermatogenesis (Hypo), with 757 and 2370 differentially down-regulated and 475 and 163 up-regulated lncRNAs in MA and Hypo, respectively. These findings were confirmed by quantitative real-time PCR (qRT-PCR) assays on select lncRNAs, including HOTTIP, imsrna320, imsrna292 and NLC1-C (narcolepsy candidate-region 1 genes). Interestingly, NLC1-C, also known as long intergenic non-protein-coding RNA162 (LINC00162), was down-regulated in the cytoplasm and accumulated in the nucleus of spermatogonia and primary spermatocytes in the testes of infertile men with mixed patterns of MA compared with normal control. The accumulation of NLC1-C in the nucleus repressed miR-320a and miR-383 transcript and promoted testicular embryonal carcinoma cell proliferation by binding to Nucleolin. Here, we define a novel mechanism by which lncRNAs modulate miRNA expression at the transcriptional level by binding to RNA-binding proteins to regulate human spermatogenesis. PMID:26539909

  12. Research highlights: microfluidic-enabled single-cell epigenetics.

    PubMed

    Dhar, Manjima; Khojah, Reem; Tay, Andy; Di Carlo, Dino

    2015-11-01

    Individual cells are the fundamental unit of life with diverse functions from metabolism to motility. In multicellular organisms, a single genome can give rise to tremendous variability across tissues at the single-cell level due to epigenetic differences in the genes that are expressed. Signals from the local environment or a history of signals can drive these variations, and tissues have many cell types that play separate roles. This epigenetic heterogeneity is of biological importance in normal functions such as tissue morphogenesis and can contribute to development or resistance of cancer, or other disease states. Therefore, an improved understanding of variations at the single cell level are fundamental to understanding biology and developing new approaches to combating disease. Traditional approaches to characterize epigenetic modifications of chromatin or the transcriptome of cells have often focused on blended responses of many cells in a tissue; however, such bulk measures lose spatial and temporal differences that occur from cell to cell, and cannot uncover novel or rare populations of cells. Here we highlight a flurry of recent activity to identify the mRNA profiles from thousands of single-cells as well as chromatin accessibility and histone marks on single to few hundreds of cells. Microfluidics and microfabrication have played a central role in the range of new techniques, and will likely continue to impact their further development towards routine single-cell epigenetic analysis. PMID:26405849

  13. Risk of tumor cell seeding through biopsy and aspiration cytology

    PubMed Central

    Shyamala, K.; Girish, H. C.; Murgod, Sanjay

    2014-01-01

    Cancer cells, besides reproducing uncontrollably, lose cohesiveness and orderliness of normal tissue, invade and get detached from the primary tumor to travel and set up colonies elsewhere. Dislodging neoplastically altered cells from a tumor during biopsy or surgical intervention or during simple procedure like needle aspiration is a possibility because they lack cohesiveness, and they attain the capacity to migrate and colonize. Considering the fact that, every tumor cell, is bathed in interstitial fluid, which drains into the lymphatic system and has an individualized arterial blood supply and venous drainage like any other normal cell in our body, inserting a needle or a knife into a tumor, there is a jeopardy of dislodging a loose tumor cell into either the circulation or into the tissue fluid. Tumor cells are easier to dislodge due to lower cell-to-cell adhesion. This theory with the possibility of seeding of tumor cells is supported by several case studies that have shown that after diagnostic biopsy of a tumor, many patients developed cancer at multiple sites and showed the presence of circulating cancer cells in the blood stream on examination. In this review, we evaluate the risk of exposure to seeding of tumor cells by biopsy and aspiration cytology and provide some suggested practices to prevent tumor cell seeding. PMID:24818087

  14. Characterization of TLX Expression in Neural Stem Cells and Progenitor Cells in Adult Brains

    PubMed Central

    Li, Shengxiu; Sun, Guoqiang; Murai, Kiyohito; Ye, Peng; Shi, Yanhong

    2012-01-01

    TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression.Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells. PMID:22952666

  15. Melanoma Cells Can Adopt the Phenotype of Stromal Fibroblasts and Macrophages by Spontaneous Cell Fusion in Vitro

    PubMed Central

    Kemény, Lajos V.; Kurgyis, Zsuzsanna; Buknicz, Tünde; Groma, Gergely; Jakab, Ádám; Zänker, Kurt; Dittmar, Thomas; Kemény, Lajos; Németh, István B.

    2016-01-01

    After the removal of primary cutaneous melanoma some patients develop local recurrences, even after having histologically tumor-free re-excision. A potential explanation behind this phenomenon is that tumor cells switch their phenotype, making their recognition via standard histopathological assessments extremely difficult. Tumor-stromal cell fusion has been proposed as a potential mechanism for tumor cells to acquire mesenchymal traits; therefore, we hypothesized that melanoma cells could acquire fibroblast- and macrophage-like phenotypes via cell fusion. We show that melanoma cells spontaneously fuse with human dermal fibroblasts and human peripheral blood monocytes in vitro. The hybrid cells’ nuclei contain chromosomes from both parental cells and are indistinguishable from the parental fibroblasts or macrophages based on their morphology and immunophenotype, as they could lose the melanoma specific MART1 marker, but express the fibroblast marker smooth muscle actin or the macrophage marker CD68. Our results suggest that, by spontaneous cell fusion in vitro, tumor cells can adopt the morphology and immunophenotype of stromal cells while still carrying oncogenic, tumor-derived genetic information. Therefore, melanoma–stromal cell fusion might play a role in missing tumor cells by routine histopathological assessments. PMID:27271591

  16. p38α controls self-renewal and fate decision of neurosphere-forming cells in adult hippocampus.

    PubMed

    Yoshioka, Kento; Namiki, Kana; Sudo, Tatsuhiko; Kasuya, Yoshitoshi

    2015-01-01

    Neural stem cells (NSC) from the adult hippocampus easily lose their activity in vitro. Efficient in vitro expansion of adult hippocampus-derived NSC is important for generation of tools for research and cell therapy. Here, we show that a single copy disruption or pharmacological inhibition of p38α enables successful long-term neurosphere culture of adult mouse hippocampal cells. Expanded neurospheres with high proliferative activity differentiated into the three neuronal lineages under differentiating conditions. Thus, inhibition of p38α can maintain adult hippocampal NSC activity in vitro. PMID:26101740

  17. p38α controls self-renewal and fate decision of neurosphere-forming cells in adult hippocampus

    PubMed Central

    Yoshioka, Kento; Namiki, Kana; Sudo, Tatsuhiko; Kasuya, Yoshitoshi

    2015-01-01

    Neural stem cells (NSC) from the adult hippocampus easily lose their activity in vitro. Efficient in vitro expansion of adult hippocampus-derived NSC is important for generation of tools for research and cell therapy. Here, we show that a single copy disruption or pharmacological inhibition of p38α enables successful long-term neurosphere culture of adult mouse hippocampal cells. Expanded neurospheres with high proliferative activity differentiated into the three neuronal lineages under differentiating conditions. Thus, inhibition of p38α can maintain adult hippocampal NSC activity in vitro. PMID:26101740

  18. Football Fans in Training: the development and optimization of an intervention delivered through professional sports clubs to help men lose weight, become more active and adopt healthier eating habits

    PubMed Central

    2013-01-01

    Background The prevalence of obesity in men is rising, but they are less likely than women to engage in existing weight management programmes. The potential of professional sports club settings to engage men in health promotion activities is being increasingly recognised. This paper describes the development and optimization of the Football Fans in Training (FFIT) programme, which aims to help overweight men (many of them football supporters) lose weight through becoming more active and adopting healthier eating habits. Methods The MRC Framework for the design and evaluation of complex interventions was used to guide programme development in two phases. In Phase 1, a multidisciplinary working group developed the pilot programme (p-FFIT) and used a scoping review to summarize previous research and identify the target population. Phase 2 involved a process evaluation of p-FFIT in 11 Scottish Premier League (SPL) clubs. Participant and coach feedback, focus group discussions and interviews explored the utility/acceptability of programme components and suggestions for changes. Programme session observations identified examples of good practice and problems/issues with delivery. Together, these findings informed redevelopment of the optimized programme (FFIT), whose components were mapped onto specific behaviour change techniques using an evidence-based taxonomy. Results p-FFIT comprised 12, weekly, gender-sensitised, group-based weight management classroom and ‘pitch-side’ physical activity sessions. These in-stadia sessions were complemented by an incremental, pedometer-based walking programme. p-FFIT was targeted at men aged 35-65 years with body mass index ≥ 27 kg/m2. Phase 2 demonstrated that participants in p-FFIT were enthusiastic about both the classroom and physical activity components, and valued the camaraderie and peer-support offered by the programme. Coaches appreciated the simplicity of the key healthy eating and physical activity messages

  19. Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications

    PubMed Central

    Rani, Sweta; Ryan, Aideen E; Griffin, Matthew D; Ritter, Thomas

    2015-01-01

    Mesenchymal stem (stromal) cells (MSCs) are multipotent cells with the ability to differentiate into several cell types, thus serving as a cell reservoir for regenerative medicine. Much of the current interest in therapeutic application of MSCs to various disease settings can be linked to their immunosuppressive and anti-inflammatory properties. One of the key mechanisms of MSC anti-inflammatory effects is the secretion of soluble factors with paracrine actions. Recently it has emerged that the paracrine functions of MSCs could, at least in part, be mediated by extracellular vesicles (EVs). EVs are predominantly released from the endosomal compartment and contain a cargo that includes miRNA, mRNA, and proteins from their cells of origin. Recent animal model-based studies suggest that EVs have significant potential as a novel alternative to whole cell therapies. Compared to their parent cells, EVs may have a superior safety profile and can be safely stored without losing function. In this article, we review current knowledge related to the potential use of MSC-derived EVs in various diseases and discuss the promising future for EVs as an alternative, cell-free therapy. PMID:25868399

  20. Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications.

    PubMed

    Rani, Sweta; Ryan, Aideen E; Griffin, Matthew D; Ritter, Thomas

    2015-05-01

    Mesenchymal stem (stromal) cells (MSCs) are multipotent cells with the ability to differentiate into several cell types, thus serving as a cell reservoir for regenerative medicine. Much of the current interest in therapeutic application of MSCs to various disease settings can be linked to their immunosuppressive and anti-inflammatory properties. One of the key mechanisms of MSC anti-inflammatory effects is the secretion of soluble factors with paracrine actions. Recently it has emerged that the paracrine functions of MSCs could, at least in part, be mediated by extracellular vesicles (EVs). EVs are predominantly released from the endosomal compartment and contain a cargo that includes miRNA, mRNA, and proteins from their cells of origin. Recent animal model-based studies suggest that EVs have significant potential as a novel alternative to whole cell therapies. Compared to their parent cells, EVs may have a superior safety profile and can be safely stored without losing function. In this article, we review current knowledge related to the potential use of MSC-derived EVs in various diseases and discuss the promising future for EVs as an alternative, cell-free therapy. PMID:25868399

  1. Time-Lapse Imaging of Cell Death.

    PubMed

    Wallberg, Fredrik; Tenev, Tencho; Meier, Pascal

    2016-03-01

    The best approach to distinguish between necrosis and apoptosis is time-lapse video microscopy. This technique enables a biological process to be photographed at regular intervals over a period, which may last from a few hours to several days, and can be applied to cells in culture or in vivo. We have established two time-lapse microscopy methods based on different ways of calculating cell death: semiautomated and automated. In the semiautomated approach, cell death can be visualized by staining with combinations of Alexa Fluor 647-conjugated Annexin V and Sytox Green (SG), or Annexin V(FITC) and Propidium iodide (PI). The automated method is similar except that all cells are labeled with dyes. This allows faster quantification of data. To this end Cell Tracker Green is used to label all cells at time zero in combination with PI and Alexa Fluor 647-conjugated Annexin V. Necrotic cell death is accompanied by either simultaneous labeling with Annexin V and PI or SG (double-positive), or direct PI or SG staining. Additionally, necrotic cells display characteristic morphology, such as cytoplasmic swelling. In contrast to necrosis where membrane permeabilization is an early event, cells that die by apoptosis lose their membrane permeability relatively late. Therefore, the time between Annexin V staining and PI or SG uptake (double-positive) can be used to distinguish necrosis from apoptosis. This protocol describes the analysis of cell death by time-lapse imaging of HT1080 and L929 cells stained with these dyes, but it can be readily adapted to other cell types of interest. PMID:26933245

  2. Components and materials issues in polymer electrolyte fuel cells for transportation applications

    NASA Astrophysics Data System (ADS)

    Derouin, C. R.; Springer, T. E.; Uribe, F. A.; Valerio, J. A.; Wilson, M. S.; Zawodzinski, T. A.; Gottesfeld, S.

    Recent research work on the polymer electrolyte fuel cell (PEFC) is described. This research work addresses the goal of bringing the PEFC technology to the performance and the cost levels required for its wide spread use in transportation. The main topics are (1) a new approach to the fabrication of Pt/C catalyst layers of high performance, employing loadings as low as 0.1 mgPt/cm(sup 2); (2) measurements and modeling of membrane, cathode catalyst and cathode backing contributions to cell loses in the PEFC; and (3) carbon monoxide poisoning of anode electrocatalysts in the PEFC -- the problem and possible solutions.

  3. Sublinear response in lacZ mutant frequency of Muta™ Mouse spermatogonial stem cells after low dose subchronic exposure to N-ethyl-N-nitrosourea.

    PubMed

    O'Brien, Jason M; Walker, Mike; Sivathayalan, Ahalya; Douglas, George R; Yauk, Carole L; Marchetti, Francesco

    2015-05-01

    The transgenic rodent mutation assay was used to compare the dose-response relationship of lacZ mutant frequency (MF) in spermatogonial stem cells exposed acutely or subchronically to N-ethyl-N-nitrosourea (ENU). Muta(™) Mouse males were exposed orally to 0, 25, 50, or 100 mg/kg ENU for acute exposures and 0, 1, 2, or 5 mg/(kg day) for 28-day subchronic exposures. LacZ MF was measured in sperm collected 70 days post-exposure to target spermatogonial stem cells. Dose-response data were fit to linear, quadratic, exponential, or power models. Acute exposure resulted in a dose-dependent increase in MF that was significant (P < 0.05) at all doses tested and was best described by a quadratic dose-response model that was linear in the low dose range. In contrast, similar total doses fragmented over a 28-day subchronic exposure only resulted in a significant increase in lacZ MF at the highest dose tested. Therefore, the subchronic no observable genotoxic effect level (NOGEL) was 2 mg/(kg day) (or 56 mg/kg total dose). The subchronic dose-response was best described by the exponential and power models, which were sublinear in the low dose range. Benchmark dose lower confidence limits (BMDLs) for acute and subchronic exposure were 3.0 and 1.0 mg/(kg day) (or 27.4 mg/kg total dose), respectively. These findings are supportive of a saturable DNA repair mechanism as the mutagenic mode of action for ENU in spermatogonia and imply that sufficiently low exposures would not cause appreciable genotoxic effects over background. This may have important implications for the quantitative risk assessment of germ cell mutagens. PMID:25598316

  4. Assessment of laryngeal muscle and testicular cell types in Xenopus laevis (Anura Pipidae) inhabiting maize and non-maize growing areas of South Africa

    USGS Publications Warehouse

    Smith, E.E.; Du Preez, L.H.; Gentles, A.; Solomon, K.R.; Tandler, B.; Carr, J.A.; Van Der Kraak, G. L.; Kendall, R.J.; Giesy, J.P.; Gross, T.S.

    2005-01-01

    We tested the hypothesis that adult African clawed frogs (Xenopus laevis) inhabiting water bodies in maize-growing areas (MGA) of South Africa would exhibit differences in testicular structure compared to frogs from water bodies in non-maize-growing areas (NMGA) in the same locale. Adults of both sexes were collected during the autumn of 2002 in South Africa, and stereological analytical techniques were used to quantify the distribution of testicular cell types. In addition, total laryngeal mass was used as a gauge of secondary sex differences in animals from MGA and NMGA study sites. Evaluation of the total laryngeal mass revealed that there were no statistically significant differences between X. laevis of the same sex from the NMGA and MGA sites. Mean percent fractional-volume values for seminiferous tubule distribution of testicular cell types of mature X. laevis, ranged from 3-4% for spermatogonia, 26-28% for spermatocytes, 54-57% for spermatozoa, and 14-15% for other cells types. The mean percent volume for blood vessels ranged from 0.3-0.4%. These values did not differ significantly between frogs from NMGA and MGA areas. Collectively, these data demonstrated no differences in gonadal and laryngeal development in X. laevis collected in South Africa from MGA and NMGA areas and that there is little evidence for an effect of agricultural chemicals used in maize production functioning as endocrine disrupters in this species. Screening of X. laevis testes revealed a small incidence of Stage 1 testicular oocytes in adult male frogs collected from the NMGA (3%) and MGA (2%).

  5. Trypanosoma brucei Co-opts NK Cells to Kill Splenic B2 B Cells

    PubMed Central

    Frenkel, Deborah; Guirnalda, Patrick; Haynes, Carole; Bockstal, Viki; Magez, Stefan; Black, Samuel J.

    2016-01-01

    After infection with T. brucei AnTat 1.1, C57BL/6 mice lost splenic B2 B cells and lymphoid follicles, developed poor parasite-specific antibody responses, lost weight, became anemic and died with fulminating parasitemia within 35 days. In contrast, infected C57BL/6 mice lacking the cytotoxic granule pore-forming protein perforin (Prf1-/-) retained splenic B2 B cells and lymphoid follicles, developed high-titer antibody responses against many trypanosome polypeptides, rapidly suppressed parasitemia and did not develop anemia or lose weight for at least 60 days. Several lines of evidence show that T. brucei infection-induced splenic B cell depletion results from natural killer (NK) cell-mediated cytotoxicity: i) B2 B cells were depleted from the spleens of infected intact, T cell deficient (TCR-/-) and FcγRIIIa deficient (CD16-/-) C57BL/6 mice excluding a requirement for T cells, NKT cell, or antibody-dependent cell-mediated cytotoxicity; ii) administration of NK1.1 specific IgG2a (mAb PK136) but not irrelevant IgG2a (myeloma M9144) prevented infection-induced B cell depletion consistent with a requirement for NK cells; iii) splenic NK cells but not T cells or NKT cells degranulated in infected C57BL/6 mice co-incident with B cell depletion evidenced by increased surface expression of CD107a; iv) purified NK cells from naïve C57BL/6 mice killed purified splenic B cells from T. brucei infected but not uninfected mice in vitro indicating acquisition of an NK cell activating phenotype by the post-infection B cells; v) adoptively transferred C57BL/6 NK cells prevented infection-induced B cell population growth in infected Prf1-/- mice consistent with in vivo B cell killing; vi) degranulated NK cells in infected mice had altered gene and differentiation antigen expression and lost cytotoxic activity consistent with functional exhaustion, but increased in number as infection progressed indicating continued generation. We conclude that NK cells in T. brucei infected mice

  6. Chaotic electrical activity of living β-cells in the mouse pancreatic islet

    NASA Astrophysics Data System (ADS)

    Kanno, Takahiro; Miyano, Takaya; Tokuda, Isao; Galvanovskis, Juris; Wakui, Makoto

    2007-02-01

    To test for chaotic dynamics of the insulin producing β-cell and explore its biological role, we observed the action potentials with the perforated patch clamp technique, for isolated cells as well as for intact cells of the mouse pancreatic islet. The time series obtained were analyzed using nonlinear diagnostic algorithms associated with the surrogate method. The isolated cells exhibited short-term predictability and visible determinism, in the steady state response to 10 mM glucose, while the intact cells did not. In the latter case, determinism became visible after the application of a gap junction inhibitor. This tendency was enhanced by the stimulation with tolbutamide. Our observations suggest that, thanks to the integration of individual chaotic dynamics via gap junction coupling, the β-cells will lose memory of fluctuations occurring at any instant in their electrical activity more rapidly with time. This is likely to contribute to the functional stability of the islet against uncertain perturbations.

  7. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    SciTech Connect

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  8. Identification of cancer stem cells and a strategy for their elimination.

    PubMed

    Dolgova, Evgenia V; Alyamkina, Ekaterina A; Efremov, Yaroslav R; Nikolin, Valeriy P; Popova, Nelly A; Tyrinova, Tamara V; Kozel, Artem V; Minkevich, Alexandra M; Andrushkevich, Oleg M; Zavyalov, Evgeniy L; Romaschenko, Alexander V; Bayborodin, Sergey I; Taranov, Oleg S; Omigov, Vladimir V; Shevela, Ekaterina Ya; Stupak, Vyacheslav V; Mishinov, Sergey V; Rogachev, Vladimir A; Proskurina, Anastasia S; Mayorov, Vladimir I; Shurdov, Mikhail A; Ostanin, Alexander A; Chernykh, Elena R; Bogachev, Sergey S

    2014-10-01

    It has been established previously that up to 40% of mouse CD34(+) hematopoietic stem cells are capable of internalizing exogenous dsDNA fragments both in vivo and ex vivo. Importantly, when mice are treated with a combination of cyclophosphamide and dsDNA, the repair of interstrand crosslinks in hematopoietic progenitors is attenuated, and their pluripotency is altered. Here we show for the first time that among various actively proliferating mammalian cell populations there are subpopulations capable of internalizing dsDNA fragments. In the context of cancer, such dsDNA-internalizing cell subpopulations display cancer stem cell-like phenotype. Furthermore, using Krebs-2 ascites cells as a model, we found that upon combined treatment with cyclophosphamide and dsDNA, engrafted material loses its tumor-initiating properties which we attribute to the elimination of tumor-initiating stem cell subpopulation or loss of its tumorigenic potential. PMID:25117082

  9. Identification of cancer stem cells and a strategy for their elimination

    PubMed Central

    Dolgova, Evgenia V; Alyamkina, Ekaterina A; Efremov, Yaroslav R; Nikolin, Valeriy P; Popova, Nelly A; Tyrinova, Tamara V; Kozel, Artem V; Minkevich, Alexandra M; Andrushkevich, Oleg M; Zavyalov, Evgeniy L; Romaschenko, Alexander V; Bayborodin, Sergey I; Taranov, Oleg S; Omigov, Vladimir V; Shevela, Ekaterina Ya; Stupak, Vyacheslav V; Mishinov, Sergey V; Rogachev, Vladimir A; Proskurina, Anastasia S; Mayorov, Vladimir I; Shurdov, Mikhail A; Ostanin, Alexander A; Chernykh, Elena R; Bogachev, Sergey S

    2014-01-01

    It has been established previously that up to 40% of mouse CD34+ hematopoietic stem cells are capable of internalizing exogenous dsDNA fragments both in vivo and ex vivo. Importantly, when mice are treated with a combination of cyclophosphamide and dsDNA, the repair of interstrand crosslinks in hematopoietic progenitors is attenuated, and their pluripotency is altered. Here we show for the first time that among various actively proliferating mammalian cell populations there are subpopulations capable of internalizing dsDNA fragments. In the context of cancer, such dsDNA-internalizing cell subpopulations display cancer stem cell-like phenotype. Furthermore, using Krebs-2 ascites cells as a model, we found that upon combined treatment with cyclophosphamide and dsDNA, engrafted material loses its tumor-initiating properties which we attribute to the elimination of tumor-initiating stem cell subpopulation or loss of its tumorigenic potential. PMID:25117082

  10. Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation

    PubMed Central

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2016-01-01

    Summary Cellular senescence suppresses cancer by arresting cells at risk of malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation and branching morphogenesis. Furthermore, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts – the ability to alter epithelial differentiation – that might also explain the loss of tissue function and organization that is a hallmark of aging. PMID:15657080

  11. Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs.

    PubMed

    Rajpert-De Meyts, Ewa; Nielsen, John E; Skakkebaek, Niels E; Almstrup, Kristian

    2015-01-01

    This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCT), with focus on the most common testicular GCT (TGCT). GCT are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic differentiation. TGCT that occur in young men are divided into two main types, seminoma and nonseminoma, both derived from a pre-invasive germ cell neoplasia in situ (GCNIS), which originates from transformed foetal gonocytes. In severely dysgenetic gonads, a GCNIS-resembling lesion is called gonadoblastoma. GCT occur rarely in young children (infantile GCT) in whom the pathogenesis is different (no GCNIS/gonadoblastoma stage) but the histopathological features are similar to the adult GCT. The rare spermatocytic tumour of older men is derived from post-pubertal spermatogonia that clonally expand due to gain-of function mutations in survival-promoting genes (e.g. FGFR3, HRAS), thus this tumour has a different expression profile than GCNIS-derived TGCT. Clinically most informative immunohistochemical markers for GCT, except teratoma, are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related factors, such as placental-like alkaline phosphatase (PLAP), OCT4 (POU5F1), NANOG, AP-2γ (TFAP2C) and LIN28, which are not expressed in normal adult germ cells. Some of these markers can also be used for immunocytochemistry to detect GCNIS or incipient tumours in semen samples. Gene expression in GCT is regulated in part by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation, except nonseminomas. In addition, a recently discovered mechanism of post-genomic gene expression regulation involves small non-coding RNAs, predominantly micro-RNA (miR). Testicular GCT display micro-RNA profiles similar to embryonic stem cells. Targeted miRNA-based blood tests for miR-371-3 and miR-367 clusters are

  12. Intracellular protein degradation in mammalian cells: recent developments.

    PubMed

    Knecht, Erwin; Aguado, Carmen; Cárcel, Jaime; Esteban, Inmaculada; Esteve, Juan Miguel; Ghislat, Ghita; Moruno, José Félix; Vidal, José Manuel; Sáez, Rosana

    2009-08-01

    In higher organisms, dietary proteins are broken down into amino acids within the digestive tract but outside the cells, which incorporate the resulting amino acids into their metabolism. However, under certain conditions, an organism loses more nitrogen than is assimilated in the diet. This additional loss was found in the past century to come from intracellular proteins and started an intensive research that produced an enormous expansion of the field and a dispersed literature. Therefore, our purpose is to provide an updated summary of the current knowledge on the proteolytic machinery involved in intracellular protein degradation and its physiological and pathological relevance, especially addressed to newcomers in the field who may find further details in more specialized reviews. However, even providing a general overview, this is an extremely wide field and, therefore, we mainly focus on mammalian cells, while other cells will be mentioned only for comparison purposes. PMID:19399586

  13. Farewell to the Lose-Lose Reality of Policing Plant Imports.

    PubMed

    Zamir, Dani

    2016-04-01

    In an age of free international shipments of mail-ordered seeds and plants, more policing will not stop the global migration of hitchhiking pests. The solution is in a preemptive response based on an internationally coordinated genomic deployment of global biodiversity in the largest breeding project since the "Garden of Eden." This plan will enrich the narrow genetic basis of annual and perennial plants with adaptations to changing environments and resistances to the pests of the future. PMID:27093460

  14. Foreclosure and Kids: Does Losing Your Home Mean Losing Your School?

    ERIC Educational Resources Information Center

    Been, Vicki; Ellen, Ingrid Gould; Schwartz, Amy Ellen; Stiefel, Leanna; Weinstein, Meryle

    2011-01-01

    The recent foreclosure crisis has plagued nearly every city in the U.S., including New York City. Despite considerable attention to the causes of these mortgage foreclosures and the consequences they have had for communities, we know little about their impacts on individual families and children. Given that more than 2.8 million U.S. property…

  15. Stem Cells

    MedlinePlus

    Stem cells are cells with the potential to develop into many different types of cells in the body. ... the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  16. Cell Structure

    MedlinePlus

    ... Cells, Tissues, & Membranes Cell Structure & Function Cell Structure Cell Function Body Tissues Epithelial Tissue Connective Tissue Muscle Tissue ... apparatus , and lysosomes . « Previous (Cell Structure & Function) Next (Cell Function) » Contact Us | Privacy Policy | Accessibility | FOIA | File Formats ...

  17. Stem Cells

    MedlinePlus

    Stem cells are cells with the potential to develop into many different types of cells in the body. They serve as a repair ... body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  18. Inhibition of T-cell Response by Escherichia coli Heat-Labile Enterotoxin-Treated Epithelial Cells

    PubMed Central

    Lopes, Luciene M.; Maroof, Asher; Dougan, Gordon; Chain, Benjamin M.

    2000-01-01

    Escherichia coli heat-labile enterotoxin (LT) is an extensively studied adjuvant of mucosal responses. Nevertheless, its mode of action as an adjuvant remains incompletely understood. In this study, we describe a simplified in vitro model with which to look at some aspects of immunoregulation by LT. The interaction of LT with the apical surface of a monolayer of CaCo-2 epithelial cells induces the release of a soluble factor which inhibits the antigen-induced release of interleukin-2 by T cells cultured at the basolateral side of the cells. The release of this factor requires the ADP-ribosylating activity of LT since the isolated B subunit, as well as an enzymatically silent LT mutant, loses biological activity in this model. The inhibitory activity is likely to be due to prostaglandin release, since it is blocked by indomethacin. The contribution of LT-induced prostaglandin release to the complex immunoregulatory activity of LT is discussed. PMID:11083810

  19. Searching for the β-Cell Fountain of Youth.

    PubMed

    Jouvet, Nathalie; Estall, Jennifer L

    2016-09-01

    Aging affects every species and tissue but not in equal ways. Human pancreatic β-cells lose their ability to replicate, regenerate, and secrete insulin as one gets older. This natural process increases risk of developing diabetes as you age and is a concern for donor islets and stem cells obtained from older subjects destined for transplantation or emerging regenerative therapies. Using fluidic sorting and RNA sequencing on single cells, Xin et al describe a transcriptional signature of mouse β-cell aging between adulthood and a very old age. Amazingly, expression levels of more than 99% of genes do not change over time, despite the long lifespan of this specialized tissue. They identify a novel set of transcription factors that can explain decreases in cell survival and proliferation genes and potentially drive age-associated decline in regenerative capacity. Yet somehow, mouse β-cells maintain pathways regulating glucose metabolism and β-cell function despite experiencing challenges commonly associated with old age, including increased weight and fat mass. The authors conclude that β-cells of old mice are overall strikingly similar to young β-cells, implying that mechanisms may exist to resist aging and maintain their 'youth'. These new discoveries have interesting implications for efforts to preserve or improve function of human β-cells, providing potential clues toward prolonging the life and health of donor tissues or islets of people with diabetes. PMID:27580804

  20. Memory T cells in organ transplantation: progress and challenges.

    PubMed

    Espinosa, Jaclyn R; Samy, Kannan P; Kirk, Allan D

    2016-06-01

    Antigen-experienced T cells, also known as memory T cells, are functionally and phenotypically distinct from naive T cells. Their enhanced expression of adhesion molecules and reduced requirement for co-stimulation enables them to mount potent and rapid recall responses to subsequent antigen encounters. Memory T cells generated in response to prior antigen exposures can cross-react with other nonidentical, but similar, antigens. This heterologous cross-reactivity not only enhances protective immune responses, but also engenders de novo alloimmunity. This latter characteristic is increasingly recognized as a potential barrier to allograft acceptance that is worthy of immunotherapeutic intervention, and several approaches have been investigated. Calcineurin inhibition effectively controls memory T-cell responses to allografts, but this benefit comes at the expense of increased infectious morbidity. Lymphocyte depletion eliminates allospecific T cells but spares memory T cells to some extent, such that patients do not completely lose protective immunity. Co-stimulation blockade is associated with reduced adverse-effect profiles and improved graft function relative to calcineurin inhibition, but lacks efficacy in controlling memory T-cell responses. Targeting the adhesion molecules that are upregulated on memory T cells might offer additional means to control co-stimulation-blockade-resistant memory T-cell responses. PMID:26923209