Science.gov

Sample records for spermatogonia cells lose

  1. A-Single Spermatogonia Heterogeneity and Cell Cycles Synchronize with Rat Seminiferous Epithelium Stages VIII–IX1

    PubMed Central

    Abid, Shadaan N.; Richardson, Timothy E.; Powell, Heather M.; Jaichander, Priscilla; Chaudhary, Jaideep; Chapman, Karen M.; Hamra, F. Kent

    2014-01-01

    ABSTRACT In mammalian testes, “A-single” spermatogonia function as stem cells that sustain sperm production for fertilizing eggs. Yet, it is not understood how cellular niches regulate the developmental fate of A-single spermatogonia. Here, immunolabeling studies in rat testes define a novel population of ERBB3+ germ cells as approximately 5% of total SNAP91+ A-single spermatogonia along a spermatogenic wave. As a function of time, ERBB3+ A-single spermatogonia are detected during a 1- to 2-day period each 12.9-day sperm cycle, representing 35%–40% of SNAP91+ A-single spermatogonia in stages VIII–IX of the seminiferous epithelium. Local concentrations of ERBB3+ A-single spermatogonia are maintained under the mean density measured for neighboring SNAP91+ A-single spermatogonia, potentially indicative of niche saturation. ERBB3+ spermatogonia also synchronize their cell cycles with epithelium stages VIII–IX, where they form physical associations with preleptotene spermatocytes transiting the blood-testis barrier and Sertoli cells undergoing sperm release. Thus, A-single spermatogonia heterogeneity within this short-lived and reoccurring microenvironment invokes novel theories on how cellular niches integrate with testicular physiology to orchestrate sperm development in mammals. PMID:24389876

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

    PubMed Central

    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.

    2015-01-01

    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 TertHigh undifferentiated spermatogonia and TertLow 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 TertHigh 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 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

  4. 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

  5. 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

  6. Transcriptional coactivator undifferentiated embryonic cell transcription factor 1 expressed in spermatogonial stem cells: a putative marker of boar spermatogonia.

    PubMed

    Lee, Won-Young; Lee, Kyung-Hoon; Heo, Young-Tae; Kim, Nam-Hyung; Kim, Jin-Hoi; Kim, Jae-Hwan; Moon, Sung-Hwan; Chung, Hak-Jae; Yoon, Min-Jung; Song, Hyuk

    2014-11-30

    Spermatogenesis is initiated from spermatogonial stem cells (SSCs), which are derived from gonocytes. Although some rodent SSC markers have been investigated, other species- and developmental stage-specific markers of spermatogonia have not been identified. The objective of this study was to characterize the expression of undifferentiated embryonic cell transcription factor 1 (UTF1) gene as a potential marker for spermatogonia and SSCs in the boar testis. In boar testis tissue at pre-pubertal stages (tissues collected at 5, 30, and 60 days of age), UTF1 gene expression was detected in almost all spermatogonia cells that expressed a protein gene product 9.5 (PGP9.5), and immunocytochemical analysis of isolated total testicular cells showed that 91.14% of cells staining for PGP9.5 also stained for UTF1. However, in boar testis tissue at pubertal and post-pubertal stages (tissues collected at 90, 120, 150, and 180 days of age), UTF1 was not detected in all PGP9.5-positive cells in the basement membrane. While some PGP9.5-positive cells stained for UTF1, other cells stained only for PGP9.5 or UTF1. PGP9.5, UTF1, and NANOG was assessed in in vitro cultures of pig SSCs (pSSCs) from testes collected at 5 days of age. The relative amounts of PGP9.5, NANOG, and UTF1 mRNA were greater in pSSC colonies than in testis and muscle tissue. Thus, the UTF1 gene is expressed in PGP9.5-positive spermatogonia cells of pigs at 5 days of age, and its expression is maintained in cultured pSSC colonies, suggesting that UTF1 is a putative marker for early-stage spermatogonia in the pre-pubertal pig testis. These findings will facilitate the study of spermatogenesis and applications in germ cell research.

  7. 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

  8. 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

  9. Cell competition: Winning out by losing notch

    PubMed Central

    Alcolea, Maria P; Jones, Philip H

    2015-01-01

    Cell competition where ‘loser’ cells are eliminated by neighbors with higher fitness is a widespread phenomenon in development. However, a growing body of evidence argues cells with somatic mutations compete with their wild type counterparts in the earliest stages of cancer development. Recent studies have begun to shed light on the molecular and cellular mechanisms that alter the competitiveness of cells carrying somatic mutations in adult tissues. Cells with a ‘winner’ phenotype create clones which may expand into extensive fields of mutant cells within normal appearing epithelium, favoring the accumulation of further genetic alterations and the evolution of cancer. Here we focus on how mutations which disrupt the Notch signaling pathway confer a ‘super competitor’ status on cells in squamous epithelia and consider the broader implications for cancer evolution. PMID:25551772

  10. 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.

  11. Transcriptional and Translational Heterogeneity among Neonatal Mouse Spermatogonia1

    PubMed Central

    Hermann, Brian P.; Mutoji, Kazadi N.; Velte, Ellen K.; Ko, Daijin; Oatley, Jon M.; Geyer, Christopher B.; McCarrey, John R.

    2015-01-01

    ABSTRACT Spermatogonial stem cells (SSCs) are a subset of undifferentiated spermatogonia responsible for ongoing spermatogenesis in mammalian testes. Spermatogonial stem cells arise from morphologically homogeneous prospermatogonia, but growing evidence suggests that only a subset of prospermatogonia develops into the foundational SSC pool. This predicts that subtypes of undifferentiated spermatogonia with discrete mRNA and protein signatures should be distinguishable in neonatal testes. We used single-cell quantitative RT-PCR to examine mRNA levels of 172 genes in individual spermatogonia from 6-day postnatal (P6) mouse testes. Cells enriched from P6 testes using the StaPut or THY1+ magnetic cell sorting methods exhibited considerable heterogeneity in the abundance of specific germ cell and stem cell mRNAs, segregating into one somatic and three distinct spermatogonial clusters. However, P6 Id4-eGFP+ transgenic spermatogonia, which are known to be enriched for SSCs, were more homogeneous in their mRNA levels, exhibiting uniform levels for the majority of genes examined (122 of 172). Interestingly, these cells displayed nonuniform (50 of 172) expression of a smaller cohort of these genes, suggesting there is substantial heterogeneity even within the Id4-eGFP+ population. Further, although immunofluorescence staining largely demonstrated conformity between mRNA and protein levels, some proteins were observed in patterns that were disparate from those detected for the corresponding mRNAs in Id4-eGFP+ spermatogonia (e.g., Kit, Sohlh2, Stra8), suggesting additional heterogeneity is introduced at the posttranscriptional level. Taken together, these data demonstrate the existence of multiple spermatogonial subtypes in P6 mouse testes and raise the intriguing possibility that these subpopulations may correlate with the development of functionally distinct spermatogenic cell types. PMID:25568304

  12. Comparison of the genetic effects of equimolar doses of ENU and MNU: While the chemicals differ dramatically in their mutagenicity in stem-cell spermatogonia, both elicit very high mutation rates in differentiating spermatogonia

    SciTech Connect

    Russell, Liane B; Hunsicker, Patricia R; Russell, William

    2007-03-01

    Mutagenoic, reproductive, and toxicity effects of two closely related chemicals, ethylnitrosourea (ENU) and methylnitrosourea (MNU), were compared at equimolar and near-equimolar doses in the mouse specific-locus test in a screen of all stages of spermatogenesis and spermiogenesis. In stem cell spermatogonial (SG), ENU is more than an order of magnitude more mutagenic than MNU. During post-SG stages, both chemicals exhibit high peaks in mutation yield when differentiating spermatogonial (DG) and preleptotene spermatocytes are exposed. The mutation frequency induced by 75 mg MNU/kg during this peak interval is, to date, the highest induced by any single- xposure mutagenic treatment chemical or radiation that allows survival of the exposed animal and its germ cells, producing an estimated 10 new mutations per genome. There is thus a vast difference between stem cell and differentiating spermatogonial in their sensitivity to MNU, but little difference between these stages in their sensitivity to ENU. During stages following meiotic metaphase, the highest mutation yield is obtained from exposed spermatids, but for both chemicals, that yield is less than one-quarter that obtained from the peak interval. Large-lesion (LL) mutations were induced only in spermatids. Although only a few of the remaining mutations were analyzed molecularly, there is considerable evidence from recent molecular characterizations of the marker genes and their flanking chromosomal regions that most, if not all, mutations induced during the peak-sensitive period did not involve lesions outside the marked loci. Both ENU and MNU treatments of post-SG stages yielded significant numbers of mutants that were recovered as mosaics, with the proportion being higher for ENU than for MNU. Comparing the chemicals for the endpoints studied and additional ones (e.g., chromosome aberrations, toxicity to germ cells and to animals, teratogenicity) revealed that while MNU is generally more effective, the opposite

  13. Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges.

    PubMed

    Manku, Gurpreet; Culty, Martine

    2015-03-01

    The production of spermatozoa relies on a pool of spermatogonial stem cells (SSCs), formed in infancy from the differentiation of their precursor cells, the gonocytes. Throughout adult life, SSCs will either self-renew or differentiate, in order to maintain a stem cell reserve while providing cells to the spermatogenic cycle. By contrast, gonocytes represent a transient and finite phase of development leading to the formation of SSCs or spermatogonia of the first spermatogenic wave. Gonocyte development involves phases of quiescence, cell proliferation, migration, and differentiation. Spermatogonia, on the other hand, remain located at the basement membrane of the seminiferous tubules throughout their successive phases of proliferation and differentiation. Apoptosis is an integral part of both developmental phases, allowing for the removal of defective cells and the maintenance of proper germ-Sertoli cell ratios. While gonocytes and spermatogonia mitosis are regulated by distinct factors, they both undergo differentiation in response to retinoic acid. In contrast to postpubertal spermatogenesis, the early steps of germ cell development have only recently attracted attention, unveiling genes and pathways regulating SSC self-renewal and proliferation. Yet, less is known on the mechanisms regulating differentiation. The processes leading from gonocytes to spermatogonia have been seldom investigated. While the formation of abnormal gonocytes or SSCs could lead to infertility, defective gonocyte differentiation might be at the origin of testicular germ cell tumors. Thus, it is important to better understand the molecular mechanisms regulating these processes. This review summarizes and compares the present knowledge on the mechanisms regulating mammalian gonocyte and spermatogonial differentiation. PMID:25670871

  14. 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

  15. Lentiviral vector-mediated transduction of goat undifferentiated spermatogonia.

    PubMed

    Abbasi, Hassan; Hosseini, Sayyed Morteza; Hajian, Mahdi; Nasiri, Zahra; Bahadorani, Mehrnoosh; Tahmoorespur, Mojtaba; Nasiri, Mohammad Reza; Nasr-Esfahani, Mohammad Hossein

    2015-12-01

    Recent studies show that spermatogonial stem cells (SSCs) are able to colonize and form mature spermatozoa following transplantation into germ cell depleted testes of recipient males. Therefore, efficient ways for enrichment and gene transfer into SSCs provides a powerful tool for production of transgenic animals. In order to adapt the technique to goats, three issues were addressed: (i) enrichment of the undifferentiated spermatogonia including SSCs using magnetic activated cell sorting (MACS), (ii) lentiviral vector-mediated transduction of an enhanced green fluorescent protein (EGFP) transgene into enriched cells, and (iii) transplantation of transduced undifferentiated spermatogonia into the germ cell depleted testes of immune-suppressed mice to assess for migration and colony formation ability. Enriched cells were transduced by lentiviral vectors and subsequently analyzed for expression of THY1, PLZF, VASA, UCHL1 and BCL6B genes. Cells were also analyzed for GFP and PLZF by flow cytometry. Enriched transduced cells were transplanted into germ cell depleted mice testis. Quantitative analysis of transcripts revealed that MACS-enrichment significantly increased the expression of SSC-characteristic genes THY1, PLZF, VASA, UCHL1 and BCL6B compared to non-enriched population (P≤0.05). EGFP transduction did not affect the expression levels of SSC-characteristic genes. Flow cytometry revealed that 72% of transduced-enriched cells were positive for EGFP. Finally, transduced-enriched goat SSCs could colonize within the cells into the seminiferous tubules of germ cell depleted recipient mice at higher frequency than non-enriched cells. The results indicated that enrichment of goat undifferentiated spermatogonia by magnetic-activated cell sorting for THY1 antibody combined with lentiviral vector-mediated transduction has the potential to be used for production of transgenic goats.

  16. Differential gene expression profiling of enriched human spermatogonia after short- and long-term culture.

    PubMed

    Conrad, Sabine; Azizi, Hossein; Hatami, Maryam; Kubista, Mikael; Bonin, Michael; Hennenlotter, Jörg; Renninger, Markus; Skutella, Thomas

    2014-01-01

    This study aimed to provide a molecular signature for enriched adult human stem/progenitor spermatogonia during short-term (<2 weeks) and long-term culture (up to more than 14 months) in comparison to human testicular fibroblasts and human embryonic stem cells. Human spermatogonia were isolated by CD49f magnetic activated cell sorting and collagen(-)/laminin(+) matrix binding from primary testis cultures obtained from ten adult men. For transcriptomic analysis, single spermatogonia-like cells were collected based on their morphology and dimensions using a micromanipulation system from the enriched germ cell cultures. Immunocytochemical, RT-PCR and microarray analyses revealed that the analyzed populations of cells were distinct at the molecular level. The germ- and pluripotency-associated genes and genes of differentiation/spermatogenesis pathway were highly expressed in enriched short-term cultured spermatogonia. After long-term culture, a proportion of cells retained and aggravated the "spermatogonial" gene expression profile with the expression of germ and pluripotency-associated genes, while in the majority of long-term cultured cells this molecular profile, typical for the differentiation pathway, was reduced and more genes related to the extracellular matrix production and attachment were expressed. The approach we provide here to study the molecular status of in vitro cultured spermatogonia may be important to optimize the culture conditions and to evaluate the germ cell plasticity in the future.

  17. 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.

  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. Lung cancer stem cell lose their stemness default state after exposure to microgravity.

    PubMed

    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.

  20. Retinoic acid induces multiple hallmarks of the prospermatogonia-to-spermatogonia transition in the neonatal mouse.

    PubMed

    Busada, Jonathan T; Kaye, Evelyn P; Renegar, Randall H; Geyer, Christopher B

    2014-03-01

    In mammals, most neonatal male germ cells (prospermatogonia) are quiescent and located in the center of the testis cords. In response to an unknown signal, prospermatogonia transition into spermatogonia, reenter the cell cycle, divide, and move to the periphery of the testis cords. In mice, these events occur by 3-4 days postpartum (dpp), which temporally coincides with the onset of retinoic acid (RA) signaling in the neonatal testis. RA has a pivotal role in initiating germ cell entry into meiosis in both sexes, yet little is known about the mechanisms and about cellular changes downstream of RA signaling. We examined the role of RA in mediating the prospermatogonia-to-spermatogonia transition in vivo and found 24 h of precocious RA exposure-induced germ cell changes mimicking those that occur during the endogenous transition at 3-4 dpp. These changes included: 1) spermatogonia proliferation; 2) maturation of cellular organelles; and 3), expression of markers characteristic of differentiating spermatogonia. We found that germ cell exposure to RA did not lead to cellular loss from apoptosis but rather resulted in a delay of ∼2 days in their entry into meiosis. Taken together, our results indicate that exogenous RA induces multiple hallmarks of the transition of prospermatogonia to spermatogonia prior to their entry into meiosis.

  1. 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

  2. Losing Things.

    ERIC Educational Resources Information Center

    Zingher, Gary

    2003-01-01

    Reviews five children's books that deal with the theme of losing things and the feelings that can accompany it. Also discusses the loss of intangible things, such as talent, concentration, temper, or patience, and presents five creative activities that deal more with the loss of objects. (LRW)

  3. 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.

  4. BMP4 Cooperates with Retinoic Acid to Induce the Expression of Differentiation Markers in Cultured Mouse Spermatogonia

    PubMed Central

    Feng, Yanmin; Feng, Xue; Wang, Xiuxia; Gan, Haiyun; Wang, Lixian; Lin, Xiwen

    2016-01-01

    Spermatogenesis is sustained by the proliferation and differentiation of spermatogonial stem cells (SSCs). However, the molecules controlling these processes remain largely unknown. Here, we developed a simplified high concentration serum-containing system for the culture of mouse SSCs. Analysis of SSCs markers and transplantation results revealed that the cultured spermatogonia retained stem cell characteristics after long-term in vitro propagation. Using this culture system, the expression and function of bone morphogenetic protein 4 (BMP4) were explored. Immunostaining showed that BMP4 was predominantly expressed in germ cells and that its level increased as spermatogenesis progresses. BMP4 receptors BMPR1A and BMPRII were present in spermatogonia, spermatocytes, and round spermatids. Moreover, despite the mRNAs of these two genes being present in mouse Sertoli cells, only BMPRII was detected by using Western blotting assays. While exogenous BMP4 by itself did not induce the expression of Stra8 and c-Kit, two marker genes of differentiating spermatogonia, a significant cooperative effect of BMP4 and retinoic acid (RA) was observed. Moreover, pretreatment of cultured spermatogonia with the BMP4 antagonist Noggin could inhibit RA-induced expression of these two marker genes. In conclusion, BMP4 may exert autocrine effects and act cooperatively with RA to induce the differentiation of spermatogonia in vivo. PMID:27795714

  5. 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

  6. 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.

  7. Distinct requirements for Sin3a in perinatal male gonocytes and differentiating spermatogonia

    PubMed Central

    Gallagher, Shannon J.; Kofman, Amber E.; Huszar, Jessica M.; Dannenberg, Jan-Hermen; DePinho, Ronald A.; Braun, Robert E.; Payne, Christopher J.

    2012-01-01

    Chromatin modifier Swi-independent 3a (SIN3A), together with associated histone deacetylases, influences gene expression during development and differentiation through a variety of transcription factors in a cell-specific manner. Sin3a is essential for the maintenance of inner cell mass cells of mouse blastocysts, embryonic fibroblasts, and myoblasts, but is not required for the survival of trophectoderm or Sertoli cells. To better understand how this transcriptional regulator modulates cells at different developmental stages within a single lineage, we used conditional gene targeting in mice to ablate Sin3a from perinatal quiescent male gonocytes and from postnatal differentiating spermatogonia. Mitotic germ cells expressing stimulated by retinoic acid gene 8 (Stra8) that lacked Sin3a exhibited increased DNA damage and apoptosis, yet collectively progressed through meiosis and spermiogenesis and generated epididymal sperm at approximately 50% of control levels, sufficient for normal fertility. In contrast, perinatal gonocytes lacking Sin3a underwent rapid depletion that coincided with cell cycle reentry, exhibiting 2.5-fold increased histone H3 phosphorylation upon cycling that suggested a prophase/metaphase block; germ cells were almost entirely absent two weeks after birth, resulting in sterility. Gene expression profiling of neonatal testes containing Sin3a-deleted gonocytes identified upregulated transcripts highly associated with developmental processes and pattern formation, and downregulated transcripts involved in nuclear receptor activity, including Nr4a1 (Nur77). Interestingly, Nr4a1 levels were elevated in testes containing Stra8-expressing, Sin3a-deleted spermatogonia. SIN3A directly binds to the Nr4a1 promoter, and Nr4a1 expression is diminished upon spermatogonial differentiation in vitro. We conclude that within the male germline, Sin3a is required for the mitotic reentry of gonocytes, but is dispensable for the maintenance of differentiating

  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.

  9. 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

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

    PubMed

    Takase, Hinako M; Nusse, Roeland

    2016-03-15

    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.

  11. 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

  12. 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 ...

  13. 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

  14. [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

  15. 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 ...

  16. THY1 as a reliable marker for enrichment of undifferentiated spermatogonia in the goat.

    PubMed

    Abbasi, Hassan; Tahmoorespur, Mojtaba; Hosseini, Sayyed Morteza; Nasiri, Zahra; Bahadorani, Mehrnoosh; Hajian, Mahdi; Nasiri, Mohammad Reza; Nasr-Esfahani, Mohammad Hossein

    2013-11-01

    Spermatogonial stem cells are unique cells of testes that can restore fertility upon transplantation into recipient testes. However, use of suitable markers for enrichment of these cells have important potential application. THY1, is an established conserved marker of spermatogonial stem cells in bovine, rodents, and primates, but there is no information available in goats. After three rounds of enzymatic digestion of prepubertal goat testicular tissues, undifferentiated spermatogonia positive for THY1 were isolated by magnetic-activated cell sorting and were used for immunocytochemistry, real-time polymerase chain reaction analysis for gene expression, protein expression, and transplantation into recipient mice. Immunocytochemical analyses showed that significantly higher percentage of THY1(+) cells were positive for PLZF and VASA when compared with unselected population. This result for PLZF was further confirmed at the protein level. Real-time polymerase chain reaction analysis revealed that expression of THY1, PLZF, VASA, BCL6B, and UCHL1 as SCCs characteristic genes in THY1(+) cells was significantly higher than in the initial population. Finally, transplantation of PKH26-labeled cells revealed that THY1(+) cells had higher capacity for colony formation when compared with unselected cells. In conclusion, the results provide indications that THY1 surface marker can be reliably used for enrichment of undifferentiated spermatogonial in the goats.

  17. 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…

  18. Type I collagen gel induces Madin-Darby canine kidney cells to become fusiform in shape and lose apical-basal polarity

    PubMed Central

    1989-01-01

    In the embryo, epithelia give rise to mesenchyme at specific times and places. Recently, it has been reported (Greenburg, G., and E. D. Hay. 1986. Dev. Biol. 115:363-379; Greenberg, G., and E. D. Hay. 1988. Development (Camb.). 102:605-622) that definitive epithelia can give rise to fibroblast-like cells when suspended within type I collagen gels. We wanted to know whether Madin-Darby canine kidney (MDCK) cells, an epithelial line, can form mesenchyme under similar conditions. Small explants of MDCK cells on basement membrane were suspended within or placed on top of extracellular matrix gels. MDCK cells on basement membrane gel are tall, columnar in shape, and ultrastructurally resemble epithelia transporting fluid and ions. MDCK explants cultured on type I collagen gel give rise to isolated fusiform-shaped cells that migrate over the gel surface. The fusiform cells extend pseudopodia and filopodia, lose cell membrane specializations, and develop an actin cortex around the entire cell. Unlike true mesenchymal cells, which express vimentin and type I collagen, fusiform cells produce both keratin and vimentin, continue to express laminin, and do not turn on type I collagen. Fusiform cells are not apically-basally polarized, but show mesenchymal cell polarity. Influenza hemagglutinin and virus budding localize to the front end or entire cell surface. Na,K-ATPase occurs intracellularly and also symmetrically distributes on the cell surface. Fodrin becomes diffusely distributed along the plasma membrane, ZO-1 cannot be detected, and desmoplakins distribute randomly in the cytoplasm. The loss of epithelial polarity and acquisition of mesenchymal cell polarity and shape by fusiform MDCK cells on type I collagen gel was previously unsuspected. The phenomenon may offer new opportunities for studying cytoplasmic and nuclear mechanisms regulating cell shape and polarity. PMID:2537838

  19. Isolation of undifferentiated and early differentiating Type A spermatogonia from Pou5f1-GFP reporter mice

    PubMed Central

    Garcia, Thomas; Hofmann, Marie-Claude

    2012-01-01

    Limited understanding of the mechanisms underlying self-renewal and differentiation of spermatogonial stem cells hampers our ability to develop new therapeutic and contraceptive approaches. Mouse models of spermatogonial stem cell development are key to developing new insights into the biology of both the normal and diseased testis. Advances in transgenic reporter mice have enabled the isolation, molecular characterization, and functional analysis of mouse Type A spermatogonia subpopulations from the normal testis, including populations enriched for spermatogonial stem cells. Application of these reporters both to the normal testis and to gene-deficient and over-expression models will promote a better understanding of the earliest steps of spermatogenesis, and the role of spermatogonial stem cells in germ cell tumor. PMID:22144234

  20. 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. PMID:27308470

  1. p53 Loses grip on PIK3CA expression leading to enhanced cell survival during platinum resistance.

    PubMed

    Thakur, Bhushan; Ray, Pritha

    2016-10-01

    Tumour suppressor p53, a master transcriptional regulator determines cell fate through preferential activation/repression of a myriad of genes during stress. Till date, activation and preferential binding of p53 on different promoters was reported to be influenced by the nature, strength and duration of stress which mediates its post translational modifications. Cisplatin, a widely used cytotoxic drug represses PIK3CA promoter activity and attenuates PI3K/AKT cell survival pathway through p53 activation in sensitive cells. However, very little is understood about the overall mechanism of p53-PIK3CA interaction and influence of p53 on the transcriptional status of PIK3CA during cisplatin resistance. Here we showed that cisplatin could dynamically alter p53 occupancy between the p53 binding sequences present in PIK3CA promoter in ovarian and breast cancer cells. This altered occupancy is dictated by higher acetylation and hyper-phosphorylation at serine 15, serine 20 and serine 46 residues. Interestingly, cisplatin resistant cells when challenged with cisplatin demonstrated abolished PIK3CA promoter attenuation, low level of p53 binding, and loss of p53 serine 46 phosphorylation. A phosphorylation deficient S46A mutant failed to repress PIK3CA in p53 deficient cells. Elevated expression of Bcl2, P27 and cFLIP indicated a pro-survival state in these resistant cells. Non-invasive real time imaging using two different luciferase reporters showed that cisplatin could simultaneously induce PIK3CA attenuation and p53 activation with growth regression in sensitive tumours but not in the resistant tumours where only low level of p53 activation and sustained growth was observed. This is the first report on phosphorylation of p53 serine 46 as a modulator of p53-PIK3CA promoter interaction which influences altered binding of p53 at different consensus sequences in the same promoter in response to chemotherapeutic stress. Absence of such modulation in resistant cellular milieu

  2. p53 Loses grip on PIK3CA expression leading to enhanced cell survival during platinum resistance.

    PubMed

    Thakur, Bhushan; Ray, Pritha

    2016-10-01

    Tumour suppressor p53, a master transcriptional regulator determines cell fate through preferential activation/repression of a myriad of genes during stress. Till date, activation and preferential binding of p53 on different promoters was reported to be influenced by the nature, strength and duration of stress which mediates its post translational modifications. Cisplatin, a widely used cytotoxic drug represses PIK3CA promoter activity and attenuates PI3K/AKT cell survival pathway through p53 activation in sensitive cells. However, very little is understood about the overall mechanism of p53-PIK3CA interaction and influence of p53 on the transcriptional status of PIK3CA during cisplatin resistance. Here we showed that cisplatin could dynamically alter p53 occupancy between the p53 binding sequences present in PIK3CA promoter in ovarian and breast cancer cells. This altered occupancy is dictated by higher acetylation and hyper-phosphorylation at serine 15, serine 20 and serine 46 residues. Interestingly, cisplatin resistant cells when challenged with cisplatin demonstrated abolished PIK3CA promoter attenuation, low level of p53 binding, and loss of p53 serine 46 phosphorylation. A phosphorylation deficient S46A mutant failed to repress PIK3CA in p53 deficient cells. Elevated expression of Bcl2, P27 and cFLIP indicated a pro-survival state in these resistant cells. Non-invasive real time imaging using two different luciferase reporters showed that cisplatin could simultaneously induce PIK3CA attenuation and p53 activation with growth regression in sensitive tumours but not in the resistant tumours where only low level of p53 activation and sustained growth was observed. This is the first report on phosphorylation of p53 serine 46 as a modulator of p53-PIK3CA promoter interaction which influences altered binding of p53 at different consensus sequences in the same promoter in response to chemotherapeutic stress. Absence of such modulation in resistant cellular milieu

  3. Protein-Losing Gastroenteropathy

    PubMed Central

    Pops, Martin A.

    1966-01-01

    In the past 10 years with the development of improved methods, particularly radioisotope techniques, it has been demonstrated that a number of patients with gastrointestinal disease and depletion of plasma proteins become hypoproteinemic because of actual leakage of albumin and other plasma proteins into the lumen of the gastrointestinal tract. The site of protein leakage is variable depending on the underlying pathological state but the loss of protein-containing lymph through the gastrointestinal lymphatic channels seems to be the major mechanism for hypoproteinemia. It has become apparent that there exists a normal mechanism for secretion of plasma proteins into the gastrointestinal tract as part of the overall metabolism of the plasma proteins. When the process is exaggerated so that resynthesis of plasma protein cannot keep pace with its degradation, sometimes severe hypoproteinemia is the result. Such a pathological process has now been described in approximately 40 disease states. A review of all the techniques which can demonstrate gastroenteric protein loss reveals that there are no widely available quantitative tests but that accurate quantitation is not necessary for the diagnosis of protein losing gastroenteropathy. PMID:18730025

  4. High-density lipoprotein from patients with coronary heart disease loses anti-thrombotic effects on endothelial cells: impact on arterial thrombus formation.

    PubMed

    Holy, Erik W; Besler, Christian; Reiner, Martin F; Camici, Giovanni G; Manz, Jasmin; Beer, Jürg H; Lüscher, Thomas F; Landmesser, Ulf; Tanner, Felix C

    2014-11-01

    Thrombus formation is determined by the balance between pro- thrombotic mediators and anti-thrombotic factors.High-density lipoprotein (HDL) from healthy subjects exerts anti-thrombotic properties. Whether this is also the case for HDL from patients with stable coronary heart disease (CHD) or acute coronary syndrome (ACS) is unknown.In human aortic endothelial cells in culture,HDL (50 µg/ml) from healthy subjects (HS) inhibited thrombin-induced tissue factor (TF) expression and activity, while HDL (50 µg/ml) from CHD and ACS patients did not. Similarly, only healthy HDL increased endothelial tissue factor pathway inhibitor (TFPI) expression and tissue plasminogen activator (tPA) release, while HDL from CHD and ACS patients had no effect. Healthy HDL inhibited thrombin-induced plasminogen activator inhibitor type 1 (PAI-1) expression, while HDL from ACS patients enhanced endothelial PAI-1 expression. Inhibition of nitric oxide (NO) formation with L-NAME (100 µmol/l) abolished the anti-thrombotic effects of healthy HDL on TF, TFPI, and tPA expression. The exogenous nitric oxide donor, DETANO, mimicked the effects of healthy HDL and counterbalanced the loss of anti-thrombotic effects of HDL from CHD and ACS patients in endothelial cells. In line with this observation, healthy HDL, in contrast to HDL from CHD and ACS patients, increased endothelial NO production. In the laser-injured carotid artery of the mouse, thrombus formation was delayed in animals treated with healthy HDL compared with mice treated with vehicle or HDL from patients with CHD or ACS. In conclusion, HDL from CHD and ACS patients loses the ability of healthy HDL to suppress TF and to increase TFPI and t-PA and instead enhances PAI-1 and arterial thrombus formation.

  5. On the disentangling modes of ortho- and para-braids in mitosing mammalian spermatogonia.

    PubMed

    Matioli, G T

    1994-10-01

    This note complements a previous one (1), regarding in particular, mitotic separation of replica homologs from their templates, in mammalian spermatogonia. Topological differences between Ortho- and Para-braids determine different modes of antipodal segregation of paired homologs prior to onset of meiosis.

  6. 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) ...

  7. The Pacific bluefin tuna (Thunnus orientalis) dead end gene is suitable as a specific molecular marker of type A spermatogonia.

    PubMed

    Yazawa, Ryosuke; Takeuchi, Yutaka; Morita, Tetsuro; Ishida, Masashi; Yoshizaki, Goro

    2013-10-01

    We developed a spermatogonial transplantation technique to produce donor-derived gametes in surrogate fish. Our ultimate aim is to establish surrogate broodstock that can produce bluefin tuna. We previously determined that only type A spermatogonia (ASG) could colonize recipient gonads in salmonids. Therefore, it is necessary to develop a precise molecular marker that can distinguish ASG in order to develop efficient spermatogonial transplantation methods. In this study, the Pacific bluefin tuna (Thunnus orientalis) dead end (BFTdnd) gene was identified as a specific marker for ASG. In situ hybridization and RT-PCR analysis with various types of spermatogenic cell populations captured by laser microdissection revealed that localization of BFTdnd mRNA was restricted to ASG, and not detected in other differentiated spermatogenic cells. In order to determine if BFTdnd can be used as a molecular marker to identify germ cells with high transplantability, transplantation of dissociated testicular cells isolated from juvenile, immature, and mature Pacific bluefin tuna, which have different proportions of dnd-positive ASG, were performed using chub mackerel as the surrogate recipient species. Colonization of transplanted donor germ cells was only successful with testicular cells from immature Pacific Bluefin tuna, which contained higher proportions of dnd-positive ASG than juvenile and mature fish. Thus, BFTdnd is a useful tool for identifying highly transplantable ASG for spermatogonial transplantation.

  8. 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

  9. Sphere-formation culture of testicular germ cells in the common marmoset, a small New World monkey.

    PubMed

    Lin, Zachary Yu-Ching; Hikabe, Orie; Suzuki, Sadafumi; Hirano, Takamasa; Siomi, Haruhiko; Sasaki, Erika; Imamura, Masanori; Okano, Hideyuki

    2016-01-01

    Spermatogonia are specialized cells responsible for continuous spermatogenesis and the production of offspring. Because of this biological property, in vitro culture of spermatogonia provides a powerful methodology to advance reproductive biology and engineering. However, methods for culturing primate spermatogonia are poorly established. We have designed a novel method for culturing spermatogonia in the common marmoset (Callithrix jacchus), a small primate. By using our method with a suite of growth factors, adult marmoset testis-derived germ cells could be cultured in the form of a floating sphere for several weeks. Notably, this method could be applied not only to freshly isolated cells but also to cryopreserved cell stocks. The spheres enriched spermatogonia and early spermatocytes, and could be assembled from a C-KIT(+) spermatogonial population. Techniques for culturing spermatogonia could facilitate increased understanding of primate reproduction as well as the preservation of valuable biomaterials from nonhuman primates.

  10. The Histone Demethylase FBXL10 Regulates the Proliferation of Spermatogonia and Ensures Long-Term Sustainable Spermatogenesis in Mice.

    PubMed

    Ozawa, Manabu; Fukuda, Tsuyoshi; Sakamoto, Reiko; Honda, Hiroaki; Yoshida, Nobuaki

    2016-04-01

    The F-box and leucine-rich repeat protein 10 (Fbxl10) gene encodes a protein that catalyzes demethylation of H3K4 and H3K36. In this study, we show the important roles of FBXL10 as a histone demethylase in sustainable sperm production using mice in which the JmjC domain of Fbxl10 was deleted (Fbxl10(DeltaJ/DeltaJ)). In histological analysis, testis sections from 10-wk-old Fbxl10(DeltaJ/DeltaJ) mice appeared normal. On the other hand, testes from 7-mo-old Fbxl10(DeltaJ/DeltaJ) mice contained a greater ratio of seminiferous tubules exhibiting degeneration of spermatogenesis. Further analysis using an in vitro spermatogonia culture system, that is, germline stem cells (GSCs), revealed that Fbxl10(DeltaJ/DeltaJ) GSCs expressed a significantly higher level of P21 and P19 mRNA, cyclin-dependent kinase inhibitors and also known as cellular senescence markers, than wild-type (WT) GSCs. Furthermore, the ratio of Fbxl10(DeltaJ/DeltaJ) GSCs in G0/G1 phase was higher and the ratios in S and G2/M phases were lower than the corresponding ratios of WT GSCs, and the doubling speed of Fbxl10(DeltaJ/DeltaJ) GSCs was significantly slower than that of WT GSCs. In addition to these in vitro results, an in vivo study indicated that recovery of spermatogenesis after a transient reduction in the number of testicular germ cells by busulfan treatment was significantly slower in Fbxl10(DeltaJ/DeltaJ) mice than in WT mice. These data suggest that Fbxl10 plays important roles in long-term sustainable spermatogenesis via regulating cell cycle. PMID:26984996

  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. Mice with a targeted disruption of the neurotrophin receptor trkB lose their gustatory ganglion cells early but do develop taste buds.

    PubMed

    Fritzsch, B; Sarai, P A; Barbacid, M; Silos-Santiago, I

    1997-07-01

    The alleged ability of taste afferents to induce taste buds in developing animals is investigated using a mouse model with a targeted deletion of the tyrosine kinase receptor trkB for the neurotrophin BDNF. This neurotrophin was recently shown to be expressed in developing taste buds and the receptor trkB has been shown to be expressed in the developing ganglion cells that innervate the taste buds. Our data show a reduction of geniculate ganglion cells to about 5% of control animals in neonates. Degeneration of ganglion cells starts when processes reach the central target (solitary tract) but before they reach the peripheral target (taste buds). Degeneration of ganglion cells is almost completed in trkB knockout mice before taste afferents reach in control animals the developing fungiform papillae. Four days later the first taste buds can be identified in fungiform papillae of both control and trkB knockout mice in about equal number and density. Many taste buds undergo a normal maturation compared to control animals. However, the more lateral and caudal fungiform papillae grow less in size and become less conspicuous in older trkB knockout mice. No intragemmal innervation can be found in trkB knockout taste buds but a few extragemmal fibers enter the apex and end between taste had cells without forming specialized synapses. Taste buds of trkB knockout mice appear less well organized than those of control mice, but some cells show similar vesicle accumulations as control taste bud cells in their base but no synaptic contact to an afferent. These data strongly suggest that the initial-development of many fungiform papillae and taste buds is independent of the specific taste innervation. It remains to be shown why others appear to be more dependent on proper innervation. PMID:9263033

  14. Loss of Vascular Endothelial Growth Factor A (VEGFA) Isoforms in the Testes of Male Mice Causes Subfertility, Reduces Sperm Numbers, and Alters Expression of Genes That Regulate Undifferentiated Spermatogonia

    PubMed Central

    Lu, Ningxia; Sargent, Kevin M.; Clopton, Debra T.; Pohlmeier, William E.; Brauer, Vanessa M.; McFee, Renee M.; Weber, John S.; Ferrara, Napoleone; Silversides, David W.

    2013-01-01

    Vascular endothelial growth factor A (VEGFA) isoform treatment has been demonstrated to alter spermatogonial stem cell homeostasis. Therefore, we generated pDmrt1-Cre;Vegfa−/− (knockout, KO) mice by crossing pDmrt1-Cre mice to floxed Vegfa mice to test whether loss of all VEGFA isoforms in Sertoli and germ cells would impair spermatogenesis. When first mated, KO males took 14 days longer to get control females pregnant (P < .02) and tended to take longer for all subsequent parturition intervals (9 days; P < .07). Heterozygous males sired fewer pups per litter (P < .03) and after the first litter took 10 days longer (P < .05) to impregnate females, suggesting a more progressive loss of fertility. Reproductive organs were collected from 6-month-old male mice. There were fewer sperm per tubule in the corpus epididymides (P < .001) and fewer ZBTB16-stained undifferentiated spermatogonia (P < .003) in the testes of KO males. Testicular mRNA abundance for Bcl2 (P < .02), Bcl2:Bax (P < .02), Neurog3 (P < .007), and Ret was greater (P = .0005), tended to be greater for Sin3a and tended to be reduced for total Foxo1 (P < .07) in KO males. Immunofluorescence for CD31 and VE-Cadherin showed no differences in testis vasculature; however, CD31-positive staining was evident in undifferentiated spermatogonia only in KO testes. Therefore, loss of VEGFA isoforms in Sertoli and germ cells alters genes necessary for long-term maintenance of undifferentiated spermatogonia, ultimately reducing sperm numbers and resulting in subfertility. PMID:24169552

  15. 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 ...

  16. 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…

  17. 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).

  18. NRG1 and KITL signal downstream of retinoic acid in the germline to support soma-free syncytial growth of differentiating spermatogonia

    PubMed Central

    Chapman, KM; Medrano, GA; Chaudhary, J; Hamra, FK

    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. Similar to the ERBB2/3 agonist NRG1, we found that 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 that NRG1 and KITL activate alternative pathways downstream of retinoic acid signaling in the germline that are essential for stem cells to undergo premeiotic steps of spermatogenesis in culture. Robust serum/soma-free spermatogonial differentiation opens new doors to study mammalian germ cell biology in culture and to discover factors that can drive meiotic progression in vitro. PMID:26500786

  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. 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 ...

  1. 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.

  2. Protein-losing enteropathies in dogs.

    PubMed

    Dossin, Olivier; Lavoué, Rachel

    2011-03-01

    Protein-losing enteropathy is common in dogs but rare in cats. In the vast majority of cases, it is associated with inflammatory bowel disease, intestinal lymphoma, or intestinal lymphangiectasia. The diagnosis is based on identification of hypoalbuminemia and ruling out urinary loss and liver failure. Identification of the intestinal lesion with appropriate biopsy method is important to rule out neoplasm or infectious causes. The treatment is based on intensive nutritional support, therapy for the causative condition, and early monitoring of possibly life-threatening complications, such as hypocobalaminemia, massive pleural or abdominal fluid collection, thromboembolism, and hypocalcemia or hypomagnesemia.

  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. 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

  5. Patients’ perceptions on losing access to FPs

    PubMed Central

    Freeman, Tom; Brown, Judith Belle; Reid, Graham; Stewart, Moira; Thind, Amardeep; Vingilis, Evelyn

    2013-01-01

    Abstract Objective To examine the health care–related experiences of individuals who have lost their FPs. Design A qualitative design using phenomenology. Setting Southwestern Ontario. Participants Eighteen participants (9 women and 9 men, with a mean age of 48.9 years) from urban or rural areas who had lost their FPs. Methods Semistructured interviews were conducted, which were audiotaped and transcribed verbatim. An iterative approach using immersion and crystallization was employed for analysis. Main findings Participants reported having lost their FPs because of reasons specific to their physicians (eg, illness, retirement, career change) or system issues (eg, poor remuneration for FPs, cutbacks in health care leading to physician emigration). Participants described feelings of loss, abandonment, frustration, and anger related to losing their physicians. They expressed concerns about the difficulty of getting prescription medications, lack of continuity of care related to medical records, and preventive care. They faced considerable hurdles in accessing primary health care, turning to walk-in clinics and emergency departments despite concerns about quality and fragmentation of care. Some of those with chronic medical conditions prevailed upon specialists to help meet primary health care needs. Conclusion Losing access to FPs evoked a variety of strong feelings among these participants. They engaged in a number of strategies to meet their primary care needs but not without reservations. In a health care system appropriately built on primary health care, the lack of access to FPs is regarded as the loss of a basic right to care. PMID:23585623

  6. Misinformed leaders lose influence over pigeon flocks.

    PubMed

    Watts, Isobel; Nagy, Máté; Burt de Perera, Theresa; Biro, Dora

    2016-09-01

    In animal groups where certain individuals have disproportionate influence over collective decisions, the whole group's performance may suffer if these individuals possess inaccurate information. Whether in such situations leaders can be replaced in their roles by better-informed group mates represents an important question in understanding the adaptive consequences of collective decision-making. Here, we use a clock-shifting procedure to predictably manipulate the directional error in navigational information possessed by established leaders within hierarchically structured flocks of homing pigeons (Columba livia). We demonstrate that in the majority of cases when leaders hold inaccurate information they lose their influence over the flock. In these cases, inaccurate information is filtered out through the rearrangement of hierarchical positions, preventing errors by former leaders from propagating down the hierarchy. Our study demonstrates that flexible decision-making structures can be valuable in situations where 'bad' information is introduced by otherwise influential individuals. PMID:27624797

  7. Misinformed leaders lose influence over pigeon flocks.

    PubMed

    Watts, Isobel; Nagy, Máté; Burt de Perera, Theresa; Biro, Dora

    2016-09-01

    In animal groups where certain individuals have disproportionate influence over collective decisions, the whole group's performance may suffer if these individuals possess inaccurate information. Whether in such situations leaders can be replaced in their roles by better-informed group mates represents an important question in understanding the adaptive consequences of collective decision-making. Here, we use a clock-shifting procedure to predictably manipulate the directional error in navigational information possessed by established leaders within hierarchically structured flocks of homing pigeons (Columba livia). We demonstrate that in the majority of cases when leaders hold inaccurate information they lose their influence over the flock. In these cases, inaccurate information is filtered out through the rearrangement of hierarchical positions, preventing errors by former leaders from propagating down the hierarchy. Our study demonstrates that flexible decision-making structures can be valuable in situations where 'bad' information is introduced by otherwise influential individuals.

  8. 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.

  9. 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

  10. 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...

  11. 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...

  12. 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...

  13. 21 CFR 182.1745 - Sodium carboxymethylcellu-lose.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 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. 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

  15. Neoparamoeba perurans loses virulence during clonal culture.

    PubMed

    Bridle, Andrew R; Davenport, Danielle L; Crosbie, Philip B B; Polinski, Mark; Nowak, Barbara F

    2015-08-01

    Amoebic Gill Disease affects farmed salmonids and is caused by Neoparamoeba perurans. Clonal cultures of this amoeba have been used for challenge experiments, however the effect of long-term culture on virulence has not been investigated. Here we show, using in vitro and in vivo methods, that a clone of N. perurans which was virulent 70 days after clonal culture lost virulence after 3 years in clonal culture. We propose that this is related either to the lack of attachment to the gills or the absence of an extracellular product, as shown by the lack of cytopathic effect on Chinook salmon embryo cells. The avirulent clonal culture of N. perurans allowed us to propose two potential virulence mechanisms/factors involved in Amoebic Gill Disease and is an invaluable tool for host-pathogen studies of Amoebic Gill Disease. PMID:26008963

  16. Germline stem cells: the first guards of heredity.

    PubMed

    Barroca, Vilma; Fouchet, Pierre

    2008-02-01

    The genes involved in the cellular response to DNA damage are crucial for ensuring DNA integrity during spermatogenesis. In this issue of Cell Stem Cell, Takubo et al. (2008) show that ATM, a key kinase of the DNA damage response, is also involved in maintaining the stem cell potential of undifferentiated spermatogonia.

  17. 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.

  18. 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

  19. 5 CFR 352.205 - Appeal of losing agency.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 352.205 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REEMPLOYMENT RIGHTS Reemployment Rights Based on Movement Between Executive Agencies During Emergencies § 352.205 Appeal of losing agency. An appointing officer who intends to employ with reemployment rights an...

  20. 5 CFR 352.205 - Appeal of losing agency.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 352.205 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REEMPLOYMENT RIGHTS Reemployment Rights Based on Movement Between Executive Agencies During Emergencies § 352.205 Appeal of losing agency. An appointing officer who intends to employ with reemployment rights an...

  1. 5 CFR 352.205 - Appeal of losing agency.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 352.205 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REEMPLOYMENT RIGHTS Reemployment Rights Based on Movement Between Executive Agencies During Emergencies § 352.205 Appeal of losing agency. An appointing officer who intends to employ with reemployment rights an...

  2. 5 CFR 352.205 - Appeal of losing agency.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 352.205 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REEMPLOYMENT RIGHTS Reemployment Rights Based on Movement Between Executive Agencies During Emergencies § 352.205 Appeal of losing agency. An appointing officer who intends to employ with reemployment rights an...

  3. 5 CFR 352.205 - Appeal of losing agency.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 352.205 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REEMPLOYMENT RIGHTS Reemployment Rights Based on Movement Between Executive Agencies During Emergencies § 352.205 Appeal of losing agency. An appointing officer who intends to employ with reemployment rights an...

  4. 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…

  5. 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…

  6. 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 182.1745 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food Substances § 182.1745...

  7. Psychological Adjustment of Adolescents Attempting to Lose or Gain Weight.

    ERIC Educational Resources Information Center

    Rosen, James C.; And Others

    1987-01-01

    Compared the psychological adjustment of high school boys and girls trying to reduce or gain weight. Reducers of both sexes and male gainers exhibited lower physical self-esteem. Girls trying to change weight in either direction showed depression and lower global self-esteem. Girls' decisions to gain or lose weight were influenced by psychological…

  8. 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

  9. 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.

  10. 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.…

  11. 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…

  12. Tumor suppressor gene Rb is required for self-renewal of spermatogonial stem cells in mice

    PubMed Central

    Hu, Yueh-Chiang; de Rooij, Dirk G.; Page, David C.

    2013-01-01

    The retinoblastoma tumor suppressor gene Rb is essential for maintaining the quiescence and for regulating the differentiation of somatic stem cells. Inactivation of Rb in somatic stem cells typically leads to their overexpansion, often followed by increased apoptosis, defective terminal differentiation, and tumor formation. However, Rb’s roles in germ-line stem cells have not been explored. We conditionally disrupted the Rb gene in mouse germ cells in vivo and discovered unanticipated consequences for GFRa1-protein-expressing Asingle (GFRa1+ As) spermatogonia, the major source of male germ-line stem cells. Rb-deficient GFRa1+ As spermatogonia were present at normal density in testes 5 d after birth, but they lacked the capacity for self-renewal, resulting in germ cell depletion by 2 mo of age. Rb deficiency did not affect the proliferative activity of GFRa1+ As spermatogonia, but their progeny were exclusively transit-amplifying progenitor spermatogonia and did not include GFRa1+ As spermatogonia. In addition, Rb deficiency caused prolonged proliferation of progenitor spermatogonia, transiently enlarging this population. Despite these defects, Rb deficiency did not block terminal differentiation into functional sperm; offspring were readily obtained from young males whose germ cell pool was not yet depleted. We conclude that Rb is required for self-renewal of germ-line stem cells, but contrary to its critical roles in somatic stem cells, it is dispensable for their proliferative activity and terminal differentiation. Thus, this study identifies an unexpected function for Rb in maintaining the stem cell pool in the male germ line. PMID:23858447

  13. The ambivalence of losing weight after bariatric surgery.

    PubMed

    Warholm, Christine; Marie Øien, Aud; 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

  14. 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

  15. 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

  16. 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

  17. Fractionation of human spermatogenic cells using STA-PUT gravity sedimentation and their miRNA profiling.

    PubMed

    Liu, Yun; Niu, Minghui; Yao, Chencheng; Hai, Yanan; Yuan, Qingqing; Liu, Yang; Guo, Ying; Li, Zheng; He, Zuping

    2015-01-30

    Human spermatogenic cells have not yet been isolated, and notably, their global miRNA profiles remain unknown. Here we have effectively isolated human spermatogonia, pachytene spermatocytes and round spermatids using STA-PUT velocity sedimentation. RT-PCR, immunocytochemistry and meiosis spread assays revealed that the purities of isolated human spermatogonia, pachytene spermatocytes, and round spermatids were 90%, and the viability of these isolated cells was over 98%. MiRNA microarrays showed distinct global miRNA profiles among human spermatogonia, pachytene spermatocytes, and round spermatids. Thirty-two miRNAs were significantly up-regulated whereas 78 miRNAs were down-regulated between human spermatogonia and pachytene spermatocytes, suggesting that these miRNAs are involved in the meiosis and mitosis, respectively. In total, 144 miRNAs were significantly up-regulated while 29 miRNAs were down-regulated between pachytene spermatocytes and round spermatids, reflecting potential roles of these miRNAs in mediating spermiogenesis. A number of novel binding targets of miRNAs were further identified using various softwares and verified by real-time PCR. Our ability of isolating human spermatogonia, pachytene spermatocytes and round spermatids and unveiling their distinct global miRNA signatures and novel targets could provide novel small RNA regulatory mechanisms mediating three phases of human spermatogenesis and offer new targets for the treatment of male infertility.

  18. 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.

  19. 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.

  20. 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...

  1. 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...

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. Losing images in digital radiology: more than you think.

    PubMed

    Oglevee, Catherine; Pianykh, Oleg

    2015-06-01

    It is a common belief that the shift to digital imaging some 20 years ago helped medical image exchange and got rid of any potential image loss that was happening with printed image films. Unfortunately, this is not the case: despite the most recent advances in digital imaging, most hospitals still keep losing their imaging data, with these losses going completely unnoticed. As a result, not only does image loss affect the faith in digital imaging but it also affects patient diagnosis and daily quality of clinical work. This paper identifies the origins of invisible image losses, provides methods and procedures to detect image loss, and demonstrates modes of action that can be taken to stop the problem from happening. PMID:25514841

  7. [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.

  8. 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

  9. Pathophysiology and clinical presentations of salt-losing tubulopathies.

    PubMed

    Seyberth, Hannsjörg W

    2016-03-01

    At least three renal tubular segments are involved in the pathophysiology of salt-losing tubulopathies (SLTs). Whether the pathogenesis starts either in the thick ascending limb of the loop of Henle (TAL) or in the distal convoluted tubule (DCT), it is the function of the downstream-localized aldosterone sensitive distal tubule (ASDT) to contribute to the adaptation process. In isolated TAL defects (loop disorders) ASDT adaptation is supported by upregulation of DCT, whereas in DCT disorders the ASDT is complemented by upregulation of TAL function. This upregulation has a major impact on the clinical presentation of SLT patients. Taking into account both the symptoms and signs of primary tubular defect and of the secondary reactions of adaptation, a clinical diagnosis can be made that eventually leads to an appropriate therapy. In addition to salt wasting, as occurs in all SLTs, characteristic features of loop disorders are hypo- or isosthenuric polyuria and hypercalciuria, whereas characteristics of DCT disorders are hypokalemia and (symptomatic) hypomagnesemia. In both SLT categories, replacement of urinary losses is the primary goal of treatment. In loop disorders COX inhibitors are also recommended to mitigate polyuria, and in DCT disorders magnesium supplementation is essential for effective treatment. Of note, the combination of a salt- and potassium-rich diet together with an adequate fluid intake is always the basis of long-term treatment in all SLTs.

  10. 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.

  11. 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

  12. Effect of experimental wood addition on hyporheic exchange and thermal dynamics in a losing meadow stream

    NASA Astrophysics Data System (ADS)

    Sawyer, Audrey H.; Cardenas, M. Bayani

    2012-10-01

    Stream restoration structures such as large wood can enhance shallow river-groundwater exchange, or hyporheic exchange, and alter temperature dynamics in restored reaches. We added and then removed channel-spanning logs in a second-order mountain meadow stream to test short-term impacts on hyporheic exchange, streambed temperatures, and surface water temperatures. Based on vertical seepage measurements and numerical simulations of hyporheic fluid and heat flow, large wood addition increased hyporheic exchange and altered streambed temperatures. In this losing stream, meter-scale hyporheic exchange cells formed beneath large wood. Upwelling pore water downstream of logs stabilized diel temperature cycles across <8% of the streambed, creating localized but potentially valuable thermal refuge. Exchange rates were <0.1% of channel discharge—too small to impact the range of diel temperature signals in surface water. However, the lag between downstream and upstream diel temperature signals was slightly greater with large wood, which may indicate that surface storage zones rather than hyporheic storage zones increased thermal retardation. Losing conditions limited the spatial extent and rates of hyporheic exchange near large wood. Impacts of large wood reintroduction on hyporheic exchange depend on ambient groundwater discharge or recharge, streambed permeability, channel Froude number, large wood blockage ratio, and large wood spacing. In many streams, large wood reintroduction may increase hyporheic habitat volume and complexity but may not increase exchange rates enough to alter surface water temperature or chemistry. Surface storage zones such as eddies and pools can still influence heat and solute retention in the channel.

  13. Feedbacks Between Bioclogging and Infiltration in Losing River Systems

    NASA Astrophysics Data System (ADS)

    Newcomer, M. E.; Hubbard, S. S.; Fleckenstein, J. H.; Schmidt, C.; Maier, U.; Thullner, M.; Ulrich, C.; Rubin, Y.

    2014-12-01

    Reduction in riverbed permeability due to biomass growth is a well-recognized yet poorly understood process associated with losing connected and disconnected rivers. Although several studies have focused on riverbed bioclogging processes at the pore-scale, few studies have quantified bioclogging feedback cycles at the scale relevant for water resources management, or at the meander-scale. At this scale, often competing hydrological-biological processes influence biomass dynamics and infiltration. Disconnection begins when declines in the water table form an unsaturated zone beneath the river maximizing seepage. Simultaneously, bioclogging reduces the point-scale infiltration flux and can either limit the nutrient flux and reduce bioclogging, or preferentially focus infiltration elsewhere and enhance bioclogging. These feedbacks are highly dependent on geomorphology and seasonal patterns of discharge and water temperature. To assess the mutual influences of disconnection, biomass growth, and temperature changes on infiltration in a geomorphologically complex river system, we built a 3D numerical model, conditioned on field data, using the reactive-transport simulator MIN3P. Results show that in disconnected regions of the river, biomass growth reduced vertical seepage downward and extended the unsaturated zone length; however these changes were contingent upon disconnection. Mid-way through the seasonal cycle, biomass declined in these same regions due to limited nutrient flux. Seepage and biomass continued to oscillate with a lag correlation of 1 month. Connected regions, however, showed the largest infiltration rates, nutrient fluxes, and concentrations of biomass. Despite the reduction in conductivity from biomass, flow remains high in connected regions because the feedback between bioclogging and infiltration is not as pronounced due to the sharpening hydraulic gradient. Bioclogging ultimately shapes the pattern of flow, however geomorphology dominates the

  14. 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.

  15. 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...

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 'Obesity Gene' Doesn't Affect Ability to Lose Weight: Report

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_161090.html 'Obesity Gene' Doesn't Affect Ability to Lose Weight: ... 21, 2016 (HealthDay News) -- Having the so-called "obesity gene" doesn't affect people's ability to shed ...

  1. 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.

  2. 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.

  3. The niche-derived glial cell line-derived neurotrophic factor (GDNF) induces migration of mouse spermatogonial stem/progenitor cells.

    PubMed

    Dovere, Lisa; Fera, Stefania; Grasso, Margherita; Lamberti, Dante; Gargioli, Cesare; Muciaccia, Barbara; Lustri, Anna Maria; Stefanini, Mario; Vicini, Elena

    2013-01-01

    In mammals, the biological activity of the stem/progenitor compartment sustains production of mature gametes through spermatogenesis. Spermatogonial stem cells and their progeny belong to the class of undifferentiated spermatogonia, a germ cell population found on the basal membrane of the seminiferous tubules. A large body of evidence has demonstrated that glial cell line-derived neurotrophic factor (GDNF), a Sertoli-derived factor, is essential for in vivo and in vitro stem cell self-renewal. However, the mechanisms underlying this activity are not completely understood. In this study, we show that GDNF induces dose-dependent directional migration of freshly selected undifferentiated spermatogonia, as well as germline stem cells in culture, using a Boyden chamber assay. GDNF-induced migration is dependent on the expression of the GDNF co-receptor GFRA1, as shown by migration assays performed on parental and GFRA1-transduced GC-1 spermatogonial cell lines. We found that the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP) is specifically expressed in undifferentiated spermatogonia. VASP belongs to the ENA/VASP family of proteins implicated in actin-dependent processes, such as fibroblast migration, axon guidance, and cell adhesion. In intact seminiferous tubules and germline stem cell cultures, GDNF treatment up-regulates VASP in a dose-dependent fashion. These data identify a novel role for the niche-derived factor GDNF, and they suggest that GDNF may impinge on the stem/progenitor compartment, affecting the actin cytoskeleton and cell migration.

  4. 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

  5. Hiding the plot: parents' moral dilemmas and strategies when helping their overweight children lose weight.

    PubMed

    Andreassen, Pernille; Grøn, Lone; Roessler, Kirsten Kaya

    2013-10-01

    In this study we investigated the moral dilemmas and strategies of a group of Danish parents who were trying to help their overweight children lose weight. Data were drawn from repeated semistructured interviews carried out over a period of 2 years with 12 families with overweight children. Using a narrative approach, we show the moral dilemmas parents found themselves in when trying to further the two seemingly incompatible goals of helping their children lose weight and simultaneously strengthening their self-worth. When the children were young, the parents tried to hide the fact that they needed to lose weight to protect them from feeling stigmatized. As the children grew older, the parents became more forthright about weight loss so the children would take on more responsibility. We suggest that for parents, weight loss is experienced as a risky undertaking because they perceive their children's self-worth as being in jeopardy during the process. PMID:24019307

  6. Testosterone changes during vicarious experiences of winning and losing among fans at sporting events.

    PubMed

    Bernhardt, P C; Dabbs, J M; Fielden, J A; Lutter, C D

    1998-08-01

    Basking in reflected glory, in which individuals increase their self-esteem by identifying with successful others, is usually regarded as a cognitive process that can affect behavior. It may also involve physiological processes, including changes in the production of endocrine hormones. The present research involved two studies of changes in testosterone levels among fans watching their favorite sports teams win or lose. In the first study, participants were eight male fans attending a basketball game between traditional college rivals. In the second study, participants were 21 male fans watching a televised World Cup soccer match between traditional international rivals. Participants provided saliva samples for testosterone assay before and after the contest. In both studies, mean testosterone level increased in the fans of winning teams and decreased in the fans of losing teams. These findings suggest that watching one's heroes win or lose has physiological consequences that extend beyond changes in mood and self-esteem.

  7. Attempts to lose weight among overweight and non-overweight adolescents: a cross-national survey

    PubMed Central

    Ojala, Kristiina; Vereecken, Carine; Välimaa, Raili; Currie, Candace; Villberg, Jari; Tynjälä, Jorma; Kannas, Lasse

    2007-01-01

    Background Despite the global obesity epidemic, few studies have performed cross-national comparisons of adolescents' attempts to lose weight and weight control practices. This study aims to investigate matters mentioned above by weight status in Europe, Israel, and North America. Methods Nationally representative samples of adolescents from over 30 countries completed an anonymous, standardized questionnaire as part of the Health Behaviour in School-aged Children 2001/2002 survey. The prevalence and likelihood of attempts to lose weight were determined. The effect of weight status, self-perception of overweight, age and country of residence upon the likelihood of current attempts to lose weight were evaluated using multilevel multivariate logistic regression in separate analyses for boys and girls. The study also presented the prevalence of weight control practices of overweight and non-overweight adolescents who had controlled their weight in seven countries. Results In general, overweight and obese adolescents were more likely to be engaged in current attempts to lose weight and had tried to control their weight during the past 12 months more often than non-overweight adolescents. Besides weight status, self-perception of overweight and age were significant individual-level factors determining current attempts to lose weight. Country of residence was a significant second-level factor but no clear geographical pattern was found. Several gender-related differences existed. Conclusion The findings indicated that most overweight adolescents were motivated to reduce their weight. The importance of promoting a healthy body image for all adolescents was highlighted by the fact that self-perception of overweight was found to be the most important factor leading to attempts to lose weight. PMID:17935629

  8. Hyporheic exchange and oxygen consumption under losing and gaining flow conditions

    NASA Astrophysics Data System (ADS)

    Arnon, S.; Fox, A.; De Falco, N.; Boano, F.

    2013-12-01

    The exchange of water between the surface and subsurface environments plays a crucial role in hydrological, biogeochemical, and ecological processes. The exchange of water is driven by the local morphology of the streambed (hyporheic exchange) and regional forcing of the hydraulic gradient, which results in losing or gaining flow conditions. We measured the effects of losing and gaining flow conditions on hyporheic exchange fluxes by conducting tracer experiments using a novel laboratory flume system (640 cm long and 30 cm wide) under various combinations of overlying velocities and losing/gaining fluxes. Tracer experiments for measuring hyporheic exchange were done using NaCl as conservative tracer, and dye tracer to visualize the active region where water exchange processes occur. Hyporheic exchange fluxes were analyzed based on a new conceptual framework, which relies on a solute mass balance with sink/source terms due to losing/gaining fluxes to evaluate water exchange between surface flow and streambed sediments. This combination of experimental observations and modeling revealed that hyporheic exchange fluxes under losing and gaining flow conditions was similar. Interfacial transport increases proportional to the square of the overlying velocity, and linearly with increasing fluxes of losing and gaining conditions in the sand bed. When the regional hydraulic forcing becomes larger, the hyporheic exchange becomes smaller. Thus, losing and gaining flow conditions becomes the dominant mechanism of water exchange at a certain flux, which depends on the competitive interaction between the overlying velocity in the stream and the losing/gaining fluxes. This type of coupling is expected to regulate nutrient and contaminant transport and microbial activity in streams and rivers. Indeed, we demonstrated using oxygen distribution along the bedform, which was measured using microelectrodes, that the local hydraulic conditions have a strong influent on microbial activity

  9. Unilateral cryptorchidism induces morphological changes of testes and hyperplasia of Sertoli cells in a dog

    PubMed Central

    Moon, Joon Ho; Yoo, Dae Young; Jo, Young Kwang; Kim, Geon A; Jung, Hyo Young; Choi, Jung Hoon

    2014-01-01

    Cryptorchidism is one of the most common genital defects in dogs. This study investigated the effects of abdominal cryptorchidism on morphology, cell proliferation, and Sertoli cell condition in a dog with spontaneous unilateral cryptorchidism. Elective orchidectomy was performed on the abdominal right testis and the scrotal left testis. Significant reductions in numbers of spermatogonia, spermatocytes, and spermatids were observed in hematoxylin and eosin stained sections of the cryptorchid testis. The size of the epididymal duct was smaller than that of the control testis. Based on Ki67 immunohistochemistry, the proliferative activity of spermatogonia and spermatocytes was significantly decreased in the cryptorchid testis. However, proliferative activity was increased in the epididymal duct. Based on GATA-4 immunohistochemistry, Sertoli cells were relatively resistant to cryptorchidism, and the proliferative activity of Sertoli cells was markedly increased in the cryptorchid testis than in the control testis. These results suggest that spontaneous unilateral cryptorchidism causes morphological defects in spermatogonia and spermatocytes in the testis and changes the size of the efferent ductule of the epididymis. In addition, spontaneous unilateral cryptorchidism increases proliferative activity of Sertoli cells, which may be a predisposing factor for Sertoli cell cancer in cryptorchid testes. PMID:25628730

  10. Novel SCC mutation in a patient of Mexican descent with sex reversal, salt-losing crisis and adrenal failure

    PubMed Central

    Kaur, Jasmeet; Rice, Alan M; O’Connor, Elizabeth; Piya, Anil; Buckler, Bradley

    2016-01-01

    Congenital adrenal hyperplasia (CAH) is caused by mutations in cytochrome P450 side chain cleavage enzyme (CYP11A1 and old name, SCC). Errors in cholesterol side chain cleavage by the mitochondrial resident CYP11A1 results in an inadequate amount of pregnenolone production. This study was performed to evaluate the cause of salt-losing crisis and possible adrenal failure in a pediatric patient whose mother had a history of two previous stillbirths and loss of another baby within a week of birth. CAH can appear in any population in any region of the world. The study was conducted at Memorial University Medical Center and Mercer University School of Medicine. The patient was admitted to Pediatric Endocrinology Clinic due to salt-losing crisis and possible adrenal failure. The patient had CAH, an autosomal recessive disease, due to a novel mutation in exon 5 of the CYP11A1 gene, which generated a truncated protein of 286 amino acids compared with wild-type protein that has 521 amino acids (W286X). Although unrelated, both parents are carriers. Mitochondrial protein import analysis of the mutant CYP11A1 in steroidogenic MA-10 cells showed that the protein is imported in a similar fashion as observed for the wild-type protein and was cleaved to a shorter fragment. However, mutant’s activity was 10% of that obtained for the wild-type protein in non-steroidogenic COS-1 cells. In a patient of Mexican descent, a homozygous CYP11A1 mutation caused CAH, suggesting that this disease is not geographically restricted even in a homogeneous population. Learning points: Novel mutation in CYP11A1 causes CAH; This is a pure population from Central Mexico; Novel mutation created early truncated protein.

  11. Diagnosing protein losing enteropathy: A new approach using Tc-99m human immunoglobulin

    SciTech Connect

    Bhatnagar, A.; Kashyap, R.; Chopra, M.K.

    1995-11-01

    Tc-99m HIG has recently come into prominence as an inflammation seeking radiotracer. The authors describe a novel use of the agent for imaging protein-losing enteropathy. The agent may have certain advantages over Tc-99m HSA, which is currently being used for imaging protein loss. 19 refs., 2 figs.

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

    PubMed

    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.

  13. 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…

  14. 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…

  15. Living with clipped wings-patients' experience of losing a leg.

    PubMed

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

    2013-10-14

    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.

  16. 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…

  17. 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…

  18. 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)

  19. 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

  20. 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…

  1. 20 CFR 663.565 - May an eligible training provider lose its eligibility?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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 2010-04-01 2010-04-01 false May an eligible training provider lose...

  2. No Time to Lose: New York State Summit on Black and Hispanic Children. Year 1 Report.

    ERIC Educational Resources Information Center

    New York State Dept. of Social Services, Albany.

    This report describes the first-year implementation of the New York State Department of Social Services' (DSS) "No Time to Lose" initiative, whose goal is to implement the recommendations of the New York State Summit on Black and Hispanic Children in conjunction with the Governor's declaration of "The Decade of the Child." During the first year of…

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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)

  8. 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.

  9. 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

  10. 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)

  11. 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.

  12. 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

  13. Proliferating cell nuclear antigen as a molecular biomarker for spermatogenesis in PTU-induced hypothyroidism of rats.

    PubMed

    Tousson, Ehab; Ali, Ehab M M; Ibrahim, Wafaa; Mansour, Mohammed A

    2011-07-01

    The thyroid hormone has few serious effects on the testes except during the neonatal stage. There is little knowledge concerning the prolonged effect of thyroid hormone deficiency throughout the rat's life span and its effect on spermatogenesis. Proliferating cell nuclear antigen (PCNA) is a nuclear matrix protein, which is essential for multiple cell cycle pathways. Here we used PCNA immunohistochemistry as a marker to differentiate between the testes of control and hypothyroid rats. About 20 rats were equally divided into 2 groups; the first group was the control group, while the second group was the experimental group in which rats were fed 0.05% 6-n-propyl thiouracil (PTU) in drinking water for 6 weeks. Immunohistochemistry, using an antibody against PCNA, showed at least 3 differences in the pattern of PCNA immunoreactivity (PCNA-ir). First, PCNA-ir was not detected in Sertoli and Leydig cells in the testes of control rats and detected in some of the hypothyroid rats. Second, in the control group more than 96% of spermatogonia were PCNA-positive cells; however, hypothyroidism caused the reduction to approximately 25% PCNA staining in spermatogonia. The third difference was in the abnormal distribution of spermatogonia seen in the hypothyroid rat testis, not in the control one. These results suggest that prepubertal hypothyroidism affects the proliferation of spermatogenic cells leading to impaired spermatogenesis and that PCNA index is a useful marker for assessing germ cell kinetics and spermatogenesis in prepubertal hypothyroidism.

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

    PubMed

    Maurel, Delphine B; Duan, Peipei; 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

  15. 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

  16. Hyporheic exchange in heterogeneous streambeds under losing and gaining flow conditions

    NASA Astrophysics Data System (ADS)

    Arnon, S.; Fox, A.; Laube, G.; Schmidt, C.; Fleckenstein, J. H.

    2015-12-01

    Recent studies have shown that stream-groundwater interactions (gaining or losing flow conditions) have a major impact on hyporheic exchange fluxes. However, the physical complexity of natural streams has limited our ability to study these types of interactions systematically in the field, and to evaluate their importance to biogeochemical processes and nutrient cycling. In this work we were able to quantify the effect of losing and gaining fluxes on hyporheic exchange in heterogeneous streambeds by combining experiments in a laboratory flume and modeling. Tracer experiments were conducted for measuring hyporheic exchange with using a dye and NaCl under various combinations of overlying water velocities and losing or gaining fluxes. The goal of the modeling was to extent and to supplement the hydraulic conditions covered by the flume experiments with a wide range of scenarios. In the model, the surface water domain was represented by a CFD model which generates the head distribution. Subsurface flow and transport is simulated in 3D using MIN3P. The flume experiments revealed that hyporheic exchange fluxes under losing and gaining flow conditions were similar, and became smaller in a comparable manner when the losing or gaining flux increases. Heterogeneity had little effect on hyporheic exchange under gaining flow conditions due to the compaction of the hyporheic zone. However, local hydraulic conductivity led to preferential flow paths of stream water under neutral conditions (strong horizontal flow component) and losing conditions (strong vertical flow component). Preferential flow paths were also evident under gaining conditions but affected mainly the upwelling groundwater. The model was set up to resemble the conditions in the flume, and reproduced the flume data very well. The propagation of dye fronts as observed in the flume is currently implemented into the model. The combination of experimental and modeling results enable us to systematically study the

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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

  5. Protein-losing enteropathy in the human and experimental rat blind-loop syndrome.

    PubMed

    King, C E; Toskes, P P

    1981-03-01

    Protein-losing enteropathy in 2 human subjects with small intestine bacterial overgrowth is reported. Partial improvement in 1 and complete normalization in the 2nd, during long-term antibiotic therapy, demonstrate for the first time antibiotic reversibility of protein-losing enteropathy in the human blind-loop syndrome. Studies in rats with experimental jejunal blind loops revealed depressed serum protein levels and excessive fecal excretion of intravenously administered 51Cr as compared with nonoperated and surgical controls. Comparison of protein loss of rats with blind loops present for varying lengths of time and paired comparison of rats tested for protein loss at two different times revealed a relatively stable degree of protein loss once it was manifest. Reversal of protein loss with antibiotic therapy was accomplished in only a small percentage of rats, and in those only after prolonged therapy. Surgical extirpation of the blind loop from rats with protein-losing enteropathy consistently corrected the protein loss, although this correction was delayed up to 9 wk from the time of corrective surgery. These studies demonstrate (a) significant protein loss as one etiologic factor for protein metabolic disturbances in the human and experimental rat blind-loop syndrome, (b) the occurrence of intestinal protein loss as a manifestation of functionally significant mucosal injury in the contaminated nonstagnant small bowel as well as the stagnant part of the small intestine affected by bacterial overgrowth, and (c) the difficulty of reversing functionally significant mucosal injury in the blind-loop syndrome once it has been manifest.

  6. 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

  7. 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

  8. The significance of losing things for nursing home residents with dementia and their families.

    PubMed

    Powers, Bethel Ann

    2003-11-01

    This article examines the significance of losing things as part of an individual's whole experience with the material aspects of life. The data on which this report is based were drawn from a broader ethnographic study of everyday ethics affecting nursing home residents with dementia. Combined anthropological methods of participant observation and in-depth interviewing were used to gather information about ordinary daily issues for residents, family members, and nursing home staff. Findings are described as themes related to personal possessions and concerns surrounding them. Discussion comprises an interpretive analysis of meanings drawn from the research and represented as ethical considerations and practice implications--general principles and strategies. PMID:14619317

  9. 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.

  10. 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.

  11. Successful diuretics treatment of protein-losing enteropathy in Noonan syndrome.

    PubMed

    Mizuochi, Tatsuki; Suda, Kenji; Seki, Yoshitaka; Yanagi, Tadahiro; Yoshimoto, Hironaga; Kudo, Yoshiyuki; Iemura, Motofumi; Tanikawa, Ken; Matsuishi, Toyojiro

    2015-04-01

    There are few reports on successful high-dose spironolactone treatment of refractory protein-losing enteropathy (PLE) caused by Fontan procedure. We report successful diuretics treatment with spironolactone and furosemide at standard dose, of refractory PLE in a patient with Noonan syndrome and repaired congenital heart disease. This is the first successful application of diuretics treatment in a patient with refractory PLE without Fontan procedure. This case illustrates that diuretics treatment can be the first-line treatment of PLE regardless of the causative physiology, and can be effective in refractory PLE with Noonan syndrome.

  12. The significance of losing things for nursing home residents with dementia and their families.

    PubMed

    Powers, Bethel Ann

    2003-11-01

    This article examines the significance of losing things as part of an individual's whole experience with the material aspects of life. The data on which this report is based were drawn from a broader ethnographic study of everyday ethics affecting nursing home residents with dementia. Combined anthropological methods of participant observation and in-depth interviewing were used to gather information about ordinary daily issues for residents, family members, and nursing home staff. Findings are described as themes related to personal possessions and concerns surrounding them. Discussion comprises an interpretive analysis of meanings drawn from the research and represented as ethical considerations and practice implications--general principles and strategies.

  13. [Protein-losing enteropathy with systemic lupus erythematosus effectively treated with octreotide and medium chain triglyceride diet: A case report].

    PubMed

    Kubo, Makoto; Uchida, Kousuke; Nakashima, Tadaaki; Oda, Seiko; Nakamura, Tomomi; Hashimoto, Shinichi; Watada, Toshiko; Nakamura, Hiroshi; Araki, Jun; Matsuzaki, Masunori; Yano, Masafumi

    2015-01-01

    In January 2009, a 62-year-old man presented with diarrhea, leg edema, and thrombopenia and was admitted to our hospital. The past medical history revealed Sjögren's syndrome and autoimmune hepatitis for which he had been administered prednisolone. On admission, a laboratory examination revealed massive hypoalbuminemia and high levels of C-reactive protein and platelet-associated IgG. Anti-double stranded DNA and anti-Sm antibodies were negative. Analysis of the bone marrow aspirate and Tc-99m albumin scintigraphy findings suggested autoimmune thrombocytopenic purpura (AITP) and protein-losing enteropathy (PLE), respectively. We diagnosed him as SLE, because past immunoserological testing had showed positivity for anti-double stranded DNA antibody and LE cells. Methylprednisolone pulse therapy and intravenous immunoglobulin therapy were ineffective. Rituximab was ineffective against PLE but was effective against AITP. Cyclosporine and Cyclophosphamide were ineffective against PLE. Subcutaneous injection of 200-μg octreotide daily and a medium chain triglyceride (MCT) diet was effective against PLE, and the patient's condition dramatically improved. The effectiveness of octreotide treatment and an MCT diet in the treatment of PLE with SLE is discussed. PMID:26725864

  14. 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.

  15. 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.

  16. Pascal's Wager, infective endocarditis and the "no-lose" philosophy in medicine.

    PubMed

    Shaw, D; Conway, D I

    2010-01-01

    Doctors and dentists have traditionally used antibiotic prophylaxis in certain patient groups in order to prevent infective endocarditis (IE). New guidelines, however, suggest that the risk to patients from using antibiotics is higher than the risk from IE. This paper analyses the relative risks of prescribing and not prescribing antibiotic prophylaxis against the background of Pascal's Wager, the infamous assertion that it is better to believe in God regardless of evidence, because of the prospective benefits should He exist. Many doctors seem to believe the parallel proposition that it is better to prescribe antibiotics, regardless of evidence, because of the prospective benefit conferred upon the patient. This has been called the "no lose philosophy" in medicine: better safe than sorry, even if the evidence inconveniently suggests that following this mantra is potentially more likely to result in sorry than safe. It transpires that, just as Pascal's Wager fails to convince because of a lack of evidence to support it and the costs incurred by trying to believe, so the "belts and braces" approach of prescribing antibiotic prophylaxis is unjustifiable given the actual evidence of potential risk and benefit to the patient. Ultimately, there is no no-lose if your clinical decisions, like Pascal's Wager, are based on faith rather than evidence.

  17. The economic consequences for parents of losing an adult child to AIDS: evidence from Thailand.

    PubMed

    Knodel, John; Im-Em, Wassana

    2004-09-01

    An examination of the economic consequences for older-age parents of losing an adult child to AIDS in Thailand based on quantitative data derived from a key informant study and a direct interview survey with parents yielded the following main findings: (1) parents frequently paid for their children's care and treatment, but government health insurance and to a lesser extent welfare measures helped alleviate these expenses; (2) parental caregiving often disrupted economic activity, although the resulting opportunity costs were limited by the typically short duration of caregiving; (3) parents commonly paid for funeral costs but benefited from funeral society memberships and customary contributions from those attending; (4) only a minority of parents supported AIDS orphans although orphaned grandchildren often ended up with their grandparents; (5) most deceased children had contributed financially to the parental household but only a minority were main providers. Poorer parents, however, were most likely to lose a main provider and experience severe financial hardship; and (6) although poorer parents spent much less on expenses related to the illness and death of their children, they were much more likely than better-off parents to be seriously burdened by these expenses. Programs are needed to address the plight of AIDS parents but should target those who are most susceptible to resulting economic hardship. PMID:15186899

  18. [Having and losing friends: necessary social-emotional competencies in adolescents].

    PubMed

    von Salisch, Maria; Lüpschen, Nadine; Kanevski, Rimma

    2013-01-01

    Supportive friendships are an invaluable resource for adolescents because of their various developmental tasks, but establishing and maintaining them requires particular interpersonal skills. In order to identify social-emotional competencies associated with having and losing friends, N = 206 early adolescents (12-14 years of age) were examined longitudinally right after the transition to secondary school in the beginning of grade 7 and again at the end of this school year. Adolescents who had at least one reciprocal friend at both times were compared to those who lost all their friends over the school year. Repeated-measures MANOVAs indicate effects of time (and development) that underline an increase of self-disclosure, explanations and humor as well as a general decrease of openly aggressive behavior when angry at the friend. Interaction effects suggest that adolescents who lost their friend(s) intensified their use of physically and relationally aggressive behavior and of fantasies of revenge over time while continuously befriended adolescents decreased in their aggressive behavior when coping with anger in their friendships. Adolescents who had friends at both times were more willing to disclose private information whereas the self-disclosure of adolescents who lost their friends stagnated. These results are discussed in terms of deficient social-emotional competencies as the cause and the consequence of losing friends. PMID:23596898

  19. Comparison of information-preserving and information-losing data-compression algorithms for CT images.

    PubMed

    Bramble, J M

    1989-02-01

    Data compression increases the number of images that can be stored on magnetic disks or tape and reduces the time required for transmission of images between stations. Two algorithms for data compression are compared in application to computed tomographic (CT) images. The first, an information-preserving algorithm combining differential and Huffman encoding, allows reconstruction of the original image. A second algorithm alters the image in a clinically acceptable manner. This second algorithm combines two processes: the suppression of data outside of the head or body and the combination of differential and Huffman encoding. Because the final image is not an exact copy, the second algorithm is information losing. Application of the information-preserving algorithm can double or triple the number of CT images that can be stored on hard disk or magnetic tape. This algorithm may also double or triple the speed with which images may be transmitted. The information-losing algorithm can increase storage or transmission speed by a factor of five. The computation time on this system is excessive, but dedicated hardware is available to allow efficient implementation.

  20. Win-Stay-Lose-Learn Promotes Cooperation in the Spatial Prisoner's Dilemma Game

    PubMed Central

    Liu, Yongkui; Chen, Xiaojie; Zhang, Lin; Wang, Long; Perc, Matjaž

    2012-01-01

    Holding on to one's strategy is natural and common if the later warrants success and satisfaction. This goes against widespread simulation practices of evolutionary games, where players frequently consider changing their strategy even though their payoffs may be marginally different than those of the other players. Inspired by this observation, we introduce an aspiration-based win-stay-lose-learn strategy updating rule into the spatial prisoner's dilemma game. The rule is simple and intuitive, foreseeing strategy changes only by dissatisfied players, who then attempt to adopt the strategy of one of their nearest neighbors, while the strategies of satisfied players are not subject to change. We find that the proposed win-stay-lose-learn rule promotes the evolution of cooperation, and it does so very robustly and independently of the initial conditions. In fact, we show that even a minute initial fraction of cooperators may be sufficient to eventually secure a highly cooperative final state. In addition to extensive simulation results that support our conclusions, we also present results obtained by means of the pair approximation of the studied game. Our findings continue the success story of related win-stay strategy updating rules, and by doing so reveal new ways of resolving the prisoner's dilemma. PMID:22363470

  1. The cost of defeat: Capuchin groups travel further, faster and later after losing conflicts with neighbors.

    PubMed

    Crofoot, Margaret C

    2013-09-01

    Although competition between social groups is central to hypotheses about the evolution of human social organization, competitive interactions among group-mates are thought to play a more dominant role in shaping the behavior and ecology of other primate species. However, few studies have directly tested the impact of intergroup conflicts in non-human primates. What is the cost of defeat? To address this question, the movements of six neighboring white-faced capuchin (Cebus capucinus) social groups living on Barro Colorado Island, Panama were tracked simultaneously using an Automated Radio Telemetry System (ARTS), for a period of six months. Groups moved 13% (441 m) further on days they lost interactions compared with days they won interactions. To cover these larger distances, they traveled faster, stopped less frequently, and remained active later in the evening. Defeat also caused groups to alter their patterns of space use. Losing groups had straighter travel paths than winning groups, larger net displacements and were more likely to change their sleeping site. These results demonstrate that losing groups pay increased travel costs and suggest that they forage in low-quality areas. They provide some of the first direct evidence that intergroup conflicts have important energetic consequences for members of competitively unsuccessful primate social groups. A better understanding of how intergroup competition impacts patterns of individual fitness is thus needed to clarify the role that this group-level process plays in shaping the evolution of human- and non-human primate behavior.

  2. An Indigenous Case of Intestinal Capillariasis with Protein-Losing Enteropathy in Korea

    PubMed Central

    Jung, Woon Tae; Kim, Hyun Jin; Min, Hyun Ju; Ha, Chang Yoon; Kim, Hong Jun; Ko, Gyung Hyuck; Na, Byoung-Kuk

    2012-01-01

    We encountered an indigenous case of intestinal capillariasis with protein-losing enteropathy in the Republic of Korea. A 37-year-old man, residing in Sacheon-si, Gyeongsangnam-do, admitted to the Gyeongsang National University Hospital (GNUH) due to long-lasting diarrhea, abdominal pain, anasarca, and weight loss. He recalled that he frequently ate raw fish, especially the common blackish goby (Acanthogobius flavimanus) and has never been abroad. Under the suspicion of protein-losing enteropathy, he received various kinds of medical examinations, and was diagnosed as intestinal capillariasis based on characteristic sectional findings of nematode worms in the biopsied small intestine. Adults, juvenile worms, and eggs were also detected in the diarrheic stools collected before and after medication. The clinical symptoms became much better after treatment with albendazole 400 mg daily for 3 days, and all findings were in normal range in laboratory examinations performed after 1 month. The present study is the 6th Korean case of intestinal capillariasis and the 3rd indigenous one in the Republic of Korea. PMID:23230331

  3. Spermatogonial stem cells from domestic animals: progress and prospects.

    PubMed

    Zheng, Yi; Zhang, Yaqing; Qu, Rongfeng; He, Ying; Tian, Xiue; Zeng, Wenxian

    2014-03-01

    Spermatogenesis, an elaborate and male-specific process in adult testes by which a number of spermatozoa are produced constantly for male fertility, relies on spermatogonial stem cells (SSCs). As a sub-population of undifferentiated spermatogonia, SSCs are capable of both self-renewal (to maintain sufficient quantities) and differentiation into mature spermatozoa. SSCs are able to convert to pluripotent stem cells during in vitro culture, thus they could function as substitutes for human embryonic stem cells without ethical issues. In addition, this process does not require exogenous transcription factors necessary to produce induced-pluripotent stem cells from somatic cells. Moreover, combining genetic engineering with germ cell transplantation would greatly facilitate the generation of transgenic animals. Since germ cell transplantation into infertile recipient testes was first established in 1994, in vivo and in vitro study and manipulation of SSCs in rodent testes have been progressing at a staggering rate. By contrast, their counterparts in domestic animals, despite the failure to reach a comparable level, still burgeoned and showed striking advances. This review outlines the recent progressions of characterization, isolation, in vitro propagation, and transplantation of spermatogonia/SSCs from domestic animals, thereby shedding light on future exploration of these cells with high value, as well as contributing to the development of reproductive technology for large animals.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. Technical and Tactical Aspects that Differentiate Winning and Losing Performances in Elite Male Karate Fighters.

    PubMed

    Vidranski, Tihomir; Sertić, Hrvoje; Jukić, Josefina

    2015-07-01

    The purpose of this research was to identify the fighters' technical and tactical activity indicators in order to determine indicator significance regarding situational efficiency and designation between winning and losing performances in a karate match. We scientifically observed a sample of 274 male contesters of 137 karate matches during the 2008 World Karate Championship in Tokyo. Each individual competitor was observed in maximum of three matches. The matches were recorded using a DVD camera in order to collect data for further analysis, and the sample was further described using 48 technical and tactical indicators of situational efficiency and match outcome variables. The obtained results indicate that a karate match is composed of 91% of non-scoring techniques and 9% of scoring techniques in the total technique frequency. On this basis a significant difference in the situational efficiency between the match winners and the losing contesters has been discovered. Those two groups of fighters exhibit a statistically significant difference (p<0.05) in 11 out of 21 observed variables of situational efficiency in the table of derived situational indicators. A prevalence of non-scoring techniques suggests that energy demand and technical and tactical requirements of a karate match are in the largest extent defined by non-scoring techniques. Therefore, it would be a grave mistake to disregard non-scoring karate techniques in any future situational efficiency studies. It has been discovered that the winners differ from the defeated contesters by a higher level of situational efficiency in their executed techniques, which incorporate versatility, biomechanical and structural complexity, topological diversity and a specific tactical concept of technique use in the attack phase.

  13. Game related statistics which discriminate between winning and losing under-16 male basketball games.

    PubMed

    Lorenzo, Alberto; Gómez, Miguel Ángel; Ortega, Enrique; Ibáñez, Sergio José; Sampaio, Jaime

    2010-01-01

    The aim of the present study was to identify the game-related statistics which discriminate between winning and losing teams in under-16 years old male basketball games. The sample gathered all 122 games in the 2004 and 2005 Under-16 European Championships. The game-related statistics analysed were the free-throws (both successful and unsuccessful), 2- and 3-points field-goals (both successful and unsuccessful) offensive and defensive rebounds, blocks, assists, fouls, turnovers and steals. The winning teams exhibited lower ball possessions per game and better offensive and defensive efficacy coefficients than the losing teams. Results from discriminant analysis were statistically significant and allowed to emphasize several structure coefficients (SC). In close games (final score differences below 9 points), the discriminant variables were the turnovers (SC = -0.47) and the assists (SC = 0.33). In balanced games (final score differences between 10 and 29 points), the variables that discriminated between the groups were the successful 2-point field-goals (SC = -0.34) and defensive rebounds (SC = -0. 36); and in unbalanced games (final score differences above 30 points) the variables that best discriminated both groups were the successful 2-point field-goals (SC = 0.37). These results allowed understanding that these players' specific characteristics result in a different game-related statistical profile and helped to point out the importance of the perceptive and decision making process in practice and in competition. Key pointsThe players' game-related statistical profile varied according to game type, game outcome and in formative categories in basketball.The results of this work help to point out the different player's performance described in U-16 men's basketball teams compared with senior and professional men's basketball teams.The results obtained enhance the importance of the perceptive and decision making process in practice and in competition.

  14. 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

  15. The spermatogonial stem cell niche in the collared peccary (Tayassu tajacu).

    PubMed

    Campos-Junior, Paulo Henrique A; Costa, Guilherme M J; Lacerda, Samyra M S N; Rezende-Neto, José V; de Paula, Ana M; Hofmann, Marie-Claude; de França, Luiz R

    2012-05-01

    In the seminiferous epithelium, spermatogonial stem cells (SSCs) are located in a particular environment called the "niche" that is controlled by the basement membrane, key testis somatic cells, and factors originating from the vascular network. However, the role of Leydig cells (LCs) as a niche component is not yet clearly elucidated. Recent studies showed that peccaries (Tayassu tajacu) present a peculiar LC cytoarchitecture in which these cells are located around the seminiferous tubule lobes, making the peccary a unique model for investigating the SSC niche. This peculiarity allowed us to subdivide the seminiferous tubule cross-sections in three different testis parenchyma regions (tubule-tubule, tubule-interstitium, and tubule-LC contact). Our aims were to characterize the different spermatogonial cell types and to determine the location and/or distribution of the SSCs along the seminiferous tubules. Compared to differentiating spermatogonia, undifferentiated spermatogonia (A(und)) presented a noticeably higher nuclear volume (P < 0.05), allowing an accurate evaluation of their distribution. Immunostaining analysis demonstrated that approximately 93% of A(und) were GDNF receptor alpha 1 positive (GFRA1(+)), and these cells were preferentially located adjacent to the interstitial compartment without LCs (P < 0.05). The expression of colony-stimulating factor 1 was observed in LCs and peritubular myoid cells (PMCs), whereas its receptor was present in LCs and in GFRA1(+) A(und). Taken together, our findings strongly suggest that LCs, different from PMCs, might play a minor role in the SSC niche and physiology and that these steroidogenic cells are probably involved in the differentiation of A(und) toward type A(1) spermatogonia.

  16. The Spermatogonial Stem Cell Niche in the Collared Peccary (Tayassu tajacu)1

    PubMed Central

    Campos-Junior, Paulo Henrique A.; Costa, Guilherme M.J.; Lacerda, Samyra M.S.N.; Rezende-Neto, José V.; de Paula, Ana M.; Hofmann, Marie-Claude; de França, Luiz R.

    2012-01-01

    ABSTRACT In the seminiferous epithelium, spermatogonial stem cells (SSCs) are located in a particular environment called the “niche” that is controlled by the basement membrane, key testis somatic cells, and factors originating from the vascular network. However, the role of Leydig cells (LCs) as a niche component is not yet clearly elucidated. Recent studies showed that peccaries (Tayassu tajacu) present a peculiar LC cytoarchitecture in which these cells are located around the seminiferous tubule lobes, making the peccary a unique model for investigating the SSC niche. This peculiarity allowed us to subdivide the seminiferous tubule cross-sections in three different testis parenchyma regions (tubule-tubule, tubule-interstitium, and tubule-LC contact). Our aims were to characterize the different spermatogonial cell types and to determine the location and/or distribution of the SSCs along the seminiferous tubules. Compared to differentiating spermatogonia, undifferentiated spermatogonia (Aund) presented a noticeably higher nuclear volume (P < 0.05), allowing an accurate evaluation of their distribution. Immunostaining analysis demonstrated that approximately 93% of Aund were GDNF receptor alpha 1 positive (GFRA1+), and these cells were preferentially located adjacent to the interstitial compartment without LCs (P < 0.05). The expression of colony-stimulating factor 1 was observed in LCs and peritubular myoid cells (PMCs), whereas its receptor was present in LCs and in GFRA1+ Aund. Taken together, our findings strongly suggest that LCs, different from PMCs, might play a minor role in the SSC niche and physiology and that these steroidogenic cells are probably involved in the differentiation of Aund toward type A1 spermatogonia. PMID:22262689

  17. Absence of mDazl produces a final block on germ cell development at meiosis.

    PubMed

    Saunders, P T K; Turner, J M A; Ruggiu, M; Taggart, M; Burgoyne, P S; Elliott, D; Cooke, H J

    2003-11-01

    The autosomal gene DAZL is a member of a family of genes (DAZL, DAZ, BOULE), all of which contain a consensus RNA binding domain and are expressed in germ cells. Adult male and female mice null for Dazl lack gametes. In order to define more precisely the developmental stages in germ cells that require Dazl expression, the patterns of germ cell loss in immature male and female wild-type (+/+, WT) and Dazl -/- (DazlKO) mice were analysed. In females, loss of germ cells occurred during fetal life and was coincident with progression of cells through meiotic prophase. In males, testes were recovered from WT and DazlKO males obtained before and during the first wave of spermatogenesis (days 2-19). Mitotically active germ cells were present up to and including day 19. Functional differentiation of spermatogonia associated with detection of c-kit positive cells did not depend upon expression of Dazl. RBMY-positive cells (A, intermediate, B spermatogonia, zygotene and preleptotene spermatocytes) were reduced in DazlKO compared with WT testes. Staining of cell squashes from day 19 testes with anti-gamma-H2AX and anti-SCP3 antibodies showed that germ cells from DazlKO males were unable to progress beyond the leptotene stage of meiotic prophase I. It was concluded that in the absence of Dazl, germ cells can complete mitosis, and embark on functional differentiation but that, in both sexes, progression through meiotic prophase requires this RNA binding protein. PMID:14611631

  18. Immunochemical Detection of Metallothionein in Specific Epithelial Cells of Rat Organs

    NASA Astrophysics Data System (ADS)

    Danielson, Keith G.; Ohi, Seigo; Huang, P. C.

    1982-04-01

    The distribution of a heavy metal binding protein, metallothionein, was studied immunocytochemically by using antimetallothionein antibody and the immunoperoxidase staining technique on histological sections of liver, kidney, intestine, lung, and testis from cadmium-treated rats. These tissues either accumulate heavy metals (e.g., liver, kidney, and testis) or are exposed to metal by ingestion or inhalation (intestine and lung). Staining for metallothionein was observed intracellularly in epithelial parenchymal cells of the liver and kidney; all hepatocytes and most renal tubular cells stained for the protein. Accumulation of metallothionein was not seen in connective tissue cells surrounding either blood vessels or renal tubules. Extracellular localization of metallothionein was also observed in the liver sinusoids and within the lumina of the renal tubules, suggesting a metal transport or excretory function for this protein. Surface columnar epithelial cells of the intestinal villi indicated the presence of metallothionein but connective tissue cells of the lamina propria were negative for the protein. The granular secretory Paneth cells of the small intestine also stained strongly for metallothionein as did respiratory epithelial cells of the lung. In the testis, metallothionein was detected in the Sertoli cells and interstitial cells but not within the spermatogonia. Sertoli cells are closely associated with the developing spermatogonia and appear to serve a nutritive role in spermatogenesis. Because of the secretory, absorptive, or nutritive function of the metallothionein-localizing cells in the organs studied, we suggest that metallothionein may be involved in metal storage or transport in addition to its commonly proposed detoxification role.

  19. 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.

  20. Enrichment of spermatogonial stem cells using side population in teleost.

    PubMed

    Hayashi, Makoto; Sato, Masanao; Nagasaka, Yasuhiko; Sadaie, Sakiko; Kobayashi, Satoru; Yoshizaki, Goro

    2014-07-01

    Spermatogenesis originates from a small population of spermatogonial stem cells; this population can maintain continuous sperm production throughout the life of fish via self-renewal and differentiation. Despite their biological importance, spermatogonial stem cells are not thoroughly characterized because they are difficult to distinguish from their progeny cells that become committed to differentiation. We previously established a novel technique for germ cell transplantation to identify spermatogonial stem cells based on their colonizing activity and their ability to initiate donor-derived gametogenesis in the rainbow trout (Oncorhynchus mykiss). Although spermatogonial stem cells can be retrospectively identified after transplantation, there is currently no technique to prospectively enrich for or purify spermatogonial stem cells. Here, we describe a method for spermatogonial stem cell enrichment using a side population. With optimized Hoechst 33342 staining conditions, we successfully identified side-population cells among type A spermatogonia. Side-population cells were transcriptomically and morphologically distinct from non-side-population cells. To functionally determine whether the transplantable spermatogonial stem cells were enriched in the side-population fraction, we compared the colonization activity of side-population cells with that of non-side-population cells. Colonization efficiency was significantly higher with side-population cells than with non-side-population cells or with total type A spermatogonia. In addition, side-population cells could produce billions of sperm in recipients. These results indicated that transplantable spermatogonial stem cells were enriched in the side-population fraction. This method will provide biological information that may advance our understanding of spermatogonial stem cells in teleosts. Additionally, this technique will increase the efficiency of germ cell transplantation used in surrogate broodstock

  1. 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

  2. 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…

  3. 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…

  4. Why Do Secondary School Students Lose Their Interest in Science? Or Does It Never Emerge? A Possible and Overlooked Explanation

    ERIC Educational Resources Information Center

    Anderhag, Per; Wickman, Per-Olof; Bergqvist, Kerstin; Jakobson, Britt; Hamza, Karim Mikael; Säljö, Roger

    2016-01-01

    In this paper, we review research on how students' interest in science changes through the primary to secondary school transition. In the literature, the findings generally show that primary students enjoy science but come to lose interest during secondary school. As this claim is based mainly on interview and questionnaire data, that is on…

  5. 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...

  6. 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…

  7. Differences in game-related statistics of basketball performance by game location for men's winning and losing teams.

    PubMed

    Gómez, Miguel A; Lorenzo, Alberto; Barakat, Rubén; Ortega, Enrique; Palao, José M

    2008-02-01

    The aim of the present study was to identify game-related statistics that differentiate winning and losing teams according to game location. The sample included 306 games of the 2004-2005 regular season of the Spanish professional men's league (ACB League). The independent variables were game location (home or away) and game result (win or loss). The game-related statistics registered were free throws (successful and unsuccessful), 2- and 3-point field goals (successful and unsuccessful), offensive and defensive rebounds, blocks, assists, fouls, steals, and turnovers. Descriptive and inferential analyses were done (one-way analysis of variance and discriminate analysis). The multivariate analysis showed that winning teams differ from losing teams in defensive rebounds (SC = .42) and in assists (SC = .38). Similarly, winning teams differ from losing teams when they play at home in defensive rebounds (SC = .40) and in assists (SC = .41). On the other hand, winning teams differ from losing teams when they play away in defensive rebounds (SC = .44), assists (SC = .30), successful 2-point field goals (SC = .31), and unsuccessful 3-point field goals (SC = -.35). Defensive rebounds and assists were the only game-related statistics common to all three analyses.

  8. 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

  9. 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

  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. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. No time to lose--high throughput screening to assess nanomaterial safety

    NASA Astrophysics Data System (ADS)

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

    2011-04-01

    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 assist 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.

  20. 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

  1. Profound Reversible Hypogammaglobulinemia Caused by Celiac Disease in the Absence of Protein Losing Enteropathy.

    PubMed

    Ameratunga, Rohan; Barker, Russell William; Steele, Richard Henderson; Deo, Maneka; Woon, See-Tarn; Yeong, Mee Ling; Koopmans, Wikke

    2015-08-01

    When patients with hypogammaglobulinemia are encountered, a vigorous search should be undertaken for secondary treatable causes. Here we describe the first case of a patient with severe asymptomatic hypogammaglobulinemia where the underlying cause was undiagnosed celiac disease. A strict gluten free diet resulted in resolution of her mild long-standing abdominal symptoms and correction of her hypogammaglobulinemia. There was corresponding improvement in her duodenal histology and normalisation of her celiac serology. Protein losing enteropathy was unlikely to have been the mechanism of her profound hypogammaglobulinemia, as her albumin was within the normal range and she had a normal fecal alpha 1 antitrypsin level. Application of the Ameratunga et al. (2013) diagnostic criteria was helpful in confirming this patient did not have Common Variable Immunodeficiency Disorder (CVID). Celiac disease must now be considered in the differential diagnosis of severe hypogammaglobulinemia. There should be a low threshold for undertaking celiac serology in patients with hypogammaglobulinemia, even if they have minimal symptoms attributable to gut disease.

  2. 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

  3. 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.

  4. Stochastic win-stay-lose-shift strategy with dynamic aspirations in evolutionary social dilemmas

    NASA Astrophysics Data System (ADS)

    Amaral, Marco A.; Wardil, Lucas; Perc, Matjaž; da Silva, Jafferson K. L.

    2016-09-01

    In times of plenty expectations rise, just as in times of crisis they fall. This can be mathematically described as a win-stay-lose-shift strategy with dynamic aspiration levels, where individuals aspire to be as wealthy as their average neighbor. Here we investigate this model in the realm of evolutionary social dilemmas on the square lattice and scale-free networks. By using the master equation and Monte Carlo simulations, we find that cooperators coexist with defectors in the whole phase diagram, even at high temptations to defect. We study the microscopic mechanism that is responsible for the striking persistence of cooperative behavior and find that cooperation spreads through second-order neighbors, rather than by means of network reciprocity that dominates in imitation-based models. For the square lattice the master equation can be solved analytically in the large temperature limit of the Fermi function, while for other cases the resulting differential equations must be solved numerically. Either way, we find good qualitative agreement with the Monte Carlo simulation results. Our analysis also reveals that the evolutionary outcomes are to a large degree independent of the network topology, including the number of neighbors that are considered for payoff determination on lattices, which further corroborates the local character of the microscopic dynamics. Unlike large-scale spatial patterns that typically emerge due to network reciprocity, here local checkerboard-like patterns remain virtually unaffected by differences in the macroscopic properties of the interaction network.

  5. 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

  6. 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

  7. Fluctuations of electrical conductivity as a natural tracer for bank filtration in a losing stream

    NASA Astrophysics Data System (ADS)

    Vogt, Tobias; Hoehn, Eduard; Schneider, Philipp; Freund, Anja; Schirmer, Mario; Cirpka, Olaf A.

    2010-11-01

    A key parameter used in the assessment of bank filtration is the travel time of the infiltrated river water during the passage through groundwater. We analyze time series of electrical conductivity (EC) in the river and adjacent groundwater observation wells to investigate travel times of young hyporheic groundwater in adjoining channelized and restored sections of River Thur in North-East Switzerland. To quantify mixing ratios and mean residence times we perform cross-correlation analysis and non-parametric deconvolution of the EC time series. Measurements of radon-222 in the groundwater samples validate the calculated residence times. A simple relationship between travel time and distance to the river has not been observed. Therefore, we speculate that the lateral position and depth of the thalweg as well as the type of bank stabilization might control the infiltration processes in losing rivers. Diurnal oscillations of EC observed in the river and in nearby observation wells facilitate analyzing the temporal variation of infiltration. The diurnal oscillations are particularly pronounced in low flow situations, while the overall EC signal is dominated by individual high-flow events. Differences in travel times derived from diurnal and overall EC signals thus reflect different infiltration regimes.

  8. Metabolic response to feeding in weight-losing pancreatic cancer patients and its modulation by a fish-oil-enriched nutritional supplement.

    PubMed

    Barber, M D; McMillan, D C; Preston, T; Ross, J A; Fearon, K C

    2000-04-01

    Weight-losing patients with advanced cancer often fail to gain weight with conventional nutritional support. This suboptimal response might be explained, in part, by an increased metabolic response to feeding. It has been suggested that eicosapentaenoic acid (EPA) can modify beneficially the metabolic response to cancer. The aim of the present study was to examine the metabolic response to feeding in cancer and the effects of an EPA-enriched oral food supplement on this response. A total of 16 weight-losing, non-diabetic patients with unresectable pancreatic adenocarcinoma and six healthy, weight-stable controls were studied by indirect calorimetry in the fasting and fed states. Body composition was estimated by bioimpedence analysis. Cancer patients were then given a fish-oil-enriched nutritional supplement providing 2 g of EPA and 2550 kJ daily, and underwent repeat metabolic study after 3 weeks of such supplementation. At baseline, resting energy expenditure whether expressed per kg body weight, lean body mass or body cell mass was significantly greater in the cancer patients compared with controls. Fat oxidation was significantly higher in the fasting state in cancer patients [median 1.26 g.kg(-1).min(-1) (interquartile range 0.95-1.38)] than in controls [0.76 g.kg(-1). min(-1) (0.62-0.92); P<0.05]. Over the 4 h feeding period, changes in insulin and glucose concentrations in cancer patients suggested relative glucose intolerance. In response to oral meal feeding, the percentage change in the area under the curve of energy expenditure was significantly lower in the cancer patients [median 7.9% (interquartile range 3.4-9.0)] than in controls [12.6% (9.9-15.1); P<0.01]. After 3 weeks of the EPA-enriched supplement, the body weight of the cancer patients had increased and the energy expenditure in response to feeding had risen significantly [9.6% (6. 3-12.4)], such that it was no different from baseline healthy control values. Similarly, fasting fat oxidation fell

  9. 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.

  10. Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects.

    PubMed

    Seyberth, Hannsjörg W; Schlingmann, Karl P

    2011-10-01

    Salt-losing tubulopathies with secondary hyperaldosteronism (SLT) comprise a set of well-defined inherited tubular disorders. Two segments along the distal nephron are primarily involved in the pathogenesis of SLTs: the thick ascending limb of Henle's loop, and the distal convoluted tubule (DCT). The functions of these pre- and postmacula densa segments are quite distinct, and this has a major impact on the clinical presentation of loop and DCT disorders - the Bartter- and Gitelman-like syndromes. Defects in the water-impermeable thick ascending limb, with its greater salt reabsorption capacity, lead to major salt and water losses similar to the effect of loop diuretics. In contrast, defects in the DCT, with its minor capacity of salt reabsorption and its crucial role in fine-tuning of urinary calcium and magnesium excretion, provoke more chronic solute imbalances similar to the effects of chronic treatment with thiazides. The most severe disorder is a combination of a loop and DCT disorder similar to the enhanced diuretic effect of a co-medication of loop diuretics with thiazides. Besides salt and water supplementation, prostaglandin E2-synthase inhibition is the most effective therapeutic option in polyuric loop disorders (e.g., pure furosemide and mixed furosemide-amiloride type), especially in preterm infants with severe volume depletion. In DCT disorders (e.g., pure thiazide and mixed thiazide-furosemide type), renin-angiotensin-aldosterone system (RAAS) blockers might be indicated after salt, potassium, and magnesium supplementation are deemed insufficient. It appears that in most patients with SLT, a combination of solute supplementation with some drug treatment (e.g., indomethacin) is needed for a lifetime.

  11. 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.

  12. Protein-Losing Enteropathy in Systemic Lupus Erythematosus: 12 Years Experience from a Chinese Academic Center

    PubMed Central

    Xu, Dong; Yang, Hong; Li, Jing; Zhao, Jiu-Liang; Zhang, Heng-Hui; Han, Shao-Mei; Xu, Tao; Zeng, Xiao-Feng

    2014-01-01

    Objective Protein-losing enteropathy (PLE) is a complication in some systemic lupus erythematosus (SLE) patients that is often misdiagnosed. With this study, we provide insight into clinical characteristics, laboratory characteristics, diagnostic tests, risk factors, treatment, and prognosis of the disease. Methods A retrospective, case-control study was performed in 44 patients with SLE-related PLE (PLE group) and 88 patients with active SLE (control group) admitted to our care from January 2000−January 2012. Risk factors for SLE-related PLE were examined, and we analyzed the accuracy of single and combined laboratory characteristics in discriminating SLE-related PLE from active SLE. Serum albumin and C3 levels were measured as outcome during and after treatment with corticosteroids and immunosuppressive agents. Results The PLE group had lower mean serum albumin and 24-hour urine protein levels, higher mean total plasma cholesterol levels, and greater frequencies of anti-SSA and SSB seropositivity compared with the control group. Anti-SSA seropositivity, hypoalbuminemia, and hypercholesterolemia were independent risk factors for SLE-related PLE. The simultaneous presence of serum albumin (<22 g/l) and 24-hour urine protein (<0.8 g/24 h) had high specificity, positive predictive value, negative predictive value, and positive likelihood ratio, a low negative likelihood ratio and no significant reduction in sensitivity. High dosage of glucocorticosteroid combined with cyclophosphomide were mostly prescribed for SLE-related PLE. Conclusion SLE-related PLE should be considered when an SLE patient presents with generalized edema, anti-SSA antibody seropositivity, hypercholesterolemia, severe hypoalbuminemia, and low 24-hour urine protein levels. Aggressive treatment for lupus might improve prognosis. PMID:25490025

  13. 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.

  14. 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

  15. Use it or lose it: enhancing milk production efficiency by frequent milking of dairy cows.

    PubMed

    Wall, E H; McFadden, T B

    2008-03-01

    In the past century, great strides have been made toward optimizing milk production efficiency of dairy cows. One of the key findings that has emerged is that the milk yield of dairy cows is responsive to demands of offspring or milk removal; hence, milk production can be increased by frequent milking. Early studies illustrated the galactopoietic effect of frequent milking during the entire lactation, with 3 times daily milking increasing milk yield by up to 20% relative to twice daily milking. Later studies reported that cows produced more milk during the entire lactation if they were allowed to suckle a calf for the first 3 to 4 mo of lactation. The results of these experiments laid the groundwork for current research, which has identified a time during early lactation wherein the mammary gland of dairy cows is especially receptive to the stimulus of frequent milking. This window of time has been slowly whittled down from the first 10 wk of lactation to the first 6 wk, and it was subsequently established that frequent milking for a short duration within the first 3 wk of lactation can increase milk production through the remainder of lactation [corrected] In addition, there is strong evidence that this milk yield response is locally regulated. Consequently, the concept of "use it or lose it" is becoming more clearly established; that is, the stimulus of frequent milking during early lactation permanently increases the milk production capacity of the mammary gland. Exciting research opportunities now present themselves, and ongoing experiments seek to identify the local factors that are involved in the regulation of milk production efficiency of dairy cows.

  16. 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

  17. 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

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

    PubMed

    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

    2015-11-10

    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 (Gata4(flox/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 Kit(W/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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. Cytotoxic effects of WR-2721 on mouse testicular cells

    SciTech Connect

    Meistrich, M.L.; Finch, M.V.; Hunter, N.; Milas, L.

    1984-09-01

    WR-2721 (S-2-(3-aminopropylamino)ethylphosphorothioic acid) has been demonstrated to be cytotoxic to stem spermatogonia in the mouse. Five and 10 injections of 300 mg/kg killed sufficient numbers of stem cells to reduce sperm production 56 days after treatment by 16 and 43%, respectively. Single injections of 300 or 400 mg/kg of WR-2721 given 15 min after irradiation produced negligible toxicity to stem cells as measured by counts of repopulated tubules; 600 mg/kg reduced stem cell survival by 47%. Four daily injections of 300 mg/kg given 4, 3, 2, and 1 days prior to irradiation reduced stem cell survival by about 60%. The cytotoxic effects of WR-2721 on testicular stem cells at least partially explains the reduced protection factors observed in the testis with low doses of radiation and during fractionated treatments involving multiple injections of drug.

  4. 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

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

    PubMed

    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

  6. 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

  7. 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

  8. The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment.

    PubMed

    Song, Hye-Won; Bettegowda, Anilkumar; Lake, Blue B; Zhao, Adrienne H; Skarbrevik, David; Babajanian, Eric; Sukhwani, Meena; Shum, Eleen Y; Phan, Mimi H; Plank, Terra-Dawn M; Richardson, Marcy E; Ramaiah, Madhuvanthi; Sridhar, Vaishnavi; de Rooij, Dirk G; Orwig, Kyle E; Zhang, Kun; Wilkinson, Miles F

    2016-09-27

    The developmental origins of most adult stem cells are poorly understood. Here, we report the identification of a transcription factor-RHOX10-critical for the initial establishment of spermatogonial stem cells (SSCs). Conditional loss of the entire 33-gene X-linked homeobox gene cluster that includes Rhox10 causes progressive spermatogenic decline, a phenotype indistinguishable from that caused by loss of only Rhox10. We demonstrate that this phenotype results from dramatically reduced SSC generation. By using a battery of approaches, including single-cell-RNA sequencing (scRNA-seq) analysis, we show that Rhox10 drives SSC generation by promoting pro-spermatogonia differentiation. Rhox10 also regulates batteries of migration genes and promotes the migration of pro-spermatogonia into the SSC niche. The identification of an X-linked homeobox gene that drives the initial generation of SSCs has implications for the evolution of X-linked gene clusters and sheds light on regulatory mechanisms influencing adult stem cell generation in general. PMID:27681428

  9. 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.

  10. 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.

  11. 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

  12. Stirred suspension bioreactors as a novel method to enrich germ cells from pre-pubertal pig testis.

    PubMed

    Dores, C; Rancourt, D; Dobrinski, I

    2015-05-01

    To study spermatogonial stem cells the heterogeneous testicular cell population first needs to be enriched for undifferentiated spermatogonia, which contain the stem cell population. When working with non-rodent models, this step requires working with large numbers of cells. Available cell separation methods rely on differential properties of testicular cell types such as expression of specific cell surface proteins, size, density, or differential adhesion to substrates to separate germ cells from somatic cells. The objective of this study was to develop an approach that allowed germ cell enrichment while providing efficiency of handling large cell numbers. Here, we report the use of stirred suspension bioreactors (SSB) to exploit the adhesion properties of Sertoli cells to enrich cells obtained from pre-pubertal porcine testes for undifferentiated spermatogonia. We also compared the bioreactor approach with an established differential plating method and the combination of both: SSB followed by differential plating. After 66 h of culture, germ cell enrichment in SSBs provided 7.3 ± 1.0-fold (n = 9), differential plating 9.8 ± 2.4-fold (n = 6) and combination of both methods resulted in 9.1 ± 0.3-fold enrichment of germ cells from the initial germ cell population (n = 3). To document functionality of cells recovered from the bioreactor, we demonstrated that cells retained their functional ability to reassemble seminiferous tubules de novo after grafting to mouse hosts and to support spermatogenesis. These results demonstrate that the SSB allows enrichment of germ cells in a controlled and scalable environment providing an efficient method when handling large cell numbers while reducing variability owing to handling.

  13. 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)

  14. [Protein losing gastroenteropathy and possible relationship to cytomegalovirus infection: Ménétrier disease in a child].

    PubMed

    Hillman, María M; Meinarde, Leonardo L; Furnes, Raquel A; Daruich, María L; Riva, Verónica; Cuestas, Eduardo

    2013-10-01

    Ménétrier's disease is a childhood protein-losing gastroenteropathy characterized by hypertrophy of the gastric mucosa, of unknown etiology, although most of reported cases have been associated with viral infections. Clinical manifestation is edema and biochemically there are hypoproteinemia and hypoalbuminemia. This disease is very rare in children and they have a benign and self-limiting course in contrast to adults where tend to be chronic and occasionally to become malignant. We present a child with Ménétrier disease with edema and ascites possibly associated with a cytomegalovirus infection.

  15. [Protein losing gastroenteropathy and possible relationship to cytomegalovirus infection: Ménétrier disease in a child].

    PubMed

    Hillman, María M; Meinarde, Leonardo L; Furnes, Raquel A; Daruich, María L; Riva, Verónica; Cuestas, Eduardo

    2013-10-01

    Ménétrier's disease is a childhood protein-losing gastroenteropathy characterized by hypertrophy of the gastric mucosa, of unknown etiology, although most of reported cases have been associated with viral infections. Clinical manifestation is edema and biochemically there are hypoproteinemia and hypoalbuminemia. This disease is very rare in children and they have a benign and self-limiting course in contrast to adults where tend to be chronic and occasionally to become malignant. We present a child with Ménétrier disease with edema and ascites possibly associated with a cytomegalovirus infection. PMID:24092036

  16. 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.

  17. 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.

  18. Theca-specific estrogen receptor-alpha knockout mice lose fertility prematurely.

    PubMed

    Lee, Sungeun; Kang, Dong-Wook; Hudgins-Spivey, Susan; Krust, Andree; Lee, Eun-Young; Koo, Youngbum; Cheon, Yongpil; Gye, Myung Chan; Chambon, Pierre; Ko, ChemYong

    2009-08-01

    Estrogen receptor-alpha (Esr1) mediates estrogen action in regulating at all levels of the hypothalamic-pituitary-ovarian axis. Whereas the importance of Esr1 in hypothalamus and pituitary has been demonstrated by loss of fertility in the neuron- and pituitary-specific Esr1 knockout mice, whether Esr1 plays a critical role in the ovary remains to be determined. In the ovary, Esr1 is mainly expressed in the theca/interstitial cells and germinal epithelium and thus is believed to mediate estrogen action in these cells. In this study, we assessed the importance of Esr1 in the ovarian theca cells in regulating female reproduction. The Cre-LoxP approach was used to selectively delete the Esr1 gene in the theca cells, and the reproductive consequence of the deletion was measured. Adolescent theca-specific Esr1 knockout (thEsr1KO) mice (<4 months of age) are fertile and cycling. However, they begin to display an erratic pattern of estrous cycles and become infertile before they reach the age of 6 months. The ovaries of thEsr1KOmice (>or=4 months) have fewer corpora lutea but more antral follicles than the age-matching wild-type mice. The numbers of 17-hydroxylase-expressing cells are largely increased in the interstitium of the thEsr1KO mouse ovary. Interestingly, whereas basal levels of serum testosterone and FSH were mildly elevated, LH level was either markedly lower or undetectable in the thEsr1KO mice. When superstimulated by exogenous gonadotropins, thEsr1KO mice released significantly fewer oocytes that wild-type littermates and developed multiple hemorrhagic cysts. Taken together, this study demonstrates that theca Esr1 plays a critical role in regulating female reproduction.

  19. 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.

  20. Game-related statistics that discriminated winning and losing teams from the Spanish men's professional basketball teams.

    PubMed

    Angel Gómez, Miguel; Lorenzo, Alberto; Sampaio, Jaime; Ibáñez, Sergio José; Ortega, Enrique

    2008-06-01

    The purpose of the present study was to analyse men's basketball competitions, trying to identify which game-related statistics allow to discriminate winning and losing teams. The sample used corresponded to 306 games from the 2004-2005 Regular Season of the Spanish Men's Professional League. The game-related statistics gathered were: 2 and 3 points field-goals (both successful and unsuccessful), free-throws (both successful and unsuccessful), offensive and defensive rebounds, blocks, assists, fouls, turnovers and steals. The data were analysed in two groups: balanced games (final score differences equal or below 12 points) and unbalanced games (final score differences above 12 points). Discriminant analysis allowed to conclude the following: (i) in balanced games, the variable that best differentiate both groups were the defensive rebounds; (ii) in unbalanced games, the variables that discriminate between both groups were the successful 2 points field-goals, the defensive rebounds and the assists; and (iii) in all games, the statistical analysis identified two variables that discriminate winning and losing teams (defensive rebounds and assists). The defensive rebounds were the only game-related statistic that discriminates both groups in all performed analysis. Coaches and players should be aware of these different profiles in order to increase knowledge about game cognitive and motor solicitation and, therefore, to enhance specificity at the time of practice and game planning.

  1. 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

  2. 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

  3. 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

  4. 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

  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. 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

  7. Germ cell expression of the transcriptional co-repressor TIF1beta is required for the maintenance of spermatogenesis in the mouse.

    PubMed

    Weber, Philipp; Cammas, Florence; Gerard, Christelle; Metzger, Daniel; Chambon, Pierre; Losson, Régine; Mark, Manuel

    2002-05-01

    The gene for transcriptional intermediary factor 1beta (TIF1beta) encodes a transcriptional co-repressor known to play essential roles in chromatin remodeling as well as in early embryonic development. During spermatogenesis, TIF1beta is preferentially associated with heterochromatin structures of Sertoli cells and round spermatids, as well as with meiotic chromosomes. Its expression is tightly regulated within spermatocyte and spermatid populations, and it is undetectable in spermatogonia. Spatiotemporally controlled ablation of TIF1beta by using a germ cell lineage-specific CreER(T)/loxP system leads to testicular degeneration. This degeneration is not due to impairment of chromatin remodeling processes during meiosis and spermiogenesis, as TIF1beta-deficient spermatocytes are able to complete their differentiation into spermatozoa. It rather occurs as a consequence of shedding of immature germ cells (spermatocytes and spermatids), and disappearance of stem spermatogonia. These results indicate that TIF1beta has important functions in the homeostasis of the seminiferous epithelium, and probably plays a crucial role in the network of paracrine interactions between germ cell subpopulations and/or Sertoli cells. PMID:11973266

  8. 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

  9. 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

  10. 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

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

    PubMed Central

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

    2015-01-01

    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

  12. Analysis of the efficacy of possessions in boys' 16-and-under basketball teams: differences between winning and losing teams.

    PubMed

    Ortega, Enrique; Palao, José Manuel; Gómez, Miguel Angel; Lorenzo, Alberto; Cárdenas, David

    2007-06-01

    The purpose of this study was to analyze the ball possessions of winning and losing basketball teams in formative years (16 years and under). The sample was 3,897 ball possessions from 24 games of the boys' 16-and-under finals of the Andalusion Championship, Spain. The variables studied were game outcome, participation, and the initiation and end of each ball possession. Winning teams used more fast breaks and fewer set offenses in their ball possessions. Winning teams had shorter ball possessions and more passes and participating players. Dynamic game styles are necessary in youth basketball, focusing on continuously off-balancing the opponent through fast breaks and a high number of passes in set offenses.

  13. 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

  14. Use it or lose it: molecular evolution of sensory signaling in primates.

    PubMed

    Liman, Emily R

    2006-11-01

    Sensory organs provide key and, in many cases, species-specific information that allows animals to effectively forage, find mates, and avoid hazards. The primary sensors for the vertebrate senses of vision, taste, and smell are G-protein-coupled receptors (GPCRs) expressed by sensory receptor cells that initiate intracellular signal transduction cascades in response to activation by appropriate stimuli. The identification of sensory GPCRs and their related downstream transduction components from a variety of species has provided an essential tool for understanding the molecular evolution of sensory systems. Expansion of the number of genes encoding sensory GPCRs has, in some cases, expanded the repertoire of signals that animals detect, allowing them to occupy new niches, while, in other cases, evolution has favored a reduction in the repertoire of receptors and their cognate signal transduction components when these signals no longer provide a selective advantage. This review will focus on recent studies that have identified molecular changes in vision, smell, taste, and pheromone detection during primate evolution.

  15. 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

  16. Homologous recombination in rat germline stem cells.

    PubMed

    Kanatsu-Shinohara, Mito; Kato-Itoh, Megumi; Ikawa, Masahito; Takehashi, Masanori; Sanbo, Makoto; Morioka, Yuka; Tanaka, Takashi; Morimoto, Hiroko; Hirabayashi, Masumi; Shinohara, Takashi

    2011-07-01

    Spermatogonial stem cells (SSCs) are the only stem cells in the body with germline potential, which makes them an attractive target for germline modification. We previously showed the feasibility of homologous recombination in mouse SSCs and produced knockout (KO) mice by exploiting germline stem (GS) cells, i.e., cultured spermatogonia with SSC activity. In this study, we report the successful homologous recombination in rat GS cells, which can be readily established by their ability to form germ cell colonies on culture plates whose surfaces are hydrophilic and neutrally charged and thus limit somatic cell binding. We established a drug selection protocol for GS cells under hypoxic conditions. The frequency of the homologous recombination of the Ocln gene was 4.2% (2 out of 48 clones). However, these GS cell lines failed to produce offspring following xenogeneic transplantation into mouse testes and microinsemination, suggesting that long-term culture and drug selection have a negative effect on GS cells. Nevertheless, our results demonstrate the feasibility of gene targeting in rat GS cells and pave the way toward the generation of KO rats.

  17. DICER Regulates the Formation and Maintenance of Cell-Cell Junctions in the Mouse Seminiferous Epithelium.

    PubMed

    Korhonen, Hanna Maria; Yadav, Ram Prakash; Da Ros, Matteo; Chalmel, Frédéric; Zimmermann, Céline; Toppari, Jorma; Nef, Serge; Kotaja, Noora

    2015-12-01

    The endonuclease DICER that processes micro-RNAs and small interfering RNAs is essential for normal spermatogenesis and male fertility. We previously showed that the deletion of Dicer1 gene in postnatal spermatogonia in mice using Ngn3 promoter-driven Cre expression caused severe defects in the morphogenesis of haploid spermatid to mature spermatozoon, including problems in cell polarization and nuclear elongation. In this study, we further analyzed the same mouse model and revealed that absence of functional DICER in differentiating male germ cells induces disorganization of the cell-cell junctions in the seminiferous epithelium. We detected discontinuous and irregular apical ectoplasmic specializations between elongating spermatids and Sertoli cells. The defective anchoring of spermatids to Sertoli cells caused a premature release of spermatids into the lumen. Our findings may help also explain the abnormal elongation process of remaining spermatids because these junctions and the correct positioning of germ cells in the epithelium are critically important for the progression of spermiogenesis. Interestingly, cell adhesion-related genes were generally upregulated in Dicer1 knockout germ cells. Claudin 5 ( Cldn5 ) was among the most upregulated genes and we show that the polarized localization of CLAUDIN5 in the apical ectoplasmic specializations was lost in Dicer1 knockout spermatids. Our results suggest that DICER-dependent pathways control the formation and organization of cell-cell junctions in the seminiferous epithelium via the regulation of cell adhesion-related genes. PMID:26510868

  18. LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA

    PubMed Central

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

    2015-01-01

    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 dysfunction of GABAergic neurons. PMID:25601362

  19. 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.

  20. The Fate of Spermatogonial Stem Cells in the Cryptorchid Testes of RXFP2 Deficient Mice

    PubMed Central

    Ferguson, Lydia; How, Javier J.; Agoulnik, Alexander I.

    2013-01-01

    The environmental niche of the spermatogonial stem cell pool is critical to ensure the continued generation of the germ cell population. To study the consequences of an aberrant testicular environment in cryptorchidism we used a mouse model with a deletion of Rxfp2 gene resulting in a high intra-abdominal testicular position. Mutant males were infertile with the gross morphology of the cryptorchid testis progressively deteriorating with age. Few spermatogonia were identifiable in 12 month old cryptorchid testes. Gene expression analysis showed no difference between mutant and control testes at postnatal day 10. In three month old males a decrease in expression of spermatogonial stem cell (SSC) markers Id4, Nanos2, and Ret was shown. The direct counting of ID4+ cells supported a significant decrease of SSCs. In contrast, the expression of Plzf, a marker for undifferentiated and differentiating spermatogonia was not reduced, and the number of PLZF+ cells in the cryptorchid testis was higher in three month old testes, but equal to control in six month old mutants. The PLZF+ cells did not show a higher rate of apoptosis in cryptorchid testis. The expression of the Sertoli cell FGF2 gene required for SSC maintenance was significantly reduced in mutant testis. Based on these findings we propose that the deregulation of somatic and germ cell genes in the cryptorchid testis, directs the SSCs towards the differentiation pathway. This leads to a depletion of the SSC pool and an increase in the number of PLZF+ spermatogonial cells, which too, eventually decreases with the exhaustion of the stem cell pool. Such a dynamic suggests that an early correction of cryptorchidism is critical for the retention of the SSC pool. PMID:24098584

  1. Germ cell transplantation: a potential treatment of severe testicular failure.

    PubMed

    Cozzolino, D J; Lamb, D J

    2000-12-01

    Although the process of spermatogenesis is relatively efficient and resistant to damage, male infertility can result from exposure to toxic agents such as chemotherapeutic regimes, radiation, or occupational exposures to chemicals. Other types of infertility may result from migratory defects or poor survival of primordial germ cells during development, abnormal repopulation of the tubules by spermatogonia during development, or low cellularity of the testis (hypospermatogenesis). Presently, there are no effective therapies available to treat these patients. Recent studies in animal models have demonstrated that isolated testicular germ cells collected from testes may be transplanted into sterile recipient mice to regenerate spermatogenesis. This technology will have widespread applications in efforts to manipulate the genome and produce transgenic offspring, to improve agricultural species, to enhance sperm production in endangered species, to improve our understanding of the control mechanisms regulating spermatogenesis, and to treat male infertility.

  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.

  3. 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

  4. Derivation of male germ cells from ram bone marrow mesenchymal stem cells by three different methods and evaluation of their fate after transplantation into the testis.

    PubMed

    Ghasemzadeh-Hasankolaei, Mohammad; Eslaminejad, Mohammadreza Baghaban; Sedighi-Gilani, Mohammadali

    2016-01-01

    Mesenchymal stem cells (MSCs) have the capacity to differentiate into germ cells (GCs). This research, for the first time, has evaluated the fate of in vitro MSC-derived GCs generated by three different induction methods and compared them after transplantation into the testes of rams. Passage-3 ram bone marrow (BM)-MSCs were divided into three treatment groups: (1) 14-d treatment with 10 μM retinoic acid (RA; RA14), (2) 21-d treatment with 10 μM RA (RA21), and (3) 21-d treatment with 10 ng/ml transforming growth factor beta-1 (TGFb1). After confirmation of the existence of germ-like cells in the culture, the treated cells were labeled and transplanted into the testes of ram lambs. After 2 mo, we conducted histological evaluations of the rams' testes. Results showed that in vitro-derived GCs from all treatment groups survived in the testes. Some of these GCs homed at the basement membrane of seminiferous tubules and formed colonies. The homed cells and cell colonies were similar to testicular native spermatogonia and expressed PGP9.5. TGFb1 exhibited the highest efficiency for in vitro production of GCs as well as the highest capability for homing and colony formation in the testes. RA21 was less efficient than TGFb1, particularly in colony formation. RA14 was the weakest group. No further differentiation of the transplanted GCs was observed. From our results, it could be concluded that a 21-d treatment period of BM-MSCs with TGFb1 is the most efficient method for in vitro generation of spermatogonia-like cells that survive, home, and form colonies in the testes.

  5. Derivation of male germ cells from ram bone marrow mesenchymal stem cells by three different methods and evaluation of their fate after transplantation into the testis.

    PubMed

    Ghasemzadeh-Hasankolaei, Mohammad; Eslaminejad, Mohammadreza Baghaban; Sedighi-Gilani, Mohammadali

    2016-01-01

    Mesenchymal stem cells (MSCs) have the capacity to differentiate into germ cells (GCs). This research, for the first time, has evaluated the fate of in vitro MSC-derived GCs generated by three different induction methods and compared them after transplantation into the testes of rams. Passage-3 ram bone marrow (BM)-MSCs were divided into three treatment groups: (1) 14-d treatment with 10 μM retinoic acid (RA; RA14), (2) 21-d treatment with 10 μM RA (RA21), and (3) 21-d treatment with 10 ng/ml transforming growth factor beta-1 (TGFb1). After confirmation of the existence of germ-like cells in the culture, the treated cells were labeled and transplanted into the testes of ram lambs. After 2 mo, we conducted histological evaluations of the rams' testes. Results showed that in vitro-derived GCs from all treatment groups survived in the testes. Some of these GCs homed at the basement membrane of seminiferous tubules and formed colonies. The homed cells and cell colonies were similar to testicular native spermatogonia and expressed PGP9.5. TGFb1 exhibited the highest efficiency for in vitro production of GCs as well as the highest capability for homing and colony formation in the testes. RA21 was less efficient than TGFb1, particularly in colony formation. RA14 was the weakest group. No further differentiation of the transplanted GCs was observed. From our results, it could be concluded that a 21-d treatment period of BM-MSCs with TGFb1 is the most efficient method for in vitro generation of spermatogonia-like cells that survive, home, and form colonies in the testes. PMID:26395124

  6. Enrichment of Mouse Spermatogonial Stem Cells by the Stem Cell Dye CDy1.

    PubMed

    Kanatsu-Shinohara, Mito; Morimoto, Hiroko; Shinohara, Takashi

    2016-01-01

    Spermatogonial stem cells (SSCs) comprise a small population of germ cells with self-renewal potential. Previous studies have shown that SSCs share several common features with stem cells in other self-renewing tissues, including surface markers and proliferative machinery. However, studies of SSCs are severely handicapped by the small number of SSCs and the lack of SSC-specific markers. In the present study, we examined the utility of CDy1 and Rh123, both of which are used for the collection of stem cells in several self-renewing tissues. CDy1 stained germline stem (GS) cells, cultured spermatogonia enriched for SSC activity, after in vitro incubation without exerting toxic effects. Unlike previously reported stem cell-specific dyes, CDy1 was also useful for enrichment of SSCs in both GS cell culture and mature adult testes. Spermatogonial transplantation showed that ∼1 in 66.7 cells exhibited SSC activity after CDH1-based magnetic cell selection and CDy1 staining. In contrast, although Rh123 was previously used successfully to collect SSCs from cryptorchid testes, it was not possible to recover SSCs from both GS cell cultures and wild-type testes. Thus, CDy1 staining will provide a useful strategy for the enrichment of SSCs and may be used in conjunction with other reagents for the enrichment of SSCs.

  7. 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.

  8. Judgments of Nonverbal Behaviour by Children with High-Functioning Autism Spectrum Disorder: Can They Detect Signs of Winning and Losing from Brief Video Clips?

    ERIC Educational Resources Information Center

    Ryan, Christian; Furley, Philip; Mulhall, Kathleen

    2016-01-01

    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…

  9. Behavioural and neural modulation of win-stay but not lose-shift strategies as a function of outcome value in Rock, Paper, Scissors

    PubMed Central

    Forder, Lewis; Dyson, Benjamin James

    2016-01-01

    Competitive environments in which individuals compete for mutually-exclusive outcomes require rational decision making in order to maximize gains but often result in poor quality heuristics. Reasons for the greater reliance on lose-shift relative to win-stay behaviour shown in previous studies were explored using the game of Rock, Paper, Scissors and by manipulating the value of winning and losing. Decision-making following a loss was characterized as relatively fast and relatively inflexible both in terms of the failure to modulate the magnitude of lose-shift strategy and the lack of significant neural modulation. In contrast, decision-making following a win was characterized as relatively slow and relatively flexible both in terms of a behavioural increase in the magnitude of win-stay strategy and a neural modulation of feedback-related negativity (FRN) and stimulus-preceding negativity (SPN) following outcome value modulation. The win-stay/lose-shift heuristic appears not to be a unified mechanism, with the former relying on System 2 processes and the latter relying on System 1 processes. Our ability to play rationally appears more likely when the outcome is positive and when the value of wins are low, highlighting how vulnerable we can be when trying to succeed during competition. PMID:27658703

  10. 40 CFR 266.240 - How could you lose the conditional exemption for your LLMW and what action must you take?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 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...

  11. 40 CFR 266.240 - How could you lose the conditional exemption for your LLMW and what action must you take?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 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...

  12. 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

  13. 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

  14. Salivary cortisol changes in humans after winning or losing a dominance contest depend on implicit power motivation.

    PubMed

    Wirth, Michelle M; Welsh, Kathryn M; Schultheiss, Oliver C

    2006-03-01

    In two studies, one with an all-male German sample and the other with a mixed-sex U.S. sample, subjects competed in pairs on reaction time-based cognitive tasks. Participants were not aware that contest outcome was experimentally varied. In both studies, implicit power motivation, defined as the non-conscious need to dominate or have impact on others, predicted changes in salivary cortisol from before to after the contest. Increased cortisol post-contest was associated with high levels of power motivation among losers but with low levels of power motivation among winners, suggesting that a dominance success is stressful for low-power individuals, whereas a social defeat is stressful for high-power individuals. These results emerged only in participants tested in the afternoon, possibly because of greater variability in cortisol in the morning due to the rapid decline after the morning peak. These studies add to the evidence that individual differences greatly influence whether a social stressor like losing a contest activates the HPA axis in humans.

  15. 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

  16. 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

  17. NIH Loses a Friend

    MedlinePlus

    ... 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 ...

  18. 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…

  19. 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 ...

  20. 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…

  1. Losing Our Favorite Teacher

    ERIC Educational Resources Information Center

    Bigelow, Bill

    2010-01-01

    Howard Zinn was a brilliant teacher, a passionate activist, and a warm and generous friend. His most influential work, "A People's History of the United States," was a gift to teachers everywhere--an eloquent anti-textbook that pointed the way to an approach to the past that was at once angry, passionate, and hopeful. Corporate textbooks delete…

  2. Direct Lending Loses Momentum.

    ERIC Educational Resources Information Center

    Burd, Stephen

    1997-01-01

    Colleges and universities are finding that improvements in the guaranteed student loan process are making it more attractive than direct lending. In its third year, the direct lending program's total loan volume remains at 33%, well below the 50% goal set in originating legislation. Even some of its strongest supporters fear the program will have…

  3. 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…

  4. Insurers lose court battle

    SciTech Connect

    Lucas, A.

    1994-09-28

    Recent court disputes concerning insurance coverage of Superfund costs have resulted in the retrial of a proinsurer ruling on environmental cleanup costs for potentially responsible parties. The court rejected the insurance industry`s pollution exclusion clause by Aetna and two nonchemical companies. Supposedly this is good news for the chemical industry, because there will be more access to insurance money in Superfund cleanups.

  5. 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

  6. Bmi1 expression in long-term germ stem cells

    PubMed Central

    Komai, Yoshihiro; Tanaka, Toshihiro; Tokuyama, Yoko; Yanai, Hirotsugu; Ohe, Shuichi; Omachi, Taichi; Atsumi, Naho; Yoshida, Naoko; Kumano, Keiki; Hisha, Hiroko; Matsuda, Tadashi; Ueno, Hiroo

    2014-01-01

    Asingle cells in undifferentiated spermatogonia are considered to be the most primitive forms of germ stem cells (GSCs). Although GFRα1 is thought to be a marker of Asingle cells, we found that Bmi1High is more specific than GFRα1 for Asingle cells. Bmi1High expression in Asingle cells is correlated with seminiferous stages, and its expression was followed by the proliferative stage of Asingle GSCs. In contrast, GFRα1 expression was seminiferous stage-independent. Fate analyses of EdU-positive Bmi1High-positive cell-derived Asingle cells revealed that these cells self-renewed or generated transient amplifying Apaired cells. Bmi1High-positive cells were resistant to irradiation-induced injury, after which they regenerated. Elimination of Bmi1High-positive cells from seminiferous tubules resulted in the appearance of tubules with seminiferous stage mismatches. Thus, in this study, we found that Bmi1High is a seminiferous stage-dependent marker for long-term GSCs and that Bmi1High-positive cells play important roles in maintaining GSCs and in regenerating spermatogenic progenitors after injury. PMID:25146451

  7. Use of Stirred Suspension Bioreactors for Male Germ Cell Enrichment.

    PubMed

    Sakib, Sadman; Dores, Camila; Rancourt, Derrick; Dobrinski, Ina

    2016-01-01

    Spermatogenesis is a stem cell based system. Both therapeutic and biomedical research applications of spermatogonial stem cells require a large number of cells. However, there are only few germ line stem cells in the testis, contained in the fraction of undifferentiated spermatogonia. The lack of specific markers makes it difficult to isolate these cells. The long term maintenance and proliferation of nonrodent germ cells in culture has so far been met with limited success, partially due to the lack of highly enriched starting populations. Differential plating, which depends on the differential adhesion properties of testicular somatic and germ cells to tissue culture dishes, has been the method of choice for germ cell enrichment, especially for nonrodent germ cells. However, for large animals, this process becomes labor intensive and increases variability due to the need for extensive handling. Here, we describe the use of stirred suspension bioreactors, as a novel system for enriching undifferentiated germ cells from 1-week-old pigs. This method capitalizes on the adherent properties of somatic cells within a controlled environment, thus promoting the enrichment of progenitor cells with minimal handling and variability.

  8. The regulated elimination of transit-amplifying cells preserves tissue homeostasis during protein starvation in Drosophila testis

    PubMed Central

    Yang, Heiko; Yamashita, Yukiko M.

    2015-01-01

    How tissues adapt to varying nutrient conditions is of fundamental importance for robust tissue homeostasis throughout the life of an organism, but the underlying mechanisms are poorly understood. Here, we show that Drosophila testis responds to protein starvation by eliminating transit-amplifying spermatogonia (SG) while maintaining a reduced pool of actively proliferating germline stem cells (GSCs). During protein starvation, SG die in a manner that is mediated by the apoptosis of somatic cyst cells (CCs) that encapsulate SG and regulate their development. Strikingly, GSCs cannot be maintained during protein starvation when CC-mediated SG death is inhibited, leading to an irreversible collapse of tissue homeostasis. We propose that the regulated elimination of transit-amplifying cells is essential to preserve stem cell function and tissue homeostasis during protein starvation. PMID:25968311

  9. 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.

  10. 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

  11. 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

  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. 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

  14. 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.

  15. 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.

  16. Cryptogenia multifocal ulcerous stenosing enteritis: an entity on its own as a cause of abdominal pain, iron deficiency anemia and protein-losing enteropathy.

    PubMed

    Guisado Vasco, P; Fraile Rodríguez, G

    2014-01-01

    We studied a patient with edema secondary to protein losing enteropathy, and recurrent bouts of bloating and abdominal pain secondary to intestinal subocclusion episodes. After the clinical study, the patient was diagnosed of cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), that is a rare disease, probably caused by mutations in the gene PLA2G4A, and characterized by multiple short stenosis of the small bowel with superficial ulcers, which do not exceed the submucosa layer. Inflammatory bowel disease (Chron's disease), intestinal tuberculosis and intestinal ulcers secondary to non-steroidal anti-inflammatory drugs are the main differential diagnosis. To sum up, physicians should included CMUSE in the differential diagnosis of recurrent abdominal pain, iron deficiency anaemia, occult intestinal bleeding, edema and protein losing enteropathy.

  17. 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

  18. 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

  19. 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

  20. 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. PMID:27419204

  1. 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

  2. Over Expression of NANOS3 and DAZL in Human Embryonic Stem Cells

    PubMed Central

    Panula, Sarita; Reda, Ahmed; Stukenborg, Jan-Bernd; Ramathal, Cyril; Sukhwani, Meena; Albalushi, Halima; Edsgärd, Daniel; Nakamura, Michiko; Söder, Olle; Orwig, Kyle E.; Yamanaka, Shinya; Reijo Pera, Renee A.; Hovatta, Outi

    2016-01-01

    The mechanisms underlying human germ cell development are largely unknown, partly due to the scarcity of primordial germ cells and the inaccessibility of the human germline to genetic analysis. Human embryonic stem cells can differentiate to germ cells in vitro and can be genetically modified to study the genetic requirements for germ cell development. Here, we studied NANOS3 and DAZL, which have critical roles in germ cell development in several species, via their over expression in human embryonic stem cells using global transcriptional analysis, in vitro germ cell differentiation, and in vivo germ cell formation assay by xenotransplantation. We found that NANOS3 over expression prolonged pluripotency and delayed differentiation. In addition, we observed a possible connection of NANOS3 with inhibition of apoptosis. For DAZL, our results suggest a post-transcriptional regulation mechanism in hES cells. In addition, we found that DAZL suppressed the translation of OCT4, and affected the transcription of several genes associated with germ cells, cell cycle arrest, and cell migration. Furthermore, DAZL over expressed cells formed spermatogonia-like colonies in a rare instance upon xenotransplantation. These data can be used to further elucidate the role of NANOS3 and DAZL in germ cell development both in vitro and in vivo. PMID:27768780

  3. 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.

  4. 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

  5. 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.…

  6. Cytoarchitectonical dynamic of Sertoli cells in Melanorivulus punctatus (Cyprinodontiformes: Rivulidae).

    PubMed

    Cassel, Mônica; Neves da Silva, Débora Fabiane; Ferreira, Adelina

    2013-02-01

    The Sertoli cell contributes to spermatogenesis acting in the differentiation of germ cells and being the only somatic cells present in the germinal compartment. So that spermatogenesis is primarily dependent of Sertoli-Sertoli and Sertoli-germ cell interactions once Sertoli cells provide critical factors necessary for a successful differentiation of germ cells to sperm. In teleost fish the cytoplasmic extensions of Sertoli cells support the cysts that remain closed until spermiogenesis. The number of Sertoli cells determines the testicular size, the number of testicular germ cells and the production capacity of spermatozoa. Our objective was to describe the morphology and the cytoarchitectonical dynamic of Sertoli cells in Melanorivulus punctatus, which were collected in the municipality of Chapada dos Guimarães, Mato Grosso, Brazil. The gonads were extracted and prepared according to histological routine for light microscopy and transmission electron microscopy. Sertoli cells have cytoplasmic extensions which provide the conformation of cysts in the interior of the lobes. These cells possess a polymorphic nucleus with a well-defined nuclear envelope and a prominent and eccentric nucleoli. Each cyst is sustained for more than one Sertoli cell and the cysts seem to share the Sertoli cells with each other regardless the stage of development of germ cells within these cysts. This disposal promotes a reticulated arrangement of Sertoli cells. The Sertoli cells lining the ducts assume rectangular shape with rounded nucleus. Thus, the morphological characteristics of Sertoli cells observed did not differ from what has been described for other teleosts. Despite the similarity in the morphology of these cells, we observed that its disposal in the extension of the gonad seems to differ from what is described for fish. The arrangement by which the cytoplasmic extensions of Sertoli cells connect the ends of lobes prevents the proliferation of spermatogonia on the lobe side

  7. 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

  8. 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

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

    PubMed

    Jung, Dajung; Kee, Kehkooi

    2015-01-01

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

  10. The social amoeba Polysphondylium pallidum loses encystation and sporulation, but can still erect fruiting bodies in the absence of cellulose.

    PubMed

    Du, Qingyou; Schaap, Pauline

    2014-09-01

    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.

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

    PubMed Central

    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. 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

  13. 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.

  14. Selective Ablation of Ppp1cc Gene in Testicular Germ Cells Causes Oligo-Teratozoospermia and Infertility in Mice1

    PubMed Central

    Sinha, Nilam; Puri, Pawan; Nairn, Angus C.; Vijayaraghavan, Srinivasan

    2013-01-01

    ABSTRACT The four isoforms of serine/threonine phosphoprotein phosphatase 1 (PP1), derived from three genes, are among the most conserved proteins known. The Ppp1cc gene encodes two alternatively spliced variants, PP1 gamma1 (PPP1CC1) and PP1 gamma2 (PPP1CC2). Global deletion of the Ppp1cc gene, which causes loss of both isoforms, results in male infertility due to impaired spermatogenesis. This phenotype was assumed to be due to the loss of PPP1CC2, which is abundant in testis. While PPP1CC2 is predominant, other PP1 isoforms are also expressed in testis. Given the significant homology between the four PP1 isoforms, the lack of compensation by the other PP1 isoforms for loss of one, only in testis, is surprising. Here we document, for the first time, expression patterns of the PP1 isoforms in postnatal developing and adult mouse testis. The timing and sites of testis expression of PPP1CC1 and PPP1CC2 in testis are nonoverlapping. PPP1CC2 is the only one of the four PP1 isoforms not detected in sertoli cells and spermatogonia. Conversely, PPP1CC2 may be the only PP1 isoform expressed in postmeiotic germ cells. Deletion of the Ppp1cc gene in germ cells at the differentiated spermatogonia stage of development and beyond in Stra8 promoter-driven Cre transgenic mice results in oligo-terato-asthenozoospermia and male infertility, thus phenocopying global Ppp1cc null (−/−) mice. Taken together, these results confirm that spermatogenic defects observed in the global Ppp1cc knockout mice and in mice expressing low levels of PPP1CC2 in testis are due to compromised functions of PPP1CC2 in meiotic and postmeiotic germ cells. PMID:24089200

  15. Immunohistological profile of the Ras homologous B protein (RhoB) in human testes showing normal spermatogenesis, spermatogenic arrest and Sertoli cell only syndrome.

    PubMed

    Adly, Mohamed A; Hussein, Mahmoud Rezk Abdelwahed

    2010-09-01

    Ras homologous B protein (RhoB) belongs to the Ras homologous subfamily which consists of low molecular weight (21 kDa) GTP-binding proteins. Rho proteins are regulatory molecules associated with various kinases and as such they mediate changes in cell shape, contractility, motility and gene expression. To date, no data are available about the expression pattern of RhoB protein in the human testis showing normal and abnormal spermatogenesis. The present study addresses these issues. Human testicular biopsy specimens were obtained from patients suffering from post-testicular infertility (testis showing normal spermatogenesis, 10 cases) and testicular infertility (testis showing Sertoli cell only syndrome and spermatogenic arrest, 10 patients each). The expression of RhoB was examined using in situ immunofluorescent staining methods. In testes showing normal spermatogenesis, RhoB had a strong expression in the seminiferous epithelium (cytoplasm of Sertoli-cells, spermatogonia and spermatocytes) and in the interstitium (Leydig cells). RhoB expression was weak in the myofibroblasts and absent in the spermatids and sperms. In the testes showing abnormal spermatogenesis, RhoB expression was moderate in the seminiferous epithelium (cytoplasm of Sertoli cells, spermatogonia and spermatocytes) and was completely absent in the Leydig cells, myofibroblasts, spermatids and sperms. To the best of our knowledge, this study provides the first morphological indication that RhoB protein is expressed in human testis and its expression undergoes testicular infertility associated changes. These findings suggest the involvement of RhoB in the process of spermatogenesis in human and their possible therapeutic ramifications in testicular infertility are open for further investigations.

  16. Id4 Marks Spermatogonial Stem Cells in the Mouse Testis.

    PubMed

    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.

  17. 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

  18. Cell Polarity As A Regulator of Cancer Cell Behavior Plasticity

    PubMed Central

    Muthuswamy, Senthil K; Xue, Bin

    2013-01-01

    Cell polarization is an evolutionarily conserved process that facilitates asymmetric distribution of organelles and proteins, is an evolutionarily conserved property that is modified dynamically during physiological processes such as cell division, migration, and morphogenesis. The plasticity with which cells change their behavior and phenotype in response to cell intrinsic and extrinsic cues is an essential feature of normal physiology. In disease states such as cancer, cells lose their ability to behave normally in response to physiological cues. A molecular understanding of mechanisms that alter the behavior of cancer cells is limited. Cell polarity proteins are an recognized class of molecules that can receive and interpret both intrinsic and extrinsic signals to modulate cell behavior. In this review, we discuss how cell polarity proteins regulate a diverse array of biological processes and how they can contribute to alterations in the behavior of cancer cells. PMID:22881459

  19. Mouse lymphoblasts lose their immunogenicity and susceptibility to specific cytotoxic T lymphocyte lysis during maintenance in culture.

    PubMed Central

    Leshem, B; Brass, D

    1998-01-01

    This study was undertaken to search for possible mechanisms by which T-cell lines become non-immunogenic and refractory to cellular-mediated lysis during culture. We demonstrate that mouse lymphoblasts (LB) lost their susceptibility to specific cytotoxic T lymphocyte (CTL)-mediated lysis following culture for more than 5 days in the presence interleukin-2 (IL-2), IL-7 but not IL-4. In contrast, the cultured lymphoblasts (CLB) were efficiently lysed by specific antibody and C' and by CTL in the presence of concanavalin A. In addition, CLB did not inhibit cytotoxicity against LB in a cold target competition assay, indicating that CLB and LB differ in the expression of certain surface molecules. Indeed, a significantly lower expression of H-2D class I antigen, the Fas antigen and the adhesion molecules intracelluar adhesion molecule-1 (ICAM-1) and very late activation antigen-4 (VLA-4) was observed on the CLB surface. Consequently, CLB could not form conjugates with specific CTL, a prerequisite for CTL-mediated lysis. In addition, there was a marked decrease in CLB immunogenicity: the cultured cells were unable to stimulate allogeneic spleen cells in mixed lymphocyte culture nor could they induce a cytotoxic response following their injection into allogeneic mice. The reduced immunogenicity enabled the prolonged survival of active CLB in an allogeneic host. We suggest that the extended survival in an allogeneic tumour-bearing host of cultured, hence weakly immunogenic, anti-tumour CTL, will enable them the in vivo implementation of their anti-tumour activity. PMID:9824505

  20. 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

  1. DMRT1 Is Required for Mouse Spermatogonial Stem Cell Maintenance and Replenishment

    PubMed Central

    Zhang, Teng; Oatley, Jon; Bardwell, Vivian J.; Zarkower, David

    2016-01-01

    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

  2. Apoptosis and autophagy as mechanisms of dinoflagellate symbiont release during cnidarian bleaching: every which way you lose.

    PubMed

    Dunn, Simon R; Schnitzler, Christine E; Weis, Virginia M

    2007-12-22

    Cnidarian bleaching results from the breakdown in the symbiosis between the host cnidarian and its dinoflagellate symbiont. Coral bleaching in recent years has increasingly caused degradation and mortality of coral reefs on a global scale. Although much is understood about the environmental causes of bleaching, the underlying cellular mechanisms of symbiont release that drive the process are just beginning to be described. In this study, we investigated the roles of two cellular pathways, host cell apoptosis and autophagy, in the bleaching process of the symbiotic anemone Aiptasia pallida. Host cell apoptosis was experimentally manipulated using gene knockdown of an anemone caspase by RNA interference, chemical inhibition of caspase using ZVAD-fmk and an apoptosis-inducer wortmannin. Autophagy was manipulated by chemical inhibition using wortmannin or induction using rapamycin. The applications of multiple single treatments resulted in some increased bleaching in anemones under control conditions but no significant drop in bleaching in individuals subjected to a hyperthermic stress. These results indicated that no single pathway is responsible for symbiont release during bleaching. However, when multiple inhibitors were applied simultaneously to block both apoptosis and autophagy, there was a significant reduction in bleaching in heat-stressed anemones. Our results allow us to formulate a model for cellular processes involved in the control of cnidarian bleaching where apoptosis and autophagy act together in a see-saw mechanism such that if one is inhibited the other is induced. Similar interconnectivity between apoptosis and autophagy has previously been shown in vertebrates including involvement in an innate immune response to pathogens and parasites. This suggests that the bleaching response could be a modified immune response that recognizes and removes dysfunctional symbionts. PMID:17925275

  3. 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

  4. 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

  5. A novel gene, Pog, is necessary for primordial germ cell proliferation in the mouse and underlies the germ cell deficient mutation, gcd.

    PubMed

    Agoulnik, Alexander I; Lu, Baisong; Zhu, Qichao; Truong, Cavatina; Ty, Maria T; Arango, Nelson; Chada, Kiran K; Bishop, Colin E

    2002-11-15

    Primordial germ cells (PGCs) are the precursor of the germ cells in adult gonads. They arise extra-gonadally and migrate through somatic tissues to the presumptive genital ridges, where they proliferate and differentiate into oogonia or spermatogonia cells. Abnormalities in this developmental process can cause embryonic depletion of germ cells leading to infertility in the adult. We report here that the mouse gcd (germ cell deficient) mutant phenotype, characterized by reduced numbers of PGCs and adult sterility, is due to reduced PGC proliferation rather than aberrant migration and is caused by the partial deletion of a single novel gene, Pog (proliferation of germ cells). Pog is critical for normal PGC proliferation, starting between 9.5 and 10.25 dpc when germ cells begin to migrate to the developing genital ridge. Deletion of Pog is also accompanied by reduced embryonic body weight and, on some genetic backgrounds, embryonic lethality. Thus, in addition to being necessary for PGC proliferation, Pog may have a wider significance in early embryonic development.

  6. 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.

  7. Cancer/testis antigen NY-SAR-35 enhances cell proliferation, migration, and invasion.

    PubMed

    Song, Myung-Ha; Kim, Ye-Rin; Lee, Jun-Won; Lee, Chang-Hun; Lee, Sang-Yull

    2016-02-01

    The cancer/testis antigen NY-SAR-35 is aberrantly expressed in various cancer tissues and cancer cell lines but not in normal tissues except for the testis. A previous study demonstrated that the expression of NY-SAR-35 is activated by hypomethylation in cancer cells. However, the functions of this antigen remain unexplored. In the present study, we investigated the role of NY-SAR‑35 in human embryonic kidney (HEK) 293 cells using exogenous expression system of the gene. NY-SAR‑35 was predominantly expressed at the cytoplasm and was mainly observed in spermatogonia and spermatocytes. Expression of NY-SAR-35 in stable HEK293 transfectant clones was 2-fold higher than the control cells promoting cell growth and proliferation. NY-SAR-35 overexpression also enhanced cell migration and invasion ~2-fold and 4-fold more than the control, respectively. In contrast, small interfering RNA-mediated knockdown of NY-SAR-35 suppressed cell proliferation, migration, and invasion in HEK293 stable transfectants. We concluded that NY-SAR-35 as a cancer/testis antigen enhanced cell proliferation and invasion.

  8. 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

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

    PubMed Central

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

    2015-01-01

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

  10. 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

  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. 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…

  13. 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.

  14. Elucidating the identity and behavior of spermatogenic stem cells in the mouse testis.

    PubMed

    Yoshida, Shosei

    2012-09-01

    Spermatogenesis in mice and other mammalians is supported by a robust stem cell system. Stem cells maintain themselves and continue to produce progeny that will differentiate into sperm over a long period. The pioneering studies conducted from the 1950s to the 1970s, which were based largely on extensive morphological analyses, have established the fundamentals of mammalian spermatogenesis and its stem cells. The prevailing so-called A(single) (A(s)) model, which was originally established in 1971, proposes that singly isolated A(s) spermatogonia are in fact the stem cells. In 1994, the first functional stem cell assay was established based on the formation of repopulating colonies after transplantation in germ cell-depleted host testes, which substantially accelerated the understanding of spermatogenic stem cells. However, because testicular tissues are dissociated into single-cell suspension before transplantation, it was impossible to evaluate the A(s) and other classical models solely by this technique. From 2007 onwards, functional assessment of stem cells without destroying the tissue architecture has become feasible by means of pulse-labeling and live-imaging strategies. Results obtained from these experiments have been challenging the classical thought of stem cells, in which stem cells are a limited number of specialized cells undergoing asymmetric division to produce one self-renewing and one differentiating daughter cells. In contrast, the emerging data suggest that an extended and heterogeneous population of cells exhibiting different degrees of self-renewing and differentiating probabilities forms a reversible, flexible, and stochastic stem cell system as a population. These features may lead to establishment of a more universal principle on stem cells that is shared by other systems.

  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. A Comparison Model of Reinforcement-Learning and Win-Stay-Lose-Shift Decision-Making Processes: A Tribute to W.K. Estes

    PubMed Central

    Worthy, Darrell A.; Maddox, W. Todd

    2013-01-01

    W.K. Estes often championed an approach to model development whereby an existing model was augmented by the addition of one or more free parameters, and a comparison between the simple and more complex, augmented model determined whether the additions were justified. Following this same approach we utilized Estes’ (1950) own augmented learning equations to improve the fit and plausibility of a win-stay-lose-shift (WSLS) model that we have used in much of our recent work. Estes also championed models that assumed a comparison between multiple concurrent cognitive processes. In line with this, we develop a WSLS-Reinforcement Learning (RL) model that assumes that the output of a WSLS process that provides a probability of staying or switching to a different option based on the last two decision outcomes is compared with the output of an RL process that determines a probability of selecting each option based on a comparison of the expected value of each option. Fits to data from three different decision-making experiments suggest that the augmentations to the WSLS and RL models lead to a better account of decision-making behavior. Our results also support the assertion that human participants weigh the output of WSLS and RL processes during decision-making. PMID:25214675

  17. Pigeons Show Near-Optimal Win-Stay/Lose-Shift Performance on a Simultaneous-Discrimination, Midsession Reversal Task with Short Intertrial Intervals

    PubMed Central

    Rayburn-Reeves, Rebecca M.; Laude, Jennifer R.; Zentall, Thomas R.

    2013-01-01

    Discrimination reversal tasks have been used as a measure of species flexibility in dealing with changes in reinforcement contingency. The simultaneous-discrimination, midsession reversal task is one in which one stimulus (S1) is correct for the first 40 trials of an 80-trial session and the other stimulus (S2) is correct for the remaining trials. After many sessions of training with this task, pigeons show a curious pattern of choices. They begin to respond to S2 well before the reversal point (they make anticipatory errors) and they continue to respond to S1 well after the reversal (they make perseverative errors). That is, they appear to be using the passage of time or number of trials into the session as a cue to reverse. We tested the hypothesis that these errors resulted in part from a memory deficit (the inability to remember over the intertrial interval, ITI, both the choice on the preceding trial and the outcome of that choice) by manipulating the duration of the ITI (1.5, 5, and 10 s). We found support for the hypothesis as pigeons with a short 1.5-s ITI showed close to optimal win-stay/lose-shift accuracy. PMID:23123672

  18. 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.

  19. Basigin null mutant male mice are sterile and exhibit impaired interactions between germ cells and Sertoli cells

    PubMed Central

    Bi, Jiajia; Li, Yanfen; Sun, Fengyun; Saalbach, Anja; Klein, Claudia; Miller, David J.; Hess, Rex; Nowak, Romana A.

    2013-01-01

    Basigin (BSG) is a multifunctional glycoprotein that plays an important role in male reproduction since male knockout (KO) mice are sterile. The Bsg KO testis lacks elongated spermatids and mature spermatozoa, a phenotype similar to that of alpha-mannosidase IIx (MX) KO mice. MX regulates formation of N-acetylglucosamine (GlcNAc) terminated N-glycans that participate in germ cell-Sertoli cell adhesion. Results showed that Bsg KO spermatocytes displayed normal homologous chromosome synapsis and progression through meiosis. However, only punctate expression of the round spermatid marker SP-10 in the acrosomal granule of germ cells of Bsg KO mice was detected indicating that spermatogenesis in Bsg KO mice was arrested at the early round spermatid stages. We observed a large increase in the number of germ cells undergoing apoptosis in Bsg KO testes. Using lectin blotting, we determined that GlcNAc terminated N-glycans are linked to BSG. GlcNAc terminated N-glycans were significantly reduced in Bsg KO testes. These observations indicate that BSG may act as a germ cell-Sertoli cell attachment molecule. Loss of BSG significantly reduced adhesion between GC-2 and SF7 cells. Moreover, wild type testes showed strong expression of N-cadherin (CDH2) while expression was greatly reduced in the testes of Bsg KO mice. In addition, the integrity of the blood-testis barrier (BTB) was compromised in Bsg KO testes. In conclusion, although some Bsg KO spermatogonia can undergo normal progression to the spermatocyte stage, BSG-mediated germ cell-Sertoli cell interactions appear to be necessary for integrity of the BTB and spermatocyte progression to mature spermatozoa. PMID:23727514

  20. 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

  1. 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:…

  2. 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…

  3. The Dropout Problem: Losing Ground

    ERIC Educational Resources Information Center

    Barton, Paul E.

    2006-01-01

    During the last two decades, estimates from the U.S. Census Bureau have suggested that the U.S. high school completion rate was steadily rising and nearing 90 percent. In the last few years, however, estimates from independent researchers have contradicted this rosy picture and found much lower completion rates ranging from 66.1 percent to 74.4…

  4. 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.

  5. 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

  6. Cell population indexes of spermatogenic yield and testicular sperm reserves in adult jaguars (Panthera onca).

    PubMed

    de Azevedo, Maria Helena Ferreira; de Paula, Tarcízio Antônio Rego; Matta, Sérgio Luis Pinto da; Fonseca, Cláudio César; da Costa, Eduardo Paulino; Costa, Deiler Sampaio; Peixoto, Juliano Vogas

    2010-03-01

    The intrinsic yield of spermatogenesis and supporting capacity of Sertoli cells are the desirable indicators of sperm production in a species. The objective of the present study was to quantify intrinsic yield and the Sertoli cell index in the spermatogenic process and estimate testicular sperm reserves by histological assessment of fragments obtained by testicular biopsy of five adult jaguars in captivity. The testicular fragments were fixed in 4% glutaric aldehyde, dehydrated at increasing alcohol concentrations, included into hydroxyethyl methacrylate, and were cut into 4 microm thickness. In the seminiferous epithelium of the jaguar, 9.2 primary spermatocytes in pre-leptotene were produced by "A" spermatogonia. During the meiotic divisions only 3.2 spermatids were produced by a primary spermatocyte. The general spermatogenic yield of the jaguar was about 23.4 cells and each Sertoli cell was able to maintain about 19.2 germ cells, 11 of them were round spermatids. In each seminiferous epithelium cycle about 166 million spermatozoa were produced by each gram of testicular tissue. In adult jaguars, the general spermatogenic yield was similar to the yield observed in pumas, greater than that observed for the domestic cat, but less compared to most domestic animals.

  7. 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

  8. 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

  9. Simplified isolation and enrichment of spermatogonial stem-like cells from pubertal domestic cats (Felis catus).

    PubMed

    Tiptanavattana, Narong; Techakumphu, Mongkol; Tharasanit, Theerawat

    2015-11-01

    The efficiency of spermatogonial stem cell (SSC) isolation and culture from pubertal donors is currently poor primarily, because of contamination with other testicular cells. This study aimed to purify SSC-like cells using different extracellular matrixes and a discontinuous gradient density. In experiment 1, testes (n=6) were analyzed for histology and SSC-related protein expressions (laminin, SSEA-4, DDX-4 and GFRα-1). After enzymatic digestion, the cell suspension was plated onto either a laminin- or gelatin-coated dish. The number of SSC-like cells was determined at 15, 30 and 60 min of culture (experiment 2). Experiment 3 was performed to test whether or not the additional step of Percoll gradient density centrifugation could really improve purification of SSC-like cells. Testicular histology revealed complete spermatogenesis with laminin expression essentially at the basal lamina of the seminiferous tubules. SSEA-4 and GFRα-1 co-localized with DDX-4 in the spermatogonia. The relative percentage of SSC-like cells, as determined by cells expressing SSEA-4 (59.42 ± 2.18%) and GFRα-1 (42.70 ± 1.28%), revealed that the highest SSC-like cell purity was obtained with the 15-min laminin-coated dish compared with other incubation times and gelatin treatment (P<0.05). Percoll treatment prior to laminin selection (15 min) significantly improved SSC-like cell recovery (91.33 ± 0.14%, P<0.001) and purity (83.82 ± 2.05% for SSEA-4 and 64.39 ± 1.51% for GFRα-1, P<0.05). These attached cells demonstrated a typical SSC-like cell morphology and also expressed POU5F1, RET and ZBTB16 mRNA. In conclusion, double enrichment with Percoll gradient density centrifugation and laminin plating highly enriched the SSC-like cells population.

  10. 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

  11. 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

  12. 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

  13. 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

  14. SpolvlgA is a DDX3/PL10-related DEAD-box RNA helicase expressed in blastomeres and embryonic cells in planarian embryonic development

    PubMed Central

    Solana, Jordi; Romero, Rafael

    2009-01-01

    Planarian flatworms have an impressive regenerative power. Although their embryonic development is still poorly studied and is highly derived it still displays some simple characteristics. We have identified SpolvlgA, a Schmidtea polychroa homolog of the DDX3/PL10 DEAD-box RNA helicase DjvlgA from the planarian species Dugesia japonica. This gene has been previously described as being expressed in planarian adult stem cells (neoblasts), as well as the germ line. Here we present the expression pattern of SpolvlgA in developing embryos of S. polychroa and show that it is expressed from the first cleavage rounds in blastomere cells and blastomere-derived embryonic cells. These cells are undifferentiated cells that engage in a massive wave of differentiation during stage 5 of development. SpolvlgA expression highlights this wave of differentiation, where nearly all previous structures are substituted by blastomere-derived embryonic cells. In late stages of development SpolvlgA is expressed in most proliferating and differentiating cells. Thus, SpolvlgA is a gene expressed in planarian embryos from the first stages of development and a good marker for the zygote-derived cell lineage in these embryos. Expression in adult worms is also monitored and is found in the planarian germ line, where it is showed to be expressed in spermatogonia, spermatocytes and differentiating spermatids. PMID:19159016

  15. Propagation of human germ stem cells in long-term culture

    PubMed Central

    Akhondi, Mohammad Mehdi; Mohazzab, Arash; Jeddi-Tehrani, Mahmood; Sadeghi, Mohammad Reza; Eidi, Akram; Khodadadi, Abbas; Piravar, Zeinab

    2013-01-01

    Background: Spermatogonial stem cells (SSCs), a subset of undifferentiated type A spermatogonia, are the foundation of complex process of spermatogenesis and could be propagated in vitro culture conditions for long time for germ cell transplantation and fertility preservation. Objective: The aim of this study was in vitro propagation of human spermatogonial stem cells (SSCs) and improvement of presence of human Germ Stem Cells (hGSCs) were assessed by specific markers POU domain, class 5, transcription factor 1 (POU5F1), also known as Octamer-binding transcription factor 4 (Oct-4) and PLZF (Promyelocytic leukaemia zinc finger protein). Materials and Methods: Human testicular cells were isolated by enzymatic digestion (Collagenase IV and Trypsin). Germ cells were cultured in Stem-Pro 34 media supplemented by growth factors such as glial cell line-derived neurotrophic factor, basic fibroblast growth factor, epidermal growth factor and leukemia inhibitory factor to support self-renewal divisions. Germline stem cell clusters were passaged and expanded every week. Immunofluorecent study was accomplished by Anti-Oct4 antibody through the culture. The spermatogonial stem cells genes expression, PLZF, was studied in testis tissue and germ stem cells entire the culture. Results: hGSCs clusters from a brain dead patient developed in testicular cell culture and then cultured and propagated up to 6 weeks. During the culture Oct4 were a specific marker for identification of hGSCs in testis tissue. Expression of PLZF was applied on RNA level in germ stem cells. Conclusion: hGSCs indicated by SSCs specific marker can be cultured and propagated for long-term in vitro conditions. This article extracted from Ph.D. Thesis. (Zeinab Piravar) PMID:24639790

  16. Late morfofunctional alterations of the Sertoli cell caused by doxorubicin administered to prepubertal rats

    PubMed Central

    2012-01-01

    Background Doxorubicin is a potent chemotherapeutic drug used against a variety of cancers. It acts through interaction with polymerases and topoisomerase II and free radical production. Doxorubicin activity is not specific to cancer cells and can also damage healthy cells, especially those undergoing rapid proliferation, such as spermatogonia. In previous studies our group showed that etoposide, another topoisomarese II poison, causes irreversible damage to Sertoli cells. Thus, the aim of this study was to address the effects of doxorubicin on Sertoli cell morphology and function and on the seminiferous epithelium cycle when administered to prepubertal rats. Methods Prepubertal rats received the dose of 5 mg/Kg of doxorubicin, which was fractioned in two doses: 3 mg/Kg at 15dpp and 2 mg/Kg at 22dpp. The testes were collected at 40, 64 and 127dpp, fixed in Bouin’s liquid and submitted to transferrin immunolabeling for Sertoli cell function analysis. Sertoli cell morphology and the frequency of the stages of the seminiferous epithelium cycle were analyzed in PAS + H-stained sections. Results The rats treated with doxorubicin showed reduction of transferrin labeling in the seminiferous epithelium at 40 and 64dpp, suggesting that Sertoli cell function is altered in these rats. All doxorubicin-treated rats showed sloughing and morphological alterations of Sertoli cells. The frequency of the stages of the seminiferous epithelium cycle was also affected in all doxorubicin-treated rats. Conclusions and discussion These data show that doxorubicin administration during prepuberty causes functional and morphological late damage to Sertoli cells; such damage is secondary to the germ cell primary injury and contributed to enhance the spermatogenic harm caused by this drug. However, additional studies are required to clarify if there is also a direct effect of doxorubicin on Sertoli cells producing a primary damage on these cells. PMID:22967030

  17. Spermatogonial Stem Cell Markers and Niche in Equids

    PubMed Central

    Costa, Guilherme M. J.; Avelar, Gleide F.; Rezende-Neto, José V.; Campos-Junior, Paulo Henrique A.; Lacerda, Samyra M. S. N.; Andrade, Bruno S. C.; Thomé, Ralph Gruppi; Hofmann, Marie-Claude; Franca, Luiz R.

    2012-01-01

    Spermatogonial stem cells (SSCs) are the foundation of spermatogenesis and are located in a highly dynamic microenvironment called “niche” that influences all aspects of stem cell function, including homing, self-renewal and differentiation. Several studies have recently identified specific proteins that regulate the fate of SSCs. These studies also aimed at identifying surface markers that would facilitate the isolation of these cells in different vertebrate species. The present study is the first to investigate SSC physiology and niche in stallions and to offer a comparative evaluation of undifferentiated type A spermatogonia (Aund) markers (GFRA1, PLZF and CSF1R) in three different domestic equid species (stallions, donkeys, and mules). Aund were first characterized according to their morphology and expression of the GFRA1 receptor. Our findings strongly suggest that in stallions these cells were preferentially located in the areas facing the interstitium, particularly those nearby blood vessels. This distribution is similar to what has been observed in other vertebrate species. In addition, all three Aund markers were expressed in the equid species evaluated in this study. These markers have been well characterized in other mammalian species, which suggests that the molecular mechanisms that maintain the niche and Aund/SSCs physiology are conserved among mammals. We hope that our findings will help future studies needing isolation and cryopreservation of equids SSCs. In addition, our data will be very useful for studies that aim at preserving the germplasm of valuable animals, and involve germ cell transplantation or xenografts of equids testis fragments/germ cells suspensions. PMID:22937157

  18. 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

  19. 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

  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.

    PubMed

    Yonehara, Takehiro; Takatsuka, Kazuo

    2012-12-14

    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)], 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 electron wavepacket

  1. BNC1 is required for maintaining mouse spermatogenesis

    PubMed Central

    Zhang, Xiaohong; Chou, Weichin; Haig-Ladewig, Lisa; Zeng, Wenxian; Cao, Wenlei; Gerton, George; Dobrinski, Ina; Tseng, Hung

    2012-01-01

    Basonuclin (BNC1) is a zinc finger protein expressed primarily in gametogenic cells and proliferative keratinocytes. Our previous work suggested that BNC1 is present in spermatogonia, spermatocytes and spermatids, but absent in the Sertoli cells. BNC1's role in spermatogenesis is unknown. Here we show that BNC1 is required for the maintenance of spermatogenesis. Bnc1-null male mice were sub-fertile, losing germ cells progressively with age. The Bnc1-null seminiferous epithelia began to degenerate before 8 weeks of age and eventually became Sertoli cell-only. Sperm count and motility also declined with age. Furthermore, Bnc1 heterozygotes, although fertile, showed a significant drop in sperm count and in testis weight by 24 weeks of age, suggesting a dosage effect of Bnc1 on testis development. In conclusion, our data demonstrate for the first time BNC1's essential role in maintaining mouse spermatogenesis. PMID:22266914

  2. The Trp53-Trp53inp1-Tnfrsf10b Pathway Regulates the Radiation Response of Mouse Spermatogonial Stem Cells

    PubMed Central

    Ishii, Kei; Ishiai, Masamichi; Morimoto, Hiroko; Kanatsu-Shinohara, Mito; Niwa, Ohtsura; Takata, Minoru; Shinohara, Takashi

    2014-01-01

    Summary Germ cells are thought to exhibit a unique DNA damage response that differs from that of somatic stem cells, and previous studies suggested that Trp53 is not involved in the survival of spermatogonial stem cells (SSCs) after irradiation. Here, we report a critical role for the Trp53-Trp53inp1-Tnfrsf10b pathway during radiation-induced SSC apoptosis. Spermatogonial transplantation revealed that Trp53 deficiency increased the survival of SSCs after irradiation. Although Bbc3, a member of the intrinsic apoptotic pathway, was implicated in apoptosis of germ and somatic stem cells, Bbc3 depletion inhibited apoptosis in committed spermatogonia, but not in SSCs. In contrast, inhibition of Tnfrsf10b, an extrinsic apoptosis regulator, rescued SSCs. Tnfrsf10b, whose deficiency protected SSCs, was upregulated by Trp53inp1 upon irradiation. These results suggest that the Trp53-Trp53inp1-Tnfrsf10b pathway responds to genotoxic damage in SSCs and that stem and progenitor cells exhibit distinct DNA damage responses in self-renewing tissue. PMID:25358794

  3. Germ cell transplantation and testis tissue xenografting in mice.

    PubMed

    Tang, Lin; Rodriguez-Sosa, Jose Rafael; Dobrinski, Ina

    2012-01-01

    Germ cell transplantation was developed by Dr. Ralph Brinster and colleagues at the University of Pennsylvania in 1994(1,2). These ground-breaking studies showed that microinjection of germ cells from fertile donor mice into the seminiferous tubules of infertile recipient mice results in donor-derived spermatogenesis and sperm production by the recipient animal(2). The use of donor males carrying the bacterial β-galactosidase gene allowed identification of donor-derived spermatogenesis and transmission of the donor haplotype to the offspring by recipient animals(1). Surprisingly, after transplantation into the lumen of the seminiferous tubules, transplanted germ cells were able to move from the luminal compartment to the basement membrane where spermatogonia are located(3). It is generally accepted that only SSCs are able to colonize the niche and re-establish spermatogenesis in the recipient testis. Therefore, germ cell transplantation provides a functional approach to study the stem cell niche in the testis and to characterize putative spermatogonial stem cells. To date, germ cell transplantation is used to elucidate basic stem cell biology, to produce transgenic animals through genetic manipulation of germ cells prior to transplantation(4,5), to study Sertoli cell-germ cell interaction(6,7), SSC homing and colonization(3,8), as well as SSC self-renewal and differentiation(9,10). Germ cell transplantation is also feasible in large species(11). In these, the main applications are preservation of fertility, dissemination of elite genetics in animal populations, and generation of transgenic animals as the study of spermatogenesis and SSC biology with this technique is logistically more difficult and expensive than in rodents. Transplantation of germ cells from large species into the seminiferous tubules of mice results in colonization of donor cells and spermatogonial expansion, but not in their full differentiation presumably due to incompatibility of the

  4. Temporally controlled site-specific mutagenesis in the germ cell lineage of the mouse testis.

    PubMed

    Weber, Philipp; Schuler, Michael; Gérard, Christelle; Mark, Manuel; Metzger, Daniel; Chambon, Pierre

    2003-02-01

    We have obtained a PrP-Cre-ER(T) transgenic mouse line (28.8) that selectively expresses in testis the tamoxifen-inducible Cre-ER(T) recombinase under the control of a mouse Prion protein (PrP) promoter-containing genomic fragment. Cre-ER(T) is expressed in spermatogonia and spermatocytes, but not in Sertoli and Leydig cells. We also established reporter PrP-L-EGFP-L transgenic mice harboring a LoxP-flanked enhanced green fluorescent protein (EGFP) Cre reporter cassette under the control of the same PrP promoter-containing genomic fragment that exhibits prominent EGFP expression in brain and testis. Using the PrP-L-EGFP-L as well as other Cre-reporter mice, we demonstrate that tamoxifen administration efficiently and selectively induces Cre-mediated recombination in the germ cell lineage. The established PrP-Cre-ER(T) line should provide a valuable tool for studying functions of germ cell-expressed genes involved in spermatogenesis. PMID:12533419

  5. 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

  6. 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.

  7. A role for kit receptor signaling in Leydig cell steroidogenesis.

    PubMed

    Rothschild, Gerson; Sottas, Chantal M; Kissel, Holger; Agosti, Valter; Manova, Katia; Hardy, Matthew P; Besmer, Peter

    2003-09-01

    Kit and its ligand, Kitl, function in hematopoiesis, melanogenesis, and gametogenesis. In the testis, Kitl is expressed by Sertoli cells and Kit is expressed by spermatogonia and Leydig cells. Kit functions are mediated by receptor autophosphorylation and subsequent association with signaling molecules, including phosphoinositide (PI) 3-kinase. We previously characterized the reproductive consequences of blocking Kit-mediated PI 3-kinase activation in KitY(719F)/Kit(Y719F) knockin mutant male mice. Only gametogenesis was affected in these mice, and males are sterile because of a block in spermatogenesis during the spermatogonial stages. In the present study, we investigated effects of the Kit(Y719F) mutation on Leydig cell development and steroidogenic function. Although the seminiferous tubules in testes of mutant animals are depleted of germ cells, the testes contain normal numbers of Leydig cells and the Leydig cells in these animals appear to have undergone normal differentiation. Evaluation of steroidogenesis in mutant animals indicates that testosterone levels are not significantly reduced in the periphery but that LH levels are increased 5-fold, implying an impairment of steroidogenesis in the mutant animals. Therefore, a role for Kit signaling in steroidogenesis in Leydig cells was sought in vitro. Purified Leydig cells from C57Bl6/J male mice were incubated with Kitl, and testosterone production was measured. Kitl-stimulated testosterone production was 2-fold higher than that in untreated controls. The Kitl-mediated testosterone biosynthesis in Leydig cells is PI 3-kinase dependent. In vitro, Leydig cells from mutant mice were steroidogenically more competent in response to LH than were normal Leydig cells. In contrast, Kitl-mediated testosterone production in these cells was comparable to that in normal cells. Because LH levels in mutant males are elevated and LH is known to stimulate testosterone biosynthesis, we proposed a model in which serum

  8. 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

  9. 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.

  10. 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

  11. 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

  12. Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6.

    PubMed

    Hidalgo-Carcedo, Cristina; Hooper, Steven; Chaudhry, Shahid I; Williamson, Peter; Harrington, Kevin; Leitinger, Birgit; Sahai, Erik

    2011-01-01

    Collective cell migration occurs in a range of contexts: cancer cells frequently invade in cohorts while retaining cell-cell junctions. Here we show that collective invasion by cancer cells depends on decreasing actomyosin contractility at sites of cell-cell contact. When actomyosin is not downregulated at cell-cell contacts, migrating cells lose cohesion. We provide a molecular mechanism for this downregulation. Depletion of discoidin domain receptor 1 (DDR1) blocks collective cancer-cell invasion in a range of two-dimensional, three-dimensional and 'organotypic' models. DDR1 coordinates the Par3/Par6 cell-polarity complex through its carboxy terminus, binding PDZ domains in Par3 and Par6. The DDR1-Par3/Par6 complex controls the localization of RhoE to cell-cell contacts, where it antagonizes ROCK-driven actomyosin contractility. Depletion of DDR1, Par3, Par6 or RhoE leads to increased actomyosin contactility at cell-cell contacts, a loss of cell-cell cohesion and defective collective cell invasion.

  13. 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

  14. 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.

  15. The effect of sampling time on radiation-induced translocation yield in spermatogonial stem cells of male mice, differing in chromosomal constitution and sexual activity.

    PubMed

    Wessels-Kaalen, M C; Bakker, R; de Boer, P

    1990-11-01

    We have investigated the frequency of reciprocal translocations in the first differentiating spermatogonia entering the first meiotic division after 2 x 2.5 Gy X-rays, given 24 h apart, as well as the development of this parameter in later stem-cell generations by studying multivalent configurations at the first meiotic division. Diakinesis-metaphase I cells were found for the first time between 30 and 40 days after irradiation. Subsequently, meiotic stages were sampled at 120, 180 and 280 days post irradiation. From day 40 post irradiation on, half of the males were allowed to impregnate females which enabled us to estimate the length of the post-irradiation sterile period, the development of litter size and the possible effect of sexual activity on the development of reciprocal translocation-containing stem cells. Half of the males were karyologically normal, the other half were homozygous for a reciprocal translocation (T/T) that affects testis weight and about halves sperm production. Irrespective of male karyotype, the first meiocytes had an induced translocation frequency of 9.00 +/- 2.56% (n = 8 males), followed by frequencies of 20.70 +/- 4.87% (n = 15) at 180 days and 20.20 +/- 4.30% (n = 20) at 280 days (males with and without mating behavior showing no difference). At 120 days post irradiation, +/+ males had a frequency of 14.59 +/- 2.97% irrespective of sexual activity. T/T males (120 days post irradiation) that had mated showed a frequency of 18.63 +/- 0.85% (n = 4) compared with 13.64 +/- 2.36% (n = 7) for those that had not. The observed rise of multivalent-carrying spermatocytes in time was highly significant. Notwithstanding the differences in testis weight and epididymal sperm count between the karyotypes, fertile matings occurred on average 72 days after irradiation, though with relatively wide margins. For the T/T karyotype, the first litter was statistically smaller than the subsequent litters. At 78 days post irradiation, testis weights were

  16. Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.

    PubMed

    Lu, Chenggang; Fuller, Margaret T

    2015-12-01

    Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s). In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC), a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs), spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages. PMID:26624996

  17. Ataxia with loss of Purkinje cells in a mouse model for Refsum disease.

    PubMed

    Ferdinandusse, Sacha; Zomer, Anna W M; Komen, Jasper C; van den Brink, Christina E; Thanos, Melissa; Hamers, Frank P T; Wanders, Ronald J A; van der Saag, Paul T; Poll-The, Bwee Tien; Brites, Pedro

    2008-11-18

    Refsum disease is caused by a deficiency of phytanoyl-CoA hydroxylase (PHYH), the first enzyme of the peroxisomal alpha-oxidation system, resulting in the accumulation of the branched-chain fatty acid phytanic acid. The main clinical symptoms are polyneuropathy, cerebellar ataxia, and retinitis pigmentosa. To study the pathogenesis of Refsum disease, we generated and characterized a Phyh knockout mouse. We studied the pathological effects of phytanic acid accumulation in Phyh(-/-) mice fed a diet supplemented with phytol, the precursor of phytanic acid. Phytanic acid accumulation caused a reduction in body weight, hepatic steatosis, and testicular atrophy with loss of spermatogonia. Phenotype assessment using the SHIRPA protocol and subsequent automated gait analysis using the CatWalk system revealed unsteady gait with strongly reduced paw print area for both fore- and hindpaws and reduced base of support for the hindpaws. Histochemical analyses in the CNS showed astrocytosis and up-regulation of calcium-binding proteins. In addition, a loss of Purkinje cells in the cerebellum was observed. No demyelination was present in the CNS. Motor nerve conduction velocity measurements revealed a peripheral neuropathy. Our results show that, in the mouse, high phytanic acid levels cause a peripheral neuropathy and ataxia with loss of Purkinje cells. These findings provide important insights in the pathophysiology of Refsum disease.

  18. 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

  19. 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

  20. 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.

  1. Suppression of meiosis of male germ cells by an antagonist of luteinizing hormone-releasing hormone.

    PubMed Central

    Szende, B; Redding, T W; Schally, A V

    1990-01-01

    Male nude mice were implanted with osmotic minipumps releasing 50 micrograms of a potent antagonist of luteinizing hormone-releasing hormone (LH-RH) per day [N-Ac-[D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-RH] (SB-75) [Nal(2), 3-(2-naphthyl)alanine; Phe(pCl), 4-chlorophenylalanine; Pal(3), 3-(3-pyridyl)alanine; Cit, citrulline], or they were treated with s.c. injections of SB-75 (25 micrograms twice a day). Another group of nude mice received an injection of microcapsules of the agonist [D-Trp6]LH-RH liberating 25 micrograms/day. One month after the initiation of treatment, the testicular weights were significantly reduced and the blood testosterone values were at castration levels in all treated groups. Histologically, only the testicles of the mice treated with SB-75 released from minipumps showed a significant decrease of meiosis. The most advanced forms of germ cells were spermatogonia in 26%, spermatocytes in 17%, and round spermatids in 35% of the seminiferous tubules. Only 22% of the tubules contained elongated spermatids. The suppression of meiotic activity by this modern LH-RH antagonist can possibly be used for the development of methods for male contraception and for the protection of germ cells against the damage caused by cytotoxic drugs and x-radiation. Images PMID:2405399

  2. 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.

  3. 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.

  4. Effect of dietary zinc deficiency on testes of Wistar rats: Morphometric and cell quantification studies.

    PubMed

    Kumari, Deepa; Nair, Neena; Bedwal, Ranveer Singh

    2011-01-01

    The present study investigates the effect of dietary zinc deficiency on testes of Wistar rats. Pre-pubertal rats (40-50g) were divided into three groups of 10 each viz. zinc control (ZC) and pair fed (PF) [100ppm zinc diet] and zinc deficient (ZD) [1ppm zinc diet]. Experiments were set for 2- and 4-weeks. Pre-pubertal rats fed zinc deficient diet for 2- and 4-weeks exhibited significant (P<0.05) decrease in diet consumption when compared with their respective control groups. Parallel to the reduced diet consumption, a significant (P<0.05) decrease in body and testicular weight of ZD animals was also observed. These observations indicate that the zinc deficiency reduces diet consumption and growth of the animals. Histological studies revealed degeneration in testes of ZD rats as evident by decreased seminiferous tubular diameter and Leydig cell nuclear diameter. Decreased Leydig cell nuclear diameter is responsible for disruption of the biochemical function of Leydig cell. Testicular atrophy (viz. wavy tunica propria, karyolysis, pyknosis, karyorhexis, apoptotic bodies, multinucleated giant cells, few sperms in the lumen, atrophied Leydig cells and accumulation of oedematous fluid in the interstitium) accompanied by significant loss of germ/somatic cells (viz. Type A and Type B spermatogonia, leptotene, zygotene, pachytene spermatocytes, Golgi, cap and acrosome spermatids, Sertoli and Leydig cell) was evident in ZD groups. The degeneration was severe after 4-weeks of zinc deficiency. These observations provide evidence that the functional and morphological changes in testes are probably due to zinc deficiency. Further, the increased oedematous fluid in the interstitial region is due to the cellular death. Impairment of spermatogenesis can be attributed to the direct action of zinc on testes or indirectly from Leydig cell degeneration indicating that zinc is a critical component for maintenance of both mitotic and meiotic stages of spermatogenesis.

  5. 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

  6. 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

  7. 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

  8. Testis specific serine/threonine protein kinase 4 (TSSK4) leads to cell apoptosis relying on its kinase activity.

    PubMed

    Wang, Xiao-li; Wei, You-heng; Fu, Guo-long; Yu, Long

    2015-04-01

    Testis specific serine/threonine protein kinase 4 (TSSK4) belongs to the TSSK family, and its members play an important role in spermatogenesis and/or spermiogenesis. Mouse TSSK4 has been reported to be expressed exclusively in the testis and can maintain its kinase activity through autophosphorylation at Thr-197. However, its biological function remains poorly understood. Here we found that GFP-TSSK4-overexpressed HeLa cells showed apoptotic bodies, indicating TSSK4 can lead to apoptosis in vitro. Furthermore, TSSK4 induced apoptosis in different cell lines including HeLa, Cos-7 and H1299 tested by flow cytometry but not its kinase-dead mutant TSSK4-K54M. TSSK4 knockout mice showed increased testes weight and decreased apoptotic spermatogonia and spermatocytes at 21st day after birth tested by TUNEL technology. So TSSK4 was able to induce cell apoptosis in vitro depending on its kinase activity, which leads to abnormal testes weight and apoptosis, shedding light on its function in the process of spermatogenesis and/or spermiogenesis.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. [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.

  14. [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

  15. 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

  16. 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

  17. Phagoptosis - Cell Death By Phagocytosis - Plays Central Roles in Physiology, Host Defense and Pathology.

    PubMed

    Brown, G C; Vilalta, A; Fricker, M

    2015-01-01

    Cell death by phagocytosis - termed 'phagoptosis' for short - is a form of cell death caused by the cell being phagocytosed i.e. recognised, engulfed and digested by another cell. Phagocytes eat cells that: i) expose 'eat-me' signals, ii) lose 'don't-eat-me' signals, and/or iii) bind opsonins. Live cells may express such signals as a result of cell stress, damage, activation or senescence, which can result in phagoptosis. Phagoptosis may be the most abundant form of cell death physiologically as it mediates erythrocyte turnover. It also regulates: reproduction by phagocytosis of sperm, development by removal stem cells and excess cells, and immunity by removal of activated neutrophils and T cells. Phagoptosis mediates the recognition of non-self and host defence against pathogens and cancer cells. However, in inflammatory conditions, excessive phagoptosis may kill our cells, leading to conditions such as hemophagy and neuronal loss.

  18. Expansion and long-term culture of human spermatogonial stem cells via the activation of SMAD3 and AKT pathways

    PubMed Central

    Guo, Ying; Liu, Linhong; Sun, Min; Hai, Yanan; Li, Zheng

    2015-01-01

    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

  19. Presence of ribonucleoproteins and basic proteins in the nuage and intermitochondrial bars of human spermatogonia.

    PubMed Central

    Paniagua, R; Nistal, M; Amat, P; Rodriguez, M C

    1985-01-01

    Ultrastructural cytochemical study of the nuage in the human adult testis revealed that this structure was a cytoplasmic fine fibrillar electron-dense mass, similar to the chromatoid body of spermatids, in all spermatogonial types and spermatocytes. The nuage was often observed in relation with the nucleus or mitochondria. Cytochemical techniques showed staining affinity of the nuage for both ethanolic phosphotungstic acid and ethylene diamine tetra-acetic acid. The intermitochondrial bars were also stained with the two procedures. The results suggest that the nuage originates from the nucleus and migrates to the cytoplasm through nuclear pores, giving rise to the intermitochondrial bars. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:3870728

  20. 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.

  1. 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

  2. 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

  3. 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

  4. Gossypol with methyltestosterone and ethinylestradiol male does not affect rat spermatogonial stem cell differentiation.

    PubMed

    Cui, G; Zheng, W; Sun, Y; Zhang, Q; Deng, X; Chen, X

    2007-01-01

    The purpose of this study was to investigate whether administration of the regimen of gossypol at 12 mg/kg/day combined with methyltestosterone at 20 mg/kg/day and ethinylestradiol at 100 microg/kg/day for a long term of twenty-four weeks could affect the existence and differentiation of rat spermatogonial stem cell. This was assessed by conducting TdT-mediated dUTP nick end-labeling detection, spermatogonial stem cell transplantation and fertility recovery evaluation. Our results showed that spontaneous apoptosis was observed in normal rats' testes from the control group with an apoptotic index (AI) average of 10.24+/-1.52. In the regimen-treated group, the predominant apoptotic cells were spermatocytes and spermatids in the seminiferous tubules. Spermatogonia were not apoptotic (AI averaged 113.42+/-13.24). Two to three months after transplantation of spermatogonial stem cells isolated from regimen-treated rats into recipient nude mice, elongated rat spermatids were identified in the seminiferous tubules of recipient nude mice. Six weeks after withdrawal of the administration, fertility of the regimen-treated rats was recovered compared with that of the control group. The number of litters produced by females mated with regimen-treated males averaged 9.88+/-0.166 matched 10.30+/-0.171 of control group and the litters of the first generation appeared to be normal. These results indicated that the administration of this regimen did not affect the existence and differentiation potential of spermatogonial stem cells of the regimen-treated rats.

  5. Alternative generation of CNS neural stem cells and PNS derivatives from neural crest-derived peripheral stem cells.

    PubMed

    Weber, Marlen; Apostolova, Galina; Widera, Darius; Mittelbronn, Michel; Dechant, Georg; Kaltschmidt, Barbara; Rohrer, Hermann

    2015-02-01

    Neural crest-derived stem cells (NCSCs) from the embryonic peripheral nervous system (PNS) can be reprogrammed in neurosphere (NS) culture to rNCSCs that produce central nervous system (CNS) progeny, including myelinating oligodendrocytes. Using global gene expression analysis we now demonstrate that rNCSCs completely lose their previous PNS characteristics and acquire the identity of neural stem cells derived from embryonic spinal cord. Reprogramming proceeds rapidly and results in a homogenous population of Olig2-, Sox3-, and Lex-positive CNS stem cells. Low-level expression of pluripotency inducing genes Oct4, Nanog, and Klf4 argues against a transient pluripotent state during reprogramming. The acquisition of CNS properties is prevented in the presence of BMP4 (BMP NCSCs) as shown by marker gene expression and the potential to produce PNS neurons and glia. In addition, genes characteristic for mesenchymal and perivascular progenitors are expressed, which suggests that BMP NCSCs are directed toward a pericyte progenitor/mesenchymal stem cell (MSC) fate. Adult NCSCs from mouse palate, an easily accessible source of adult NCSCs, display strikingly similar properties. They do not generate cells with CNS characteristics but lose the neural crest markers Sox10 and p75 and produce MSC-like cells. These findings show that embryonic NCSCs acquire a full CNS identity in NS culture. In contrast, MSC-like cells are generated from BMP NCSCs and pNCSCs, which reveals that postmigratory NCSCs are a source for MSC-like cells up to the adult stage.

  6. Regulatory T cells: balancing protection versus pathology.

    PubMed

    Rakebrandt, Nikolas; Littringer, Katharina; Joller, Nicole

    2016-01-01

    Foxp3+ regulatory T cells (Tregs) maintain immune tolerance, prevent autoimmunity and modulate immune responses during infection and cancer. Recent studies have revealed considerable heterogeneity and plasticity within the Treg compartment, depending on the immunological context, which may result in Tregs losing their suppressive function in inflammatory environments. We review how dysfunctional Tregs contribute to disease pathogenesis in inflammatory conditions and how inappropriate regulatory responses may hamper protective immunity in the context of infection and cancer. We also discuss how Tregs might be targeted therapeutically to re-establish a proper balance between regulatory and effector responses in autoimmunity, infections, and cancer. PMID:27497235

  7. 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.

  8. Mechanical properties of cells and ageing.

    PubMed

    Starodubtseva, Maria N

    2011-01-01

    Mechanical properties are fundamental properties of the cells and tissues of living organisms. The mechanical properties of a single cell as a biocomposite are determined by the interdependent combination of cellular components mechanical properties. Quantitative estimate of the cell mechanical properties depends on a cell state, method of measurement, and used theoretical model. Predominant tendency for the majority of cells with ageing is an increase of cell stiffness and a decrease of cell ability to undergo reversible large deformations. The mechanical signal transduction in old cells becomes less effective than that in young cells, and with ageing, the cells lose the ability of the rapid functional rearrangements of cellular skeleton. The article reviews the theoretical and experimental facts touching the age-related changes of the mechanical properties of cellular components and cells in the certain systems of an organism (the blood, the vascular system, the musculoskeletal system, the lens, and the epithelium). In fact, the cell mechanical parameters (including elastic modulii) can be useful as specific markers of cell ageing.

  9. Prox1 postmitotically defines dentate gyrus cells by specifying granule cell identity over CA3 pyramidal cell fate in the hippocampus.

    PubMed

    Iwano, Tomohiko; Masuda, Aki; Kiyonari, Hiroshi; Enomoto, Hideki; Matsuzaki, Fumio

    2012-08-01

    The brain is composed of diverse types of neurons that fulfill distinct roles in neuronal circuits, as manifested by the hippocampus, where pyramidal neurons and granule cells constitute functionally distinct domains: cornu ammonis (CA) and dentate gyrus (DG), respectively. Little is known about how these two types of neuron differentiate during hippocampal development, although a set of transcription factors that is expressed in progenitor cells is known to be required for the survival of granule cells. Here, we demonstrate in mice that Prox1, a transcription factor constitutively expressed in the granule cell lineage, postmitotically functions to specify DG granule cell identity. Postmitotic elimination of Prox1 caused immature DG neurons to lose the granule cell identity and in turn terminally differentiate into the pyramidal cell type manifesting CA3 neuronal identity. By contrast, Prox1 overexpression caused opposing effects on presumptive hippocampal pyramidal cells. These results indicate that the immature DG cell has the potential to become a granule cell or a pyramidal cell, and Prox1 defines the granule cell identity. This bi-potency is lost in mature DG cells, although Prox1 is still required for correct gene expression in DG granule cells. Thus, our data indicate that Prox1 acts as a postmitotic cell fate determinant for DG granule cells over the CA3 pyramidal cell fate and is crucial for maintenance of the granule cell identity throughout the life.

  10. Calibrating Sickle Cell Disease.

    PubMed

    Yosmanovich, Donna; Rotter, Maria; Aprelev, Alexey; Ferrone, Frank A

    2016-04-24

    Sickle cell disease is fundamentally a kinetic disorder, in which cells containing the mutated hemoglobin (hemoglobin S; HbS) will cause occlusion if they sickle in the microvasculature, but have minimal (or no) consequences if they sickle in the venous return. Physiologically, sickling always occurs when some ligands are present; nonetheless, the kinetics in the presence of ligands are virtually unstudied. Sickling arises from nucleation-controlled polymer formation, triggered when the HbS loses ligands (e.g., oxygen). Thus, understanding how nucleation responds to the presence of oxygen is the key to understanding how sickling proceeds in a physiological context. We have measured the rate of nucleus formation in HbS partially liganded with NO or CO, which we find have equivalent effects in reducing the nucleation rates. We find that hemoglobin must be in the T (tense) quaternary structure for nucleation, but the presence of ligands inhibits nucleus formation even when the correct quaternary structure is present. From these results, we can predict the fraction of cells that will sickle at any given partial ligand saturations. The ability to make such predictions may prove especially useful in designing future therapies, particularly those where the oxygen affinity is perturbed.

  11. Signaling events during male germ cell differentiation: bases and perspectives.

    PubMed

    Berruti, G

    1998-11-01

    In all species, reproductive function depends on the ability of the individual to produce functional differentiated gametes. Spermatogenesis is a cyclic process in which diploid spermatogonia differentiate into mature haploid spermatozoa. Thus from a genetic point of view, spermatogenesis can be divided into two phases, namely the diploid and haploid phase. Indeed, this complex differentiation process is still more intriguing since primary spermatocytes, if genetically diploid, are functionally tetraploid, while elongating spermatids, the germ cells undergoing the most dramatic morphological changes, if genetically haploid, become functionally anucleate due to ongoing condensation of chromatin resulting in an inactive nuclear DNA. This multi-step differentiative pathway is dependent on a specific environment provided by the anatomical and cellular relationships that take place in the testis and more specifically within the seminiferous tubules. Already, early anatomists (mind comes to Enrico Sertoli and Gustaf Retzius) were fascinated by the mixed cellular composition of the testis correctly deciphered as a whole of interacting and interdependent cell types despite the fact these belong to two well-established and different cell lineages, i.e, the somatic and germinal line. Since their time (the XIX century) up to-day a conspicuous bulk of experimental work and a relative massive bibliographic documentation have been provided. From this it stands out : a) a sophisticated role played by the cyclic hormonal control elicited by the hypothalamic-pituitary axis; b) the structural membrane specializations of Sertoli-germ cell communications; c) the existence and action of a paracrine and autocrine testicular regulative secretion; d) a regulation of germ cell gene expression, highly specialized both at transcriptional, posttranscriptional, and translational level; e) an active participation of the haploid genome in the final steps of cell differentiation. Each of these

  12. Molecular analysis of cell type-specific gene expression profile during mouse spermatogenesis by laser microdissection and qRT-PCR.

    PubMed

    Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Moley, Kelle H

    2013-03-01

    Laser microdissection (LMD) is a selective cell isolation technique that enables the separation of desired homogenous cell subpopulations from complex tissues such as the testes under direct microscopic visualization. The LMD accompanied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) represents an indispensable tool in quantifying messenger RNA (mRNA) expression among defined cell populations. Gene expression is temporally and spatially regulated at 3 sequential phases of mitotic, meiotic, and postmeiotic stages of spermatogenesis. The present study demonstrates a short modified LMD protocol based upon hematoxylin and eosin (H&E) staining. Stage-specific LMD success was validated by the use of mRNA profiling of "marker genes" which are conserved across species and are known to be differentially expressed during spermatogenesis. Magea4, Hspa2, Cox6b2, Tnp1, Prm1, and Prm2 are used to differentiate among the microdissected cell populations, namely spermatogonia (group I), spermatocytes (group II), round and condensing spermatids (group III), and elongated and condensed spermatids (group IV), respectively. The LMD combined with qRT-PCR is further extended to assess the cell stage-specific distribution of selected stress response genes such as Hsp90aa1, Gpx4, Ucp2, Sod1, and Sod2. The germ cell-specific mRNA profiles are suitably complemented by Western blot of the LMD samples, immunohistochemistry, and confocal localization of the corresponding proteins. The current study suggests that LMD can successfully isolate cell subpopulations from the complex tissues of the testes; and establish cell stage-specific basal expression patterns of selected stress response genes and proteins. It is our hypothesis that the baseline expression of stress response genes will differ by cell stage to create discrete stage-specific vulnerabilities to reproductive toxicants.

  13. 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

  14. 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

  15. Notch-mediated patterning and cell fate allocation of pancreatic progenitor cells

    PubMed Central

    Afelik, Solomon; Qu, Xiaoling; Hasrouni, Edy; Bukys, Michael A.; Deering, Tye; Nieuwoudt, Stephan; Rogers, William; MacDonald, Raymond J.; Jensen, Jan

    2012-01-01

    Early pancreatic morphogenesis is characterized by the transformation of an uncommitted pool of pancreatic progenitor cells into a branched pancreatic epithelium that consists of ‘tip’ and ‘trunk’ domains. These domains have distinct molecular signatures and differentiate into distinct pancreatic cell lineages. Cells at the branched tips of the epithelium develop into acinar cells, whereas cells in the trunk subcompartment differentiate into endocrine and duct cells. Recent genetic analyses have highlighted the role of key transcriptional regulators in the specification of these subcompartments. Here, we analyzed in mice the role of Notch signaling in the patterning of multipotent pancreatic progenitor cells through mosaic overexpression of a Notch signaling antagonist, dominant-negative mastermind-like 1, resulting in a mixture of wild-type and Notch-suppressed pancreatic progenitor cells. We find that attenuation of Notch signaling has pronounced patterning effects on multipotent pancreatic progenitor cells prior to terminal differentiation. Relative to the wild-type cells, the Notch-suppressed cells lose trunk marker genes and gain expression of tip marker genes. The Notch-suppressed cells subsequently differentiate into acinar cells, whereas duct and endocrine populations are formed predominantly from the wild-type cells. Mechanistically, these observations could be explained by a requirement of Notch for the expression of the trunk determination gene Nkx6.1. This was supported by the finding of direct binding of RBP-jκ to the Nkx6.1 proximal promoter. PMID:22461559

  16. 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

  17. 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

  18. Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers.

    PubMed

    Lee-Chang, Catalina; Bodogai, Monica; Moritoh, Kanako; Chen, Xin; Wersto, Robert; Sen, Ranjan; Young, Howard A; Croft, Michael; Ferrucci, Luigi; Biragyn, Arya

    2016-04-15

    B cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL(+)MHC class-I(Hi)CD86(Hi)B cells of unknown origin. In this article, we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. The activation is mediated by aging human monocytes and murine peritoneal macrophages. They induce expression and activation of 4-1BBL and IFN-γR1 on B1a cells to subsequently upregulate membrane TNF-α and CD86. As a result, activated B1a/4BL cells induce expression of granzyme B in CD8(+)T cells by targeting TNFR2 via membrane TNF-α and providing costimulation with CD86. Thus, for the first time, to our knowledge, these results indicate that aging affects the function of B1a cells. Upon aging, these cells lose their tumor-supporting activity and become inducers of potentially antitumor and autoimmune CD8(+)T cells.

  19. 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

  20. Expression of an accessory cell phenotype by hairy cells during lymphocyte colony formation in agar culture.

    PubMed

    Farcet, J P; Gourdin, M F; Testa, U; Andre, C; Jouault, H; Reyes, F

    1983-01-01

    Human T lymphocytes require the cooperation of accessory cells to generate lymphocyte colonies in agar culture under PHA stimulation. Various hairy cell enriched fractions, as well as normal monocytes, have been found to be able to initiate colony formation by normal lymphocytes. Leukemic monocytes from CMML patients were also effective, but not the leukemic lymphocytes from CLL patients. The phenotype expressed by HC in agar colonies was further studied using cell surface and enzymatic markers. We have concluded that HC in agar culture in the presence of both normal T lymphocytes and PHA lose the B phenotype that they express in vivo and function like an accessory cell in contrast to normal or leukemic B lymphocytes. PMID:6601222

  1. Imparting regenerative capacity to limbs by progenitor cell transplantation

    PubMed Central

    Lin, Gufa; Chen, Ying; Slack, Jonathan M.W.

    2012-01-01

    Summary The frog Xenopus can normally regenerate its limbs at early developmental stages but loses the ability during metamorphosis. This behavior provides a potential gain-of-function model for measures that can enhance limb regeneration. Here we show that frog limbs can be caused to form multidigit regenerates after receiving transplants of larval limb progenitor cells. It is necessary to activate Wnt/β -catenin signaling in the cells, and to add Sonic hedgehog, FGF10 and thymosin β4. These factors promote survival and growth of the grafted cells and also provide pattern information. The eventual regenerates are not composed solely of donor tissue; the host cells also make a substantial contribution despite their lack of regeneration-competence. Cells from adult frog legs or from regenerating tadpole tails do not promote limb regeneration, demonstrating the necessity for limb progenitor cells. These findings have obvious implications for the development of a technology to promote limb regeneration in mammals. PMID:23273877

  2. 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

  3. Neonatal bisphenol A exposure induces meiotic arrest and apoptosis of spermatogenic cells.

    PubMed

    Xie, Meina; Bu, Pengli; Li, Fengjie; Lan, Shijian; Wu, Hongjuan; Yuan, Lu; Wang, Ying

    2016-03-01

    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

  4. 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.

  5. Carboxybetaine methacrylate polymers offer robust, long-term protection against cell adhesion

    PubMed Central

    Mahmud, Goher; Huda, Sabil; Yang, Wei; Kandere-Grzybowska, Kristiana; Pilans, Didzis; Jiang, Shaoyi; Grzybowski, Bartosz A.

    2013-01-01

    Films of poly(carboxybetaine methacrylate), poly(CBMA), grafted onto microetched gold slides are effective in preventing non-specific adhesion of cells of different types. The degree of adhesion resistance is comparable to that achieved with the self-assembled monolayers, SAMs, of oligo(ethylene glycol) alkanethiolates. In sharp contrast to the SAMs, however, substrates protected with poly(CBMA) can be stored in dry state without losing their protective properties for periods up to two weeks. PMID:21711048

  6. Cell cycles and proliferation patterns in Haematococcus pluvialis

    NASA Astrophysics Data System (ADS)

    Zhang, Chunhui; Liu, Jianguo; Zhang, Litao

    2016-09-01

    Most studies on Haematococcus pluvialis have been focused on cell growth and astaxanthin accumulation; far less attention has been paid to cell cycles and proliferation patterns. The purpose of this study was to clarify cell cycles and proliferation patterns in H. pluvialis microscopically using a camera and video recorder system. The complicated life history of H. pluvialis can be divided into two stages: the motile stage and the non-motile stage. All the cells can be classified into forms as follows: motile cell, non-motile cell, zoospore and aplanospore. The main cell proliferation, both in the motile phase and non-motile phase in H. pluvialis, is by asexual reproduction. Under normal growth conditions, a motile cell usually produces two, sometimes four, and exceptionally eight zoospores. Under unfavorable conditions, the motile cell loses its flagella and transforms into a non-motile cell, and the non-motile cell usually produces 2, 4 or 8 aplanospores, and occasionally 20-32 aplanospores, which further develop into non-motile cells. Under suitable conditions, the non-motile cell is also able to release zoospores. The larger non-motile cells produce more than 16 zoospores, and the smaller ones produce 4 or 8 zoospores. Vegetative reproduction is by direct cell division in the motile phase and by occasional cell budding in the non-motile phase. There is, as yet, no convincing direct evidence for sexual reproduction.

  7. How can we not 'lose it' if we still don't understand how to 'use it'? Unanswered questions about the influence of activity participation on cognitive performance in older age--a mini-review.

    PubMed

    Bielak, Allison A M

    2010-01-01

    The 'use it or lose it' hypothesis of cognitive aging predicts that engagement in intellectual, social, and physical activities offers protective benefits from age-related cognitive decline and lowers dementia risk. Although this hypothesis has not yet been supported conclusively, there is some empirical evidence in favor of the proposal. However, a number of questions surrounding the relationship between activity participation and cognitive ability in older adulthood are not yet well answered. This mini-review identifies seven key methodological and theoretical issues that are critical to our understanding and eventual possible promotion of activity participation as a way to maintain cognitive well-being. These include the mechanisms involved, the optimal ways of assessing activity engagement, which cognitive domains receive the most benefit from activity engagement, the temporal nature and the directionality of the relationship, the influence of demographic variables such as age, gender, or education, and whether one activity domain offers the most benefit to cognition. The current knowledge on each of these issues is critically evaluated, including describing what we already know about the issue, and identifying potential difficulties and opportunities that may exist in finding an answer. More studies need to take on the challenge of specifically targeting these issues, as each is essential to moving the field forward.

  8. 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

  9. Gaining Momentum, Losing Ground. Progress Report, 2008

    ERIC Educational Resources Information Center

    Business Roundtable, 2008

    2008-01-01

    This report presents an update of the progress of Tapping America's Potential (TAP), a coalition of 15 of the nation's leading business organizations, and assesses three years' progress since 2005 in working towards the goal of doubling the number of students earning bachelor's degrees in science, technology, engineering and math (STEM) by 2015.…

  10. Nothing to Lose but Your Career Structure

    PubMed Central

    Gauntlett, Tim

    1972-01-01

    A growing number of students are casting aside the traditional view of work as a means of earning money, preferring to identify themselves more closely with a Particular community, where they can create their own life-style.

  11. 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…

  12. 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.

  13. 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.

  14. Losing touch in the era of superbugs?

    PubMed

    Hass, Leif

    2010-01-01

    Nosocomial infections are increasingly multidrug resistant and at times more virulent. As such, they pose real threats to patients and clinicians. In this essay the author discusses his own methacillin-resistant staphylococcus infection and how it has affected his work in the hospital. In so doing, he reflects on the value of touch in the doctor-patient relationship. In particular, he discusses how gloves serve as a barrier to infection but also create a small distance between the doctors and their patients. The implications of contact precautions must be considered as we reflect on balancing patient-centered care with infection control.

  15. Momentum: "Losing Money/Making Money."

    ERIC Educational Resources Information Center

    Meservey, Lynne

    1990-01-01

    Considers ways in which ancillary income can help child care centers recover losses resulting from discounts and increase income for child care centers. Ancillary income can be derived from service activities, enrichment programs, product sales, and fund raising. Such income depends on thorough evaluation, planning, staff involvement, and…

  16. AIDS: losing the battle and the war?

    PubMed

    Potts, M; Carswell, W

    1993-06-01

    The World Health Organization (WHO) Global Programme on AIDS (GPA) was initiated February, 1987, and became the major recipient of Western support for AIDS prevention. While the WHO/GPA has successfully provided policies and technical assistance, available funds were not spent quickly enough or on the right things. Other mechanisms for channeling funds to recipients are needed. Many early programs designed to secure safe blood supplies received the largest proportion of resources, even though HIV infection via transfusion was the least common route of spread. Despite models demonstrating that treating sexually transmitted diseases (STD) costs $4-7.50/HIV case prevented in adult populations with 10% HIV prevalences, STD treatment is supported less than programs which urge individuals to have fewer sex partners and those which distribute condoms. Even so, no global plan exists to supply life-saving commodities such as condoms in countries most in need. Poor management further cripples programs' potential scope and effectiveness. This commentary holds that AIDS interventions could be organized under the following separate and distinct groupings: urban STD control; prostitute and client services; condom marketing to entrepreneurs in developing countries; and blood supply security. The supply of commodities must be assured; system administration simplified; small projects supported; and program funds transferred directly to nongovernmental organizations and the private sector. Further, those on national AIDS committees who oppose programs for the marginalized or who believe condoms cause promiscuity should not be allowed to delay or veto projects; the overlap between family planning and HIV prevention programs needs to be rationalized; manager must be responsible for programs; and institutions must act quickly and be judged on that basis. PMID:8099144

  17. 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

  18. 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

  19. 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

  20. 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

  1. Losing a child: finding meaning in bereavement

    PubMed Central

    Bogensperger, Julia; Lueger-Schuster, Brigitte

    2014-01-01

    Background Confronting the loss of a loved one leads us to the core questions of human existence. Bereaved parents have to deal with the rupture of a widely shared concept of what is perceived to be the natural course of life and are forced into meaning reconstruction. Objective This study aims to expand upon existing work concerning specific themes of meaning reconstruction in a sample of bereaved parents. More specifically, the relationship between meaning reconstruction, complicated grief, and posttraumatic growth was analyzed, with special attention focused on traumatic and unexpected losses. Method In a mixed methods approach, themes of meaning reconstruction (sense-making and benefit-finding) were assessed in in-depth interviews with a total of 30 bereaved parents. Posttraumatic growth and complicated grief were assessed using standardized questionnaires, and qualitative and quantitative results were then merged using data transformation methods. Results In total 42 themes of meaning reconstruction were abstracted from oral material. It was shown that sense-making themes ranged from causal explanations to complex philosophical beliefs about life and death. Benefit-finding themes contained thoughts about personal improvement as well as descriptions about social actions. Significant correlations were found between the extent of sense-making and posttraumatic growth scores (r s=0.54, r s=0.49; p<0.01), especially when the death was traumatic or unexpected (r s=0.67, r s=0.63; p<0.01). However, analysis revealed no significant correlation with complicated grief. Overall results corroborate meaning reconstruction themes and the importance of meaning reconstruction for posttraumatic growth. PMID:24765248

  2. 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.

  3. 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…

  4. Order Lunch Early, Lose Weight Later?

    MedlinePlus

    ... in the Center for Health Incentives and Behavioral Economics at the University of Pennsylvania. "The implication is that restaurants and ... study senior author George Loewenstein, a professor of economics and psychology at Carnegie Mellon University in Pittsburgh. "For example, people who plan to ...

  5. Americans with Disabilities: Are They Losing Ground?

    ERIC Educational Resources Information Center

    Essex, Nathan L.

    2002-01-01

    Offers as brief overview of the 1990 Americans with Disabilities Act (ADA), intended to protect disabled individuals against discriminatory practices in employment. Discusses implications for educators of three Supreme Court decisions dealing with the ADA, and offers 10 guidelines to ensure that the intent of the ADA statute is followed by school…

  6. Social Studies Losing out to Reading, Math

    ERIC Educational Resources Information Center

    Manzo, Kathleen Kennedy

    2005-01-01

    "Johnny" may be learning more about reading and mathematics, but he may have little time to study the discoveries of Columbus, the tenets of the U.S. Constitution, or the social and political causes of the Civil War. Those time-honored topics--as well as lesser-known events and figures throughout history--are fighting to maintain their place in…

  7. 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

  8. 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…

  9. 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.

  10. Finding brands and losing your religion?

    PubMed

    Cutright, Keisha M; Erdem, Tülin; Fitzsimons, Gavan J; Shachar, Ron

    2014-12-01

    Religion is a powerful force in many people's lives, impacting decisions about life, death, and everything in between. It may be difficult, then, to imagine that something as seemingly innocuous as the usage of brand name products might influence individuals' commitment to religion. However, we demonstrate across 6 studies that when brands are a highly salient tool for self-expression, individuals are less likely to report and demonstrate strong religious commitment. We suggest that a desire to maintain consistency among self-identities is one important driver of this relationship and find that the effect is mitigated when the perceived distance between brands and religious values is minimized.

  11. "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…

  12. 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…

  13. Sharing Educational Materials without Losing Rights

    ERIC Educational Resources Information Center

    Johnstone, Sally M.

    2003-01-01

    Not all materials created by faculty should be freely shared. When an institution has a profitable course being offered electronically, the creator of those materials and the institution want to protect them. However, most materials created for students will never be profitably marketed. Creative Commons offers faculty members who have concerns…

  14. 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 ...

  15. Rural areas losing appeal for young doctors.

    PubMed

    Kirk, K

    1991-01-01

    Since fewer and fewer medical students are choosing to practice in rural communities, these areas are scrambling to recruit physicians. So far, however, such lures as interest-free loans and other incentives are not enticing enough for young physicians. What are the rural areas to do? One Ohio county thinks a foreign medical graduate may be the answer, and it's working overtime to bring her onboard.

  16. Stochastic particle barcoding for single-cell tracking and multiparametric analysis.

    PubMed

    Castellarnau, M; Szeto, G L; Su, H-W; Tokatlian, T; Love, J C; Irvine, D J; Voldman, J

    2015-01-27

    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 is 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 are recovered by digesting the hydrogel, allowing subsequent genotyping and phenotyping of cell lysates. Finally, a model scaling is developed to illustrate how different parameters affect the accuracy of SPB and to motivate scaling of the method to thousands of unique blocks.

  17. Monitoring of TGF-β 1-Induced Human Lung Adenocarcinoma A549 Cells Epithelial-Mesenchymal Transformation Process by Measuring Cell Adhesion Force with a Microfluidic Device.

    PubMed

    Li, Yuan; Gao, AnXiu; Yu, Ling

    2016-01-01

    The epithelial-mesenchymal transition (EMT) is a process in which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties. It is believed that EMT is associated with initiation and completion of the invasion-metastasis cascade. In this study, an economic approach was developed to fabricate a microfluidic device with less instrumentation requirement for the investigation of EMT by quantifying cell adhesion force. Fluid shear force was precisely controlled by a homemade microfluidic perfusion apparatus and interface. The adhesion capability of the human lung adenocarcinoma cell line A549 on different types of extracellular matrix protein was studied. In addition, effects of transforming growth factor-β (TGF-β) on EMT in A549 cells were investigated by characterizing the adhesion force changes and on-chip fluorescent staining. The results demonstrate that the microfluidic device is a potential tool to characterize the epithelial-mesenchymal transition process by measuring cell adhesion force.

  18. Oncogenic Functions of the Cancer-Testis Antigen SSX on the Proliferation, Survival, and Signaling Pathways of Cancer Cells

    PubMed Central

    Wolahan, Barry; Ma, Limin; Brodin, Bertha

    2014-01-01

    SSX is a transcription factor with elusive oncogenic functions expressed in a variety of human tumors of epithelial and mesenchymal origin. It has raised substantial interest as a target for cancer therapy since it elicits humoral responses and displays restricted expression to cancer, spermatogonia and mesenchymal stem cells. Here, we investigated the oncogenic properties of SSX by employing a RNA interference to knock-down the endogenous expression of SSX in melanoma and osteosarcoma cell lines. Depletion of SSX expression resulted in reduced proliferation with cells accumulating in the G1 phase of the cell cycle. We found that the growth promoting and survival properties of SSX are mediated in part though modulation of MAPK/Erk and Wnt signaling pathways, since SSX silencing inhibited Erk-mediated signaling and transcription of cMYC and Akt-1. We also found that SSX forms a transient complex with β-catenin at the G1-S phase boundary resulting in the altered expression of β-catenin target genes such as E-cadherin, snail-2 and vimentin, involved in epithelial-mesenchymal transitions. Importantly the silencing of SSX expression in in vivo significantly impaired the growth of melanoma tumor xenografts. Tumor biopsies from SSX silenced tumors displayed reduced cyclin A staining, indicative of low proliferation and predominantly cycloplasmic β-catenin compared to SSX expressing tumors. The present study demonstrates a previously unknown function of SSX, that as an oncogene and as a tumor target for the development of novel anti-cancer drugs. PMID:24787708

  19. 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

  20. Germ cell mutagenesis in medaka fish after exposures to high-energy cosmic ray nuclei: A human model.

    PubMed

    Shimada, Atsuko; Shima, Akihiro; Nojima, Kumie; Seino, Yo; Setlow, Richard B

    2005-04-26

    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 gamma-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 approximately 50 at LET values of approximately 100-200 keV/microm. 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 gamma-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. PMID:15829584

  1. The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells

    PubMed Central

    1990-01-01

    Staphylococcal enterotoxin B (SEB) has been shown in the past to be a potent T cell stimulant in mouse or man. The toxin acts as a superantigen that is, it binds to class II MHC proteins and, as such a complex, stimulates T cells bearing particular V beta s as part of their receptors. The toxin also has several pathological effects, causing, in mice, rapid weight loss, thymus atrophy, immunosuppression, and, at high doses, death. The data in this paper show that at least one of these effects, weight loss, is T cell mediated. Staphylococcal enterotoxin-mediated weight loss is MHC dependent, and is almost absent in animals expressing MHC class II molecules, which, complexed with SEB, are poor T cell stimulants. Also, mice that lack T cell function, genetically or because of cyclosporin A treatment, lose no or less weight than controls in response to SEB. Finally, animals bred such that they express few T cells bearing V beta s with which SEB can interact lose much less weight in response to the toxin than littermate controls that have higher numbers of reactive T cells. It is therefore suggested that the pathological effects of the staphylococcal, T cell- stimulating toxins in mouse and man may be partially or wholly the consequence of massive T cell stimulation. PMID:2303780

  2. 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

  3. 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

  4. 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.

  5. Cell-cell transmission enables HIV-1 to evade inhibition by potent CD4bs directed antibodies.

    PubMed

    Abela, Irene A; Berlinger, Livia; Schanz, Merle; Reynell, Lucy; Günthard, Huldrych F; Rusert, Peter; Trkola, Alexandra

    2012-01-01

    HIV is known to spread efficiently both in a cell-free state and from cell to cell, however the relative importance of the cell-cell transmission mode in natural infection has not yet been resolved. Likewise to what extent cell-cell transmission is vulnerable to inhibition by neutralizing antibodies and entry inhibitors remains to be determined. Here we report on neutralizing antibody activity during cell-cell transmission using specifically tailored experimental strategies which enable unambiguous discrimination between the two transmission routes. We demonstrate that the activity of neutralizing monoclonal antibodies (mAbs) and entry inhibitors during cell-cell transmission varies depending on their mode of action. While gp41 directed agents remain active, CD4 binding site (CD4bs) directed inhibitors, including the potent neutralizing mAb VRC01, dramatically lose potency during cell-cell transmission. This implies that CD4bs mAbs act preferentially through blocking free virus transmission, while still allowing HIV to spread through cell-cell contacts. Thus providing a plausible explanation for how HIV maintains infectivity and rapidly escapes potent and broadly active CD4bs directed antibody responses in vivo. PMID:22496655

  6. 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

  7. 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

  8. 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.

  9. Lactating Ctcgrp Nulls Lose Twice the Normal Bone Mineral Content due to Fewer Osteoblasts and More Osteoclasts, Whereas Bone Mass Is Fully Restored After Weaning in Association With Up-Regulation of Wnt Signaling and Other Novel Genes

    PubMed Central

    Collins, Jillian N.; Kirby, Beth J.; Woodrow, Janine P.; Gagel, Robert F.; Rosen, Clifford J.; Sims, Natalie A.

    2013-01-01

    The maternal skeleton resorbs during lactation to provide calcium to milk and the lost mineral content is restored after weaning. The changes are particularly marked in Ctcgrp null mice, which lose 50% of spine mineral content during lactation but restore it fully. The known calciotropic hormones are not required for skeletal recovery to occur; therefore, unknown factors that stimulate bone formation may be responsible. We hypothesized that the genes responsible for regulating postweaning bone formation are differentially regulated in bone or marrow, and this regulation may be more marked in Ctcgrp null mice. We confirmed that Ctcgrp null mice had twice as many osteoclasts and 30–40% fewer osteoblasts as compared with wild-type mice during lactation but no deficit in osteoblast numbers after weaning. Genome-wide microarray analyses on tibial RNA showed differential expression of 729 genes in wild-type mice at day 7 after weaning vs prepregnancy, whereas the same comparison in Ctcgrp null mice revealed only 283 genes. Down-regulation of Wnt family inhibitors, Sost and Dkk1, and inhibition of Mef2c, a sclerostin stimulator, were observed. Ctsk, a gene expressed during osteoclast differentiation, and Igfbp2, which stimulates bone resorption, were inhibited. Differential regulation of genes involved in energy use was compatible with a net increase in bone formation. The most marked changes occurred in genes not previously associated with bone metabolism. In conclusion, the postlactation skeleton shows dynamic activity with more than 700 genes differentially expressed. Some of these genes are likely to promote bone formation during postweaning by stimulating the proliferation and activity of osteoblasts, inhibiting osteoclasts, and increasing energy use. PMID:23462960

  10. Assembly of enveloped viruses in Madin-Darby canine kidney cells: polarized budding from single attached cells and from clusters of cells in suspension

    PubMed Central

    1983-01-01

    In confluent monolayers of the dog kidney epithelial cell line Madin- Darby canine kidney (MDCK) assembly of RNA enveloped viruses reflects the functional polarization of the cells. Thus, influenza, Sendai, and Simian virus 5 bud from the apical (free) surface, while vesicular stomatitis virions (VSV) are assembled at basolateral plasma membrane domains (Rodriguez-Boulan, E., and D.D. Sabatini, 1978, Proc. Natl. Acad. Sci. U.S.A., 75:5071-5075). MDCK cells derived from confluent monolayers by dissociation with trypsin-EDTA and maintained as single cells in spinner medium for 12-20 h before infection, lose their characteristic structural polarity. Furthermore, when these cells were infected with influenza or VSV, virions assembled in a nonpolarized fashion over most of the cell surface. However, when dissociated MDCK cells infected in suspension were sparsely plated on collagen gels to prevent intercellular contact and the formation of junctions, the characteristic polarity of viral budding observed in confluent monolayers was again manifested; i.e., VSV budded preferentially from adherent surfaces and influenza almost exclusively from free surface regions. Similar polarization was observed in cells which became aggregated during incubation in spinner medium: influenza budded from the free surface, while VSV was produced at regions of cell-cell contact. It therefore appears that in isolated epithelial cells attachment to a substrate or to another cell is sufficient to trigger the expression of plasma membrane polarity which is manifested in the asymmetric budding of viruses. PMID:6300140

  11. 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.

  12. CELL CONTACTS IN THE MOUSE MAMMARY GLAND

    PubMed Central

    Pitelka, Dorothy R.; Hamamoto, Susan T.; Duafala, Joan G.; Nemanic, Michael K.

    1973-01-01

    The nature and distribution of cell contacts have been examined in thin sections and freeze-fracture replicas of mammary gland samples from female C3H/Crgl mice at stages from birth through pregnancy, lactation, and postweaning involution. Epithelial cells of major mammary ducts at all stages examined are linked at their luminal borders by junctional complexes consisting of tight junctions, variable intermediate junctions, occasional small gap junctions, and one or more series of desmosomes. Scattered desmosomes and gap junctions link ductal epithelial and myoepithelial cells in all combinations; hemidesmosomes attach myoepithelial cells to the basal lamina. Freeze-fracture replicas confirm the erratic distribution of gap junctions and reveal a loose, irregular network of ridges comprising the continuous tight-junctional belts. Alveoli develop early in gestation and initially resemble ducts. Later, as alveoli and small ducts become actively secretory, they lose all desmosomes and most intermediate junctions, whereas tight and gap junctions persist, The tight-junctional network becomes compact and orderly, its undulating ridges oriented predominantly parallel to the luminal surface. It is suggested that these changes in junctional morphology, occurring in secretory cells around parturition, may be related to the greatly enhanced rate of movement of milk precursors and products through the lactating epithelium, or to the profound and recurrent changes in shape of secretory cells that occur in relation to myoepithelial cell contraction, or to both. PMID:4569313

  13. 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.

  14. Adaptations of higher plant cell walls to water loss: drought vs desiccation.

    PubMed

    Moore, John P; Vicré-Gibouin, Mäite; Farrant, Jill M; Driouich, Azeddine

    2008-10-01

    Water-deficit stress poses unique challenges to plant cells dependent on a hydrostatic skeleton and a polysaccharide-rich cell wall for growth and development. How the plant cell wall is adapted to loss of water is of interest in developing a general understanding of water stress tolerance in plants and of relevance in strategies related to crop improvement. Drought tolerance involves adaptations to growth under reduced water potential and the concomitant restructuring of the cell wall that allow growth processes to occur at lower water contents. Desiccation tolerance, by contrast, is the evolution of cell walls that are capable of losing the majority of cellular water without suffering permanent and irreversible damage to cell wall structure and polymer organization. This minireview highlights common features and differences between these two water-deficit responses observed in plants, emphasizing the role of the cell wall, while suggesting future research avenues that could benefit fundamental understanding in this area.

  15. 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.

  16. Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells

    PubMed Central

    Guillermet-Guibert, Julie; Smith, Lee B.; Halet, Guillaume; Whitehead, Maria A.; Pearce, Wayne; Rebourcet, Diane; León, Kelly; Crépieux, Pascale; Nock, Gemma; Strömstedt, Maria; Enerback, Malin; Chelala, Claude; Graupera, Mariona; Carroll, John; Cosulich, Sabina; Saunders, Philippa T. K.; Huhtaniemi, Ilpo; Vanhaesebroeck, Bart

    2015-01-01

    The organismal roles of the ubiquitously expressed class I PI3K isoform p110β remain largely unknown. Using a new kinase-dead knockin mouse model that mimics constitutive pharmacological inactivation of p110β, we document that full inactivation of p110β leads to embryonic lethality in a substantial fraction of mice. Interestingly, the homozygous p110β kinase-dead mice that survive into adulthood (maximum ~26% on a mixed genetic background) have no apparent phenotypes, other than subfertility in females and complete infertility in males. Systemic inhibition of p110β results in a highly specific blockade in the maturation of spermatogonia to spermatocytes. p110β was previously suggested to signal downstream of the c-kit tyrosine kinase receptor in germ cells to regulate their proliferation and survival. We now report that p110β also plays a germ cell-extrinsic role in the Sertoli cells (SCs) that support the developing sperm, with p110β inactivation dampening expression of the SC-specific Androgen Receptor (AR) target gene Rhox5, a homeobox gene critical for spermatogenesis. All extragonadal androgen-dependent functions remain unaffected by global p110β inactivation. In line with a crucial role for p110β in SCs, selective inactivation of p110β in these cells results in male infertility. Our study is the first documentation of the involvement of a signalling enzyme, PI3K, in the regulation of AR activity during spermatogenesis. This developmental pathway may become active in prostate cancer where p110β and AR have previously been reported to functionally interact. PMID:26132308

  17. 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

  18. 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

  19. Production of chicken progeny (Gallus gallus domesticus) from interspecies germline chimeric duck (Anas domesticus) by primordial germ cell transfer.

    PubMed

    Liu, Chunhai; Khazanehdari, Kamal A; Baskar, Vijaya; Saleem, Shazia; Kinne, Joerg; Wernery, Ulrich; Chang, Il-Kuk

    2012-04-01

    The present study aimed to investigate the differentiation of chicken (Gallus gallus domesticus) primordial germ cells (PGCs) in duck (Anas domesticus) gonads. Chimeric ducks were produced by transferring chicken PGCs into duck embryos. Transfer of 200 and 400 PGCs resulted in the detection of a total number of 63.0 ± 54.3 and 116.8 ± 47.1 chicken PGCs in the gonads of 7-day-old duck embryos, respectively. The chimeric rate of ducks prior to hatching was 52.9% and 90.9%, respectively. Chicken germ cells were assessed in the gonad of chimeric ducks with chicken-specific DNA probes. Chicken spermatogonia were detected in the seminiferous tubules of duck testis. Chicken oogonia, primitive and primary follicles, and chicken-derived oocytes were also found in the ovaries of chimeric ducks, indicating that chicken PGCs are able to migrate, proliferate, and differentiate in duck ovaries and participate in the progression of duck ovarian folliculogenesis. Chicken DNA was detected using PCR from the semen of chimeric ducks. A total number of 1057 chicken eggs were laid by Barred Rock hens after they were inseminated with chimeric duck semen, of which four chicken offspring hatched and one chicken embryo did not hatch. Female chimeric ducks were inseminated with chicken semen; however, no fertile eggs were obtained. In conclusion, these results demonstrated that chicken PGCs could interact with duck germinal epithelium and complete spermatogenesis and eventually give rise to functional sperm. The PGC-mediated germline chimera technology may provide a novel system for conserving endangered avian species.

  20. 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