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Sample records for induces ectopic meiosis

  1. Meiosis in autologous ectopic transplants of immature testicular tissue grafted to Callithrix jacchus.

    PubMed

    Wistuba, Joachim; Luetjens, C Marc; Wesselmann, Ramona; Nieschlag, Eberhard; Simoni, Manuela; Schlatt, Stefan

    2006-04-01

    Grafting of immature testicular tissue provides a tool to examine testicular development and may offer a perspective for preservation of fertility in prepubertal patients. Successful xenografting in mice, resulting in mature spermatids, has been performed in several species but has failed with testicular tissues from the common marmoset, Callithrix jacchus. Previous data indicate that the hormonal milieu provided by the mouse host might cause this failure. We conducted autologous ectopic transplantation of testicular fragments under the back skin in newborn marmoset monkeys. Seventeen months after transplantation, we found viable transplants in 2 out of the 4 grafted animals. In the transplants, tubules developed up to a state intermediate between the pregraft situation and adult controls. Dividing spermatogonia and primary spermatocytes were present. Boule-like positivity and CDC25A negativity indicated that spermatogenesis was arrested at early meiosis. Immunohistochemistry revealed normal maturation of Sertoli cells, Leydig cells, and peritubular cells. Serum testosterone values were not restored to the normal range and bioactive chorionic gonadotropin levels increased to castrate levels. Meiotic arrest could have occurred in the grafts because of lack of sufficient testosterone or because of hyperthermia caused by the ectopic position of the grafts. We conclude that autologous transplants of immature testicular tissues in the marmoset can mature up to meiosis but that normal serum testosterone levels are not restored. Further studies have to be performed to overcome the meiotic arrest to explore the model further and to develop therapeutic options.

  2. [Signaling pathway of meiosis induced by retinoic acid during spermatogenesis].

    PubMed

    Wang, Ke; Wu, Ying-Ji

    2013-02-01

    Retinoic acid (RA) is an oxidative metabolite of vitamin A (retinol, ROH) and plays an important role in the spermatogenesis (as in meiosis) of mammals. In mammalian testes, RA, in combination with its retinoic acid receptor (RAR), regulates the expressions of related target genes in various types of cells at different times. It activates meiosis by up-regulating the expressions of the genes that promote meiosis and down-regulate those that inhibit it during spermatogenesis in a specific stage. The results of researches on mammalian spermatogenesis have a great application value in reproductive biology, developmental biology, and reproductive engineering. Therefore, it is of considerable significance to study the signaling pathway of RA-induced meiosis during mammalian spermatogenesis. This article presents an introduction of the RA signal transduction system and its action mechanisms, as well as an overview on the signaling pathway of RA-activated meiosis during spermatogenesis.

  3. HO endonuclease-induced recombination in yeast meiosis resembles Spo11-induced events.

    PubMed

    Malkova, A; Klein, F; Leung, W Y; Haber, J E

    2000-12-19

    In meiosis, gene conversions are accompanied by higher levels of crossing over than in mitotic cells. To determine whether the special properties of meiotic recombination can be attributed to the way in which Spo11p creates double-strand breaks (DSBs) at special hot spots in Saccharomyces cerevisiae, we expressed the site-specific HO endonuclease in meiotic cells. We could therefore compare HO-induced recombination in a well-defined region both in mitosis and meiosis, as well as compare Spo11p- and HO-induced meiotic events. HO-induced gene conversions in meiosis were accompanied by crossovers at the same high level (52%) as Spo11p-induced events. Moreover, HO-induced crossovers were reduced 3-fold by a msh4Delta mutation that similarly affects Spo11p-promoted events. In a spo11Delta diploid, where the only DSB is made by HO, crossing over was significantly higher (27%) than in mitotic cells (induce the formation of a synaptonemal complex. We also show that HO-induced gene conversion tract lengths are shorter in meiotic than in mitotic cells. We conclude that a hallmark of meiotic recombination, the production of crossovers, is independent of the nature of Spo11p-generated DSBs at special hotspots, but some functions of Spo11p are required in trans to achieve maximum crossing over.

  4. Ectopically tethered CP190 induces large-scale chromatin decondensation

    NASA Astrophysics Data System (ADS)

    Ahanger, Sajad H.; Günther, Katharina; Weth, Oliver; Bartkuhn, Marek; Bhonde, Ramesh R.; Shouche, Yogesh S.; Renkawitz, Rainer

    2014-01-01

    Insulator mediated alteration in higher-order chromatin and/or nucleosome organization is an important aspect of epigenetic gene regulation. Recent studies have suggested a key role for CP190 in such processes. In this study, we analysed the effects of ectopically tethered insulator factors on chromatin structure and found that CP190 induces large-scale decondensation when targeted to a condensed lacO array in mammalian and Drosophila cells. In contrast, dCTCF alone, is unable to cause such a decondensation, however, when CP190 is present, dCTCF recruits it to the lacO array and mediates chromatin unfolding. The CP190 induced opening of chromatin may not be correlated with transcriptional activation, as binding of CP190 does not enhance luciferase activity in reporter assays. We propose that CP190 may mediate histone modification and chromatin remodelling activity to induce an open chromatin state by its direct recruitment or targeting by a DNA binding factor such as dCTCF.

  5. Clusterin signals via ApoER2/VLDLR and induces meiosis of male germ cells

    PubMed Central

    Riaz, Muhammad Assad; Stammler, Angelika; Borgers, Mareike; Konrad, Lutz

    2017-01-01

    Clusterin (CLU) is a ubiquitously expressed heterodimeric glycoprotein that is involved in a variety of functions like cell-cell interactions, apoptosis, epithelial-mesenchymal transition, carcinogenesis, and chaperone function. In the testis, CLU is strongly expressed especially in Sertoli cells but very little is known about its testicular function, regulation of secretion and most enigmatic, its receptor(s). In this study, we approached these questions with a special emphasis on the link between CLU and meiosis. In cultured seminiferous tubules, we found that secretion of CLU protein is upregulated by transforming growth factor-betas (TGF-β1-3) and observed inhibition of staurosporine-induced apoptosis by recombinant CLU. Clusterin signaling in testicular cells seems to be modulated by very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), because these members of the low density lipoprotein (LDL) receptor family are present in rat germ cells. Furthermore, inhibition of VLDLR/ApoER2 by a specific inhibitor abrogates CLU-mediated phosphorylation of Akt, which mediates VLDLR/ApoER2 signaling. We could also show in tubules treated with recombinant CLU a significant upregulation of several meiosis-associated proteins such as V-myb avian myeloblastosis viral oncogene homolog-like 1 (Mybl1), stimulated by retinoic acid gene 8 (Stra8), lactate dehydrogenase C (LDHC), cAMP response element-binding protein (CREB) and histone H3 (H3S10P). Collectively, our data show for the first time the involvement of CLU in upregulation of meiosis through VLDLR/ApoER2 in male germ cells. PMID:28386352

  6. Ameliorative Effect of Grape Seed Proanthocyanidin Extract on Cadmium-Induced Meiosis Inhibition During Oogenesis in Chicken Embryos.

    PubMed

    Hou, Fuyin; Xiao, Min; Li, Jian; Cook, Devin W; Zeng, Weidong; Zhang, Caiqiao; Mi, Yuling

    2016-04-01

    Cadmium (Cd) is an environmental endocrine disruptor that has toxic effects on the female reproductive system. Here the ameliorative effect of grape seed proanthocyanidin extract (GSPE) on Cd-induced meiosis inhibition during oogenesis was explored. As compared with controls, chicken embryos exposed to Cd (3 µg/egg) displayed a changed oocyte morphology, decreased number of meiotic germ cells, and decreased expression of the meiotic marker protein γH2AX. Real time RT-PCR also revealed a significant down-regulation in the mRNA expressions of various meiosis-specific markers (Stra8, Spo11, Scp3, and Dmc1) together with those of Raldh2, a retinoic acid (RA) synthetase, and of the receptors (RARα and RARβ). In addition, exposure to Cd increased the production of H2 O2 and malondialdehyde in the ovaries and caused a corresponding reduction in glutathione and superoxide dismutase. Simultaneous supplementation of GSPE (150 µg/egg) markedly alleviated the aforementioned Cd-induced embryotoxic effects by upregulating meiosis-related proteins and gene expressions and restoring the antioxidative level. Collectively, the findings provided novel insights into the underlying mechanism of Cd-induced meiosis inhibition and indicated that GSPE might potentially ameliorate related reproductive disorders.

  7. ANA deficiency enhances bone morphogenetic protein-induced ectopic bone formation via transcriptional events.

    PubMed

    Miyai, Kentaro; Yoneda, Mitsuhiro; Hasegawa, Urara; Toita, Sayaka; Izu, Yayoi; Hemmi, Hiroaki; Hayata, Tadayoshi; Ezura, Yoichi; Mizutani, Shuki; Miyazono, Kohei; Akiyoshi, Kazunari; Yamamoto, Tadashi; Noda, Masaki

    2009-04-17

    Ectopic bone formation after joint replacement or brain injury in humans is a serious complication that causes immobility of joints and severe pain. However, mechanisms underlying such ectopic bone formation are not fully understood. Bone morphogenetic protein (BMPs) are defined as inducers of ectopic bone formation, and they are regulated by several types of inhibitors. ANA is an antiproliferative molecule that belongs to Tob/BTG family, but its activity in bone metabolism has not been known. Here, we examined the role of ANA on ectopic bone formation activity of BMP. In ANA-deficient and wild-type mice, BMP2 was implanted to induce ectopic bone formation in muscle. ANA deficiency increased mass of newly formed bone in vivo compared with wild-type based on 3D-muCT analyses. ANA mRNA was expressed in bone in vivo as well as in osteoblastic cells in vitro. Such ANA mRNA levels were increased by BMP2 treatment in MC3T3-E1 osteoblastic cells. Overexpression of ANA suppressed BMP-induced expression of luciferase reporter gene linked to BMP response elements in these cells. Conversely, ANA mRNA knockdown by small interference RNA enhanced the BMP-dependent BMP response element reporter expression. It also enhanced BMP-induced osteoblastic differentiation in muscle-derived C2C12 cells. Immunoprecipitation assay indicated that ANA interacts with Smad8. Thus, ANA is a suppressor of ectopic bone formation induced by BMP, and this inhibitory ANA activity is a part of the negative feedback regulation of BMP function.

  8. ALDH1A1 provides a source of meiosis-inducing retinoic acid in mouse fetal ovaries.

    PubMed

    Bowles, Josephine; Feng, Chun-Wei; Miles, Kim; Ineson, Jessica; Spiller, Cassy; Koopman, Peter

    2016-02-19

    Substantial evidence exists that during fetal ovarian development in mammals, retinoic acid (RA) induces germ cells to express the pre-meiotic marker Stra8 and enter meiosis, and that these effects are prevented in the fetal testis by the RA-degrading P450 enzyme CYP26B1. Nonetheless, the role of RA has been disputed principally because germ cells in embryos lacking two major RA-synthesizing enzymes, ALDH1A2 and ALDH1A3, remain able to enter meiosis. Here we show that a third RA-synthesizing enzyme, ALDH1A1, is expressed in fetal ovaries, providing a likely source of RA in the absence of ALDH1A2 and ALDH1A3. In ovaries lacking ALDH1A1, the onset of germ cell meiosis is delayed. Our data resolve the conundrum posed by conflicting published data sets and reconfirm the model that meiosis is triggered by endogenous RA in the developing ovary.

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

    PubMed

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

    2012-10-09

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

  10. Stimulation-induced ectopicity and propagation windows in model damaged axons.

    PubMed

    Lachance, Mathieu; Longtin, André; Morris, Catherine E; Yu, Na; Joós, Béla

    2014-12-01

    Neural tissue injuries render voltage-gated Na+ channels (Nav) leaky, thereby altering excitability, disrupting propagation and causing neuropathic pain related ectopic activity. In both recombinant systems and native excitable membranes, membrane damage causes the kinetically-coupled activation and inactivation processes of Nav channels to undergo hyperpolarizing shifts. This damage-intensity dependent change, called coupled left-shift (CLS), yields a persistent or "subthreshold" Nav window conductance. Nodes of Ranvier simulations involving various degrees of mild CLS showed that, as the system's channel/pump fluxes attempt to re-establish ion homeostasis, the CLS elicits hyperexcitability, subthreshold oscillations and neuropathic type action potential (AP) bursts. CLS-induced intermittent propagation failure was studied in simulations of stimulated axons, but pump contributions were ignored, leaving open an important question: does mild-injury (small CLS values, pumps functioning well) render propagation-competent but still quiescent axons vulnerable to further impairments as the system attempts to cope with its normal excitatory inputs? We probe this incipient diffuse axonal injury scenario using a 10-node myelinated axon model. Fully restabilized nodes with mild damage can, we show, become ectopic signal generators ("ectopic nodes") because incoming APs stress Na+ / K+ gradients, thereby altering spike thresholds. Comparable changes could contribute to acquired sodium channelopathies as diverse as epileptic phenomena and to the neuropathic amplification of normally benign sensory inputs. Input spike patterns, we found, propagate with good fidelity through an ectopically firing site only when their frequencies exceed the ectopic frequency. This "propagation window" is a robust phenomenon, occurring despite Gaussian noise, large jitter and the presence of several consecutive ectopic nodes.

  11. Marshmallow Meiosis.

    ERIC Educational Resources Information Center

    Soderberg, Patti

    1992-01-01

    Presents an activity in which students model the processes of meiosis, fertilization, development, and birth using model creatures called reebops. Students breed reebops to analyze chromosome combinations. Makes recommendations for activity utilization and identifies the strengths of the activity. (MDH)

  12. Ectopic Pregnancy

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Ectopic Pregnancy KidsHealth > For Parents > Ectopic Pregnancy Print A A ... lower back pain continue What Causes an Ectopic Pregnancy? An ectopic pregnancy usually happens because a fertilized ...

  13. Ectopic Pregnancy

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Ectopic Pregnancy KidsHealth > For Parents > Ectopic Pregnancy A A A ... lower back pain continue What Causes an Ectopic Pregnancy? An ectopic pregnancy usually happens because a fertilized ...

  14. Nitric oxide synthases and tubal ectopic pregnancies induced by Chlamydia infection: basic and clinical insights.

    PubMed

    Shao, Ruijin; Zhang, Sean X; Weijdegård, Birgitta; Zou, Shien; Egecioglu, Emil; Norström, Anders; Brännström, Mats; Billig, Håkan

    2010-12-01

    Human ectopic pregnancy (EP) remains a common cause of pregnancy-related first trimester death. Nitric oxide (NO) is synthesized from L-arginine by three NO synthases (NOS) in different tissues, including the Fallopian tube. Studies of knockout mouse models have improved our understanding of the function of NOS isoforms in reproduction, but their roles and specific mechanisms in infection-induced tubal dysfunction have not been fully elucidated. Here, we provide an overview of the expression, regulation and possible function of NOS isoforms in the Fallopian tube, highlighting the effects of infection-induced changes in the tubal cellular microenvironment (imbalance of NO production) on tubal dysfunction and the potential involvement of NOS isoforms in tubal EP after Chlamydia trachomatis genital infection. The non-equivalent regulation of tubal NOS isoforms during the menstrual cycle suggests that endogenous ovarian steroid hormones regulate NOS in an isoform-specific manner. The current literature suggests that infection with C. trachomatis induces an inflammatory response that eventually leads to tubal epithelial destruction and functional impairment, caused by a high NO output mediated by inducible NOS (iNOS). Therefore, tissue-specific therapeutic approaches to suppress iNOS expression may help to prevent ectopic implantation in patients with prior C. trachomatis infection of the Fallopian tube.

  15. HMGB1 Induces Secretion of Matrix Vesicles by Macrophages to Enhance Ectopic Mineralization

    PubMed Central

    Chen, Qiang; Bei, Jun-Jie; Liu, Chuan; Feng, Shi-Bin; Zhao, Wei-Bo; Zhou, Zhou; Yu, Zheng-Ping; Du, Xiao-Jun; Hu, Hou-Yuan

    2016-01-01

    Numerous clinical conditions have been linked to ectopic mineralization (EM). This process of pathological biomineralization is complex and not fully elucidated, but thought to be started within matrix vesicles (MVs). We hypothesized that high mobility group box 1 (HMGB1), a cytokine associated with biomineralizing process under physiological and pathological conditions, induces EM via promoting MVs secretion from macrophages. In this study, we found that HMGB1 significantly promoted secretion of MVs from macrophages and subsequently led to mineral deposition in elevated Ca/Pi medium in vitro. Transmission electron microscopy of calcifying MVs showed formation of hydroxyapatite crystals in the vesicle interior. Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization. Mechanistic experiments revealed that HMGB1 activated neutral sphingomyelinase2 (nSMase2) that involved the receptor for advanced glycation end products (RAGE) and p38 MAPK (upstream of nSMase2). Inhibition of nSMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and mineral deposition. Collectively, HMGB1 induces MVs secretion from macrophages at least in part, via the RAGE/p38 MAPK/nSMase2 signaling pathway. Our findings thus reveal a novel mechanism by which HMGB1 induces ectopic mineralization. PMID:27243975

  16. Noise-induced ectopic activity in a simple cardiac cell model

    NASA Astrophysics Data System (ADS)

    Hastings, Harold

    2005-03-01

    Ectopic activity in the form of premature ventricular contractions (PVCs) is relatively common in the normal heart. Although PVCs are normally harmless, sometimes but rarely PVCs can generate spiral waves of activation through interaction with other waves of activation, potentially progressing to ventricular tachycardia, followed by ventricular fibrillation and sudden cardiac death. Clusters of PVCs have been found to be significantly more dangerous than isolated PVCs. We model PVC generation by applying triggers (noise) to the generic FitzHugh-Nagumo model as substrate, and study the effects the noise level and excitability. We find: exponential waiting time behavior at fixed parameter levels; no evidence of clustering at fixed parameter levels; and a sharp increase in PVCs as excitability approaches the auto-oscillatory threshold or noise increases beyond a similar threshold. This produces sharp increases in theoretical rates of PVC-induced fibrillation, consistent with results of A Gelzer et al. in animal models. Partially supported by the NSF and NIH.

  17. Ectopic Pregnancy

    MedlinePlus

    ... woman is pregnant. If you have an ectopic pregnancy, the fertilized egg grows in the wrong place, ... tubes. The result is usually a miscarriage. Ectopic pregnancy can be a medical emergency if it ruptures. ...

  18. The Arabidopsis MEI1 gene encodes a protein with five BRCT domains that is involved in meiosis-specific DNA repair events independent of SPO11-induced DSBs.

    PubMed

    Grelon, Mathilde; Gendrot, Ghislaine; Vezon, Daniel; Pelletier, Georges; Mathilde, Grelon; Ghislaine, Gendrot; Daniel, Vezon; Georges, Pelletier

    2003-08-01

    Arabidopsis thaliana MEI1 was first described as a gene involved in male meiosis, encoding a short protein showing homology with a human acrosin-trypsin inhibitor. We have isolated a new allele of mei1, and shown that in both mutants male and female meiosis are affected. In both reproductive pathways, meiosis proceeds while chromosomes become fragmented, resulting in aberrant meiotic products and in a strongly reduced fertility. We have shown that the gene mutated in mei1 mutants actually encodes a protein of 972 amino acids that contains five BRCA1 C-terminus (BRCT) domains and is similar to proteins involved in the response to DNA damage and replication blocks in eukaryotes. During meiosis, recombination is initiated by the formation of DNA double strand breaks (DSBs) induced by the protein SPO11. We analysed meiotic chromosome behaviour of the mei1 mutant in a spo11 mutant background and proved that the meiotic fragmentation observed in mei1 mutants was not the consequence of defects in the repair of meiotic DSBs induced by SPO11. We also analysed the effect of mei1 on the mitotic cell cycle but could not detect any sensitivity of mei1 seedlings to DNA-damaging agents like gamma-rays or UV. Therefore, MEI1 is a BRCT-domain-containing protein that could be specific to the meiotic cell cycle and that plays a crucial role in some DNA repair events independent of SPO11 DSB recombination repair.

  19. Factors That Affect the Location and Frequency of Meiosis-Induced Double-Strand Breaks in Saccharomyces Cerevisiae

    PubMed Central

    Wu, T. C.; Lichten, M.

    1995-01-01

    Double-strand DNA breaks (DSBs) initiate meiotic recombination in Saccharomyces cerevisiae. DSBs occur at sites that are hypersensitive in nuclease digests of chromatin, suggesting a role for chromatin structure in determining DSB location. We show here that the frequency of DSBs at a site is not determined simply by DNA sequence or by features of chromatin structure. An arg4-containing plasmid was inserted at several different locations in the yeast genome. Meiosis-induced DSBs occurred at similar sites in pBR322-derived portions of the construct at all insert loci, and the frequency of these breaks varied in a manner that mirrored the frequency of meiotic recombination in the arg4 portion of the insert. However, DSBs did not occur in the insert-borne arg4 gene at a site that is frequently broken at the normal ARG4 locus, even though the insert-borne arg4 gene and the normal ARG4 locus displayed similar DNase I hypersensitivity patterns. Deletions that removed active DSB sites from an insert at HIS4 restored breaks to the insert-borne arg4 gene and to a DSB site in flanking chromosomal sequences. We conclude that the frequency of DSB at a site can be affected by sequences several thousands nucleotides away and suggest that this is because of competition between DSB sites for locally limited factors. PMID:7635308

  20. Ectopic expression of ceramide synthase 2 in neurons suppresses neurodegeneration induced by ceramide synthase 1 deficiency

    PubMed Central

    Spassieva, Stefka D.; Ji, Xiaojie; Liu, Ye; Gable, Kenneth; Bielawski, Jacek; Dunn, Teresa M.; Bieberich, Erhard; Zhao, Lihong

    2016-01-01

    Sphingolipids exhibit extreme functional and chemical diversity that is in part determined by their hydrophobic moiety, ceramide. In mammals, the fatty acyl chain length variation of ceramides is determined by six (dihydro)ceramide synthase (CerS) isoforms. Previously, we and others showed that mutations in the major neuron-specific CerS1, which synthesizes 18-carbon fatty acyl (C18) ceramide, cause elevation of long-chain base (LCB) substrates and decrease in C18 ceramide and derivatives in the brain, leading to neurodegeneration in mice and myoclonus epilepsy with dementia in humans. Whether LCB elevation or C18 ceramide reduction leads to neurodegeneration is unclear. Here, we ectopically expressed CerS2, a nonneuronal CerS producing C22–C24 ceramides, in neurons of Cers1-deficient mice. Surprisingly, the Cers1 mutant pathology was almost completely suppressed. Because CerS2 cannot replenish C18 ceramide, the rescue is likely a result of LCB reduction. Consistent with this hypothesis, we found that only LCBs, the substrates common for all of the CerS isoforms, but not ceramides and complex sphingolipids, were restored to the wild-type levels in the Cers2-rescued Cers1 mutant mouse brains. Furthermore, LCBs induced neurite fragmentation in cultured neurons at concentrations corresponding to the elevated levels in the CerS1-deficient brain. The strong association of LCB levels with neuronal survival both in vivo and in vitro suggests high-level accumulation of LCBs is a possible underlying cause of the CerS1 deficiency-induced neuronal death. PMID:27162368

  1. Ectopic norrin induces growth of ocular capillaries and restores normal retinal angiogenesis in Norrie disease mutant mice.

    PubMed

    Ohlmann, Andreas; Scholz, Michael; Goldwich, Andreas; Chauhan, Bharesh K; Hudl, Kristiane; Ohlmann, Anne V; Zrenner, Eberhart; Berger, Wolfgang; Cvekl, Ales; Seeliger, Mathias W; Tamm, Ernst R

    2005-02-16

    Norrie disease is an X-linked retinal dysplasia that presents with congenital blindness, sensorineural deafness, and mental retardation. Norrin, the protein product of the Norrie disease gene (NDP), is a secreted protein of unknown biochemical function. Norrie disease (Ndp(y/-)) mutant mice that are deficient in norrin develop blindness, show a distinct failure in retinal angiogenesis, and completely lack the deep capillary layers of the retina. We show here that the transgenic expression of ectopic norrin under control of a lens-specific promoter restores the formation of a normal retinal vascular network in Ndp(y/-) mutant mice. The improvement in structure correlates with restoration of neuronal function in the retina. In addition, lenses of transgenic mice with ectopic expression of norrin show significantly more capillaries in the hyaloid vasculature that surrounds the lens during development. In vitro, lenses of transgenic mice in coculture with microvascular endothelial cells induce proliferation of the cells. Transgenic mice with ectopic expression of norrin show more bromodeoxyuridine-labeled retinal progenitor cells at embryonic day 14.5 and thicker retinas at postnatal life than wild-type littermates, indicating a putative direct neurotrophic effect of norrin. These data provide direct evidence that norrin induces growth of ocular capillaries and that pharmacologic modulation of norrin might be used for treatment of the vascular abnormalities associated with Norrie disease or other vascular disorders of the retina.

  2. In vitro steroid-induced meiosis in Rhinella arenarum oocytes: role of pre-MPF activation.

    PubMed

    Arias Torres, Ana Josefina; Bühler, Marta Inés; Zelarayán, Liliana Isabel

    2016-04-01

    In this work we showed the relationship between seasonal periods and the response of R. arenarum follicles and oocytes to different steroids. Using in vitro germinal vesicle breakdown (GVBD) assays, we demonstrated that P4 is the main steroid capable of inducing maturation in R. arenarum oocytes and follicles. In the second part of this work we showed that androgens can activate pre-maturation promoting factors (pre-MPFs) such as P4, by cytoplasm microinjection experiments. The results indicated that the steroids assayed induced oocyte and follicle maturation in a dose- and time-dependent manner. In oocytes, P4 was the most efficient steroid as a maturation inducer (EC50 of the reproductive period, 6 nM, EC50 of the non-reproductive period ≅ 30 nM). Androgens (DHEA, dehydroepiandrosterone; T, testosterone; and AD, androstenedione) were less efficient maturation inducers than P4 (EC50 reproductive period ≅ 50, 120 and 600 nM respectively). Similar results were obtained with intact follicles in both seasonal periods. Although the response of follicles to the different androgens was variable, in no case was it above the above the response induced by P4. Independently of the season, oocytes and follicles incubated in P4, P5 and T underwent GVBD after 6-10 h while oocytes and follicles incubated in DHEA and AD matured more slowly. Furthermore, we demonstrated that microinjection of mature cytoplasm from androgen-treated oocytes is sufficient to promote GVBD in immature recipient oocytes (DHEA, 57 ± 12%; AD, 60 ± 8%; T, 56 ± 13%). Thus, androgens such as DHEA, T and AD are as competent as P4 to activate pre-MPF.

  3. Ectopic pregnancy

    MedlinePlus

    Tubal pregnancy; Cervical pregnancy; Tubal ligation - ectopic pregnancy ... In most pregnancies, the fertilized egg travels through the fallopian tube to the womb (uterus). If the movement of the egg ...

  4. The cohesin subunit Rad21 is required for synaptonemal complex maintenance, but not sister chromatid cohesion, during Drosophila female meiosis.

    PubMed

    Urban, Evelin; Nagarkar-Jaiswal, Sonal; Lehner, Christian F; Heidmann, Stefan K

    2014-08-01

    Replicated sister chromatids are held in close association from the time of their synthesis until their separation during the next mitosis. This association is mediated by the ring-shaped cohesin complex that appears to embrace the sister chromatids. Upon proteolytic cleavage of the α-kleisin cohesin subunit at the metaphase-to-anaphase transition by separase, sister chromatids are separated and segregated onto the daughter nuclei. The more complex segregation of chromosomes during meiosis is thought to depend on the replacement of the mitotic α-kleisin cohesin subunit Rad21/Scc1/Mcd1 by the meiotic paralog Rec8. In Drosophila, however, no clear Rec8 homolog has been identified so far. Therefore, we have analyzed the role of the mitotic Drosophila α-kleisin Rad21 during female meiosis. Inactivation of an engineered Rad21 variant by premature, ectopic cleavage during oogenesis results not only in loss of cohesin from meiotic chromatin, but also in precocious disassembly of the synaptonemal complex (SC). We demonstrate that the lateral SC component C(2)M can interact directly with Rad21, potentially explaining why Rad21 is required for SC maintenance. Intriguingly, the experimentally induced premature Rad21 elimination, as well as the expression of a Rad21 variant with destroyed separase consensus cleavage sites, do not interfere with chromosome segregation during meiosis, while successful mitotic divisions are completely prevented. Thus, chromatid cohesion during female meiosis does not depend on Rad21-containing cohesin.

  5. The Cohesin Subunit Rad21 Is Required for Synaptonemal Complex Maintenance, but Not Sister Chromatid Cohesion, during Drosophila Female Meiosis

    PubMed Central

    Lehner, Christian F.; Heidmann, Stefan K.

    2014-01-01

    Replicated sister chromatids are held in close association from the time of their synthesis until their separation during the next mitosis. This association is mediated by the ring-shaped cohesin complex that appears to embrace the sister chromatids. Upon proteolytic cleavage of the α-kleisin cohesin subunit at the metaphase-to-anaphase transition by separase, sister chromatids are separated and segregated onto the daughter nuclei. The more complex segregation of chromosomes during meiosis is thought to depend on the replacement of the mitotic α-kleisin cohesin subunit Rad21/Scc1/Mcd1 by the meiotic paralog Rec8. In Drosophila, however, no clear Rec8 homolog has been identified so far. Therefore, we have analyzed the role of the mitotic Drosophila α-kleisin Rad21 during female meiosis. Inactivation of an engineered Rad21 variant by premature, ectopic cleavage during oogenesis results not only in loss of cohesin from meiotic chromatin, but also in precocious disassembly of the synaptonemal complex (SC). We demonstrate that the lateral SC component C(2)M can interact directly with Rad21, potentially explaining why Rad21 is required for SC maintenance. Intriguingly, the experimentally induced premature Rad21 elimination, as well as the expression of a Rad21 variant with destroyed separase consensus cleavage sites, do not interfere with chromosome segregation during meiosis, while successful mitotic divisions are completely prevented. Thus, chromatid cohesion during female meiosis does not depend on Rad21-containing cohesin. PMID:25101996

  6. Doing the Meiosis Shuffle.

    ERIC Educational Resources Information Center

    Krauskopf, Sara

    1999-01-01

    Presents a game called the Meiosis Shuffle that helps students simulate the process of meiosis in which homologous cards representing chromosomes pair up, line up, and split apart. Students respond well to the simulation and are better able to conceptualize what chromosomes do and how independent assortment causes genetic variation. (CCM)

  7. Main features of meiosis

    SciTech Connect

    1993-12-31

    Chapter 17, outlines the main features of meiosis, beginning with its significance and proceeding through the meiotic stages. Meiosis is the most important modification of mitosis because it is the reduction division that gives rise to the haploid generation in the life cycle. 17 refs., 6 figs.

  8. Meiosis in male Drosophila

    PubMed Central

    McKee, Bruce D.; Yan, Rihui; Tsai, Jui-He

    2012-01-01

    Meiosis entails sorting and separating both homologous and sister chromatids. The mechanisms for connecting sister chromatids and homologs during meiosis are highly conserved and include specialized forms of the cohesin complex and a tightly regulated homolog synapsis/recombination pathway designed to yield regular crossovers between homologous chromatids. Drosophila male meiosis is of special interest because it dispenses with large segments of the standard meiotic script, particularly recombination, synapsis and the associated structures. Instead, Drosophila relies on a unique protein complex composed of at least two novel proteins, SNM and MNM, to provide stable connections between homologs during meiosis I. Sister chromatid cohesion in Drosophila is mediated by cohesins, ring-shaped complexes that entrap sister chromatids. However, unlike other eukaryotes Drosophila does not rely on the highly conserved Rec8 cohesin in meiosis, but instead utilizes two novel cohesion proteins, ORD and SOLO, which interact with the SMC1/3 cohesin components in providing meiotic cohesion. PMID:23087836

  9. Ectopic over-expression of oncogene Pim-2 induce malignant transformation of nontumorous human liver cell line L02.

    PubMed

    Ren, Ke; Duan, Wentao; Shi, Yujun; Li, Bo; Liu, Zuojin; Gong, Jiangping

    2010-07-01

    In order to prove that ectopic over-expression of Pim-2 could induce malignant transformation of human liver cell line L02, three groups of cells were set up including human liver cell line L02 (L02), L02 cells transfected with Pim-2 gene (L02/Pim-2) and L02 cells transfected with empty-vector (L02/Vector). Pim-2 expression levels were detected. The morphology, proliferation level, apoptosis rate and migration ability of the cells were detected respectively. Then the cells were subcutaneously inoculated into athymic mice and the microstructures of the neoplasm were observed. Compared with the controls, Pim-2 expression levels were significantly higher in L02/Pim-2 cells (P<0.05), and their morphology had obvious malignant changes. They also showed a significantly increased proliferation rate (P<0.05) and migration capacity (P<0.05), as well as a significantly decreased apoptosis rate (P<0.05). Only the athymic mice inoculated with L02/Pim-2 cells could generate neoplasm, and the morphology of the neoplasm coincided with that of the hepatoma. The results manifest that ectopic Pim-2 gene could be stably expressed in L02/Pim-2 cells. Both the morphological and biological changes of L02/Pim-2 cells demonstrate the trend of malignant transformation. L02/Pim-2 cells could generate hepatoma in athymic mice. In conclusion, Pim-2 could induce malignant transformation of human liver cell line L02.

  10. Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis.

    PubMed

    Jiang, Xiu Xiu; Fei, Xiang Wei; Zhao, Li; Ye, Xiao Lei; Xin, Liao Bin; Qu, Yang; Xu, Kai Hong; Wu, Rui Jin; Lin, Jun

    2015-01-01

    Aquaporin 5 (AQP5) participates in the migration of endometrial cells. Elucidation of the molecular mechanisms associated with AQP5-mediated, migration of endometrial cells may contribute to a better understanding of endometriosis. Our objectives included identifying the estrogen-response element (ERE) in the promoter region of the AQP5 gene, and, investigating the effects of AQP5 on ectopic implantation of endometrial cells. Luciferase reporter assays and electrophoretic mobility shift assay (EMSA) identified the ERE-like motif in the promoter region of the AQP5 gene. After blocking and up-regulating estradiol (E2) levels, we analysed the expression of AQP5 in endometrial stromal (ES) cells. After blocking E2 /or phosphatidylinositol 3 kinase(PI3K), we analysed the role of AQP5 in signaling pathways. We constructed an AQP5, shRNA, lentiviral vector to knock out the AQP5 gene in ES cells. After knock-out of the AQP5 gene, we studied the role of AQP5 in cell invasion, proliferation, and the formation of ectopic endometrial implants in female mice. We identified an estrogen-response element in the promoter region of the AQP5 gene. Estradiol (E2) increased AQP5 expression in a dose-dependent fashion, that was blocked by ICI182,780(an estrogen receptor inhibitor). E2 activated PI3K /protein kinase B(AKT) pathway (PI3K/AKT), that, in turn, increased AQP5 expression. LY294002(PI3K inhibitor) attenuated estrogen-enhanced, AQP5 expression. Knock-out of the AQP5 gene with AQP5 shRNA lentiviral vector significantly inhibited E2-enhanced invasion, proliferation of ES cells and formation of ectopic implants. Estrogen induces AQP5 expression by activating ERE in the promoter region of the AQP5gene, activates the PI3K/AKT pathway, and, promotes endometrial cell invasion and proliferation. These results provide new insights into some of the mechanisms that may underpin the development of deposits of ectopic endometrium.

  11. Ectopic ERK Expression Induces Phenotypic Conversion of C10 Cells and Alters DNA Methyltransferase Expression

    SciTech Connect

    Sontag, Ryan L.; Weber, Thomas J.

    2012-05-04

    In some model systems constitutive extracellular signal regulated kinase (ERK) activation is sufficient to promote an oncogenic phenotype. Here we investigate whether constitutive ERK expression influences phenotypic conversion in murine C10 type II alveolar epithelial cells. C10 cells were stably transduced with an ERK1-green fluorescent protein (ERK1-GFP) chimera or empty vector and ectopic ERK expression was associated with the acquisition of soft agar focus-forming potential in late passage, but not early passage cells. Late passage ERK1-GFP cells exhibited a significant increase in the expression of DNA methyl transferases (DNMT1 and 3b) and a marked increase in sensitivity to 5-azacytidine (5-azaC)-mediated toxicity, relative to early passage ERK1-GFP cells and vector controls. The expression of xeroderma pigmentosum complementation group A (XPA) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) were significantly increased in late passage cells, suggesting enhanced DNA damage recognition and repair activity which we interpret as a reflection of genomic instability. Phospho-ERK levels were dramatically decreased in late passage ERK1-GFP cells, relative to early passage and vector controls, and phospho-ERK levels were restored by treatment with sodium orthovanadate, indicating a role for phosphatase activity in this response. Collectively these observations suggest that ectopic ERK expression promotes phenotypic conversion of C10 cells that is associated with latent effects on epigenetic programming and phosphatase activities.

  12. Details of meiosis

    SciTech Connect

    1993-12-31

    Chapter 18, discusses the details of meiosis, beginning with the structure and number of chiasmata, i.e., the cytological term for two homologous chromosomes forming a bivalent which begin to repel each other until they are held together only at the point of crossing-over. The synaptonemal complex which consists of two lateral elements which contain protein and RNA is also discussed. The chapter concludes with a description of meiosis in polyploids, human meiosis, and the behavior of X and Y chromosomes. 28 refs., 8 figs.

  13. Tinkering with meiosis

    PubMed Central

    Crismani, Wayne; Girard, Chloé; Mercier, Raphael

    2013-01-01

    Meiosis is at the heart of Mendelian heredity. Recently, much progress has been made in the understanding of this process, in various organisms. In the last fifteen years, the functional characterization of numerous genes involved in meiosis has dramatically deepened our knowledge of key events, including recombination, cell cycle and chromosome distribution. Through a constantly advancing tool set and knowledge base, a number of advances have been made that will allow manipulation of meiosis from a plant breeding perspective. This review focuses on the aspects of meiosis that can be tinkered with to create and propagate new varieties. We would like to dedicate this review to the memory of Simon W. Chan (1974-2012) http://www.plb.ucdavis.edu/labs/srchan/ PMID:23136169

  14. Tinkering with meiosis.

    PubMed

    Crismani, Wayne; Girard, Chloé; Mercier, Raphael

    2013-01-01

    Meiosis is at the heart of Mendelian heredity. Recently, much progress has been made in the understanding of this process, in various organisms. In the last 15 years, the functional characterization of numerous genes involved in meiosis has dramatically deepened our knowledge of key events, including recombination, the cell cycle, and chromosome distribution. Through a constantly advancing tool set and knowledge base, a number of advances have been made that will allow manipulation of meiosis from a plant breeding perspective. This review focuses on the aspects of meiosis that can be tinkered with to create and propagate new varieties. We would like to dedicate this review to the memory of Simon W. Chan (1974-2012) (http://www.plb.ucdavis.edu/labs/srchan/).

  15. Hemorrhagic ascites from spontaneous ectopic mesenteric varices rupture in NASH induced cirrhosis and successful outcome: a case report.

    PubMed

    Edula, Raja G R; Qureshi, Kamran; Khallafi, Hicham

    2014-07-07

    Bleeding from gastro-esophageal varices can often present as the first decompensating event in patients with cirrhosis. This can be a potentially life threatening event associated with a 15%-20% early mortality. We present a rare case of new onset ascites due to intra-abdominal hemorrhage from ruptured mesenteric varices; in a 37 years old male with newly diagnosed nonalcoholic steatohepatitis induced cirrhosis as the first decompensating event. The patient was successfully resuscitated with emergent evacuation of ascites for diagnosis, identification and control of bleeding mesenteric varices and eventually orthotopic liver transplantation with successful outcome. Various clinical presentations, available treatment options and outcomes of ectopic variceal bleeding are discussed in this report.

  16. Nerve injury induces robust allodynia and ectopic discharges in Nav1.3 null mutant mice

    PubMed Central

    Nassar, Mohammed A; Baker, Mark D; Levato, Alessandra; Ingram, Rachel; Mallucci, Giovanna; McMahon, Stephen B; Wood, John N

    2006-01-01

    Changes in sodium channel activity and neuronal hyperexcitability contribute to neuropathic pain, a major clinical problem. There is strong evidence that the re-expression of the embryonic voltage-gated sodium channel subunit Nav1.3 underlies neuronal hyperexcitability and neuropathic pain. Here we show that acute and inflammatory pain behaviour is unchanged in global Nav1.3 mutant mice. Surprisingly, neuropathic pain also developed normally in the Nav1.3 mutant mouse. To rule out any genetic compensation mechanisms that may have masked the phenotype, we investigated neuropathic pain in two conditional Nav1.3 mutant mouse lines. We used Nav1.8-Cre mice to delete Nav1.3 in nociceptors at E14 and NFH-Cre mice to delete Nav1.3 throughout the nervous system postnatally. Again normal levels of neuropathic pain developed after nerve injury in both lines. Furthermore, ectopic discharges from damaged nerves were unaffected by the absence of Nav1.3 in global knock-out mice. Our data demonstrate that Nav1.3 is neither necessary nor sufficient for the development of nerve-injury related pain. PMID:17052333

  17. Microscopic Procedures for Plant Meiosis.

    ERIC Educational Resources Information Center

    Braselton, James P.

    1997-01-01

    Describes laboratory techniques designed to familiarize students with meiosis and how microscopic preparations of meiosis are made. These techniques require the use of fresh or fixed flowers. Contains 18 references. (DDR)

  18. Meiosis-Driven Genome Variation in Plants

    PubMed Central

    Cai, Xiwen; Xu, Steven S

    2007-01-01

    Meiosis includes two successive divisions of the nucleus with one round of DNA replication and leads to the formation of gametes with half of the chromosomes of the mother cell during sexual reproduction. It provides a cytological basis for gametogenesis and nheritance in eukaryotes. Meiotic cell division is a complex and dynamic process that involves a number of molecular and cellular events, such as DNA and chromosome replication, chromosome pairing, synapsis and recombination, chromosome segregation, and cytokinesis. Meiosis maintains genome stability and integrity over sexual life cycles. On the other hand, meiosis generates genome variations in several ways. Variant meiotic recombination resulting from specific genome structures induces deletions, duplications, and other rearrangements within the genic and non-genic genomic regions and has been considered a major driving force for gene and genome evolution in nature. Meiotic abnormalities in chromosome segregation lead to chromosomally imbalanced gametes and aneuploidy. Meiotic restitution due to failure of the first or second meiotic division gives rise to unreduced gametes, which triggers polyploidization and genome expansion. This paper reviews research regarding meiosis-driven genome variation, including deletion and duplication of genomic regions, aneuploidy, and polyploidization, and discusses the effect of related meiotic events on genome variation and evolution in plants. Knowledge of various meiosis-driven genome variations provides insight into genome evolution and genetic variability in plants and facilitates plant genome research. PMID:18645601

  19. Identification of a Copper-Inducible Promoter for Use in Ectopic Expression in the Fungal Pathogen Histoplasma capsulatum†

    PubMed Central

    Gebhart, Dana; Bahrami, Adam K.; Sil, Anita

    2006-01-01

    Despite the existence of a number of genetic tools to study the fungal pathogen Histoplasma capsulatum, strategies for conditional gene expression have not been developed. We used microarray analysis to identify genes that are transcriptionally induced or repressed by the addition of copper sulfate (CuSO4) to H. capsulatum yeast cultures. One of these genes, CRP1, encodes a putative copper efflux pump that is significantly induced in the presence of CuSO4. The upstream regulatory region of CRP1 was sufficient to drive copper-regulated expression of two reporter genes, lacZ and the gene encoding green fluorescent protein. Microarray experiments were performed to determine a copper concentration that triggers accumulation of the CRP1 transcript without significant perturbation of global gene expression. These studies show that the CRP1 upstream regulatory region can be used for ectopic expression of heterologous genes in H. capsulatum. Furthermore, they demonstrate the strategic use of microarrays to identify conditional promoters that confer induction in the absence of large-scale shifts in gene expression. PMID:16757741

  20. A 140-Bp-Long Palindromic Sequence Induces Double-Strand Breaks during Meiosis in the Yeast Saccharomyces Cerevisiae

    PubMed Central

    Nag, D. K.; Kurst, A.

    1997-01-01

    Palindromic sequences have the potential to form hairpin or cruciform structures, which are putative substrates for several nucleases and mismatch repair enzymes. A genetic method was developed to detect such structures in vivo in the yeast Saccharomyces cerevisiae. Using this method we previously showed that short hairpin structures are poorly repaired by the mismatch repair system in S. cerevisiae. We show here that mismatches, when present in the stem of the hairpin structure, are not processed by the repair machinery, suggesting that they are treated differently than those in the interstrand base-paired duplex DNA. A 140-bp-long palindromic sequence, on the contrary, acts as a meiotic recombination hotspot by generating a site for a double-strand break, an initiator of meiotic recombination. We suggest that long palindromic sequences undergo cruciform extrusion more readily than short ones. This cruciform structure then acts as a substrate for structure-specific nucleases resulting in the formation of a double-strand break during meiosis in yeast. In addition, we show that residual repair of the short hairpin structure occurs in an MSH2-independent pathway. PMID:9215890

  1. Cdc14 phosphatase directs centrosome re-duplication at the meiosis I to meiosis II transition in budding yeast

    PubMed Central

    2017-01-01

    Background Gametes are generated through a specialized cell division called meiosis, in which ploidy is reduced by half because two consecutive rounds of chromosome segregation, meiosis I and meiosis II, occur without intervening DNA replication. This contrasts with the mitotic cell cycle where DNA replication and chromosome segregation alternate to maintain the same ploidy. At the end of mitosis, CDKs are inactivated. This low CDK state in late mitosis/G1 allows for critical preparatory events for DNA replication and centrosome/spindle pole body (SPB) duplication. However, their execution is inhibited until S phase, where further preparatory events are also prevented. This “licensing” ensures that both the chromosomes and the centrosomes/SPBs replicate exactly once per cell cycle, thereby maintaining constant ploidy. Crucially, between meiosis I and meiosis II, centrosomes/SPBs must be re-licensed, but DNA re-replication must be avoided. In budding yeast, the Cdc14 protein phosphatase triggers CDK down regulation to promote exit from mitosis. Cdc14 also regulates the meiosis I to meiosis II transition, though its mode of action has remained unclear. Methods Fluorescence and electron microscopy was combined with proteomics to probe SPB duplication in cells with inactive or hyperactive Cdc14. Results We demonstrate that Cdc14 ensures two successive nuclear divisions by re-licensing SPBs at the meiosis I to meiosis II transition. We show that Cdc14 is asymmetrically enriched on a single SPB during anaphase I and provide evidence that this enrichment promotes SPB re-duplication. Cells with impaired Cdc14 activity fail to promote extension of the SPB half-bridge, the initial step in morphogenesis of a new SPB. Conversely, cells with hyper-active Cdc14 duplicate SPBs, but fail to induce their separation. Conclusion Our findings implicate reversal of key CDK-dependent phosphorylations in the differential licensing of cyclical events at the meiosis I to meiosis I

  2. Regulation of germ cell meiosis in the fetal ovary.

    PubMed

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

    2012-01-01

    Fertility depends on correct regulation of meiosis, the special form of cell division that gives rise to haploid gametes. In female mammals, germ cells enter meiosis during fetal ovarian development, while germ cells in males avoid entering meiosis until puberty. Decades of research have shown that meiotic entry, and germ cell sex determination, are not initiated intrinsically within the germ cells. Instead, meiosis is induced by signals produced by the surrounding somatic cells. More recently, retinoic acid (RA), the active derivative of vitamin A, has been implicated in meiotic induction during fetal XX and postnatal XY germ cell development. Evidence for an intricate system of RA synthesis and degradation in the fetal ovary and testis has emerged, explaining past observations of infertility in vitamin A-deficient rodents. Here we review how meiosis is triggered in fetal ovarian germ cells, paying special attention to the role of RA in this process.

  3. Evolutionary mysteries in meiosis.

    PubMed

    Lenormand, Thomas; Engelstädter, Jan; Johnston, Susan E; Wijnker, Erik; Haag, Christoph R

    2016-10-19

    Meiosis is a key event of sexual life cycles in eukaryotes. Its mechanistic details have been uncovered in several model organisms, and most of its essential features have received various and often contradictory evolutionary interpretations. In this perspective, we present an overview of these often 'weird' features. We discuss the origin of meiosis (origin of ploidy reduction and recombination, two-step meiosis), its secondary modifications (in polyploids or asexuals, inverted meiosis), its importance in punctuating life cycles (meiotic arrests, epigenetic resetting, meiotic asymmetry, meiotic fairness) and features associated with recombination (disjunction constraints, heterochiasmy, crossover interference and hotspots). We present the various evolutionary scenarios and selective pressures that have been proposed to account for these features, and we highlight that their evolutionary significance often remains largely mysterious. Resolving these mysteries will likely provide decisive steps towards understanding why sex and recombination are found in the majority of eukaryotes.This article is part of the themed issue 'Weird sex: the underappreciated diversity of sexual reproduction'.

  4. Bdf1 Bromodomains Are Essential for Meiosis and the Expression of Meiotic-Specific Genes

    PubMed Central

    Perot, Jonathan; Arlotto, Marie; Mietton, Flore; Boland, Anne; Deleuze, Jean-François; Ferro, Myriam; Govin, Jérôme

    2017-01-01

    Bromodomain and Extra-terminal motif (BET) proteins play a central role in transcription regulation and chromatin signalling pathways. They are present in unicellular eukaryotes and in this study, the role of the BET protein Bdf1 has been explored in Saccharomyces cerevisiae. Mutation of Bdf1 bromodomains revealed defects on both the formation of spores and the meiotic progression, blocking cells at the exit from prophase, before the first meiotic division. This phenotype is associated with a massive deregulation of the transcription of meiotic genes and Bdf1 bromodomains are required for appropriate expression of the key meiotic transcription factor NDT80 and almost all the Ndt80-inducible genes, including APC complex components. Bdf1 notably accumulates on the promoter of Ndt80 and its recruitment is dependent on Bdf1 bromodomains. In addition, the ectopic expression of NDT80 during meiosis partially bypasses this dependency. Finally, purification of Bdf1 partners identified two independent complexes with Bdf2 or the SWR complex, neither of which was required to complete sporulation. Taken together, our results unveil a new role for Bdf1 –working independently from its predominant protein partners Bdf2 and the SWR1 complex–as a regulator of meiosis-specific genes. PMID:28068333

  5. Turning Meiosis into Mitosis

    PubMed Central

    d'Erfurth, Isabelle; Jolivet, Sylvie; Froger, Nicole; Catrice, Olivier; Novatchkova, Maria; Mercier, Raphaël

    2009-01-01

    Apomixis, or asexual clonal reproduction through seeds, is of immense interest due to its potential application in agriculture. One key element of apomixis is apomeiosis, a deregulation of meiosis that results in a mitotic-like division. We isolated and characterised a novel gene that is directly involved in controlling entry into the second meiotic division. By combining a mutation in this gene with two others that affect key meiotic processes, we created a genotype called MiMe in which meiosis is totally replaced by mitosis. The obtained plants produce functional diploid gametes that are genetically identical to their mother. The creation of the MiMe genotype and apomeiosis phenotype is an important step towards understanding and engineering apomixis. PMID:19513101

  6. Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish

    PubMed Central

    Lisse, Thomas S.; Middleton, Leah J.; Pellegrini, Adriana D.; Martin, Paige B.; Spaulding, Emily L.; Lopes, Olivia; Brochu, Elizabeth A.; Carter, Erin V.; Waldron, Ashley; Rieger, Sandra

    2016-01-01

    Paclitaxel is a microtubule-stabilizing chemotherapeutic agent that is widely used in cancer treatment and in a number of curative and palliative regimens. Despite its beneficial effects on cancer, paclitaxel also damages healthy tissues, most prominently the peripheral sensory nervous system. The mechanisms leading to paclitaxel-induced peripheral neuropathy remain elusive, and therapies that prevent or alleviate this condition are not available. We established a zebrafish in vivo model to study the underlying mechanisms and to identify pharmacological agents that may be developed into therapeutics. Both adult and larval zebrafish displayed signs of paclitaxel neurotoxicity, including sensory axon degeneration and the loss of touch response in the distal caudal fin. Intriguingly, studies in zebrafish larvae showed that paclitaxel rapidly promotes epithelial damage and decreased mechanical stress resistance of the skin before induction of axon degeneration. Moreover, injured paclitaxel-treated zebrafish skin and scratch-wounded human keratinocytes (HEK001) display reduced healing capacity. Epithelial damage correlated with rapid accumulation of fluorescein-conjugated paclitaxel in epidermal basal keratinocytes, but not axons, and up-regulation of matrix-metalloproteinase 13 (MMP-13, collagenase 3) in the skin. Pharmacological inhibition of MMP-13, in contrast, largely rescued paclitaxel-induced epithelial damage and neurotoxicity, whereas MMP-13 overexpression in zebrafish embryos rendered the skin vulnerable to injury under mechanical stress conditions. Thus, our studies provide evidence that the epidermis plays a critical role in this condition, and we provide a previously unidentified candidate for therapeutic interventions. PMID:27035978

  7. Ectopic AtCBF1 over-expression enhances freezing tolerance and induces cold acclimation-associated physiological modifications in potato.

    PubMed

    Pino, María-Teresa; Skinner, Jeffrey S; Jeknić, Zoran; Hayes, Patrick M; Soeldner, Alfred H; Thomashow, Michael F; Chen, Tony H H

    2008-04-01

    We studied the effect of ectopic AtCBF over-expression on physiological alterations that occur during cold exposure in frost-sensitive Solanum tuberosum and frost-tolerant Solanum commersonii. Relative to wild-type plants, ectopic AtCBF1 over-expression induced expression of COR genes without a cold stimulus in both species, and imparted a significant freezing tolerance gain in both species: 2 degrees C in S. tuberosum and up to 4 degrees C in S. commersonii. Transgenic S. commersonii displayed improved cold acclimation potential, whereas transgenic S. tuberosum was still incapable of cold acclimation. During cold treatment, leaves of wild-type S. commersonii showed significant thickening resulting from palisade cell lengthening and intercellular space enlargement, whereas those of S. tuberosum did not. Ectopic AtCBF1 activity induced these same leaf alterations in the absence of cold in both species. In transgenic S. commersonii, AtCBF1 activity also mimicked cold treatment by increasing proline and total sugar contents in the absence of cold. Relative to wild type, transgenic S. commersonii leaves were darker green, had higher chlorophyll and lower anthocyanin levels, greater stomatal numbers, and displayed greater photosynthetic capacity, suggesting higher productivity potential. These results suggest an endogenous CBFpathway is involved in many of the structural, biochemical and physiological alterations associated with cold acclimation in these Solanum species.

  8. Constitutive activation of ectodermal β-catenin induces ectopic outgrowths at various positions in mouse embryo and affects abdominal ventral body wall closure.

    PubMed

    Zhu, Xuming; Huang, Sixia; Zhang, Lingling; Wu, Yumei; Chen, Yingwei; Tao, Yixin; Wang, Yushu; He, Shigang; Shen, Sanbing; Wu, Ji; Li, Baojie; Guo, Xizhi; He, Lin; Ma, Gang

    2014-01-01

    Vertebrate limbs originate from the lateral plate mesoderm (LPM) and the overlying ectoderm. While normal limb formation in defined regions has been well studied, the question of whether other positions retain limb-forming potential has not been fully investigated in mice. By ectopically activating β-catenin in the ectoderm with Msx2-cre, we observed that local tissue outgrowths were induced, which either progressed into limb-like structure within the inter-limb flank or formed extra tissues in other parts of the mouse embryo. In the presumptive abdominal region of severely affected embryos, ectopic limb formation was coupled with impaired abdominal ventral body wall (AVBW) closure, which indicates the existence of a potential counterbalance of limb formation and AVBW closure. At the molecular level, constitutive β-catenin activation was sufficient to trigger, but insufficient to maintain the ectopic expression of a putative limb-inducing factor, Fgf8, in the ectoderm. These findings provide new insight into the mechanism of limb formation and AVBW closure, and the crosstalk between the Wnt/β-catenin pathway and Fgf signal.

  9. Transient ectopic overexpression of agouti-signalling protein 1 (asip1) induces pigment anomalies in flatfish.

    PubMed

    Guillot, Raúl; Ceinos, Rosa Maria; Cal, Rosa; Rotllant, Josep; Cerdá-Reverter, José Miguel

    2012-01-01

    While flatfish in the wild exhibit a pronounced countershading of the dorso-ventral pigment pattern, malpigmentation is commonly observed in reared animals. In fish, the dorso-ventral pigment polarity is achieved because a melanization inhibition factor (MIF) inhibits melanoblast differentiation and encourages iridophore proliferation in the ventrum. A previous work of our group suggested that asip1 is the uncharacterized MIF concerned. In order to further support this hypothesis, we have characterized asip1 mRNAs in both turbot and sole and used deduced peptide alignments to analyze the evolutionary history of the agouti-family of peptides. The putative asip precursors have the characteristics of a secreted protein, displaying a putative hydrophobic signal. Processing of the potential signal peptide produces mature proteins that include an N-terminal region, a basic central domain with a high proportion of lysine residues as well as a proline-rich region that immediately precedes the C-terminal poly-cysteine domain. The expression of asip1 mRNA in the ventral area was significantly higher than in the dorsal region. Similarly, the expression of asip1 within the unpigmented patches in the dorsal skin of pseudoalbino fish was higher than in the pigmented dorsal regions but similar to those levels observed in the ventral skin. In addition, the injection/electroporation of asip1 capped mRNA in both species induced long term dorsal skin paling, suggesting the inhibition of the melanogenic pathways. The data suggest that fish asip1 is involved in the dorsal-ventral pigment patterning in adult fish, where it induces the regulatory asymmetry involved in precursor differentiation into mature chromatophore. Adult dorsal pseudoalbinism seems to be the consequence of the expression of normal developmental pathways in an inaccurate position that results in unbalanced asip1 production levels. This, in turn, generates a ventral-like differentiation environment in dorsal regions.

  10. A phenotypic screen in zebrafish identifies a novel small-molecule inducer of ectopic tail formation suggestive of alterations in non-canonical Wnt/PCP signaling.

    PubMed

    Gebruers, Evelien; Cordero-Maldonado, María Lorena; Gray, Alexander I; Clements, Carol; Harvey, Alan L; Edrada-Ebel, Ruangelie; de Witte, Peter A M; Crawford, Alexander D; Esguerra, Camila V

    2013-01-01

    Zebrafish have recently emerged as an attractive model for the in vivo bioassay-guided isolation and characterization of pharmacologically active small molecules of natural origin. We carried out a zebrafish-based phenotypic screen of over 3000 plant-derived secondary metabolite extracts with the goal of identifying novel small-molecule modulators of the BMP and Wnt signaling pathways. One of the bioactive plant extracts identified in this screen - Jasminum gilgianum, an Oleaceae species native to Papua New Guinea - induced ectopic tails during zebrafish embryonic development. As ectopic tail formation occurs when BMP or non-canonical Wnt signaling is inhibited during the tail protrusion process, we suspected a constituent of this extract to act as a modulator of these pathways. A bioassay-guided isolation was carried out on the basis of this zebrafish phenotype, identifying para-coumaric acid methyl ester (pCAME) as the active compound. We then performed an in-depth phenotypic analysis of pCAME-treated zebrafish embryos, including a tissue-specific marker analysis of the secondary tails. We found pCAME to synergize with the BMP-inhibitors dorsomorphin and LDN-193189 in inducing ectopic tails, and causing convergence-extension defects in compound-treated embryos. These results indicate that pCAME may interfere with non-canonical Wnt signaling. Inhibition of Jnk, a downstream target of Wnt/PCP signaling (via morpholino antisense knockdown and pharmacological inhibition with the kinase inhibitor SP600125) phenocopied pCAME-treated embryos. However, immunoblotting experiments revealed pCAME to not directly inhibit Jnk-mediated phosphorylation of c-Jun, suggesting additional targets of SP600125, and/or other pathways, as possibly being involved in the ectopic tail formation activity of pCAME. Further investigation of pCAME's mechanism of action will help determine this compound's pharmacological utility.

  11. ATP analog-sensitive Pat1 protein kinase for synchronous fission yeast meiosis at physiological temperature

    PubMed Central

    Cipak, Lubos; Hyppa, Randy; Smith, Gerald; Gregan, Juraj

    2012-01-01

    To study meiosis, synchronous cultures are often indispensable, especially for physical analyses of DNA and proteins. A temperature-sensitive allele of the Pat1 protein kinase (pat1-114) has been widely used to induce synchronous meiosis in the fission yeast Schizosaccharomyces pombe, but pat1-114-induced meiosis differs from wild-type meiosis, and some of these abnormalities might be due to higher temperature needed to inactivate the Pat1 kinase. Here, we report an ATP analog-sensitive allele of Pat1 [Pat1(L95A), designated pat1-as2] that can be used to generate synchronous meiotic cultures at physiological temperature. In pat1-as2 meiosis, chromosomes segregate with higher fidelity, and spore viability is higher than in pat1-114 meiosis, although recombination is lower by a factor of 2–3 in these mutants than in starvation-induced pat1+ meiosis. Addition of the mat-Pc gene improved chromosome segregation and spore viability to nearly the level of starvation-induced meiosis. We conclude that pat1-as2 mat-Pc cells offer synchronous meiosis with most tested properties similar to those of wild-type meiosis. PMID:22487684

  12. Directly auto-transplanted mesenchymal stem cells induce bone formation in a ceramic bone substitute in an ectopic sheep model.

    PubMed

    Boos, Anja M; Loew, Johanna S; Deschler, Gloria; Arkudas, Andreas; Bleiziffer, Oliver; Gulle, Heinz; Dragu, Adrian; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

    2011-06-01

    Bone tissue engineering approaches increasingly focus on the use of mesenchymal stem cells (MSC). In most animal transplantation models MSC are isolated and expanded before auto cell transplantation which might be critical for clinical application in the future. Hence this study compares the potential of directly auto-transplanted versus in vitro expanded MSC with or without bone morphogenetic protein-2 (BMP-2) to induce bone formation in a large volume ceramic bone substitute in the sheep model. MSC were isolated from bone marrow aspirates and directly auto-transplanted or expanded in vitro and characterized using fluorescence activated cell sorting (FACS) and RT-PCR analysis before subcutaneous implantation in combination with BMP-2 and β-tricalcium phosphate/hydroxyapatite (β-TCP/HA) granules. Constructs were explanted after 1 to 12 weeks followed by histological and RT-PCR evaluation. Sheep MSC were CD29(+), CD44(+) and CD166(+) after selection by Ficoll gradient centrifugation, while directly auto-transplanted MSC-populations expressed CD29 and CD166 at lower levels. Both, directly auto-transplanted and expanded MSC, were constantly proliferating and had a decreasing apoptosis over time in vivo. Directly auto-transplanted MSC led to de novo bone formation in a heterotopic sheep model using a β-TCP/HA matrix comparable to the application of 60 μg/ml BMP-2 only or implantation of expanded MSC. Bone matrix proteins were up-regulated in constructs following direct auto-transplantation and in expanded MSC as well as in BMP-2 constructs. Up-regulation was detected using immunohistology methods and RT-PCR. Dense vascularization was demonstrated by CD31 immunohistology staining in all three groups. Ectopic bone could be generated using directly auto-transplanted or expanded MSC with β-TCP/HA granules alone. Hence BMP-2 stimulation might become dispensable in the future, thus providing an attractive, clinically feasible approach to bone tissue engineering.

  13. MAPK Phosphatase AP2C3 Induces Ectopic Proliferation of Epidermal Cells Leading to Stomata Development in Arabidopsis

    PubMed Central

    Kazanaviciute, Vaiva; Magyar, Zoltan; Ayatollahi, Zahra; Unterwurzacher, Verena; Choopayak, Chonnanit; Boniecka, Justyna; Murray, James A. H.; Bogre, Laszlo; Meskiene, Irute

    2010-01-01

    In plant post-embryonic epidermis mitogen-activated protein kinase (MAPK) signaling promotes differentiation of pavement cells and inhibits initiation of stomata. Stomata are cells specialized to modulate gas exchange and water loss. Arabidopsis MAPKs MPK3 and MPK6 are at the core of the signaling cascade; however, it is not well understood how the activity of these pleiotropic MAPKs is constrained spatially so that pavement cell differentiation is promoted only outside the stomata lineage. Here we identified a PP2C-type phosphatase termed AP2C3 (Arabidopsis protein phosphatase 2C) that is expressed distinctively during stomata development as well as interacts and inactivates MPK3, MPK4 and MPK6. AP2C3 co-localizes with MAPKs within the nucleus and this localization depends on its N-terminal extension. We show that other closely related phosphatases AP2C2 and AP2C4 are also MAPK phosphatases acting on MPK6, but have a distinct expression pattern from AP2C3. In accordance with this, only AP2C3 ectopic expression is able to stimulate cell proliferation leading to excess stomata development. This function of AP2C3 relies on the domains required for MAPK docking and intracellular localization. Concomitantly, the constitutive and inducible AP2C3 expression deregulates E2F-RB pathway, promotes the abundance and activity of CDKA, as well as changes of CDKB1;1 forms. We suggest that AP2C3 downregulates the MAPK signaling activity to help maintain the balance between differentiation of stomata and pavement cells. PMID:21203456

  14. The chemokine receptor CXCR5 is pivotal for ectopic mucosa-associated lymphoid tissue neogenesis in chronic Helicobacter pylori-induced inflammation.

    PubMed

    Winter, Susann; Loddenkemper, Christoph; Aebischer, Anton; Räbel, Katrin; Hoffmann, Kirstin; Meyer, Thomas F; Lipp, Martin; Höpken, Uta E

    2010-11-01

    Ectopic lymphoid follicles are a key feature of chronic inflammatory autoimmune and infectious diseases, such as rheumatoid arthritis, Sjögren's syndrome, and Helicobacter pylori-induced gastritis. Homeostatic chemokines are considered to be involved in the formation of such tertiary lymphoid tissue. High expression of CXCL13 and its receptor, CXCR5, has been associated with the formation of ectopic lymphoid follicles in chronic infectious diseases. Here, we defined the role of CXCR5 in the development of mucosal tertiary lymphoid tissue and gastric inflammation in a mouse model of chronic H. pylori infection. CXCR5-deficient mice failed to develop organized gastric lymphoid follicles despite similar bacterial colonization density as infected wild-type mice. CXCR5 deficiency altered Th17 responses but not Th1-type cellular immune responses to H. pylori infection. Furthermore, CXCR5-deficient mice exhibited lower H. pylori-specific serum IgG and IgA levels and an overall decrease in chronic gastric immune responses. In conclusion, the development of mucosal tertiary ectopic follicles during chronic H. pylori infection is strongly dependent on the CXCL13/CXCR5 signaling axis, and lack of de novo lymphoid tissue formation attenuates chronic immune responses.

  15. Ectopic pregnancy (image)

    MedlinePlus

    An ectopic pregnancy is one in which the fertilized egg implants in tissue outside of the uterus and the placenta ... common site is within a Fallopian tube, however, ectopic pregnancies can occur in the ovary, the abdomen, and ...

  16. [Sex chromosomes and meiosis].

    PubMed

    Guichaoua, M-R; Geoffroy-Siraudin, C; Tassistro, V; Ghalamoun-Slaimi, R; Perrin, J; Metzler-Guillemain, C

    2009-01-01

    Sex chromosome behaviour fundamentally differs between male and female meiosis. In oocyte, X chromosomes synapse giving a XX bivalent which is not recognizable in their morphology and behaviour from autosomal bivalents. In human male, X and Y chromosomes differ from one another in their morphology and their genetic content, leading to a limited pairing and preventing genetic recombination, excepted in homologous region PAR1. During pachytene stage of the first meiotic prophase, X and Y chromosomes undergo a progressive condensation and form a transcriptionally silenced peripheral XY body. The condensation of the XY bivalent during pachytene stage led us to describe four pachytene substages and to localize the pachytene checkpoint between substages 2 and 3. We also defined the pachytene index (PI=P1+P2/P1+P2+P3+P4) which is always less than 0.50 in normal meiosis. XY body undergoes decondensation at diplotene stage, but transcriptional inactivation of the two sex chromosomes or Meiotic Sex Chromosome Inactivation (MSCI) persists through to the end of spermatogenesis. Sex chromosome inactivation involves several proteins, some of them were now identified. Two isoforms of the HP1 protein, HP1beta and HP1gamma, are involved in the facultative heterochromatinization of the XY body, but the initiation of this process involves the phosphorylation of the protein H2AX by the kinase ATR whose recruitment depends on BRCA1. Extensive researches on the inactivation of the sex chromosomes during male meiosis will allow to a better understanding of some male infertilities.

  17. TOPping off meiosis.

    PubMed

    Haber, James E

    2015-02-19

    Double-strand breaks (DSBs) threaten chromosome integrity. The most accurate repair of DSBs is by homologous recombination (HR), catalyzed by recombination proteins such as Rad51. Three papers in this issue of Molecular Cell (Fasching et al., 2015; Kaur et al., 2015; Tang et al., 2015) now reveal the role of three of these proteins in budding yeast: Sgs1 (BLM homolog), Top3 (TOPIIIα homolog), and Rmi1. They demonstrate several steps where all three proteins act together, and find additional functions of the Top3-Rmi1 subcomplex that are critical for the completion of meiosis.

  18. Atypical ploidy cycles, Spo11, and the evolution of meiosis.

    PubMed

    Bloomfield, Gareth

    2016-06-01

    The Spo11 protein induces DNA double strand breaks before the first division of meiosis, enabling the formation of the chiasmata that physically link homologous chromosomes as they align. Spo11 is an ancient and well conserved protein, related in sequence and structure to a DNA topoisomerase subunit found in Archaea as well as a subset of eukaryotes. However the origins of its meiotic function are unclear. This review examines some apparent exceptions to the rule that Spo11 activity is specific to, and required for meiosis. Spo11 appears to function in the context of unusual forms of ploidy reduction in some protists and fungi. One lineage of amoebae, the dictyostelids, is thought to undergo meiosis during its sexual cycle despite having lost Spo11 entirely. Further experimental characterisation of these and other non-canonical ploidy cycling mechanisms may cast light of the evolution of meiosis.

  19. Dose-response study and threshold estimation of griseofulvin-induced aneuploidy during female mouse meiosis I and II.

    PubMed

    Marchetti, F; Mailhes, J B; Bairnsfather, L; Nandy, I; London, S N

    1996-03-01

    The relative sensitivity of the two meiotic divisions of mouse oogenesis to griseofulvin (GF)-induced aneuploidy was investigated. The first meiotic division was studied by administering GF 4 h after human chorionic gonadotrophin (HCG) injection and analyzing metaphase II (MII) oocytes, whereas study of the second meiotic division involved treating the females 10 h after HCG and analyzing one-cell (1-Cl) zygotes. Data from previous studies have shown that these treatment times represented the most sensitive times for aneuploidy induction during meioses I and II. The statistical analyses of the data showed that the dose-response curves for aneuploidy induction did not differ quantitatively or qualitatively between the two meiotic divisions. The percentages of hyperploid MII oocytes and 1-Cl zygotes were significantly higher (P < 0.001) than in the controls for all doses except 125 mg/kg GF. The highest percentages of hyperploid cells were found after administering 1500 mg/kg GF. However, these percentages were not different (P > 0.05) from those observed after 500 or 1000 mg/kg GF, suggesting saturation of the GF aneuploid target(s). These results suggest that the relative sensitivity to GF-induced aneuploidy between the two meiotic divisions of oogenesis are similar. They also suggest the presence of a lower (125 mg/kg) and an upper 500 mg/kg) threshold for GF-induced aneuploidy.

  20. Two DNA repair and recombination genes in Saccharomyces cerevisiae, RAD52 and RAD54, are induced during meiosis

    SciTech Connect

    Cole, G.M.; Mortimer, R.K. ); Schild, D. )

    1989-07-01

    The DNA repair and recombination genes of Saccharomyces cerevisiae, RAD52 and RAD54, were transcriptionally induced approximately 10- to 15-fold in sporulating MATa/{alpha} cells. Congenic MATa/a cells, which did not sporulate, did not show similar increases. Assays of {beta}-galactosidase activity in strains harboring either a RAD52- or RAD54-lacZ gene fusion indicated that this induction occurred at a time concomitant with a commitment to meiotic recombination, as measured by prototroph formation from his1 heteroalleles.

  1. Differentiation of osteoblast‑like cells and ectopic bone formation induced by bone marrow stem cells transfected with chitosan nanoparticles containing plasmid‑BMP2 sequences.

    PubMed

    Hong, Zhang Qing; Tao, Liu Meng; Bin, Zhang Xiao

    2017-03-01

    The present study investigated the efficiency of the use of chitosan nanoparticles containing plasmid‑bone morphogenetic protein 2 (pBMP2) sequences (CNPBs) to induce the differentiation of bone marrow stem cells (BMSCs) into osteoblast‑like cells that may be able to promote ectopic bone formation. pBMP2s were constructed, and chitosan nanoparticles were incubated with 50, 100 or 200 µg/ml pBMP2. BMSCs were collected from the tibiae and femurs of 6‑week old rats, cultured and treated with the CNPBs or 200 µg/ml pBMP2 as a positive control. Transfection efficiency was confirmed using the green fluorescent protein assay. Histological staining methods, including alkaline phosphatase, Wright's and von Kasso staining, were used to identify features of osteoblast‑like cells differentiated from BMSCs. Expression levels of the markers of osteoblasts, such as alkaline phosphatase, osteoprotegerin, osteocalcin and osteopontin, were determined to verify the differentiation of BMSCs into osteoblast‑like cells. Ectopic bone formation was observed following the integration of polyglycolic acid (PGA) scaffolds with CNPBs and BMSCs, which were implanted into the dorsal muscles of Sprague‑Dawley rats. Exposure to CNPBs led to the transfection of BMSCs with BMP2. The transfected BMSCs possessed the characteristic phenotypes of osteoblasts. The expression levels of alkaline phosphatase, osteoprotegerin, osteocalcin and osteopontin were significantly higher in the transfected cells compared with the control group, particularly the CBP200 group. PGA scaffolds integrated with BMSCs and CNPBs induced ectopic bone formation, as changes in the morphology of cells were observed using histological staining. Therefore, CNPBs may be a promising method of promoting the formation of novel bone tissue.

  2. Control of mammalian germ cell entry into meiosis.

    PubMed

    Feng, Chun-Wei; Bowles, Josephine; Koopman, Peter

    2014-01-25

    Germ cells are unique in undergoing meiosis to generate oocytes and sperm. In mammals, meiosis onset is before birth in females, or at puberty in males, and recent studies have uncovered several regulatory steps involved in initiating meiosis in each sex. Evidence suggests that retinoic acid (RA) induces expression of the critical pre-meiosis gene Stra8 in germ cells of the fetal ovary, pubertal testis and adult testis. In the fetal testis, CYP26B1 degrades RA, while FGF9 further antagonises RA signalling to suppress meiosis. Failsafe mechanisms involving Nanos2 may further suppress meiosis in the fetal testis. Here, we draw together the growing knowledge relating to these meiotic control mechanisms, and present evidence that they are co-ordinately regulated and that additional factors remain to be identified. Understanding this regulatory network will illuminate not only how the foundations of mammalian reproduction are laid, but also how mis-regulation of these steps can result in infertility or germline tumours.

  3. Black hole meiosis

    NASA Astrophysics Data System (ADS)

    van Herck, Walter; Wyder, Thomas

    2010-04-01

    The enumeration of BPS bound states in string theory needs refinement. Studying partition functions of particles made from D-branes wrapped on algebraic Calabi-Yau 3-folds, and classifying states using split attractor flow trees, we extend the method for computing a refined BPS index, [1]. For certain D-particles, a finite number of microstates, namely polar states, exclusively realized as bound states, determine an entire partition function (elliptic genus). This underlines their crucial importance: one might call them the ‘chromosomes’ of a D-particle or a black hole. As polar states also can be affected by our refinement, previous predictions on elliptic genera are modified. This can be metaphorically interpreted as ‘crossing-over in the meiosis of a D-particle’. Our results improve on [2], provide non-trivial evidence for a strong split attractor flow tree conjecture, and thus suggest that we indeed exhaust the BPS spectrum. In the D-brane description of a bound state, the necessity for refinement results from the fact that tachyonic strings split up constituent states into ‘generic’ and ‘special’ states. These are enumerated separately by topological invariants, which turn out to be partitions of Donaldson-Thomas invariants. As modular predictions provide a check on many of our results, we have compelling evidence that our computations are correct.

  4. Arabidopsis homeodomain-leucine zipper IV proteins promote stomatal development and ectopically induce stomata beyond the epidermis.

    PubMed

    Peterson, Kylee M; Shyu, Christine; Burr, Christian A; Horst, Robin J; Kanaoka, Masahiro M; Omae, Minami; Sato, Yutaka; Torii, Keiko U

    2013-05-01

    The shoot epidermis of land plants serves as a crucial interface between plants and the atmosphere: pavement cells protect plants from desiccation and other environmental stresses, while stomata facilitate gas exchange and transpiration. Advances have been made in our understanding of stomatal patterning and differentiation, and a set of 'master regulatory' transcription factors of stomatal development have been identified. However, they are limited to specifying stomatal differentiation within the epidermis. Here, we report the identification of an Arabidopsis homeodomain-leucine zipper IV (HD-ZIP IV) protein, HOMEODOMAIN GLABROUS2 (HDG2), as a key epidermal component promoting stomatal differentiation. HDG2 is highly enriched in meristemoids, which are transient-amplifying populations of stomatal-cell lineages. Ectopic expression of HDG2 confers differentiation of stomata in internal mesophyll tissues and occasional multiple epidermal layers. Conversely, a loss-of-function hdg2 mutation delays stomatal differentiation and, rarely but consistently, results in aberrant stomata. A closely related HD-ZIP IV gene, Arabidopsis thaliana MERISTEM LAYER1 (AtML1), shares overlapping function with HDG2: AtML1 overexpression also triggers ectopic stomatal differentiation in the mesophyll layer and atml1 mutation enhances the stomatal differentiation defects of hdg2. Consistently, HDG2 and AtML1 bind the same DNA elements, and activate transcription in yeast. Furthermore, HDG2 transactivates expression of genes that regulate stomatal development in planta. Our study highlights the similarities and uniqueness of these two HD-ZIP IV genes in the specification of protodermal identity and stomatal differentiation beyond predetermined tissue layers.

  5. Ectopic expression of class 1 KNOX genes induce adventitious shoot regeneration and alter growth and development of tobacco (Nicotiana tabacum L) and European plum (Prunus domestica L).

    PubMed

    Srinivasan, C; Liu, Zongrang; Scorza, Ralph

    2011-04-01

    Transgenic plants of tobacco (Nicotiana tabacum L) and European plum (Prunus domestica L) were produced by transforming with the apple class 1 KNOX genes (MdKN1 and MdKN2) or corn KNOX1 gene. Transgenic tobacco plants were regenerated in vitro from transformed leaf discs cultured in a medium lacking cytokinin. Ectopic expression of KNOX genes retarded shoot growth by suppressing elongation of internodes in transgenic tobacco plants. Expression of each of the three KNOX1 genes induced malformation and extensive lobbing in tobacco leaves. In situ regeneration of adventitious shoots was observed from leaves and roots of transgenic tobacco plants expressing each of the three KNOX genes. In vitro culture of leaf explants and internode sections excised from in vitro grown MdKN1 expressing tobacco shoots regenerated adventitious shoots on MS (Murashige and Skoog 1962) basal medium in the absence of exogenous cytokinin. Transgenic plum plants that expressed the MdKN2 or corn KNOX1 gene grew normally but MdKN1 caused a significant reduction in plant height, leaf shape and size and produced malformed curly leaves. A high frequency of adventitious shoot regeneration (96%) was observed in cultures of leaf explants excised from corn KNOX1-expressing transgenic plum shoots. In contrast to KNOX1-expressing tobacco, leaf and internode explants of corn KNOX1-expressing plum required synthetic cytokinin (thidiazuron) in the culture medium to induce adventitious shoot regeneration. The induction of high-frequency regeneration of adventitious shoots in vitro from leaves and stem internodal sections of plum through the ectopic expression of a KNOX1 gene is the first such report for a woody perennial fruit trees.

  6. Impact of ectopic pregnancy for reproductive prognosis in next generation.

    PubMed

    Kårhus, Line Lund; Egerup, Pia; Skovlund, Charlotte Wessel; Lidegaard, Øjvind

    2014-04-01

    The impact of an ectopic pregnancy in the next generation is unknown. Our aim was to compare reproductive outcomes in daughters of women with and without ectopic pregnancy. Designed as a historical prospective controlled cohort study with data collected in four Danish registries from 1977-2009, women with ectopic pregnancy during 1977-1982 were age-matched to women without ectopic pregnancy. Daughters of these two cohorts were followed until 2009. We compared 5126 daughters of women with ectopic pregnancy with 19 928 daughters of women without ectopic pregnancy. The daughters of women with ectopic pregnancy had a 1.5-fold (95% confidence interval 1.2-1.9) increased risk of ectopic pregnancy, while for deliveries this was 1.0 (1.0-1.1), for miscarriages 1.1 (1.0-1.2), and for induced abortions 1.3 (1.2-1.4). Daughters of mothers with ectopic pregnancy have a 50% higher risk of ectopic pregnancy than daughters of women without an ectopic pregnancy, but a normal delivery rate.

  7. [Transverse ectopic testis].

    PubMed

    Jouini, Riadh; Lefi, Mounir; Sami, Chelly; Manef, Gesmi; Mohsen, Belguith; Nouri, Abdellatif

    2002-09-01

    Transverse ectopic testis (TET) is a rare form of ectopic testis. The authors report the case of a 2-month-old infant presenting with right inguinoscrotal hernia and ectopic left testis with an impalpable testis. Opening of the hernia sac revealed two testes with two distally fused vasa deferentes. The contralateral testis was easily descended by translocation through the other inguinal canal. A favourable result was obtained with two testes situated in a normal position. In the light of this case, the authors emphasize the clinical and therapeutic features of this anomaly.

  8. Bioinformatic identification of Ustilago maydis meiosis genes.

    PubMed

    Donaldson, Michael E; Saville, Barry J

    2008-08-01

    In the corn smut pathogen, Ustilago maydis, meiosis and teliospore germination are temporally linked. We review teliospore dormancy and germination in U. maydis and present an overview of meiosis in basidiomycetes. The relevant available expressed sequence tag data is discussed, the databases used in reciprocal best hit blastp analysis are presented and potential U. maydis meiosis genes are identified. The implications of identifying these genes are discussed and hypotheses are presented regarding the control of meiosis in U. maydis.

  9. The colocalization transition of homologous chromosomes at meiosis

    NASA Astrophysics Data System (ADS)

    Nicodemi, Mario; Panning, Barbara; Prisco, Antonella

    2008-06-01

    Meiosis is the specialized cell division required in sexual reproduction. During its early stages, in the mother cell nucleus, homologous chromosomes recognize each other and colocalize in a crucial step that remains one of the most mysterious of meiosis. Starting from recent discoveries on the system molecular components and interactions, we discuss a statistical mechanics model of chromosome early pairing. Binding molecules mediate long-distance interaction of special DNA recognition sequences and, if their concentration exceeds a critical threshold, they induce a spontaneous colocalization transition of chromosomes, otherwise independently diffusing.

  10. Development of a Meiosis Concept Inventory

    ERIC Educational Resources Information Center

    Kalas, Pamela; O'Neill, Angie; Pollock, Carol; Birol, Gulnur

    2013-01-01

    We have designed, developed, and validated a 17-question Meiosis Concept Inventory (Meiosis CI) to diagnose student misconceptions on meiosis, which is a fundamental concept in genetics. We targeted large introductory biology and genetics courses and used published methodology for question development, which included the validation of questions by…

  11. Inhibition of SRY-calmodulin complex formation induces ectopic expression of ovarian cell markers in developing XY gonads.

    PubMed

    Sim, Helena; Argentaro, Anthony; Czech, Daniel P; Bagheri-Fam, Stefan; Sinclair, Andrew H; Koopman, Peter; Boizet-Bonhoure, Brigitte; Poulat, Francis; Harley, Vincent R

    2011-07-01

    The transcription factor sex-determining region of the Y chromosome (SRY) plays a key role in human sex determination, because mutations in SRY cause disorders of sex development in XY individuals. During gonadal development, Sry in pre-Sertoli cells activates Sox9 gene transcription, committing the fate of the bipotential gonad to become a testis rather than an ovary. The high-mobility group domain of human SRY contains two independent nuclear localization signals, one bound by calmodulin (CaM) and the other by importin-β. Although XY females carry SRY mutations in these nuclear localization signals that affect SRY nuclear import in transfected cells, it is not known whether these transport mechanisms are essential for gonadal development and sex determination. Here, we show that mouse Sry protein binds CaM and that a CaM antagonist reduces CaM binding, nuclear accumulation, and transcriptional activity of Sry in transfected cells. CaM antagonist treatment of cultured, sexually indifferent XY mouse fetal gonads led to reduced expression of the Sry target gene Sox9, defects in testicular cord formation, and ectopic expression of the ovarian markers Rspondin1 and forkhead box L2. These results indicate the importance of CaM for SRY nuclear import, transcriptional activity, testis differentiation, and sex determination.

  12. Biglycan (Bgn) and fibromodulin (Fmod) in ectopic ossification of tendon induced by exercise and in rotarod performance

    PubMed Central

    Kilts, T.; Ameye, L.; Syed-Picard, F.; Ono, M.; Berendsen, A. D.; Oldberg, A.; Heegaard, A-M.; Bi, Y.; Young, M.F.

    2009-01-01

    We describe the ectopic ossification (EO) found in tendons of biglycan (Bgn), fibromodulin (Fmod) single and double Bgn/Fmod deficient (DKO) mice with aging. At 3 months, Fmod KO, Bgn KO and DKO displayed torn cruciate ligaments and EO in their quadriceps tendon, menisci and cruciate and patellar ligaments. The phenotype was the least severe in the Fmod KO, intermediate in the Bgn KO and the most severe in the DKO. This condition progressed with age in all 3 mouse strains and resulted in the development of large supernumerary sesmoid bones. To determine the role of exercise on the extent of EO, we subjected normal and DKO mice to treadmill exercise for 3 days a week for 4 weeks. The EO in moderately exercised DKO was decreased compared to unexercised DKO mice. Finally, DKO and Bgn KO mice tested using a rotarod showed they had a reduced ability to maintain their grip on a rotating cylinder compared to WT controls. In summary, we show: 1) a detailed description of EO formed by Bgn, Fmod or combined depletion, 2) the role of exercise in modulating EO, and 3) that Bgn and Fmod are critical in controlling motor function. PMID:19422643

  13. [Ectopic pregnancy in Senegal].

    PubMed

    Cissé, Cheikh A Tidiane; Bernis, Luc De; Faye, El Hadj Ousseynou; Diadhiou, Fadel

    2002-01-01

    The objective of this prospective study was to analyse the epidemiology and prognosis of ectopic pregnancy in Senegal. From January 1 to December 31, 1996, 255 ectopic pregnancies were registered. The national rate of ectopic pregnancy was 0.6%. of expected pregnancies. However, rates differed greatly between areas in Senegal, with extremes ranging from 0.85%. in Dakar to 0.32%. in Thiès. The epidemiological profile was that of a young woman-mean age: 23 years old, mean parity=3, admitted with broken ectopic pregnancy (95%). A salpingectomy was performed in all cases. The maternal mortality rate was 1.20%, while morbidity, mainly due to post-operative infection, was found in 2.7% of the cases.

  14. Ectopic expression of DREF induces DNA synthesis, apoptosis, and unusual morphogenesis in the Drosophila eye imaginal disc: possible interaction with Polycomb and trithorax group proteins.

    PubMed

    Hirose, F; Ohshima, N; Shiraki, M; Inoue, Y H; Taguchi, O; Nishi, Y; Matsukage, A; Yamaguchi, M

    2001-11-01

    The promoters of Drosophila genes encoding DNA replication-related proteins contain transcription regulatory element DRE (5'-TATCGATA) in addition to E2F recognition sites. A specific DRE-binding factor, DREF, positively regulates DRE-containing genes. In addition, it has been reported that DREF can bind to a sequence in the hsp70 scs' chromatin boundary element that is also recognized by boundary element-associated factor, and thus DREF may participate in regulating insulator activity. To examine DREF function in vivo, we established transgenic flies in which ectopic expression of DREF was targeted to the eye imaginal discs. Adult flies expressing DREF exhibited a severe rough eye phenotype. Expression of DREF induced ectopic DNA synthesis in the cells behind the morphogenetic furrow, which are normally postmitotic, and abolished photoreceptor specifications of R1, R6, and R7. Furthermore, DREF expression caused apoptosis in the imaginal disc cells in the region where commitment to R1/R6 cells takes place, suggesting that failure of differentiation of R1/R6 photoreceptor cells might cause apoptosis. The DREF-induced rough eye phenotype was suppressed by a half-dose reduction of the E2F gene, one of the genes regulated by DREF, indicating that the DREF overexpression phenotype is useful to screen for modifiers of DREF activity. Among Polycomb/trithorax group genes, we found that a half-dose reduction of some of the trithorax group genes involved in determining chromatin structure or chromatin remodeling (brahma, moira, and osa) significantly suppressed and that reduction of Distal-less enhanced the DREF-induced rough eye phenotype. The results suggest a possibility that DREF activity might be regulated by protein complexes that play a role in modulating chromatin structure. Genetic crosses of transgenic flies expressing DREF to a collection of Drosophila deficiency stocks allowed us to identify several genomic regions, deletions of which caused enhancement or

  15. Holocentric plant meiosis: first sisters, then homologues.

    PubMed

    Heckmann, Stefan; Schubert, Veit; Houben, Andreas

    2014-01-01

    Meiosis is a crucial process of sexual reproduction by forming haploid gametes from diploid precursor cells. It involves 2 subsequent divisions (meiosis I and meiosis II) after one initial round of DNA replication. Homologous monocentric chromosomes are separated during the first and sister chromatids during the second meiotic division. The faithful segregation of monocentric chromosomes is realized by mono-orientation of fused sister kinetochores at metaphase I and by bi-orientation of sister kinetochores at metaphase II. Conventionally this depends on a 2-step loss of cohesion, along chromosome arms during meiosis I and at sister centromeres during meiosis II.

  16. Molecular diagnostics and therapeutics for ectopic pregnancy.

    PubMed

    Tong, Stephen; Skubisz, Monika M; Horne, Andrew W

    2015-02-01

    Ectopic pregnancies are a serious gynaecological emergency that can be fatal. As such, prompt diagnosis and safe timely treatment is essential. Here, we review the literature on the development of molecularly targeted diagnostics and therapeutics for ectopic pregnancy. A blood-based biomarker that accurately identifies an ectopic pregnancy could be used to offer early diagnostic certainty in cases where ultrasound cannot determine the location of the embryo ('a pregnancy of unknown location'). Molecules examined so far can be broadly grouped into biological themes of relevance to reproduction: (i) Fallopian tube (dys)function, (ii) embryo/trophoblast growth, (iii) corpus luteum function, (iv) inflammation, (v) uterine function and (vi) angiogenesis. While a sensitive and specific biomarker for ectopic pregnancy has yet to be identified, it is possible that improvements in platform technologies or a multi-modal biomarker approach may yield an accurate diagnostic biomarker test. Furthermore, with the advent of better imaging technology, the need for a blood-based biomarker test may be superseded by improvements in ultrasound or magnetic resonance imaging technology. There have been some recent preclinical studies describing molecularly targeted therapeutic approaches for ectopic pregnancy. Notably, bench-to-bedside studies have examined the use of combination gefitinib (orally available epidermal growth factor receptor inhibitor) and methotrexate. Preclinical studies suggest that combination gefitinib and methotrexate is highly effective in inducing placental cell death, and is significantly more effective than methotrexate alone. In early human trials, encouraging preliminary efficacy data have shown that combination gefitinib and methotrexate can rapidly resolve tubal ectopic pregnancies, and large extra-tubal ectopic pregnancies. If a large clinical randomized controlled trial confirms these findings, combination gefitinib and methotrexate could become a new

  17. Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age.

    PubMed

    Jones, Keith T

    2008-01-01

    Mammalian oocytes begin meiosis in the fetal ovary, but only complete it when fertilized in the adult reproductive tract. This review examines the cell biology of this protracted process: from entry of primordial germ cells into meiosis to conception. The defining feature of meiosis is two consecutive cell divisions (meiosis I and II) and two cell cycle arrests: at the germinal vesicle (GV), dictyate stage of prophase I and at metaphase II. These arrests are spanned by three key events, the focus of this review: (i) passage from mitosis to GV arrest during fetal life, regulated by retinoic acid; (ii) passage through meiosis I and (iii) completion of meiosis II following fertilization, both meiotic divisions being regulated by cyclin-dependent kinase (CDK1) activity. Meiosis I in human oocytes is associated with an age-related high rate of chromosomal mis-segregation, such as trisomy 21 (Down's syndrome), resulting in aneuploid conceptuses. Although aneuploidy is likely to be multifactorial, oocytes from older women may be predisposed to be becoming aneuploid as a consequence of an age-long decline in the cohesive ties holding chromosomes together. Such loss goes undetected by the oocyte during meiosis I either because its ability to respond and block division also deteriorates with age, or as a consequence of being inherently unable to respond to the types of segregation defects induced by cohesion loss.

  18. Elevated mutation rate during meiosis in Saccharomyces cerevisiae.

    PubMed

    Rattray, Alison; Santoyo, Gustavo; Shafer, Brenda; Strathern, Jeffrey N

    2015-01-01

    Mutations accumulate during all stages of growth, but only germ line mutations contribute to evolution. While meiosis contributes to evolution by reassortment of parental alleles, we show here that the process itself is inherently mutagenic. We have previously shown that the DNA synthesis associated with repair of a double-strand break is about 1000-fold less accurate than S-phase synthesis. Since the process of meiosis involves many programmed DSBs, we reasoned that this repair might also be mutagenic. Indeed, in the early 1960's Magni and Von Borstel observed elevated reversion of recessive alleles during meiosis, and found that the revertants were more likely to be associated with a crossover than non-revertants, a process that they called "the meiotic effect." Here we use a forward mutation reporter (CAN1 HIS3) placed at either a meiotic recombination coldspot or hotspot near the MAT locus on Chromosome III. We find that the increased mutation rate at CAN1 (6 to 21 -fold) correlates with the underlying recombination rate at the locus. Importantly, we show that the elevated mutation rate is fully dependent upon Spo11, the protein that introduces the meiosis specific DSBs. To examine associated recombination we selected for random spores with or without a mutation in CAN1. We find that the mutations isolated this way show an increased association with recombination (crossovers, loss of crossover interference and/or increased gene conversion tracts). Polζ appears to contribute about half of the mutations induced during meiosis, but is not the only source of mutations for the meiotic effect. We see no difference in either the spectrum or distribution of mutations between mitosis and meiosis. The correlation of hotspots with elevated mutagenesis provides a mechanism for organisms to control evolution rates in a gene specific manner.

  19. Modulation of Stromal Cell-Derived Factor-1/CXC Chemokine Receptor 4 Axis Enhances rhBMP-2-Induced Ectopic Bone Formation

    PubMed Central

    Wise, Joel K.; Sumner, Dale Rick

    2012-01-01

    Enhancement of in vivo mobilization and homing of endogenous mesenchymal stem cells (MSCs) to an injury site is an innovative strategy for improvement of bone tissue engineering and repair. The present study was designed to determine whether mobilization by AMD3100 and/or local homing by delivery of stromal cell-derived factor-1 (SDF-1) enhances recombinant human bone morphogenetic protein-2 (rhBMP-2) induced ectopic bone formation in an established rat model. Rats received an injection of either saline or AMD3100 treatment 1 h before harvesting of bone marrow for in vitro colony-forming unit-fibroblasts (CFU-F) culture or the in vivo subcutaneous implantation of absorbable collagen sponges (ACSs) loaded with saline, recombinant human bone morphogenetic protein-2 (rhBMP-2), SDF-1, or the combination of SDF-1 and rhBMP-2. AMD3100 treatment resulted in a significant decrease in CFU-F number, compared with saline, which confirmed that a single systemic AMD3100 treatment rapidly mobilized MSCs from the bone marrow. At 28 and 56 days, bone formation in the explanted ACS was assessed by microcomputed tomography (μCT) and histology. At 28 days, AMD3100 and/or SDF-1 had no statistically significant effect on bone volume (BV) or bone mineral content (BMC), but histology revealed more active bone formation with treatment of AMD3100, loading of SDF-1, or the combination of both AMD3100 and SDF-1, compared with saline-treated rhBMP-2 loaded ACS. At 56 days, the addition of AMD3100 treatment, loading of SDF-1, or the combination of both resulted in a statistically significant stimulatory effect on BV and BMC, compared with the saline-treated rhBMP-2 loaded ACS. Histology of the 56-day ACS were consistent with the μCT analysis, exhibiting more mature and mineralized bone formation with AMD3100 treatment, SDF-1 loading, or the combination of both, compared with the saline-treated rhBMP-2 loaded ACS. The present study is the first that provides evidence of the efficacy of AMD

  20. Ectopic Hidradenoma Papilliferum

    PubMed Central

    Rosmaninho, Aristóteles David Neiva; de Almeida, Maria Teresa Duarte Pinto; Costa, Vírgilio; Sanches, Maria Madalena Vasconcelos; Lopes, Carlos; Selores Gomes Meirinhos, Maria Manuela

    2010-01-01

    Hidradenoma papilliferum is a rare tumor that occurs almost exclusively in females on the anogenital area. Rare cases of ectopic (nongenital) hidradenoma papilliferum have been described. The lesions usually present as an asymptomatic slow-growing, red, firm, mobile, well-delimitated nodule that grows for a long time before resection. We describe a case of an 26-year-old man that presented with an enlarging nodule on his right eyelid. The histological findings revealed a hidradenoma papilliferum. So far, among the very few reports of ectopic hidradenoma papilliferum, only a very small number were localized to the eyelid. PMID:21197082

  1. Oocyte development, meiosis and aneuploidy.

    PubMed

    MacLennan, Marie; Crichton, James H; Playfoot, Christopher J; Adams, Ian R

    2015-09-01

    Meiosis is one of the defining events in gametogenesis. Male and female germ cells both undergo one round of meiotic cell division during their development in order to reduce the ploidy of the gametes, and thereby maintain the ploidy of the species after fertilisation. However, there are some aspects of meiosis in the female germline, such as the prolonged arrest in dictyate, that appear to predispose oocytes to missegregate their chromosomes and transmit aneuploidies to the next generation. These maternally-derived aneuploidies are particularly problematic in humans where they are major contributors to miscarriage, age-related infertility, and the high incidence of Down's syndrome in human conceptions. This review will discuss how events that occur in foetal oocyte development and during the oocytes' prolonged dictyate arrest can influence meiotic chromosome segregation and the incidence of aneuploidy in adult oocytes.

  2. Oocyte development, meiosis and aneuploidy

    PubMed Central

    MacLennan, Marie; Crichton, James H.; Playfoot, Christopher J.; Adams, Ian R.

    2015-01-01

    Meiosis is one of the defining events in gametogenesis. Male and female germ cells both undergo one round of meiotic cell division during their development in order to reduce the ploidy of the gametes, and thereby maintain the ploidy of the species after fertilisation. However, there are some aspects of meiosis in the female germline, such as the prolonged arrest in dictyate, that appear to predispose oocytes to missegregate their chromosomes and transmit aneuploidies to the next generation. These maternally-derived aneuploidies are particularly problematic in humans where they are major contributors to miscarriage, age-related infertility, and the high incidence of Down's syndrome in human conceptions. This review will discuss how events that occur in foetal oocyte development and during the oocytes’ prolonged dictyate arrest can influence meiotic chromosome segregation and the incidence of aneuploidy in adult oocytes. PMID:26454098

  3. Vandetanib induces a marked anti-tumor effect and amelioration of ectopic Cushing’s syndrome in a medullary thyroid carcinoma patient

    PubMed Central

    Bseiso, Hashem; Lev-Cohain, Naama; Gross, David J

    2016-01-01

    Summary A 55-year-old woman diagnosed with sporadic MTC underwent total thyroidectomy 20 years ago. After the first surgery, elevated calcitonin levels in parallel with local disease persistence were noted and therefore she underwent repeated neck dissections. During follow-up, multiple foci of metastatic disease were noted in the neck and mediastinal lymph nodes, lungs and bones; however, the disease had an indolent course for a number of years, in parallel with a calcitonin doubling time of more than two years and without significant symptoms. During a routine follow-up visit 2 years ago, findings suggestive of Cushing’s syndrome were observed on physical examination. The biochemical evaluation demonstrated markedly elevated serum calcitonin level, in parallel with lack of cortisol suppression after an overnight 1 mg dexamethasone suppression test, lack of cortisol and ACTH suppression after high-dose IV dexamethasone 8 mg, elevated plasma ACTH up to 79 pg/mL (normal <46 pg/mL) and elevated 24-h urinary free cortisol up to 501 µg/24 h (normal 9–90 µg/24 h). After a negative pituitary MRI, she underwent IPSS, which was compatible with EAS. Whole-body CT demonstrated progressive disease at most of the tumor sites. Treatment with vandetanib at a dosage of 200 mg/day was commenced. The patient showed a significant, rapid and consistent clinical improvement already after two months of treatment, in parallel with biochemical improvement, whereas a decrease in tumor size was demonstrated on follow-up CT. Learning points: Ectopic Cushing’s syndrome due to ectopic ACTH secretion (EAS) by MTC is an uncommon and a poor prognostic event, being associated with significant morbidity and mortality. We demonstrate that vandetanib is effective in controlling the signs and symptoms related to the EAS in patients with advanced progressive MTC. We demonstrate that vandetanib is effective in decreasing tumor size and in inducing tumor control. PMID:27855236

  4. Spermatogenesis: The Commitment to Meiosis

    PubMed Central

    Griswold, Michael D.

    2015-01-01

    Mammalian spermatogenesis requires a stem cell pool, a period of amplification of cell numbers, the completion of reduction division to haploid cells (meiosis), and the morphological transformation of the haploid cells into spermatozoa (spermiogenesis). The net result of these processes is the production of massive numbers of spermatozoa over the reproductive lifetime of the animal. One study that utilized homogenization-resistant spermatids as the standard determined that human daily sperm production (dsp) was at 45 million per day per testis (60). For each human that means ∼1,000 sperm are produced per second. A key to this level of gamete production is the organization and architecture of the mammalian testes that results in continuous sperm production. The seemingly complex repetitious relationship of cells termed the “cycle of the seminiferous epithelium” is driven by the continuous commitment of undifferentiated spermatogonia to meiosis and the period of time required to form spermatozoa. This commitment termed the A to A1 transition requires the action of retinoic acid (RA) on the undifferentiated spermatogonia or prospermatogonia. In stages VII to IX of the cycle of the seminiferous epithelium, Sertoli cells and germ cells are influenced by pulses of RA. These pulses of RA move along the seminiferous tubules coincident with the spermatogenic wave, presumably undergoing constant synthesis and degradation. The RA pulse then serves as a trigger to commit undifferentiated progenitor cells to the rigidly timed pathway into meiosis and spermatid differentiation. PMID:26537427

  5. Spermatogenesis: The Commitment to Meiosis.

    PubMed

    Griswold, Michael D

    2016-01-01

    Mammalian spermatogenesis requires a stem cell pool, a period of amplification of cell numbers, the completion of reduction division to haploid cells (meiosis), and the morphological transformation of the haploid cells into spermatozoa (spermiogenesis). The net result of these processes is the production of massive numbers of spermatozoa over the reproductive lifetime of the animal. One study that utilized homogenization-resistant spermatids as the standard determined that human daily sperm production (dsp) was at 45 million per day per testis (60). For each human that means ∼1,000 sperm are produced per second. A key to this level of gamete production is the organization and architecture of the mammalian testes that results in continuous sperm production. The seemingly complex repetitious relationship of cells termed the "cycle of the seminiferous epithelium" is driven by the continuous commitment of undifferentiated spermatogonia to meiosis and the period of time required to form spermatozoa. This commitment termed the A to A1 transition requires the action of retinoic acid (RA) on the undifferentiated spermatogonia or prospermatogonia. In stages VII to IX of the cycle of the seminiferous epithelium, Sertoli cells and germ cells are influenced by pulses of RA. These pulses of RA move along the seminiferous tubules coincident with the spermatogenic wave, presumably undergoing constant synthesis and degradation. The RA pulse then serves as a trigger to commit undifferentiated progenitor cells to the rigidly timed pathway into meiosis and spermatid differentiation.

  6. Chromosome segregation in plant meiosis

    PubMed Central

    Zamariola, Linda; Tiang, Choon Lin; De Storme, Nico; Pawlowski, Wojtek; Geelen, Danny

    2014-01-01

    Faithful chromosome segregation in meiosis is essential for ploidy stability over sexual life cycles. In plants, defective chromosome segregation caused by gene mutations or other factors leads to the formation of unbalanced or unreduced gametes creating aneuploid or polyploid progeny, respectively. Accurate segregation requires the coordinated execution of conserved processes occurring throughout the two meiotic cell divisions. Synapsis and recombination ensure the establishment of chiasmata that hold homologous chromosomes together allowing their correct segregation in the first meiotic division, which is also tightly regulated by cell-cycle dependent release of cohesin and monopolar attachment of sister kinetochores to microtubules. In meiosis II, bi-orientation of sister kinetochores and proper spindle orientation correctly segregate chromosomes in four haploid cells. Checkpoint mechanisms acting at kinetochores control the accuracy of kinetochore-microtubule attachment, thus ensuring the completion of segregation. Here we review the current knowledge on the processes taking place during chromosome segregation in plant meiosis, focusing on the characterization of the molecular factors involved. PMID:24987397

  7. Meiosis I: when chromosomes undergo extreme makeover.

    PubMed

    Miller, Matthew P; Amon, Angelika; Ünal, Elçin

    2013-12-01

    The ultimate success of cell division relies on the accurate partitioning of the genetic material. Errors in this process occur in nearly all tumors and are the leading cause of miscarriages and congenital birth defects in humans. Two cell divisions, mitosis and meiosis, use common as well as unique mechanisms to ensure faithful chromosome segregation. In mitosis, alternating rounds of DNA replication and chromosome segregation preserve the chromosome complement of the progenitor cell. In contrast, during meiosis two consecutive rounds of nuclear division, meiosis I and meiosis II, follow a single round of DNA replication to reduce the chromosome complement by half. Meiosis likely evolved through changes to the mitotic cell division program. This review will focus on the recent findings describing the modifications that transform mitosis into meiosis.

  8. Piwil1 mediates meiosis during spermatogenesis in chicken.

    PubMed

    Xu, Lu; Chang, Guobin; Ma, Teng; Wang, Hongzhi; Chen, Jing; Li, Zhiteng; Guo, Xiaomin; Wan, Fang; Ren, Lichen; Lu, Wei; Chen, Guohong

    2016-03-01

    Piwil1 mediates spermatogenesis and ensures stable cell division rates in germline cells in mammals. However, the involvement of Piwil1 in poultry spermatogenesis and meiosis is poorly understood. In the present study, we used TaqMan RT-qPCR to characterize Piwil1 mRNA expression in different types of spermatogenic cells, including primordial germ cells (PGCs), spermatogonial stem cells (SSCs), spermatogonia cells (Sa), tetraploid cells (Tp), round sperm cells (Rs), mature sperm, and in PGCs treated with retinoic acid. Our results revealed that Piwil1 is differentially expressed during spermatogenesis in chicken. Compared to PGCs, SSCs, Tp, and Sa, Rs cells presented the highest Piwil1 mRNA expression levels. Retinoic acid significantly upregulated Piwil1 and Stra8 mRNA expression as well as Piwil1 levels in chicken PGCs. In addition, retinoic acid induced PGCs to progress through all the meiotic stages, eventually leading to haploid cell formation, which was determined using flow cytometry and western blot analysis. Taken together, our results showed that during spermatogenesis, Piwil1 was first expressed at low levels in germ stem cells, PGCs, and SSCs. Its expression levels increased during later meiosis stages. Finally, no expression was detected in mature sperm after meiosis. Treatment of PGCs with retinoic acid further demonstrated that Piwil1 plays a key role in meiosis during chicken spermatogenesis.

  9. The molecular biology of meiosis in plants.

    PubMed

    Mercier, Raphaël; Mézard, Christine; Jenczewski, Eric; Macaisne, Nicolas; Grelon, Mathilde

    2015-01-01

    Meiosis is the cell division that reshuffles genetic information between generations. Recently, much progress has been made in understanding this process; in particular, the identification and functional analysis of more than 80 plant genes involved in meiosis have dramatically deepened our knowledge of this peculiar cell division. In this review, we provide an overview of advancements in the understanding of all aspects of plant meiosis, including recombination, chromosome synapsis, cell cycle control, chromosome distribution, and the challenge of polyploidy.

  10. Primary ectopic frontotemporal craniopharyngioma

    PubMed Central

    Ortega-Porcayo, Luis Alberto; Ponce-Gómez, Juan Antonio; Martínez-Moreno, Mauricio; Portocarrero-Ortíz, Lesly; Tena-Suck, Martha Lilia; Gómez-Amador, Juan Luis

    2015-01-01

    Introduction Primary ectopic craniopharyngiomas have only rarely been reported. Craniopharyngiomas involve usually the sellar and suprasellar region, but can be originated from cell remnants of the obliterated craniopharyngeal duct or metaplastic change of andenohypophyseal cells. We present the first case of a primary ectopic frontotemporal craniopharyngioma. Presentation of case A 35-year old woman presented with a one-year history of headache and diplopia. MRI showed a large frontotemporal cystic lesion. Tumor resection was performed with a keyhole endoscopic frontal lateral approach. The pathological features showed an adamantinomatous craniopharyngioma with a cholesterol granuloma reaction. Discussion There have been reported different localizations for primary ectopic craniopharyngioma. Our case presented a lobulated frontotemporal cystic mass formed by a dense eosinophilic proteinaceous material dystrophic calcifications and cholesterol crystals, with epithelial remnants. No tumor regrowth was observed in the magnetic resonance image 27 months postoperatively. Conclusion Primary ectopic craniopharyngioma is a rare entity with a pathogenesis that remains uncertain. This is an unusual anatomic location associated with unique clinical findings. PMID:25725331

  11. Prevalence of cytomegalovirus, and its effect on the expression of inducible and endothelial nitric oxide synthases in Fallopian tubes collected from women with and without ectopic pregnancy.

    PubMed

    Batwa, S A; Ashshi, A M; Kamfar, F F; Ahmad, J; Idris, S; Khojah, A; Al-Qadi, N M; Refaat, B

    2016-01-01

    To measure the prevalence of cytomegalovirus (CMV) infection in ectopic pregnancy (EP) and its effect on the expression of inducible and endothelial nitric oxide synthases (iNOS, eNOS) by Fallopian tubes (FT) bearing an EP. This was a prospective case-control study. Blood and tubal samples were collected from 84 Eps and 51 controls (20 total abdominal hysterectomy (TAH) during the luteal phase and another 31 tubal ligations). CMV IgM and IgG antibodies were measured by ELISA, and an IVD CE PCR kit was used to detect CMV in the FTs. iNOS and eNOS were measured by immunohistochemistry and quantitative RT-PCR in FTs obtained from CMV-positive EP (n = 12), and the results were compared with those obtained from CMV-negative EP (n = 11) and TAH (n = 8). The frequencies of CMV IgM (51.2 % vs 17.6 %), IgG (77.4 % vs 52.9 %) or both antibodies (41.6 % vs 11.7 %) were significantly higher in EP compared with control. CMV was more common by PCR in FTs from EP (21.4 %) than controls (5.9 %). Twelve women from the PCR positive EP cases (66.6 %) were also simultaneously positive for both CMV IgM & IgG antibodies and had higher expression of eNOS and iNOS at the protein and gene levels compared with negative EP and TAH. Tubal infection with CMV may lead to EP by increasing the production of endothelial and inducible NOS by the FT epithelial cells. Further studies are required to illustrate the role of CMV in the pathogenesis of EP.

  12. Retinoic acid derived from the fetal ovary initiates meiosis in mouse germ cells.

    PubMed

    Mu, Xinyi; Wen, Jing; Guo, Meng; Wang, Jianwei; Li, Ge; Wang, Zhengpin; Wang, Yijing; Teng, Zhen; Cui, Yan; Xia, Guoliang

    2013-03-01

    Meiotic initiation of germ cells at 13.5 dpc (days post-coitus) indicates female sex determination in mice. Recent studies reveal that mesonephroi-derived retinoic acid (RA) is the key signal for induction of meiosis. However, whether the mesonephroi is dispensable for meiosis is unclear and the role of the ovary in this meiotic process remains to be clarified. This study provides data that RA derived from fetal ovaries is sufficient to induce germ cell meiosis in a fetal ovary culture system. When fetal ovaries were collected from 11.5 to 13.5 dpc fetuses, isolated and cultured in vitro, germ cells enter meiosis in the absence of mesonephroi. To exclude RA sourcing from mesonephroi, 11.5 dpc urogenital ridges (UGRs; mesonephroi and ovary complexes) were treated with diethylaminobenzaldehyde (DEAB) to block retinaldehyde dehydrogenase (RALDH) activity in the mesonephros and the ovary. Meiosis occurred when DEAB was withdrawn and the mesonephros was removed 2 days later. Furthermore, RALDH1, rather than RALDH2, serves as the major RA synthetase in UGRs from 12.5 to 15.5 dpc. DEAB treatment to the ovary alone was able to block germ cell meiotic entry. We also found that exogenously supplied RA dose-dependently reduced germ cell numbers in ovaries by accelerating the entry into meiosis. These results suggest that ovary-derived RA is responsible for meiosis initiation.

  13. The selective elimination of messenger RNA underlies the mitosis-meiosis switch in fission yeast.

    PubMed

    Yamamoto, Masayuki

    2010-01-01

    The cellular programs for meiosis and mitosis must be strictly distinguished but the mechanisms controlling the entry to meiosis remain largely elusive in higher organisms. In contrast, recent analyses in yeast have shed new light on the mechanisms underlying the mitosis-meiosis switch. In this review, the current understanding of these mechanisms in the fission yeast Schizosaccharomyces pombe is discussed. Meiosis-inducing signals in this microbe emanating from environmental conditions including the nutrient status converge on the activity of an RRM-type RNA-binding protein, Mei2. This protein plays pivotal roles in both the induction and progression of meiosis and has now been found to govern the meiotic program in a quite unexpected manner. Fission yeast contains an RNA degradation system that selectively eliminates meiosis-specific mRNAs during the mitotic cell cycle. Mmi1, a novel RNA-binding protein of the YTH-family, is essential for this process. Mei2 tethers Mmi1 and thereby stabilizes the transcripts necessary for the progression of meiosis.

  14. Role of activins and inducible nitric oxide in the pathogenesis of ectopic pregnancy in patients with or without Chlamydia trachomatis infection.

    PubMed

    Refaat, Bassem; Al-Azemi, Majedah; Geary, Ian; Eley, Adrian; Ledger, William

    2009-10-01

    Chlamydia trachomatis infection can lead to pelvic inflammatory disease, ectopic pregnancy (EP), infertility, and chronic pelvic pain in women. Activins and inducible nitric oxide synthase (iNOS) are produced by the human fallopian tube, and we speculate that tubal activins and iNOS may be involved in the immune response to C. trachomatis in humans and their pathological alteration may result in tubal pathology and the development of EP. Blood and fallopian tubes were collected from 14 women with EP. Sera were analyzed by enzyme-linked immunosorbent assay to detect antibodies against chlamydial heat shock protein 60 (chsp60) and the major outer membrane protein of C. trachomatis. Confirmation of C. trachomatis serology was made using the microimmunofluorescence test. The patients were classified into three groups according to their serological results, and immunohistochemistry and quantitative reverse transcription-PCR were performed to investigate the expression of candidate molecules by tubal epithelial cells among the three groups. This is the first study to show an increase in the expression of activin betaA subunit, type II receptors, follistatin, and iNOS within the human fallopian tube of EP patients who were serologically positive for C. trachomatis. A similar expression profile was observed in the fallopian tubes with detectable antibodies only against chsp60. These results were shown at the mRNA and protein levels. We suggest that tubal activin A, its type II receptors, follistatin, and NO could be involved in the microbial-mediated immune response within the fallopian tube, and their pathological expression may lead to tubal damage and the development of EP.

  15. Implementation of meiosis prophase I programme requires a conserved retinoid-independent stabilizer of meiotic transcripts

    PubMed Central

    Abby, Emilie; Tourpin, Sophie; Ribeiro, Jonathan; Daniel, Katrin; Messiaen, Sébastien; Moison, Delphine; Guerquin, Justine; Gaillard, Jean-Charles; Armengaud, Jean; Langa, Francina; Toth, Attila; Martini, Emmanuelle; Livera, Gabriel

    2016-01-01

    Sexual reproduction is crucially dependent on meiosis, a conserved, specialized cell division programme that is essential for the production of haploid gametes. Here we demonstrate that fertility and the implementation of the meiotic programme require a previously uncharacterized meiosis-specific protein, MEIOC. Meioc invalidation in mice induces early and pleiotropic meiotic defects in males and females. MEIOC prevents meiotic transcript degradation and interacts with an RNA helicase that binds numerous meiotic mRNAs. Our results indicate that proper engagement into meiosis necessitates the specific stabilization of meiotic transcripts, a previously little-appreciated feature in mammals. Remarkably, the upregulation of MEIOC at the onset of meiosis does not require retinoic acid and STRA8 signalling. Thus, we propose that the complete induction of the meiotic programme requires both retinoic acid-dependent and -independent mechanisms. The latter process involving post-transcriptional regulation likely represents an ancestral mechanism, given that MEIOC homologues are conserved throughout multicellular animals. PMID:26742488

  16. Meiosis.

    ERIC Educational Resources Information Center

    Henderson, Paula

    This autoinstructional lesson deals with the study of cytology (or cells) with emphasis placed on cell reproduction. Knowledge of the structure of the DNA molecule and of the stages of mitotic cell division are considered prerequisites for this lesson. Approximately 15 minutes is the established time set for the activity. The behavioral objectives…

  17. Role of the planar cell polarity pathway in regulating ectopic hair cell-like cells induced by Math1 and testosterone treatment.

    PubMed

    Yang, Xiao-Yu; Jin, Kai; Ma, Rui; Yang, Juan-Mei; Luo, Wen-Wei; Han, Zhao; Cong, Ning; Ren, Dong-Dong; Chi, Fang-Lu

    2015-07-30

    Planar cell polarity (PCP) signaling regulates cochlear extension and coordinates orientation of sensory hair cells in the inner ear. Retroviral-mediated introduction of the Math1 transcription factor leads to the transdifferentiation of some mature supporting cells into hair cells. Testosterone, a gonadal sex steroid hormone, is associated with neuroprotection and regeneration in Central Nervous System (CNS) development. Experiments were performed in vitro using Ad5-EGFP-Math1/Ad5-Math1 in neonatal mouse cochleas. Establishment of ectopic hair-cell like cell(HCLC) polarity in the lesser epithelial ridge (LER) with or without testosterone-3-(O-carboxymethyl) oxime bovine serum albumin (testosterone-BSA) treatment was investigated to determine the role of the PCP pathway in regulating ectopic regenerated (HCLCs) through induction by Math1 and testosterone treatment. After Math1 infection, new ectopic regenerated HCLCs were detected in the LER. After the HCLCs developed actin-rich stereocilia, the basal bodies moved from the center to the distal side. Moreover, the narrower, non-sensory LER region meant that the convergent extension (CE) was also established after transfection with Math1. After 9 days of in vitro testosterone-BSA treatment, more Edu(+), Sox2(+), and HCLC cells were observed in the LER with an accompanying downregulation of E-cadherin. Interestingly, the CE of the Ad5-EGFP-math1 treated LER is altered, but the intrinsic cellular polarity of the HCLCs is not obviously changed. In summary, our results indicate that PCP signaling is involved in the development of ectopic HCLCs and the CE of the ectopic sensory region is altered by testosterone-BSA through downregulation of cell-cell adhesion. Testosterone-BSA and Math1 treatment could promote an increase in HCLCs in the LER through proliferation and transdifferentiation.

  18. Homolog pairing and segregation in Drosophila meiosis.

    PubMed

    McKee, B D

    2009-01-01

    Pairing of homologous chromosomes is fundamental to their reliable segregation during meiosis I and thus underlies sexual reproduction. In most eukaryotes homolog pairing is confined to prophase of meiosis I and is accompanied by frequent exchanges, known as crossovers, between homologous chromatids. Crossovers give rise to chiasmata, stable interhomolog connectors that are required for bipolar orientation (orientation to opposite poles) of homologs during meiosis I. Drosophila is unique among model eukaryotes in exhibiting regular homolog pairing in mitotic as well as meiotic cells. I review the results of recent molecular studies of pairing in both mitosis and meiosis in Drosophila. These studies show that homolog pairing is continuous between pre-meiotic mitosis and meiosis but that pairing frequencies and patterns are altered during the mitotic-meiotic transition. They also show that, with the exception of X-Y pairing in male meiosis, which is mediated specifically by the 240-bp rDNA spacer repeats, chromosome pairing is not restricted to specific sites in either mitosis or meiosis. Instead, virtually all chromosome regions, both heterochromatic and euchromatic, exhibit autonomous pairing capacity. Mutations that reduce the frequencies of both mitotic and meiotic pairing have been recently described, but no mutations that abolish pairing completely have been discovered, and the genetic control of pairing in Drosophila remains to be elucidated.

  19. Intra-cholecystic ectopic liver.

    PubMed

    Natori, T; Hawkin, S; Aizawa, M; Asai, T; Kameda, Y; Ikuyohashi, K

    1986-08-01

    A 56-year-old Japanese woman who had an ectopic liver attached to the inner surface of the gallbladder is reported. The ectopic nodule measuring 1.2 X 0.5 X 0.8 cm was found incidentally when her gallbladder was resected because of cholelithiasis. Ectopic liver tissue in reported cases war located on the serosal surface, or in the wall of the gallbladder. This report described, to our knowledge, the first case of an ectopic liver nodule attached to the mucosal surface of the gallbladder with a thin pedicle.

  20. A stubborn anemia caused by ectopic pancreas bleeding in the jejunum revealed by capsule endoscopy

    PubMed Central

    Wang, Qun-Ying; Yang, Xiao-Yun

    2015-01-01

    Ectopic pancreas is extremely rare in clinical setting. Meanwhile, a stubborn anemia without obvious dark bloody stool due to ectopic pancreas diagnosed by capsule endoscopy has not been reported. We reported a case of an ectopic pancreas inducing obscure gastrointestinal bleeding in a 70-year-old woman presenting as stubborn anemia, which was diagnosed by capsule endoscopy. The patient recovered well after resection the lesion. Diagnosis of ectopic pancreas is extremely difficult with conventional techniques. Endoscopists should pay more attention to the ectopic pancreas as a rare differential consideration for occult intestinal bleeding. PMID:26682148

  1. Leaf-Like Sepals Induced by Ectopic Expression of a SHORT VEGETATIVE PHASE (SVP)-Like MADS-Box Gene from the Basal Eudicot Epimedium sagittatum

    PubMed Central

    Li, Zhineng; Zeng, Shaohua; Li, Yanbang; Li, Mingyang; Souer, Erik

    2016-01-01

    Epimedium L. (Berberidaceae, Ranales), a perennial traditional Chinese medicinal herb, has become a new popular landscape plant for ground cover and pot culture in many countries based on its excellent ornamental characteristics and, distinctive and diverse floral morphology. However, little is known about the molecular genetics of flower development in Epimedium sagittatum. Here, we describe the characterization of EsSVP that encodes a protein sharing 68, 54, and 35% similarity with SVP, AGAMOUS-like 24 (AGL24) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) in Arabidopsis, respectively. Quantitative RT-PCR (qRT-PCR) indicated that EsSVP transcripts were principally found in petiole and leaf tissues, with little expression in roots and flowers and no in fruits. The highest EsSVP expression was observed in leaves. The flowering time of 35S::EsSVP in most Arabidopsis thaliana and in all petunia plants was not affected in both photoperiod conditions, but 35S::EsSVP 5# and 35S::EsSVP 1# Arabidopsis lines induced late and early flowering under long day (LD, 14 h light/10 h dark) and short day (SD, 10 h light/14 h dark) conditions, respectively. The 35S::EsSVP Arabidopsis produced extra secondary inflorescence or floral meristems in the axils of the leaf-like sepals with excrescent trichomes, and leaf-like sepals not able to enclose the inner three whorls completely. Moreover, almost all transgenic Arabidopsis plants showed persistent sepals around the completely matured fruits. Upon ectopic expression of 35S::EsSVP in Petunia W115, sepals were enlarged, sometimes to the size of leaves; corollas were greenish and did not fully open. These results suggest that EsSVP is involved in inflorescence meristem identity and flowering time regulation in some conditions. Although, the SVP homologs might have suffered functional diversification among diverse species between core and basal eudicots, the protein functions are conserved between Arabidopsis/Petunia and Epimedium

  2. The Chromosomes of Birds during Meiosis.

    PubMed

    Pigozzi, María I

    2016-01-01

    The cytological analysis of meiotic chromosomes is an exceptional tool to approach complex processes such as synapsis and recombination during the division. Chromosome studies of meiosis have been especially valuable in birds, where naturally occurring mutants or experimental knock-out animals are not available to fully investigate the basic mechanisms of major meiotic events. This review highlights the main contributions of synaptonemal complex and lampbrush chromosome research to the current knowledge of avian meiosis, with special emphasis on the organization of chromosomes during prophase I, the impact of chromosome rearrangements during meiosis, and distinctive features of the ZW pair.

  3. Baicalin attenuates high fat diet-induced insulin resistance and ectopic fat storage in skeletal muscle, through modulating the protein kinase B/Glycogen synthase kinase 3 beta pathway.

    PubMed

    Xi, You-Li; Li, Hong-Xia; Chen, Chen; Liu, Ya-Qun; Lv, Hong-Mei; Dong, Shi-Qi; Luo, Er-Fei; Gu, Ming-Bo; Liu, Hua

    2016-01-01

    Insulin resistance is the pathophysiological basis of many diseases. Overcoming early insulin resistance highly significant in prevention diabetes, non-alcoholic fatty liver, and atherosclerosis. The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice, and exploring the potential molecular mechanisms. Insulin resistance in mice was induced with a high fat diet for 16 weeks. Animals were then treated with three different doses of baicalin (100, 200, and 400 mg·kg(-1)·d(-1)) for 14 weeks. Fasting blood glucose, fasting serum insulin, glucose tolerance test (GTT), insulin tolerance test (ITT), and skeletal muscle lipid deposition were measured. Additionally, the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated. Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance. Moreover, insulin resistance was significantly reversed. Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle. The properties of baicalin were mediated, at least in part, by inhibition of the AMPK/ACC pathway, a key regulator of de novo lipogenesis and activation of the Akt/GSK-3β pathway, a key regulator of Glycogen synthesis. These data suggest that baicalin, at dose up to 400 mg·kg(-1)·d(-1), is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage, through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3β pathway.

  4. Cervical ectopic pregnancy.

    PubMed

    Samal, Sunil Kumar; Rathod, Setu

    2015-01-01

    Cervical pregnancy is a rare type of ectopic pregnancy and it represents <1% of all ectopic pregnancies. Early diagnosis and medical management with systemic or local administration of methotrexate is the treatment of choice. If the pregnancy is disturbed, it may lead to massive hemorrhage, which may require hysterectomy to save the patient. We report three cases of cervical pregnancy managed successfully with different approaches of management. Our first case, 28 years old G3P2L2 with previous two lower segment cesarean sections, presented with bleeding per vaginum following 6 weeks of amenorrhea. Clinical examination followed by transvaginal ultrasound confirmed the diagnosis of cervical pregnancy. Total abdominal hysterectomy was done in view of intractable bleeding to save the patient. The second case, a 26-year-old second gravida with previous normal vaginal delivery presented with pain abdomen and single episode of spotting per vaginum following 7 weeks of amenorrhea. Transvaginal ultrasound revealed empty endometrial cavity, closed internal os with gestational sac containing live fetus of 7 weeks gestational age in cervical canal and she was treated with intra-amniotic potassium chloride followed by systemic methotrexate. Follow up with serum beta human chorionic gonadotropin level revealed successful outcome. Our third case, a 27-year-old primigravida with history of infertility treatment admitted with complaints of bleeding per vaginum for 1 day following 8 weeks amenorrhea. She was diagnosed as cervical pregnancy by clinical examination, confirmed by transvaginal ultrasonography and subsequently managed by dilation and curettage with intracervical Foleys' ballon tamponade.

  5. Follow-up study on histogenesis of microcephaly associated with ectopic gray matter induced by prenatal {gamma}-irradiation in the mouse

    SciTech Connect

    Sun, Xue-Zhi; Inouye, Monoru; Takagishi, Yoshiko

    1996-03-01

    Brain malformation with ectopic gray matter was visualized with magnetic resonance imaging in small-sized heads of prenatally exposed atomic bomb survivors. The identical brain malformation was reproduced in mice and its histogenesis was studied in the present experiment. Pregnant mice were exposed to {sup 60}Co {gamma}-irradiation at a single dose of 1.5 Gy on embryonic day 13 (E13), and then injected intraperitoneally with 30 mg/kg BrdU on E15. The extensive dead cells appeared throughout the brain mantle at 6 hours (h) after exposure. On E16 cell aggregations formed rosettes. On E18 a high proportion of BrdU-labeled cells reached the superficial layers of the cortical plate with the remaining cells located in the ectopic neuronal masses. The quantitative study showed that labeled cells in layers II to III were fewer and those in layers IV to VI more numerous in the prenatally irradiated adult mice than in controls. The anti-GFAP immunostaining revealed that the glial fibers in the irradiated mice were preserved, but disorganized. These findings suggested that the majority of migrating neurons were able to arrive at their normal layers, but some neurons remained due to the interrupted migratory pathway and eventually formed ectopic neuronal masses beneath the subcortical white matter. 60 refs., 5 figs., 1 tab.

  6. Tradescantia: A Tool for Teaching Meiosis.

    ERIC Educational Resources Information Center

    Hammersmith, Robert L.; Mertens, Thomas R.

    1997-01-01

    Describes a procedure for making slides of microsporogenesis in Tradescantia. Uses photographs to demonstrate that Tradescantia is an ideal organism for studying meiosis in the classroom. Contains 17 references. (JRH)

  7. Regulation of wee1(+) expression during meiosis in fission yeast.

    PubMed

    Murakami-Tonami, Yuko; Ohtsuka, Hokuto; Aiba, Hirofumi; Murakami, Hiroshi

    2014-01-01

    In eukaryotes, the cyclin-dependent kinase Cdk1p (Cdc2p) plays a central role in entry into and progression through nuclear division during mitosis and meiosis. Cdk1p is activated during meiotic nuclear divisions by dephosphorylation of its tyrosine-15 residue. The phosphorylation status of this residue is largely determined by the Wee1p kinase and the Cdc25p phosphatase. In fission yeast, the forkhead-type transcription factor Mei4p is essential for entry into the first meiotic nuclear division. We recently identified cdc25(+) as an essential target of Mei4p in the control of entry into meiosis I. Here, we show that wee1(+) is another important target of Mei4p in the control of entry into meiosis I. Mei4p bound to the upstream region of wee1(+) in vivo and in vitro and inhibited expression of wee1(+), whereas Mei4p positively regulated expression of the adjacent pseudogene. Overexpression of Mei4p inhibited expression of wee1(+) and induced that of the pseudogene. Conversely, deletion of Mei4p did not decrease expression of wee1(+) but inhibited that of the pseudogene. In addition, deletion of Mei4p-binding regions delayed repression of wee1(+) expression as well as induction of expression of the pseudogene. These results suggest that repression of wee1(+) expression is primarily owing to Mei4p-mediated transcriptional interference.

  8. Cervical ectopic pregnancy

    PubMed Central

    Samal, Sunil Kumar; Rathod, Setu

    2015-01-01

    Cervical pregnancy is a rare type of ectopic pregnancy and it represents <1% of all ectopic pregnancies. Early diagnosis and medical management with systemic or local administration of methotrexate is the treatment of choice. If the pregnancy is disturbed, it may lead to massive hemorrhage, which may require hysterectomy to save the patient. We report three cases of cervical pregnancy managed successfully with different approaches of management. Our first case, 28 years old G3P2L2 with previous two lower segment cesarean sections, presented with bleeding per vaginum following 6 weeks of amenorrhea. Clinical examination followed by transvaginal ultrasound confirmed the diagnosis of cervical pregnancy. Total abdominal hysterectomy was done in view of intractable bleeding to save the patient. The second case, a 26-year-old second gravida with previous normal vaginal delivery presented with pain abdomen and single episode of spotting per vaginum following 7 weeks of amenorrhea. Transvaginal ultrasound revealed empty endometrial cavity, closed internal os with gestational sac containing live fetus of 7 weeks gestational age in cervical canal and she was treated with intra-amniotic potassium chloride followed by systemic methotrexate. Follow up with serum beta human chorionic gonadotropin level revealed successful outcome. Our third case, a 27-year-old primigravida with history of infertility treatment admitted with complaints of bleeding per vaginum for 1 day following 8 weeks amenorrhea. She was diagnosed as cervical pregnancy by clinical examination, confirmed by transvaginal ultrasonography and subsequently managed by dilation and curettage with intracervical Foleys’ ballon tamponade. PMID:25810679

  9. Genetics of mammalian meiosis: regulation, dynamics and impact on fertility.

    PubMed

    Handel, Mary Ann; Schimenti, John C

    2010-02-01

    Meiosis is an essential stage in gamete formation in all sexually reproducing organisms. Studies of mutations in model organisms and of human haplotype patterns are leading to a clearer understanding of how meiosis has adapted from yeast to humans, the genes that control the dynamics of chromosomes during meiosis, and how meiosis is tied to gametic success. Genetic disruptions and meiotic errors have important roles in infertility and the aetiology of developmental defects, especially aneuploidy. An understanding of the regulation of meiosis, coupled with advances in genomics, may ultimately allow us to diagnose the causes of meiosis-based infertilities, more wisely apply assisted reproductive technologies, and derive functional germ cells.

  10. DLH1 is a functional Candida albicans homologue of the meiosis-specific gene DMC1

    SciTech Connect

    Diener, A.C.; Fink, G.R.

    1996-06-01

    DMC1/LIM15 homologue 1 (DLH1), a gene related to meiosis-specific genes, has been isolated from Candida albicans, a fungus thought not to undergo meiosis. The deduced protein sequence of DLH1 contains 74% amino acid identity with Dmc1p from Saccharomyces cerevisiae and 63% with Lim15p from the plant Lilium longiflorum, meiosis-specific homologous of Escherichia coli RecA. Candida DLH1 complements a dmc1/dmc1 null mutant in S. cerevisiae. High copy expression of DLH1 restores both sporulation and meiotic recombination to a Saccharomyces dmc1/{Delta}/dmc1{Delta} strain. Unlike the DMC1 gene, which is transcribed only in meiotic cells, the heterologous Candida DLH1 gene is transcribed in both vegetative and meiotic cells of S. cerevisiae. Transcription of DLH1 is not detected or induced in C. albicans under conditions that induce DMC1 and meiosis in S. cerevisiae. The presence of an intact homologue of a meiosis-specific gene in C. albicans raises the possibility that this organism has a cryptic meiotic pathway. 25 refs., 6 figs., 3 tabs.

  11. The oxidative damage initiation hypothesis for meiosis.

    PubMed

    Hörandl, Elvira; Hadacek, Franz

    2013-12-01

    The maintenance of sexual reproduction in eukaryotes is still a major enigma in evolutionary biology. Meiosis represents the only common feature of sex in all eukaryotic kingdoms, and thus, we regard it a key issue for discussing its function. Almost all asexuality modes maintain meiosis either in a modified form or as an alternative pathway, and facultatively apomictic plants increase frequencies of sexuality relative to apomixis after abiotic stress. On the physiological level, abiotic stress causes oxidative stress. We hypothesize that repair of oxidative damage on nuclear DNA could be a major driving force in the evolution of meiosis. We present a hypothetical model for the possible redox chemistry that underlies the binding of the meiosis-specific protein Spo11 to DNA. During prophase of meiosis I, oxidized sites at the DNA molecule are being targeted by the catalytic tyrosine moieties of Spo11 protein, which acts like an antioxidant reducing the oxidized target. The oxidized tyrosine residues, tyrosyl radicals, attack the phosphodiester bonds of the DNA backbone causing DNA double strand breaks that can be repaired by various mechanisms. Polyploidy in apomictic plants could mitigate oxidative DNA damage and decrease Spo11 activation. Our hypothesis may contribute to explaining various enigmatic phenomena: first, DSB formation outnumbers crossovers and, thus, effective recombination events by far because the target of meiosis may be the removal of oxidative lesions; second, it offers an argument for why expression of sexuality is responsive to stress in many eukaryotes; and third, repair of oxidative DNA damage turns meiosis into an essential characteristic of eukaryotic reproduction.

  12. Sonography of Methotrexate for Ectopics

    NASA Astrophysics Data System (ADS)

    Urzicǎ, Denise; Dorohoi, Dana-Ortansa

    2007-04-01

    Treatment unruptured ectopic pregnancy with methotrexate (MTX) and citrovorum factor is now an established alternative to surgical therapy. Serial measurements of serum beta-HCG and early ultrasound examination have allowed detection of early and unruptured tubal ectopic pregnancies, permitting treatment without removal of the tube. It is believed that preserving the tube increases the chance of subsequent live births. Our findings suggest that outpatient transvaginal intratubal methorexate administration can provide a safe and effective alternative to surgical treatment for patients with early and unruptured tubal ectopic pregnancy.

  13. Nociceptin and meiosis during spermatogenesis in postnatal testes.

    PubMed

    Eto, Ko

    2015-01-01

    Phosphorylated Rec8, a key component of cohesin, mediates the association and disassociation, "dynamics," of chromosomes occurring in synaptonemal complex formation, crossover recombination, and sister chromatid cohesion during meiosis in germ cells. Yet, the extrinsic factors triggering meiotic chromosome dynamics remained unclear. In postnatal testes, follicle-stimulating hormone (FSH) acts directly on somatic Sertoli cells to activate gene expression via an intracellular signaling pathway composed of cAMP, cAMP-dependent protein kinase (PKA), and cAMP-response element-binding protein (CREB), and promotes germ cell development and spermatogenesis indirectly. Yet, the paracrine factors mediating the FSH effects to germ cells remained elusive. We have shown that nociceptin, known as a neuropeptide, is upregulated by FSH signaling through cAMP/PKA/CREB pathway in Sertoli cells of postnatal murine testes. Chromatin immunoprecipitation from Sertoli cells demonstrated that CREB phosphorylated at Ser133 associates with prepronociceptin gene encoding nociceptin. Analyses with Sertoli cells and testes revealed that both prepronociceptin mRNA and the nociceptin peptide are induced after FSH signaling is activated. In addition, the nociceptin peptide is induced in testes after 9 days post partum following FSH surge. Thus, our findings may identify nociceptin as a novel paracrine mediator of the FSH effects in the regulation of spermatogenesis; however, very little has known about the functional role of nociceptin in spermatogenesis. We have shown that nociceptin induces Rec8 phosphorylation, triggering chromosome dynamics, during meiosis in spermatocytes of postnatal murine testes. The nociceptin receptor Oprl-1 is exclusively expressed in the plasma membrane of testicular germ cells, mostly spermatocytes. Treatment of testes with nociceptin resulted in a rapid phosphorylation of Rec8. Injection of nociceptin into mice stimulated Rec8 phosphorylation and meiotic chromosome

  14. Evolution of meiosis timing during floral development

    PubMed Central

    Johnston, M. O.

    1999-01-01

    Meiosis divides the haploid and diploid portions of the life cycle in all sexual organisms. In angiosperms meiosis occurs during flower development, the duration of which varies widely among species and is affected by environmental conditions within species. For 36 species representing 13 angiosperm families, we determined the time at which meiosis ceased in the anthers as a fraction of the total time from floral primordium initiation (beginning of development) to flower opening (end). It was found that this fraction, rather than being continuously distributed among species, occurred in three discrete classes despite wide variations within and among species in absolute developmental durations. Each species was characterized by a single timing class. For all species within a given timing class, therefore, the durations before and after the end of microsporocyte meiosis existed in constant ratio. Each timing class was found in phylogenetically distant species; conversely, a plant family often contained more than one class. Timing class was not related to ploidy level, inflorescence architecture, pollination syndrome or mating system. These findings show that either the durations before and after microsporocyte meiosis are regulated by the same exogenous process, or one duration determines the other. They further imply that the underlying developmental processes have evolved in a limited number of ways among flowering plants.

  15. Meiosis and its deviations in polyploid animals.

    PubMed

    Stenberg, P; Saura, A

    2013-01-01

    We review the different modes of meiosis and its deviations encountered in polyploid animals. Bisexual reproduction involving normal meiosis occurs in some allopolyploid frogs with variable degrees of polyploidy. Aberrant modes of bisexual reproduction include gynogenesis, where a sperm stimulates the egg to develop. The sperm may enter the egg but there is no fertilization and syngamy. In hybridogenesis, a genome is eliminated to produce haploid or diploid eggs or sperm. Ploidy can be elevated by fertilization with a haploid sperm in meiotic hybridogenesis, which elevates the ploidy of hybrid offspring such that they produce diploid gametes. Polyploids are then produced in the next generation. In kleptogenesis, females acquire full or partial genomes from their partners. In pre-equalizing hybrid meiosis, one genome is transmitted in the Mendelian fashion, while the other is transmitted clonally. Parthenogenetic animals have a very wide range of mechanisms for restoring or maintaining the mother's ploidy level, including gamete duplication, terminal fusion, central fusion, fusion of the first polar nucleus with the product of the first division, and premeiotic duplication followed by a normal meiosis. In apomictic parthenogenesis, meiosis is replaced by what is effectively mitotic cell division. The above modes have different evolutionary consequences, which are discussed. See also the sister article by Grandont et al. in this themed issue.

  16. Ectopic expression of Msx-2 in posterior limb bud mesoderm impairs limb morphogenesis while inducing BMP-4 expression, inhibiting cell proliferation, and promoting apoptosis.

    PubMed

    Ferrari, D; Lichtler, A C; Pan, Z Z; Dealy, C N; Upholt, W B; Kosher, R A

    1998-05-01

    During early stages of chick limb development, the homeobox-containing gene Msx-2 is expressed in the mesoderm at the anterior margin of the limb bud and in a discrete group of mesodermal cells at the midproximal posterior margin. These domains of Msx-2 expression roughly demarcate the anterior and posterior boundaries of the progress zone, the highly proliferating posterior mesodermal cells underneath the apical ectodermal ridge (AER) that give rise to the skeletal elements of the limb and associated structures. Later in development as the AER loses its activity, Msx-2 expression expands into the distal mesoderm and subsequently into the interdigital mesenchyme which demarcates the developing digits. The domains of Msx-2 expression exhibit considerably less proliferation than the cells of the progress zone and also encompass several regions of programmed cell death including the anterior and posterior necrotic zones and interdigital mesenchyme. We have thus suggested that Msx-2 may be in a regulatory network that delimits the progress zone by suppressing the morphogenesis of the regions of the limb mesoderm in which it is highly expressed. In the present study we show that ectopic expression of Msx-2 via a retroviral expression vector in the posterior mesoderm of the progress zone from the time of initial formation of the limb bud severely impairs limb morphogenesis. Msx-2-infected limbs are typically very narrow along the anteroposterior axis, are occasionally truncated, and exhibit alterations in the pattern of formation of skeletal elements, indicating that as a consequence of ectopic Msx-2 expression the morphogenesis of large portions of the posterior mesoderm has been suppressed. We further show that Msx-2 impairs limb morphogenesis by reducing cell proliferation and promoting apoptosis in the regions of the posterior mesoderm in which it is ectopically expressed. The domains of ectopic Msx-2 expression in the posterior mesoderm also exhibit ectopic

  17. [Early diagnosis of ectopic pregnancy].

    PubMed

    Belics, Zoran; Gérecz, Balázs; Csákány, M György

    2014-07-20

    Ectopic pregnancy is a high-risk condition that occurs in 2% of reported pregnancies. This percentage is fivefold higher than that registered in the 1970s. Since 1970 there has been a two-fold increase in the ratio of ectopic pregnancies to all reported pregnancies in Hungary and in 2012 7.4 ectopic pregnancies per thousand registered pregnancies were reported. Recently, the majority (80%) of cases can be diagnosed in early stage, and the related mortality objectively decreased in the past few decades to 3.8/10,000 ectopic pregnancies. If a woman with positive pregnancy test has abdominal pain and/or vaginal bleeding the physician should perform a work-up to safely exclude the possibility of ectopic pregnancy. The basis of diagnosis is ultrasonography, especially vaginal ultrasound examination and measurement of the β-subunit of human chorionic gonadotropin. The ultrasound diagnosis is based on the visualization of an ectopic mass rather than the inability to visualize an intrauterine pregnancy. In some questionable cases the diagnostic uterine curettage or laparoscopy may be useful. The actuality of this topic is justified by practical difficulties in obtaining correct diagnosis, especially in the early gestational time.

  18. Assessing Understanding of Biological Processes: Elucidating Students' Models of Meiosis.

    ERIC Educational Resources Information Center

    Kindfield, Ann C.

    1994-01-01

    Presents a meiosis reasoning problem that provides direct access to students' current models of chromosomes and meiosis. Also included in the article are tips for classroom implementation and a summary of the solution evaluation. (ZWH)

  19. Genetics of meiosis and recombination in mice.

    PubMed

    Bolcun-Filas, Ewelina; Schimenti, John C

    2012-01-01

    Meiosis is one of the most critical developmental processes in sexually reproducing organisms. One round of DNA replication followed by two rounds of cell divisions results in generation of haploid gametes (sperm and eggs in mammals). Meiotic failure typically leads to infertility in mammals. In the process of meiotic recombination, maternal and paternal genomes are shuffled, creating new allelic combinations and thus genetic variety. However, in order to achieve this, meiotic cells must self-inflict DNA damage in the form of programmed double-strand breaks (DSBs). Complex processes evolved to ensure proper DSB repair, and to do so in a way that favors interhomolog reciprocal recombination and crossovers. The hallmark of meiosis, a structurally conserved proteinaceous structure called the synaptonemal complex, is found only in meiotic cells. Conversely, meiotic homologous recombination is an adaptation of the mitotic DNA repair process but involving specialized proteins. In this chapter, we summarize current developments in mammalian meiosis enabled by genetically modified mice.

  20. Ectopic Granule Cells of the Rat Dentate Gyrus

    PubMed Central

    Scharfman, Helen; Goodman, Jeffrey; McCloskey, Daniel

    2007-01-01

    Granule cells of the mammalian dentate gyrus normally form a discrete layer, and virtually all granule cells migrate to this location. Exceptional granule cells that are positioned incorrectly, in ‘ectopic’ locations, are rare. Although the characteristics of such ectopic granule cells appear similar in many respects to granule cells located in the granule cell layer, their rare occurrence has limited a full evaluation of their structure and function. More information about ectopic granule cells has been obtained by studying those that develop after experimental manipulations that increase their number. For example, after severe seizures, the number of ectopic granule cells located in the hilus increases dramatically. These experimentally induced ectopic granule cells may not be equivalent to normal ectopic granule cells necessarily, but the vastly increased numbers have allowed much more information to be obtained. Remarkably, the granule cells that are positioned ectopically develop intrinsic properties and an axonal projection that are similar to granule cells that are located normally, i.e., in the granule cell layer. However, dendritic structure and synaptic structure/function appear to differ. These studies have provided new insight into a rare type of granule cell in the dentate gyrus, and the plastic characteristics of dentate granule cells that appear to depend on the location of the cell body. PMID:17148946

  1. Meiosis and its deviations in polyploid plants.

    PubMed

    Grandont, L; Jenczewski, E; Lloyd, A

    2013-01-01

    Meiosis is a fundamental process in all sexual organisms that ensures fertility and genome stability and creates genetic diversity. For each of these outcomes, the exclusive formation of crossovers between homologous chromosomes is needed. This is more difficult to achieve in polyploid species which have more than 2 sets of chromosomes able to recombine. In this review, we describe how meiosis and meiotic recombination 'deviate' in polyploid plants compared to diploids, and give an overview of current knowledge on how they are regulated. See also the sister article focusing on animals by Stenberg and Saura in this themed issue.

  2. High School Students' Use of Meiosis When Solving Genetics Problems.

    ERIC Educational Resources Information Center

    Wynne, Cynthia F.; Stewart, Jim; Passmore, Cindy

    2001-01-01

    Paints a different picture of students' reasoning with meiosis as they solved complex, computer-generated genetics problems, some of which required them to revise their understanding of meiosis in response to anomalous data. Students were able to develop a rich understanding of meiosis and can utilize that knowledge to solve genetics problems.…

  3. Possible Role of Aurora-C in Meiosis.

    PubMed

    Yang, Kuo-Tai; Tang, Chieh-Ju C; Tang, Tang K

    2015-01-01

    The meiotic generation of haploid gametes with equal contents of genetic material is important for sexual reproduction in mammals. Errors in the transmission of chromosomes during meiosis may lead to aneuploidy, which is the leading cause of miscarriage and congenital birth defects in humans. The Aurora kinases, which include Aurora-A, Aurora-B, and Aurora-C, are highly conserved serine-threonine kinases that play essential roles in centrosome function, chromosome segregation, and cytokinesis during mitosis and meiosis. While Aurora-A and Aurora-B have been extensively studied in mitosis, the role of Aurora-C in meiosis is only now starting to be revealed. For example, the perturbation of Aurora-C kinase activity by microinjection of Aurora-C-kinase-dead mutant mRNAs into mouse oocytes induced multiple defects, including chromosome misalignment, abnormal kinetochore-microtubule attachment, premature chromosome segregation, and failure of cytokinesis during meiotic division. However, the analysis of such defects is complicated by the possibility that Aurora-B may be present in mammalian germ cells. Interestingly, a homozygous mutation of Aurora-C in humans leads to the production of large-headed polyploid spermatozoa and causes male infertility, but homozygous females are fertile. Mouse studies regarding the roles of Aurora-B and Aurora-C in female meiotic divisions have yielded inconsistent results, and it has proven difficult to explain why homozygous human females have no significant clinical phenotype. In this review, we will discuss the controversial status of Aurora-B in oocytes and the possible role of Aurora-C during meiotic division.

  4. Possible Role of Aurora-C in Meiosis

    PubMed Central

    Yang, Kuo-Tai; Tang, Chieh-Ju C.; Tang, Tang K.

    2015-01-01

    The meiotic generation of haploid gametes with equal contents of genetic material is important for sexual reproduction in mammals. Errors in the transmission of chromosomes during meiosis may lead to aneuploidy, which is the leading cause of miscarriage and congenital birth defects in humans. The Aurora kinases, which include Aurora-A, Aurora-B, and Aurora-C, are highly conserved serine–threonine kinases that play essential roles in centrosome function, chromosome segregation, and cytokinesis during mitosis and meiosis. While Aurora-A and Aurora-B have been extensively studied in mitosis, the role of Aurora-C in meiosis is only now starting to be revealed. For example, the perturbation of Aurora-C kinase activity by microinjection of Aurora-C-kinase-dead mutant mRNAs into mouse oocytes induced multiple defects, including chromosome misalignment, abnormal kinetochore–microtubule attachment, premature chromosome segregation, and failure of cytokinesis during meiotic division. However, the analysis of such defects is complicated by the possibility that Aurora-B may be present in mammalian germ cells. Interestingly, a homozygous mutation of Aurora-C in humans leads to the production of large-headed polyploid spermatozoa and causes male infertility, but homozygous females are fertile. Mouse studies regarding the roles of Aurora-B and Aurora-C in female meiotic divisions have yielded inconsistent results, and it has proven difficult to explain why homozygous human females have no significant clinical phenotype. In this review, we will discuss the controversial status of Aurora-B in oocytes and the possible role of Aurora-C during meiotic division. PMID:26322271

  5. Meiosis: an overview of key differences from mitosis.

    PubMed

    Ohkura, Hiroyuki

    2015-01-20

    Meiosis is the specialized cell division that generates gametes. In contrast to mitosis, molecular mechanisms and regulation of meiosis are much less understood. Meiosis shares mechanisms and regulation with mitosis in many aspects, but also has critical differences from mitosis. This review highlights these differences between meiosis and mitosis. Recent studies using various model systems revealed differences in a surprisingly wide range of aspects, including cell-cycle regulation, recombination, postrecombination events, spindle assembly, chromosome-spindle interaction, and chromosome segregation. Although a great degree of diversity can be found among organisms, meiosis-specific processes, and regulation are generally conserved.

  6. The transcriptome landscape of early maize meiosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Meiosis, particularly meiotic recombination, is a major factor affecting yield and breeding of plants. To gain insight into the transcriptome landscape during early initiation steps of meiotic recombination, we profiled early prophase I meiocytes from maize using RNA-seq. Our analyses of genes prefe...

  7. Cytological Analysis of Meiosis in Caenorhabditis elegans

    PubMed Central

    Phillips, Carolyn M.; McDonald, Kent L.; Dernburg, Abby F.

    2011-01-01

    The nematode Caenorhabditis elegans has emerged as an informative experimental system for analysis of meiosis, in large part because of the advantageous physical organization of meiotic nuclei as a gradient of stages within the germline. Here we provide tools for detailed observational studies of cells within the worm gonad, including techniques for light and electron microscopy. PMID:19685325

  8. Ectopic testis: a rare case.

    PubMed

    Ebrahimi, Ali

    2010-01-01

    Congenital undescending testis is a common anomaly of testis, but we had a rare case of ectopic testis. A 15-month-old infant was operated emergently because of left incarcerate inguinal hernia. Intraoperative exploration of hernial sac revealed two ectopic testes with one spermatic cord proximally but in the middle divided to two spermatic cords in a 8 shape. There was an important point about vas deferens as it was single proximal to the chord, but divided into two in the middle of the chord. Vessels showed a similar condition about. We released both testes and brought down both of them into scrotum. This is a rare case of ectopic testis transectopia with partially common vas and vessels.

  9. Sister kinetochores are mechanically fused during meiosis I in yeast.

    PubMed

    Sarangapani, Krishna K; Duro, Eris; Deng, Yi; Alves, Flavia de Lima; Ye, Qiaozhen; Opoku, Kwaku N; Ceto, Steven; Rappsilber, Juri; Corbett, Kevin D; Biggins, Sue; Marston, Adèle L; Asbury, Charles L

    2014-10-10

    Production of healthy gametes requires a reductional meiosis I division in which replicated sister chromatids comigrate, rather than separate as in mitosis or meiosis II. Fusion of sister kinetochores during meiosis I may underlie sister chromatid comigration in diverse organisms, but direct evidence for such fusion has been lacking. We used laser trapping and quantitative fluorescence microscopy to study native kinetochore particles isolated from yeast. Meiosis I kinetochores formed stronger attachments and carried more microtubule-binding elements than kinetochores isolated from cells in mitosis or meiosis II. The meiosis I-specific monopolin complex was both necessary and sufficient to drive these modifications. Thus, kinetochore fusion directs sister chromatid comigration, a conserved feature of meiosis that is fundamental to Mendelian inheritance.

  10. Spontaneous triplet, tubal ectopic gestation.

    PubMed Central

    Nwanodi, Oroma; Berry, Robert

    2006-01-01

    Only six cases of spontaneous, unilateral, triplet ectopic gestations have previously been reported. We now present a seventh case. The patient's prior obstetrical history was significant for a term stillbirth and a term cesarean section for breech. Quantitative betahCG was normal for gestational age; however, the increased trophoblastic mass of an inappropriately implanted multiple gestation may produce sufficient betahCG to mimic an intrauterine singleton gestation. Resolution was achieved via salpingostomy. This case is significant for being spontaneously conceived and not the result of assisted reproductive technologies. Furthermore, this case supports an association between prior cesarean section and ectopic gestation. Images Figure 1 PMID:16775922

  11. Spontaneous bilateral tubal ectopic pregnancy.

    PubMed

    Marasinghe, Jeevan P; Condous, George; Amarasinghe, W I

    2009-03-01

    A 28-year-old woman presented at eight weeks and four days of gestation, according to her menstrual dates, complaining of painless vaginal bleeding for three days. Her urinary pregnancy test was positive. Initial transvaginal ultrasound demonstrated an irregular complex structure with a fluid filled centre in the right adnexum. Despite the diagnosis of a possible underlying unruptured right tubal ectopic pregnancy, she declined surgical intervention and was managed expectantly as an inpatient. When she complained of increasing abdominal pain with haemodynamic instability, an emergency laparotomy was performed and a diagnosis of bilateral tubal ectopic pregnancy was made.

  12. Surgical management of ectopic pregnancy.

    PubMed

    Stock, Laura; Milad, Magdy

    2012-06-01

    Surgery remains an acceptable, and sometimes necessary, modality for the treatment of ectopic pregnancy. Laparoscopy is the preferred method of access, yet controversy remains regarding the optimal procedure and postoperative management. Generally, salpingostomy is employed with the goal of maintaining fertility, although data to support this tenet are lacking. In most cases, the decision to perform conservative versus radical surgery is on the basis of the patient's history, her desire for future fertility, and surgical findings. The procedures of salpingostomy and salpingectomy, techniques to prevent and control blood loss at the time of surgery, and surgical options for nontubal ectopic pregnancies are reviewed.

  13. Heterochronic bilateral ectopic pregnancy after ovulation induction.

    PubMed

    Zhu, Bo; Xu, Gu-feng; Liu, Yi-feng; Qu, Fan; Yao, Wei-miao; Zhu, Yi-min; Gao, Hui-juan; Zhang, Dan

    2014-08-01

    Ectopic pregnancy is identified with the widely-applied assisted reproductive technology (ART). Bilateral ectopic pregnancy is a rare form of ectopic pregnancy which is difficult to be diagnosed at the pre-operation stage. In this paper, we presented an unusual case of heterochronic bilateral ectopic pregnancy after stimulated intrauterine insemination (IUI), where there has been a delay of 22 d between the diagnoses of the two ectopic pregnancies. Literature was reviewed on the occurrence of bilateral ectopic pregnancy during the past four years in the MEDLINE database. We found 16 cases of bilateral ectopic pregnancy reported since 2008, and analyzed the characteristics of those cases of bilateral ectopic pregnancy. We emphasize that ovulation induction and other ARTs may increase the risk of bilateral ectopic pregnancy. Because of the difficulty in identification of bilateral ectopic pregnancy by ultrasonography, the clinician should be aware that the treatment of one ectopic pregnancy does not preclude the occurrence of a second ectopic pregnancy in the same patient and should pay attention to the intra-operation inspection of both side fallopian tubes in any ectopic pregnancy case.

  14. Ectopic expression of an apple apomixis-related gene MhFIE induces co-suppression and results in abnormal vegetative and reproductive development in tomato.

    PubMed

    Liu, Dan-Dan; Dong, Qing-Long; Fang, Mou-Jing; Chen, Ke-Qin; Hao, Yu-Jin

    2012-12-15

    It has been well documented that FERTILIZATION-INDEPENDENT ENDOSPERM (FIE) plays important regulatory roles in diverse developmental processes in model plant Arabidopsis thaliana. However, it is largely unknown how FIE genes function in economically important crops. In this study, MhFIE gene, which was previously isolated from apomictic tea crabapple (Malus hupehensis Redh. var. pingyiensis), was introduced into tomato. The hemizygous transgenic tomato lines produced curly leaves and decreased in seed germination. In addition, the co-suppression of the transgenic MhFIE and endogenous (SlFIE) genes occurred in homozygous transgenic tomatoes. As a result, FIE silencing brought about abnormal phenotypes during reproductive development in tomato, such as increased sepal and petal numbers in flower, a fused ovule and pistil and parthenocarpic fruit formation. A yeast two-hybrid assay and bimolecular fluorescence complementation (BiFC) demonstrated that MhFIE interacted with a tomato protein, EZ2 (SlEZ2). Its ectopic expression and SlFIE co-suppression notably influenced the expression of genes associated with leaf, flower, and fruit development. Therefore, together with other PcG proteins, FIE was involved in the regulation of vegetative and reproductive development by modulating the expression of related genes in plants.

  15. Possible link between ectopic pancreas and holoprosencephaly.

    PubMed

    Kin, Tatsuya; Korbutt, Gregory S; Shapiro, A M James

    2012-01-01

    We report on the incidental observation of ectopic pancreas in a donor for islet cell transplantation. The donor's clinical and imaging presentation was definitive for holoprosencephaly. This case report discusses a possible link between ectopic pancreas and holoprosencephaly.

  16. The Flexibility of Ectopic Lipids.

    PubMed

    Loher, Hannah; Kreis, Roland; Boesch, Chris; Christ, Emanuel

    2016-09-14

    In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL), skeletal (intramyocellular lipids; IMCL) or cardiac muscle cells (intracardiomyocellular lipids; ICCL). Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. ¹H-magnetic resonance spectroscopy (¹H-MRS) is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass), insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term) appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations.

  17. The Flexibility of Ectopic Lipids

    PubMed Central

    Loher, Hannah; Kreis, Roland; Boesch, Chris; Christ, Emanuel

    2016-01-01

    In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL), skeletal (intramyocellular lipids; IMCL) or cardiac muscle cells (intracardiomyocellular lipids; ICCL). Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. 1H-magnetic resonance spectroscopy (1H-MRS) is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass), insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term) appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations. PMID:27649157

  18. [Ectopic breast fibroadenoma. Case report].

    PubMed

    Senatore, G; Zanotti, S; Cambrini, P; Montroni, I; Pellegrini, A; Montanari, E; Santini, D; Taffurelli, M

    2010-03-01

    Among the rare anomalies of the breast development, polythelia is the most common, between 1% and 5% of women and men present supernumerary nipples. Polymastia, usually presenting as ectopic breast tissue without areola-nipple complex, is seen mostly along the milk line, extending from the axilla to the pubic region. Ectopic breast tissue is functionally analogous to mammary gland and it is subjected to the same alterations and diseases, whether benign or malignant, that affect normal breast tissue. We report the case of a 21 years-old female evaluated by the medical staff after founding a solid nodular mass by suspect axillary lymphadenopathy. Differential diagnosis with lymphoma is the major problem in these cases. The mass was removed and the intraoperative histological examination showed fibroadenoma in axillary supernumerary breast. Presence of ectopic breast tissue is a rare condition; development of benign mass or malignant degeneration is possible, but it is very unusual. In case of polymastia diagnosis is simple; in case of isolated nodule, without local inflammation or infection, there are greater difficulties. Ultrasonography is diagnostic in case of breast fibroadenoma, but it might be inadequate in ectopic localizations owing to the shortage of mammary tissue around the mass. Preoperative diagnosis is important to plan an adequate surgical treatment; lumpectomy is indicated in case of benign tissue; in case of malignancy, therapy is based on the standard treatment used for breast cancer (surgery, chemotherapy and radiation therapy).

  19. MRI atlas of ectopic endometriosis.

    PubMed

    Dallaudière, B; Salut, C; Hummel, V; Pouquet, M; Piver, P; Rouanet, J-P; Maubon, A

    2013-03-01

    Ectopic endometriosis is a common condition which is often underdiagnosed, where MRI can help make a diagnosis simply, non-invasively and without irradiation. However, imagery signs of it are enormously polymorphic with a wide range of possible locations. In this paper, we have tried to illustrate comprehensively all its MRI appearances depending on the different locations where it occurs.

  20. Upper gastrointestinal ectopic variceal bleeding treated with various endoscopic modalities

    PubMed Central

    Park, Sang Woo; Cho, Eunae; Jun, Chung Hwan; Choi, Sung Kyu; Kim, Hyun Soo; Park, Chang Hwan; Rew, Jong Sun; Cho, Sung Bum; Kim, Hee Joon; Han, Mingui; Cho, Kyu Man

    2017-01-01

    Abstract Rationale: Ectopic variceal bleeding is a rare (2–5%) but fatal gastrointestinal bleed in patients with portal hypertension. Patients with ectopic variceal bleeding manifest melena, hematochezia, or hematemesis, which require urgent managements. Definitive therapeutic modalities of ectopic varices are not yet standardized because of low incidence. Various therapeutic modalities have been applied on the basis of the experiences of experts or availability of facilities, with varying results. Patient concerns: We have encountered eight cases of gastrointestinal ectopic variceal bleeding in five patients in the last five years. Diagnoses: All patients were diagnosed with liver cirrhosis presenting melena or hematemesis. Interventions: All patients were treated with various endoscopic modalities (endoscopic variceal obturation [EVO] with cyanoacrylate in five cases, endoscopic variceal band ligation (EVL) in two cases, hemoclipping in one case). Outcomes: Satisfactory hemostasis was achieved without radiologic interventions in all cases. EVO and EVL each caused one case of portal biliopathy, and EVL induced ulcer bleeding in one case. Lessons: EVO generally accomplished better results of variceal obturations than EVL or hemoclipping, without serious adverse events. EVO may be an effective modality for control of ectopic variceal bleeding without radiologic intervention or surgery. PMID:28072750

  1. N-ethyl-N-Nitrosourea (ENU) Induced Mutations within the Klotho Gene Lead to Ectopic Calcification and Reduced Lifespan in Mouse Models

    PubMed Central

    Babinsky, Valerie N.; Potter, Paul; Thomas, Gethin P.; Croucher, Peter I.; Brown, Matthew A.; Brown, Steve D. M.; Cox, Roger D.; Thakker, Rajesh V.

    2015-01-01

    Ectopic calcification (EC), which is the pathological deposition of calcium and phosphate in extra-skeletal tissues, may be associated with hypercalcaemic and hyperphosphataemic disorders, or it may occur in the absence of metabolic abnormalities. In addition, EC may be inherited as part of several monogenic disorders and studies of these have provided valuable insights into the metabolic pathways regulating mineral metabolism. For example, studies of tumoural calcinosis, a disorder characterised by hyperphosphataemia and progressive EC, have revealed mutations of fibroblast growth factor 23 (FGF23), polypeptide N-acetyl galactosaminyltransferase 3 (GALNT3) and klotho (KL), which are all part of a phosphate-regulating pathway. However, such studies in humans are limited by the lack of available large families with EC, and to facilitate such studies we assessed the progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) for EC. This identified two mutants with autosomal recessive forms of EC, and reduced lifespan, designated Ecalc1 and Ecalc2. Genetic mapping localized the Ecalc1 and Ecalc2 loci to a 11.0 Mb region on chromosome 5 that contained the klotho gene (Kl), and DNA sequence analysis identified nonsense (Gln203Stop) and missense (Ile604Asn) Kl mutations in Ecalc1 and Ecalc2 mice, respectively. The Gln203Stop mutation, located in KL1 domain, was severely hypomorphic and led to a 17-fold reduction of renal Kl expression. The Ile604Asn mutation, located in KL2 domain, was predicted to impair klotho protein stability and in vitro expression studies in COS-7 cells revealed endoplasmic reticulum retention of the Ile604Asn mutant. Further phenotype studies undertaken in Ecalc1 (kl203X/203X) mice demonstrated elevations in plasma concentrations of phosphate, FGF23 and 1,25-dihydroxyvitamin D. Thus, two allelic variants of Kl that develop EC and represent mouse models for tumoural calcinosis have been established. PMID:25860694

  2. Dephosphorylation and inactivation of NPR2 guanylyl cyclase in granulosa cells contributes to the LH-induced decrease in cGMP that causes resumption of meiosis in rat oocytes

    PubMed Central

    Egbert, Jeremy R.; Shuhaibar, Leia C.; Edmund, Aaron B.; Van Helden, Dusty A.; Robinson, Jerid W.; Uliasz, Tracy F.; Baena, Valentina; Geerts, Andreas; Wunder, Frank; Potter, Lincoln R.; Jaffe, Laurinda A.

    2014-01-01

    In mammals, the meiotic cell cycle of oocytes starts during embryogenesis and then pauses. Much later, in preparation for fertilization, oocytes within preovulatory follicles resume meiosis in response to luteinizing hormone (LH). Before LH stimulation, the arrest is maintained by diffusion of cyclic (c)GMP into the oocyte from the surrounding granulosa cells, where it is produced by the guanylyl cyclase natriuretic peptide receptor 2 (NPR2). LH rapidly reduces the production of cGMP, but how this occurs is unknown. Here, using rat follicles, we show that within 10 min, LH signaling causes dephosphorylation and inactivation of NPR2 through a process that requires the activity of phosphoprotein phosphatase (PPP)-family members. The rapid dephosphorylation of NPR2 is accompanied by a rapid phosphorylation of the cGMP phosphodiesterase PDE5, an enzyme whose activity is increased upon phosphorylation. Later, levels of the NPR2 agonist C-type natriuretic peptide decrease in the follicle, and these sequential events contribute to the decrease in cGMP that causes meiosis to resume in the oocyte. PMID:25183874

  3. Initiating meiosis: the case for retinoic acid.

    PubMed

    Griswold, Michael D; Hogarth, Cathryn A; Bowles, Josephine; Koopman, Peter

    2012-02-01

    The requirement for vitamin A in reproduction and development was first determined from studies of nutritional deficiencies. Subsequent research has shown that embryonic development and both male and female reproduction are modulated by retinoic acid (RA), the active form of vitamin A. Because RA is active in multiple developmental systems, its synthesis, transport, and degradation are tightly regulated in different tissues. A growing body of evidence implicates RA as a requirement for the initiation of meiosis in both male and female mammals, resulting in a mechanistic model involving the interplay of RA, RA synthesis enzymes, RA receptors, and degradative cytochrome P450 enzymes in this system. Recently, that model has been challenged, prompting a review of the established paradigm. While it remains possible that additional molecules may be involved in regulating entry into meiosis, the weight of evidence supporting a key role for RA is incontrovertible.

  4. Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability

    PubMed Central

    Nielsen, Aaraby Yoheswaran; Gjerstorff, Morten Frier

    2016-01-01

    Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the similarities between meiosis and genomic instability, it has been proposed that activation of meiotic programs may drive genomic instability in cancer cells. Some germ cell proteins with ectopic expression in cancer cells indeed seem to promote genomic instability, while others reduce polyploidy and maintain mitotic fidelity. Furthermore, oncogenic germ cell proteins may indirectly contribute to genomic instability through induction of replication stress, similar to classic oncogenes. Thus, current evidence suggests that testis germ cell proteins are implicated in cancer development by regulating genomic instability during tumorigenesis, and these proteins therefore represent promising targets for novel therapeutic strategies. PMID:27275820

  5. Sister chromatid segregation in meiosis II: deprotection through phosphorylation.

    PubMed

    Wassmann, Katja

    2013-05-01

    Meiotic divisions (meiosis I and II) are specialized cell divisions to generate haploid gametes. The first meiotic division with the separation of chromosomes is named reductional division. The second division, which takes place immediately after meiosis I without intervening S-phase, is equational, with the separation of sister chromatids, similar to mitosis. This meiotic segregation pattern requires the two-step removal of the cohesin complex holding sister chromatids together: cohesin is removed from chromosome arms that have been subjected to homologous recombination in meiosis I and from the centromere region in meiosis II. Cohesin in the centromere region is protected from removal in meiosis I, but this protection has to be removed--deprotected--for sister chromatid segregation in meiosis II. Whereas the mechanisms of cohesin protection are quite well understood, the mechanisms of deprotection have been largely unknown until recently. In this review I summarize our current knowledge on cohesin deprotection.

  6. How to halve ploidy: lessons from budding yeast meiosis.

    PubMed

    Kerr, Gary William; Sarkar, Sourav; Arumugam, Prakash

    2012-09-01

    Maintenance of ploidy in sexually reproducing organisms requires a specialized form of cell division called meiosis that generates genetically diverse haploid gametes from diploid germ cells. Meiotic cells halve their ploidy by undergoing two rounds of nuclear division (meiosis I and II) after a single round of DNA replication. Research in Saccharomyces cerevisiae (budding yeast) has shown that four major deviations from the mitotic cell cycle during meiosis are essential for halving ploidy. The deviations are (1) formation of a link between homologous chromosomes by crossover, (2) monopolar attachment of sister kinetochores during meiosis I, (3) protection of centromeric cohesion during meiosis I, and (4) suppression of DNA replication following exit from meiosis I. In this review we present the current understanding of the above four processes in budding yeast and examine the possible conservation of molecular mechanisms from yeast to humans.

  7. Humanized mice with ectopic artificial liver tissues.

    PubMed

    Chen, Alice A; Thomas, David K; Ong, Luvena L; Schwartz, Robert E; Golub, Todd R; Bhatia, Sangeeta N

    2011-07-19

    "Humanized" mice offer a window into aspects of human physiology that are otherwise inaccessible. The best available methods for liver humanization rely on cell transplantation into immunodeficient mice with liver injury but these methods have not gained widespread use due to the duration and variability of hepatocyte repopulation. In light of the significant progress that has been achieved in clinical cell transplantation through tissue engineering, we sought to develop a humanized mouse model based on the facile and ectopic implantation of a tissue-engineered human liver. These human ectopic artificial livers (HEALs) stabilize the function of cryopreserved primary human hepatocytes through juxtacrine and paracrine signals in polymeric scaffolds. In contrast to current methods, HEALs can be efficiently established in immunocompetent mice with normal liver function. Mice transplanted with HEALs exhibit humanized liver functions persistent for weeks, including synthesis of human proteins, human drug metabolism, drug-drug interaction, and drug-induced liver injury. Here, mice with HEALs are used to predict the disproportionate metabolism and toxicity of "major" human metabolites using multiple routes of administration and monitoring. These advances may enable manufacturing of reproducible in vivo models for diverse drug development and research applications.

  8. Sequestration of mRNAs Modulates the Timing of Translation during Meiosis in Budding Yeast

    PubMed Central

    Jin, Liang; Zhang, Kai; Xu, Yifeng; Sternglanz, Rolf

    2015-01-01

    Starvation of diploid cells of the budding yeast Saccharomyces cerevisiae induces them to enter meiosis and differentiate into haploid spores. During meiosis, the precise timing of gene expression is controlled at the level of transcription, and also translation. If cells are returned to rich medium after they have committed to meiosis, the transcript levels of most meiotically upregulated genes decrease rapidly. However, for a subset of transcripts whose translation is delayed until the end of meiosis II, termed protected transcripts, the transcript levels remain stable even after nutrients are reintroduced. The Ime2-Rim4 regulatory circuit controls both the delayed translation and the stability of protected transcripts. These protected mRNAs localize in discrete foci, which are not seen for transcripts of genes with different translational timing and are regulated by Ime2. These results suggest that Ime2 and Rim4 broadly regulate translational delay but that additional factors, such as mRNA localization, modulate this delay to tune the timing of gene expression to developmental transitions during sporulation. PMID:26217015

  9. Sequestration of mRNAs Modulates the Timing of Translation during Meiosis in Budding Yeast.

    PubMed

    Jin, Liang; Zhang, Kai; Xu, Yifeng; Sternglanz, Rolf; Neiman, Aaron M

    2015-10-01

    Starvation of diploid cells of the budding yeast Saccharomyces cerevisiae induces them to enter meiosis and differentiate into haploid spores. During meiosis, the precise timing of gene expression is controlled at the level of transcription, and also translation. If cells are returned to rich medium after they have committed to meiosis, the transcript levels of most meiotically upregulated genes decrease rapidly. However, for a subset of transcripts whose translation is delayed until the end of meiosis II, termed protected transcripts, the transcript levels remain stable even after nutrients are reintroduced. The Ime2-Rim4 regulatory circuit controls both the delayed translation and the stability of protected transcripts. These protected mRNAs localize in discrete foci, which are not seen for transcripts of genes with different translational timing and are regulated by Ime2. These results suggest that Ime2 and Rim4 broadly regulate translational delay but that additional factors, such as mRNA localization, modulate this delay to tune the timing of gene expression to developmental transitions during sporulation.

  10. From meiosis to postmeiotic events: alignment and recognition of homologous chromosomes in meiosis.

    PubMed

    Ding, Da-Qiao; Haraguchi, Tokuko; Hiraoka, Yasushi

    2010-02-01

    Recombination of homologous chromosomes is essential for correct reductional segregation of homologous chromosomes, which characterizes meiosis. To accomplish homologous recombination, chromosomes must find their homologous partners and pair with them within the spatial constraints of the nucleus. Although various mechanisms have developed in different organisms, two major steps are involved in the process of pairing: first, alignment of homologous chromosomes to bring them close to each other for recognition; and second, recognition of the homologous partner of each chromosome so that they can form an intimate pair. Here, we discuss the various mechanisms used for alignment and recognition of homologous chromosomes in meiosis.

  11. Is there evidence of sexual reproduction (meiosis) in Acanthamoeba?

    PubMed

    Khan, Naveed A; Siddiqui, Ruqaiyyah

    2015-06-01

    Evolution of independently breeding species into males and females (gametes) has remained a puzzle. Given the significant advantages of sexual reproduction over asexual reproduction as a long-term species survival strategy; here, we pose the question whether there is some form of meiosis in Acanthamoeba species, which represents our ancient lineage. The recently available Acanthamoeba genome revealed several genes implicated in meiosis in sexual eukaryotes such as Spo11, Mre11, Rad50, Rad51, Rad52, Mnd1, Dmc1, Msh, and Mlh, suggesting that Acanthamoeba is capable of some form of meiosis, inferring the presence of sexual reproduction in Acanthamoeba, and that meiosis evolved early in eukaryotic evolution.

  12. Meiosis in flowering plants and other green organisms.

    PubMed

    Harrison, C Jill; Alvey, Elizabeth; Henderson, Ian R

    2010-06-01

    Sexual eukaryotes generate gametes using a specialized cell division called meiosis that serves both to halve the number of chromosomes and to reshuffle genetic variation present in the parent. The nature and mechanism of the meiotic cell division in plants and its effect on genetic variation are reviewed here. As flowers are the site of meiosis and fertilization in angiosperms, meiotic control will be considered within this developmental context. Finally, we review what is known about the control of meiosis in green algae and non-flowering land plants and discuss evolutionary transitions relating to meiosis that have occurred in the lineages giving rise to the angiosperms.

  13. Acentrosomal spindle assembly and chromosome segregation during oocyte meiosis.

    PubMed

    Dumont, Julien; Desai, Arshad

    2012-05-01

    The ability to reproduce relies in most eukaryotes on specialized cells called gametes. Gametes are formed by the process of meiosis in which, after a single round of replication, two successive cell divisions reduce the ploidy of the genome. Fusion of gametes at fertilization reconstitutes diploidy. In most animal species, chromosome segregation during female meiosis occurs on spindles assembled in the absence of the major microtubule-organizing center, the centrosome. In mammals, oocyte meiosis is error prone and underlies most birth aneuploidies. Here, we review recent work on acentrosomal spindle formation and chromosome alignment/separation during oocyte meiosis in different animal models.

  14. Geometry and force behind kinetochore orientation: lessons from meiosis.

    PubMed

    Watanabe, Yoshinori

    2012-05-16

    During mitosis, replicated chromosomes (sister chromatids) become attached at the kinetochore by spindle microtubules emanating from opposite poles and segregate equationally. In the first division of meiosis, however, sister chromatids become attached from the same pole and co-segregate, whereas homologous chromosomes connected by chiasmata segregate to opposite poles. Disorder in this specialized chromosome attachment in meiosis is the leading cause of miscarriage in humans. Recent studies have elucidated the molecular mechanisms determining chromosome orientation, and consequently segregation, in meiosis. Comparative studies of meiosis and mitosis have led to the general principle that kinetochore geometry and tension exerted by microtubules synergistically generate chromosome orientation.

  15. Ectopic ACTH syndrome: clinicopathological correlations.

    PubMed Central

    Singer, W; Kovacs, K; Ryan, N; Horvath, E

    1978-01-01

    Ten out of 164 cases of bronchogenic carcinoma showed pathological evidence at necropsy of the ectopic ACTH syndrome. All occurred in association with oat-cell carcinoma, constituting 19% of that group. The pathological features consisted of adrenocortical hyperplasia confined to the zona fasciculata and Crooke's hyaline change in the pituitary. Immunoperoxidase stainable ACTH was detected in the pituitary but not in the carcinoma tissue, a surprising finding, which may be due to the different nature of ACTH present in tumour tissue. The ectopic ACTH syndrome was diagnosed ante mortem in only four out of 10 patients on the basis of hypokalaemia and metabolic alkalosis. The lack of clinical pointers in all but terminal cases is discussed as well as possible measures for earlier diagnosis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:209063

  16. Nicotinamide impairs entry into and exit from meiosis I in mouse oocytes.

    PubMed

    Riepsamen, Angelique; Wu, Lindsay; Lau, Laurin; Listijono, Dave; Ledger, William; Sinclair, David; Homer, Hayden

    2015-01-01

    Following exit from meiosis I, mammalian oocytes immediately enter meiosis II without an intervening interphase, accompanied by rapid reassembly of a bipolar spindle that maintains condensed chromosomes in a metaphase configuration (metaphase II arrest). Here we study the effect of nicotinamide (NAM), a non-competitive pan-sirtuin inhibitor, during meiotic maturation in mouse oocytes. Sirtuins are a family of seven NAD+-dependent deacetylases (Sirt1-7), which are involved in multiple cellular processes and are emerging as important regulators in oocytes and embryos. We found that NAM significantly delayed entry into meiosis I associated with delayed accumulation of the Cdk1 co-activator, cyclin B1. GVBD was also inhibited by the Sirt2-specific inhibitor, AGK2, and in a very similar pattern to NAM, supporting the notion that as in somatic cells, NAM inhibits sirtuins in oocytes. NAM did not affect subsequent spindle assembly, chromosome alignment or the timing of first polar body extrusion (PBE). Unexpectedly, however, in the majority of oocytes with a polar body, chromatin was decondensed and a nuclear structure was present. An identical phenotype was observed when flavopiridol was used to induce Cdk1 inactivation during late meiosis I prior to PBE, but not if Cdk1 was inactivated after PBE when metaphase II arrest was already established, altogether indicating that NAM impaired establishment rather than maintenance of metaphase II arrest. During meiosis I exit in NAM-treated medium, we found that cyclin B1 levels were lower and inhibitory Cdk1 phosphorylation was increased compared with controls. Although activation of the anaphase-promoting complex-Cdc20 (APC-Cdc20) occurred on-time in NAM-treated oocytes, Cdc20 levels were higher in very late meiosis I, pointing to exaggerated APC-Cdc20-mediated proteolysis as a reason for lower cyclin B1 levels. Collectively, therefore, our data indicate that by disrupting Cdk1 regulation, NAM impairs entry into meiosis I and

  17. Towards a new understanding on the regulation of mammalian oocyte meiosis resumption.

    PubMed

    Sun, Qing-Yuan; Miao, Yi-Liang; Schatten, Heide

    2009-09-01

    Mammalian oocytes reach prophase of first meiosis around the time of birth, and remain at this stage for months or years, depending on the species. Only after puberty will the fully-grown oocytes begin to resume meiosis which is stimulated by gonadotropin surge. It has long been known that a high level of intra-oocyte cyclic adenosine 3',5'-monophosphate (cAMP) prevents oocyte meiosis resumption as indicated by germinal vesicle breakdown (GVBD). Recently, guanosine triphosphate-binding (G) protein-coupled receptors/G proteins/adenyl cyclase pathway endogenous to the oocyte as well as cAMP diffusion from the somatic compartment through gap junctions have been implicated in maintaining cAMP at levels that prevent oocytes from resuming meiosis. Another second messager molecule, guanosine 3',5'-cyclic monophosphate (cGMP), has also recently been found to play important roles in maintaining oocyte meiosis arrest. cGMP in the follicular somatic cells diffuses into the oocyte and causes an increase in oocyte cAMP, presumably by acting on phosphodiesterase 3 (PDE3). The cGMP level in the somatic compartment of the follicle decreases in response to luteinizing hormone (LH), and this change may be mediated through the epidermal growth factor (EGF)-like factors and specific cGMP-phosphodiesterase subtype activity. It is well known that gonadotropic stimulation of meiotic resumption depends on mitogen-activated protein kinase (MAPK) activation in the somatic compartment of the follicle; recent studies show that LH, through cAMP/protein kinase A (PKA) and protein kinase C (PKC) pathways, induces the synthesis of paracine factors such as EGF-like facors and meiosis activating sterol (MAS) to regulate oocyte GVBD via the MAPK pathway in follicle cells. A recent granulosa cell-specific knockout study has for the first time provided in vivo evidence for the important role of extracellular regulated kinase 1 and 2 (ERK1/2), two main forms of MAPK, and their downstream molecules in

  18. Ectopic AP4 expression induces cellular senescence via activation of p53 in long-term confluent retinal pigment epithelial cells.

    PubMed

    Wang, Yiping; Wong, Matthew Man-Kin; Zhang, Xiaojian; Chiu, Sung-Kay

    2015-11-15

    When cells are grown to confluence, cell-cell contact inhibition occurs and drives the cells to enter reversible quiescence rather than senescence. Confluent retinal pigment epithelial (RPE) cells exhibiting contact inhibition was used as a model in this study to examine the role of overexpression of transcription factor AP4, a highly expressed transcription factor in many types of cancer, in these cells during long-term culture. We generated stable inducible RPE cell clones expressing AP4 or AP4 without the DNA binding domain (DN-AP4) and observed that, when cultured for 24 days, RPE cells with a high level of AP4 exhibit a large, flattened morphology and even cease proliferating; these changes were not observed in DN-AP4-expressing cells or non-induced cells. In addition, AP4-expressing cells exhibited senescence-associated β-galactosidase activity and the senescence-associated secretory phenotype. We demonstrated that the induced cellular senescence was mediated by enhanced p53 expression and that AP4 regulates the p53 gene by binding directly to two of the three E-boxes present on the promoter of the p53 gene. Moreover, we showed that serum is essential for AP4 in inducing p53-associated cellular senescence. Collectively, we showed that overexpression of AP4 mediates cellular senescence involving in activation of p53 in long-term post-confluent RPE cells.

  19. Meiotic and mitotic recombination in meiosis.

    PubMed

    Kohl, Kathryn P; Sekelsky, Jeff

    2013-06-01

    Meiotic crossovers facilitate the segregation of homologous chromosomes and increase genetic diversity. The formation of meiotic crossovers was previously posited to occur via two pathways, with the relative use of each pathway varying between organisms; however, this paradigm could not explain all crossovers, and many of the key proteins involved were unidentified. Recent studies that identify some of these proteins reinforce and expand the model of two meiotic crossover pathways. The results provide novel insights into the evolutionary origins of the pathways, suggesting that one is similar to a mitotic DNA repair pathway and the other evolved to incorporate special features unique to meiosis.

  20. Different Sonographic Faces of Ectopic Pregnancy

    PubMed Central

    Chanana, Charu; Gupta, Nishant; Bansal, Itisha; Hooda, Kusum; Sharma, Pranav; Gupta, Mohit; Gandhi, Darshan; Kumar, Yogesh

    2017-01-01

    Vaginal bleeding in the first trimester has wide differential diagnoses, the most common being a normal early intrauterine pregnancy, with other potential causes including spontaneous abortion and ectopic pregnancy. The incidence of ectopic pregnancy is approximately 2% of all reported pregnancies and is one of the leading causes of maternal mortality worldwide. Clinical signs and symptoms of ectopic pregnancy are often nonspecific. History of pelvic pain with bleeding and positive β-human chorionic gonadotropin should raise the possibility of ectopic pregnancy. Knowledge of the different locations of ectopic pregnancy is of utmost importance, in which ultrasound imaging plays a crucial role. This pictorial essay depicts sonographic findings and essential pitfalls in diagnosing ectopic pregnancy. PMID:28299234

  1. Different Sonographic Faces of Ectopic Pregnancy.

    PubMed

    Chanana, Charu; Gupta, Nishant; Bansal, Itisha; Hooda, Kusum; Sharma, Pranav; Gupta, Mohit; Gandhi, Darshan; Kumar, Yogesh

    2017-01-01

    Vaginal bleeding in the first trimester has wide differential diagnoses, the most common being a normal early intrauterine pregnancy, with other potential causes including spontaneous abortion and ectopic pregnancy. The incidence of ectopic pregnancy is approximately 2% of all reported pregnancies and is one of the leading causes of maternal mortality worldwide. Clinical signs and symptoms of ectopic pregnancy are often nonspecific. History of pelvic pain with bleeding and positive β-human chorionic gonadotropin should raise the possibility of ectopic pregnancy. Knowledge of the different locations of ectopic pregnancy is of utmost importance, in which ultrasound imaging plays a crucial role. This pictorial essay depicts sonographic findings and essential pitfalls in diagnosing ectopic pregnancy.

  2. The Retention of Meaningful Understanding of Meiosis and Genetics.

    ERIC Educational Resources Information Center

    Cavallo, Ann Liberatore

    This study investigated the retention of meaningful understanding of the biological topics of meiosis, the Punnett square method and the relations between these two topics. This study also explored the predictive influence of students' general tendency to learn meaningfully or by rote (meaningful learning orientation), prior knowledge of meiosis,…

  3. Chemical genetic induction of meiosis in Schizosaccharomyces pombe.

    PubMed

    Guerra-Moreno, Angel; Alves-Rodrigues, Isabel; Hidalgo, Elena; Ayté, José

    2012-04-15

    In the fission yeast Schizosaccharomyces pombe, meiosis is inhibited by the protein kinase Pat1, which phosphorylates and inactivates Mei2, an RNA binding protein essential for the initiation of meiosis. When diploid cells are deprived of nutrients, they initiate a cascade of events leading to the inactivation of Pat1 and entry into meiosis. Strains carrying the temperature-sensitive pat1-114 allele are forced to enter into meiosis when shifted to the non-permissive temperature, independently of the ploidity of the cell. This system has been extensively used, since it is possible to achieve a highly synchronous meiosis, which is a must for any molecular or microscopic approach that aims to decipher the mechanisms governing meiosis. Here, we have designed a new system to obtain a similarly synchronous meiosis, but independently of temperature shifts. Thus, by introducing a mutation in the ATP pocket of Pat1, we have generated a protein kinase that, in the presence of small specific inhibitors, can be inactivated. This results in forced entry into meiosis without the need of a temperature shift, minimizing the introduction of heat shock or any other stress responses along the meiotic waves of transcription.

  4. Ectopic Premolar Tooth in the Sigmoid Notch

    PubMed Central

    Akgül, H. M.; Bayrakdar, I. S.

    2016-01-01

    Impaction of a mandibular premolar is relatively uncommon. Ectopic placement is more unusual and there has been no discussion in the literature of an ectopic mandibular premolar in the coronoid process. In this case report, we present an impacted ectopic mandibular permanent premolar in the sigmoid notch (incisura mandibulae) region. Etiology of the tooth and treatment options are discussed and illustrated by Cone Beam Computed Tomography (CBCT) images. PMID:27547475

  5. Laparoscope resection of retroperitoneal ectopic insulinoma: A rare case

    PubMed Central

    Liu, Jie; Zhang, Cheng-Wu; Hong, De-Fei; Wu, Jia; Yang, Hong-Guo; Chen, Yuan; Zhao, Da-Jian; Zhang, Yu-Hua

    2015-01-01

    Ectopic insulinoma is a very rare and dormant tumor. Here we report the case of a 79-year-old female who presented with repeated episodes of hypoglycemia and was diagnosed with insulinoma based on laboratory and imaging examinations. Computed tomography and positron emission tomography revealed a tumor in the retroperitoneum under and left of the hepatoduodenal ligament, which was resected successfully using a laparoscopic approach. Pathologic results revealed an ectopic insulinoma, which was confirmed immunohistochemically. Ectopic insulinomas are accompanied by hypoglycemia that can be misdiagnosed as drug- or disease-induced. These tumors are difficult to diagnose and locate, particularly in atypical cases or for very small tumors. Synthetic or targeted examinations, including low blood glucose, elevated insulin, proinsulin, and C-peptide levels, 48-h fasting tests, and relevant imaging methods should be considered for suspected cases of insulinoma. Surgery is the treatment of choice for patients with insulinoma, and laparoscopic resection is a feasible and effective method for select ectopic insulinoma cases. PMID:25892896

  6. Cutaneous ectopic schistosomiasis: diagnostic challenge*

    PubMed Central

    Barros, Cláudia Renata Castro do Rêgo; Maia, Daniela Cristina Caetano; dos Santos, Josemir Belo; Medeiros, Camila Carolina Queiroz; de Araújo, Jessica Guido

    2016-01-01

    Cutaneous schistosomiasis is a rare clinical manifestation of schistosomiasis, an infectious and parasitic disease, caused in Brazil by the trematode Schistosoma mansoni. The lesions are due to the deposition of eggs or, rarely, adult worms, usually involving the genital and groin areas. Extra-genital lesions occur mainly on the torso as papules of zosteriform appearance. The case of a patient with ectopic cutaneous schistosomiasis is reported in this article, due to the rarity of its occurrence and its difficult clinical diagnosis. PMID:26982792

  7. Use of a stress inducible promoter to drive ectopic AtCBF expression improves potato freezing tolerance while minimizing negative effects on tuber yield.

    PubMed

    Pino, María-Teresa; Skinner, Jeffrey S; Park, Eung-Jun; Jeknić, Zoran; Hayes, Patrick M; Thomashow, Michael F; Chen, Tony H H

    2007-09-01

    Solanum tuberosum is a frost-sensitive species incapable of cold acclimation. A brief exposure to frost can significantly reduce its yields, while hard frosts can completely destroy entire crops. Thus, gains in freezing tolerance of even a few degrees would be of considerable benefit relative to frost damage. The S. tuberosum cv. Umatilla was transformed with three Arabidopsis CBF genes (AtCBF1-3) driven by either a constitutive CaMV35S or a stress-inducible Arabidopsis rd29A promoter. AtCBF1 and AtCBF3 over-expression via the 35S promoter increased freezing tolerance about 2 degrees C, whereas AtCBF2 over-expression failed to increase freezing tolerance. Transgenic plants of AtCBF1 and AtCBF3 driven by the rd29A promoter reached the same level of freezing tolerance as the 35S versions within a few hours of exposure to low but non-freezing temperatures. Constitutive expression of AtCBF genes was associated with negative phenotypes, including smaller leaves, stunted plants, delayed flowering, and reduction or lack of tuber production. While imparting the same degree of freezing tolerance, control of AtCBF expression via the stress-inducible promoter ameliorated these negative phenotypic effects and restored tuber production to levels similar to wild-type plants. These results suggest that use of a stress-inducible promoter to direct CBF transgene expression can yield significant gains in freezing tolerance without negatively impacting agronomically important traits in potato.

  8. Adenovirus-mediated ectopic expression of Msx2 in even-numbered rhombomeres induces apoptotic elimination of cranial neural crest cells in ovo.

    PubMed

    Takahashi, K; Nuckolls, G H; Tanaka, O; Semba, I; Takahashi, I; Dashner, R; Shum, L; Slavkin, H C

    1998-05-01

    Distinct cranial neural crest-derived cell types (a number of neuronal as well as non-neuronal cell lineages) are generated at characteristic times and positions in the rhombomeres of the hindbrain in developing vertebrate embryos. To examine this developmental process, we developed a novel strategy designed to test the efficacy of gain-of-function Msx2 expression within rhombomeres in ovo prior to the emigration of cranial neural crest cells (CNCC). Previous studies indicate that CNCC from odd-numbered rhombomeres (r3 and r5) undergo apoptosis in response to exogenous BMP4. We provide evidence that targeted infection in ovo using adenovirus containing Msx2 and a reporter molecule indicative of translation can induce apoptosis in either even- or odd-numbered rhombomeres. Furthermore, infected lacZ-control explants indicated that CNCC emigrated, and that 20% of these cells were double positive for crest cell markers HNK-1 and beta-gal. In contrast, there were no HNK-1 and Msx2 double positive cells emigrating from Msx2 infected explants. These results support the hypothesis that apoptotic elimination of CNCC can be induced by 'gain-of-function' Msx2 expression in even-numbered rhombomeres. These inductive interactions involve qualitative, quantitative, positional and temporal differences in TGF-beta-related signals, Msx2 expression and other transcriptional control.

  9. Stage-specific effects of X-irradiation on Yeast meiosis

    SciTech Connect

    Thorne, L.W.; Byers, B. )

    1993-05-01

    Previous work has shown that cdc 13 causes meiotic arrest of Saccharomyces cerevisiae following DNA replication by a RAD9-dependent mechanism. In the present work, the authors have further investigated the implicit effects of chromosomal lesions on progression through meiosis by exposing yeast cells to X-irradiation at various times during sporulation. They find that exposure of RAD9 cells to X-irradiation early in meiosis prevents sporulation, arresting the cells at a stage prior to premeiotic DNA replication. rad9 meiotic cells are much less responsive to X-irradiation damage, completing sporulation after treatment with doses sufficient to cause arrest of RAD9 strains. These findings thereby reveal a RAD9-dependent checkpoint function in meiosis that is distinct from the G[sub 2] arrest previously shown to result from cdc 13 dysfunction. Analysis of the spores that continued to be produced by either RAD9 or rad9 cultures that were X-irradiated in later stages of sporulation revealed most spores to be viable, even after exposure to radiation doses sufficient to kill most vegetative cells. This finding demonstrates that the lesions induced by X-irradiation at later times fail to trigger the checkpoint function revealed by cdc 13 arrest and suggests that the lesions may be subject to repair by serving as intermediates in the recombination process. Strains mutant for chromosomal synapsis and recombination, and therefore defective in meiotic disjunction, were tested for evidence that X-ray-induced lesions might alleviate inviability by promoting recombination. Enhancement of spore viability when spo 11 (but not hop 1) diploids were X-irradiated during meiosis indicates that induced lesions may partially substitute for SPO 11-dependent functions that are required for the initiation of recombination. 74 refs., 3 figs., 6 tabs.

  10. Evidence of ectopic recombination and a repeat-induced point (RIP) mutation in the genome of Sclerotinia sclerotiorum, the agent responsible for white mold

    PubMed Central

    Goldfarb, Míriam; Santana, Mateus Ferreira; Salomão, Tânia Maria Fernandes; de Queiroz, Marisa Vieira; de Barros, Everaldo Gonçalves

    2016-01-01

    Abstract Two retrotransposons from the superfamilies Copia and Gypsy named as Copia-LTR_SS and Gypsy-LTR_SS, respectively, were identified in the genomic bank of Sclerotinia sclerotiorum. These transposable elements (TEs) contained direct and preserved long terminal repeats (LTR). Domains related to codified regions for gag protein, integrase, reverse transcriptase and RNAse H were identified in Copia-LTR_SS, whereas in Gypsy-LTR_SS only domains for gag, reverse transcriptase and RNAse H were found. The abundance of identified LTR-Solo suggested possible genetic recombination events in the S. sclerotiorum genome. Furthermore, alignment of the sequences for LTR elements from each superfamily suggested the presence of a RIP (repeat-induced point mutation) silencing mechanism that may directly affect the evolution of this species. PMID:27560652

  11. Ectopic expression of a novel peach (Prunus persica) CBF transcription factor in apple (Malus × domestica) results in short-day induced dormancy and increased cold hardiness.

    PubMed

    Wisniewski, Michael; Norelli, John; Bassett, Carole; Artlip, Timothy; Macarisin, Dumitru

    2011-05-01

    Low, non-freezing temperatures and/or short daylength (SD) regulates cold acclimation and dormancy in fruit trees. Regarding cold acclimation, C-repeat binding factor (CBF/DREB) transcriptional activator genes have the well-documented ability to induce the expression of a suite of genes associated with increased cold tolerance. We isolated a full-length cDNA of a peach CBF gene, designated PpCBF1 (GenBank Accession HM992943), and constitutively expressed it using an enhanced 35S promoter in apple. Unexpectedly, constitutive overexpression of the PpCBF1 in apple resulted in strong sensitivity to short daylength. Growth cessation and leaf senescence were induced in transgenic lines exposed to SD and optimal growth temperatures of 25°C over a 4-week period. Following 1-4 weeks of SD and 25°C trees were returned to LD and 25°C in the greenhouse. Control (untransformed) plants continued to grow while transgenic lines receiving two or more weeks of SD remained dormant and began to drop leaves. Constitutive overexpression of the PpCBF1 in apple resulted in a 4-6°C increase in freezing tolerance in both the non-acclimated and acclimated states, respectively, compared with untransformed M.26 trees. This is the first instance that constitutive overexpression of a CBF gene has resulted in SD-induction of dormancy and to our knowledge the first time apple has been shown to strongly respond to short daylength as a result of the insertion of a transgene.

  12. Autotransplantation of Ectopic Permanent Maxillary Incisors

    PubMed Central

    Abd Jalil, Laila; Muhd Noor, Nurhidayah

    2017-01-01

    The report presents examples of successful cases of autotransplantation of ectopic teeth as donor in the treatment of clinically missing maxillary anterior teeth in young patients. The transplanted teeth were either severely ectopic, inverted, rotated or in an unfavourable position that they are commonly sacrificed as a result. Details of surgical technique as well as clinical and radiographic assessments were discussed. PMID:28352481

  13. Control of the mitotic exit network during meiosis.

    PubMed

    Attner, Michelle A; Amon, Angelika

    2012-08-01

    The mitotic exit network (MEN) is an essential GTPase signaling pathway that triggers exit from mitosis in budding yeast. We show here that during meiosis, the MEN is dispensable for exit from meiosis I but contributes to the timely exit from meiosis II. Consistent with a role for the MEN during meiosis II, we find that the signaling pathway is active only during meiosis II. Our analysis further shows that MEN signaling is modulated during meiosis in several key ways. Whereas binding of MEN components to spindle pole bodies (SPBs) is necessary for MEN signaling during mitosis, during meiosis MEN signaling occurs off SPBs and does not require the SPB recruitment factor Nud1. Furthermore, unlike during mitosis, MEN signaling is controlled through the regulated interaction between the MEN kinase Dbf20 and its activating subunit Mob1. Our data lead to the conclusion that a pathway essential for vegetative growth is largely dispensable for the specialized meiotic divisions and provide insights into how cell cycle regulatory pathways are modulated to accommodate different modes of cell division.

  14. Ectopic Atoh1 expression drives Merkel cell production in embryonic, postnatal and adult mouse epidermis

    PubMed Central

    Ostrowski, Stephen M.; Wright, Margaret C.; Bolock, Alexa M.; Geng, Xuehui; Maricich, Stephen M.

    2015-01-01

    Merkel cells are mechanosensitive skin cells whose production requires the basic helix-loop-helix transcription factor Atoh1. We induced ectopic Atoh1 expression in the skin of transgenic mice to determine whether Atoh1 was sufficient to create additional Merkel cells. In embryos, ectopic Atoh1 expression drove ectopic expression of the Merkel cell marker keratin 8 (K8) throughout the epidermis. Epidermal Atoh1 induction in adolescent mice similarly drove widespread K8 expression in glabrous skin of the paws, but in the whisker pads and body skin ectopic K8+ cells were confined to hair follicles and absent from interfollicular regions. Ectopic K8+ cells acquired several characteristics of mature Merkel cells in a time frame similar to that seen during postnatal development of normal Merkel cells. Although ectopic K8+ cell numbers decreased over time, small numbers of these cells remained in deep regions of body skin hair follicles at 3 months post-induction. In adult mice, greater numbers of ectopic K8+ cells were created by Atoh1 induction during anagen versus telogen and following disruption of Notch signaling by conditional deletion of Rbpj in the epidermis. Our data demonstrate that Atoh1 expression is sufficient to produce new Merkel cells in the epidermis, that epidermal cell competency to respond to Atoh1 varies by skin location, developmental age and hair cycle stage, and that the Notch pathway plays a key role in limiting epidermal cell competency to respond to Atoh1 expression. PMID:26138479

  15. Ectopic Atoh1 expression drives Merkel cell production in embryonic, postnatal and adult mouse epidermis.

    PubMed

    Ostrowski, Stephen M; Wright, Margaret C; Bolock, Alexa M; Geng, Xuehui; Maricich, Stephen M

    2015-07-15

    Merkel cells are mechanosensitive skin cells whose production requires the basic helix-loop-helix transcription factor Atoh1. We induced ectopic Atoh1 expression in the skin of transgenic mice to determine whether Atoh1 was sufficient to create additional Merkel cells. In embryos, ectopic Atoh1 expression drove ectopic expression of the Merkel cell marker keratin 8 (K8) throughout the epidermis. Epidermal Atoh1 induction in adolescent mice similarly drove widespread K8 expression in glabrous skin of the paws, but in the whisker pads and body skin ectopic K8+ cells were confined to hair follicles and absent from interfollicular regions. Ectopic K8+ cells acquired several characteristics of mature Merkel cells in a time frame similar to that seen during postnatal development of normal Merkel cells. Although ectopic K8+ cell numbers decreased over time, small numbers of these cells remained in deep regions of body skin hair follicles at 3 months post-induction. In adult mice, greater numbers of ectopic K8+ cells were created by Atoh1 induction during anagen versus telogen and following disruption of Notch signaling by conditional deletion of Rbpj in the epidermis. Our data demonstrate that Atoh1 expression is sufficient to produce new Merkel cells in the epidermis, that epidermal cell competency to respond to Atoh1 varies by skin location, developmental age and hair cycle stage, and that the Notch pathway plays a key role in limiting epidermal cell competency to respond to Atoh1 expression.

  16. Revisiting Ectopic Pregnancy: A Pictorial Essay

    PubMed Central

    Petrides, Artemis; Dinglas, Cheryl; Chavez, Martin; Taylor, Sharon; Mahboob, Sabrina

    2014-01-01

    Ectopic pregnancies occur in approximately 1.4% of all pregnancies and account for 15% of pregnancy-related deaths. Considering the high degree of mortality, recognizing an ectopic pregnancy is important. Signs and symptoms of an ectopic pregnancy are nonspecific and include pain, vaginal bleeding, and an adnexal mass. Therefore, imaging can play a critical role in diagnosis. There are different types of ectopic pregnancies, which are tubal, cornual, cesarean scar, cervical, heterotopic, abdominal, and ovarian. Initial imaging evaluation of pregnant patients with pelvic symptoms is by ultrasonography, transabdominal, transvaginal or both. We review the sonographic appearance of different types of ectopic pregnancies that will aid in accurate and prompt diagnosis. PMID:25161806

  17. Ovarian ectopic pregnancy: A rare case

    PubMed Central

    Ghasemi Tehrani, Hatav; Hamoush, Zaynab; Ghasemi, Mojdeh; Hashemi, Leila

    2014-01-01

    Background: Ovarian pregnancy is a rare form of the non-tubal ectopic pregnancy. It ends with rupture before the end of the first trimester. One of the important risk factors for ovarian pregnancy is in the use of Intra uterine devices (IUD). Case: We report here one such uncommon case of ovarian ectopic pregnancy. Our patient is a 30 years old multiparous woman with two previous cesarean sections with severe hypogastric abdominal pain. During laparotomy, ruptured ovarian ectopic pregnancy was diagnosed, and wedge resection of the ovary was only done. Histopathological examination confirmed it to be an ovarian ectopic pregnancy. Conclusion: IUD is one of contraceptive methods which prevents intra-uterine implantation in 99.5%, if implant occurs with IUD, it is tubal implantation in 95% of cases, and it is very rare in other places such as ovary. The most important risk factor of ovarian ectopic pregnancy is IUD as in this study it was showed. PMID:24976824

  18. [Ectopic Decidualization: A Forgotten Entity].

    PubMed

    Mendes, Joana; Costa, Antónia

    2016-01-01

    Introdução: Apesar da decidualização ectópica ser uma entidade frequentemente subdiagnosticada, pode ter impacto clínico adverso na morbimortalidade materno-fetal. O objetivo deste trabalho foi rever a evidência científica relativa a etiopatogenia, clínica, abordagem diagnóstica e terapêutica sobre esta temática. Material e Métodos: A pesquisa bibliográfica foi realizada na PubMed, Web of Science e Scopus, através da query ('deciduosis' OR 'ectopic decidualization' OR 'ectopic decidua' OR 'ectopic decidua reaction'), incluindo-se artigos publicados até 31/6/2014 e de todos os níveis de evidência. Resultados: A decidualização ectópica, geralmente, representa uma condição benigna, assintomática e sem necessidade de intervenção terapêutica. Encontra-se, maioritariamente, associada à gravidez, com regressão completa no período pós-parto. A frequência do seu diagnóstico depende da suspeição clínica, bem como do local onde surge, sendo o omento e o ovário os locais mais comuns. Quando sintomática, as principais manifestações clínicas são quadros hemorrágicos, nomeadamente hemorragia genital e hemoperitoneu. Os diagnósticos diferenciais incluem patologia maligna, sendo essencial, nestas situações, a confirmação histopatológica. O baixo índice de suspeição clínica pode levar à realização de biópsia, que pode acarretar impacto adverso grave devido à elevada friabilidade destas lesões. Discussão e Conclusão: O reconhecimento desta entidade e das suas características clínicas torna-se essencial na conduta destas doentes. Tal permite por um lado a abordagem médica precoce e adequada nos casos graves, e por outro lado (na maioria dos casos) manter a atitude expectante minimizando a iatrogenia, mantendo o desfecho favorável da decidualização ectópica.

  19. From equator to pole: splitting chromosomes in mitosis and meiosis.

    PubMed

    Duro, Eris; Marston, Adèle L

    2015-01-15

    During eukaryotic cell division, chromosomes must be precisely partitioned to daughter cells. This relies on a mechanism to move chromosomes in defined directions within the parental cell. While sister chromatids are segregated from one another in mitosis and meiosis II, specific adaptations enable the segregation of homologous chromosomes during meiosis I to reduce ploidy for gamete production. Many of the factors that drive these directed chromosome movements are known, and their molecular mechanism has started to be uncovered. Here we review the mechanisms of eukaryotic chromosome segregation, with a particular emphasis on the modifications that ensure the segregation of homologous chromosomes during meiosis I.

  20. [The pairing, synapsis and recombination of meiosis in plant].

    PubMed

    Liu, Chun-Xia; He, Qun-Yan; Jin, Wei-Wei

    2010-12-01

    Meiosis is the crucial step for sexual reproduction, while the pairing, synapsis and recombination are the key events in this process and have become the hotspots in meiosis studies. In recent years, with the development of the molecular biology and cell biology, associated with the mutant screened from mutant libraries, much advances were achieved in pairing, synapsis and recombination of meiosis in plant. In this review, we have gave an overview of the genes identification in this field and further studies of its molecular mechanism in plant.

  1. Retinoic acid, meiosis and germ cell fate in mammals.

    PubMed

    Bowles, Josephine; Koopman, Peter

    2007-10-01

    Although mammalian sex is determined genetically, the sex-specific development of germ cells as sperm or oocytes is initiated by cues provided by the gonadal environment. During embryogenesis, germ cells in an ovary enter meiosis, thereby committing to oogenesis. By contrast, germ cells in a testicular environment do not enter meiosis until puberty. Recent findings indicate that the key to this sex-specific timing of meiosis entry is the presence or absence of the signaling molecule retinoic acid. Although this knowledge clarifies a long-standing mystery in reproductive biology, it also poses many new questions, which we discuss in this review.

  2. Ectopic molar pregnancy: a case report.

    PubMed

    Bousfiha, Najoua; Erarhay, Sanaa; Louba, Adnane; Saadi, Hanan; Bouchikhi, Chahrazad; Banani, Abdelaziz; El Fatemi, Hind; Sekkal, Med; Laamarti, Afaf

    2012-01-01

    The incidence of hydatidiform moles is 1 per 1,000 pregnancies. Ectopic pregnancy occurs in 20 per 1,000 pregnancies. Thus, the incidence of the ectopic molar gestation is very rare. We report a case of tubal molar pregnancy diagnosed at the systematic histology exam of an ectopic pregnancy. We report the case of 32 years old nulliparus women who presented a vaginal bleeding, lower abdominal pain and 6 weeks amenorrhea corresponding to the last menstrual period. At the clinical examination, the arterial pressure was 100/60 mmHG. The gynecological examination was difficult because of lower abdominal pain. Serum gonadotropin activity was 3454 ui/l. Pelvic ultrasound revealed an irregular echogenic mass in the left adnexa. Diagnostic laparoscopy revealed a left-sided unruptured ampullary ectopic pregnancy. A left laparoscopic salpingectomy was performed. The systematic histologic test identified an ectopic partial molar pregnancy, which was confirmed by DNA ploidy image analysis. The patient was followed with weekly quantitative B-hCG titers until three successive B-hCG levels were negative. It is pertinent that clinicians take routine histological examination of tubal specimens in ectopic pregnancy very seriously in order to diagnose cases of ectopic molar gestations early and mount appropriate post treatment surveillance.

  3. Nuclear membrane: nuclear envelope PORosity in fission yeast meiosis.

    PubMed

    Sazer, Shelley

    2010-11-09

    The fission yeast Schizosaccharomyces pombe undergoes closed mitosis but 'virtual nuclear envelope breakdown' at anaphase of meiosis II, in which the nuclear envelope is structurally closed but functionally open.

  4. H4K44 Acetylation Facilitates Chromatin Accessibility during Meiosis.

    PubMed

    Hu, Jialei; Donahue, Greg; Dorsey, Jean; Govin, Jérôme; Yuan, Zuofei; Garcia, Benjamin A; Shah, Parisha P; Berger, Shelley L

    2015-12-01

    Meiotic recombination hotspots are associated with histone post-translational modifications and open chromatin. However, it remains unclear how histone modifications and chromatin structure regulate meiotic recombination. Here, we identify acetylation of histone H4 at Lys44 (H4K44ac) occurring on the nucleosomal lateral surface. We show that H4K44 is acetylated at pre-meiosis and meiosis and displays genome-wide enrichment at recombination hotspots in meiosis. Acetylation at H4K44 is required for normal meiotic recombination, normal levels of double-strand breaks (DSBs) during meiosis, and optimal sporulation. Non-modifiable H4K44R results in increased nucleosomal occupancy around DSB hotspots. Our results indicate that H4K44ac functions to facilitate chromatin accessibility favorable for normal DSB formation and meiotic recombination.

  5. The spindle checkpoint and chromosome segregation in meiosis.

    PubMed

    Gorbsky, Gary J

    2015-07-01

    The spindle checkpoint is a key regulator of chromosome segregation in mitosis and meiosis. Its function is to prevent precocious anaphase onset before chromosomes have achieved bipolar attachment to the spindle. The spindle checkpoint comprises a complex set of signaling pathways that integrate microtubule dynamics, biomechanical forces at the kinetochores, and intricate regulation of protein interactions and post-translational modifications. Historically, many key observations that gave rise to the initial concepts of the spindle checkpoint were made in meiotic systems. In contrast with mitosis, the two distinct chromosome segregation events of meiosis present a special challenge for the regulation of checkpoint signaling. Preservation of fidelity in chromosome segregation in meiosis, controlled by the spindle checkpoint, also has a significant impact in human health. This review highlights the contributions from meiotic systems in understanding the spindle checkpoint as well as the role of checkpoint signaling in controlling the complex divisions of meiosis.

  6. Analysis of Recombination and Chromosome Structure during Yeast Meiosis.

    PubMed

    Börner, G Valentin; Cha, Rita S

    2015-11-02

    Meiosis is a diploid-specific differentiation program that consists of a single round of genome duplication followed by two rounds of chromosome segregation. These events result in halving of the genetic complement, which is a requirement for formation of haploid reproductive cells (i.e., spores in yeast and gametes in animals and plants). During meiosis I, homologous maternal and paternal chromosomes (homologs) pair and separate, whereas sister chromatids remain connected at the centromeres and separate during the second meiotic division. In most organisms, accurate homolog disjunction requires crossovers, which are formed as products of meiotic recombination. For the past two decades, studies of yeast meiosis have provided invaluable insights into evolutionarily conserved mechanisms of meiosis.

  7. Inverted meiosis: the true bugs as a model to study.

    PubMed

    Viera, A; Page, J; Rufas, J S

    2009-01-01

    Most of the meiotic literature is based on species with monocentric chromosomes, however meiosis in protoctist, plant and animal species with holocentric chromosomes is less characterized. In some cases, an inverted meiotic sequence is claimed to occur, in which segregation of homologs is postponed until the second meiotic division. Additionally, other features also deserve interest, namely: (i) the different behavior of sex chromosomes if compared to that of the autosomes; (ii) the absence of a canonical kinetochore structure; (iii) the restriction of the kinetic activity to the chromosomal ends; (iv) the variations in the orientation of bivalents at the division plate, and (v) the possible occurrence of chiasma terminalization. Here we summarize the current knowledge on these topics in the meiosis of Hemiptera (Heteroptera) and present novel results that illustrate some of the special features mentioned above. We also point out the necessity of reviewing the term 'inverted meiosis' and propose some future prospects to study this peculiar meiosis.

  8. The role of chromosomal retention of noncoding RNA in meiosis.

    PubMed

    Ding, Da-Qiao; Haraguchi, Tokuko; Hiraoka, Yasushi

    2013-12-01

    Meiosis is a process of fundamental importance for sexually reproducing eukaryotes. During meiosis, homologous chromosomes pair with each other and undergo homologous recombination, ultimately producing haploid sets of recombined chromosomes that will be inherited by the offspring. Compared with the extensive progress that has been made in understanding the molecular mechanisms underlying recombination, how homologous sequences pair with each other is still poorly understood. The diversity of the underlying mechanisms of pairing present in different organisms further increases the complexity of this problem. Involvement of meiosis-specific noncoding RNA in the pairing of homologous chromosomes has been found in the fission yeast Schizosaccharomyces pombe. Although different organisms may have developed other or additional systems that are involved in chromosome pairing, the findings in S. pombe will provide new insights into understanding the roles of noncoding RNA in meiosis.

  9. Fungal meiosis and parasexual reproduction--lessons from pathogenic yeast.

    PubMed

    Sherwood, Racquel K; Bennett, Richard J

    2009-12-01

    Meiosis is an integral part of sexual reproduction in eukaryotic species. It performs the dual functions of halving the genetic content in the cell, as well as increasing genetic diversity by promoting recombination between chromosome homologs. Despite extensive studies of meiosis in model yeast, it is now apparent that both the regulation of meiosis and the machinery mediating recombination have significantly diverged, even between closely related species. To highlight this, we discuss new studies on sex in Candida species, a diverse collection of hemiascomycetes that are related to Saccharomyces cerevisiae and are important human pathogens. These provide new insights into the most conserved, as well as the most plastic, aspects of meiosis, meiotic recombination, and related parasexual processes.

  10. Methylation of histone H3K23 blocks DNA damage in pericentric heterochromatin during meiosis

    PubMed Central

    Papazyan, Romeo; Voronina, Ekaterina; Chapman, Jessica R; Luperchio, Teresa R; Gilbert, Tonya M; Meier, Elizabeth; Mackintosh, Samuel G; Shabanowitz, Jeffrey; Tackett, Alan J; Reddy, Karen L; Coyne, Robert S; Hunt, Donald F; Liu, Yifan; Taverna, Sean D

    2014-01-01

    Despite the well-established role of heterochromatin in protecting chromosomal integrity during meiosis and mitosis, the contribution and extent of heterochromatic histone posttranslational modifications (PTMs) remain poorly defined. Here, we gained novel functional insight about heterochromatic PTMs by analyzing histone H3 purified from the heterochromatic germline micronucleus of the model organism Tetrahymena thermophila. Mass spectrometric sequencing of micronuclear H3 identified H3K23 trimethylation (H3K23me3), a previously uncharacterized PTM. H3K23me3 became particularly enriched during meiotic leptotene and zygotene in germline chromatin of Tetrahymena and C. elegans. Loss of H3K23me3 in Tetrahymena through deletion of the methyltransferase Ezl3p caused mislocalization of meiosis-induced DNA double-strand breaks (DSBs) to heterochromatin, and a decrease in progeny viability. These results show that an evolutionarily conserved developmental pathway regulates H3K23me3 during meiosis, and our studies in Tetrahymena suggest this pathway may function to protect heterochromatin from DSBs. DOI: http://dx.doi.org/10.7554/eLife.02996.001 PMID:25161194

  11. H3 Thr3 phosphorylation is crucial for meiotic resumption and anaphase onset in oocyte meiosis.

    PubMed

    Wang, Qian; Wei, Haojie; Du, Juan; Cao, Yan; Zhang, Nana; Liu, Xiaoyun; Liu, Xiaoyu; Chen, Dandan; Ma, Wei

    2016-01-01

    Haspin-catalyzed histone H3 threonine 3 (Thr3) phosphorylation facilitates chromosomal passenger complex (CPC) docking at centromeres, regulating indirectly chromosome behavior during somatic mitosis. It is not fully known about the expression and function of H3 with phosphorylated Thr3 (H3T3-P) during meiosis in oocytes. In this study, we investigated the expression and sub-cellular distribution of H3T3-P, as well as its function in mouse oocytes during meiotic division. Western blot analysis revealed that H3T3-P expression was only detected after germinal vesicle breakdown (GVBD), and gradually increased to peak level at metaphase I (MI), but sharply decreased at metaphase II (MII). Immunofluorescence showed H3T3-P was only brightly labeled on chromosomes after GVBD, with relatively high concentration across the whole chromosome axis from pro-metaphase I (pro-MI) to MI. Specially, H3T3-P distribution was exclusively limited to the local space between sister centromeres at MII stage. Haspin inhibitor, 5-iodotubercidin (5-ITu), dose- and time-dependently blocked H3T3-P expression in mouse oocytes. H3T3-P inhibition delayed the resumption of meiosis (GVBD) and chromatin condensation. Moreover, the loss of H3T3-P speeded up the meiotic transition to MII of pro-MI oocytes in spite of the presence of non-aligned chromosomes, even reversed MI-arrest induced with Nocodazole. The inhibition of H3T3-P expression distinguishably damaged MAD1 recruitment on centromeres, which indicates the spindle assembly checkpoint was impaired in function, logically explaining the premature onset of anaphase I. Therefore, Haspin-catalyzed histone H3 phosphorylation is essential for chromatin condensation and the following timely transition from meiosis I to meiosis II in mouse oocytes during meiotic division.

  12. Formation of ectopic osteogenesis in weightlessness

    NASA Technical Reports Server (NTRS)

    1977-01-01

    An ectopic osteogenesis experiment aboard the Cosmos-936 biosatellite is described. Decalcified, lyophilized femur and tibia were implanted under the fascia or in the anterior wall of the abdomen in rats. Bone formation before and after the tests is described and illustrated. The extent of formation of ectopic bone in weightlessness did not differ significantly from that in the ground controls, but the bone marrow of the ectopic bone of the flight rats consisted exclusively of fat cells. The deficit of support-muscle loading was considered to cause the disturbance in skeletal bone tissue development.

  13. Selection on Meiosis Genes in Diploid and Tetraploid Arabidopsis arenosa

    PubMed Central

    Wright, Kevin M.; Arnold, Brian; Xue, Katherine; Šurinová, Maria; O’Connell, Jeremy; Bomblies, Kirsten

    2015-01-01

    Meiotic chromosome segregation is critical for fertility across eukaryotes, and core meiotic processes are well conserved even between kingdoms. Nevertheless, recent work in animals has shown that at least some meiosis genes are highly diverse or strongly differentiated among populations. What drives this remains largely unknown. We previously showed that autotetraploid Arabidopsis arenosa evolved stable meiosis, likely through reduced crossover rates, and that associated with this there is strong evidence for selection in a subset of meiosis genes known to affect axis formation, synapsis, and crossover frequency. Here, we use genome-wide data to study the molecular evolution of 70 meiosis genes in a much wider sample of A. arenosa. We sample the polyploid lineage, a diploid lineage from the Carpathian Mountains, and a more distantly related diploid lineage from the adjacent, but biogeographically distinct Pannonian Basin. We find that not only did selection act on meiosis genes in the polyploid lineage but also independently on a smaller subset of meiosis genes in Pannonian diploids. Functionally related genes are targeted by selection in these distinct contexts, and in two cases, independent sweeps occurred in the same loci. The tetraploid lineage has sustained selection on more genes, has more amino acid changes in each, and these more often affect conserved or potentially functional sites. We hypothesize that Pannonian diploid and tetraploid A. arenosa experienced selection on structural proteins that mediate sister chromatid cohesion, the formation of meiotic chromosome axes, and synapsis, likely for different underlying reasons. PMID:25543117

  14. Meiosis evolves: adaptation to external and internal environments.

    PubMed

    Bomblies, Kirsten; Higgins, James D; Yant, Levi

    2015-10-01

    306 I. 306 II. 307 III. 312 IV. 317 V. 318 319 References 319 SUMMARY: Meiosis is essential for the fertility of most eukaryotes and its structures and progression are conserved across kingdoms. Yet many of its core proteins show evidence of rapid or adaptive evolution. What drives the evolution of meiosis proteins? How can constrained meiotic processes be modified in response to challenges without compromising their essential functions? In surveying the literature, we found evidence of two especially potent challenges to meiotic chromosome segregation that probably necessitate adaptive evolutionary responses: whole-genome duplication and abiotic environment, especially temperature. Evolutionary solutions to both kinds of challenge are likely to involve modification of homologous recombination and synapsis, probably via adjustments of core structural components important in meiosis I. Synthesizing these findings with broader patterns of meiosis gene evolution suggests that the structural components of meiosis coevolve as adaptive modules that may change in primary sequence and function while maintaining three-dimensional structures and protein interactions. The often sharp divergence of these genes among species probably reflects periodic modification of entire multiprotein complexes driven by genomic or environmental changes. We suggest that the pressures that cause meiosis to evolve to maintain fertility may cause pleiotropic alterations of global crossover rates. We highlight several important areas for future research.

  15. Selection on meiosis genes in diploid and tetraploid Arabidopsis arenosa.

    PubMed

    Wright, Kevin M; Arnold, Brian; Xue, Katherine; Šurinová, Maria; O'Connell, Jeremy; Bomblies, Kirsten

    2015-04-01

    Meiotic chromosome segregation is critical for fertility across eukaryotes, and core meiotic processes are well conserved even between kingdoms. Nevertheless, recent work in animals has shown that at least some meiosis genes are highly diverse or strongly differentiated among populations. What drives this remains largely unknown. We previously showed that autotetraploid Arabidopsis arenosa evolved stable meiosis, likely through reduced crossover rates, and that associated with this there is strong evidence for selection in a subset of meiosis genes known to affect axis formation, synapsis, and crossover frequency. Here, we use genome-wide data to study the molecular evolution of 70 meiosis genes in a much wider sample of A. arenosa. We sample the polyploid lineage, a diploid lineage from the Carpathian Mountains, and a more distantly related diploid lineage from the adjacent, but biogeographically distinct Pannonian Basin. We find that not only did selection act on meiosis genes in the polyploid lineage but also independently on a smaller subset of meiosis genes in Pannonian diploids. Functionally related genes are targeted by selection in these distinct contexts, and in two cases, independent sweeps occurred in the same loci. The tetraploid lineage has sustained selection on more genes, has more amino acid changes in each, and these more often affect conserved or potentially functional sites. We hypothesize that Pannonian diploid and tetraploid A. arenosa experienced selection on structural proteins that mediate sister chromatid cohesion, the formation of meiotic chromosome axes, and synapsis, likely for different underlying reasons.

  16. Tet1 controls meiosis by regulating meiotic gene expression.

    PubMed

    Yamaguchi, Shinpei; Hong, Kwonho; Liu, Rui; Shen, Li; Inoue, Azusa; Diep, Dinh; Zhang, Kun; Zhang, Yi

    2012-12-20

    Meiosis is a germ-cell-specific cell division process through which haploid gametes are produced for sexual reproduction. Before the initiation of meiosis, mouse primordial germ cells undergo a series of epigenetic reprogramming steps, including the global erasure of DNA methylation at the 5-position of cytosine (5mC) in CpG-rich DNA. Although several epigenetic regulators, such as Dnmt3l and the histone methyltransferases G9a and Prdm9, have been reported to be crucial for meiosis, little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. Using a loss-of-function approach in mice, here we show that the 5mC-specific dioxygenase Tet1 has an important role in regulating meiosis in mouse oocytes. Tet1 deficiency significantly reduces female germ-cell numbers and fertility. Univalent chromosomes and unresolved DNA double-strand breaks are also observed in Tet1-deficient oocytes. Tet1 deficiency does not greatly affect the genome-wide demethylation that takes place in primordial germ cells, but leads to defective DNA demethylation and decreased expression of a subset of meiotic genes. Our study thus establishes a function for Tet1 in meiosis and meiotic gene activation in female germ cells.

  17. Tet1 controls meiosis by regulating meiotic gene expression

    PubMed Central

    Yamaguchi, Shinpei; Hong, Kwonho; Liu, Rui; Shen, Li; Inoue, Azusa; Diep, Dinh; Zhang, Kun; Zhang, Yi

    2012-01-01

    Meiosis is a germ cell-specific cell division process through which haploid gametes are produced for sexual reproduction1. Prior to initiation of meiosis, mouse primordial germ cells (PGCs) undergo a series of epigenetic reprogramming steps2,3, including global erasure of DNA methylation on the 5-position of cytosine (5mC) at CpG4,5. Although several epigenetic regulators, such as Dnmt3l, histone methyltransferases G9a and Prdm9, have been reported to be critical for meiosis6, little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. Using a loss of function approach, here we demonstrate that the 5mC-specific dioxygenase Tet1 plays an important role in regulating meiosis in mouse oocytes. Tet1 deficiency significantly reduces female germ cell numbers and fertility. Univalent chromosomes and unresolved DNA double strand breaks are also observed in Tet1-deficient oocytes. Tet1 deficiency does not greatly affect the genome-wide demethylation that takes place in PGCs but leads to defective DNA demethylation and decreased expression of a subset of meiotic genes. Our study thus establishes a function for Tet1 in meiosis and meiotic gene activation in female germ cells. PMID:23151479

  18. Spindle assembly checkpoint and its regulators in meiosis.

    PubMed

    Sun, Shao-Chen; Kim, Nam-Hyung

    2012-01-01

    BACKGROUND Meiosis is a unique form of cell division in which cells divide twice but DNA is duplicated only once. Errors in chromosome segregation during meiosis will result in aneuploidy, followed by loss of the conceptus during pregnancy or birth defects. During mitosis, cells utilize a mechanism called the spindle assembly checkpoint (SAC) to ensure faithful chromosome segregation. A similar mechanism has been uncovered for meiosis in the last decade, especially in the past several years. METHODS For this review, we included data and relevant information obtained through a PubMed database search for all articles published in English from 1991 through 2011 which included the term 'meiosis', 'spindle assembly checkpoint', or 'SAC'. RESULTS There are 91 studies included. Evidence for the existence of SAC functions in meiosis is provided by studies on the SAC proteins mitotic-arrest deficient-1 (Mad1), Mad2, budding uninhibited by benzimidazole-1 (Bub1), Bub3, BubR1 and Mps1; microtubule-kinetochore attachment regulators Ndc80 complex, chromosomal passenger complex, mitotic centromere-associated kinesin (MCAK), kinetochore null 1 (KNL1) and Mis12 complex and spindle stability regulators. CONCLUSIONS SAC and its regulators exist and function in meiosis, and their malfunctions may cause germ cell aneuploidy. However, species and sexual differences exist. Moreover, interaction of SAC components with other regulators is still poorly understood, which needs further study.

  19. Risk factors for ectopic pregnancy: a case-control study in France, with special focus on infectious factors.

    PubMed

    Coste, J; Job-Spira, N; Fernandez, H; Papiernik, E; Spira, A

    1991-05-01

    A case-control study was conducted in 1988 in seven Paris area maternity hospitals to evaluate the role of several risk factors, particularly infectious factors, in ectopic pregnancy. A total of 279 cases and 279 controls were compared for sociodemographic characteristics, cigarette smoking, sexual, reproductive and surgical histories, and conditions of conception. Pelvic inflammatory disease confirmed by celioscopy (odds ratio (OR) = 5.5, 95% confidence interval (CI) 2.1-13.9) and Chlamydia trachomatis seropositivity (OR = 3.9, 95% CI 2.3-6.7) appeared to be important risk factors for ectopic pregnancy. Other risk factors found to be associated with an increased risk of ectopic pregnancy were dose-related cigarette smoking at the time of conception (ORs 1.3 to 2.5), appendectomy (OR = 1.6, 95% CI 1.1-2.5), prior tubal surgery (OR = 5.1, 95% CI 1.7-15.4), induced conception cycle (OR = 3.2, 95% CI 1.1-9.3), and prior ectopic pregnancy (OR = 13.3, 95% CI 4.5-39.2). However, some of the latter risk factors, i.e., prior tubal surgery, prior ectopic pregnancy, and perhaps appendectomy, may be considered to be the results of pelvic inflammatory disease and sexually transmitted diseases. Maternal age, parity, prior induced abortion, and prior spontaneous abortion were not associated with ectopic pregnancy. Use of intrauterine device, progestagen micropill, and also combined estroprogestative pill at the time of conception were associated with a better prevention of intrauterine pregnancy than of ectopic pregnancy. These findings confirm the importance of several previously reported risk factors of ectopic pregnancy: sexually transmitted diseases, cigarette smoking, and prior ectopic pregnancy. They also identified new risk factors, appendectomy and induced conception cycle, and revealed that the combined estroprogestative pill does not prevent ectopic pregnancy as effectively as it does intrauterine pregnancy.

  20. Mastl is required for timely activation of APC/C in meiosis I and Cdk1 reactivation in meiosis II.

    PubMed

    Adhikari, Deepak; Diril, M Kasim; Busayavalasa, Kiran; Risal, Sanjiv; Nakagawa, Shoma; Lindkvist, Rebecca; Shen, Yan; Coppola, Vincenzo; Tessarollo, Lino; Kudo, Nobuaki R; Kaldis, Philipp; Liu, Kui

    2014-09-29

    In mitosis, the Greatwall kinase (called microtubule-associated serine/threonine kinase like [Mastl] in mammals) is essential for prometaphase entry or progression by suppressing protein phosphatase 2A (PP2A) activity. PP2A suppression in turn leads to high levels of Cdk1 substrate phosphorylation. We have used a mouse model with an oocyte-specific deletion of Mastl to show that Mastl-null oocytes resume meiosis I and reach metaphase I normally but that the onset and completion of anaphase I are delayed. Moreover, after the completion of meiosis I, Mastl-null oocytes failed to enter meiosis II (MII) because they reassembled a nuclear structure containing decondensed chromatin. Our results show that Mastl is required for the timely activation of anaphase-promoting complex/cyclosome to allow meiosis I exit and for the rapid rise of Cdk1 activity that is needed for the entry into MII in mouse oocytes.

  1. Polo kinase Cdc5 is a central regulator of meiosis I.

    PubMed

    Attner, Michelle A; Miller, Matthew P; Ee, Ly-sha; Elkin, Sheryl K; Amon, Angelika

    2013-08-27

    During meiosis, two consecutive rounds of chromosome segregation yield four haploid gametes from one diploid cell. The Polo kinase Cdc5 is required for meiotic progression, but how Cdc5 coordinates multiple cell-cycle events during meiosis I is not understood. Here we show that CDC5-dependent phosphorylation of Rec8, a subunit of the cohesin complex that links sister chromatids, is required for efficient cohesin removal from chromosome arms, which is a prerequisite for meiosis I chromosome segregation. CDC5 also establishes conditions for centromeric cohesin removal during meiosis II by promoting the degradation of Spo13, a protein that protects centromeric cohesin during meiosis I. Despite CDC5's central role in meiosis I, the protein kinase is dispensable during meiosis II and does not even phosphorylate its meiosis I targets during the second meiotic division. We conclude that Cdc5 has evolved into a master regulator of the unique meiosis I chromosome segregation pattern.

  2. Ectopic pregnancy in Conakry, Guinea.

    PubMed Central

    Thonneau, Patrick; Hijazi, Yolande; Goyaux, Nathalie; Calvez, Thierry; Keita, Namory

    2002-01-01

    OBJECTIVE: To assess the incidence of ectopic pregnancy (EP) in hospitals in Conakry, the capital of Guinea, West Africa. Data on EP incidence in developing countries are rare and often out of date, particularly in Africa. METHODS: A retrospective study was carried out, examining all cases of EP registered in the medical files of two referral maternity units at the Donka and Ignace Deen university hospitals between 1995 and 1999. FINDINGS: The EP incidence at the two maternity units increased from 0.41% to 1.5% of annual deliveries over this period. Haemoperitoneum was observed in most women, with tubal rupture in 93%; only 6 women received conservative treatment. CONCLUSION: The results suggest that the hospital-based incidence of EP per delivery has increased over the last decade in this West African capital, and that health professionals and public health officials in developing countries, especially those in Africa, should consider EP as a major obstetric problem for maternal morbidity. PMID:12077611

  3. [The laparoscopic management of ectopic pregnancy].

    PubMed

    Solar, O; Gómez, E

    1992-01-01

    Twenty-five ectopics pregnancies were treated successfully by laparoscopic approach from november 1990 to april 1992. The technics used were: salpingostomy, salpingectomy and taking out trophoblastic tissue exclusively. At the present time, two out of eight women who have wanted become pregnant, have delivered a healthy babies. We concluded that the ectopic pregnancy is efficiently managed by laparoscopy with advantages such as: minimal scar, short time in the hospital, quickly return to total activity, low costs, etc.

  4. Bilateral tubal ectopic pregnancies: a report of two cases.

    PubMed

    Eze, Justus N; Obuna, Johnson A; Ejikeme, Brown N

    2012-01-01

    Bilateral tubal ectopic pregnancies are rare occurrences. Two recently managed cases are discussed. The first was a single, sexually active 23-year-old nullipara with family history of twinning who presented with eight weeks amenorrhea, positive pregnancy test, lower abdominal discomfort and other clinical and ultrasound findings suggestive of unruptured left tubal pregnancy. Intra-operatively, unruptured bilateral tubal pregnancies were found and bilateral salpingotomy performed with uneventful recovery. Histology of the specimens confirmed the intra-operative diagnosis. She was appropriately counseled. Case 2, a 30-year-old multiparous housewife who had been on clomid for secondary infertility, presented with signs and symptoms of ruptured tubal ectopic. Intra-operatively, ruptured left and unruptured right tubal pregnancies were found and salpingectomy and salpingotomy were done respectively, with uneventful recovery. The diagnosis was also confirmed histologically and counseling given as in case 1. Bilateral tubal ectopic pregnancies appear to be increasing with twin proneness and use of fertility drugs as risk factors. Whether spontaneous or induced, the hallmarks of good management include early presentation, high index of suspicion, meticulous ultrasound scanning, good case selection, judicious intra-operative inspection of the contralateral tube, histology of specimens and appropriate patient counseling.

  5. Diagnosis and management of ectopic pregnancy.

    PubMed

    Barash, Joshua H; Buchanan, Edward M; Hillson, Christina

    2014-07-01

    Ectopic pregnancy affects 1% to 2% of all pregnancies and is responsible for 9% of pregnancy-related deaths in the United States. When a pregnant patient presents with first-trimester bleeding or abdominal pain, physicians should consider ectopic pregnancy as a possible cause. The patient history, physical examination, and imaging with transvaginal ultrasonography can usually confirm the diagnosis. When ultrasonography does not clearly identify the pregnancy location, the physician must determine whether the pregnancy is intrauterine (either viable or failing) or ectopic. Use of the beta subunit of human chorionic gonadotropin (ß-hCG) discriminatory level, the ß-hCG value above which an intrauterine pregnancy should be visualized by transvaginal ultrasonography, may be helpful. Failure to visualize an intrauterine pregnancy when ß-hCG is above the discriminatory level suggests ectopic pregnancy. In addition to single measurements of ß-hCG levels, serial levels can be monitored to detect changes. ß-hCG values in approximately 99% of viable intrauterine pregnancies increase by about 50% in 48 hours. The remaining 1% of patients have a slower rate of increase; these patients may have pregnancies that are misdiagnosed as nonviable intrauterine or ectopic. After an ectopic pregnancy has been confirmed, treatment options include medical, surgical, or expectant management. For patients who are medically unstable or experiencing life-threatening hemorrhage, a surgical approach is indicated. For others, management should be based on patient preference after discussion of the risks, benefits, and monitoring requirements of all approaches.

  6. Ectopic recurrent craniopharyngioma of the frontal bone.

    PubMed

    Jakobs, Martin; Orakcioglu, Berk

    2012-09-01

    Ectopic recurrence of craniopharyngioma is a rare phenomenon after transcranial resection of the primary tumor. The authors present a case of ectopic recurrent adamantinomatous craniopharyngioma of the frontal bone resected 16 years after initial transcranial resection of the primary tumor. The lesion was first radiographically described 12 years after surgery and was adjacent to the osteosynthesis plate that had been implanted at the craniotomy site. The recurrent craniopharyngioma was totally resected via a lateral eyebrow approach. No infiltration of the meninges or the brain was detected. Only 50 cases of ectopic recurrent craniopharyngioma have been described to date, with the present case being the first one with recurrence located at the skull bone. So far 2 mechanisms have been described: contamination with tumor cells alongside the surgical tract and spreading via CSF and the subarachnoid space. The authors reviewed the literature, provided the largest collection of cases so far, and performed basic statistical analysis regarding ectopic recurrence. Pediatric and adult patients as well as male and female ones are affected equally by this phenomenon. The mean time of ectopic recurrence after initial surgery was 7.1 years. Ectopic recurrence, although rare, should always be considered in a patient with a newly diagnosed intracranial lesion who has undergone transcranial craniopharyngioma resection before.

  7. Regulation of the meiosis-inhibited protein kinase, a p38(MAPK) isoform, during meiosis and following fertilization of seastar oocytes.

    PubMed

    Morrison, D L; Yee, A; Paddon, H B; Vilimek, D; Aebersold, R; Pelech, S L

    2000-11-03

    A p38(MAPK) homolog Mipk (meiosis-inhibited protein kinase) was cloned from seastar oocytes. This 40-kDa protein shares approximately 65% amino acid identity with mammalian p38-alpha isoforms. Mipk was one of the major tyrosine-phosphorylated proteins in immature oocytes arrested at the G(2)/M transition of meiosis I. The tyrosine phosphorylation of Mipk was increased in response to anisomycin, heat, and osmotic shock of oocytes. During 1-methyladenine-induced oocyte maturation, Mipk underwent tyrosine dephosphorylation and remained dephosphorylated in mature oocytes and during the early mitotic cell divisions until approximately 12 h after fertilization. At the time of differentiation and acquisition of G phases in the developing embryos, Mipk was rephosphorylated on tyrosine. In oocytes that were microinjected with Mipk antisense oligonucleotides and subsequently were allowed to mature and become fertilized, differentiation was blocked. Because MipK antisense oligonucleotides and a dominant-negative (K62R)Mipk when microinjected into immature oocytes failed to induce germinal vesicle breakdown, inhibition of Mipk function was not sufficient by itself to cause oocyte maturation. These findings point to a putative role for Mipk in cell cycle control as a G-phase-promoting factor.

  8. Global Identification of Genes Specific for Rice Meiosis.

    PubMed

    Zhang, Bingwei; Xu, Meng; Bian, Shiquan; Hou, Lili; Tang, Ding; Li, Yafei; Gu, Minghong; Cheng, Zhukuan; Yu, Hengxiu

    2015-01-01

    The leptotene-zygotene transition is a major step in meiotic progression during which pairing between homologous chromosomes is initiated and double strand breaks occur. OsAM1, a homologue of maize AM1 and Arabidopsis SWI1, encodes a protein with a coiled-coil domain in its central region that is required for the leptotene-zygotene transition during rice meiosis. To gain more insight into the role of OsAM1 in rice meiosis and identify additional meiosis-specific genes, we characterized the transcriptomes of young panicles of Osam1 mutant and wild-type rice plants using RNA-Seq combined with bioinformatic and statistical analyses. As a result, a total of 25,750 and 28,455 genes were expressed in young panicles of wild-type and Osam1 mutant plants, respectively, and 4,400 differentially expressed genes (DEGs; log2 Ratio ≥ 1, FDR ≤ 0.05) were identified. Of these DEGs, four known rice meiosis-specific genes were detected, and 22 new putative meiosis-related genes were found by mapping these DEGs to reference biological pathways in the KEGG database. We identified eight additional well-conserved OsAM1-responsive rice meiotic genes by comparing our RNA-Seq data with known meiotic genes in Arabidopsis and fission yeast.

  9. Regulation of APC/C activators in mitosis and meiosis.

    PubMed

    Pesin, Jillian A; Orr-Weaver, Terry L

    2008-01-01

    The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit E3 ubiquitin ligase that triggers the degradation of multiple substrates during mitosis. Cdc20/Fizzy and Cdh1/Fizzy-related activate the APC/C and confer substrate specificity through complex interactions with both the core APC/C and substrate proteins. The regulation of Cdc20 and Cdh1 is critical for proper APC/C activity and occurs in multiple ways: targeted protein degradation, phosphorylation, and direct binding of inhibitory proteins. During the specialized divisions of meiosis, the activity of the APC/C must be modified to achieve proper chromosome segregation. Recent studies show that one way in which APC/C activity is modified is through the use of meiosis-specific APC/C activators. Furthermore, regulation of the APC/C during meiosis is carried out by both mitotic regulators of the APC/C as well as meiosis-specific regulators. Here, we review the regulation of APC/C activators during mitosis and the role and regulation of the APC/C during female meiosis.

  10. Xenopus oocyte meiosis lacks spindle assembly checkpoint control

    PubMed Central

    Shao, Hua; Ma, Chunqi; Chen, Eric

    2013-01-01

    The spindle assembly checkpoint (SAC) functions as a surveillance mechanism to detect chromosome misalignment and to delay anaphase until the errors are corrected. The SAC is thought to control mitosis and meiosis, including meiosis in mammalian eggs. However, it remains unknown if meiosis in the eggs of nonmammalian vertebrate species is also regulated by SAC. Using a novel karyotyping technique, we demonstrate that complete disruption of spindle microtubules in Xenopus laevis oocytes did not affect the bivalent-to-dyad transition at the time oocytes are undergoing anaphase I. These oocytes also acquired the ability to respond to parthenogenetic activation, which indicates proper metaphase II arrest. Similarly, oocytes exhibiting monopolar spindles, via inhibition of aurora B or Eg5 kinesin, underwent monopolar anaphase on time and without additional intervention. Therefore, the metaphase-to-anaphase transition in frog oocytes is not regulated by SAC. PMID:23569212

  11. Heteromorphic sex chromosomes: navigating meiosis without a homologous partner.

    PubMed

    Checchi, Paula M; Engebrecht, Joanne

    2011-09-01

    Accurate chromosome segregation during meiosis relies on homology between the maternal and paternal chromosomes. Yet by definition, sex chromosomes of the heterogametic sex lack a homologous partner. Recent studies in a number of systems have shed light on the unique meiotic behavior of heteromorphic sex chromosomes, and highlight both the commonalities and differences in divergent species. During meiotic prophase, the homology-dependent processes of pairing, synapsis, and recombination have been modified in many different ways to ensure segregation of heteromorphic sex chromosomes at the first meiotic division. Additionally, an almost universal feature of heteromorphic sex chromosomes during meiosis is transcriptional silencing, or meiotic sex chromosome inactivation, an essential process proposed to prevent expression of genes deleterious to meiosis in the heterogametic sex as well as to shield unpaired sex chromosomes from recognition by meiotic checkpoints. Comparative analyses of the meiotic behavior of sex chromosomes in nematodes, mammals, and birds reveal important conserved features as well as provide insight into sex chromosome evolution.

  12. Nuclear compartmentalization is abolished during fission yeast meiosis.

    PubMed

    Arai, Kunio; Sato, Masamitsu; Tanaka, Kayoko; Yamamoto, Masayuki

    2010-11-09

    In eukaryotic cells, the nuclear envelope partitions the nucleus from the cytoplasm. The fission yeast Schizosaccharomyces pombe undergoes closed mitosis in which the nuclear envelope persists rather than being broken down, as in higher eukaryotic cells. It is therefore assumed that nucleocytoplasmic transport continues during the cell cycle. Here we show that nuclear transport is, in fact, abolished specifically during anaphase of the second meiotic nuclear division. During that time, both nucleoplasmic and cytoplasmic proteins disperse throughout the cell, reminiscent of the open mitosis of higher eukaryotes, but the architecture of the S. pombe nuclear envelope itself persists. This functional alteration of the nucleocytoplasmic barrier is likely induced by spore wall formation, because ectopic induction of sporulation signaling leads to premature dispersion of nucleoplasmic proteins. A photobleaching assay demonstrated that nuclear envelope permeability increases abruptly at the onset of anaphase of the second meiotic division. The permeability was not altered when sporulation was inhibited by blocking the trafficking of forespore-membrane vesicles from the endoplasmic reticulum to the Golgi. The evidence indicates that yeast gametogenesis produces vesicle transport-mediated forespore membranes by inducing nuclear envelope permeabilization.

  13. Effect of guaianolides in the meiosis reinitiation of amphibian oocytes.

    PubMed

    Zapata-Martínez, J; Sánchez-Toranzo, G; Chaín, F; Catalán, C A N; Bühler, M I

    2017-02-01

    Sesquiterpene lactones (STLs) are a large and structurally diverse group of plant metabolites generally found in the Asteraceae family. STLs exhibit a wide spectrum of biological activities and it is generally accepted that their major mechanism of action is the alkylation of the thiol groups of biological molecules. The guaianolides is one of various groups of STLs. Anti-tumour and anti-migraine effects, an allergenic agent, an inhibitor of smooth muscle cells and of meristematic cell proliferation are only a few of the most commonly reported activities of STLs. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under stimulus with progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. There are previous records of the inhibitory effect of dehydroleucodin (DhL), a guaianolide lactone, on the progression of meiosis. It has been also shown that DhL and its 11,13-dihydroderivative (2H-DhL; a mixture of epimers at C-11) act as blockers of the resumption of meiosis in fully grown ovarian oocytes from the amphibian Rhinella arenarum (formerly classified as Bufo arenarum). The aim of this study was to analyze the effect of four closely related guaianolides, i.e., DhL, achillin, desacetoxymatricarin and estafietin as possible inhibitors of meiosis in oocytes of amphibians in vitro and discuss some structure-activity relationships. It was found that the inhibitory effect on meiosis resumption is greater when the lactone has two potentially reactive centres, either a α,β-α',β'-diunsaturated cyclopentanone moiety or an epoxide group plus an exo-methylene-γ-lactone function.

  14. Unravelling the proteomic profile of rice meiocytes during early meiosis

    PubMed Central

    Collado-Romero, Melania; Alós, Enriqueta; Prieto, Pilar

    2014-01-01

    Transfer of genetic traits from wild or related species into cultivated rice is nowadays an important aim in rice breeding. Breeders use genetic crosses to introduce desirable genes from exotic germplasms into cultivated rice varieties. However, in many hybrids there is only a low level of pairing (if existing) and recombination at early meiosis between cultivated rice and wild relative chromosomes. With the objective of getting deeper into the knowledge of the proteins involved in early meiosis, when chromosomes associate correctly in pairs and recombine, the proteome of isolated rice meiocytes has been characterized by nLC-MS/MS at every stage of early meiosis (prophase I). Up to 1316 different proteins have been identified in rice isolated meiocytes in early meiosis, being 422 exclusively identified in early prophase I (leptotene, zygotene, or pachytene). The classification of proteins in functional groups showed that 167 were related to chromatin structure and remodeling, nucleic acid binding, cell-cycle regulation, and cytoskeleton. Moreover, the putative roles of 16 proteins which have not been previously associated to meiosis or were not identified in rice before, are also discussed namely: seven proteins involved in chromosome structure and remodeling, five regulatory proteins [such as SKP1 (OSK), a putative CDK2 like effector], a protein with RNA recognition motifs, a neddylation-related protein, and two microtubule-related proteins. Revealing the proteins involved in early meiotic processes could provide a valuable tool kit to manipulate chromosome associations during meiosis in rice breeding programs. The data have been deposited to the ProteomeXchange with the PXD001058 identifier. PMID:25104955

  15. Ovarian tumor-derived ectopic hyperprolactinemia.

    PubMed

    Elms, Autumn F; Carlan, S J; Rich, Amy E; Cerezo, Lizardo

    2012-12-01

    To describe extreme hyperprolactinemia originating from a pituitary adenoma in the wall of an ovarian dermoid. This is a description of an unusual case and a review of ectopic prolactin production. Ectopic production of prolactin is a rare condition that has been reported in isolated organ system pathology including ovaries. An ovarian dermoid is a benign neoplasm that has the potential for active unregulated endocrine function. Hyperprolactinemia can result from functioning lactotrophs found in ovarian dermoids and can lead to clinical sequelae. Definitive treatment of the condition requires surgical removal of the functioning endocrine tissue. Extreme hyperprolactinemia caused by a pituitary tumor located within a dermoid has not been reported before. We present a case of profound hyperprolactinemia originating from a pituitary adenoma found in the wall of an ovarian dermoid and give a broad overview of the condition and literature. Ectopic prolactin production should always be considered in symptomatic patients found to have elevated serum levels and no findings on brain imaging.

  16. Epigenetic transitions in germ cell development and meiosis.

    PubMed

    Kota, Satya K; Feil, Robert

    2010-11-16

    Germ cell development is controlled by unique gene expression programs and involves epigenetic reprogramming of histone modifications and DNA methylation. The central event is meiosis, during which homologous chromosomes pair and recombine, processes that involve histone alterations. At unpaired regions, chromatin is repressed by meiotic silencing. After meiosis, male germ cells undergo chromatin remodeling, including histone-to-protamine replacement. Male and female germ cells are also differentially marked by parental imprints, which contribute to sex determination in insects and mediate genomic imprinting in mammals. Here, we review epigenetic transitions during gametogenesis and discuss novel insights from animal and human studies.

  17. The meiosis-specific modification of mammalian telomeres.

    PubMed

    Shibuya, Hiroki; Watanabe, Yoshinori

    2014-01-01

    During meiosis, rapid chromosome movements within the nucleus enable homologous chromosomes to acquire physical juxtaposition. In most organisms, chromosome ends, telomeres, tethered to the transmembrane LINC-complex mediate this movement by transmitting cytoskeletal forces to the chromosomes. While the majority of molecular studies have been performed using lower eukaryotes as model systems, recent studies have identified mammalian meiotic telomere regulators, including the LINC-complex SUN1/KASH5 and the meiosis-specific telomere binding protein TERB1. This review highlights the molecular regulations of mammalian meiotic telomeres in comparison with other model systems and discusses some future perspectives.

  18. Chromosome pairing and synapsis during Caenorhabditis elegans meiosis.

    PubMed

    Rog, Ofer; Dernburg, Abby F

    2013-06-01

    Meiosis is the specialized cell division cycle that produces haploid gametes to enable sexual reproduction. Reduction of chromosome number by half requires elaborate chromosome dynamics that occur in meiotic prophase to establish physical linkages between each pair of homologous chromosomes. Caenorhabditis elegans has emerged as an excellent model organism for molecular studies of meiosis, enabling investigators to combine the power of molecular genetics, cytology, and live analysis. Here we focus on recent studies that have shed light on how chromosomes find and identify their homologous partners, and the structural changes that accompany and mediate these interactions.

  19. Understanding a Basic Biological Process: Expert and Novice Models of Meiosis.

    ERIC Educational Resources Information Center

    Kindfield, Ann C. H.

    The results of a study of the meiosis models utilized by individuals at varying levels of expertise while reasoning about the process of meiosis are presented. Based on these results, the issues of sources of misconceptions/difficulties and the construction of a sound understanding of meiosis are discussed. Five individuals from each of three…

  20. Students as "Humans Chromosomes" in Role-Playing Mitosis and Meiosis

    ERIC Educational Resources Information Center

    Chinnici, Joseph P.; Yue, Joyce W.; Torres, Kieron M.

    2004-01-01

    Students often find it challenging to understand mitosis and meiosis and determine their processes. To develop an easier way to understand these terms, students are asked to role-play mitosis and meiosis and students themselves act as human chromosomes, which help students to learn differences between mitosis and meiosis.

  1. What Is the Risk for a Second Ectopic Pregnancy?

    MedlinePlus

    ... Old What Is the Risk for a Second Ectopic Pregnancy? KidsHealth > For Parents > What Is the Risk for ... TOPIC Medical Care During Pregnancy Pregnancy & Newborn Center Pregnancy Precautions: FAQs Ectopic Pregnancy Contact Us Print Resources Send to a ...

  2. Using pool noodles to teach mitosis and meiosis.

    PubMed

    Locke, John; McDermid, Heather E

    2005-05-01

    Although mitosis and meiosis are fundamental to understanding genetics, students often find them difficult to learn. We suggest using common "pool noodles" as teaching aids to represent chromatids in classroom demonstrations. Students use these noodles to demonstrate the processes of synapsis, segregation, and recombination. Student feedback has been overwhelmingly positive.

  3. Kif4 Is Essential for Mouse Oocyte Meiosis

    PubMed Central

    Camlin, Nicole J.; McLaughlin, Eileen A.; Holt, Janet E.

    2017-01-01

    Progression through the meiotic cell cycle must be strictly regulated in oocytes to generate viable embryos and offspring. During mitosis, the kinesin motor protein Kif4 is indispensable for chromosome condensation and separation, midzone formation and cytokinesis. Additionally, the bioactivity of Kif4 is dependent on phosphorylation via Aurora Kinase B and Cdk1, which regulate Kif4 function throughout mitosis. Here, we examine the role of Kif4 in mammalian oocyte meiosis. Kif4 localized in the cytoplasm throughout meiosis I and II, but was also observed to have a dynamic subcellular distribution, associating with both microtubules and kinetochores at different stages of development. Co-localization and proximity ligation assays revealed that the kinetochore proteins, CENP-C and Ndc80, are potential Kif4 interacting proteins. Functional analysis of Kif4 in oocytes via antisense knock-down demonstrated that this protein was not essential for meiosis I completion. However, Kif4 depleted oocytes displayed enlarged polar bodies and abnormal metaphase II spindles, indicating an essential role for this protein for correct asymmetric cell division in meiosis I. Further investigation of the phosphoregulation of meiotic Kif4 revealed that Aurora Kinase and Cdk activity is critical for Kif4 kinetochore localization and interaction with Ndc80 and CENP-C. Finally, Kif4 protein but not gene expression was found to be upregulated with age, suggesting a role for this protein in the decline of oocyte quality with age. PMID:28125646

  4. Sperm should evolve to make female meiosis fair.

    PubMed

    Brandvain, Yaniv; Coop, Graham

    2015-04-01

    Genomic conflicts arise when an allele gains an evolutionary advantage at a cost to organismal fitness. Oögenesis is inherently susceptible to such conflicts because alleles compete for inclusion into the egg. Alleles that distort meiosis in their favor (i.e., meiotic drivers) often decrease organismal fitness, and therefore indirectly favor the evolution of mechanisms to suppress meiotic drive. In this light, many facets of oögenesis and gametogenesis have been interpreted as mechanisms of protection against genomic outlaws. That females of many animal species do not complete meiosis until after fertilization, appears to run counter to this interpretation, because this delay provides an opportunity for sperm-acting alleles to meddle with the outcome of female meiosis and help like alleles drive in heterozygous females. Contrary to this perceived danger, the population genetic theory presented herein suggests that, in fact, sperm nearly always evolve to increase the fairness of female meiosis in the face of genomic conflicts. These results are consistent with the apparent sperm dependence of the best characterized female meiotic driversin animals. Rather than providing an opportunity for sperm collaboration in female meiotic drive, the "fertilization requirement" indirectly protects females from meiotic drivers by providing sperm an opportunity to suppress drive.

  5. Comparative transcriptomics of early meiosis in Arabidopsis and maize.

    PubMed

    Dukowic-Schulze, Stefanie; Harris, Anthony; Li, Junhua; Sundararajan, Anitha; Mudge, Joann; Retzel, Ernest F; Pawlowski, Wojciech P; Chen, Changbin

    2014-03-20

    Though sexually reproductive plants share the same principle and most processes in meiosis, there are distinct features detectable. To address the similarities and differences of early meiosis transcriptomes from the dicot model system Arabidopsis and monocot model system maize, we performed comparative analyses of RNA-seq data of isolated meiocytes, anthers and seedlings from both species separately and via orthologous genes. Overall gene expression showed similarities, such as an increased number of reads mapping to unannotated features, and differences, such as the amount of differentially expressed genes. We detected major similarities and differences in functional annotations of genes up-regulated in meiocytes, which point to conserved features as well as unique features. Transcriptional regulation seems to be quite similar in Arabidopsis and maize, and we could reveal known and novel transcription factors and cis-regulatory elements acting in early meiosis. Taken together, meiosis between Arabidopsis and maize is conserved in many ways, but displays key distinctions that lie in the patterns of gene expression.

  6. "Dropping Your Genes." A Genetics Simulation in Meiosis, Fertilization & Reproduction.

    ERIC Educational Resources Information Center

    Atkins, Thomas; Roderick, Joyce MacFall

    1991-01-01

    An activity that introduces students to the concepts of independent assortment of alleles during meiosis and gametogenesis, the richness of the variation that occurs as a result of allele recombination, and the unique phenotypes of offspring. Reproducible handouts with the directions and model chromosomes are provided. (KR)

  7. Meiosis in cereal crops: the grasses are back.

    PubMed

    Martinez-perez, E

    2009-01-01

    A major goal of breeding programs is to increase and manipulate the genetic diversity of crops. The incorporation of beneficial genes from wild relatives into crops is achieved by producing hybrid plants in which meiotic recombination events occur between the two genomes. Furthering our understanding of meiosis in the cereals could enable the manipulation of homolog pairing and recombination, significantly enhancing the efficiency of breeding programs. The main obstacle to the genetic analysis of meiosis in cereal crops has been the complex organization of most cereal genomes, many of which are polyploid. However, the recent sequencing of the rice genome, the use of insertional mutagenesis and reverse genetics approaches has opened the door for the genetic and genomic analysis of cereal meiosis. The goal of this review is to show how these new resources, as well as the use of three-dimensional microscopy, are rapidly providing insights into the mechanisms that control pairing, recombination and segregation of homologous chromosomes during meiosis in four major cereal crops: wheat, rice, maize and rye.

  8. The spatial and mechanical challenges of female meiosis.

    PubMed

    Evans, Janice P; Robinson, Douglas N

    2011-01-01

    Recent work shows that cytokinesis and other cellular morphogenesis events are tuned by an interplay among biochemical signals, cell shape, and cellular mechanics. In cytokinesis, this includes cross-talk between the cortical cytoskeleton and the mitotic spindle in coordination with cell cycle control, resulting in characteristic changes in cellular morphology and mechanics through metaphase and cytokinesis. The changes in cellular mechanics affect not just overall cell shape, but also mitotic spindle morphology and function. This review will address how these principles apply to oocytes undergoing the asymmetric cell divisions of meiosis I and II. The biochemical signals that regulate cell cycle timing during meiotic maturation and egg activation are crucial for temporal control of meiosis. Spatial control of the meiotic divisions is also important, ensuring that the chromosomes are segregated evenly and that meiotic division is clearly asymmetric, yielding two daughter cells - oocyte and polar body - with enormous volume differences. In contrast to mitotic cells, the oocyte does not undergo overt changes in cell shape with its progression through meiosis, but instead maintains a relatively round morphology with the exception of very localized changes at the time of polar body emission. Placement of the metaphase-I and -II spindles at the oocyte periphery is clearly important for normal polar body emission, although this is likely not the only control element. Here, consideration is given to how cellular mechanics could contribute to successful mammalian female meiosis, ultimately affecting egg quality and competence to form a healthy embryo.

  9. The template choice decision in meiosis: is the sister important?

    PubMed

    Pradillo, Mónica; Santos, Juan L

    2011-10-01

    Recombination between homologous chromosomes is crucial to ensure their proper segregation during meiosis. This is achieved by regulating the choice of recombination template. In mitotic cells, double-strand break repair with the sister chromatid appears to be preferred, whereas interhomolog recombination is favoured during meiosis. However, in the last year, several studies in yeast have shown the importance of the meiotic recombination between sister chromatids. Although this thinking seems to be new, evidences for sister chromatid exchange during meiosis were obtained more than 50 years ago in non-model organisms. In this mini-review, we comment briefly on the most recent advances in this hot topic and also describe observations which suggest the existence of inter-sister repair during meiotic recombination. For instance, the behaviour of mammalian XY bivalents and that of trivalents in heterozygotes for chromosomal rearrangements are cited as examples. The "rediscovering" of the requirement for the sister template, although it seems to occur at a low frequency, will probably prompt further investigations in organisms other than yeast to understand the complexity of the partner choice during meiosis.

  10. Role of compensatory meiosis mechanisms in human spermatogenesis.

    PubMed

    Borgers, Mareike; Wolter, Martin; Hentrich, Anna; Bergmann, Martin; Stammler, Angelika; Konrad, Lutz

    2014-09-01

    Disturbances of checkpoints in distinct stages of spermatogenesis (mitosis, meiosis, and spermiogenesis) contribute to impaired spermatogenesis; however, the efficiency of meiotic entry has not been investigated in more detail. In this study, we analyzed azoospermic patients with defined spermatogenic defects by the use of octamer-binding protein 2 for type A spermatogonia, sarcoma antigen 1 for mitosis-meiosis transition and SMAD3 for pachytene spermatocytes. Especially patients with maturation arrest (MA) at the level of primary spermatocytes showed significantly reduced numbers of spermatogonia compared with patients with histologically intact spermatogenesis or patients with hypospermatogenesis (Hyp). For a detailed individual classification of the patients, we distinguished between 'high efficiency of meiotic entry' (high numbers of pachytene spermatocytes) and 'low efficiency of meiotic entry' (low numbers of pachytene spermatocytes). Only patients with histologically normal spermatogenesis (Nsp) and patients with Hyp showed normal numbers of spermatogonia and a high efficiency of meiotic entry. Of note, only patients with histologically Nsp or patients with Hyp could compensate low numbers of spermatogonia with a high efficiency of meiotic entry. In contrast, patients with MA always showed a low efficiency of meiotic entry. This is the first report on patients with impaired spermatogenesis, showing that half of the patients with Hyp but all patients with MA cannot compensate reduced numbers in spermatogonia with a highly efficient meiosis. Thus, we suggest that compensatory meiosis mechanisms in human spermatogenesis exist.

  11. Using Pool Noodles to Teach Mitosis and Meiosis

    PubMed Central

    Locke, John; McDermid, Heather E.

    2005-01-01

    Although mitosis and meiosis are fundamental to understanding genetics, students often find them difficult to learn. We suggest using common “pool noodles” as teaching aids to represent chromatids in classroom demonstrations. Students use these noodles to demonstrate the processes of synapsis, segregation, and recombination. Student feedback has been overwhelmingly positive. PMID:15781711

  12. Triplets—one ectopic, two intrauterine

    PubMed Central

    Khan, A. A.

    1973-01-01

    A case of ovarian ectopic conception, complicating a simultaneous twin intra-uterine pregnancy is described, in which the operative diagnosis was confirmed by histological examination. Such cases are extremely rare and comment is made upon this with references. PMID:4786440

  13. Ectopic pregnancy in an apparently healthy bitch.

    PubMed

    Eddey, Philip D

    2012-01-01

    This case describes an extrauterine fetus that was discovered in an apparently healthy bitch 5 mo after whelping. The extrauterine fetus was surgically removed, and the bitch made a complete recovery. The topic of canine ectopic pregnancy is discussed, and a review of previously reported cases is presented.

  14. Ectopic pregnancy comparison of different treatments

    PubMed Central

    Kopani, Fatmir; Rrugia, Arben; Manoku, Nikita

    2010-01-01

    Objectives: We would like to determine the best treatment option depending of ectopic pregnancy situation. Methods. This is a retrospective cohort study that registered all women admitted in Obstetrics and Gynecologic “Queen Geraldine” Hospital June 2003 until 2008 dicember. There were admitted 228 women diagnosed with Ectopic Pregnancy that were treated in our Hospital. Results: Unruptured ectopic pregnancy is diagnosed in 5,2 week of pregnancy and ruptured ectopic in an average of 6,4 weeks. Surgical intervention is registered in 170 patients and we did tubectomy. Success rate of Methotrexate application was more successful if β-hCG level was lower. If the β-hCG level is higher over 10 000 the success rate will decrease in 83 % and in β-hCG levels over 15 000 the success rate will be until 50%. Conclusions: The treatment will be determined by combination of clinical symptoms, ultrasound examination and β-hCG levels. MTX is recommended for all women without hemodinamic problems, unruptured pregnancy and low β-hCG level (β-hCG < 5000 mlU/mL). It is confirmed that the reduction of 15% of β-hCG in the fourth day after application of MTX is a success guide. PMID:22439058

  15. Ectopic eyes outside the head in Xenopus tadpoles provide sensory data for light-mediated learning.

    PubMed

    Blackiston, Douglas J; Levin, Michael

    2013-03-15

    A major roadblock in the biomedical treatment of human sensory disorders, including blindness, has been an incomplete understanding of the nervous system and its ability to adapt to changes in sensory modality. Likewise, fundamental insight into the evolvability of complex functional anatomies requires understanding brain plasticity and the interaction between the nervous system and body architecture. While advances have been made in the generation of artificial and biological replacement components, the brain's ability to interpret sensory information arising from ectopic locations is not well understood. We report the use of eye primordia grafts to create ectopic eyes along the body axis of Xenopus tadpoles. These eyes are morphologically identical to native eyes and can be induced at caudal locations. Cell labeling studies reveal that eyes created in the tail send projections to the stomach and trunk. To assess function we performed light-mediated learning assays using an automated machine vision and environmental control system. The results demonstrate that ectopic eyes in the tail of Xenopus tadpoles could confer vision to the host. Thus ectopic visual organs were functional even when present at posterior locations. These data and protocols demonstrate the ability of vertebrate brains to interpret sensory input from ectopic structures and incorporate them into adaptive behavioral programs. This tractable new model for understanding the robust plasticity of the central nervous system has significant implications for regenerative medicine and sensory augmentation technology.

  16. Using a meiosis detection toolkit to investigate ancient asexual "scandals" and the evolution of sex.

    PubMed

    Schurko, Andrew M; Logsdon, John M

    2008-06-01

    Sexual reproduction is the dominant reproductive mode in eukaryotes but, in many taxa, it has never been observed. Molecular methods that detect evidence of sex are largely based on the genetic consequences of sexual reproduction. Here we describe a powerful new approach to directly search genomes for genes that function in meiosis. We describe a "meiosis detection toolkit", a set of meiotic genes that represent the best markers for the presence of meiosis. These genes are widely present in eukaryotes, function only in meiosis and can be isolated by degenerate PCR. The presence of most, or all, of these genes in a genome would suggest they have been maintained for meiosis and, implicitly, sexual reproduction. In contrast, their absence would be consistent with the loss of meiosis and asexuality. This approach will help to understand both meiotic gene evolution and the capacity for meiosis and sex in putative obligate asexuals.

  17. Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption.

    PubMed

    Li, Nan; Mruk, Dolores D; Mok, Ka-Wai; Li, Michelle W M; Wong, Chris K C; Lee, Will M; Han, Daishu; Silvestrini, Bruno; Cheng, C Yan

    2016-04-01

    Earlier studies have shown that rats treated with an acute dose of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (adjudin, a male contraceptive under development) causes permanent infertility due to irreversible blood-testis barrier (BTB) disruption even though the population of undifferentiated spermatogonia remains similar to normal rat testes, because spermatogonia fail to differentiate into spermatocytes to enter meiosis. Since other studies have illustrated the significance of connexin 43 (Cx43)-based gap junction in maintaining the homeostasis of BTB in the rat testis and the phenotypes of Sertoli cell-conditional Cx43 knockout mice share many of the similarities of the adjudin-treated rats, we sought to examine if overexpression of Cx43 in these adjudin-treated rats would reseal the disrupted BTB and reinitiate spermatogenesis. A full-length Cx43 cloned into mammalian expression vector pCI-neo was used to transfect testes of adjudin-treated ratsversusempty vector. It was found that overexpression of Cx43 indeed resealed the Sertoli cell tight junction-permeability barrier based on a functionalin vivoassay in tubules displaying signs of meiosis as noted by the presence of round spermatids. Thus, these findings suggest that overexpression of Cx43 reinitiated spermatogenesis at least through the steps of meiosis to generate round spermatids in testes of rats treated with an acute dose of adjudin that led to aspermatogenesis. It was also noted that the round spermatids underwent eventual degeneration with the formation of multinucleated cells following Cx43 overexpression due to the failure of spermiogenesis because no elongating/elongated spermatids were detected in any of the tubules examined. The mechanism by which overexpression of Cx43 reboots meiosis and rescues BTB function was also examined. In summary, overexpression of Cx43 in the testis with aspermatogenesis reboots meiosis and reseals toxicant-induced BTB disruption, even though it fails to

  18. Cyclin A2 is required for sister chromatid segregation, but not separase control, in mouse oocyte meiosis.

    PubMed

    Touati, Sandra A; Cladière, Damien; Lister, Lisa M; Leontiou, Ioanna; Chambon, Jean-Philippe; Rattani, Ahmed; Böttger, Franziska; Stemmann, Olaf; Nasmyth, Kim; Herbert, Mary; Wassmann, Katja

    2012-11-29

    In meiosis, two specialized cell divisions allow the separation of paired chromosomes first, then of sister chromatids. Separase removes the cohesin complex holding sister chromatids together in a stepwise manner from chromosome arms in meiosis I, then from the centromere region in meiosis II. Using mouse oocytes, our study reveals that cyclin A2 promotes entry into meiosis, as well as an additional unexpected role; namely, its requirement for separase-dependent sister chromatid separation in meiosis II. Untimely cyclin A2-associated kinase activity in meiosis I leads to precocious sister separation, whereas inhibition of cyclin A2 in meiosis II prevents it. Accordingly, endogenous cyclin A is localized to kinetochores throughout meiosis II, but not in anaphase I. Additionally, we found that cyclin B1, but not cyclin A2, inhibits separase in meiosis I. These findings indicate that separase-dependent cohesin removal is differentially regulated by cyclin B1 and A2 in mammalian meiosis.

  19. Ectopic Epithelial Deaminase in IBD

    DTIC Science & Technology

    2014-05-01

    transducers and activators of transcription 3 (STAT3). We initially hypothesized the deleterious role of AID in colitis , but our new data rather...disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) is a chronic intestinal disorder that is caused by dysregulated host/microbial...after exposure to dextran sulfate sodium (DSS) that induces acute colitis . During the first budget year, we have successfully collected DNA from

  20. Recurrent ectopic pregnancy after ipsilateral partial salpingectomy: a case report.

    PubMed

    Lee, D H

    2015-01-01

    Ectopic pregnancy is associated with maternal morbidity and mortality during early pregnancy. Ectopic pregnancy occurs in approximately 2% of all pregnancies, and the risk of ectopic pregnancy is increased by eight-fold in women with a history of eopic pregnancy. However, recurrent ectopic pregnancy after ipsilateral partial salpingectomy is quite rare. The authors experienced a case of recurrent ectopic pregnancy in the distal remnant after right partial salpingectomy. In this case report, they discuss this unusual case and provide a brief review of the literature.

  1. Ectopic Osteoid and Bone Formation by Three Calcium-Phosphate Ceramics in Rats, Rabbits and Dogs

    PubMed Central

    Wang, Liao; Zhang, Bi; Bao, Chongyun; Habibovic, Pamela; Hu, Jing; Zhang, Xingdong

    2014-01-01

    Calcium phosphate ceramics with specific physicochemical properties have been shown to induce de novo bone formation upon ectopic implantation in a number of animal models. In this study we explored the influence of physicochemical properties as well as the animal species on material-induced ectopic bone formation. Three bioceramics were used for the study: phase-pure hydroxyapatite (HA) sintered at 1200°C and two biphasic calcium phosphate (BCP) ceramics, consisting of 60 wt.% HA and 40 wt.% TCP (β-Tricalcium phosphate), sintered at either 1100°C or 1200°C. 108 samples of each ceramic were intramuscularly implanted in dogs, rabbits, and rats for 6, 12, and 24 weeks respectively. Histological and histomorphometrical analyses illustrated that ectopic bone and/or osteoid tissue formation was most pronounced in BCP sintered at 1100°C and most limited in HA, independent of the animal model. Concerning the effect of animal species, ectopic bone formation reproducibly occurred in dogs, while in rabbits and rats, new tissue formation was mainly limited to osteoid. The results of this study confirmed that the incidence and the extent of material-induced bone formation are related to both the physicochemical properties of calcium phosphate ceramics and the animal model. PMID:25229501

  2. Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

    PubMed Central

    Medhi, Darpan; Goldman, Alastair SH; Lichten, Michael

    2016-01-01

    The budding yeast genome contains regions where meiotic recombination initiates more frequently than in others. This pattern parallels enrichment for the meiotic chromosome axis proteins Hop1 and Red1. These proteins are important for Spo11-catalyzed double strand break formation; their contribution to crossover recombination remains undefined. Using the sequence-specific VMA1-derived endonuclease (VDE) to initiate recombination in meiosis, we show that chromosome structure influences the choice of proteins that resolve recombination intermediates to form crossovers. At a Hop1-enriched locus, most VDE-initiated crossovers, like most Spo11-initiated crossovers, required the meiosis-specific MutLγ resolvase. In contrast, at a locus with lower Hop1 occupancy, most VDE-initiated crossovers were MutLγ-independent. In pch2 mutants, the two loci displayed similar Hop1 occupancy levels, and VDE-induced crossovers were similarly MutLγ-dependent. We suggest that meiotic and mitotic recombination pathways coexist within meiotic cells, and that features of meiotic chromosome structure determine whether one or the other predominates in different regions. DOI: http://dx.doi.org/10.7554/eLife.19669.001 PMID:27855779

  3. The cohesion stabilizer sororin favors DNA repair and chromosome segregation during mouse oocyte meiosis.

    PubMed

    Huang, Chun-Jie; Yuan, Yi-Feng; Wu, Di; Khan, Faheem Ahmed; Jiao, Xiao-Fei; Huo, Li-Jun

    2017-03-01

    Maintenance and timely termination of cohesion on chromosomes ensures accurate chromosome segregation to guard against aneuploidy in mammalian oocytes and subsequent chromosomally abnormal pregnancies. Sororin, a cohesion stabilizer whose relevance in antagonizing the anti-cohesive property of Wings-apart like protein (Wapl), has been characterized in mitosis; however, the role of Sororin remains unclear during mammalian oocyte meiosis. Here, we show that Sororin is required for DNA damage repair and cohesion maintenance on chromosomes, and consequently, for mouse oocyte meiotic program. Sororin is constantly expressed throughout meiosis and accumulates on chromatins at germinal vesicle (GV) stage/G2 phase. It localizes onto centromeres from germinal vesicle breakdown (GVBD) to metaphase II stage. Inactivation of Sororin compromises the GVBD and first polar body extrusion (PBE). Furthermore, Sororin inactivation induces DNA damage indicated by positive γH2AX foci in GV oocytes and precocious chromatin segregation in MII oocytes. Finally, our data indicate that PlK1 and MPF dissociate Sororin from chromosome arms without affecting its centromeric localization. Our results define Sororin as a determinant during mouse oocyte meiotic maturation by favoring DNA damage repair and chromosome separation, and thereby, maintaining the genome stability and generating haploid gametes.

  4. Ipl1/Aurora B kinase coordinates synaptonemal complex disassembly with cell cycle progression and crossover formation in budding yeast meiosis

    PubMed Central

    Jordan, Philip; Copsey, Alice; Newnham, Louise; Kolar, Elizabeth; Lichten, Michael; Hoffmann, Eva

    2009-01-01

    Several protein kinases collaborate to orchestrate and integrate cellular and chromosomal events at the G2/M transition in both mitotic and meiotic cells. During the G2/M transition in meiosis, this includes the completion of crossover recombination, spindle formation, and synaptonemal complex (SC) breakdown. We identified Ipl1/Aurora B kinase as the main regulator of SC disassembly. Mutants lacking Ipl1 or its kinase activity assemble SCs with normal timing, but fail to dissociate the central element component Zip1, as well as its binding partner, Smt3/SUMO, from chromosomes in a timely fashion. Moreover, lack of Ipl1 activity causes delayed SC disassembly in a cdc5 as well as a CDC5-inducible ndt80 mutant. Crossover levels in the ipl1 mutant are similar to those observed in wild type, indicating that full SC disassembly is not a prerequisite for joint molecule resolution and subsequent crossover formation. Moreover, expression of meiosis I and meiosis II-specific B-type cyclins occur normally in ipl1 mutants, despite delayed formation of anaphase I spindles. These observations suggest that Ipl1 coordinates changes to meiotic chromosome structure with resolution of crossovers and cell cycle progression at the end of meiotic prophase. PMID:19759266

  5. Ndrg3 gene regulates DSB repair during meiosis through modulation the ERK signal pathway in the male germ cells.

    PubMed

    Pan, Hongjie; Zhang, Xuan; Jiang, Hanwei; Jiang, Xiaohua; Wang, Liu; Qi, Qi; Bi, Yuan; Wang, Jian; Shi, Qinghua; Li, Runsheng

    2017-03-14

    The N-myc downstream regulated gene (NDRG) family consists of 4 members, NDRG-1, -2, -3, -4. Physiologically, we found Ndrg3, a critical gene which led to homologous lethality in the early embryo development, regulated the male meiosis in mouse. The expression of Ndrg3 was enhanced specifically in germ cells, and reached its peak level in the pachytene stage spermatocyte. Haplo-insufficiency of Ndrg3 gene led to sub-infertility during the male early maturation. In the Ndrg3(+/-) germ cells, some meiosis events such as DSB repair and synaptonemal complex formation were impaired. Disturbances on meiotic prophase progression and spermatogenesis were observed. In mechanism, the attenuation of pERK1/2 signaling was detected in the heterozygous testis. With our primary spermatocyte culture system, we found that lactate promoted DSB repair via ERK1/2 signaling in the male mouse germ cells in vitro. Deficiency of Ndrg3 gene attenuated the activation of ERK which further led to the aberrancy of DSB repair in the male germ cells in mouse. Taken together, we reported that Ndrg3 gene modulated the lactate induced ERK pathway to facilitate DSB repair in male germ cells, which further regulated meiosis and subsequently fertility in male mouse.

  6. Ndrg3 gene regulates DSB repair during meiosis through modulation the ERK signal pathway in the male germ cells

    PubMed Central

    Pan, Hongjie; Zhang, Xuan; Jiang, Hanwei; Jiang, Xiaohua; Wang, Liu; Qi, Qi; Bi, Yuan; Wang, Jian; Shi, Qinghua; Li, Runsheng

    2017-01-01

    The N-myc downstream regulated gene (NDRG) family consists of 4 members, NDRG-1, -2, -3, -4. Physiologically, we found Ndrg3, a critical gene which led to homologous lethality in the early embryo development, regulated the male meiosis in mouse. The expression of Ndrg3 was enhanced specifically in germ cells, and reached its peak level in the pachytene stage spermatocyte. Haplo-insufficiency of Ndrg3 gene led to sub-infertility during the male early maturation. In the Ndrg3+/− germ cells, some meiosis events such as DSB repair and synaptonemal complex formation were impaired. Disturbances on meiotic prophase progression and spermatogenesis were observed. In mechanism, the attenuation of pERK1/2 signaling was detected in the heterozygous testis. With our primary spermatocyte culture system, we found that lactate promoted DSB repair via ERK1/2 signaling in the male mouse germ cells in vitro. Deficiency of Ndrg3 gene attenuated the activation of ERK which further led to the aberrancy of DSB repair in the male germ cells in mouse. Taken together, we reported that Ndrg3 gene modulated the lactate induced ERK pathway to facilitate DSB repair in male germ cells, which further regulated meiosis and subsequently fertility in male mouse. PMID:28290521

  7. Autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast.

    PubMed

    Matsuhara, Hirotada; Yamamoto, Ayumu

    2016-01-01

    Autophagy is a conserved intracellular degradation system, which contributes to development and differentiation of various organisms. Yeast cells undergo meiosis under nitrogen-starved conditions and require autophagy for meiosis initiation. However, the precise roles of autophagy in meiosis remain unclear. Here, we show that autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast. Autophagy-defective strains bearing a mutation in the autophagy core factor gene atg1, atg7, or atg14 exhibit deformed nuclear structures during meiosis. These mutant cells require an extracellular nitrogen supply for meiosis progression following their entry into meiosis and show delayed meiosis progression even with a nitrogen supply. In addition, they show frequent chromosome dissociation from the spindle together with spindle overextension, forming extra nuclei. Furthermore, Aurora kinase, which regulates chromosome segregation and spindle elongation, is significantly increased at the centromere and spindle in the mutant cells. Aurora kinase down-regulation eliminated delayed initiation of meiosis I and II, chromosome dissociation, and spindle overextension, indicating that increased Aurora kinase activity may cause these aberrances in the mutant cells. Our findings show a hitherto unrecognized relationship of autophagy with the nuclear structure, regulation of cell cycle progression, and chromosome segregation in meiosis.

  8. Ectopic Lymphoid Structures: Powerhouse of Autoimmunity

    PubMed Central

    Corsiero, Elisa; Nerviani, Alessandra; Bombardieri, Michele; Pitzalis, Costantino

    2016-01-01

    Ectopic lymphoid structures (ELS) often develop at sites of inflammation in target tissues of autoimmune diseases, such as rheumatoid arthritis, Sjögren’s syndrome, multiple sclerosis, myasthenia gravis, and systemic lupus erythematosus. ELS are characterized by the formation of organized T/B cells aggregates, which can acquire follicular dendritic cells network supporting an ectopic germinal center response. In this review, we shall summarize the mechanisms that regulate the formation of ELS in tertiary lymphoid organs, with particular emphasis on the role of lymphoid chemokines in both formation and maintenance of ELS, the role of emerging positive and negative regulators of ELS development and function, including T follicular helper cells and IL-27, respectively. Finally, we shall discuss the main functions of ELS in supporting the affinity maturation, clonal selection, and differentiation of autoreactive B cells contributing to the maintenance and perpetuation of humoral autoimmunity. PMID:27799933

  9. The paracrinology of tubal ectopic pregnancy.

    PubMed

    Shaw, Julie L V; Horne, Andrew W

    2012-07-25

    As part of successful human reproduction, the Fallopian tube must provide a suitable environment for pre-implantation development of the embryo and for efficient transport of the embryo to the uterus for implantation. These functions are coordinated by paracrine interactions between tubal epithelial, smooth muscle and immune cells and the cells of the developing embryo. Alterations in these signals can lead to a tubal microenvironment encouraging of embryo implantation and to dysregulated tubal motility, ultimately resulting in inappropriate and early implantation of the embryo in the Fallopian tube. Here, we highlight novel and emerging concepts in tubal physiology and pathobiology, such as the induction of a receptive phenotype within the Fallopian tube, leading to ectopic implantation. Chlamydia trachomatis infection is a risk factor for tubal ectopic pregnancy. Activation of toll-like receptor 2 (TLR-2) in the Fallopian tube epithelium, by C. trachomatis has recently been demonstrated, leading to the dysregulation of factors involved in implantation and smooth muscle contractility, such as prokineticins (PROK), activin A and interleukin 1 (IL-1). The Fallopian tube has also recently been shown to harbour a unique population of immune cells, compared to the endometrium. In addition, the complement of immune cells in the Fallopian tube has been reported to be altered in Fallopian tube from women with ectopic pregnancy. There are increasing data suggesting that vascularisation of the Fallopian tube, by the embryo during ectopic pregnancy, differs from that initiated in the uterus during normal pregnancy. This too, is likely the result of paracrine signals between the embryo and the tubal microenvironment.

  10. Perforation of jejunal diverticulum with ectopic pancreas.

    PubMed

    Shiratori, Hiroshi; Nishikawa, Takeshi; Shintani, Yukako; Murono, Koji; Sasaki, Kazuhito; Yasuda, Koji; Otani, Kensuke; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Nozawa, Hiroaki; Ishihara, Soichiro; Fukayama, Masashi; Watanabe, Toshiaki

    2017-04-01

    Perforation of jejunal diverticulum is a rare complication. Here, we report a case of jejunal diverticulum penetration with surrounding ectopic pancreas. An 83-year-old female patient was admitted to our department with acute onset of severe abdominal pain lasting for half a day. Abdominal computed tomography showed outpouching of the small intestine that contained air/fluid, with multiple surrounding air bubbles in the mesentery of the small intestine. She was diagnosed with penetration of the small intestine, and an emergency laparotomy was indicated. The penetrated jejunal diverticulum was identified ~20-cm distal to the ligament of Treitz. Partial resection of the jejunum was performed, and her postoperative course was uneventful. The pathological findings confirmed diverticulum penetration into the mesentery and severe inflammation at the site, with surrounding ectopic pancreas. Furthermore, the pancreatic ducts were opened through the penetrated diverticulum. This rare case shows that the ectopic pancreas might have caused penetration of jejunal diverticulum owing to the pancreatic duct opening through the diverticulum.

  11. Laparoscopic Treatment of Cesarean Scar Ectopic Pregnancy

    PubMed Central

    Felsingerová, Zuzana; Felsinger, Michal; Jandakova, Eva

    2014-01-01

    Abstract Background: An ectopic pregnancy within a Cesarean scar represents a rare type of extrauterine pregnancy in which the fertilized egg nidates in the myometrium of the uterine wall within a scar left from a previous Cesarean delivery. An unrecognized growing Cesarian scar pregnancy may result in uterine rupture, uncontrollable metrorrhagia, and bleeding into the abdominal cavity; therefore, early diagnosis and therapy are necessary to prevent the development of severe complications. Case: A 34-year-old woman after a previous Cesarean delivery presented with amenorrhoa of 7 weeks' duration. Transvaginal ultrasonography revealed an ectopic pregnancy in the Cesarean scar, and a laparoscopic removal of the gestational sac was performed with no complications. Results: Three months later, another laparoscopy with chromopertubation showed no signs of penetration in the suture, both the Fallopian tubes being bilaterally passable. The patient was advised that she could try to achieve pregnancy through spontaneous conception, after which monitoring of the gestational development and a careful assessment of the nidation site would be needed. Conclusions: Laparoscopic surgical management of a viable ectopic pregnancy is technically simple, and is followed by a good recovery. (J GYNECOL SURG 30:309) PMID:25336858

  12. Simulation of Ectopic Pacemakers in the Heart: Multiple Ectopic Beats Generated by Reentry inside Fibrotic Regions

    PubMed Central

    Gouvêa de Barros, Bruno; Weber dos Santos, Rodrigo; Lobosco, Marcelo; Alonso, Sergio

    2015-01-01

    The inclusion of nonconducting media, mimicking cardiac fibrosis, in two models of cardiac tissue produces the formation of ectopic beats. The fraction of nonconducting media in comparison with the fraction of healthy myocytes and the topological distribution of cells determines the probability of ectopic beat generation. First, a detailed subcellular microscopic model that accounts for the microstructure of the cardiac tissue is constructed and employed for the numerical simulation of action potential propagation. Next, an equivalent discrete model is implemented, which permits a faster integration of the equations. This discrete model is a simplified version of the microscopic model that maintains the distribution of connections between cells. Both models produce similar results when describing action potential propagation in homogeneous tissue; however, they slightly differ in the generation of ectopic beats in heterogeneous tissue. Nevertheless, both models present the generation of reentry inside fibrotic tissues. This kind of reentry restricted to microfibrosis regions can result in the formation of ectopic pacemakers, that is, regions that will generate a series of ectopic stimulus at a fast pacing rate. In turn, such activity has been related to trigger fibrillation in the atria and in the ventricles in clinical and animal studies. PMID:26583127

  13. Ectopic hippocampal neurogenesis in adolescent male rats following alcohol dependence.

    PubMed

    McClain, Justin A; Morris, Stephanie A; Marshall, S Alexander; Nixon, Kimberly

    2014-07-01

    The adolescent hippocampus is highly vulnerable to alcohol-induced damage, which could contribute to their increased susceptibility to alcohol use disorder. Altered adult hippocampal neurogenesis represents one potential mechanism by which alcohol (ethanol) affects hippocampal function. Based on the vulnerability of the adolescent hippocampus to alcohol-induced damage, and prior reports of long-term alcohol-induced effects on adult neurogenesis, we predicted adverse effects on adult neurogenesis in the adolescent brain following abstinence from alcohol dependence. Thus, we examined neurogenesis in adolescent male rats during abstinence following a 4-day binge model of alcohol dependence. Bromodeoxyuridine and Ki67 immunohistochemistry revealed a 2.2-fold increase in subgranular zone cell proliferation after 7 days of abstinence. Increased proliferation was followed by a 75% increase in doublecortin expression and a 56% increase in surviving bromodeoxyuridine-labeled cells 14 and 35 days post-ethanol exposure, respectively. The majority of newborn cells in ethanol and control groups co-localized with NeuN, indicating a neuronal phenotype and therefore a 1.6-fold increase in hippocampal neurogenesis during abstinence. Although these results mirror the magnitude of reactive neurogenesis described in adult rat studies, ectopic bromodeoxyuridine and doublecortin positive cells were detected in the molecular layer and hilus of adolescent rats displaying severe withdrawal symptoms, an effect that has not been described in adults. The presence of ectopic neuroblasts suggests that a potential defect exists in the functional incorporation of new neurons into the existing hippocampal circuitry for a subset of rats. Age-related differences in functional incorporation could contribute to the increased vulnerability of the adolescent hippocampus to ethanol.

  14. DNA Strand Exchange and RecA Homologs in Meiosis

    PubMed Central

    Brown, M. Scott; Bishop, Douglas K.

    2015-01-01

    Homology search and DNA strand–exchange reactions are central to homologous recombination in meiosis. During meiosis, these processes are regulated such that the probability of choosing a homolog chromatid as recombination partner is enhanced relative to that of choosing a sister chromatid. This regulatory process occurs as homologous chromosomes pair in preparation for assembly of the synaptonemal complex. Two strand–exchange proteins, Rad51 and Dmc1, cooperate in regulated homology search and strand exchange in most organisms. Here, we summarize studies on the properties of these two proteins and their accessory factors. In addition, we review current models for the assembly of meiotic strand–exchange complexes and the possible mechanisms through which the interhomolog bias of recombination partner choice is achieved. PMID:25475089

  15. Meiosis specific coiled-coil proteins in Shizosaccharomyces pombe.

    PubMed

    Ohtaka, Ayami; Saito, Takamune T; Okuzaki, Daisuke; Nojima, Hiroshi

    2007-05-18

    Many meiosis-specific proteins in Schizosaccharomyces pombe contain coiled-coil motifs which play essential roles for meiotic progression. For example, the coiled-coil motifs present in Meu13 and Mcp7 are required for their function as a putative recombinase cofactor complex during meiotic recombination. Mcp6/Hrs1 and Mcp5/Num1 control horsetail chromosome movement by astral microtubule organization and anchoring dynein respectively. Dhc1 and Ssm4 are also required for horsetail chromosome movement. It is clear from these examples that the coiled-coil motif in these proteins plays an important role during the progression of cells through meiosis. However, there are still many unanswered questions on how these proteins operate. In this paper, we briefly review recent studies on the meiotic coiled-coil proteins in Sz. pombe.

  16. Meiosis specific coiled-coil proteins in Shizosaccharomyces pombe

    PubMed Central

    Ohtaka, Ayami; Saito, Takamune T; Okuzaki, Daisuke; Nojima, Hiroshi

    2007-01-01

    Many meiosis-specific proteins in Schizosaccharomyces pombe contain coiled-coil motifs which play essential roles for meiotic progression. For example, the coiled-coil motifs present in Meu13 and Mcp7 are required for their function as a putative recombinase cofactor complex during meiotic recombination. Mcp6/Hrs1 and Mcp5/Num1 control horsetail chromosome movement by astral microtubule organization and anchoring dynein respectively. Dhc1 and Ssm4 are also required for horsetail chromosome movement. It is clear from these examples that the coiled-coil motif in these proteins plays an important role during the progression of cells through meiosis. However, there are still many unanswered questions on how these proteins operate. In this paper, we briefly review recent studies on the meiotic coiled-coil proteins in Sz. pombe. PMID:17509158

  17. Chromosome in situ suppression hybridisation in human male meiosis.

    PubMed Central

    Goldman, A S; Hultén, M A

    1992-01-01

    Chromosome in situ suppression hybridisation with biotinylated whole chromosome libraries permits the unequivocable identification of specific human somatic chromosomes in numerous situations. We have now used this so called 'chromosome painting' technique in meiotically dividing cells, isolated from human testicular biopsy. It is shown that the method allows identification of target homologues, bivalents, and sister chromatids throughout the relevant stages of meiosis. Thus, a more accurate study of meiosis per se is now available to increase our understanding of such processes as first meiotic synapsis of homologues and chiasma formation/meiotic crossing over, which are still outstanding biological enigmas. The new technology also makes it possible, for the first time, (1) to obtain direct numerical data in first meiotic non-disjunction for individual chromosomes, and (2) to quantify segregation in male carriers of structural rearrangements. We exemplify the use of the chromosome painting technique for a first meiotic segregation analysis of an insertional translocation carrier. Images PMID:1613773

  18. Recombination, Pairing, and Synapsis of Homologs during Meiosis.

    PubMed

    Zickler, Denise; Kleckner, Nancy

    2015-05-18

    Recombination is a prominent feature of meiosis in which it plays an important role in increasing genetic diversity during inheritance. Additionally, in most organisms, recombination also plays mechanical roles in chromosomal processes, most notably to mediate pairing of homologous chromosomes during prophase and, ultimately, to ensure regular segregation of homologous chromosomes when they separate at the first meiotic division. Recombinational interactions are also subject to important spatial patterning at both early and late stages. Recombination-mediated processes occur in physical and functional linkage with meiotic axial chromosome structure, with interplay in both directions, before, during, and after formation and dissolution of the synaptonemal complex (SC), a highly conserved meiosis-specific structure that links homolog axes along their lengths. These diverse processes also are integrated with recombination-independent interactions between homologous chromosomes, nonhomology-based chromosome couplings/clusterings, and diverse types of chromosome movement. This review provides an overview of these diverse processes and their interrelationships.

  19. DNA strand exchange and RecA homologs in meiosis.

    PubMed

    Brown, M Scott; Bishop, Douglas K

    2014-12-04

    Homology search and DNA strand-exchange reactions are central to homologous recombination in meiosis. During meiosis, these processes are regulated such that the probability of choosing a homolog chromatid as recombination partner is enhanced relative to that of choosing a sister chromatid. This regulatory process occurs as homologous chromosomes pair in preparation for assembly of the synaptonemal complex. Two strand-exchange proteins, Rad51 and Dmc1, cooperate in regulated homology search and strand exchange in most organisms. Here, we summarize studies on the properties of these two proteins and their accessory factors. In addition, we review current models for the assembly of meiotic strand-exchange complexes and the possible mechanisms through which the interhomolog bias of recombination partner choice is achieved.

  20. Functions of Aurora kinase C in meiosis and cancer.

    PubMed

    Quartuccio, Suzanne M; Schindler, Karen

    2015-01-01

    The mammalian genome encodes three Aurora kinase protein family members: A, B, and C. While Aurora kinase A (AURKA) and B (AURKB) are found in cells throughout the body, significant protein levels of Aurora kinase C (AURKC) are limited to cells that undergo meiosis (sperm and oocyte). Despite its discovery nearly 20 years ago, we know little about the function of AURKC compared to that of the other 2 Aurora kinases. This lack of understanding can be attributed to the high sequence homology between AURKB and AURKC preventing the use of standard approaches to understand non-overlapping and meiosis I (MI)-specific functions of the two kinases. Recent evidence has revealed distinct functions of AURKC in meiosis and may aid in our understanding of why chromosome segregation during MI often goes awry in oocytes. Many cancers aberrantly express AURKC, but because we do not fully understand AURKC function in its normal cellular context, it is difficult to predict the biological significance of this expression on the disease. Here, we consolidate and update what is known about AURKC signaling in meiotic cells to better understand why it has oncogenic potential.

  1. Meiosis and retrotransposon silencing during germ cell development in mice.

    PubMed

    Ollinger, Rupert; Reichmann, Judith; Adams, Ian R

    2010-03-01

    In mammals, germ cells derive from the pluripotent cells that are present early in embryogenesis, and then differentiate into male sperm or female eggs as development proceeds. Fusion between an egg and a sperm at fertilization allows genetic information from both parents to be transmitted to the next generation, and produces a pluripotent zygote to initiate the next round of embryogenesis. Meiosis is a central event in this self-perpetuating cycle that creates genetic diversity by generating new combinations of existing genetic alleles, and halves the number of chromosomes in the developing male and female germ cells to allow chromosome number to be maintained through successive generations. The developing germ cells also help to maintain genetic and chromosomal stability through the generations by protecting the genome from excessive de novo mutation. Several mouse mutants have recently been characterised whose germ cells exhibit defects in silencing the potentially mutagenic endogenous retroviruses and other retrotransposons that are prevalent in mammalian genomes, and these germ cells also exhibit defects in progression through meiosis. Here we review how mouse germ cells develop and proceed through meiosis, how mouse germ cells silence endogenous retroviruses and other retrotransposons, and discuss why silencing of endogenous retroviruses and other retrotransposons may be required for meiotic progression in mice.

  2. Homologous pairing and the role of pairing centers in meiosis.

    PubMed

    Tsai, Jui-He; McKee, Bruce D

    2011-06-15

    Homologous pairing establishes the foundation for accurate reductional segregation during meiosis I in sexual organisms. This Commentary summarizes recent progress in our understanding of homologous pairing in meiosis, and will focus on the characteristics and mechanisms of specialized chromosome sites, called pairing centers (PCs), in Caenorhabditis elegans and Drosophila melanogaster. In C. elegans, each chromosome contains a single PC that stabilizes chromosome pairing and initiates synapsis of homologous chromosomes. Specific zinc-finger proteins recruited to PCs link chromosomes to nuclear envelope proteins--and through them to the microtubule cytoskeleton--thereby stimulating chromosome movements in early prophase, which are thought to be important for homolog sorting. This mechanism appears to be a variant of the 'telomere bouquet' process, in which telomeres cluster on the nuclear envelope, connect chromosomes through nuclear envelope proteins to the cytoskeleton and lead chromosome movements that promote homologous synapsis. In Drosophila males, which undergo meiosis without recombination, pairing of the largely non-homologous X and Y chromosomes occurs at specific repetitive sequences in the ribosomal DNA. Although no other clear examples of PC-based pairing mechanisms have been described, there is evidence for special roles of telomeres and centromeres in aspects of chromosome pairing, synapsis and segregation; these roles are in some cases similar to those of PCs.

  3. The SMC-5/6 Complex and the HIM-6 (BLM) Helicase Synergistically Promote Meiotic Recombination Intermediate Processing and Chromosome Maturation during Caenorhabditis elegans Meiosis.

    PubMed

    Hong, Ye; Sonneville, Remi; Agostinho, Ana; Meier, Bettina; Wang, Bin; Blow, J Julian; Gartner, Anton

    2016-03-01

    Meiotic recombination is essential for the repair of programmed double strand breaks (DSBs) to generate crossovers (COs) during meiosis. The efficient processing of meiotic recombination intermediates not only needs various resolvases but also requires proper meiotic chromosome structure. The Smc5/6 complex belongs to the structural maintenance of chromosome (SMC) family and is closely related to cohesin and condensin. Although the Smc5/6 complex has been implicated in the processing of recombination intermediates during meiosis, it is not known how Smc5/6 controls meiotic DSB repair. Here, using Caenorhabditis elegans we show that the SMC-5/6 complex acts synergistically with HIM-6, an ortholog of the human Bloom syndrome helicase (BLM) during meiotic recombination. The concerted action of the SMC-5/6 complex and HIM-6 is important for processing recombination intermediates, CO regulation and bivalent maturation. Careful examination of meiotic chromosomal morphology reveals an accumulation of inter-chromosomal bridges in smc-5; him-6 double mutants, leading to compromised chromosome segregation during meiotic cell divisions. Interestingly, we found that the lethality of smc-5; him-6 can be rescued by loss of the conserved BRCA1 ortholog BRC-1. Furthermore, the combined deletion of smc-5 and him-6 leads to an irregular distribution of condensin and to chromosome decondensation defects reminiscent of condensin depletion. Lethality conferred by condensin depletion can also be rescued by BRC-1 depletion. Our results suggest that SMC-5/6 and HIM-6 can synergistically regulate recombination intermediate metabolism and suppress ectopic recombination by controlling chromosome architecture during meiosis.

  4. Roles of cohesin and condensin in chromosome dynamics during mammalian meiosis.

    PubMed

    Lee, Jibak

    2013-10-01

    Meiosis is a key step for sexual reproduction in which chromosome number is halved by two successive meiotic divisions after a single round of DNA replication. In the first meiotic division (meiosis I), homologous chromosomes pair, synapse, and recombine with their partners in prophase I. As a result, homologous chromosomes are physically connected until metaphase I and then segregated from each other at the onset of anaphase I. In the subsequent second meiotic division (meiosis II), sister chromatids are segregated. Chromosomal abnormality arising during meiosis is one of the major causes of birth defects and congenital disorders in mammals including human and domestic animals. Hence understanding of the mechanism underlying these unique chromosome behavior in meiosis is of great importance. This review focuses on the roles of cohesin and condensin, and their regulation in chromosome dynamics during mammalian meiosis.

  5. Distinct temporal requirements for autophagy and the proteasome in yeast meiosis.

    PubMed

    Wen, Fu-ping; Guo, Yue-shuai; Hu, Yang; Liu, Wei-xiao; Wang, Qian; Wang, Yuan-ting; Yu, Hai-Yan; Tang, Chao-ming; Yang, Jun; Zhou, Tao; Xie, Zhi-ping; Sha, Jia-hao; Guo, Xuejiang; Li, Wei

    2016-01-01

    Meiosis is a special type of cellular renovation that involves 2 successive cell divisions and a single round of DNA replication. Two major degradation systems, the autophagy-lysosome and the ubiquitin-proteasome, are involved in meiosis, but their roles have yet to be elucidated. Here we show that autophagy mainly affects the initiation of meiosis but not the nuclear division. Autophagy works not only by serving as a dynamic recycling system but also by eliminating some negative meiotic regulators such as Ego4 (Ynr034w-a). In a quantitative proteomics study, the proteasome was found to be significantly upregulated during meiotic divisions. We found that proteasomal activity is essential to the 2 successive meiotic nuclear divisions but not for the initiation of meiosis. Our study defines the roles of autophagy and the proteasome in meiosis: Autophagy mainly affects the initiation of meiosis, whereas the proteasome mainly affects the 2 successive meiotic divisions.

  6. From meiosis to postmeiotic events: uncovering the molecular roles of the meiosis-specific recombinase Dmc1.

    PubMed

    Kagawa, Wataru; Kurumizaka, Hitoshi

    2010-02-01

    In meiosis, the accurate segregation of maternal and paternal chromosomes is accomplished by homologous recombination. A central player in meiotic recombination is the Dmc1 recombinase, a member of the RecA/Rad51 recombinase superfamily, which is widely conserved from viruses to humans. Dmc1 is a meiosis-specific protein that functions with the ubiquitously expressed homolog, the Rad51 recombinase, which is essential for both mitotic and meiotic recombination. Since its discovery, it has been speculated that Dmc1 is important for unique aspects of meiotic recombination. Understanding the distinctive properties of Dmc1, namely, the features that distinguish it from Rad51, will further clarify the mechanisms of meiotic recombination. Recent structural, biochemical, and genetic findings are now revealing the molecular mechanisms of Dmc1-mediated homologous recombination and its regulation by various recombination mediators.

  7. Ectopic calcification in lambs from feeding the plant Cestrum diurnum.

    PubMed

    Simpson, C F; Bruss, M L

    1979-01-01

    Hypercalcemia and ectopic calcification were induced in 5 lambs by supplementing the diet with the dried leaves of the plant Cestrum diurnum, for 8 to 9 weeks. Lambs developed mineralization of blood vessels, heart, kidneys, and lungs. These tissues were examined by light and electron microscopy. In the vascular tissue there was calcification of elastic fibers in the hyperplastic intima and the media, along with mineralization of mitochondria of aortic smooth muscle cells. Myocardial cells and their mitochondria were mineralized. In the kidney, there was calcification of the epithelium of the distal convoluted tubules and collecting tubules, Bowman's capsule, and the mesangial cells of the glomeruli. In the lung, there was mineralization of the alveolar septal walls and the bronchi and bronchioles. Feeding of the calcinogenic plant to lambs caused extensive soft tissue calcification. Results of the study indicated that degeneration was the early soft tissue lesion in this plant toxicity.

  8. [Abdominal ectopic pregnancy. A case report and literature review].

    PubMed

    Puch-Ceballos, Eduardo Erik; Vázquez-Castro, Rosbel; Osorio-Pérez, Ana Isabel; Ramos-Ayala, Montserrat; Villarreal-Sosa, Conrado Otoniel; Ruvalcaba-Rivera, Everardo

    2015-07-01

    Abdominal ectopic pregnancy is an extremely rare entity, which represents 1% of all ectopic pregnancies and is associated with high maternal and fetal morbidity and mortality. The maternal mortality risk of an abdominal ectopic pregnancy is seven to eight times greater than the risk of a tubal ectopic pregnancy and is 90 times greater than the risk of intrauterine pregnancy. This is a disease of difficult diagnosis that often takes place late. We report the case of a patient with an abdominal ectopic pregnancy, which was diagnosed by abdominal ultrasound in the second trimester; the patient was suc- cessfully treated with exploratory laparotomy with complete removal of the fetus and placenta. We provide a review of the literature on the risk factors for abdominal ectopic pregnancy, diagnostic tests and therapeutic options.

  9. Distinct and Overlapping Requirements for Cyclins A, B, and B3 in Drosophila Female Meiosis

    PubMed Central

    Bourouh, Mohammed; Dhaliwal, Rajdeep; Rana, Ketki; Sinha, Sucheta; Guo, Zhihao; Swan, Andrew

    2016-01-01

    Meiosis, like mitosis, depends on the activity of the cyclin dependent kinase Cdk1 and its cyclin partners. Here, we examine the specific requirements for the three mitotic cyclins, A, B, and B3 in meiosis of Drosophila melanogaster. We find that all three cyclins contribute redundantly to nuclear envelope breakdown, though cyclin A appears to make the most important individual contribution. Cyclin A is also required for biorientation of homologs in meiosis I. Cyclin B3, as previously reported, is required for anaphase progression in meiosis I and in meiosis II. We find that it also plays a redundant role, with cyclin A, in preventing DNA replication during meiosis. Cyclin B is required for maintenance of the metaphase I arrest in mature oocytes, for spindle organization, and for timely progression through the second meiotic division. It is also essential for polar body formation at the completion of meiosis. With the exception of its redundant role in meiotic maturation, cyclin B appears to function independently of cyclins A and B3 through most of meiosis. We conclude that the three mitotic cyclin-Cdk complexes have distinct and overlapping functions in Drosophila female meiosis. PMID:27652889

  10. Role of animal pole protuberance and microtubules during meiosis in sea cucumber Apostichopus japonicus oocytes

    NASA Astrophysics Data System (ADS)

    Pang, Zhenguo; Chang, Yaqing; Sun, Huiling; Yu, Jiaping

    2010-05-01

    Fully grown oocytes of Apostichopus japonicus have a cytoplasmic protuberance where the oocyte attaches to the follicle. The protuberance and the oolamina located on the opposite side of the oocyte indicate the animal-vegetal axis. Two pre-meiotic centrosomes are anchored to the protuberance by microtubules between centrosomes and protuberance. After meiosis reinitiation induced by DTT solution, the germinal vesicle (GV) migrates towards the protuberance. The GV breaks down after it migrates to the oocyte membrane on the protuberance side. The protuberance then contracts back into the oocyte and the first polar body extrudes from the site of the former protuberance. The second polar body forms beneath the first. Thus the oocyte protuberance indicates the presumptive animal pole well before maturation of the oocyte.

  11. The Drosophila Fab-7 chromosomal element conveys epigenetic inheritance during mitosis and meiosis.

    PubMed

    Cavalli, G; Paro, R

    1998-05-15

    Polycomb group (PcG) and trithorax group (trxG) gene products are responsible for the maintenance of repressed and active expression patterns of many developmentally important regulatory genes including the homeotic genes. In Drosophila embryos, Polycomb protein and the trxG protein GAGA factor colocalize at the Fab-7 DNA element of the bithorax complex. In transgenic lines, the Fab-7 element induces extensive silencing on a flanking GAL4-driven lacZ reporter and mini-white genes. However, a short single pulse of GAL4 during embryogenesis is sufficient to release PcG-dependent silencing from the transgene. Such an activated state of Fab-7 is mitotically inheritable through development and can be transmitted in a GAL4-independent manner to the subsequent generations through female meiosis. Thus, Fab-7 is a switchable chromosomal element, which can convey memory of epigenetically determined active and repressed chromatin states.

  12. [Ectopic parathyroid glands. Imaging methods and surgical access].

    PubMed

    Fialová, M; Adámková, J; Adámek, S; Libánský, P; Kubinyi, J

    2014-08-01

    We discuss the benefits of imaging methods in localizing ectopic parathyroid glands in patients with primary hyperparathyroidism. The ectopic localizations are discussed within the context of the orthotopic norm. In the sample of 123 patients, a 23% rate of ectopic parathyroid glands was detected. Three selected case studies are presented, supporting the benefit of SPECT/CT imaging in terms of surgical access strategy selection.

  13. Molar tubal ectopic pregnancy: Report of two cases.

    PubMed

    Mbarki, Chaouki; Jerbi, Emna; Hsayaoui, Najeh; Zouari, Fatma; Ben Brahim, Ehsen; Oueslati, Hedhili

    2015-06-01

    Ectopic molar pregnancy is a rare occurrence and consequently not often considered as a diagnostic possibility. We report two cases of molar hydatidiform tubal pregnancy. Diagnosis of ectopic pregnancy was confirmed on clinical biological and sonographic investigations. Diagnosis of molar pregnancy was done on histopathology. The clinical course was favorable for both patients. Although rare, molar changes can occur at any site of an ectopic pregnancy. Clinical diagnosis of a molar pregnancy is difficult but histopathology is the gold standard for diagnosis.

  14. Recurrent Ectopic Pregnancy in the Tubal Remnant after Salpingectomy

    PubMed Central

    Samiei-Sarir, Bahareh; Diehm, Christopher

    2013-01-01

    We present two cases of ectopic pregnancy located within the remnant tube following ipsilateral salpingectomy. This particular pathology is rare and yet has significant consequences for the patient, with mortality rates 10–15 times higher than other ectopic pregnancies. It demonstrates that salpingectomy does not exclude ectopic pregnancy on the ipsilateral side. We suggest careful clinical consideration and bring attention to the current surgical technique. PMID:24151570

  15. Ectopic Expression of WRINKLED1 Affects Fatty Acid Homeostasis in Brachypodium distachyon Vegetative Tissues1[OPEN

    PubMed Central

    Yang, Yang; Munz, Jacob; Cass, Cynthia; Zienkiewicz, Agnieszka; Kong, Que; Ma, Wei; Sedbrook, John; Benning, Christoph

    2015-01-01

    Triacylglycerol (TAG) is a storage lipid used for food purposes and as a renewable feedstock for biodiesel production. WRINKLED1 (WRI1) is a transcription factor that governs fatty acid (FA) synthesis and, indirectly, TAG accumulation in oil-storing plant tissues, and its ectopic expression has led to TAG accumulation in vegetative tissues of different dicotyledonous plants. The ectopic expression of BdWRI1 in the grass Brachypodium distachyon induced the transcription of predicted genes involved in glycolysis and FA biosynthesis, and TAG content was increased up to 32.5-fold in 8-week-old leaf blades. However, the ectopic expression of BdWRI1 also caused cell death in leaves, which has not been observed previously in dicotyledonous plants such as Arabidopsis (Arabidopsis thaliana). Lipid analysis indicated that the free FA content was 2-fold elevated in BdWRI1-expressing leaf blades of B. distachyon. The transcription of predicted genes involved in β-oxidation was induced. In addition, linoleic FA treatment caused cell death in B. distachyon leaf blades, an effect that was reversed by the addition of the FA biosynthesis inhibitor cerulenin. Taken together, ectopic expression of BdWRI1 in B. distachyon enhances FA biosynthesis and TAG accumulation in leaves, as expected, but also leads to increased free FA content, which has cytotoxic effects leading to cell death. Thus, while WRI appears to ubiquitously affect FA biosynthesis and TAG accumulation in diverse plants, its ectopic expression can lead to undesired side effects depending on the context of the specific lipid metabolism of the respective plant species. PMID:26419778

  16. Ectopic Expression of WRINKLED1 Affects Fatty Acid Homeostasis in Brachypodium distachyon Vegetative Tissues.

    PubMed

    Yang, Yang; Munz, Jacob; Cass, Cynthia; Zienkiewicz, Agnieszka; Kong, Que; Ma, Wei; Sedbrook, John; Benning, Christoph

    2015-11-01

    Triacylglycerol (TAG) is a storage lipid used for food purposes and as a renewable feedstock for biodiesel production. WRINKLED1 (WRI1) is a transcription factor that governs fatty acid (FA) synthesis and, indirectly, TAG accumulation in oil-storing plant tissues, and its ectopic expression has led to TAG accumulation in vegetative tissues of different dicotyledonous plants. The ectopic expression of BdWRI1 in the grass Brachypodium distachyon induced the transcription of predicted genes involved in glycolysis and FA biosynthesis, and TAG content was increased up to 32.5-fold in 8-week-old leaf blades. However, the ectopic expression of BdWRI1 also caused cell death in leaves, which has not been observed previously in dicotyledonous plants such as Arabidopsis (Arabidopsis thaliana). Lipid analysis indicated that the free FA content was 2-fold elevated in BdWRI1-expressing leaf blades of B. distachyon. The transcription of predicted genes involved in β-oxidation was induced. In addition, linoleic FA treatment caused cell death in B. distachyon leaf blades, an effect that was reversed by the addition of the FA biosynthesis inhibitor cerulenin. Taken together, ectopic expression of BdWRI1 in B. distachyon enhances FA biosynthesis and TAG accumulation in leaves, as expected, but also leads to increased free FA content, which has cytotoxic effects leading to cell death. Thus, while WRI appears to ubiquitously affect FA biosynthesis and TAG accumulation in diverse plants, its ectopic expression can lead to undesired side effects depending on the context of the specific lipid metabolism of the respective plant species.

  17. Radiologic features of primary intracranial ectopic germinomas

    PubMed Central

    Wei, Xin-Hua; Shen, Hui-Cong; Tang, Shou-Xian; Gao, Cui-Hua; Ren, Ji-Liang; Ai, Lin; Dai, Jian-Ping

    2016-01-01

    Abstract Rationale: Germinomas are sensitive to radiation therapy and chemotherapy; therefore, correct imaging diagnosis is crucial for them. However, the imaging findings of germinomas originating from off-midline regions displayed different patterns from those originating from midline areas. Patient concerns: The objective of this study is to describe the radiologic features of primary ectopic germinoma. We reviewed the MR and CT findings of 12 patients with histologically proven off-midline ectopic germinomas with off-midline locations. Interventions: All of these patients underwent conventional MR images and 3 of them underwent diffusion images. Additional CT images were available in 3 patients. Analysis was focused on the shape and entity of tumors in images, signs of hemiatrophy, and the involvement of fibers in diffusion images. Outcomes: Well-defined (8/12) and ill-defined margin masses (4/12) were identified according to the shape of the mass. Multicystic masses were seen in 11 of the 12 patients. The solid component of the tumors had a high density (3/3) with calcifications (2/3) on CT images, iso- to hypointensity in T2WI (11/12) and restricted diffusion on apparent diffusion coefficient (ADC) maps (3/3). Hemiatrophy was observed in 5 cases and progressive hemiatrophy was observed in 1 case. Other signs included mild peritumoral edema (10/12), and hydrocephalus (7/12). Additionally, infiltration of the corticospinal tract (CST) was identified on diffusion tensor imaging (DTI) (2/2). Lessons: The results indicate that multicysitic entities and hypointensities in solid components on T2WI and hemiatrophy are the imaging features of ectopic germinomas. DTI has potential for assessing CST involvement. PMID:28033250

  18. Submandibular ectopic thyroid with normally located thyroid gland.

    PubMed

    Yılmaz, Mahmut Sinan; Aytürk, Semra; Güven, Mehmet; Dilek, Fatma Hüsniye

    2014-01-01

    Ectopic thyroid is a rare developmental anomaly of the thyroid gland which is defined as the presence of thyroid tissue at a site other than the pretracheal area. Nearly 1 to 3% of all ectopic thyroids are located in the lateral neck. Simultaneous submandibular ectopic thyroid tissue presenting with a functional orthotopic thyroid gland is extremely rare. In this article, we report a 37-year-old female case admitted to our clinic with a complaint of swollen neck in whom ultrasonography revealed submandibular ectopic thyroid tissue presenting with an orthotopic thyroid gland.

  19. Ruptured ectopic pregnancy with a negative urine pregnancy test.

    PubMed

    Hughes, Mallory; Lupo, Andrew; Browning, Adrianne

    2017-01-01

    Ectopic pregnancy is commonly seen as a differential diagnosis of first-trimester vaginal bleeding. Often the diagnosis is made based on a combination of exam findings, transvaginal ultrasound, and a positive pregnancy test. Our case describes a patient with a history of ectopic pregnancy treated with methotrexate and serial human chorionic gonadotropin measurements that were decreasing appropriately. At the time of evaluation, her urine pregnancy test was negative; however, she was confirmed to have a ruptured tubal ectopic pregnancy. This case highlights the variable presentation of ectopic pregnancies and the importance of combining exam findings with ultrasound and laboratory results.

  20. Ruptured ectopic pregnancy with a negative urine pregnancy test

    PubMed Central

    Hughes, Mallory; Lupo, Andrew

    2017-01-01

    Ectopic pregnancy is commonly seen as a differential diagnosis of first-trimester vaginal bleeding. Often the diagnosis is made based on a combination of exam findings, transvaginal ultrasound, and a positive pregnancy test. Our case describes a patient with a history of ectopic pregnancy treated with methotrexate and serial human chorionic gonadotropin measurements that were decreasing appropriately. At the time of evaluation, her urine pregnancy test was negative; however, she was confirmed to have a ruptured tubal ectopic pregnancy. This case highlights the variable presentation of ectopic pregnancies and the importance of combining exam findings with ultrasound and laboratory results. PMID:28127150

  1. Close, stable homolog juxtaposition during meiosis in budding yeast is dependent on meiotic recombination, occurs independently of synapsis, and is distinct from DSB-independent pairing contacts

    PubMed Central

    Peoples, Tamara L.; Dean, Eric; Gonzalez, Oscar; Lambourne, Lindsey; Burgess, Sean M.

    2002-01-01

    A site-specific recombination system that probes the relative probabilities that pairs of chromosomal loci collide with one another in living cells of budding yeast was used to explore the relative contributions of pairing, recombination, synaptonemal complex formation, and telomere clustering to the close juxtaposition of homologous chromosome pairs during meiosis. The level of Cre-mediated recombination between a pair of loxP sites located at an allelic position on homologous chromosomes was 13-fold greater than that between a pair of loxP sites located at ectopic positions on nonhomologous chromosomes. Mutations affecting meiotic recombination initiation and the processing of DNA double-strand breaks (DSBs) into single-end invasions (SEIs) reduced the levels of allelic Cre-mediated recombination levels by three- to sixfold. The severity of Cre/loxP phenotypes is presented in contrast to relatively weak DSB-independent pairing defects as assayed using fluorescence in situ hybridization for these mutants. Mutations affecting synaptonemal complex (SC) formation or crossover control gave wild-type levels of allelic Cre-mediated recombination. A delay in attaining maximum levels of allelic Cre-mediated recombination was observed for a mutant defective in telomere clustering. None of the mutants affected ectopic levels of recombination. These data suggest that stable, close homolog juxtaposition in yeast is distinct from pre-DSB pairing interactions, requires both DSB and SEI formation, but does not depend on crossovers or SC. PMID:12101126

  2. Characterization of the effects of metformin on porcine oocyte meiosis and on AMP-activated protein kinase activation in oocytes and cumulus cells.

    PubMed

    Bilodeau-Goeseels, Sylvie; Magyara, Nora; Collignon, Coralie

    2014-05-01

    The adenosine monophosphate-activated protein kinase (AMPK) activators 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR) and metformin (MET) inhibit resumption of meiosis in porcine cumulus-enclosed oocytes. The objective of this study was to characterize the inhibitory effect of MET on porcine oocyte meiosis by: (1) determining the effects of an AMPK inhibitor and of inhibitors of signalling pathways involved in MET-induced AMPK activation in other cell types on MET-mediated meiotic arrest in porcine cumulus-enclosed oocytes; (2) determining whether MET and AICAR treatments lead to increased activation of porcine oocyte and/or cumulus cell AMPK as measured by phosphorylation of its substrate acetyl-CoA carboxylase; and (3) determining the effects of inhibition of the AMPK kinase, Ca2+/calmodulin-dependent protein kinase kinase (CaMKK), and Ca2+ chelation on oocyte meiotic maturation and AMPK activation in porcine oocytes and cumulus cells. The AMPK inhibitor compound C (CC; 1 μM) did not reverse the inhibitory effect of AICAR (1 mM) and MET (2 mM) on porcine oocyte meiosis. Additionally, CC had a significant inhibitory effect on its own. eNOS, c-Src and PI-3 kinase pathway inhibitors did not reverse the effect of metformin on porcine oocyte meiosis. The level of acetyl-CoA carboxylase (ACC) phosphorylation in oocytes and cumulus cells did not change in response to culture in the presence of MET, AICAR, CC, the CaMKK inhibitor STO-609 or the Ca2+ chelator BAPTA-AM for 3 h, but STO-609 increased the percentage of porcine cumulus-enclosed oocytes (CEO) that remained at the germinal vesicle (GV) stage after 24 h of culture. These results indicate that the inhibitory effect of MET and AICAR on porcine oocyte meiosis was probably not mediated through activation of AMPK.

  3. Ectopic pregnancy treatment by combination therapy

    PubMed Central

    Chudecka-Głaz, Anita; Kuźniak, Sławomir; Menkiszak, Janusz

    2016-01-01

    Abstract Detectability of early stages of ectopic pregnancies has increased due to improvements in ultrasonographic and biochemical techniques. Since the patients’ future procreative plans must be taken into consideration when commencing treatment, the goal of this work was to compare the effects of treatment methods and their impact on fertility. The study included 91 patients treated surgically for ectopic pregnancy. The choice of treatment depended on patients’ general condition, ultrasonographic evaluation and serum level of beta-hCG. A combination of laparoscopic and conservative systemic treatment was applied in 70% of cases. More rapid beta-hCG reduction was noted when laparoscopy and intra-oviductal injection of hyperosmolar glucose or methotrexate (MTX) were combined with intramuscular administration of MTX at a dose of 50 mg/m2. Follow-up examination of 66 patients revealed that the greatest number of spontaneous pregnancies (48%) resulted after this combination therapy. We conclude that this combination treatment is safe and provides satisfactory results in terms of future fertility. PMID:28352846

  4. Laboratory models for studying ectopic pregnancy

    PubMed Central

    Brown, Jeremy K; Horne, Andrew W

    2011-01-01

    Purpose of Review Understanding of the aetiology of tubal ectopic pregnancy (tEP) remains incomplete. We aim to summarize the latest advances in laboratory models of tEP that we believe will, ultimately, contribute to improving the diagnosis and management of the condition. Recent Findings Progress in proteome pre-fractionation and multidimensional protein identification technology has proved particularly effective in identifying novel biomarkers of tEP. These, and related global proteomic and genomic approaches, have as yet to be fully exploited in this context but do have substantial potential to inform future hypothesis driven studies. The majority of data generated since 2009 to explain the aetiology of tEP continues to derive from descriptive human ex-vivo studies. In-vitro models of Fallopian tube ciliary and smooth muscle function have improved to a limited degree, on the back of continuing advances in imaging and data acquisition. We believe that the recent development of a primary human Fallopian tube epithelium culture system represents the most significant recent advance in laboratory models for studying ectopic pregnancy. There remain no good animal models of tEP. Summary The establishment of a viable animal model of tEP remains the key obstacle to a complete understanding the aetiology of the condition. PMID:21666470

  5. Functional specialization of chordate CDK1 paralogs during oogenic meiosis

    PubMed Central

    Øvrebø, Jan Inge; Campsteijn, Coen; Kourtesis, Ioannis; Hausen, Harald; Raasholm, Martina; Thompson, Eric M

    2015-01-01

    Cyclin-dependent kinases (CDKs) are central regulators of eukaryotic cell cycle progression. In contrast to interphase CDKs, the mitotic phase CDK1 is the only CDK capable of driving the entire cell cycle and it can do so from yeast to mammals. Interestingly, plants and the marine chordate, Oikopleura dioica, possess paralogs of the highly conserved CDK1 regulator. However, whereas in plants the 2 CDK1 paralogs replace interphase CDK functions, O. dioica has a full complement of interphase CDKs in addition to its 5 odCDK1 paralogs. Here we show specific sub-functionalization of odCDK1 paralogs during oogenesis. Differential spatiotemporal dynamics of the odCDK1a, d and e paralogs and the meiotic polo-like kinase 1 (Plk1) and aurora kinase determine the subset of meiotic nuclei in prophase I arrest that will seed growing oocytes and complete meiosis. Whereas we find odCDK1e to be non-essential, knockdown of the odCDK1a paralog resulted in the spawning of non-viable oocytes of reduced size. Knockdown of odCDK1d also resulted in the spawning of non-viable oocytes. In this case, the oocytes were of normal size, but were unable to extrude polar bodies upon exposure to sperm, because they were unable to resume meiosis from prophase I arrest, a classical function of the sole CDK1 during meiosis in other organisms. Thus, we reveal specific sub-functionalization of CDK1 paralogs, during the meiotic oogenic program. PMID:25714331

  6. Restarting life: fertilization and the transition from meiosis to mitosis.

    PubMed

    Clift, Dean; Schuh, Melina

    2013-09-01

    Fertilization triggers a complex cellular programme that transforms two highly specialized meiotic germ cells, the oocyte and the sperm, into a totipotent mitotic embryo. Linkages between sister chromatids are remodelled to support the switch from reductional meiotic to equational mitotic divisions; the centrosome, which is absent from the egg, is reintroduced; cell division shifts from being extremely asymmetric to symmetric; genomic imprinting is selectively erased and re-established; and protein expression shifts from translational control to transcriptional control. Recent work has started to reveal how this remarkable transition from meiosis to mitosis is achieved.

  7. Mammalian ovary differentiation - a focus on female meiosis.

    PubMed

    Baillet, Adrienne; Mandon-Pepin, Béatrice

    2012-06-05

    Over the past 50 years, the ovary development has been subject of fewer studies as compare to the male pathway. Nevertheless due to the advancement of genetics, mouse ES cells and the development of genetic models, studies of ovarian differentiation was boosted. This review emphasizes some of new progresses in the research field of the mammalian ovary differentiation that have occurred in recent years with focuses of the period around prophase I of meiosis and of recent roles of small non-RNAs in the ovarian gene expression.

  8. A non-sister act: recombination template choice during meiosis.

    PubMed

    Humphryes, Neil; Hochwagen, Andreas

    2014-11-15

    Meiotic recombination has two key functions: the faithful assortment of chromosomes into gametes and the creation of genetic diversity. Both processes require that meiotic recombination occurs between homologous chromosomes, rather than sister chromatids. Accordingly, a host of regulatory factors are activated during meiosis to distinguish sisters from homologs, suppress recombination between sister chromatids and promote the chromatids of the homologous chromosome as the preferred recombination partners. Here, we discuss the recent advances in our understanding of the mechanistic basis of meiotic recombination template choice, focusing primarily on developments in the budding yeast, Saccharomyces cerevisiae, where the regulation is currently best understood.

  9. Meiosis I chromosome segregation is established through regulation of microtubule-kinetochore interactions.

    PubMed

    Miller, Matthew P; Unal, Elçin; Brar, Gloria A; Amon, Angelika

    2012-12-18

    During meiosis, a single round of DNA replication is followed by two consecutive rounds of nuclear divisions called meiosis I and meiosis II. In meiosis I, homologous chromosomes segregate, while sister chromatids remain together. Determining how this unusual chromosome segregation behavior is established is central to understanding germ cell development. Here we show that preventing microtubule-kinetochore interactions during premeiotic S phase and prophase I is essential for establishing the meiosis I chromosome segregation pattern. Premature interactions of kinetochores with microtubules transform meiosis I into a mitosis-like division by disrupting two key meiosis I events: coorientation of sister kinetochores and protection of centromeric cohesin removal from chromosomes. Furthermore we find that restricting outer kinetochore assembly contributes to preventing premature engagement of microtubules with kinetochores. We propose that inhibition of microtubule-kinetochore interactions during premeiotic S phase and prophase I is central to establishing the unique meiosis I chromosome segregation pattern.DOI:http://dx.doi.org/10.7554/eLife.00117.001.

  10. An Interactive Modeling Lesson Increases Students' Understanding of Ploidy during Meiosis

    ERIC Educational Resources Information Center

    Wright, L. Kate; Newman, Dina L.

    2011-01-01

    Chromosome structure is confusing to students at all levels, and chromosome behavior during meiosis is a notoriously difficult topic. Undergraduate biology majors are exposed to the process of meiosis numerous times during their presecondary and postsecondary education, yet understanding of key concepts, such as the point at which haploidy is…

  11. First-Year Biology Students' Understandings of Meiosis: An Investigation Using a Structural Theoretical Framework

    ERIC Educational Resources Information Center

    Quinn, Frances; Pegg, John; Panizzon, Debra

    2009-01-01

    Meiosis is a biological concept that is both complex and important for students to learn. This study aims to explore first-year biology students' explanations of the process of meiosis, using an explicit theoretical framework provided by the Structure of the Observed Learning Outcome (SOLO) model. The research was based on responses of 334…

  12. Inferior ectopic pupil and typical ocular coloboma in RCS rats.

    PubMed

    Tsuji, Naho; Ozaki, Kiyokazu; Narama, Isao; Matsuura, Tetsuro

    2011-08-01

    Ocular coloboma is sometimes accompanied by corectopia in humans and therefore ectopic pupil may indicate ocular coloboma in experimental animals. The RCS strain of rats has a low incidence of microphthalmia. We found that inferior ectopic pupil is associated exclusively with small-sized eyes in this strain. The objective of the current study was to evaluate whether inferior ectopic pupil is associated with iridal coloboma and other types of ocular coloboma in RCS rats. Both eyes of RCS rats were examined clinically, and those with inferior ectopic pupils underwent morphologic and morphometric examinations. In a prenatal study, coronal serial sections of eyeballs from fetuses at gestational day 16.5 were examined by using light microscopy. Ectopic pupils in RCS rats were found exclusively in an inferior position, where the iris was shortened. Fundic examination revealed severe chorioretinal coloboma in all cases of inferior ectopic pupil. The morphologic characteristics closely resembled those of chorioretinal coloboma in humans. Histopathologic examination of primordia showed incomplete closure of the optic fissure in 4 eyeballs of RCS fetuses. Neither F(1) rats nor N(2) (progeny of RCS × BN matings) displayed any ocular anomalies, including ectopic pupils. The RCS strain is a suitable model for human ocular coloboma, and inferior ectopic pupil appears to be a strong indicator of ocular coloboma.

  13. [Ectopic pancreas mimicking advanced gastric malignancy--case report].

    PubMed

    Zawada, Iwona; Lewosiuk, Agnieszka; Hnatyszyn, Krzysztof; Patalan, Michał; Woyke, Stanisław; Kostyrka, Roman; Marlicz, Krzysztof; Starzyńska, Teresa

    2012-04-01

    Ectopic pancreas is the most common type of ectopic tissue in gastrointestinal tract. It is typically asymptomatic, presenting as a small submucosal lesion in prepyloric region of stomach. The diagnosis is usually incidental, during gastroscopy. The patient with symptomatic heterotropic pancreas, mimicking gastric malignancy was described.

  14. Assembly of RecA-like recombinases: Distinct roles for mediator proteins in mitosis and meiosis

    PubMed Central

    Gasior, Stephen L.; Olivares, Heidi; Ear, Uy; Hari, Danielle M.; Weichselbaum, Ralph; Bishop, Douglas K.

    2001-01-01

    Members of the RecA family of recombinases from bacteriophage T4, Escherichia coli, yeast, and higher eukaryotes function in recombination as higher-order oligomers assembled on tracts of single-strand DNA (ssDNA). Biochemical studies have shown that assembly of recombinase involves accessory factors. These studies have identified a class of proteins, called recombination mediator proteins, that act by promoting assembly of recombinase on ssDNA tracts that are bound by ssDNA-binding protein (ssb). In the absence of mediators, ssb inhibits recombination reactions by competing with recombinase for DNA-binding sites. Here we briefly review mediated recombinase assembly and present results of new in vivo experiments. Immuno-double-staining experiments in Saccharomyces cerevisiae suggest that Rad51, the eukaryotic recombinase, can assemble at or near sites containing ssb (replication protein A, RPA) during the response to DNA damage, consistent with a need for mediator activity. Correspondingly, mediator gene mutants display defects in Rad51 assembly after DNA damage and during meiosis, although the requirements for assembly are distinct in the two cases. In meiosis, both Rad52 and Rad55/57 are required, whereas either Rad52 or Rad55/57 is sufficient to promote assembly of Rad51 in irradiated mitotic cells. Rad52 promotes normal amounts of Rad51 assembly in the absence of Rad55 at 30°C but not 20°C, accounting for the cold sensitivity of rad55 null mutants. Finally, we show that assembly of Rad51 is induced by radiation during S phase but not during G1, consistent with the role of Rad51 in repairing the spontaneous damage that occurs during DNA replication. PMID:11459983

  15. Synchronized fission yeast meiosis using an ATP analog-sensitive Pat1 protein kinase

    PubMed Central

    Cipak, Lubos; Polakova, Silvia; Hyppa, Randy W.; Smith, Gerald R.; Gregan, Juraj

    2014-01-01

    Synchronous cultures are often indispensable for studying meiosis. Here, we present an optimized protocol for induction of synchronous meiosis in the fission yeast Schizosaccharomyces pombe. Chemical inactivation of an ATP analog-sensitive form of the Pat1 kinase (pat1-as2) by adding the ATP-analog 1-NM-PP1 in G1-arrested cells allows induction of synchronous meiosis at optimal temperature (25 °C). Importantly, this protocol eliminates detrimental effects of elevated temperature (34 °C) which is required to inactivate the commonly used temperature-sensitive Pat1 kinase mutant (pat1-114). Addition of the mat-Pc gene to a mat1-M strain further improves chromosome segregation and spore viability. Thus, our protocol offers highly synchronous meiosis at optimal temperature with most characteristics similar to those of wild-type meiosis. The synchronization protocol can be completed in 5 days. PMID:24385151

  16. Understanding a basic biological process: Expert and novice models of meiosis

    NASA Astrophysics Data System (ADS)

    Kindfield, Ann C. H.

    Central to secondary and college-level biology instruction is the development of student understanding of a number of subcellular processes. Yet some of the most crucial are consistently cited as the most difficult components of biology to learn. Among these is meiosis. In this article I report on the meiosis models utilized by five individuals at each of three levels of expertise in genetics as each reasoned about this process in an individual interview setting. Detailed characterization of individual meiosis models and comparison among models revealed a set of biologically correct features common to all individuals' models as well as a variety of model flaws (i.e., meiosis misunderstandings) which are categorized according to type and level of expertise. These results are suggestive of both sources of various misunderstandings and factors that might contribute to the construction of a sound understanding of meiosis. Each of these is addressed in relation to their respective implications for instruction.

  17. Commitment to meiosis: what determines the mode of division in budding yeast?

    PubMed

    Simchen, Giora

    2009-02-01

    In budding yeast, commitment to meiosis is attained when meiotic cells cannot return to the mitotic cell cycle even if the triggering cue (nutrients deprivation) is withdrawn. Commitment is arrived at gradually, and different aspects of meiosis may be committed at different times. Cells become fully committed to meiosis at the end of Prophase I, long after DNA replication and just before the first meiotic division (M(I)). Whole-genome gene expression analysis has shown that committed cells have a distinct and rapid response to nutrients, and are not simply insulated from environmental signals. Thus becoming committed to meiosis is an active process. The cellular event most likely to be associated with commitment to meiosis is the separation of the duplicated spindle-pole bodies (SPBs) and the formation of the spindle. Commitment to the mitotic cell cycle is also associated with the separation of SPBs, although it occurs in G1, before DNA replication.

  18. Ventricular ectopic activity and its relevance to aircrew licensing.

    PubMed

    Campbell, R W

    1984-03-01

    Ventricular ectopic complex ( VEC ) activity is seen frequently, both in patients with cardiovascular disease and in normal subjects. It has been claimed to be predictive of cardiovascular disease but in the asymptomatic individual it may be benign. Unifocal ventricular ectopic complexes with activity greater than 2 per 100 on the resting electrocardiogram of an applicant for a flying licence should be assessed. Further investigation including exercise electrocardiography and tape monitoring may be indicated. Even following investigation, empirically high counts may be acceptable only for multi-crew operation. Complex ventricular ectopic activity including multiformity, pairs, ventricular tachycardia, R-on-T ectopic beats, bigeminy and trigeminy, and parasystole, are incompatible with unrestricted certification and most are incompatible with any form of certification as individual risk-stratification is not yet possible. Of these, bigeminal arrhythmias are, however, likely to be the most benign, while R-on-T ectopic complexes and ventricular tachycardia are the most malignant.

  19. Medullary thyroid carcinoma with ectopic adrenocorticotropic hormone syndrome.

    PubMed

    Choi, Hong Seok; Kim, Min Joo; Moon, Chae Ho; Yoon, Jong Ho; Ku, Ha Ra; Kang, Geon Wook; Na, Im Il; Lee, Seung-Sook; Lee, Byung-Chul; Park, Young Joo; Kim, Hong Il; Ku, Yun Hyi

    2014-03-01

    Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.

  20. A pragmatic and evidence-based management of ectopic pregnancy.

    PubMed

    Oron, Galia; Tulandi, Togas

    2013-01-01

    The incidence of ectopic pregnancy is approximately 2% of all pregnancies, and it remains the leading cause of death in early pregnancy. Over 95% of ectopic pregnancies are tubal pregnancies, and the remainders are nontubal pregnancies. The highest risk factor for ectopic pregnancy is a previous tubal pregnancy followed by previous tubal surgery, tubal sterilization, tubal pathology, and current intrauterine device use. The apparent increase in the incidence of nontubal ectopic pregnancy including heterotopic pregnancy may be attributed to the increasing number of pregnancies because of in vitro fertilization treatment. In most cases, an ectopic pregnancy can be treated medically with a single dose of methotrexate. Surgical treatment is still needed in women who are hemodynamically unstable and in those who do not fulfill the criteria for methotrexate treatment. Usually surgical treatment can be performed by laparoscopy and in some cases by hysteroscopy. Laparotomy is rarely needed even in women with intraperitoneal bleeding.

  1. Laparoscope resection of ectopic corticosteroid-secreting adrenal adenoma.

    PubMed

    Wang, Xian-Ling; Dou, Jing-Tao; Gao, Jiang-Ping; Zhong, Wen-Wen; Jin, Du; Hui, Lüzhao; Lu, Ju-Ming; Mu, Yi-Ming

    2012-01-01

    Tumors originating from ectopic adrenal tissue are relatively rare. In this article, we describe a case with Cushing's syndrome caused by an ectopic adrenal adenoma. A 38 year-old male patient presenting with cushingoid appearance for 2 years was diagnosed to have ACTH-independent Cushing's syndrome based on endocrinological evaluation. Mutiple radiological examinations detected bilateral adrenal atrophy. When the images were investigated in a more expanded scope, a 3.0×3.5×5.3 cm mass was detected in the anterior of left renal hilum and left renal vein. The mass was successfully resected with intraoperative endoscopy and pathological evaluation revealed an ectopic adrenal tumor. It is suggested that when the endocrinlogically confirmed adrenal neoplasm could not be well and definitely localized, the possibility of ectopic adrenal should be presumed and further radiography examinations should extend to the field where ectopic adrenal usually presents.

  2. Dual Ectopic Thyroid with Normally Located Thyroid: A Case Report

    PubMed Central

    Kumar Choudhury, Bipul; Kaimal Saikia, Uma; Sarma, Dipti; Saikia, Mihir; Dutta Choudhury, Sarojini; Barua, Santanu; Dewri, Swapna

    2011-01-01

    Dual ectopic thyroid is a rare presentation of thyroid ectopia. Only a few cases have been reported in the world literature. Dual ectopic thyroid in the presence of a normally located thyroid is even rarer. We report a case of dual ectopic thyroid in the lingual and submandibular areas in a seventeen-year-old female with hypoplastic thyroid gland in its normal location. The patient presented with a midline swelling at the base of tongue with dysphagia. Thyroid function test revealed primary hypothyroidism. Ultrasonography of the neck showed hypoplastic thyroid in its normal location. A thyroid scan with Technetium-99 m pertechnate showed two intensely hyperfunctioning foci of ectopic thyroid tissue at a higher level in the midline consistent with dual ectopic thyroid, one at the base of tongue and the other in submental region. No uptake was seen in the normal bed. PMID:21765986

  3. Regulation of mitogen-activated protein kinase 3/1 activity during meiosis resumption in mammals.

    PubMed

    Prochazka, Radek; Blaha, Milan

    2015-01-01

    In vivo, resumption of oocyte meiosis occurs in large ovarian follicles after the preovulatory surge of luteinizing hormone (LH). The LH surge leads to the activation of a broad signaling network in mural granulosa cells equipped with LH receptors. The signals generated in the mural granulosa cells are further augmented by locally produced peptides or steroids and transferred to the cumulus cell compartment and the oocyte itself. Over the last decade, essential progress has been made in the identification of molecular events associated with the final maturation and ovulation of mammalian oocytes. All new evidence argues for a multiple roles of mitogen-activated protein kinase 3/1 (MAPK3/1) in the gonadotropin-induced ovulation processes. However, the knowledge of gonadotropin-induced signaling pathways leading to MAPK3/1 activation in follicular cells seems limited. To date, only the LH-induced transactivation of the epidermal growth factor receptor/MAPK3/1 pathway has been described in granulosa/cumulus cells even though other mechanisms of MAPK3/1 activation have been detected in other types of cells. In this review, we aimed to summarize recent advances in the elucidation of gonadotropin-induced mechanisms leading to the activation of MAPK3/1 in preovulatory follicles and cultured cumulus-oocyte complexes and to point out a specific role of this kinase in the processes accompanying final maturation of the mammalian oocyte.

  4. Virtual breakdown of the nuclear envelope in fission yeast meiosis.

    PubMed

    Asakawa, Haruhiko; Kojidani, Tomoko; Mori, Chie; Osakada, Hiroko; Sato, Mamiko; Ding, Da-Qiao; Hiraoka, Yasushi; Haraguchi, Tokuko

    2010-11-09

    Asymmetric localization of Ran regulators (RanGAP1 and RanGEF/RCC1) produces a gradient of RanGTP across the nuclear envelope. In higher eukaryotes, the nuclear envelope breaks down as the cell enters mitosis (designated "open" mitosis). This nuclear envelope breakdown (NEBD) leads to collapse of the RanGTP gradient and the diffusion of nuclear and cytoplasmic macromolecules in the cell, resulting in irreversible progression of the cell cycle. On the other hand, in many fungi, chromosome segregation takes place without NEBD (designated "closed" mitosis). Here we report that in the fission yeast Schizosaccharomyces pombe, despite the nuclear envelope and the nuclear pore complex remaining intact throughout both the meiotic and mitotic cell cycles, nuclear proteins diffuse into the cytoplasm transiently for a few minutes at the onset of anaphase of meiosis II. We also found that nuclear protein diffusion into the cytoplasm occurred coincidently with nuclear localization of Rna1, an S. pombe RanGAP1 homolog that is usually localized in the cytoplasm. These results suggest that nuclear localization of RanGAP1 and depression of RanGTP activity in the nucleus may be mechanistically tied to meiosis-specific diffusion of nuclear proteins into the cytoplasm. This nucleocytoplasmic shuffling of RanGAP1 and nuclear proteins represents virtual breakdown of the nuclear envelope.

  5. Centromere pairing--tethering partner chromosomes in meiosis I.

    PubMed

    Kurdzo, Emily L; Dawson, Dean S

    2015-07-01

    In meiosis, homologous chromosomes face the obstacle of finding, holding onto and segregating away from their partner chromosome. There is increasing evidence, in a diverse range of organisms, that centromere-centromere interactions that occur in late prophase are an important mechanism in ensuring segregation fidelity. Centromere pairing appears to initiate when homologous chromosomes synapse in meiotic prophase. Structural proteins of the synaptonemal complex have been shown to help mediate centromere pairing, but how the structure that maintains centromere pairing differs from the structure of the synaptonemal complex along the chromosomal arms remains unknown. When the synaptonemal complex proteins disassemble from the chromosome arms in late prophase, some of these synaptonemal complex components persist at the centromeres. In yeast and Drosophila these centromere-pairing behaviors promote the proper segregation of chromosome partners that have failed to become linked by chiasmata. Recent studies of mouse spermatocytes have described centromere pairing behaviors that are similar in several respects to what has been described in the fly and yeast systems. In humans, chromosomes that fail to experience crossovers in meiosis are error-prone and are a major source of aneuploidy. The finding that centromere pairing is a conserved phenomenon raises the possibility that it may play a role in promoting the segregation fidelity of non-exchange chromosome pairs in humans.

  6. Centromere pairing – tethering partner chromosomes in meiosis I

    PubMed Central

    Kurdzo, Emily L; Dawson, Dean S

    2015-01-01

    In meiosis, homologous chromosomes face the obstacle of finding, holding onto and segregating away from their partner chromosome. There is increasing evidence, in a diverse range of organisms, that centromere–centromere interactions that occur in late prophase are an important mechanism in ensuring segregation fidelity. Centromere pairing appears to initiate when homologous chromosomes synapse in meiotic prophase. Structural proteins of the synaptonemal complex have been shown to help mediate centromere pairing, but how the structure that maintains centromere pairing differs from the structure of the synaptonemal complex along the chromosomal arms remains unknown. When the synaptonemal complex proteins disassemble from the chromosome arms in late prophase, some of these synaptonemal complex components persist at the centromeres. In yeast and Drosophila these centromere-pairing behaviors promote the proper segregation of chromosome partners that have failed to become linked by chiasmata. Recent studies of mouse spermatocytes have described centromere pairing behaviors that are similar in several respects to what has been described in the fly and yeast systems. In humans, chromosomes that fail to experience crossovers in meiosis are error-prone and are a major source of aneuploidy. The finding that centromere pairing is a conserved phenomenon raises the possibility that it may play a role in promoting the segregation fidelity of non-exchange chromosome pairs in humans. PMID:25817724

  7. Differential Mitotic Stability of Yeast Disomes Derived from Triploid Meiosis

    PubMed Central

    Campbell, Douglas; Doctor, John S.; Feuersanger, Jeane H.; Doolittle, Mark M.

    1981-01-01

    The frequencies of recovered disomy among the meiotic segregants of yeast (Saccharomyces cerevisiae) triploids were assessed under conditions in which all 17 yeast chromosomes were monitored simultaneously. The studies employed inbred triploids, in which all homologous centromeres were identical by descent, and single haploid testers carrying genetic markers for all 17 linkage groups. The principal results include: (1) Ascospores from triploid meiosis germinate at frequencies comparable to those from normal diploids, but most fail to produce visible colonies due to the growth-retarding effects of high multiple disomy. (2) The probability of disome formation during triploid meiosis is the same for all chromosomes; disomy for any given chromosome does not exclude simultaneous disomy for any other chromosome. (3) The 17 yeast chromosomes fall into three frequency classes in terms of disome recovery. The results support the idea that multiply disomic meiotic segregants of the triploid experience repeated, nonrandom, post-germination mitotic chromosome losses (N+1→N) and that the observed variations in individual disome recovery are wholly attributable to inherent differences in disome mitotic stability. PMID:7035289

  8. The multiple ultrasound patterns of ectopic pregnancy.

    PubMed

    Hourani, Roula; Hachem, Kamal; Haddad-Zebouni, Soha; Mansour, Fersan; Elhage, Abdo; Checrallah, Antoine; Ghossain, Michel A

    2008-01-01

    Ectopic pregnancy (EP) has a variable and misleading clinical presentation contributing to the confusion with medical or other gynecological disorders. The rapid recourse to diagnostic methods, human chorionic gonadotropin (beta-hCG) titers and transvaginal ultrasonography, represents the best approach not only in the early diagnosis but also in the management and monitoring of patients with diagnosed EP. The purpose of this article is to provide a pictorial essay about EP and its multiple ultrasound (US) patterns. We present a large spectrum of EP aspects diagnosed on US and confirmed by pathology. We also review miscellaneous gynecologic diseases that may mimic EP on US. Although endovaginal US combined with quantitative (beta-hCG) analysis is an excellent tool for identifying EP, it may be normal sometimes in early pregnancies. Knowledge of all these patterns is helpful in establishing an early correct diagnosis, therefore leading to elective and conservative management in stable patients and preventing tubal rupture or substantial hemorrhage.

  9. Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy

    PubMed Central

    Christ, Emanuel R.; Egger, Andrea; Allemann, Sabin; Buehler, Tania; Kreis, Roland; Boesch, Chris

    2016-01-01

    Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50–60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn’t significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids. PMID:26792091

  10. Dma1-dependent degradation of SIN proteins during meiosis in Schizosaccharomyces pombe.

    PubMed

    Krapp, Andrea; Simanis, Viesturs

    2014-07-15

    The Schizosaccharomyces pombe septation initiation network (SIN) is required for cytokinesis during vegetative growth and for spore formation during meiosis. Regulation of the SIN during mitosis has been studied extensively, but less is known about its meiotic regulation. Here, we show that several aspects of SIN regulation differ between mitosis and meiosis. First, the presence of GTP-bound Spg1p is not the main determinant of the timing of Cdc7p and Sid1p association with the spindle pole body (SPB) during meiosis. Second, the localisation dependencies of SIN proteins differ from those in mitotic cells, suggesting a modified functional organisation of the SIN during meiosis. Third, there is stage-specific degradation of SIN components in meiosis; Byr4p is degraded after meiosis I, whereas the degradation of Cdc7p, Cdc11p and Sid4p occurs after the second meiotic division and depends upon the ubiquitin ligase Dma1p. Finally, Dma1p-dependent degradation is not restricted to the SIN, as we show that Dma1p is needed for the degradation of Mcp6p (also known as Hrs1p) during meiosis I. Taken together, these data suggest that stage-specific targeted proteolysis plays an important role in regulating meiotic progression.

  11. A nutrient dependant switch explains mutually exclusive existence of meiosis and mitosis initiation in budding yeast.

    PubMed

    Wannige, C T; Kulasiri, D; Samarasinghe, S

    2014-01-21

    Nutrients from living environment are vital for the survival and growth of any organism. Budding yeast diploid cells decide to grow by mitosis type cell division or decide to create unique, stress resistant spores by meiosis type cell division depending on the available nutrient conditions. To gain a molecular systems level understanding of the nutrient dependant switching between meiosis and mitosis initiation in diploid cells of budding yeast, we develop a theoretical model based on ordinary differential equations (ODEs) including the mitosis initiator and its relations to budding yeast meiosis initiation network. Our model accurately and qualitatively predicts the experimentally revealed temporal variations of related proteins under different nutrient conditions as well as the diverse mutant studies related to meiosis and mitosis initiation. Using this model, we show how the meiosis and mitosis initiators form an all-or-none type bistable switch in response to available nutrient level (mainly nitrogen). The transitions to and from meiosis or mitosis initiation states occur via saddle node bifurcation. This bidirectional switch helps the optimal usage of available nutrients and explains the mutually exclusive existence of meiosis and mitosis pathways.

  12. Exposure to Brefeldin A promotes initiation of meiosis in murine female germ cells.

    PubMed

    Zhang, Lian-Jun; Chen, Bo; Feng, Xin-Lei; Ma, Hua-Gang; Sun, Li-Lan; Feng, Yan-Min; Liang, Gui-Jin; Cheng, Shun-Feng; Li, Lan; Shen, Wei

    2015-01-01

    In mammals, ontogenesis starts from a fusion of spermatozoon and oocyte, which are produced by reductive nuclear division of a diploid germ cell in a specialised but complex biological process known as meiosis. However, little is known about the mechanism of meiotic initiation in germ cells, although many factors may be responsible for meiosis both in male and female gonads. In this study, 11.5 days post coitum (dpc) female fetal mouse genital ridges were cultured in vitro with exposure to Brefeldin A (BFA) for 6h, and the changes in meiosis were detected. Synaptonemal-complex analysis implied that BFA played a positive role in meiosis initiation and this hypothesis was confirmed by quantitative PCR of meiosis-specific genes: stimulated by retinoic acid gene 8 (Stra8) and deleted in a zoospermia-like (DAZL). At the same time, mRNA expression of retinoic acid synthetase (Raldh2) and retinoic acid (RA) receptors increased in female gonads with in vitro exposure to BFA. Transplanting genital ridges treated with BFA into the kidney capsule of immunodeficient mice demonstrated that the development capacity of female germ cells was normal, while formation of primordial follicles was seen to be a result of accelerated meiosis after exposure to BFA. In conclusion, the study indicated that BFA stimulated meiosis initiation partly by RA signalling and then promoted the development of follicles.

  13. Recent advances in understanding of meiosis initiation and the apomictic pathway in plants.

    PubMed

    Wang, Chung-Ju R; Tseng, Ching-Chih

    2014-01-01

    Meiosis, a specialized cell division to produce haploid cells, marks the transition from a sporophytic to a gametophytic generation in the life cycle of plants. In angiosperms, meiosis takes place in sporogenous cells that develop de novo from somatic cells in anthers or ovules. A successful transition from the mitotic cycle to the meiotic program in sporogenous cells is crucial for sexual reproduction. By contrast, when meiosis is bypassed or a mitosis-like division occurs to produce unreduced cells, followed by the development of an embryo sac, clonal seeds can be produced by apomixis, an asexual reproduction pathway found in 400 species of flowering plants. An understanding of the regulation of entry into meiosis and molecular mechanisms of apomictic pathway will provide vital insight into reproduction for plant breeding. Recent findings suggest that AM1/SWI1 may be the key gene for entry into meiosis, and increasing evidence has shown that the apomictic pathway is epigenetically controlled. However, the mechanism for the initiation of meiosis during sexual reproduction or for its omission in the apomictic pathway still remains largely unknown. Here we review the current understanding of meiosis initiation and the apomictic pathway and raised several questions that are awaiting further investigation.

  14. The Chromatin Protein DUET/MMD1 Controls Expression of the Meiotic Gene TDM1 during Male Meiosis in Arabidopsis.

    PubMed

    Andreuzza, Sébastien; Nishal, Bindu; Singh, Aparna; Siddiqi, Imran

    2015-09-01

    Meiosis produces haploid cells essential for sexual reproduction. In yeast, entry into meiosis activates transcription factors which trigger a transcriptional cascade that results in sequential co-expression of early, middle and late meiotic genes. However, these factors are not conserved, and the factors and regulatory mechanisms that ensure proper meiotic gene expression in multicellular eukaryotes are poorly understood. Here, we report that DUET/MMD1, a PHD finger protein essential for Arabidopsis male meiosis, functions as a transcriptional regulator in plant meiosis. We find that DUET-PHD binds H3K4me2 in vitro, and show that this interaction is critical for function during meiosis. We also show that DUET is required for proper microtubule organization during meiosis II, independently of its function in meiosis I. Remarkably, DUET protein shows stage-specific expression, confined to diplotene. We identify two genes TDM1 and JAS with critical functions in cell cycle transitions and spindle organization in male meiosis, as DUET targets, with TDM1 being a direct target. Thus, DUET is required to regulate microtubule organization and cell cycle transitions during male meiosis, and functions as a direct transcription activator of the meiotic gene TDM1. Expression profiling showed reduced expression of a subset comprising about 12% of a known set of meiosis preferred genes in the duet mutant. Our results reveal the action of DUET as a transcriptional regulator during male meiosis in plants, and suggest that transcription of meiotic genes is under stagewise control in plants as in yeast.

  15. Persistent trophoblastic tissue following salpingostomy for unruptured ectopic pregnancy

    SciTech Connect

    Rivlin, M.E.; Meeks, G.R.; Cowan, B.D.; Bates, G.W.

    1985-02-01

    Radioimmunoassay of beta-hCG was used to diagnose an ectopic pregnancy in a 30 year old patient and the site of pregnancy was determined by ultrasonography. A salpingostomy was performed; the ectopic pregnancy and the residual trophoblastic tissue were removed. Six weeks later a right salpingectomy was performed to remove persistent trophoblastic tissue. Histologic examination of the surgical specimen demonstrated viable chorionic villi. Serial measurements of beta-hCG are recommended following conservative surgery for ectopic gestation to assure the patient and the surgeon that the tube contains no residual products of conception.

  16. Ectopic presacral choroid plexus cyst in a neonate.

    PubMed

    Gross, Eitan; Koplewitz, Benjamin Z; Arbell, Dan; Fellig, Jakob; Udassin, Raphael

    2009-05-01

    An unusual case of a presacral ectopic choroid plexus cyst in a neonate is described. After birth, a soft lump was noticed at the left buttock. Imaging studies including sonography and magnetic resonance imaging demonstrated a presacral cystic lesion extending to the buttocks, composed of several septated cystic masses with no connection to the spinal canal or rectum. After total resection, the tumor was diagnosed as an ectopic choroid plexus cyst. To our knowledge, this is the first case report in the English literature of a presacral ectopic choroid plexus cyst.

  17. Management of Ectopically Erupting Maxillary Incisors: A Case Series

    PubMed Central

    Suresh, Kotumachagi Sangappa; Uma, HL; Nagarathna, J

    2015-01-01

    ABSTRACT Eruption disturbances related to the position include ectopic eruption and transpositions. The occurrence of ectopic eruption is most commonly associated with maxillary incisors. The normal eruption, position and morphology of these teeth are crucial to craniofacial development, facial esthetics as well as phonetics. It is essential that the clinicians have thorough knowledge of the eruption disturbances in order to make an appropriate, as well as timely intervention, as dictated by the complexity of the problem. How to cite this article: Suresh KS, Uma HL, Nagarathna J, Kumar P. Management of Ectopically Erupting Maxillary Incisors: A Case Series. Int J Clin Pediatr Dent 2015;8(3):227-233. PMID:26604543

  18. Management of Ectopically Erupting Maxillary Incisors: A Case Series.

    PubMed

    Suresh, Kotumachagi Sangappa; Uma, H L; Nagarathna, J; Kumar, Pravin

    2015-01-01

    Eruption disturbances related to the position include ectopic eruption and transpositions. The occurrence of ectopic eruption is most commonly associated with maxillary incisors. The normal eruption, position and morphology of these teeth are crucial to craniofacial development, facial esthetics as well as phonetics. It is essential that the clinicians have thorough knowledge of the eruption disturbances in order to make an appropriate, as well as timely intervention, as dictated by the complexity of the problem. How to cite this article: Suresh KS, Uma HL, Nagarathna J, Kumar P. Management of Ectopically Erupting Maxillary Incisors: A Case Series. Int J Clin Pediatr Dent 2015;8(3):227-233.

  19. Papillary Carcinoma in Median Aberrant Thyroid (Ectopic) - Case Report

    PubMed Central

    K, Shashidhar; Deshmane, Vijaya Laxmi; Kumar, Veerendra; Arjunan, Ravi

    2014-01-01

    Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed. PMID:25121039

  20. Bulk cytoplasmic actin and its functions in meiosis and mitosis.

    PubMed

    Field, Christine M; Lénárt, Péter

    2011-10-11

    Discussions of actin cell biology generally focus on the cortex, a thin, actin-rich layer of cytoplasm under the plasma membrane. Here we review the much less studied biology of actin filaments deeper in the cytoplasm and their recently revealed functions in mitosis and meiosis that are most prominent in large oocyte, egg and early embryo cells. The cellular functions of cytoplasmic actin range from the assembly and positioning of meiotic spindles to the prevention of cytoplasmic streaming. We discuss the possible use of evolutionarily conserved mechanisms to nucleate and organize actin filaments to achieve these diverse cellular functions, the cell-cycle regulation of these functions, and the many unanswered questions about this largely unexplored mechanism of cytoplasmic organization.

  1. The Chromosomal Courtship Dance-homolog pairing in early meiosis.

    PubMed

    Klutstein, Michael; Cooper, Julia Promisel

    2014-02-01

    The intermingling of genomes that characterizes sexual reproduction requires haploid gametes in which parental homologs have recombined. For this, homologs must pair during meiosis. In a crowded nucleus where sequence homology is obscured by the enormous scale and packaging of the genome, partner alignment is no small task. Here we review the early stages of this process. Chromosomes first establish an initial docking site, usually at telomeres or centromeres. The acquisition of chromosome-specific patterns of binding factors facilitates homolog recognition. Chromosomes are then tethered to the nuclear envelope (NE) and subjected to nuclear movements that 'shake off' inappropriate contacts while consolidating homolog associations. Thereafter, homolog connections are stabilized by building the synaptonemal complex or its equivalent and creating genetic crossovers. Recent perspectives on the roles of these stages will be discussed.

  2. Genetic regulation of meiosis in polyploid species: new insights into an old question.

    PubMed

    Cifuentes, Marta; Grandont, Laurie; Moore, Graham; Chèvre, Anne Marie; Jenczewski, Eric

    2010-04-01

    Precise chromosome segregation is vital for polyploid speciation. Here, we highlight recent findings that revitalize the old question of the genetic control of diploid-like meiosis behaviour in polyploid species. We first review new information on the genetic control of autopolyploid and allopolyploid cytological diploidization, notably in wheat and Brassica. These major advances provide new opportunities for speculating about the adaptation of meiosis during polyploid evolution. Some of these advances are discussed, and it is suggested that research on polyploidy and on meiosis should no longer be unlinked.

  3. [Meiosis passing age dependence in Solanum linnaeum L. x solanum incanum L. F1 interspecific hybrid].

    PubMed

    Montvid, P Iu

    2011-01-01

    Meiosis passing in the first- and second-year-plants of F1 interspecific hybrid Solanum linnaeum L. x Solanum incanum L. has been carried out. Fruit with seeds were formed during a second year of vegetation. The quantities of uni- and tetravalents and main disorders frequency lowered with plant age. Meiosis in parental forms was normal. The conclusion was drawn about F1 Solanum linnaeum L. x Solanum incanum L. meiosis regularity connection with heterozygous genotype, influence of environmental factors and plant age.

  4. Ectopic expression of PtaRHE1, encoding a poplar RING-H2 protein with E3 ligase activity, alters plant development and induces defence-related responses

    PubMed Central

    Mukoko Bopopi, Johnny; Vandeputte, Olivier M.; Himanen, Kristiina; Mol, Adeline; Vaessen, Quentin; El Jaziri, Mondher; Baucher, Marie

    2010-01-01

    RING (really interesting new gene)-H2 domain-containing proteins are widely represented in plants and play important roles in the regulation of many developmental processes as well as in plant–environment interactions. In the present report, experiments were performed to unravel the role of the poplar gene PtaRHE1, coding for a RING-H2 protein. In vitro ubiquitination assays indicate a functional E3 ligase activity for PtaRHE1 with the specific E2 ubiquitin-conjugating enzyme UbcH5a. The overexpression of PtaRHE1 in tobacco resulted in a pleiotropic phenotype characterized by a curling of the leaves, the formation of necrotic lesions on leaf blades, growth retardation, and a delay in floral transition. The plant gene expression response to PtaRHE1 overexpression provided evidence for the up-regulation of defence- and/or programmed cell death-related genes. Moreover, genes coding for WRKY transcription factors as well as for mitogen-activated protein kinases, such as wound-induced protein kinase (WIPK), were also found to be induced in the transgenic lines as compared with the wild type. In addition, histochemical β-glucuronidase staining showed that the PtaRHE1 promoter is induced by plant pathogens and by elicitors such as salicylic acid and cellulase. Taken together, these results suggest that the E3 ligase PtaRHE1 plays a role in the ubiquitination-mediated regulation of defence response, possibly by acting upstream of WIPK and/or in the activation of WRKY factors. PMID:19892745

  5. Spontaneous live unilateral twin ectopic pregnancy – A case presentation

    PubMed Central

    Mahsood, Shazia; Shelton, Hannah; Zaedi, Khaled; Economides, DL

    2014-01-01

    The incidence of ectopic pregnancy has increased in recent years and now is around one in 100 pregnancies. However, the incidence of live twin ectopic pregnancy in a spontaneous conception is still quite rare. A 34-year-old gravida 3, para 0 presented in the Early Pregnancy Unit with a positive pregnancy test, lower abdominal pain and vaginal spotting. Her quantitative serum Beta hCG was high, and the transvaginal scan revealed an empty uterine cavity with a twin ectopic pregnancy in the left adnexa with cardiac activity in both embryos. The patient was taken for laparoscopic surgery and a left ampullary twin pregnancy was confirmed. She underwent a left salpingectomy and is well on a one-year follow-up. This case report discusses the incidence, diagnoses and treatment of ectopic pregnancies in general. PMID:27433227

  6. Twin tubal pregnancy: A large unruptured ectopic pregnancy.

    PubMed

    Goswami, Deepti; Agrawal, Nidhi; Arora, Vrinda

    2015-11-01

    Twin ectopic pregnancy is a rare occurrence, with an estimated incidence of 1 in 20 000 spontaneous pregnancies. We describe a case of unilateral twin ectopic pregnancy in which the gravid fallopian tube showed no signs of tubal rupture despite marked tubal distension. A 25-year-old woman presented with clinical features suggestive of large right-sided tubal ectopic pregnancy. Serum β-human chorionic gonadotropin was 10 800 IU/mL. Laparotomy revealed markedly distended right fallopian tube. There was no hemoperitoneum. The tube contained twin gestational sacs. The crown-rump length of the embryos was 2 cm. The ectopic gestation was thus unique, in that despite marked tubal distension, the trophoblastic invasion was not significant to cause tubal rupture. There may be a role for medical management based on individual gestational sac size in selected cases of twin tubal pregnancy in which there is no evidence of hemoperitoneum.

  7. [Conservative therapy of ectopic pregnancy with methotrexate].

    PubMed

    Molina Sosa, A; Morales Garcia, V E

    1993-07-01

    Ectopic pregnancy (EP) treated by traditional methods, signifies an approximate lose of fertility capacity of the patient, of 50%. The early diagnosis allows conservative treatment with metotrexate (MTXE), with the objective of preserving the affected tube (salpynx) and its function. Early detection of EP, intact, was done, in 11 cases, with the following parameters: clinical picture, ultrasonography (Us) (empty uterus, adnexial mass and free fluid; adnexial ring or extrauterine embryo); quantitative determination of beta fraction of chorionic gonadotropin (CGH b) and laparoscopic observation, when the following characteristics were met: tubal pregnancy, no greater than 30 mm, intact tubarian serosa, lack of active bleeding and visualization of all pelvic cavity. MTXE 12.5 mg, intrasacularly via laparoscopy in eight patients, and three by laparotomy. The ulterior control of the procedure was: careful surveillance during eight days, Us daily and CGH b in two occasions; ten patients evolutionated satisfactorily, two of them required additional dosis of MTXE, parenterally, 0.5 mg/kg and citovorum factor, 0.1 mg/kg/4 days. The obtained conclusions are: 1. Conservative treatment with MTXE may be carried out provided the conditions established before, are met. 2. The patient's follow up must be precise and because of the high cost of the determination every third day of CGH b, Us may be used. Hysterosalpingography was done in five patients after six months of the procedure, and tubal permeability was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. A case of an ectopic prolactinoma.

    PubMed

    Simsir, Ilgin Yildirim; Kocabas, Gokcen Unal; Sahin, Serap Baydur; Erdogan, Mehmet; Cetinkalp, Sevki; Saygili, Fusun; Yilmaz, Candeger; Ozgen, Ahmet Gokhan

    2012-02-01

    A 34-year-old female presented to our clinic with a 1.5 year history of secondary amenorrhea and galactorrhea. Prolactin (PRL) level was found to be 151.89 ng/ml. Pituitary imaging was reported to be normal. An examination of the patient revealed that PRL level was still high so the dose of cabergoline was further increased and subsequently, bromocriptine was added to the treatment. There was no reduction in PRL levels in controls. A scanning was performed to look for an ectopic focus. Abdominal computerized tomography revealed a heterogenous mass lesion originating from the uterus. Octreotide scintigraphy was performed and we observed an involvement consistent with the mass in the uterus. The patient underwent abdominal total hysterectomy. PRL dropped to 0.4 ng/ml the next day after the operation. The pathology result was a low-grade malignant mesenchymal tumor. Prolactin was found to be immunohistochemically negative. However, galactorrhea disappeared postoperative and PRL levels are still low. Elevated levels of PRL, resistant to bromocriptine and cabergoline, rapidly returned to normal after hysterectomy, which obviously indicates that hyperprolactinemia was associated with the myoma of the uterus.

  9. Diagnosis and management of intramural ectopic pregnancy.

    PubMed

    Bannon, Kimberly; Fernandez, Carlos; Rojas, David; Levine, Elliot M; Locher, Stephen

    2013-01-01

    Intramural pregnancy, a gestation completely surrounded by the myometrium located within the uterine wall with separation from the uterine cavity, is an extremely unusual form of pregnancy. Complications resulting from intramural pregnancy include inevitable uterine rupture with resultant hemorrhage and possible hysterectomy if diagnosis is not made early and treatment is not initiated. An asymptomatic patient was initially diagnosed with a missed abortion at approximately 6 weeks of gestation after a routine ultrasound. Suction curettage was performed approximately 1 month after the initial diagnosis. The pathology specimen failed to reveal placental villi. Ultimately, the diagnosis of intramural pregnancy was made via ultrasound and a computed tomography scan. She was treated with a single dose of systemically administered methotrexate. Over a period of 4 months, β-human chorionic gonadotropin levels trended downward; however, the intramural pregnancy failed to resolve completely, and a persistent mass remained. The intramural pregnancy was removed using the da Vinci laparoscopic procedure (Intuitive Surgical, Sunnyvale, CA). If the diagnosis of intramural ectopic pregnancy is made sufficiently early, conservative measures can be taken, which can preserve a patient's future fertility.

  10. B cell repertoire expansion occurs in meningeal ectopic lymphoid tissue

    PubMed Central

    Lehmann-Horn, Klaus; Wang, Sheng-zhi; Sagan, Sharon A.; Zamvil, Scott S.

    2016-01-01

    Ectopic lymphoid tissues (ELT) can be found in multiple sclerosis (MS) and other organ-specific inflammatory conditions. Whether ELT in the meninges of central nervous system (CNS) autoimmune disease exhibit local germinal center (GC) activity remains unknown. In an experimental autoimmune encephalomyelitis model of CNS autoimmunity, we found activation-induced cytidine deaminase, a GC-defining enzyme, in meningeal ELT (mELT) densely populated by B and T cells. To determine GC activity in mELT, we excised meningeal lymphoid aggregates using laser capture microscopy and evaluated B cell repertoires in mELT and secondary lymphoid organs by next-generation immune repertoire sequencing. We found immunoglobulin heavy chain variable region sequences that were unique to mELT and had accumulated functionally relevant somatic mutations, together indicating localized antigen-driven affinity maturation. Our results suggest that B cells in mELT actively participate in CNS autoimmunity, which may be relevant to mELT in MS and ELT in other chronic inflammatory conditions. PMID:27942581

  11. Leptin responsiveness in mice that ectopically express agouti protein.

    PubMed

    Harris, Ruth B S; Mitchell, Tiffany D; Mynatt, Randall L

    Agouti protein is an endogenous antagonist of melanocortin receptors (MCR), including MCR3 and MCR4, which have been implicated as part of the hypothalamic mechanism that mediates leptin-induced hypophagia. In this experiment we examined the effects of peripheral and central leptin administration in male and female beta-actin promoter (BAPa) mice that express agouti protein ectopically and have a phenotype that includes obesity and diabetes which is exaggerated in males compared with females. Intraperitoneal infusion of 10 microg leptin/day for 13 days caused weight loss and a transient inhibition of food intake in wild-type mice, with a greater effect in males than females. Male BAPa mice were resistant to leptin infusion whereas female mice lost weight. All of the mice lost body weight following a single intracerebroventricular injection of leptin but the effect was greater in female BAPa mice than any other group. There also was a delayed suppression of food intake that was the same for wild-type and BAPa female mice, whereas food intake recovered faster in BAPa than wild-type males. The dissociation between food intake and body weight loss implies a significant effect of leptin on energy expenditure in BAPa mice. These results demonstrate that the effect of leptin on energy balance is not entirely dependent upon the melanocortin system.

  12. [Bilateral tubal ectopic pregnancy in a spontaneous cycle--a case report].

    PubMed

    Kubiaczyk, Filip; Suchocki, Sławomir; Puskarz, Roman; Zaborowski, Adam; Zaranek, Krzysztof

    2014-08-01

    Ectopic pregnancy occurs in 0.5-2% of all pregnancies. A double ectopic pregnancy is very rare and has the incidence of 1 in 725 ectopic pregnancies. We describe a case of a 30-year-old patient with double ectopic pregnancy located in tubas in spontaneous cycle--diagnosed and treated at the Gynecology and Obstetrics Hospital in Walbrzych. The patient had no risk factors for ectopic pregnancy. This case shows that even the diagnosis of an evident ectopic pregnancy cannot exclude the possibility of a double ectopic pregnancy.

  13. Intrinsic neurophysiological properties of hilar ectopic and normotopic dentate granule cells in human temporal lobe epilepsy and a rat model

    PubMed Central

    Althaus, A. L.; Sagher, O.; Parent, J. M.

    2014-01-01

    Hilar ectopic dentate granule cells (DGCs) are a salient feature of aberrant plasticity in human temporal lobe epilepsy (TLE) and most rodent models of the disease. Recent evidence from rodent TLE models suggests that hilar ectopic DGCs contribute to hyperexcitability within the epileptic hippocampal network. Here we investigate the intrinsic excitability of DGCs from humans with TLE and the rat pilocarpine TLE model with the objective of comparing the neurophysiology of hilar ectopic DGCs to their normotopic counterparts in the granule cell layer (GCL). We recorded from 36 GCL and 7 hilar DGCs from human TLE tissue. Compared with GCL DGCs, hilar DGCs in patient tissue exhibited lower action potential (AP) firing rates, more depolarized AP threshold, and differed in single AP waveform, consistent with an overall decrease in excitability. To evaluate the intrinsic neurophysiology of hilar ectopic DGCs, we made recordings from retrovirus-birthdated, adult-born DGCs 2–4 mo after pilocarpine-induced status epilepticus or sham treatment in rats. Hilar DGCs from epileptic rats exhibited higher AP firing rates than normotopic DGCs from epileptic or control animals. They also displayed more depolarized resting membrane potential and wider AP waveforms, indicating an overall increase in excitability. The contrasting findings between disease and disease model may reflect differences between the late-stage disease tissue available from human surgical specimens and the earlier disease stage examined in the rat TLE model. These data represent the first neurophysiological characterization of ectopic DGCs from human hippocampus and prospectively birthdated ectopic DGCs in a rodent TLE model. PMID:25429123

  14. A rare case of ectopic thoracic kidney and spleen.

    PubMed

    Krishnan, Babu; Lakshminarayanan, P; Sudhakar, M K; Vishwanathan, K N

    2011-07-01

    A 23-year-old male presented with fever of 5 days duration. His peripheral smear was positive for Plasmodium vivax. He was treated for malaria and responded. During investigation with USG it was found that he had absent left kidney. An abdominal contrast enhanced CT scan revealed ectopic kidney and spleen in the left hemithorax. This was a rare case of ectopic thoracic kidney and spleen.

  15. Site-specific DNA double-strand break generated by I-SceI endonuclease enhances ectopic homologous recombination in Pyricularia oryzae.

    PubMed

    Arazoe, Takayuki; Younomaru, Tetsuya; Ohsato, Shuichi; Kimura, Makoto; Arie, Tsutomu; Kuwata, Shigeru

    2014-03-01

    To evaluate the contribution of DNA double-strand breaks (DSBs) to somatic homologous recombination (HR) in Pyricularia oryzae, we established a novel detection/selection system of DSBs-mediated ectopic HR. This system consists of donor and recipient nonfunctional yellow fluorescent protein (YFP)/blasticidin S deaminase (BSD) fusion genes and the yeast endonuclease I-SceI gene as a recipient-specific DSB inducer. The system enables to detect and select ectopic HR events by the restoration of YFP fluorescence and blasticidin S resistance. The transformed lines with donor and recipient showed low frequencies of endogenous ectopic HR (> 2.1%). Compared with spontaneous HR, c. 20-fold increases in HR and absolute frequency of HR as high as 40% were obtained by integration of I-SceI gene, indicating that I-SceI-mediated DSB was efficiently repaired via ectopic HR. Furthermore, to validate the impact of DSB on targeted gene replacement (TGR), the transformed lines with a recipient gene were transfected with an exogenous donor plasmid in combination with the DSB inducer. TGR events were not observed without the DSB inducer, whereas hundreds of colonies resulting from TGR events were obtained with the DSB inducer. These results clearly demonstrated that the introduction of site-specific DSB promotes ectopic HR repair in P. oryzae.

  16. Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium.

    PubMed

    Castillo, David; Seidel, Kerstin; Salcedo, Ernesto; Ahn, Christina; de Sauvage, Frederic J; Klein, Ophir D; Barlow, Linda A

    2014-08-01

    Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation.

  17. Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium

    PubMed Central

    Castillo, David; Seidel, Kerstin; Salcedo, Ernesto; Ahn, Christina; de Sauvage, Frederic J.; Klein, Ophir D.; Barlow, Linda A.

    2014-01-01

    Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation. PMID:24993944

  18. Genetic conflicts: stronger centromeres win tug-of-war in female meiosis.

    PubMed

    Ross, Benjamin D; Malik, Harmit S

    2014-10-06

    Female meiosis presents unique opportunities for competition between chromosomes for evolutionary dominance. A new study reveals that centromere strength dictates meiotic success, driving karyotype evolution and reproductive isolation in mice.

  19. High glucose diets shorten lifespan of Caenorhabditis elegans via ectopic apoptosis induction.

    PubMed

    Choi, Shin Sik

    2011-06-01

    Diets based on carbohydrates increase rapidly the blood glucose level due to the fast conversion of carbohydrates to glucose. High glucose diets have been known to induce many lifestyle diseases. Here, we demonstrated that high glucose diet shortened the lifespan of Caenorhabditis elegans through apoptosis induction. Control adult groups without glucose diet lived for 30 days, whereas animals fed 10 mg/L of D-glucose lived only for 20 days. The reduction of lifespan by glucose diet showed a dose-dependent profile in the concentration range of glucose from 1 to 20 mg/L. Aging effect of high glucose diet was examined by measurement of response time for locomotion after stimulating movement of the animals by touching. Glucose diet decreased the locomotion capacity of the animals during mid-adulthood. High glucose diets also induced ectopic apoptosis in the body of C. elegans, which is a potent mechanism that can explain the shortened lifespan and aging. Apoptotic cell corpses stained with SYTO 12 were found in the worms fed 10 mg/L of glucose. Mutation of core apoptotic regulatory genes, CED-3 and CED-4, inhibited the reduction of viability induced by high glucose diet, which indicates that these regulators were required for glucose-induced apoptosis or lifespan shortening. Thus, we conclude that high glucose diets have potential for inducing ectopic apoptosis in the body, resulting in a shortened lifespan accompanied with loss of locomotion capacity.

  20. Inhibition of the Smc5/6 Complex during Meiosis Perturbs Joint Molecule Formation and Resolution without Significantly Changing Crossover or Non-crossover Levels

    PubMed Central

    Lilienthal, Ingrid; Kanno, Takaharu; Sjögren, Camilla

    2013-01-01

    Meiosis is a specialized cell division used by diploid organisms to form haploid gametes for sexual reproduction. Central to this reductive division is repair of endogenous DNA double-strand breaks (DSBs) induced by the meiosis-specific enzyme Spo11. These DSBs are repaired in a process called homologous recombination using the sister chromatid or the homologous chromosome as a repair template, with the homolog being the preferred substrate during meiosis. Specific products of inter-homolog recombination, called crossovers, are essential for proper homolog segregation at the first meiotic nuclear division in budding yeast and mice. This study identifies an essential role for the conserved Structural Maintenance of Chromosomes (SMC) 5/6 protein complex during meiotic recombination in budding yeast. Meiosis-specific smc5/6 mutants experience a block in DNA segregation without hindering meiotic progression. Establishment and removal of meiotic sister chromatid cohesin are independent of functional Smc6 protein. smc6 mutants also have normal levels of DSB formation and repair. Eliminating DSBs rescues the segregation block in smc5/6 mutants, suggesting that the complex has a function during meiotic recombination. Accordingly, smc6 mutants accumulate high levels of recombination intermediates in the form of joint molecules. Many of these joint molecules are formed between sister chromatids, which is not normally observed in wild-type cells. The normal formation of crossovers in smc6 mutants supports the notion that mainly inter-sister joint molecule resolution is impaired. In addition, return-to-function studies indicate that the Smc5/6 complex performs its most important functions during joint molecule resolution without influencing crossover formation. These results suggest that the Smc5/6 complex aids primarily in the resolution of joint molecules formed outside of canonical inter-homolog pathways. PMID:24244180

  1. The RNA-binding protein Spo5 promotes meiosis II by regulating cyclin Cdc13 in fission yeast.

    PubMed

    Arata, Mayumi; Sato, Masamitsu; Yamashita, Akira; Yamamoto, Masayuki

    2014-03-01

    Meiosis comprises two consecutive nuclear divisions, meiosis I and II. Despite this unique progression through the cell cycle, little is known about the mechanisms controlling the sequential divisions. In this study, we carried out a genetic screen to identify factors that regulate the initiation of meiosis II in the fission yeast Schizosaccharomyces pombe. We identified mutants deficient in meiosis II progression and repeatedly isolated mutants defective in spo5, which encodes an RNA-binding protein. Using fluorescence microscopy to visualize YFP-tagged protein, we found that spo5 mutant cells precociously lost Cdc13, the major B-type cyclin in fission yeast, before meiosis II. Importantly, the defect in meiosis II was rescued by increasing CDK activity. In wild-type cells, cdc13 transcripts increased during meiosis II, but this increase in cdc13 expression was weaker in spo5 mutants. Thus, Spo5 is a novel regulator of meiosis II that controls the level of cdc13 expression and promotes de novo synthesis of Cdc13. We previously reported that inhibition of Cdc13 degradation is necessary to initiate meiosis II; together with the previous information, the current findings indicate that the dual control of Cdc13 by de novo synthesis and suppression of proteolysis ensures the progression of meiosis II.

  2. Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis.

    PubMed

    Hua, Hui; Namdar, Mandana; Ganier, Olivier; Gregan, Juraj; Méchali, Marcel; Kearsey, Stephen E

    2013-03-01

    Meiosis involves two successive rounds of chromosome segregation without an intervening S phase. Exit from meiosis I is distinct from mitotic exit, in that replication origins are not licensed by Mcm2-7 chromatin binding, but spindle disassembly occurs during a transient interphase-like state before meiosis II. The absence of licensing is assumed to explain the block to DNA replication, but this has not been formally tested. Here we attempt to subvert this block by expressing the licensing control factors Cdc18 and Cdt1 during the interval between meiotic nuclear divisions. Surprisingly, this leads only to a partial round of DNA replication, even when these factors are overexpressed and effect clear Mcm2-7 chromatin binding. Combining Cdc18 and Cdt1 expression with modulation of cyclin-dependent kinase activity, activation of Dbf4-dependent kinase, or deletion of the Spd1 inhibitor of ribonucleotide reductase has little additional effect on the extent of DNA replication. Single-molecule analysis indicates this partial round of replication results from inefficient progression of replication forks, and thus both initiation and elongation replication steps may be inhibited in late meiosis. In addition, DNA replication or damage during the meiosis I-II interval fails to arrest meiotic progress, suggesting absence of checkpoint regulation of meiosis II entry.

  3. Dynamics of DNA replication during premeiosis and early meiosis in wheat.

    PubMed

    Rey, María-Dolores; Prieto, Pilar

    2014-01-01

    Meiosis is a specialised cell division that involves chromosome replication, two rounds of chromosome segregation and results in the formation of the gametes. Meiotic DNA replication generally precedes chromosome pairing, recombination and synapsis in sexually developing eukaryotes. In this work, replication has been studied during premeiosis and early meiosis in wheat using flow cytometry, which has allowed the quantification of the amount of DNA in wheat anther in each phase of the cell cycle during premeiosis and each stage of early meiosis. Flow cytometry has been revealed as a suitable and user-friendly tool to detect and quantify DNA replication during early meiosis in wheat. Chromosome replication was detected in wheat during premeiosis and early meiosis until the stage of pachytene, when chromosomes are associated in pairs to further recombine and correctly segregate in the gametes. In addition, the effect of the Ph1 locus, which controls chromosome pairing and affects replication in wheat, was also studied by flow cytometry. Here we showed that the Ph1 locus plays an important role on the length of meiotic DNA replication in wheat, particularly affecting the rate of replication during early meiosis in wheat.

  4. The molecular features of chromosome pairing at meiosis: the polyploid challenge using wheat as a reference.

    PubMed

    Yousafzai, Faridoon K; Al-Kaff, Nadia; Moore, Graham

    2010-05-01

    During meiosis, chromosome numbers are halved, leading to haploid gametes, a process that is crucial for the maintenance of a stable genome through successive generations. The process for the accurate segregation of the homologues starts in pre-meiosis as each homologue is replicated and the respective products are held together as two sister chromatids via specific cohesion proteins. At the start of meiosis, each chromosome must recognise its homologue from amongst all the chromosomes present in the nucleus and then associate or pair with that homologue. This process of homologue recognition in meiosis is more complicated in polyploids because of the greater number of related chromosomes. Despite the presence of these related chromosomes, for polyploids such as wheat to produce viable gametes, they must behave as diploids during meiosis with only true homologues pairing. In this review, the relationship between the Ph1 cyclin-dependent kinase (CDK)-like genes in wheat and the CDK2 genes in mammals and their involvement in controlling this process at meiosis is examined.

  5. Studies of meiosis disclose distinct roles of cohesion in the core centromere and pericentromeric regions.

    PubMed

    Sakuno, Takeshi; Watanabe, Yoshinori

    2009-01-01

    During meiosis, a single round of genome duplication is followed by two sequential rounds of chromosome segregation. Through this process, a diploid parent cell generates gametes with a haploid set of chromosomes. A characteristic of meiotic chromosome segregation is a stepwise loss of sister chromatid cohesion along chromosomal arms and at centromeres. Whereas arm cohesion plays an important role in ensuring homologue disjunction at meiosis I, persisting cohesion at pericentromeric regions throughout meiosis I is essential for the faithful equational segregation of sisters in the following meiosis II, similar to mitosis. A widely conserved pericentromeric protein called shugoshin, which associates with protein phosphatase 2A (PP2A), plays a critical role in this protection of cohesin. Another key aspect of meiosis I is the establishment of monopolar attachment of sister kinetochores to spindle microtubules. Cohesion or physical linkage at the core centromeres, where kinetochores assemble, may conjoin sister kinetochores, leading to monopolar attachment. A meiosis-specific kinetochore factor such as fission yeast Moa1 or budding yeast monopolin contributes to this regulation. We propose that cohesion at the core centromere and pericentromeric regions plays distinct roles, especially in defining the orientation of kinetochores.

  6. Proteomic analysis of male 4C germ cell proteins involved in mouse meiosis.

    PubMed

    Guo, Xuejiang; Zhang, Ping; Qi, Yujuan; Chen, Wen; Chen, Xiangxiang; Zhou, Zuomin; Sha, Jiahao

    2011-01-01

    Male meiosis is a specialized type of cell division that gives rise to sperm. Errors in this process can result in the generation of aneuploid gametes, which are associated with birth defects and infertility in humans. Until now, there has been a lack of a large-scale identification of proteins involved in male meiosis in mammals. In this study, we report the high-confidence identification of 3625 proteins in mouse male germ cells with 4C DNA content undergoing meiosis I. Of these, 397 were found to be testis specific. Bioinformatics analysis of the proteome led to the identification of 28 proteins known to be essential for male meiosis in mice. We also found 172 proteins that had yeast orthologs known to be essential for meiosis. Chromosome distribution analysis of the proteome showed underrepresentation of the identified proteins on the X chromosome, which may be due to meiotic sex chromosome inactivation. Characterization of the proteome of 4C germ cells from mouse testis provides an inventory of proteins, which is useful for understanding meiosis and the mechanisms of male infertility.

  7. Orai1 internalization and STIM1 clustering inhibition modulate SOCE inactivation during meiosis.

    PubMed

    Yu, Fang; Sun, Lu; Machaca, Khaled

    2009-10-13

    Store-operated Ca(2+) entry (SOCE) is a ubiquitous Ca(2+) influx pathway activated in response to depletion of intracellular Ca(2+) stores. SOCE is a primary modulator of intracellular Ca(2+) dynamics, which specify cellular responses. Interestingly, SOCE inactivates during M phase but the mechanisms involved remain unclear. SOCE is mediated by clustering of the ER Ca(2+) sensor STIM1 in response to Ca(2+) store depletion, leading to gating of the plasma membrane SOCE channel Orai1. Here we show that SOCE inactivation in meiosis is the result of internalization of Orai1 into an intracellular vesicular compartment and to the inability of STIM1 to cluster in response to store depletion. At rest, Orai1 continuously recycles between the cell membrane and an endosomal compartment. We further show that STIM1-STIM1 interactions are inhibited during meiosis, which appears to mediate the inability of STIM1 to form puncta following store depletion. In contrast, STIM1-Orai1 interactions remain functional during meiosis. Combined, the removal of Orai1 from the cell membrane and STIM1 clustering inhibition effectively uncouple store depletion from SOCE activation in meiosis. Although STIM1 is phosphorylated during meiosis, phosphomimetic and alanine substitution mutations do not modulate STIM1 clustering, arguing that phosphorylation does not mediate STIM1 clustering inhibition during meiosis.

  8. The Sum1/Ndt80 transcriptional switch and commitment to meiosis in Saccharomyces cerevisiae.

    PubMed

    Winter, Edward

    2012-03-01

    Cells encounter numerous signals during the development of an organism that induce division, differentiation, and apoptosis. These signals need to be present for defined intervals in order to induce stable changes in the cellular phenotype. The point after which an inducing signal is no longer needed for completion of a differentiation program can be termed the "commitment point." Meiotic development in the yeast Saccharomyces cerevisiae (sporulation) provides a model system to study commitment. Similar to differentiation programs in multicellular organisms, the sporulation program in yeast is regulated by a transcriptional cascade that produces early, middle, and late sets of sporulation-specific transcripts. Although critical meiosis-specific events occur as early genes are expressed, commitment does not take place until middle genes are induced. Middle promoters are activated by the Ndt80 transcription factor, which is produced and activated shortly before most middle genes are expressed. In this article, I discuss the connection between Ndt80 and meiotic commitment. A transcriptional regulatory pathway makes NDT80 transcription contingent on the prior expression of early genes. Once Ndt80 is produced, the recombination (pachytene) checkpoint prevents activation of the Ndt80 protein. Upon activation, Ndt80 triggers a positive autoregulatory loop that leads to the induction of genes that promote exit from prophase, the meiotic divisions, and spore formation. The pathway is controlled by multiple feed-forward loops that give switch-like properties to the commitment transition. The conservation of regulatory components of the meiotic commitment pathway and the recently reported ability of Ndt80 to increase replicative life span are discussed.

  9. Prophase I arrest and progression to metaphase I in mouse oocytes: comparison of resumption of meiosis and recovery from G2-arrest in somatic cells.

    PubMed

    Solc, Petr; Schultz, Richard M; Motlik, Jan

    2010-09-01

    Mammalian oocytes are arrested at prophase I until puberty when luteinizing hormone (LH) induces resumption of meiosis of follicle-enclosed oocytes. Resumption of meiosis is tightly coupled with regulating cyclin-dependent kinase 1 (CDK1) activity. Prophase I arrest depends on inhibitory phosphorylation of CDK1 and anaphase-promoting complex-(APC-CDH1)-mediated regulation of cyclin B levels. Prophase I arrest is maintained by endogenously produced cyclic adenosine monophosphate (cAMP), which activates protein kinase A (PKA) that in turn phosphorylates (and activates) the nuclear kinase WEE2. In addition, PKA-mediated phosphorylation of the phosphatase CDC25B results in its cytoplasmic retention. The combined effect maintains low levels of CDK1 activity that are not sufficient to initiate resumption of meiosis. LH triggers synthesis of epidermal growth factor-like factors in mural granulosa cells and leads to reduced cGMP transfer from cumulus cells to oocytes via gap junctions that couple the two cell types. cGMP inhibits oocyte phosphodiesterase 3A (PDE3A) and a decline in oocyte cGMP results in increased PDE3A activity. The ensuing decrease in oocyte cAMP triggers maturation by alleviating the aforementioned phosphorylations of WEE2 and CDC25B. As a direct consequence CDC25B translocates into the nucleus. The resulting activation of CDK1 also promotes extrusion of WEE2 from the nucleus thereby providing a positive amplification mechanism for CDK1 activation. Other kinases, e.g. protein kinase B, Aurora kinase A and polo-like kinase 1, also participate in resumption of meiosis. Mechanisms governing meiotic prophase I arrest and resumption of meiosis share common features with DNA damage-induced mitotic G2-checkpoint arrest and checkpoint recovery, respectively. These common features include CDC14B-dependent activation of APC-CDH1 in prophase I arrested oocytes or G2-arrested somatic cells, and CDC25B-dependent cell cycle resumption in both oocytes and somatic

  10. Connexin 43 contributes to ectopic orofacial pain following inferior alveolar nerve injury

    PubMed Central

    Shinoda, Masamichi; Honda, Kuniya; Unno, Syumpei; Shimizu, Noriyoshi; Iwata, Koichi

    2016-01-01

    Background Clinically, it is well known that injury of mandibular nerve fiber induces persistent ectopic pain which can spread to a wide area of the orofacial region innervated by the uninjured trigeminal nerve branches. However, the exact mechanism of such persistent ectopic orofacial pain is not still known. The present study was undertaken to determine the role of connexin 43 in the trigeminal ganglion on mechanical hypersensitivity in rat whisker pad skin induced by inferior alveolar nerve injury. Here, we examined changes in orofacial mechanical sensitivity following inferior alveolar nerve injury. Furthermore, changes in connexin 43 expression in the trigeminal ganglion and its localization in the trigeminal ganglion were also examined. In addition, we investigated the functional significance of connexin 43 in relation to mechanical allodynia by using a selective gap junction blocker (Gap27). Results Long-lasting mechanical allodynia in the whisker pad skin and the upper eyelid skin, and activation of satellite glial cells in the trigeminal ganglion, were induced after inferior alveolar nerve injury. Connexin 43 was expressed in the activated satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin, and the connexin 43 protein expression was significantly increased after inferior alveolar nerve injury. Administration of Gap27 in the trigeminal ganglion significantly reduced satellite glial cell activation and mechanical hypersensitivity in the whisker pad skin. Moreover, the marked activation of satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin following inferior alveolar nerve injury implies that the satellite glial cell activation exerts a major influence on the excitability of nociceptive trigeminal ganglion neurons. Conclusions These findings indicate that the propagation of satellite glial cell activation throughout the trigeminal ganglion via gap junctions, which are

  11. Distinct functions of S. pombe Rec12 (Spo11) protein and Rec12-dependent crossover recombination (chiasmata) in meiosis I; and a requirement for Rec12 in meiosis II.

    PubMed

    Sharif, Wallace D; Glick, Gloria G; Davidson, Mari K; Wahls, Wayne P

    2002-09-19

    BACKGROUND: In most organisms proper reductional chromosome segregation during meiosis I is strongly correlated with the presence of crossover recombination structures (chiasmata); recombination deficient mutants lack crossovers and suffer meiosis I nondisjunction. We report that these functions are separable in the fission yeast Schizosaccharomyces pombe. RESULTS: Intron mapping and expression studies confirmed that Rec12 is a member of the Spo11/Top6A topoisomerase family required for the formation of meiotic dsDNA breaks and recombination. rec12-117, rec12-D15 (null), and rec12-Y98F (active site) mutants lacked most crossover recombination and chromosomes segregated abnormally to generate aneuploid meiotic products. Since S. pombe contains only three chromosome pairs, many of those aneuploid products were viable. The types of aberrant chromosome segregation were inferred from the inheritance patterns of centromere linked markers in diploid meiotic products. The rec12-117 and rec12-D15 mutants manifest segregation errors during both meiosis I and meiosis II. Remarkably, the rec12-Y98F (active site) mutant exhibited essentially normal meiosis I segregation patterns, but still exhibited meiosis II segregation errors. CONCLUSIONS: Rec12 is a 345 amino acid protein required for most crossover recombination and for chiasmatic segregation of chromosomes during meiosis I. Rec12 also participates in a backup distributive (achiasmatic) system of chromosome segregation during meiosis I. In addition, catalytically-active Rec12 mediates some signal that is required for faithful equational segregation of chromosomes during meiosis II.

  12. Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice

    SciTech Connect

    Otsuru, Satoru; Tamai, Katsuto . E-mail: tamai@gts.med.osaka-u.ac.jp; Yamazaki, Takehiko; Yoshikawa, Hideki; Kaneda, Yasufumi

    2007-03-09

    Recent studies have suggested the existence of osteoblastic cells in the circulation, but the origin and role of these cells in vivo are not clear. Here, we examined how these cells contribute to osteogenesis in a bone morphogenetic protein (BMP)-induced model of ectopic bone formation. Following lethal dose-irradiation and subsequent green fluorescent protein-transgenic bone marrow cell-transplantation (GFP-BMT) in mice, a BMP-2-containing collagen pellet was implanted into muscle. Three weeks later, a significant number of GFP-positive osteoblastic cells were present in the newly generated ectopic bone. Moreover, peripheral blood mononuclear cells (PBMNCs) from the BMP-2-implanted mouse were then shown to include osteoblast progenitor cells (OPCs) in culture. Passive transfer of the PBMNCs isolated from the BMP-2-implanted GFP-mouse to the BMP-2-implanted nude mouse led to GFP-positive osteoblast accumulation in the ectopic bone. These data provide new insight into the mechanism of ectopic bone formation involving bone marrow-derived OPCs in circulating blood.

  13. Separase Is Required for Homolog and Sister Disjunction during Drosophila melanogaster Male Meiosis, but Not for Biorientation of Sister Centromeres.

    PubMed

    Blattner, Ariane C; Chaurasia, Soumya; McKee, Bruce D; Lehner, Christian F

    2016-04-01

    Spatially controlled release of sister chromatid cohesion during progression through the meiotic divisions is of paramount importance for error-free chromosome segregation during meiosis. Cohesion is mediated by the cohesin protein complex and cleavage of one of its subunits by the endoprotease separase removes cohesin first from chromosome arms during exit from meiosis I and later from the pericentromeric region during exit from meiosis II. At the onset of the meiotic divisions, cohesin has also been proposed to be present within the centromeric region for the unification of sister centromeres into a single functional entity, allowing bipolar orientation of paired homologs within the meiosis I spindle. Separase-mediated removal of centromeric cohesin during exit from meiosis I might explain sister centromere individualization which is essential for subsequent biorientation of sister centromeres during meiosis II. To characterize a potential involvement of separase in sister centromere individualization before meiosis II, we have studied meiosis in Drosophila melanogaster males where homologs are not paired in the canonical manner. Meiosis does not include meiotic recombination and synaptonemal complex formation in these males. Instead, an alternative homolog conjunction system keeps homologous chromosomes in pairs. Using independent strategies for spermatocyte-specific depletion of separase complex subunits in combination with time-lapse imaging, we demonstrate that separase is required for the inactivation of this alternative conjunction at anaphase I onset. Mutations that abolish alternative homolog conjunction therefore result in random segregation of univalents during meiosis I also after separase depletion. Interestingly, these univalents become bioriented during meiosis II, suggesting that sister centromere individualization before meiosis II does not require separase.

  14. The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis.

    PubMed

    Potapova, Tamara; Gorbsky, Gary J

    2017-02-08

    Mistakes during cell division frequently generate changes in chromosome content, producing aneuploid or polyploid progeny cells. Polyploid cells may then undergo abnormal division to generate aneuploid cells. Chromosome segregation errors may also involve fragments of whole chromosomes. A major consequence of segregation defects is change in the relative dosage of products from genes located on the missegregated chromosomes. Abnormal expression of transcriptional regulators can also impact genes on the properly segregated chromosomes. The consequences of these perturbations in gene expression depend on the specific chromosomes affected and on the interplay of the aneuploid phenotype with the environment. Most often, these novel chromosome distributions are detrimental to the health and survival of the organism. However, in a changed environment, alterations in gene copy number may generate a more highly adapted phenotype. Chromosome segregation errors also have important implications in human health. They may promote drug resistance in pathogenic microorganisms. In cancer cells, they are a source for genetic and phenotypic variability that may select for populations with increased malignance and resistance to therapy. Lastly, chromosome segregation errors during gamete formation in meiosis are a primary cause of human birth defects and infertility. This review describes the consequences of mitotic and meiotic errors focusing on novel concepts and human health.

  15. Are oocytes from the anestrous bitch competent for meiosis?

    PubMed

    Chastant-Maillard, S; Saint-Dizier, M; Grimard, B; Chebrout, M; Thoumire, S; Reynaud, K

    2012-12-01

    In the bitch, oocyte meiosis resumption takes place in the oviduct. Using oocytes from anestrous bitches, in vitro maturation (IVM) generally gives very poor results. To investigate the contribution of oocyte competence to the low IVM yield, we compared in vivo maturation in an optimal environment with conventional IVM. A total of 418 grade 1 cumulus-oocyte complexes (COCs) from 10 anestrous bitches were transferred into the oviducts of recipient bitches either on Day -1 (n = 3 recipients), Day 0 (n = 2) or on Day +1 (n = 2) relative to ovulation. For each donor bitch, 20 grade 1 COCs were also cultured in vitro. After 72 h of in vivo or IVM, the nuclear stage of oocytes was determined after DNA and tubulin staining. Of the 154 oocytes recovered and examined after intratubal transfer, only 2% reached the metaphase I or II stage and 38.3% were degenerated. Oocytes cultured in vitro displayed a higher metaphase rate (7.6%, n = 170) and lower degeneration rate (12.9%) compared with transferred oocytes (p < 0.001). These results clearly demonstrate that the oocyte competence is the major limiting factor of IVM efficiency in the dog. Mimicking the tubal environment may thus not be sufficient to increase IVM yield in this species.

  16. Nicotine alters bovine oocyte meiosis and affects subsequent embryonic development.

    PubMed

    Liu, Ying; Li, Guang-Peng; White, Kenneth L; Rickords, Lee F; Sessions, Benjamin R; Aston, Kenneth I; Bunch, Thomas D

    2007-11-01

    The effects of nicotine on nuclear maturation and meiotic spindle dynamics of bovine oocytes and subsequent embryonic development were investigated. Maturation rates (85%-94%) derived from nicotine treatments at 0.01 to 1.0 mM were similar to the control (86%), but significantly decreased at 2.0 to 6.0 mM. Haploid complements of metaphase II oocytes in 0.01 to 1.0 mM nicotine (approximately 90%) were similar to the control, while lower (ranged from 63% to 76%, P < 0.05 or P < 0.01) haploid oocytes were observed in the 2.0 to 6.0 mM nicotine groups. The majority of the PB1-free oocytes derived from 3.0 to 6.0 mM nicotine treatments were diploidy (2n = 60). Spindle microtubules changed from characteristically being asymmetrical in the controls to being equally distributed into two separate chromosome groups in the nicotine treatments. Nicotine disorganized the microfilament organization and inhibited the movement of anaphase or telophase chromosomes to the cortical area. The inhibited two chromosome groups became two spindles that either moved close in proximity or merged entirely together resulting in diploidy within the affected oocyte. Nicotine treatment significantly reduced the rate of cleavage and blastocyst development after parthenogenetic activation. Diploidy and cell number were drastically reduced in the resultant blastocysts. In conclusion, nicotine can alter the normal process of bovine oocyte meiosis and affects subsequent embryonic development.

  17. The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis

    PubMed Central

    Potapova, Tamara; Gorbsky, Gary J.

    2017-01-01

    Mistakes during cell division frequently generate changes in chromosome content, producing aneuploid or polyploid progeny cells. Polyploid cells may then undergo abnormal division to generate aneuploid cells. Chromosome segregation errors may also involve fragments of whole chromosomes. A major consequence of segregation defects is change in the relative dosage of products from genes located on the missegregated chromosomes. Abnormal expression of transcriptional regulators can also impact genes on the properly segregated chromosomes. The consequences of these perturbations in gene expression depend on the specific chromosomes affected and on the interplay of the aneuploid phenotype with the environment. Most often, these novel chromosome distributions are detrimental to the health and survival of the organism. However, in a changed environment, alterations in gene copy number may generate a more highly adapted phenotype. Chromosome segregation errors also have important implications in human health. They may promote drug resistance in pathogenic microorganisms. In cancer cells, they are a source for genetic and phenotypic variability that may select for populations with increased malignance and resistance to therapy. Lastly, chromosome segregation errors during gamete formation in meiosis are a primary cause of human birth defects and infertility. This review describes the consequences of mitotic and meiotic errors focusing on novel concepts and human health. PMID:28208750

  18. Inna Golubovskaya: the life of a geneticist studying meiosis.

    PubMed

    Cande, W Zacheus; Freeling, Michael

    2011-07-01

    Maize, with its excellent forward genetics and male sterility screens, was used to identify >50 meiotic mutants representing at least 35 genes that affect key prophase processes such as pairing, synapsis, and homologous recombination. Most of these mutants were found by Inna Golubovskaya during the course of her remarkable career as a cytogeneticist. In addition to undertaking general cytological surveys to classify mutant phenotypes, Golubovskaya focused her efforts on characterizing several key regulatory mutants: ameiotic1 (am1), required to establish the meiotic cell cycle in maize; absence of first division (afd1), required for proper prophase chromosome morphology and for meiotic sister-chromatid cohesion leading to a reductive chromosome segregation at the first meiotic division; and plural abnormalities of meiosis (pam1), required for the clustering of telomeres on the nuclear envelope needed for pairing and synapsis. Her dramatic childhood in Leningrad during its siege in World War II, her fortuitous education in genetics at Leningrad State University, her continued research at the forward-looking Institute of Cytology and Genetics of the USSR Academy of Science Siberian branch, her plight at the fall of the Soviet Union, and her work in America helped engender a unique and valuable plant geneticist. Inna Golubovskaya related this personal history to the authors in conversation.

  19. Inna Golubovskaya: The Life of a Geneticist Studying Meiosis

    PubMed Central

    Cande, W. Zacheus; Freeling, Michael

    2011-01-01

    Maize, with its excellent forward genetics and male sterility screens, was used to identify >50 meiotic mutants representing at least 35 genes that affect key prophase processes such as pairing, synapsis, and homologous recombination. Most of these mutants were found by Inna Golubovskaya during the course of her remarkable career as a cytogeneticist. In addition to undertaking general cytological surveys to classify mutant phenotypes, Golubovskaya focused her efforts on characterizing several key regulatory mutants: ameiotic1 (am1), required to establish the meiotic cell cycle in maize; absence of first division (afd1), required for proper prophase chromosome morphology and for meiotic sister-chromatid cohesion leading to a reductive chromosome segregation at the first meiotic division; and plural abnormalities of meiosis (pam1), required for the clustering of telomeres on the nuclear envelope needed for pairing and synapsis. Her dramatic childhood in Leningrad during its siege in World War II, her fortuitous education in genetics at Leningrad State University, her continued research at the forward-looking Institute of Cytology and Genetics of the USSR Academy of Science Siberian branch, her plight at the fall of the Soviet Union, and her work in America helped engender a unique and valuable plant geneticist. Inna Golubovskaya related this personal history to the authors in conversation. PMID:21742729

  20. Transvection effects involving DNA methylation during meiosis in the mouse

    PubMed Central

    Rassoulzadegan, Minoo; Magliano, Marc; Cuzin, François

    2002-01-01

    High efficiencies of recombination between LoxP elements were initially recorded when the Cre recombinase was expressed in meiotic spermatocytes. However, it was unexpectedly found that LoxP recombination fell to very low values at the second generation of mice expressing Cre during meiosis. The inability of the LoxP elements to serve as recombination substrates was correlated with cytosine methylation, initially in LoxP and transgene sequences, but later extending for distances of at least several kilobases into chromosomal sequences. It also affected the allelic locus, implying a transfer of structural information between alleles similar to the transvection phenomenon described in Drosophila. Once initiated following Cre–LoxP interaction, neither cis-extension nor transvection of the methylated state required the continuous expression of Cre, as they occurred both in germinal and somatic cells and in the fraction of the offspring that had not inherited the Sycp1-Cre transgene. Therefore, these processes depend on a physiological mechanism of establishment and extension of an epigenetic state, for which they provide an experimental model. PMID:11823436

  1. Ectopic parathyroid glands and their anatomical, clinical and surgical implications.

    PubMed

    Noussios, G; Anagnostis, P; Natsis, K

    2012-11-01

    Ectopic parathyroid glands result from aberrant migration during early stages of development and lack of successful identification may lead to lack of success in parathyroid surgery. They constitute a common etiology of persistent or recurrent hyperparathyroidism, when they are missed at initial diagnosis. Their prevalence is about 2-43% in anatomical series and up to 16% and 14% in patients with primary and secondary hyperparathyroidism, respectively. Ectopic inferior parathyroids are most frequently found in the anterior mediastinum, in association with the thymus or the thyroid gland, while the most common position for ectopic superior parathyroids is the tracheoesophageal groove and retroesophageal region. Neck ultrasound and 99mTc Sestamibi scan are first-line imaging modalities, although with low sensitivity and specificity. However, their combination with modern techniques, such as single photon emission computed tomography (SPECT) alone or in combination with CT (SPECT/CT) increases their diagnostic accuracy. Fine needle-aspiration cytology of a lesion suspicious for parathyroid tissue and measurement of parathyroid hormone (PTH) in the aspired material further assist to the successful preoperative localization of ectopic glands. Common sites for surgical investigation are the upper thyroid pole and the upper vascular thyroid stalk behind the hypopharynx and cervical esophagus for the superior parathyroids, and the carotid artery bifurcation and the thymic tongue, for the inferior parathyroids. Radioguided minimally invasive parathyroidectomy after successful localization, assisted by rapid PTH measurement postoperatively, significantly improves surgical outcomes in patients with ectopic parathyroid adenomas.

  2. Hydatidiform mole presentation as a tubal ectopic pregnancy.

    PubMed

    Nakeer, Tabassum; Shahid, Muhammad; Ansari, Muhammad Asad; Nakeer, Rooham

    2014-05-01

    Presentation of hydatidiform mole as tubal ectopic pregnancy is very rare. These patients usually present with ectopic pregnancy and are later diagnosed with hydatidiform mole on the basis of histological examination following surgery. We present the case of a 32-year-old female who presented with abdominal pain and vaginal bleed since 2 days of presentation. She was vitally stable. There was mild tenderness in hypogastrium and left iliac fossa. Pelvic examination showed mild bleeding per vaginum and fullness in both fornices. The patient was suspected of having an ectopic pregnancy. Ultrasonography of pelvis revealed fluid in cul-de-sac and a sac like mass of 1.8 cm attached to the left ovary. On laparotomy, there was a left sided tubal ectopic pregnancy and subsequently left salpingectomy was done. Histopathology of the tissue sample showed features of partial hydatidiform mole. Ectopic pregnancy can present as hydatidiform mole in rare cases for which histological examination of the tissue is required to establish the diagnosis.

  3. RALDH2, the enzyme for retinoic acid synthesis, mediates meiosis initiation in germ cells of the female embryonic chickens.

    PubMed

    Yu, Minli; Yu, Ping; Leghari, Imdad H; Ge, Chutian; Mi, Yuling; Zhang, Caiqiao

    2013-02-01

    Meiosis is a process unique to the differentiation of germ cells and exhibits sex-specific in timing. Previous studies showed that retinoic acid (RA) as the vitamin A metabolite is crucial for controlling Stra8 (Stimulated by retinoic acid gene 8) expression in the gonad and to initiate meiosis; however, the mechanism by which retinoid-signaling acts has remained unclear. In the present study, we investigated the role of the enzyme retinaldehyde dehydrogenase 2 (RALDH2) which catalyzes RA synthesizes by initiating meiosis in chicken ovarian germ cells. Meiotic germ cells were first detected at day 15.5 in chicken embryo ovary when the expression of synaptonemal complex protein 3 (Scp3) and disrupted meiotic cDNA 1 homologue (Dmc1) became elevated, while Stra8 expression was specifically up-regulated at day 12.5 before meiosis onset. It was observed from the increase in Raldh2 mRNA expression levels and decreases in Cyp26b1 (the enzyme for RA catabolism) expression levels during meiosis that requirement for RA accumulation is essential to sustain meiosis. This was also revealed by RA stimulation of the cultured ovaries with the initiation of meiosis response, and the knocking down of the Raldh2 expression during meiosis, leading to abolishment of RA-dependent action. Altogether, these studies indicate that RA synthesis by the enzyme RALDH2 and signaling through its receptor is crucial for meiosis initiation in chicken embryonic ovary.

  4. [Ectopic pregnancy: Its current interest in Primary Health Care].

    PubMed

    López-Luque, P R; Bergal-Mateo, G J; López-Olivares, M C

    2014-01-01

    An ectopic pregnancy is the implantation and development of the ovum fertilized outside the endometrial cavity. Its incidence has increased in the last 30 years, and although its morbimortality has decreased, it is still the first cause of mortality in the first trimester of the pregnancy. Early suspicion is important, particularly in women of fertile age and with risk factors indicative of an extrauterine gestation. The symptomatology is usually amenorrhea, abdominal pain, metrorrhagia, general pregnancy symptoms, and even syncope and shock. The diagnosis of ectopic pregnancy is based on the clinical information, analytical results on mother blood and urine, ultrasound examination, transvaginal culdocentesis, laparoscopic or laparotomic inspection, and a histological study. The treatment can be surgical (salpingostomy or salpingectomy), medical (methotrexate) or expectant, depending on the factors of the ectopic pregnancy: early diagnosis, presence of acute complications, clinical condition of the patient, etc.

  5. Pancreatic solitary fibrous tumor causing ectopic adrenocorticotropic hormone syndrome.

    PubMed

    Murakami, Keigo; Nakamura, Yasuhiro; Felizola, Saulo J A; Morimoto, Ryo; Satoh, Fumitoshi; Takanami, Kentaro; Katakami, Hideki; Hirota, Seiichi; Takeda, Yoshiyu; Meguro-Horike, Makiko; Horike, Shin-Ichi; Unno, Michiaki; Sasano, Hironobu

    2016-11-15

    Solitary fibrous tumors occasionally present with hypoglycemia because of the excessive release of insulin-like growth factor II. We report the first case of pancreatic solitary fibrous tumor causing ectopic adrenocorticotropic hormone syndrome. An 82-year-old Japanese man presented with lower limb edema, uncontrolled hypertension, hypokalemia, and baseline hypercortisolism. Distal pancreatectomy was performed after the clinical diagnosis of a neuroendocrine tumor with ectopic secretion of adrenocorticotropic hormone. On histological examination, the tumor showed spindle cells in a fascicular arrangement. The diagnosis of the solitary fibrous tumor was confirmed by the identification of the NAB2-STAT6 fusion gene and positive immuno-histochemical staining for STAT6 and CD34. Using quantitative real-time polymerase chain reaction, mRNA that encoded proopiomelanocortin, precursor of adrenocorticotropic hormone, was detected. Proopiomelanocortin production through the demethylation of the promoter region Domain IV was detected. Pancreatic solitary fibrous tumors represent a new cause of ectopic adrenocorticotropic hormone syndrome.

  6. Reduced recombination in maternal meiosis coupled with non-disjunction at meiosis II leading to recurrent 47,XXX.

    PubMed

    Reish, Orit; Berryman, Todd; Cunningham, Thomas R; Sher, Carron; Oetting, William S

    2004-01-01

    We determined the meiotic origin and the stage of non-disjunction of the extra X chromosomes in two sisters with 47,XXX chromosomal complements. Segregation of the X chromosomes in all family members was analyzed using X-linked short tandem repeat polymorphic (STRP) markers. Densitometric analysis of two STRP markers confirmed that both sisters had three copies of the X chromosome and the extra X chromosomes were maternally derived. Both sisters did not share the same maternal homologue suggesting that the recurrent trisomy is non-homologous X chromosome-specific. Haplotype analysis demonstrated a reduction to homozygosity for markers examined, covering most of the length of the X chromosomes in both sisters. These findings suggested that the extra X chromosomes have derived from meiotic II non-disjunction following a nullitransitional meiosis I (MI). A lack of recombination in the X chromosomes of both sisters suggests a possible maternal genetic defect leading to an erratic recombination at MI. This information may contribute to further understanding of mechanisms leading to X chromosome non-disjunction and may assist in counseling of families with this chromosomal rearrangement.

  7. Delayed puberty due to pituitary stalk dysgenesis and ectopic neurohypophysis.

    PubMed

    Yoo, Hye Jin; Choi, Kyung Mook; Ryu, Ohk Hyun; Suh, Sang Il; Kim, Nan Hee; Baik, Sei Hyun; Choi, Dong Seop

    2006-03-01

    Hypopituitarism is not a common cause of delayed puberty. A 22 year old man was referred to our clinic because of the absence of the development of secondary sexual characteristics. The patient had no complaints of physical discomfort. Random serum testosterone and luteinizing hormone level were obtained and found to be low. The combined pituitary function stimulation test revealed a partial hypopituitarism. A pituitary magnetic resonance imaging (MRI) was obtained and showed decreased pituitary stalk enhancement and ectopic neurohypophysis. Therefore, we conclude that the delayed puberty was a result of hypopituitarism due to pituitary stalk dysgenesis and ectopic neurohypophysis. The patient was started on hormone replacement therapy and gradually developed secondary sexual characteristics.

  8. Heterotopic pregnancy: discovery of ectopic pregnancy after elective abortion.

    PubMed

    DeFrancesch, F; DiLeo, L; Martinez, J

    1999-03-01

    We report a case of combined intrauterine and tubal pregnancy in a 23-year-old woman. The patient came to the emergency department complaining of lower abdominal pain after having had an elective abortion 2 weeks earlier. Her physician had done pelvic ultrasonography, noting an intrauterine pregnancy before the abortion. Our working diagnosis in the emergency department was retained products of conception versus postabortion endometritis. Pelvic ultrasonography in the emergency department revealed an ectopic pregnancy without evidence of retained products of conception, and the patient had a right salpingotomy with removal of the ectopic fetus without complications.

  9. Pulmonary agenesis associated with dextrocardia, sternal defects, and ectopic kidney.

    PubMed

    Eroglu, Atilla; Alper, Fatih; Turkyilmaz, Atila; Karaoglanoglu, Nurettin; Okur, Adnan

    2005-12-01

    Pulmonary agenesis is a rare embryological defect, usually unilateral, and is associated with skeletal, cardiovascular, and other anomalies. A 22-month-old girl was admitted to our clinic with recurrent pulmonary infections. A chest X-ray and multidetector computed tomography (MDCT) revealed pulmonary agenesis with dextrocardia, sternal defects, and a right pelvic ectopic kidney. We report on the first known case of right-sided pulmonary agenesis combined with isolated dextrocardia, sternal defects, and an ectopic kidney. The importance of MDCT for the diagnosis of pulmonary agenesis and associated other anomalies is demonstrated.

  10. DrRad51 is required for chiasmata formation in meiosis in planarian Dugesia ryukyuensis.

    PubMed

    Chinone, Ayako; Matsumoto, Midori

    2014-05-01

    Rad51, a conserved eukaryotic protein, mediates the homologous-recombination repair of DNA double-strand breaks that occur during both mitosis and meiosis. During prophase I of meiosis, homologous recombination enhances the linkage between homologous chromosomes to increase the accuracy of segregation at anaphase I. In polyploidy situations, however, difficulties with homologous chromosome segregation often disrupt meiosis. Yet, triploid individuals of the planarian Dugesia ryukyuensis are able to produce functional gametes through a specialized form of meiosis. To shed light on the molecular mechanisms that promote successful meiosis in triploid D. ryukyuensis, we investigated rad51 gene function. We isolated three genes of the Rad51 family, the Rad51 homolog Dr-rad51 and the Rad51 paralogs Dr-rad51B and Dr-rad51C. Dr-rad51 was expressed in germ-line and presumably in somatic stem cells, but was not necessary for the regeneration of somatic tissue. RNA-interference (RNAi) depletion of Dr-rad51 during sexualization did not affect chromosome behavior in zygotene oocytes, but did result in the loss of chiasmata at the diplotene stage. Thus, homologous recombination does not appear to be necessary for synapsis, but is needed for crossover and proper segregation in D. ryukyuensis.

  11. Role of Securin, Separase and Cohesins in female meiosis and polar body formation in Drosophila.

    PubMed

    Guo, Zhihao; Batiha, Osamah; Bourouh, Mohammed; Fifield, Eric; Swan, Andrew

    2016-02-01

    Chromosome segregation in meiosis is controlled by a conserved pathway that culminates in Separase-mediated cleavage of the α-kleisin Rec8, leading to dissolution of cohesin rings. Drosophila has no gene encoding Rec8, and the absence of a known Separase target raises the question of whether Separase and its regulator Securin (Pim in Drosophila) are important in Drosophila meiosis. Here, we investigate the role of Securin, Separase and the cohesin complex in female meiosis using fluorescence in situ hybridization against centromeric and arm-specific sequences to monitor cohesion. We show that Securin destruction and Separase activity are required for timely release of arm cohesion in anaphase I and centromere-proximal cohesion in anaphase II. They are also required for release of arm cohesion on polar body chromosomes. Cohesion on polar body chromosomes depends on the cohesin components SMC3 and the mitotic α-kleisin Rad21 (also called Vtd in Drosophila). We provide cytological evidence that SMC3 is required for arm cohesion in female meiosis, whereas Rad21, in agreement with recent findings, is not. We conclude that in Drosophila meiosis, cohesion is regulated by a conserved Securin-Separase pathway that targets a diverged Separase target, possibly within the cohesin complex.

  12. Meikin is a conserved regulator of meiosis-I-specific kinetochore function.

    PubMed

    Kim, Jihye; Ishiguro, Kei-ichiro; Nambu, Aya; Akiyoshi, Bungo; Yokobayashi, Shihori; Kagami, Ayano; Ishiguro, Tadashi; Pendas, Alberto M; Takeda, Naoki; Sakakibara, Yogo; Kitajima, Tomoya S; Tanno, Yuji; Sakuno, Takeshi; Watanabe, Yoshinori

    2015-01-22

    The kinetochore is the crucial apparatus regulating chromosome segregation in mitosis and meiosis. Particularly in meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase. Although meiotic kinetochore factors have been identified only in budding and fission yeasts, these molecules and their functions are thought to have diverged earlier. Therefore, a conserved mechanism for meiotic kinetochore regulation remains elusive. Here we have identified in mouse a meiosis-specific kinetochore factor that we termed MEIKIN, which functions in meiosis I but not in meiosis II or mitosis. MEIKIN plays a crucial role in both mono-orientation and centromeric cohesion protection, partly by stabilizing the localization of the cohesin protector shugoshin. These functions are mediated mainly by the activity of Polo-like kinase PLK1, which is enriched to kinetochores in a MEIKIN-dependent manner. Our integrative analysis indicates that the long-awaited key regulator of meiotic kinetochore function is Meikin, which is conserved from yeasts to humans.

  13. Synchronized fission yeast meiosis using an ATP analog-sensitive Pat1 protein kinase.

    PubMed

    Cipak, Lubos; Polakova, Silvia; Hyppa, Randy W; Smith, Gerald R; Gregan, Juraj

    2014-01-01

    Synchronous cultures are often indispensable for studying meiosis. Here we present an optimized protocol for induction of synchronous meiosis in the fission yeast Schizosaccharomyces pombe. Chemical inactivation of an ATP analog-sensitive form of the Pat1 kinase (pat1-as2) by adding the ATP analog 1-NM-PP1 in G1-arrested cells allows the induction of synchronous meiosis at optimal temperature (25°C). Importantly, this protocol eliminates detrimental effects of elevated temperature (34°C), which is required to inactivate the commonly used temperature-sensitive Pat1 kinase mutant (pat1-114). The addition of the mat-Pc gene to a mat1-M strain further improves chromosome segregation and spore viability. Thus, our protocol offers highly synchronous meiosis at optimal temperature, with most characteristics similar to those of wild-type meiosis. The synchronization protocol can be completed in 5 d (not including strain production, which may take as long as 2 or 3 months).

  14. Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes.

    PubMed

    Pfender, Sybille; Kuznetsov, Vitaliy; Pasternak, Michał; Tischer, Thomas; Santhanam, Balaji; Schuh, Melina

    2015-08-13

    During fertilization, an egg and a sperm fuse to form a new embryo. Eggs develop from oocytes in a process called meiosis. Meiosis in human oocytes is highly error-prone, and defective eggs are the leading cause of pregnancy loss and several genetic disorders such as Down's syndrome. Which genes safeguard accurate progression through meiosis is largely unclear. Here we develop high-content phenotypic screening methods for the systematic identification of mammalian meiotic genes. We targeted 774 genes by RNA interference within follicle-enclosed mouse oocytes to block protein expression from an early stage of oocyte development onwards. We then analysed the function of several genes simultaneously by high-resolution imaging of chromosomes and microtubules in live oocytes and scored each oocyte quantitatively for 50 phenotypes, generating a comprehensive resource of meiotic gene function. The screen generated an unprecedented annotated data set of meiotic progression in 2,241 mammalian oocytes, which allowed us to analyse systematically which defects are linked to abnormal chromosome segregation during meiosis, identifying progression into anaphase with misaligned chromosomes as well as defects in spindle organization as risk factors. This study demonstrates how high-content screens can be performed in oocytes, and allows systematic studies of meiosis in mammals.

  15. Ipl1/Aurora-B is necessary for kinetochore restructuring in meiosis I in Saccharomyces cerevisiae.

    PubMed

    Meyer, Régis E; Chuong, Hoa H; Hild, Marrett; Hansen, Christina L; Kinter, Michael; Dawson, Dean S

    2015-09-01

    In mitosis, the centromeres of sister chromosomes are pulled toward opposite poles of the spindle. In meiosis I, the opposite is true: the sister centromeres move together to the same pole, and the homologous chromosomes are pulled apart. This change in segregation patterns demands that between the final mitosis preceding meiosis and the first meiotic division, the kinetochores must be restructured. In budding yeast, unlike mammals, kinetochores are largely stable throughout the mitotic cycle. In contrast, previous work with budding and fission yeast showed that some outer kinetochore proteins are lost in early meiosis. We use quantitative mass spectrometry methods and imaging approaches to explore the kinetochore restructuring process that occurs in meiosis I in budding yeast. The Ndc80 outer kinetochore complex, but not other subcomplexes, is shed upon meiotic entry. This shedding is regulated by the conserved protein kinase Ipl1/Aurora-B and promotes the subsequent assembly of a kinetochore that will confer meiosis-specific segregation patterns on the chromosome.

  16. Comparative expression profiling reveals gene functions in female meiosis and gametophyte development in Arabidopsis.

    PubMed

    Zhao, Lihua; He, Jiangman; Cai, Hanyang; Lin, Haiyan; Li, Yanqiang; Liu, Renyi; Yang, Zhenbiao; Qin, Yuan

    2014-11-01

    Megasporogenesis is essential for female fertility, and requires the accomplishment of meiosis and the formation of functional megaspores. The inaccessibility and low abundance of female meiocytes make it particularly difficult to elucidate the molecular basis underlying megasporogenesis. We used high-throughput tag-sequencing analysis to identify genes expressed in female meiocytes (FMs) by comparing gene expression profiles from wild-type ovules undergoing megasporogenesis with those from the spl mutant ovules, which lack megasporogenesis. A total of 862 genes were identified as FMs, with levels that are consistently reduced in spl ovules in two biological replicates. Fluorescence-assisted cell sorting followed by RNA-seq analysis of DMC1:GFP-labeled female meiocytes confirmed that 90% of the FMs are indeed detected in the female meiocyte protoplast profiling. We performed reverse genetic analysis of 120 candidate genes and identified four FM genes with a function in female meiosis progression in Arabidopsis. We further revealed that KLU, a putative cytochrome P450 monooxygenase, is involved in chromosome pairing during female meiosis, most likely by affecting the normal expression pattern of DMC1 in ovules during female meiosis. Our studies provide valuable information for functional genomic analyses of plant germline development as well as insights into meiosis.

  17. The Ime2 protein kinase family in fungi: more duties than just meiosis.

    PubMed

    Irniger, Stefan

    2011-04-01

    Ime2 of the budding yeast Saccharomyces cerevisiae belongs to a family of conserved protein kinases displaying sequence similarities to both cyclin-dependent kinases and mitogen-activated protein kinases. Ime2 has a pivotal role for meiosis and sporulation. The involvement of this protein kinase in the regulation of various key events in meiosis, such as the initiation of DNA replication, the expression of meiosis-specific genes and the passage through the two consecutive rounds of nuclear divisions has been characterized in detail. More than 20 years after the identification of the IME2 gene, a recent report has provided the first evidence for a function of this gene outside of meiosis, which is the regulation of pseudohyphal growth. In the last few years, Ime2-related protein kinases from various fungal species were studied. Remarkably, these homologues are not generally required for meiosis, but instead have other specific tasks. In filamentous ascomycete species, Ime2 homologues are involved in the inhibition of fruiting body formation in response to environmental signals. In the pathogenic basidiomycetes Ustilago maydis and Cryptococcus neoformans, members of this kinase family apparently have primary roles in regulating mating. Thus, Ime2-related kinases exhibit an amazing variety in controlling sexual developmental programs in fungi.

  18. Genetic and epigenetic factors affecting meiosis induction in eukaryotes revealed in paramecium research.

    PubMed

    Prajer, Małgorzata

    2008-01-01

    This review presents studies of the induction of meiosis undertaken on the ciliate Paramecium, a unicellular model eukaryotic organism. Meiosis in Paramecium, preceding the process of fertilization, appears in starved cells after passing a defined number of divisions (cell generations), starting from the last fertilization. Investigations were performed on clones of cells entering autogamy, a self-fertilization process. Genetic as well as epigenetic factors, i.e. endo- and exogenous factors, affecting the induction ofmeiosis and changing the duration of the interautogamous interval (IAI), were analyzed. The results show that: (1) Meiosis induction is controlled genetically by the somatic macronucleus. However, besides the nuclear factors, the cytoplasmic protein immaturin also affects this process (Haga & Hiwatashi 1981); (2) Epigenetic factors, such as non-genetically disturbed cytoskeleton structures and changes in the cell architecture observed in doublet Paramecium cells, exert internal mechanical stress (Ingber 2003), which constitutes the endogenous impulse accelerating meiosis; (3) Mild osmotic stress, acting as an exogenous factor, can initiate the specific MAP kinases signaling pathway resulting in earlier meiosis induction, as in other unicellular eukaryotes (Seet & Pawson 2004).

  19. FEAR but not MEN genes are required for exit from meiosis I.

    PubMed

    Kamieniecki, Rebecca J; Liu, Li; Dawson, Dean S

    2005-08-01

    Exit from mitosis is regulated by Cdc14, which plays an essential role in triggering cyclin-dependent kinase inactivation. Throughout most of the cell cycle, Cdc14 is sequestered in the nucleolus where it remains inactive. After the completion of anaphase, an essential signaling cascade, named the Mitotic Exit Network, or MEN, promotes Cdc14 release. Cdc14 is also released from the nucleolus in early anaphase by another, nonessential, pathway called FEAR (CdcFourteen Early Anaphase Release). Separase (Esp1), polo kinase (Cdc5), the kinetochore protein Slk19, and Spo12, whose molecular function remains unknown, have been identified as members of the FEAR pathway. In meiosis, mutations in CDC14 and its FEAR pathway regulators, CDC5, SLK19, and SPO12, all result it asci that contain only two diploid spores because of a defect in the ability to exit meiosis I. Thus although the FEAR pathway is dispensible for mitotic exit, it is essential for meiosis I exit. The way that the genes of the Mitotic Exit Network contribute to coordinating meiotic progression is less clear. Here, we explore this issue. Our results demonstrate that the orderly transition from meiosis I to meiosis II is accomplished by eliminating MEN function and using the FEAR pathway to modulate cyclin dependent kinase activity, in part through the actions of SIC1.

  20. [Studies of the meiosis of 2n gamete apomictic wheat grass (Elymus rectisetus)].

    PubMed

    Li, M T; Cai, D T; Huang, L M

    2001-01-01

    The formation of polyploid was mainly through the combination of 2n gamete, and the apomixis played an important role in plant evolution and plant breeding. In general, the formation of male gamete and female gamete in apomictic plants are obviously different, i.e., the formation of embryo sac was through apomixis (form into 2n female gamete); however, the formation of male gamete was through normal meiosis (form into 1n male gamete). The 2n male gamete apomictic wheat grass was more important than 1n male gamete apomictic wheat grass, because the 2n male gamete can bring all genes including apomictic gene into other plant. The meiosis of 2n male gamete apomictic wheat grass (Elymus. rectisetus) was observed through Olympus AH3 microscope; the results showed that the meiosis of 2n gamete apomictic wheat grass was very abnomal. In the interphase, lots of mini-nucleus were found. Inverted cycle, multibivalent and lagging chromosome were also found in the prophase. In metaphase, chromosomes frequently show unequal division tendency; In anaphase I and telophase I, completely unequal division, modified meiosis, the tendency of nucleus fusion and other abnormal phenomena were found. These phenomena directly lead to the production of 2n gamete. In meiosis II, the abnormalities mainly lie in the proceeding of microspore, dyad (55.7%), triad (23.7%) and tetrad (21.6%) were found. The abnormal of those proceeding also lead to the production of 2n gamete.

  1. Aurora B regulates spindle bipolarity in meiosis in vertebrate oocytes.

    PubMed

    Shao, Hua; Ma, Chunqi; Zhang, Xuan; Li, Ruizhen; Miller, Ann L; Bement, William M; Liu, X Johné

    2012-07-15

    Aurora B (Aur-B) plays multiple roles in mitosis, of which the best known are to ensure bi-orientation of sister chromatids by destabilizing incorrectly attached kinetochore microtubules and to participate in cytokinesis. Studies in Xenopus egg extracts, however, have indicated that Aur-B and the chromosome passenger complex play an important role in stabilizing chromosome-associated spindle microtubules. Aur-B stabilizes spindle microtubules in the egg extracts by inhibiting the catastrophe kinesin MCAK. Whether or not Aur-B plays a similar role in intact oocytes remains unknown. Here we have employed a dominant-negative Aur-B mutant (Aur-B122R, in which the ATP-binding lysine(122) is replaced with arginine) to investigate the function of Aur-B in spindle assembly in Xenopus oocytes undergoing meiosis. Overexpression of Aur-B122R results in short bipolar spindles or monopolar spindles, with higher concentrations of Aur-B122R producing mostly the latter. Simultaneous inhibition of MCAK translation in oocytes overexpressing Aur-B122R results in suppression of monopolar phenotype, suggesting that Aur-B regulates spindle bipolarity by inhibiting MCAK. Furthermore, recombinant MCAK-4A protein, which lacks all four Aur-B phosphoryaltion sites and is therefore insensitive to Aur-B inhibition but not wild-type MCAK, recapitulated the monopolar phenotype in the oocytes. These results suggest that in vertebrate oocytes that lack centrosomes, one major function of Aur-B is to stabilize chromosome-associated spindle microtubules to ensure spindle bipolarity.

  2. Ectopic DNMT3B expression delays leukemogenesis.

    PubMed

    Stanley, Robert F; Steidl, Ulrich

    2016-03-24

    In this issue of Blood, Schulze et al use a tetracycline-inducible Dnmt3b knock-in mouse model to investigate how DNMT3B-mediated DNA methylation affects leukemogenesis. Increased DNMT3B expression prolonged survival in retrovirally induced Myc-Bcl2– or MLL-AF9–driven leukemia, and acute myeloid leukemia (AML) patients with high expression of DNMT3B target genes showed inferior overall survival.

  3. A DNA-binding surface of SPO11-1, an Arabidopsis SPO11 orthologue required for normal meiosis.

    PubMed

    Shingu, Yoshinori; Mikawa, Tsutomu; Onuma, Mariko; Hirayama, Takashi; Shibata, Takehiko

    2010-05-01

    Meiotic recombination is initiated by DNA double-stranded breaks introduced by the SPO11 protein. Despite a decade of research, the biochemical functions of SPO11 remain largely unknown, perhaps because of difficulties in studying the functionally active SPO11. Arabidopsis thaliana encodes three SPO11-related proteins, two of which (SPO11-1 and SPO11-2) are required for, and cooperate in, meiosis. We isolated soluble SPO11-1, fused with or free of a trigger factor-tag at its N terminus. The tag-free SPO11-1 needed to interact physically with soluble SPO11-1 to maintain its solubility, suggesting a multimeric active form including a solubilizing protein cofactor. An N-terminal fragment of PRD1, a SPO11-1-interacting protein required for normal meiosis, but not SPO11-2, forms a soluble complex with trigger factor-tagged SPO11-1, but the trigger factor-tag was required for the solubility. Formation of the complex is not sufficient to express endonuclease activity. Trigger factor-tagged SPO11-1 exhibited DNA-binding activities: Glu substitutions of the invariant Gly215 and Arg222 and of the nonconserved Arg223 and Arg226 in a conserved motif (G215E, R222E, R223E, R226E) reduced the DNA-binding ability in vitro, but substitutions of the conserved Arg130 and invariant Tyr103 (a residue in the putative endonuclease-active center) and of Arg residues outside conserved motifs by Glu or Phe (R130E, Y103F, R207E and R254E), did not. Tests for the ability of mutant spo11-1 proteins to complement the silique-defective phenotype of a spo11-1-homozygous mutant in vivo revealed that R222E and G215E induced serious deficiencies, while R130E caused a partial defect in silique formation. Thus, the Gly215, Arg222 and Arg223 residues of SPO11-1 form a DNA-binding surface that is functional in meiosis.

  4. Transcriptional activities of the Pax6 gene eyeless regulate tissue specificity of ectopic eye formation in Drosophila

    PubMed Central

    Weasner, Bonnie M.; Weasner, Brandon; DeYoung, Stephanie M.; Michaels, Scott D.; Kumar, Justin P.

    2009-01-01

    Pax genes encode DNA binding proteins that play pivotal roles in the determination of complex tissues. Members of one subclass, Pax6, function as selector genes and play key roles in the retinal development of all seeing animals. Mutations within the Pax6 homologs including fly eyeless, mouse Small eye and human Pax6 lead to severe retinal defects in their respective systems. In Drosophila eyeless and twin of eyeless, play non-redundant roles in the developing retina. One particularly interesting characteristic of these genes is that, although expression of either gene can induce ectopic eye formation in non-retinal tissues, there are differences in the location and frequencies at which the eyes develop. eyeless induces much larger ectopic eyes, at higher frequencies, and in a broader range of tissues than twin of eyeless. In this report we describe a series of experiments conducted in both yeast and flies that has identified protein modules that are responsible for the differences in tissue transformation. These domains appear to contain transcriptional activator and repressor activity of distinct strengths. We propose a model in which the selective presence of these activities and their relative strengths accounts, in part, for the disparity to which ectopic eyes are induced in response to the forced expression of eyeless and twin of eyeless. The identification of both transcriptional activator and repressor activity within the Pax6 protein furthers our understanding of how this gene family regulates tissue determination. PMID:19406113

  5. Restriction of Ectopic Eye Formation by Drosophila Teashirt and Tiptop to the Developing Antenna

    PubMed Central

    Datta, Rhea R.; Lurye, Jessica M.; Kumar, Justin P.

    2009-01-01

    Summary In Drosophila, the retinal determination network comprises a set of nuclear factors whose loss-of-function phenotypes often include the complete or near total elimination of the developing eye. These genes also share the ability of being able to induce ectopic eye formation when forcibly expressed in non-retinal tissues such as the antennae, legs, halteres, wings and genitals. However, it appears that the ability to redirect and transform tissue fates is limited; not all tissues and cell populations can be forced into adopting an eye fate. In this report we demonstrate that ectopic eye formation by teashirt and its paralog tiptop, a potential new eye specification gene, is restricted to the developing antennae. Interestingly, tiptop appears to be a more effective inducer of retinal formation than teashirt. A genetic screen for interacting proteins failed to identify paralog specific relationships suggesting that the differences between these two genes may be attributed instead to structural differences between the duplicates. We also demonstrate that in addition to being expressed in co-incident patterns within the developing eye, both paralogs are transcribed at very similar levels. PMID:19347955

  6. YA is needed for proper nuclear organization to transition between meiosis and mitosis in Drosophila

    PubMed Central

    Sackton, Katharine L; Lopez, Jacqueline M; Berman, Cindy L; Wolfner, Mariana F

    2009-01-01

    Background The Drosophila YA protein is required to initiate the embryonic cleavage divisions. After egg activation, YA enters nuclei and interacts with chromatin and the nuclear lamina. This study was designed to define more precisely the events prior to the first cleavage division that are dependent upon YA. Results We find that meiosis is completed normally in the absence of YA function. The first defects in embryos and eggs from mutant mothers first appear just after the completion of meiosis, and are seen as abnormal associations among the resultant haploid nuclei. These defects are associated with asynchronies in the cell cycle-dependent chromatin condensation state of the haploid nuclei. However, we find evidence of DNA replication in the absence of YA function. Conclusion Our data suggest YA function is needed at a control point, following meiosis II and the initiation of the first postmeiotic S phase, which is sensitive to the chromatin condensation state of the haploid meiotic products. PMID:19627584

  7. Commitment to Meiosis in Saccharomyces Cerevisiae: Involvement of the Spo14 Gene

    PubMed Central

    Honigberg, S. M.; Conicella, C.; Espositio, R. E.

    1992-01-01

    This paper describes the identification, cloning and phenotypic analysis of SPO14, a new gene required for meiosis and spore formation. Studies of strains carrying a temperature-sensitive mutation or a disruption/duplication allele indicate that spo14 mutants have the unusual property of being able to return to mitotic division, even from the late stages of meiotic development. Early meiotic events, such as DNA replication and intragenic and intergenic recombination, occur normally. In contrast, later meiotic processes are defective in spo14 mutants: the meiosis I division appears to be executed at slightly depressed levels, the meiosis II division is reduced more severely, and no spores are formed. Epistasis tests using mutants defective in recombination or reductional division support these findings. Based on these data, we suggest that the SPO14 gene product is involved in the coordinate induction of late meiotic events and that this induction is responsible for the phenomenon of commitment. PMID:1582554

  8. Rad61/Wpl1 (Wapl), a cohesin regulator, controls chromosome compaction during meiosis

    PubMed Central

    Challa, Kiran; Lee, Min-Su; Shinohara, Miki; Kim, Keun P.; Shinohara, Akira

    2016-01-01

    Meiosis-specific cohesin, required for the linking of the sister chromatids, plays a critical role in various chromosomal events during meiotic prophase I, such as chromosome morphogenesis and dynamics, as well as recombination. Rad61/Wpl1 (Wapl in other organisms) negatively regulates cohesin functions. In this study, we show that meiotic chromosome axes are shortened in the budding yeast rad61/wpl1 mutant, suggesting that Rad61/Wpl1 negatively regulates chromosome axis compaction. Rad61/Wpl1 is required for efficient resolution of telomere clustering during meiosis I, indicating a positive effect of Rad61/Wpl1 on the cohesin function required for telomere dynamics. Additionally, we demonstrate distinct activities of Rad61/Wpl1 during the meiotic recombination, including its effects on the efficient processing of intermediates. Thus, Rad61/Wpl1 both positively and negatively regulates various cohesin-mediated chromosomal processes during meiosis. PMID:26825462

  9. Male meiosis in Crustacea: synapsis, recombination, epigenetics and fertility in Daphnia magna.

    PubMed

    Gómez, Rocío; Van Damme, Kay; Gosálvez, Jaime; Morán, Eugenio Sánchez; Colbourne, John K

    2016-09-01

    We present the first detailed cytological study of male meiosis in Daphnia (Crustacea: Branchiopoda: Cladocera)-an aquatic microcrustacean with a cyclical parthenogenetic life cycle. Using immunostaining of the testes in Daphnia magna for baseline knowledge, we characterized the different stages of meiotic division and spermiogenesis in relation to the distribution of proteins involved in synapsis, early recombination events and sister chromatid cohesion. We also studied post-translational histone modifications in male spermatocytes, in relation to the dynamic chromatin progression of meiosis. Finally, we applied a DNA fragmentation test to measure sperm quality of D. magna, with respect to levels of inbreeding. As a proxy for fertility, this technique may be used to assess the reproductive health of a sentinel species of aquatic ecosystems. Daphnia proves to be a model species for comparative studies of meiosis that is poised to improve our understanding of the cytological basis of sexual and asexual reproduction.

  10. Complete Meiosis from Embryonic Stem Cell-Derived Germ Cells In Vitro.

    PubMed

    Zhou, Quan; Wang, Mei; Yuan, Yan; Wang, Xuepeng; Fu, Rui; Wan, Haifeng; Xie, Mingming; Liu, Mingxi; Guo, Xuejiang; Zheng, Ying; Feng, Guihai; Shi, Qinghua; Zhao, Xiao-Yang; Sha, Jiahao; Zhou, Qi

    2016-03-03

    In vitro generation of functional gametes is a promising approach for treating infertility, although faithful replication of meiosis has proven to be a substantial obstacle to deriving haploid gamete cells in culture. Here we report complete in vitro meiosis from embryonic stem cell (ESC)-derived primordial germ cells (PGCLCs). Co-culture of PGCLCs with neonatal testicular somatic cells and sequential exposure to morphogens and sex hormones reproduced key hallmarks of meiosis, including erasure of genetic imprinting, chromosomal synapsis and recombination, and correct nuclear DNA and chromosomal content in the resulting haploid cells. Intracytoplasmic injection of the resulting spermatid-like cells into oocytes produced viable and fertile offspring, showing that this robust stepwise approach can functionally recapitulate male gametogenesis in vitro. These findings provide a platform for investigating meiotic mechanisms and the potential generation of human haploid spermatids in vitro.

  11. Coordinating cohesion, co-orientation, and congression during meiosis: lessons from holocentric chromosomes.

    PubMed

    Schvarzstein, Mara; Wignall, Sarah M; Villeneuve, Anne M

    2010-02-01

    Organisms that reproduce sexually must reduce their chromosome number by half during meiosis to generate haploid gametes. To achieve this reduction in ploidy, organisms must devise strategies to couple sister chromatids so that they stay together during the first meiotic division (when homologous chromosomes separate) and then segregate away from one another during the second division. Here we review recent findings that shed light on how Caenorhabditis elegans, an organism with holocentric chromosomes, deals with these challenges of meiosis by differentiating distinct chromosomal subdomains and remodeling chromosome structure during prophase. Furthermore, we discuss how features of chromosome organization established during prophase affect later chromosome behavior during the meiotic divisions. Finally, we illustrate how analysis of holocentric meiosis can inform our thinking about mechanisms that operate on monocentric chromosomes.

  12. Retinoic acid and meiosis induction in adult versus embryonic gonads of medaka

    PubMed Central

    Adolfi, Mateus C.; Herpin, Amaury; Regensburger, Martina; Sacquegno, Jacopo; Waxman, Joshua S.; Schartl, Manfred

    2016-01-01

    In vertebrates, one of the first recognizable sex differences in embryos is the onset of meiosis, known to be regulated by retinoic acid (RA) in mammals. We investigated in medaka a possible meiotic function of RA during the embryonic sex determination (SD) period and in mature gonads. We found RA mediated transcriptional activation in germ cells of both sexes much earlier than the SD stage, however, no such activity during the critical stages of SD. In adults, expression of the RA metabolizing enzymes indicates sexually dimorphic RA levels. In testis, RA acts directly in Sertoli, Leydig and pre-meiotic germ cells. In ovaries, RA transcriptional activity is highest in meiotic oocytes. Our results show that RA plays an important role in meiosis induction and gametogenesis in adult medaka but contrary to common expectations, not for initiating the first meiosis in female germ cells at the SD stage. PMID:27677591

  13. A retroperitoneal neuroendocrine tumor in ectopic pancreatic tissue.

    PubMed

    Okasha, Hussein Hassan; Al-Bassiouni, Fahim; El-Ela, Monir Abo; Al-Gemeie, Emad Hamza; Ezzat, Reem

    2013-07-01

    Ectopic pancreas is the relatively uncommon presence of pancreatic tissue outside the normal location of the pancreas. We report a case of abdominal pain due to retroperitoneal neuroendocrine tumor arising from heterotopic pancreatic tissue between the duodenal wall and the head of the pancreas. Patient underwent surgical enucleation of the tumor.

  14. Ectopic ovary with torsion: uncommon diagnosis made by ultrasound

    PubMed Central

    Castro, Adham do Amaral e; Morandini, Fernando; Calixto, Caroline Paludo; Barros, Wagner Haese; Nakatani, Edson Tetsuya; Castro, Allan do Amaral e

    2017-01-01

    Ultrasound is an important diagnostic tool in inguinal hernia and in the evaluation of the contents of the hernia sac. This report presents a case in which ultrasound revealed a herniated ectopic ovary, complicated by torsion of its vascular pedicle, in the right labia majora. We also present a brief discussion of ovarian hernia, its potential complications, and the treatments available. PMID:28298734

  15. Research Progress in Pseudoxanthoma Elasticum and Related Ectopic Mineralization Disorders

    PubMed Central

    Li, Qiaoli; Arányi, Tamás; Váradi, András; Terry, Sharon F.; Uitto, Jouni

    2015-01-01

    Heritable ectopic mineralization disorders represent a phenotypically diverse group of conditions characterized by deposition of calcium phosphate complexes in soft connective tissues. The prototype of such conditions is pseudoxanthoma elasticum (PXE), and related conditions with overlapping clinical features include generalized arterial calcification of infancy (GACI) and arterial calcification due to CD73 deficiency (ACDC). Molecular genetic investigations have revealed mutations in the genes physiologically involved in generation of inorganic pyrophosphate (PPi) and phosphate (Pi), and the findings suggest a unifying pathomechanism relating to reduced PPi/Pi ratio. This hypothesis is based on the notion that PPi serves as a powerful inhibitor of mineralization while Pi is a pro-mineralization factor, and an appropriate PPi/Pi ratio is critical for prevention of ectopic mineralization under homeostatic conditions. PXE International, the premiere patient support organization, advocating on behalf of patients and families with PXE, sponsors regular research meetings evaluating the progress in this and related ectopic mineralization disorders. The latest meetings were held in September 2014 in Bethesda, MD and in September 2015 in Budapest, Hungary. This report summarizes the latest progress in research on PXE and related ectopic mineralization disorders, based on presentations and discussions in these meetings, with pharmacologic implications for currently intractable disorders. PMID:26902123

  16. Robotic resection of an ectopic goiter in the mediastinum.

    PubMed

    Bodner, Johannes; Fish, John; Lottersberger, Andreas C; Wetscher, Gerold; Schmid, Thomas

    2005-08-01

    We report the first robotic resection of an ectopic mediastinal thyroid adenoma in a 72-year-old woman. This intervention was part of staged management for excessive bilateral cervical goiter with intrathoracic dispersion. The robotic resection was found to be feasible and safe. The robotic operating system offers better visual control and operative accuracy than does conventional thoracoscopy.

  17. Ectopic tubal pregnancy after hysterectomy and tubal ligation.

    PubMed

    Rosa, Marilin; Mohammadi, Amir; Monteiro, Carmela

    2009-01-01

    Posthysterectomy ectopic pregnancy is an unusual condition that may present soon after hysterectomy or several years later. Similarly, although tubal ligation is a widespread method of contraception, tubal pregnancy after tubal ligation is not common either. If any of these conditions are rare, having an ectopic pregnancy after hysterectomy and tubal ligation is even more infrequent and only one of such cases was found in our review of the literature. We describe the case of a 35-year-old patient, with history of bilateral tubal ligation and vaginal hysterectomy that looked for medical attention due to abdominal pain. A pregnancy test was positive and a transvaginal ultrasound demonstrated the presence of a gestational sac at the vaginal cuff, adjacent to the ovary. An exploratory laparotomy showed a ruptured ectopic pregnancy located in the distal portion of the left fallopian tube. The occurrence of an ectopic pregnancy several years following tubal ligation and vaginal hysterectomy is a rare phenomenon that appears to be secondary to a fistulous connection into the peritoneal cavity.

  18. Brief review of models of ectopic bone formation.

    PubMed

    Scott, Michelle A; Levi, Benjamin; Askarinam, Asal; Nguyen, Alan; Rackohn, Todd; Ting, Kang; Soo, Chia; James, Aaron W

    2012-03-20

    Ectopic bone formation is a unique biologic entity--distinct from other areas of skeletal biology. Animal research models of ectopic bone formation most often employ rodent models and have unique advantages over orthotopic (bone) environments, including a relative lack of bone cytokine stimulation and cell-to-cell interaction with endogenous (host) bone-forming cells. This allows for relatively controlled in vivo experimental bone formation. A wide variety of ectopic locations have been used for experimentation, including subcutaneous, intramuscular, and kidney capsule transplantation. The method, benefits and detractions of each method are summarized in the following review. Briefly, subcutaneous implantation is the simplest method. However, the most pertinent concern is the relative paucity of bone formation in comparison to other models. Intramuscular implantation is also widely used and relatively simple, however intramuscular implants are exposed to skeletal muscle satellite progenitor cells. Thus, distinguishing host from donor osteogenesis becomes challenging without cell-tracking studies. The kidney capsule (perirenal or renal capsule) method is less widely used and more technically challenging. It allows for supraphysiologic blood and nutrient resource, promoting robust bone growth. In summary, ectopic bone models are extremely useful in the evaluation of bone-forming stem cells, new osteoinductive biomaterials, and growth factors; an appropriate choice of model, however, will greatly increase experimental success.

  19. "Chromoseratops Meiosus": A Simple, Two-Phase Exercise to Represent the Connection between Meiosis & Increased Genetic Diversity

    ERIC Educational Resources Information Center

    Eliyahu, Dorit

    2014-01-01

    I present an activity to help students make the connection between meiosis and genetic variation. The students model meiosis in the first phase of the activity, and by that process they produce gametes of a fictitious reptilobird species, "Chromoseratops meiosus." Later on, they will "mate" their gametes and produce a zygote…

  20. A Paper-and-Pencil Strategy for Teaching Mitosis and Meiosis, Diagnosing Learning Problems and Predicting Examination Performance.

    ERIC Educational Resources Information Center

    Mertens, Thomas R.; Walker, Julie O.

    1992-01-01

    Describes the Bajema strategy for teaching meiosis and how it is used in the general genetics course at Ball State University and can be used to identify students who have misconceptions of meiosis that can interfere with their learning the basics of Mendelian inheritance. (Contains 11 references.) (MDH)

  1. Distinct function of COAR and B3 domains of maize VP1 in induction of ectopic gene expression and plant developmental phenotypes in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maize VP1 enhancement of ABA sensitivity in roots is B3 independent. ABA and VP1 mediated suppression of auxin induced lateral root development is B3 independent. Arabidopsis transgenic system to delineate B3 dependent and COAR domain dependent regulatory functions of VP1. Analyses of ectopic ABA re...

  2. Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1

    PubMed Central

    Callender, Tracy L.; Laljee, Saif; Zhou, Sai; Suhandynata, Ray T.; Gaines, William A.; Kwon, YoungHo; Börner, G. Valentin; Nicolas, Alain; Neiman, Aaron M.

    2016-01-01

    During meiosis, programmed double strand breaks (DSBs) are repaired preferentially between homologs to generate crossovers that promote proper chromosome segregation at Meiosis I. In many organisms, there are two strand exchange proteins, Rad51 and the meiosis-specific Dmc1, required for interhomolog (IH) bias. This bias requires the presence, but not the strand exchange activity of Rad51, while Dmc1 is responsible for the bulk of meiotic recombination. How these activities are regulated is less well established. In dmc1Δ mutants, Rad51 is actively inhibited, thereby resulting in prophase arrest due to unrepaired DSBs triggering the meiotic recombination checkpoint. This inhibition is dependent upon the meiosis-specific kinase Mek1 and occurs through two different mechanisms that prevent complex formation with the Rad51 accessory factor Rad54: (i) phosphorylation of Rad54 by Mek1 and (ii) binding of Rad51 by the meiosis-specific protein Hed1. An open question has been why inhibition of Mek1 affects Hed1 repression of Rad51. This work shows that Hed1 is a direct substrate of Mek1. Phosphorylation of Hed1 at threonine 40 helps suppress Rad51 activity in dmc1Δ mutants by promoting Hed1 protein stability. Rad51-mediated recombination occurring in the absence of Hed1 phosphorylation results in a significant increase in non-exchange chromosomes despite wild-type levels of crossovers, confirming previous results indicating a defect in crossover assurance. We propose that Rad51 function in meiosis is regulated in part by the coordinated phosphorylation of Rad54 and Hed1 by Mek1. PMID:27483004

  3. Exposure to Low-Dose Bisphenol A Impairs Meiosis in the Rat Seminiferous Tubule Culture Model: A Physiotoxicogenomic Approach

    PubMed Central

    Ali, Sazan; Steinmetz, Gérard; Montillet, Guillaume; Perrard, Marie-Hélène; Loundou, Anderson; Durand, Philippe

    2014-01-01

    Background Bisphenol A (BPA) is one of the most widespread chemicals in the world and is suspected of being responsible for male reproductive impairments. Nevertheless, its molecular mode of action on spermatogenesis is unclear. This work combines physiology and toxicogenomics to identify mechanisms by which BPA affects the timing of meiosis and induces germ-cell abnormalities. Methods We used a rat seminiferous tubule culture model mimicking the in vivo adult rat situation. BPA (1 nM and 10 nM) was added to the culture medium. Transcriptomic and meiotic studies were performed on the same cultures at the same exposure times (days 8, 14, and 21). Transcriptomics was performed using pangenomic rat microarrays. Immunocytochemistry was conducted with an anti-SCP3 antibody. Results The gene expression analysis showed that the total number of differentially expressed transcripts was time but not dose dependent. We focused on 120 genes directly involved in the first meiotic prophase, sustaining immunocytochemistry. Sixty-two genes were directly involved in pairing and recombination, some of them with high fold changes. Immunocytochemistry indicated alteration of meiotic progression in the presence of BPA, with increased leptotene and decreased diplotene spermatocyte percentages and partial meiotic arrest at the pachytene checkpoint. Morphological abnormalities were observed at all stages of the meiotic prophase. The prevalent abnormalities were total asynapsis and apoptosis. Transcriptomic analysis sustained immunocytological observations. Conclusion We showed that low doses of BPA alter numerous genes expression, especially those involved in the reproductive system, and severely impair crucial events of the meiotic prophase leading to partial arrest of meiosis in rat seminiferous tubule cultures. PMID:25181051

  4. The Parasexual Cycle in Candida albicans Provides an Alternative Pathway to Meiosis for the Formation of Recombinant Strains

    PubMed Central

    Forche, Anja; Alby, Kevin; Schaefer, Dana; Johnson, Alexander D; Berman, Judith; Bennett, Richard J

    2008-01-01

    Candida albicans has an elaborate, yet efficient, mating system that promotes conjugation between diploid a and α strains. The product of mating is a tetraploid a/α cell that must undergo a reductional division to return to the diploid state. Despite the presence of several “meiosis-specific” genes in the C. albicans genome, a meiotic program has not been observed. Instead, tetraploid products of mating can be induced to undergo efficient, random chromosome loss, often producing strains that are diploid, or close to diploid, in ploidy. Using SNP and comparative genome hybridization arrays we have now analyzed the genotypes of products from the C. albicans parasexual cycle. We show that the parasexual cycle generates progeny strains with shuffled combinations of the eight C. albicans chromosomes. In addition, several isolates had undergone extensive genetic recombination between homologous chromosomes, including multiple gene conversion events. Progeny strains exhibited altered colony morphologies on laboratory media, demonstrating that the parasexual cycle generates phenotypic variants of C. albicans. In several fungi, including Saccharomyces cerevisiae and Schizosaccharomyces pombe, the conserved Spo11 protein is integral to meiotic recombination, where it is required for the formation of DNA double-strand breaks. We show that deletion of SPO11 prevented genetic recombination between homologous chromosomes during the C. albicans parasexual cycle. These findings suggest that at least one meiosis-specific gene has been re-programmed to mediate genetic recombination during the alternative parasexual life cycle of C. albicans. We discuss, in light of the long association of C. albicans with warm-blooded animals, the potential advantages of a parasexual cycle over a conventional sexual cycle. PMID:18462019

  5. Usefulness of Transjugular Intrahepatic Portosystemic Shunt in the Management of Bleeding Ectopic Varices in Cirrhotic Patients

    SciTech Connect

    Vidal, V.; Joly, L.; Perreault, P.; Bouchard, L.; Lafortune, M.; Pomier-Layrargues, G.

    2006-04-15

    Purpose. To evaluate the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in the control of bleeding from ectopic varices. Methods. From 1995 to 2004, 24 cirrhotic patients, bleeding from ectopic varices, mean age 54.5 years (range 15-76 years), were treated by TIPS. The etiology of cirrhosis was alcoholic in 13 patients and nonalcoholic in 11 patients. The location of the varices was duodenal (n = 5), stomal (n = 8), ileocolic (n = 6), anorectal (n = 3), umbilical (n = 1), and peritoneal (n 1). Results. TIPS controlled the bleeding in all patients and induced a decrease in the portacaval gradient from 19.7 {+-} 5.4 to 6.4 {+-} 3.1 mmHg. Postoperative complications included self-limited intra-abdominal bleeding (n = 2), self-limited hemobilia (n = 1), acute thrombosis of the shunt (n = 1), and bile leak treated by a covered stent (n = 1). Median follow-up was 592 days (range 28-2482 days). Rebleeding occurred in 6 patients. In 2 cases rebleeding was observed despite a post-TIPS portacaval gradient lower than 12 mmHg and was controlled by variceal embolization; 1 patient underwent surgical portacaval shunt and never rebled; in 3 patients rebleeding was related to TIPS stenosis and treated with shunt dilatation with addition of a new stent. The cumulative rate of rebleeding was 23% and 31% at 1 and 2 years, respectively. One- and 2-year survival rates were 80% and 76%, respectively. Conclusion. The present series demonstrates that bleeding from ectopic varices, a challenging clinical problem, can be managed safely by TIPS placement with low rebleeding and good survival rates.

  6. Elastic discontinuity due to ectopic calcification in a human fibrous joint

    PubMed Central

    Lin, Jeremy D.; Aloni, Shaul; Altoe, Virginia; Webb, Samuel M.; Ryder, Mark I.; Ho, Sunita P.

    2012-01-01

    Disease can alter the natural ramp-like elastic gradients to steeper step-like profiles at soft-hard tissue interfaces. Prolonged function can further mediate mechanochemical events that alter biomechanical response within diseased organs. In this study a human bone-tooth fibrous joint was chosen as a model system, in which the effects of bacterial-induced disease, i.e. periodontitis, on natural elastic gradients were investigated. Specifically, the effects of ectopic biomineral, i.e. calculus, on innate chemical and elastic gradients within the diseased cementum-dentin complex in comparison to a healthy complex, both of which are fundamental parameters to load-bearing tissues, will be discussed. Complementary techniques for mapping changes in physicochemical properties as a result of disease, included micro-X-ray computed tomography, microprobe micro X-ray fluorescence imaging, transmission electron and atomic force microscopy (TEM, AFM) techniques, and AFM-based nanoindentation. Results demonstrated primary effects as derivatives of ectopic mineralization within the diseased fibrous joint. Ectopic mineralization with no cementum resorption, but altered cementum physicochemical properties with increasing X-ray attenuation, exhibited stratified concretion with increasing X-ray fluorescence counts of calcium and phosphorus elements in the extracellular matrix. These were correlated to decreased hygroscopicity, indenter displacement, and apparent strain relieving characteristics. Disease progression identified as concretion through the periodontal ligament (PDL)-cementum enthesis and sometimes the originally hygroscopic cementum-dentin junction, resulted in a significantly increased indentation elastic modulus (3.16±1.19 GPa) and a shift toward a discontinuous interface compared to healthy conditions (1.54±0.83 GPa) (Student’s t-test, p<0.05). The observed primary effects could result in secondary downstream effects, such as compromised mechanobiology at the

  7. Gradual meiosis-to-mitosis transition in the early mouse embryo.

    PubMed

    Courtois, Aurélien; Hiiragi, Takashi

    2012-01-01

    The transition from meiosis to mitosis is a fundamental process to guarantee the successful development of the embryo. In the mouse, the transition includes extensive reorganisation of the division machinery, centrosome establishment and changes in spindle proprieties and characteristic. Recent findings indicate that this transition is gradual and lasts until the late blastocyst stage. In-depth knowledge of the mechanisms underlying the transition would provide new insight into de novo centrosome formation and regulation of spindle size and proprieties. Here, we review recent advances in the understanding of acentrosomal spindle formation, centriole establishment and the meiosis-to-mitosis transition in the mouse pre-implantation embryo.

  8. [Process of meiosis in interspecific hybrid F1 Lycopersicon esculentum Mill. x Lycopersicon chilense Dun].

    PubMed

    Montvid, P Iu; Samovol, O P; Miroshnychenko, V P

    2011-01-01

    The investigation concerns meiosis behaviour in embryo-culture-obtained Lycopersicon esculentum Mill. (mutant seedline Mo 638) x L. chilense Dun. F1 hybrid and its parental forms. It was determined that chiasma frequency decreased while univalent and meiotic disorder frequencies increased in F1 plants in comparison with parents forms. Univalent number and the percent of main disorders lowered with bud tier increasing. The conclusion was made about meiosis regularity connection with the influence of environment factors and heterozygous genotype of F1 plants Lycopersicon esculentum x L. chilense.

  9. Fission yeast APC/C activators Slp1 and Fzr1 sequentially trigger two consecutive nuclear divisions during meiosis.

    PubMed

    Chikashige, Yuji; Yamane, Miho; Okamasa, Kasumi; Osakada, Hiroko; Tsutsumi, Chihiro; Nagahama, Yuki; Fukuta, Noriko; Haraguchi, Tokuko; Hiraoka, Yasushi

    2017-02-28

    In meiosis, two rounds of nuclear division occur consecutively without DNA replication between the divisions. We isolated a fission yeast mutant in which the nucleus divides only once to generate two spores, as opposed to four, in meiosis. In this mutant, we found that the initiation codon of the slp1(+) gene is converted to ATA, producing a reduced amount of Slp1. As a member of the Fizzy family of APC/C activators, Slp1 is essential for vegetative growth; however, the mutant allele shows a phenotype only in meiosis. Slp1 insufficiency delays degradation of maturation-promoting factor (MPF) at the first meiotic division, and another APC/C activator, Fzr1, which acts late in meiosis, terminates meiosis immediately after the delayed first division to produce two viable spores. This article is protected by copyright. All rights reserved.

  10. Monopolin subunit Csm1 associates with MIND complex to establish monopolar attachment of sister kinetochores at meiosis I.

    PubMed

    Sarkar, Sourav; Shenoy, Rajesh T; Dalgaard, Jacob Z; Newnham, Louise; Hoffmann, Eva; Millar, Jonathan B A; Arumugam, Prakash

    2013-01-01

    Sexually reproducing organisms halve their cellular ploidy during gametogenesis by undergoing a specialized form of cell division known as meiosis. During meiosis, a single round of DNA replication is followed by two rounds of nuclear divisions (referred to as meiosis I and II). While sister kinetochores bind to microtubules emanating from opposite spindle poles during mitosis, they bind to microtubules originating from the same spindle pole during meiosis I. This phenomenon is referred to as mono-orientation and is essential for setting up the reductional mode of chromosome segregation during meiosis I. In budding yeast, mono-orientation depends on a four component protein complex referred to as monopolin which consists of two nucleolar proteins Csm1 and Lrs4, meiosis-specific protein Mam1 of unknown function and casein kinase Hrr25. Monopolin complex binds to kinetochores during meiosis I and prevents bipolar attachments. Although monopolin associates with kinetochores during meiosis I, its binding site(s) on the kinetochore is not known and its mechanism of action has not been established. By carrying out an imaging-based screen we have found that the MIND complex, a component of the central kinetochore, is required for monopolin association with kinetochores during meiosis. Furthermore, we demonstrate that interaction of monopolin subunit Csm1 with the N-terminal domain of MIND complex subunit Dsn1, is essential for both the association of monopolin with kinetochores and for monopolar attachment of sister kinetochores during meiosis I. As such this provides the first functional evidence for a monopolin-binding site at the kinetochore.

  11. A Novel Low-Molecular-Weight Compound Enhances Ectopic Bone Formation and Fracture Repair

    PubMed Central

    Wong, Eugene; Sangadala, Sreedhara; Boden, Scott D.; Yoshioka, Katsuhito; Hutton, William C.; Oliver, Colleen; Titus, Louisa

    2013-01-01

    Background: Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) is expensive and may cause local side effects. A small synthetic molecule, SVAK-12, has recently been shown in vitro to potentiate rhBMP-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype. The aims of this study were to test the ability of SVAK-12 to enhance bone formation in a rodent ectopic model and to test whether a single percutaneous injection of SVAK-12 can accelerate callus formation in a rodent femoral fracture model. Methods: Collagen disks with rhBMP-2 alone or with rhBMP-2 and SVAK-12 were implanted in a standard athymic rat chest ectopic model, and radiographic analysis was performed at four weeks. In a second set of rats (Sprague-Dawley), SVAK-12 was percutaneously injected into the site of a closed femoral fracture. The fractures were analyzed radiographically and biomechanically (with torsional testing) five weeks after surgery. Results: In the ectopic model, there was dose-dependent enhancement of rhBMP-2 activity with use of SVAK-12 at doses of 100 to 500 μg. In the fracture model, the SVAK-12-treated group had significantly higher radiographic healing scores than the untreated group (p = 0.028). Biomechanical testing revealed that the fractured femora in the 200 to 250-μg SVAK-12 group were 43% stronger (p = 0.008) and 93% stiffer (p = 0.014) than those in the control group. In summary, at five weeks the femoral fracture group injected with SVAK-12 showed significantly improved radiographic and biomechanical evidence of healing compared with the controls. Conclusions: A single local dose of a low-molecular-weight compound, SVAK-12, enhanced bone-healing in the presence of low-dose exogenous rhBMP-2 (in the ectopic model) and endogenous rhBMPs (in the femoral fracture model). Clinical Relevance: This study demonstrates that rhBMP-2 responsiveness can be enhanced by a novel small molecule, SVAK-12. Local application of anabolic small molecules has

  12. Uncommon Implantation Sites of Ectopic Pregnancy: Thinking beyond the Complex Adnexal Mass.

    PubMed

    Chukus, Anjeza; Tirada, Nikki; Restrepo, Ricardo; Reddy, Neelima I

    2015-01-01

    Ectopic pregnancy occurs when implantation of the blastocyst takes place in a site other than the endometrium of the uterine cavity. Uncommon implantation sites of ectopic pregnancy include the cervix, interstitial segment of the fallopian tube, scar from a prior cesarean delivery, uterine myometrium, ovary, and peritoneal cavity. Heterotopic and twin ectopic pregnancies are other rare manifestations. Ultrasonography (US) plays a central role in diagnosis of uncommon ectopic pregnancies. US features of an interstitial ectopic pregnancy include an echogenic interstitial line and abnormal bulging of the myometrial contour. A gestational sac that is located below the internal os of the cervix and that contains an embryo with a fetal heartbeat is indicative of a cervical ectopic pregnancy. In a cesarean scar ectopic pregnancy, the gestational sac is implanted in the anterior lower uterine segment at the site of the cesarean scar, with thinning of the myometrium seen anterior to the gestational sac. An intramural gestational sac implants in the uterine myometrium, separate from the uterine cavity and fallopian tubes. In an ovarian ectopic pregnancy, a gestational sac with a thick hyperechoic circumferential rim is located in or on the ovarian parenchyma. An intraperitoneal gestational sac is present in an abdominal ectopic pregnancy. Intra- and extrauterine gestational sacs are seen in a heterotopic pregnancy. Two adnexal heartbeats suggest a live twin ectopic pregnancy. Recognition of the specific US features will help radiologists diagnose these uncommon types of ectopic pregnancy.

  13. Clones of ectopic stem cells in the regeneration of muscle defects in vivo.

    PubMed

    Yang, Rujing; Chen, Mo; Lee, Chang Hun; Yoon, Richard; Lal, Shan; Mao, Jeremy J

    2010-10-20

    Little is known about whether clones of ectopic, non-muscle stem cells contribute to muscle regeneration. Stem/progenitor cells that are isolated for experimental research or therapeutics are typically heterogeneous. Non-myogenic lineages in a heterogeneous population conceptually may compromise tissue repair. In this study, we discovered that clones of mononucleated stem cells of human tooth pulp fused into multinucleated myotubes that robustly expressed myosin heavy chain in vitro with or without co-culture with mouse skeletal myoblasts (C2C12 cells). Cloned cells were sustainably Oct4+, Nanog+ and Stro1+. The fusion indices of myogenic clones were approximately 16-17 folds greater than their parent, heterogeneous stem cells. Upon infusion into cardio-toxin induced tibialis anterior muscle defects, undifferentiated clonal progenies not only engrafted and colonized host muscle, but also expressed human dystrophin and myosin heavy chain more efficaciously than their parent heterogeneous stem cell populations. Strikingly, clonal progenies yielded ∼9 times more human myosin heavy chain mRNA in regenerating muscles than those infused with their parent, heterogeneous stem cells. The number of human dystrophin positive cells in regenerating muscles infused with clonal progenies was more than ∼3 times greater than muscles infused with heterogeneous stem cells from which clonal progenies were derived. These findings suggest the therapeutic potential of ectopic myogenic clones in muscle regeneration.

  14. Mutation of the rice gene PAIR3 results in lack of bivalent formation in meiosis.

    PubMed

    Yuan, Wenya; Li, Xingwang; Chang, Yuxiao; Wen, Ruoyu; Chen, Guoxing; Zhang, Qifa; Wu, Changyin

    2009-07-01

    Meiosis is essential for eukaryotic sexual reproduction and important for genetic diversity among individuals. Although a number of genes regulating homologous chromosome pairing and synapsis have been identified in the plant kingdom, their molecular basis remains poorly understood. In this study, we identified a novel gene, PAIR3 (HOMOLOGOUS PAIRING ABERRATION IN RICE MEIOSIS 3), required for homologous chromosome pairing and synapsis in rice. Two independent alleles, designated pair3-1 and pair3-2, were identified in our T-DNA insertional mutant library which could not form bivalents due to failure of homologous chromosome pairing and synapsis at diakinesis, resulting in sterility in both male and female gametes. Suppression of PAIR3 by RNAi produced similar results to the T-DNA insertion lines. PAIR3 encodes a protein that contains putative coiled-coil motifs, but does not have any close homologs in other organisms. PAIR3 is preferentially expressed in reproductive organs, especially in pollen mother cells and the ovule tissues during meiosis. Our results suggest that PAIR3 plays a crucial role in homologous chromosome pairing and synapsis in meiosis.

  15. Virtual Nuclear Envelope Breakdown and Its Regulators in Fission Yeast Meiosis.

    PubMed

    Asakawa, Haruhiko; Yang, Hui-Ju; Hiraoka, Yasushi; Haraguchi, Tokuko

    2016-01-01

    Ran, a small GTPase, is required for the spindle formation and nuclear envelope (NE) formation. After NE breakdown (NEBD) during mitosis in metazoan cells, the Ran-GTP gradient across the NE is lost and Ran-GTP becomes concentrated around chromatin, thus affecting the stability of microtubules and promoting the assembly of spindle microtubules and segregation of chromosomes. Mitosis in which chromosomes are segregated subsequent to NEBD is called "open mitosis." In contrast, many fungi undergo a process termed "closed mitosis" in which chromosome segregation and spindle formation occur without NEBD. Although the fission yeast Schizosaccharomyces pombe undergoes a closed mitosis, it exhibits a short period during meiosis (anaphase of the second meiosis; called "anaphase II") when nuclear and cytoplasmic proteins are mixed in the presence of intact NE and nuclear pore complexes (NPC). This "virtual" nuclear envelope breakdown (vNEBD) involves changes in the localization of RanGAP1, an activator of Ran-GTP hydrolysis. Recently, Nup132, a component of the structural core Nup107-160 subcomplex of the NPC, has been shown to be involved in the maintenance of the nuclear cytoplasmic barrier in yeast meiosis. In this review, we highlight the possible roles of RanGAP1 and Nup132 in vNEBD and discuss the biological significance of vNEBD in S. pombe meiosis.

  16. Dance of the Chromosomes: A Kinetic Learning Approach to Mitosis and Meiosis

    ERIC Educational Resources Information Center

    Kreiser, Brian; Hairston, Rosalina

    2007-01-01

    Understanding mitosis and meiosis is fundamental to understanding the basics of Mendelian inheritance, yet many students find these concepts challenging or confusing. Here we present a visually and physically stimulating activity using minimal supplies to supplement traditional instruction in order to engage the students and facilitate…

  17. E-type cyclins modulate telomere integrity in mammalian male meiosis.

    PubMed

    Manterola, Marcia; Sicinski, Piotr; Wolgemuth, Debra J

    2016-06-01

    We have shown that E-type cyclins are key regulators of mammalian male meiosis. Depletion of cyclin E2 reduced fertility in male mice due to meiotic defects, involving abnormal pairing and synapsis, unrepaired DNA, and loss of telomere structure. These defects were exacerbated by additional loss of cyclin E1, and complete absence of both E-type cyclins produces a meiotic catastrophe. Here, we investigated the involvement of E-type cyclins in maintaining telomere integrity in male meiosis. Spermatocytes lacking cyclin E2 and one E1 allele (E1+/-E2-/-) displayed a high rate of telomere abnormalities but can progress to pachytene and diplotene stages. We show that their telomeres exhibited an aberrant DNA damage repair response during pachynema and that the shelterin complex proteins TRF2 and RAP2 were significantly decreased in the proximal telomeres. Moreover, the insufficient level of these proteins correlated with an increase of γ-H2AX foci in the affected telomeres and resulted in telomere associations involving TRF1 and telomere detachment in later prophase-I stages. These results suggest that E-type cyclins are key modulators of telomere integrity during meiosis by, at least in part, maintaining the balance of shelterin complex proteins, and uncover a novel role of E-type cyclins in regulating chromosome structure during male meiosis.

  18. Tomato Male sterile 1035 is essential for pollen development and meiosis in anthers.

    PubMed

    Jeong, Hee-Jin; Kang, Jin-Ho; Zhao, Meiai; Kwon, Jin-Kyung; Choi, Hak-Soon; Bae, Jung Hwan; Lee, Hyun-Ah; Joung, Young-Hee; Choi, Doil; Kang, Byoung-Cheorl

    2014-12-01

    Male fertility in flowering plants depends on proper cellular differentiation in anthers. Meiosis and tapetum development are particularly important processes in pollen production. In this study, we showed that the tomato male sterile (ms10(35)) mutant of cultivated tomato (Solanum lycopersicum) exhibited dysfunctional meiosis and an abnormal tapetum during anther development, resulting in no pollen production. We demonstrated that Ms10(35) encodes a basic helix-loop-helix transcription factor that is specifically expressed in meiocyte and tapetal tissue from pre-meiotic to tetrad stages. Transgenic expression of the Ms10(35) gene from its native promoter complemented the male sterility of the ms10(35) mutant. In addition, RNA-sequencing-based transcriptome analysis revealed that Ms10(35) regulates 246 genes involved in anther development processes such as meiosis, tapetum development, cell-wall degradation, pollen wall formation, transport, and lipid metabolism. Our results indicate that Ms10(35) plays key roles in regulating both meiosis and programmed cell death of the tapetum during microsporogenesis.

  19. Meiosis Drives Extraordinary Genome Plasticity in the Haploid Fungal Plant Pathogen Mycosphaerella Graminicola

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Meiosis in the plant-pathogenic fungus Mycosphaerella graminicola results in eight ascospores due to a mitotic division following the two meiotic divisions. The transient diploid phase allows for recombination among homologous chromosomes. However, some chromosomes of M. graminicola lack homologs an...

  20. Students' Meaningful Learning Orientation and Their Meaningful Understandings of Meiosis and Genetics.

    ERIC Educational Resources Information Center

    Cavallo, Ann Liberatore

    This 1-week study explored the extent to which high school students (n=140) acquired meaningful understanding of selected biological topics (meiosis and the Punnett square method) and the relationship between these topics. This study: (1) examined "mental modeling" as a technique for measuring students' meaningful understanding of the…

  1. Creating a Double-Spring Model to Teach Chromosome Movement during Mitosis & Meiosis

    ERIC Educational Resources Information Center

    Luo, Peigao

    2012-01-01

    The comprehension of chromosome movement during mitosis and meiosis is essential for understanding genetic transmission, but students often find this process difficult to grasp in a classroom setting. I propose a "double-spring model" that incorporates a physical demonstration and can be used as a teaching tool to help students understand this…

  2. Analysis of chromosome segregation during mammalian meiosis using combined immunofluorescence and fluorescence in situ hubridization

    SciTech Connect

    Hunt, P.A.; Embury, P.B.; Mroz, K.M.

    1994-09-01

    Meiotic non-disjunction is thought to occur in 10-20% of all human oocytes, making this the most common genetic abnormality in our species. Aberrant recombination has been implicated in the genesis of these errors; however, direct studies of the meiotic process have been hampered by the lack of material and appropriate technology. We have developed a technique for the evaluation of meiosis in intact mammalian oocytes that combines immunofluorescence and fluorescence in situ hybridization (FISH). This allows for simultaneous, 3-dimensional visualization of the meiotic spindle, the alignment of the chromosomes on the spindle, and the placement of specific chromosomes. We have used this technology to follow meiotic progression in oocytes from XO female mice to evaluate the behavior of an unsynapsed chromosome during mammalian meiosis. Perturbations in chromosome behavior are evident early in meiosis: during the formation of the first meiotic spindle, the univalent X chromosome is properly positioned. With the onset of anaphase, the single X chromosome most commonly segregates as an intact chromosome, although equational segregation of the X chromatids is seen in a significant minority (approximately 20%) of oocytes. These observations demonstrate that failure of pairing/recombination can result in segregation of sister chromatids at meiosis I. This has obvious implications for human non-disjunction, much of which is thought to be due to recombination deficiencies; accordingly, we are now extending our studies to include analyses of human oocytes.

  3. NDT80, a meiosis-specific gene required for exit from pachytene in Saccharomyces cerevisiae

    SciTech Connect

    Xu, Liuzhong; Ajimura, M.; Padmore, R.; Klein, C.; Kleckner, N.

    1995-12-01

    This report describes the identification of a new meiosis-specific gene of Saccharomyces cerevisiae called NDT80. DNA cloning and molecular analysis revealed that the NDT80 gene maps on the right arm of chromosome 8 and is transcribed during middle meiotic prophase. 82 refs., 6 figs., 3 tabs.

  4. Cell type-specific translational repression of Cyclin B during meiosis in males.

    PubMed

    Baker, Catherine Craig; Gim, Byung Soo; Fuller, Margaret T

    2015-10-01

    The unique cell cycle dynamics of meiosis are controlled by layers of regulation imposed on core mitotic cell cycle machinery components by the program of germ cell development. Although the mechanisms that regulate Cdk1/Cyclin B activity in meiosis in oocytes have been well studied, little is known about the trans-acting factors responsible for developmental control of these factors in male gametogenesis. During meiotic prophase in Drosophila males, transcript for the core cell cycle protein Cyclin B1 (CycB) is expressed in spermatocytes, but the protein does not accumulate in spermatocytes until just before the meiotic divisions. Here, we show that two interacting proteins, Rbp4 and Fest, expressed at the onset of spermatocyte differentiation under control of the developmental program of male gametogenesis, function to direct cell type- and stage-specific repression of translation of the core G2/M cell cycle component cycB during the specialized cell cycle of male meiosis. Binding of Fest to Rbp4 requires a 31-amino acid region within Rbp4. Rbp4 and Fest are required for translational repression of cycB in immature spermatocytes, with Rbp4 binding sequences in a cell type-specific shortened form of the cycB 3' UTR. Finally, we show that Fest is required for proper execution of meiosis I.

  5. Silencing of meiosis-critical genes for engineering male sterility in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Engineering sterile traits in plants through the tissue-specific expression of a cytotoxic gene provides an effective way for containing transgene flow; however, the microbial origin of cytotoxic genes has raised concerns. In an attempt to develop a safe alternative, we have chosen the meiosis-crit...

  6. Genome-Wide Crossover Distribution in Arabidopsis thaliana Meiosis Reveals Sex-Specific Patterns along Chromosomes

    PubMed Central

    Drouaud, Jan; Pereira, Lucie; Martin, Olivier C.; Mézard, Christine

    2011-01-01

    In most species, crossovers (COs) are essential for the accurate segregation of homologous chromosomes at the first meiotic division. Their number and location are tightly regulated. Here, we report a detailed, genome-wide characterization of the rate and localization of COs in Arabidopsis thaliana, in male and female meiosis. We observed dramatic differences between male and female meiosis which included: (i) genetic map length; 575 cM versus 332 cM respectively; (ii) CO distribution patterns: male CO rates were very high at both ends of each chromosome, whereas female CO rates were very low; (iii) correlations between CO rates and various chromosome features: female CO rates correlated strongly and negatively with GC content and gene density but positively with transposable elements (TEs) density, whereas male CO rates correlated positively with the CpG ratio. However, except for CpG, the correlations could be explained by the unequal repartition of these sequences along the Arabidopsis chromosome. For both male and female meiosis, the number of COs per chromosome correlates with chromosome size expressed either in base pairs or as synaptonemal complex length. Finally, we show that interference modulates the CO distribution both in male and female meiosis. PMID:22072983

  7. The PP2A inhibitor I2PP2A is essential for sister chromatid segregation in oocyte meiosis II.

    PubMed

    Chambon, Jean-Philippe; Touati, Sandra A; Berneau, Stéphane; Cladière, Damien; Hebras, Céline; Groeme, Rachel; McDougall, Alex; Wassmann, Katja

    2013-03-18

    Haploid gametes are generated through two consecutive meiotic divisions, with the segregation of chromosome pairs in meiosis I and sister chromatids in meiosis II. Separase-mediated stepwise removal of cohesion, first from chromosome arms and later from the centromere region, is a prerequisite for maintaining sister chromatids together until their separation in meiosis II [1]. In all model organisms, centromeric cohesin is protected from separase-dependent removal in meiosis I through the activity of PP2A-B56 phosphatase, which is recruited to centromeres by shugoshin/MEI-S332 (Sgo) [2-5]. How this protection of centromeric cohesin is removed in meiosis II is not entirely clear; we find that all the PP2A subunits remain colocalized with the cohesin subunit Rec8 at the centromere of metaphase II chromosomes. Here, we show that sister chromatid separation in oocytes depends on a PP2A inhibitor, namely I2PP2A. I2PP2A colocalizes with the PP2A enzyme at centromeres at metaphase II, independently of bipolar attachment. When I2PP2A is depleted, sister chromatids fail to segregate during meiosis II. Our findings demonstrate that in oocytes I2PP2A is essential for faithful sister chromatid segregation by mediating deprotection of centromeric cohesin in meiosis II.

  8. Ectopic pregnancies: rising incidence rates in Northern California.

    PubMed Central

    Shiono, P H; Harlap, S; Pellegrin, F

    1982-01-01

    In a population of about 300,000 Northern California women aged 15--44, the age-adjusted incidence of ectopic pregnancy rose from 55.5 to 84.2/100,000 women, 1972--1978. The ratio of ectopics to 1,000 deliveries-plus-spontaneous abortions rose from 9.4 to 14.8. The change occurred mainly in women under age 30, and was observed in seven of the eight hospitals in the area. There was no alteration in the frequency of hospitalized pelvic inflammatory disease (PID); salpingitis decreased over the years studied; and tubal sterilization events remained constant at around 0.9 per cent per year of women aged 15--44. PMID:7055319

  9. Upper Tract Urothelial Carcinoma in Ectopic Pelvic Kidney.

    PubMed

    Halalsheh, Omar; Ghawanmeh, Hamzeh M; Alshammari, Ahmed; Sahawneh, Firas; Al-Okour, Radwan; Al Karasneh, Anas; Ghawanmeh, Malik

    2017-02-01

    Upper tract urothelial carcinoma (UC) is an uncommon tumor. Ectopic kidney is also a rare entity. The combination of these two conditions is very rare. A 49-year-old male complained of right flank pain with hematuria. On CT scan he was found to have a malrotated right kidney with soft tissue seen in the upper calyceal group and a normal left kidney. Diagnostic cystoscopy was unremarkable. Radical nephroureterectomy with bladder cuff excision was performed. Pathology report revealed low grade urothelial carcinoma. Patient's symptoms disappeared postoperatively. Follow up showed no recurrence during the first two years in the bladder and upper tract in the contralateral kidney. Isolated UC of ectopic kidney is rare disease three cases were reported in literature. Although treatment of this tumor can be challenging due to its complex blood supply and position inside the pelvis, treatment strategy is still similar as for orthotopic kidneys.

  10. Mifepristone Improves Octreotide Efficacy in Resistant Ectopic Cushing's Syndrome

    PubMed Central

    Moraitis, Andreas G.; Auchus, Richard J.

    2016-01-01

    A 30-year-old Caucasian man presented with severe Cushing's syndrome (CS) resulting from ectopic adrenocorticotropin syndrome (EAS) from a metastatic pancreatic neuroendocrine tumor. The patient remained hypercortisolemic despite treatment with steroidogenesis inhibitors, chemotherapy, and octreotide long-acting release (LAR) and was enrolled in a 24-week, phase 3 clinical trial of mifepristone for inoperable hypercortisolemia. After mifepristone was added to ongoing octreotide LAR treatment, EAS symptoms essentially resolved. Cortisol decreased dramatically, despite mifepristone's competitive glucocorticoid receptor antagonist effects. The clinical and biochemical effects reversed upon mifepristone discontinuation despite the continued use of octreotide LAR therapy. Substantial improvement in octreotide LAR efficacy with mifepristone use was noted in this patient with ectopic CS, consistent with upregulation of somatostatin receptors previously downregulated by hypercortisolemia. PMID:26989527

  11. Management of Class II malocclusion with ectopic maxillary canines

    PubMed Central

    Mascarenhas, Rohan; Parveen, Shahista; Ansari, Tariq Aziz

    2015-01-01

    Correction of Class II relationship, deep bite and ectopically erupting canines is an orthodontic challenge for the clinician. A 13-year-old male patient presented with Class II malocclusion, ectopically erupting canines, and cross bite with maxillary left lateral incisor. He was treated with a combination of Headgear, Forsus™ fatigue resistant device [FFRD] with fixed mechanotherapy for the management of space deficiency and correction of Class II malocclusions. Headgear was used to distalize upper first molars and also to prevent further downward and forward growth of the maxilla. Then Forsus™ FFRD was used for the advancement of the mandible. The molar and canine relationship were corrected from a Class II to a Class I. The objectives were to establish good occlusion and enable eruption of unerupted canines. All these objectives were achieved and remained stable. PMID:26097371

  12. The fission yeast MTREC and EJC orthologs ensure the maturation of meiotic transcripts during meiosis.

    PubMed

    Marayati, Bahjat Fadi; Hoskins, Victoria; Boger, Robert W; Tucker, James F; Fishman, Emily S; Bray, Andrew S; Zhang, Ke

    2016-09-01

    Meiosis is a highly regulated process by which genetic information is transmitted through sexual reproduction. It encompasses unique mechanisms that do not occur in vegetative cells, producing a distinct, well-regulated meiotic transcriptome. During vegetative growth, many meiotic genes are constitutively transcribed, but most of the resulting mRNAs are rapidly eliminated by the Mmi1-MTREC (Mtl1-Red1 core) complex. While Mmi1-MTREC targets premature meiotic RNAs for degradation by the nuclear 3'-5' exoribonuclease exosome during mitotic growth, its role in meiotic gene expression during meiosis is not known. Here, we report that Red5, an essential MTREC component, interacts with pFal1, an ortholog of eukaryotic translation initiation factor eIF4aIII in the fission yeast Schizosaccharomyces pombe In mammals, together with MAGO (Mnh1), Rnps1, and Y14, elF4AIII (pFal1) forms the core of the exon junction complex (EJC), which is essential for transcriptional surveillance and localization of mature mRNAs. In fission yeast, two EJC orthologs, pFal1 and Mnh1, are functionally connected with MTREC, specifically in the process of meiotic gene expression during meiosis. Although pFal1 interacts with Mnh1, Y14, and Rnps1, its association with Mnh1 is not disrupted upon loss of Y14 or Rnps1. Mutations of Red1, Red5, pFal1, or Mnh1 produce severe meiotic defects; the abundance of meiotic transcripts during meiosis decreases; and mRNA maturation processes such as splicing are impaired. Since studying meiosis in mammalian germline cells is difficult, our findings in fission yeast may help to define the general mechanisms involved in accurate meiotic gene expression in higher eukaryotes.

  13. The fission yeast MTREC and EJC orthologs ensure the maturation of meiotic transcripts during meiosis

    PubMed Central

    Marayati, Bahjat Fadi; Hoskins, Victoria; Boger, Robert W.; Tucker, James F.; Fishman, Emily S.; Bray, Andrew S.; Zhang, Ke

    2016-01-01

    Meiosis is a highly regulated process by which genetic information is transmitted through sexual reproduction. It encompasses unique mechanisms that do not occur in vegetative cells, producing a distinct, well-regulated meiotic transcriptome. During vegetative growth, many meiotic genes are constitutively transcribed, but most of the resulting mRNAs are rapidly eliminated by the Mmi1-MTREC (Mtl1-Red1 core) complex. While Mmi1-MTREC targets premature meiotic RNAs for degradation by the nuclear 3′–5′ exoribonuclease exosome during mitotic growth, its role in meiotic gene expression during meiosis is not known. Here, we report that Red5, an essential MTREC component, interacts with pFal1, an ortholog of eukaryotic translation initiation factor eIF4aIII in the fission yeast Schizosaccharomyces pombe. In mammals, together with MAGO (Mnh1), Rnps1, and Y14, elF4AIII (pFal1) forms the core of the exon junction complex (EJC), which is essential for transcriptional surveillance and localization of mature mRNAs. In fission yeast, two EJC orthologs, pFal1 and Mnh1, are functionally connected with MTREC, specifically in the process of meiotic gene expression during meiosis. Although pFal1 interacts with Mnh1, Y14, and Rnps1, its association with Mnh1 is not disrupted upon loss of Y14 or Rnps1. Mutations of Red1, Red5, pFal1, or Mnh1 produce severe meiotic defects; the abundance of meiotic transcripts during meiosis decreases; and mRNA maturation processes such as splicing are impaired. Since studying meiosis in mammalian germline cells is difficult, our findings in fission yeast may help to define the general mechanisms involved in accurate meiotic gene expression in higher eukaryotes. PMID:27365210

  14. AtMND1 is required for homologous pairing during meiosis in Arabidopsis

    PubMed Central

    Panoli, Aneesh P; Ravi, Maruthachalam; Sebastian, Jose; Nishal, Bindu; Reddy, Thamalampudi V; Marimuthu, Mohan PA; Subbiah, Veeraputhiran; Vijaybhaskar, Virupapuram; Siddiqi, Imran

    2006-01-01

    Background Pairing of homologous chromosomes at meiosis is an important requirement for recombination and balanced chromosome segregation among the products of meiotic division. Recombination is initiated by double strand breaks (DSBs) made by Spo11 followed by interaction of DSB sites with a homologous chromosome. This interaction requires the strand exchange proteins Rad51 and Dmc1 that bind to single stranded regions created by resection of ends at the site of DSBs and promote interactions with uncut DNA on the homologous partner. Recombination is also considered to be dependent on factors that stabilize interactions between homologous chromosomes. In budding yeast Hop2 and Mnd1 act as a complex to promote homologous pairing and recombination in conjunction with Rad51 and Dmc1. Results We have analyzed the function of the Arabidopsis orthologue of the budding yeast MND1 gene (AtMND1). Loss of AtMND1 did not affect normal vegetative development but caused fragmentation and missegregation of chromosomes in male and female meiosis, formation of inviable gametes, and sterility. Analysis of the Atmnd1 Atspo11-1 double mutant indicated that chromosome fragmentation in Atmnd1 was suppressed by loss of Atspo11-1. Fluorescence in situ hybridization (FISH) analysis showed that homologous pairing failed to occur and homologues remained apart throughout meiosis. AtMND1 showed strong expression in meiocytes as revealed by RNA in situs. Conclusion We conclude that AtMND1 is required for homologous pairing and is likely to play a role in the repair of DNA double strand breaks during meiosis in Arabidopsis, thus showing conservation of function with that of MND1 during meiosis in yeast. PMID:16872528

  15. Notch pathway regulates female germ cell meiosis progression and early oogenesis events in fetal mouse.

    PubMed

    Feng, Yan-Min; Liang, Gui-Jin; Pan, Bo; Qin, Xun-Si; Zhang, Xi-Feng; Chen, Chun-Lei; Li, Lan; Cheng, Shun-Feng; De Felici, Massimo; Shen, Wei

    2014-01-01

    A critical process of early oogenesis is the entry of mitotic oogonia into meiosis, a cell cycle switch regulated by a complex gene regulatory network. Although Notch pathway is involved in numerous important aspects of oogenesis in invertebrate species, whether it plays roles in early oogenesis events in mammals is unknown. Therefore, the rationale of the present study was to investigate the roles of Notch signaling in crucial processes of early oogenesis, such as meiosis entry and early oocyte growth. Notch receptors and ligands were localized in mouse embryonic female gonads and 2 Notch inhibitors, namely DAPT and L-685,458, were used to attenuate its signaling in an in vitro culture system of ovarian tissues from 12.5 days post coitum (dpc) fetus. The results demonstrated that the expression of Stra8, a master gene for germ cell meiosis, and its stimulation by retinoic acid (RA) were reduced after suppression of Notch signaling, and the other meiotic genes, Dazl, Dmc1, and Rec8, were abolished or markedly decreased. Furthermore, RNAi of Notch1 also markedly inhibited the expression of Stra8 and SCP3 in cultured female germ cells. The increased methylation status of CpG islands within the Stra8 promoter of the oocytes was observed in the presence of DAPT, indicating that Notch signaling is probably necessary for maintaining the epigenetic state of this gene in a way suitable for RA stimulation. Furthermore, in the presence of Notch inhibitors, progression of oocytes through meiosis I was markedly delayed. At later culture periods, the rate of oocyte growth was decreased, which impaired subsequent primordial follicle assembly in cultured ovarian tissues. Taken together, these results suggested new roles of the Notch signaling pathway in female germ cell meiosis progression and early oogenesis events in mammals.

  16. Interorganelle interactions and inheritance patterns of nuclei and vacuoles in budding yeast meiosis.

    PubMed

    Tsai, I-Ting; Lin, Jyun-Liang; Chiang, Yi-Hsuan; Chuang, Yu-Chien; Liang, Shu-Shan; Chuang, Chi-Ning; Huang, Tzyy-Nan; Wang, Ting-Fang

    2014-02-01

    Many of the mechanisms by which organelles are inherited by spores during meiosis are not well understood. Dramatic chromosome motion and bouquet formation are evolutionarily conserved characteristics of meiotic chromosomes. The budding yeast bouquet genes (NDJ1, MPS3, CSM4) mediate these movements via telomere attachment to the nuclear envelope (NE). Here, we report that during meiosis the NE is in direct contact with vacuoles via nucleus-vacuole junctions (NVJs). We show that in meiosis NVJs are assembled through the interaction of the outer NE-protein Nvj1 and the vacuolar membrane protein Vac8. Notably, NVJs function as diffusion barriers that exclude the nuclear pore complexes, the bouquet protein Mps3 and NE-tethered telomeres from the outer nuclear membrane and nuclear ER, resulting in distorted NEs during early meiosis. An increase in NVJ area resulting from Nvj1-GFP overexpression produced a moderate bouquet mutant-like phenotype in wild-type cells. NVJs, as the vacuolar contact sites of the nucleus, were found to undergo scission alongside the NE during meiotic nuclear division. The zygotic NE and NVJs were partly segregated into 4 spores. Lastly, new NVJs were also revealed to be synthesized de novo to rejoin the zygotic NE with the newly synthesized vacuoles in the mature spores. In conclusion, our results revealed that budding yeast nuclei and vacuoles exhibit dynamic interorganelle interactions and different inheritance patterns in meiosis, and also suggested that nvj1Δ mutant cells may be useful to resolve the technical challenges pertaining to the isolation of intact nuclei for the biochemical study of meiotic nuclear proteins.

  17. Hyponatremia in pulmonary TB: evidence of ectopic antidiuretic hormone production.

    PubMed

    Lee, Paul; Ho, Ken K Y

    2010-01-01

    Hyponatremia is among the most common biochemical abnormalities in hospital inpatients. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of several causes of hyponatremia, particularly in patients with pulmonary diseases. The mechanism of SIADH associated with pulmonary infection is, however, poorly understood. We report an unusual case of hyponatremia in a man with pulmonary TB and central diabetes insipidus with biochemical evidence of ectopic antidiuretic hormone production as a possible mechanism causing hyponatremia.

  18. Ectopic prolactinoma in the clivus: a case report.

    PubMed

    Narese, D; Virzì, V; Virzì, G; Narese, F; Sciortino, A; Culmone, G; Virzì, F; Maira, G

    2015-01-01

    We report the case of an ectopic pituitary adenoma in a 65-year-old man with an empty sella who initially presented with right ptosis and eyelid edema and headache. Neuroimaging studies revealed a large tumoral process at the height of the clivus, with partial destruction of surrounding bone structure. He underwent transphenoidal surgery and histopathologic examination, including immunohistochemical studies, revealed a prolactin-producing pituitary adenoma. A careful review of the literature was done.

  19. Fibroadenoma in axilla: another manifestation of ectopic breast.

    PubMed

    Tiwary, Satyendra K; Kumar, Puneet; Khanna, Ajay Kumar

    2015-04-26

    Fibroadenoma of an accessory breast is a rare disease. The clinical significance lies in the fact that a number of cystic, inflammatory, neoplastic diseases similar to those of a normal breast have been reported in accessory breasts as well. Vigilant self-assessment and complete clinical examination are always encouraged to detect earliest malignancy in the axilla. We report two cases of ectopic breast fibroadenoma with the relevant literature.

  20. Transcatheter Embolotherapy with N-Butyl Cyanoacrylate for Ectopic Varices

    SciTech Connect

    Choi, Jin Woo; Kim, Hyo-Cheol Jae, Hwan Jun Jung, Hyun-Seok; Hur, Saebeom; Lee, Myungsu; Chung, Jin Wook

    2015-04-15

    PurposeTo address technical feasibility and clinical outcome of transcatheter embolotherapy with N-butyl cyanoacrylate (NBCA) for bleeding ectopic varices.MethodsThe institutional review board approved this retrospective study and waived informed consent. From January 2004 to June 2013, a total of 12 consecutive patients received transcatheter embolotherapy using NBCA for bleeding ectopic varices in our institute. Clinical and radiologic features of the endovascular procedures were comprehensively reviewed.ResultsPreprocedural computed tomography images revealed ectopic varices in the jejunum (n = 7), stoma (n = 2), rectum (n = 2), and duodenum (n = 1). The 12 procedures consisted of solitary embolotherapy (n = 8) and embolotherapy with portal decompression (main portal vein stenting in 3, transjugular intrahepatic portosystemic shunt in 1). With regard to vascular access, percutaneous transhepatic access (n = 7), transsplenic access (n = 4), and transjugular intrahepatic portosystemic shunt tract (n = 1) were used. There was no failure in either the embolotherapy or the vascular accesses (technical success rate, 100 %). Two patients died within 1 month from the procedure from preexisting fatal medical conditions. Only one patient, with a large varix that had been partially embolized by using coils and NBCA, underwent rebleeding 5.5 months after the procedure. The patient was retreated with NBCA and did not undergo any bleeding afterward for a follow-up period of 2.5 months. The remaining nine patients did not experience rebleeding during the follow-up periods (range 1.5–33.2 months).ConclusionTranscatheter embolotherapy using NBCA can be a useful option for bleeding ectopic varices.

  1. Doppler findings in chronic ectopic pregnancy: case report.

    PubMed

    Abramov, Y; Nadjari, M; Shushan, A; Prus, D; Anteby, S O

    1997-05-01

    Chronic ectopic pregnancy is an uncommon form of tubal pregnancy manifested as a pelvic mass with minimal symptoms and a low or absent titer of human chorionic gonadotropin. For this reason, most of the reported cases have been diagnosed only after explorative laparotomy. The value of Doppler ultrasonography for preoperative diagnosis of this entity has not yet been established. We report on a 36-year-old patient who was admitted for intermittent right lower quadrant abdominal pain of 3 months' duration, and a right adnexal mass found on pelvic examination. On Doppler ultrasonography, a right complex adnexal mass was demonstrated, characterized by extensive external vascularization, aberrant vessels and arteriovenous shunting, but with no internal blood flow. Explorative laparotomy revealed a right tubal mass adherent to the omentum, and covered by numerous enlarged and tortuous blood vessels originating in the omentum. Pathological examination of the mass revealed a chronic ectopic pregnancy. The possible contribution of Doppler-specific characteristics for the diagnosis of chronic ectopic pregnancy is described and discussed.

  2. Laparoscopic tube-preserving surgical procedures for ectopic tubal pregnancy

    PubMed Central

    Lee, Dong Hee; Kim, Hwa Cheung; Seong, Seok Ju

    2016-01-01

    Objective To present our experience with laparoscopic tube-preserving surgery for ectopic tubal pregnancy and evaluate its feasibility and efficacy. Methods This was a prospective study of 57 consecutive patients with ectopic tubal pregnancies undergoing laparoscopic tube-preserving procedures including salpingotomy, salpingostomy, segmental resection and reanastomosis, and fimbrial milking. The outcome measures were treatment success rates and homolateral patency rates. Results Of the 57 surgical procedures, 55 (96.4%) were performed successfully without any additional intervention. The number of patients receiving salpingotomy, salpingostomy, segmental resection and reanastomosis, and fimbrial milking were 24 (42.1%), 25 (43.9%), 4 (7.0%), and 2 (3.5%), respectively. Two case was switched to salpingectomy because excessive bipolar coagulation was required to obtain hemostasis at the tubal bleeding bed. Over a mean β-human chorionic gonadotropin resolution time of 18.3±5.9 days, no persistent trophoblast or postoperative complications occurred. A tubal patency test using hysterosalpingography was performed in 15 cases at 3 months postoperatively. Among these, the homolateral tubal patency rate was 75% (11 of 15) and the contralateral patency rate was 80% (12 of 15). Conclusion Tube-preserving surgery is a feasible and safe treatment option for ectopic tubal pregnancy. However, considering that the optimal goal of tube-preserving surgical procedures is not the treatment success, some caution is warranted in interpreting results of this study. PMID:27896254

  3. Rates of ectopic pregnancy, sterility follow PID rise.

    PubMed

    1980-05-01

    500,000 cases of PID (pelvic inflammatory disease) are reported annually in the US, with 34,000 to 92,000 women becoming sterile as a consequence of the disease. In addition, the contraceptive methods women use during their exposure to PID-causing agents may directly affect their relative risk of developing PID, at an annual cost of $2.7 billion in health-care expenses. Another sequelae of PID is ectopic pregnancy. The STD epidemic years from 1965 to 1975 are projected to increase the rate of ectopic pregnancies to 50,000 a year, or one for every 60 live births before leveling off. By 1990, 1 out of 32 women will have had an ectopic pregnancy. Tubal occlusion can result in involuntary infertility. The National Survey of Family Growth estimates that the prevalence of infertile women aged 15 to 44 who are married and use no contraceptive method has increased in the past 2-1/2 years from 2.7% to 6.1%. These women number 142,000 annually and resort to nonsurgical sterilization, with PID as a major reason. Gonococcal PID accounts for 34,000 to 92,000 women becoming involuntarily sterile each year. However, over 80% of PID is nongonococcal PID, which is a worst disease. Chronic PID and infertility are found "more often in women who have had nongonococcal PID than in women who have had gonococcal PID." Etiologic organisms of PID include gonorrhea; E. coli, anaerobes and Chlamydia trachomatis.

  4. Pleomorphic adenoma of a deep orbital ectopic lacrimal gland.

    PubMed

    Misra, Somen; Bhandari, Akshay; Misra, Neeta; Gogri, Pratik; Mahajan, Shruti

    2016-10-01

    Ectopic lacrimal gland, being one of the choristomas, is comprised of lacrimal gland tissue outside the lacrimal gland fossa in the fronto-lateral part of the orbital roof. Ectopic lacrimal gland is a rare condition where the gland may be found in the orbit, eyelids, ocular adnexa or within the globe. Neoplastic transformation of such tissue may occur. A sixty-two-year old male patient presented with right eye proptosis and slight nasal displacement of the globe. Computerized tomography scan revealed a well-defined hypodense lesion of size 19 x 18 x 20 mm supero-lateral to lateral rectus muscle, with mild proptosis and thinning of the right lateral orbital wall. Excisional biopsy was performed through a lateral orbitotomy approach. A well circumscribed globular mass was removed from the right orbit, well behind the fossa for the lacrimal gland in the retrobulbar space. Histopathology was suggestive of pleomorphic adenoma of lacrimal gland. Pleomorphic adenoma is an epithelial tumor of the lacrimal gland which is extremely rare from an ectopic lacrimal gland and only few cases have been reported in literature till date.

  5. Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics

    PubMed Central

    Pozza, Carlotta; Graziadio, Chiara; Giannetta, Elisa; Lenzi, Andrea; Isidori, Andrea M.

    2012-01-01

    Cushing's syndrome (CS) is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing's disease, CD) or an ectopic source (ectopic ACTH secretion, EAS). The remaining causes (20%) are ACTH independent. As soon as the diagnosis is established, the therapeutic goal is the removal of the tumor. Whenever surgery is not curative, management of patients with CS requires a major effort to control hypercortisolemia and associated symptoms. A multidisciplinary approach that includes endocrinologists, neurosurgeons, oncologists, and radiotherapists should be adopted. This paper will focus on traditional and novel medical therapy for aggressive ACTH-dependent CS. Several drugs are able to reduce cortisol levels. Their mechanism of action involves blocking adrenal steroidogenesis (ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidate) or inhibiting the peripheral action of cortisol through blocking its receptors (mifepristone “RU-486”). Other drugs include centrally acting agents (dopamine agonists, somatostatin receptor agonists, retinoic acid, peroxisome proliferator-activated receptor γ “PPAR-γ” ligands) and novel chemotherapeutic agents (temozolomide and tyrosine kinase inhibitors) which have a significant activity against aggressive pituitary or ectopic tumors. PMID:22934113

  6. Multiple ectopic hepatocellular carcinomas arising in the abdominal cavity.

    PubMed

    Miyake, Toru; Hoshino, Seiichiro; Yoshida, Yoichiro; Aisu, Naoya; Tanimura, Syu; Hisano, Satoshi; Kuno, Nobuaki; Sohda, Tetsuro; Sakisaka, Shotaro; Yamashita, Yuichi

    2012-09-01

    Ectopic hepatocellular carcinoma (HCC) is a very rare clinical entity that is defined as HCC arising from extrahepatic liver tissue. This report presents a case of ectopic multiple HCC arising in the abdominal cavity. A 42-year-old otherwise healthy male presented with liver dysfunction at a general health checkup. Both HCV antibody and hepatitis B surface antigen were negative. Laboratory examination showed elevations in serum alpha-fetoprotein and PIVKA-II. Ultrasonography and computed tomography revealed multiple nodular lesions in the abdominal cavity with ascites without a possible primary tumor. Exploratory laparoscopy was performed, which revealed bloody ascites and multiple brown nodular tumors measuring approximately 10 mm in size that were disseminated on the perineum and mesentery. A postoperative PET-CT scan was performed but it did not reveal any evidence of a tumor in the liver. The tumors resected from the peritoneum were diagnosed as HCC. The present case of HCC was thought to have possibly developed from ectopic liver on the peritoneum or mesentery.

  7. Ectopic Esthesioneuroblastoma of the Sphenoclivus: A Rare Entity.

    PubMed

    Zahedi, Farah Dayana; Gendeh, Balwant Singh; Husain, Salina; Kumar, Ramesh; Kew, Thean Yean

    2017-03-01

    Esthesioneuroblastoma is a rare malignant neoplasm of oflactory neuroepithelium and usually located at the olfactory cleft at superior nasal cavity. Ectopic localization of esthesioneuroblastoma is even rarer and usually posed with a diagnostic dilemma and delay in the diagnosis and management, We report a rare case of ectopic esthesioneuroblastoma of the sphenoclivus with the presentation of intermittent unilateral epistaxis, intermittent intractable headache without anosmia. Nasal endoscopy findings showed a pulsatile mass at the anterior face of the sphenoid sinus with extension posteriorly towards the clivus region and occupying the floor of the sphenoid sinus. Endonasal transclival endoscopic excision of tumour was performed which involved otorhinolaryngology surgeon and neurosurgeon with intraoperative navigation imaging and frozen section. The histopathological findings was esthesioneuroblastoma. Due to its rarity and unusual presentation, the diagnosis of ectopic esthesioneuroblastoma is difficult and can be misdiagnosed with the other type of malignancy. Therefore, the histopathological result is important in confirming the type of tumour and can lead to the next step of management.

  8. Ectopic Pancreas Imitating Gastrointestinal Stromal Tumor (GIST) In The Stomach.

    PubMed

    Zińczuk, Justyna; Bandurski, Roman; Pryczynicz, Anna; Konarzewska-Duchnowska, Emilia; Kemona, Andrzej; Kędra, Bogusław

    2015-05-01

    Ectopic pancreas is a rare congenital disorder defined as pancreatic tissue lacking vascular or anatomic communication with the normal body of the pancreas. Most cases of ectopic pancreas are asymptomatic, but it may become clinically evident depending on the size, location and the pathological changes similar to those observed in case of the normal pancreas. It is often an incidental finding and can be located at different sites in the gastrointestinal tract. The most common locations are: the stomach, duodenum or the proximal part of small intestine. The risk of malignancy, bleeding and occlusion are the most serious complications. Despite the development in diagnostics, it still remains a challenge for the clinician to differentiate it from neoplasm. In this report, we described a case of 28-years old woman who presented recurrent epigastric pain. The upper gastrointestinal endoscopy revealed gastrointestinal stromal tumor on the border of the body and antrum of the back wall of great curvature of the stomach. The histopathological examination after surgery showed heterotopic pancreatic tissue. Ectopic pancreas should be considered in the differential diagnosis of gastric mass lesions.

  9. [Risk factors for ectopic pregnancy. Results of a case control study in the Rhone-Alpes region].

    PubMed

    Job-Spira, N; Collet, P; Coste, J; Brémond, A; Laumon, B

    1993-04-01

    A case-control study was conducted in 14 Rhône-Alpes area (France) maternity hospitals to evaluate the role of several risk factors, particularly infectious factors, in ectopic pregnancy. A total of 624 cases and 1,247 controls were compared for sociodemographic characteristics, cigarette smoking, sexual reproductive and surgical histories, and condition of conception. Different risk factors were found to be associated with an increased risk of ectopic pregnancy: pelvic inflammatory disease confirmed by celioscopy (OR = 3.8, 95%, CI = 2.1-6.9), Chlamydia trachomatis seropositivity (OR = 4.6, 95%, CI = 3.4-6.3), cigarette smoking at the time of conception with a dose-related effect (OR = 1.6 to 2.6), prior tubal surgery (OR = 1.8, 95%, CI = 1.0-3.1), prior uterus, surgery (OR = 3.2, 95%, CI = 1.4-7.1), prior ectopic pregnancy (OR = 6.4, 95%, CI = 3.6-11.3), induced conception cycle by clomiphene citrate (OR = 4.5, 95%, CI = 1.7-12.0), endometriosis (OR = 6.7, 95%, CI = 2.6-17.4) and maternal age, with a strong relation after the age of 35. These findings confirm the major role of pelvic inflammatory disease which could explain fifty percent of the cases and the one of cigarette smoking at the time of conception which could explain twenty percent of the cases.

  10. Site-specific phosphorylation of Tau protein is associated with deacetylation of microtubules in mouse spermatogenic cells during meiosis.

    PubMed

    Inoue, Hiroki; Hiradate, Yuuki; Shirakata, Yoshiki; Kanai, Kenta; Kosaka, Keita; Gotoh, Aina; Fukuda, Yasuhiro; Nakai, Yutaka; Uchida, Takafumi; Sato, Eimei; Tanemura, Kentaro

    2014-05-29

    Tau is one of the microtubule-associated proteins and a major component of paired helical filaments, a hallmark of Alzheimer's disease. Its expression has also been indicated in the testis. However, its function and modification in the testis have not been established. Here, we analyzed the dynamics of phosphorylation patterns during spermatogenesis. The expression of Tau protein and its phosphorylation were shown in the mouse testis. Immunohistochemistry revealed that the phosphorylation was strongly detected during meiosis. Correspondingly, the expression of acetylated tubulin was inversely weakened during meiosis. These results suggest that phosphorylation of Tau protein contributes to spermatogenesis, especially in meiosis.

  11. Induction and activation of meiosis and subsequent parthenogenetic development of growing pig oocytes using calcium ionophore A23187.

    PubMed

    Sedmíková, Markéta; Burdová, Jana; Petr, Jaroslav; Etrych, Milan; Rozinek, Jirí; Jílek, Frantisek

    2003-12-01

    The pig ovary contains a large number of growing oocytes, which do not mature in vitro and cannot be readily used in various biotechnologies. This study was conducted to determine the possibility of inducing meiotic maturation in growing pig oocytes with an internal diameter of 110 microm, which had developed partial meiotic competence. Most of these oocytes spontaneously stopped maturation at the metaphase I stage (68%); a limited number proceeded to the metaphase II stage (26%). Treatment with calcium ionophore A23187 (50 microM for 5 or 10 min) after 24h in vitro culture overcame the block at the metaphase I stage, and treated growing pig oocytes matured to the metaphase II stage (66%). Oocytes in which maturation had been induced by calcium ionophore were again treated with calcium ionophore. Up to 58% of the treated oocytes were activated. Parthenogenetic development in oocytes treated with ionophore for meiosis induction and activation was very limited. The portion which reached morula stage did not exceed 8% and at most 3% developed to the blastocyst stage.

  12. Meiosis, egg activation, and nuclear envelope breakdown are differentially reliant on Ca2+, whereas germinal vesicle breakdown is Ca2+ independent in the mouse oocyte

    NASA Technical Reports Server (NTRS)

    Tombes, R. M.; Simerly, C.; Borisy, G. G.; Schatten, G.

    1992-01-01

    During early development, intracellular Ca2+ mobilization is not only essential for fertilization, but has also been implicated during other meiotic and mitotic events, such as germinal vesicle breakdown (GVBD) and nuclear envelope breakdown (NEBD). In this study, the roles of intracellular and extracellular Ca2+ were examined during meiotic maturation and reinitiation at parthenogenetic activation and during first mitosis in a single species using the same methodologies. Cumulus-free metaphase II mouse oocytes immediately resumed anaphase upon the induction of a large, transient Ca2+ elevation. This resumption of meiosis and associated events, such as cortical granule discharge, were not sensitive to extracellular Ca2+ removal, but were blocked by intracellular Ca2+ chelators. In contrast, meiosis I was dependent on external Ca2+; in its absence, the formation and function of the first meiotic spindle was delayed, the first polar body did not form and an interphase-like state was induced. GVBD was not dependent on external Ca2+ and showed no associated Ca2+ changes. NEBD at first mitosis in fertilized eggs, on the other hand, was frequently, but not always associated with a brief Ca2+ transient and was dependent on Ca2+ mobilization. We conclude that GVBD is Ca2+ independent, but that the dependence of NEBD on Ca2+ suggests regulation by more than one pathway. As cells develop from Ca(2+)-independent germinal vesicle oocytes to internal Ca(2+)-dependent pronuclear eggs, internal Ca2+ pools increase by approximately fourfold.

  13. Meiosis, egg activation, and nuclear envelope breakdown are differentially reliant on Ca2+, whereas germinal vesicle breakdown is Ca2+ independent in the mouse oocyte

    PubMed Central

    1992-01-01

    During early development, intracellular Ca2+ mobilization is not only essential for fertilization, but has also been implicated during other meiotic and mitotic events, such as germinal vesicle breakdown (GVBD) and nuclear envelope breakdown (NEBD). In this study, the roles of intracellular and extracellular Ca2+ were examined during meiotic maturation and reinitiation at parthenogenetic activation and during first mitosis in a single species using the same methodologies. Cumulus- free metaphase II mouse oocytes immediately resumed anaphase upon the induction of a large, transient Ca2+ elevation. This resumption of meiosis and associated events, such as cortical granule discharge, were not sensitive to extracellular Ca2+ removal, but were blocked by intracellular Ca2+ chelators. In contrast, meiosis I was dependent on external Ca2+; in its absence, the formation and function of the first meiotic spindle was delayed, the first polar body did not form and an interphase-like state was induced. GVBD was not dependent on external Ca2+ and showed no associated Ca2+ changes. NEBD at first mitosis in fertilized eggs, on the other hand, was frequently, but not always associated with a brief Ca2+ transient and was dependent on Ca2+ mobilization. We conclude that GVBD is Ca2+ independent, but that the dependence of NEBD on Ca2+ suggests regulation by more than one pathway. As cells develop from Ca(2+)-independent germinal vesicle oocytes to internal Ca(2+)-dependent pronuclear eggs, internal Ca2+ pools increase by approximately fourfold. PMID:1577859

  14. Mouse Y-linked Zfy1 and Zfy2 are expressed during the male-specific interphase between meiosis I and meiosis II and promote the 2nd meiotic division.

    PubMed

    Vernet, Nadège; Mahadevaiah, Shantha K; Yamauchi, Yasuhiro; Decarpentrie, Fanny; Mitchell, Michael J; Ward, Monika A; Burgoyne, Paul S

    2014-06-01

    Mouse Zfy1 and Zfy2 encode zinc finger transcription factors that map to the short arm of the Y chromosome (Yp). They have previously been shown to promote meiotic quality control during pachytene (Zfy1 and Zfy2) and at the first meiotic metaphase (Zfy2). However, from these previous studies additional roles for genes encoded on Yp during meiotic progression were inferred. In order to identify these genes and investigate their function in later stages of meiosis, we created three models with diminishing Yp and Zfy gene complements (but lacking the Y-long-arm). Since the Y-long-arm mediates pairing and exchange with the X via their pseudoautosomal regions (PARs) we added a minute PAR-bearing X chromosome derivative to enable formation of a sex bivalent, thus avoiding Zfy2-mediated meiotic metaphase I (MI) checkpoint responses to the unpaired (univalent) X chromosome. Using these models we obtained definitive evidence that genetic information on Yp promotes meiosis II, and by transgene addition identified Zfy1 and Zfy2 as the genes responsible. Zfy2 was substantially more effective and proved to have a much more potent transactivation domain than Zfy1. We previously established that only Zfy2 is required for the robust apoptotic elimination of MI spermatocytes in response to a univalent X; the finding that both genes potentiate meiosis II led us to ask whether there was de novo Zfy1 and Zfy2 transcription in the interphase between meiosis I and meiosis II, and this proved to be the case. X-encoded Zfx was also expressed at this stage and Zfx over-expression also potentiated meiosis II. An interphase between the meiotic divisions is male-specific and we previously hypothesised that this allows meiosis II critical X and Y gene reactivation following sex chromosome silencing in meiotic prophase. The interphase transcription and meiosis II function of Zfx, Zfy1 and Zfy2 validate this hypothesis.

  15. How-to-Do-It: Hands-on Activity for Mitosis, Meiosis and the Fundamentals of Heredity.

    ERIC Educational Resources Information Center

    Taylor, Mark F.

    1988-01-01

    Described is an exercise which uses inexpensive and easy-to-make materials to demonstrate the basic fundamentals of heredity. Discusses two approaches using a hypothetical insert to demonstrate inheritance, mitosis, meiosis, and genotypic and phenotypic frequencies. (CW)

  16. Directing Cardiomyogenic Differentiation and Transdifferentiation By Ectopic Gene Expression - Direct Transition Or Reprogramming Detour?

    PubMed

    Andrée, Birgit; Zweigerdt, Robert

    2016-01-01

    Cardiovascular disorders and associated morbidities remain the leading cause of premature death worldwide. Since the regeneration of diseased hearts is very limited and the insufficient supply of donor organs persists, hopes rely on new therapies for heart repair. Reviving the proliferation of endogenous cardiomyocytes (CMs) or the administration of adult stem cells to the heart was of limited curative success to date. Thus, the administration of in vitro generated CMs is under investigation to replenish loss of functional heart muscle tissue. This requires a sustainable source of CMs. Induced pluripotent stem cells (iPSC) have raised hopes for developing autologous cell therapies. To serve for heart repair, efficient and safe iPSC differentiation protocols for CMs production are required. iPSC differentiation into CMs and even functional subtypes was indeed achieved in recent years, either by the ectopic expression of cardiac transcription factors or the supplementation of chemical pathway modulators. An alternative approach aims at the direct transdifferentiation of fibroblasts, which are present in the interstitial tissue of many organs, into functional lineage-specific cell types. As a result the formation of induced cardiomyocyte-like cells (iCMs) by the ectopic expression of specific transcription factors combinations has been demonstrated in vitro and in vivo. This is an important proof-of-concept that the intermediate state of iPSC induction is dispensable. However, most of the early experiments were conducted in mice and translation to more relevant large animal models and subsequently to the clinic are challenging. Progress, drawbacks, and perspectives in this field will be discussed.

  17. Dual ectopic thyroid gland: sonography and scintigraphy of lingual and sublingual thyroid.

    PubMed

    Marković, Vinko; Glavina, Gordana; Eterović, Davor; Punda, Ante; Brdar, Dubravka

    2014-06-01

    Dual ectopic lingual and sublingual thyroid gland is an extraordinarily rare condition. We present 1 patient with subclinical hypothyroidism. The clinical examination revealed that the thyroid gland was not palpable in its usual cervical location, whereas ultrasonography confirmed an empty thyroid bed without any ectopic thyroid tissue in the rest of the neck. The final diagnosis of dual ectopic lingual and sublingual thyroid was established by ultrasound examination through the mouth floor and confirmed by scintigraphy and CT thereafter.

  18. Haploid meiosis in Arabidopsis: double-strand breaks are formed and repaired but without synapsis and crossovers.

    PubMed

    Cifuentes, Marta; Rivard, Maud; Pereira, Lucie; Chelysheva, Liudmila; Mercier, Raphael

    2013-01-01

    Two hallmark features of meiosis are i) the formation of crossovers (COs) between homologs and ii) the production of genetically-unique haploid spores that will fuse to restore the somatic ploidy level upon fertilization. In this study we analysed meiosis in haploid Arabidopsis thaliana plants and a range of haploid mutants to understand how meiosis progresses without a homolog. Extremely low chiasma frequency and very limited synapsis occurred in wild-type haploids. The resulting univalents segregated in two uneven groups at the first division, and sister chromatids segregated to opposite poles at the second division, leading to the production of unbalanced spores. DNA double-strand breaks that initiate meiotic recombination were formed, but in half the number compared to diploid meiosis. They were repaired in a RAD51- and REC8-dependent manner, but independently of DMC1, presumably using the sister chromatid as a template. Additionally, turning meiosis into mitosis (MiMe genotype) in haploids resulted in the production of balanced haploid gametes and restoration of fertility. The variability of the effect on meiosis of the absence of homologous chromosomes in different organisms is then discussed.

  19. Male and female meiosis in the mountain scorpion Zabius fuscus (Scorpiones, Buthidae): heterochromatin, rDNA and TTAGG telomeric repeats.

    PubMed

    Adilardi, Renzo Sebastián; Ojanguren-Affilastro, Andrés Alejandro; Mattoni, Camilo Iván; Mola, Liliana María

    2015-08-01

    All cytogenetically studied scorpions present male achiasmatic meiosis and lack heteromorphic sex chromosomes. In contrast, information about female meiosis in scorpions is scarce due to the difficulty of finding meiotic cells. The genus Zabius includes three described species and no chromosome studies have been performed on it until now. We analyzed the constitutive heterochromatin distribution, NORs and telomeric sequences in mitosis and meiosis of males and females of different populations of Zabius fuscus. All specimens presented 2n = 18 holokinetic chromosomes that gradually decreased in size. Male meiosis presented nine bivalents and a polymorphism for one reciprocal translocation in one population. Telomeric signals were detected at every terminal region, confirming also the presence of a (TTAGG) n motif in Buthidae. Constitutive heterochromatin was found in three chromosome pairs at a terminal region; moreover, NORs were embedded in the heterochromatic region of the largest pair. Chromosome size and landmarks allowed us to propose the chromosomes involved in the rearrangement. In four females, cells at different prophase I stages were analyzed. We describe a diffuse stage and the presence of ring-shaped bivalents. We discuss the possible origin of these bivalents in the framework of chiasmatic or achiasmatic female meiosis. These results contribute to increase the scarce evidence of female meiosis in scorpions and raise new questions about its mechanism.

  20. Regulation of centromere localization of the Drosophila Shugoshin MEI-S332 and sister-chromatid cohesion in meiosis.

    PubMed

    Nogueira, Cristina; Kashevsky, Helena; Pinto, Belinda; Clarke, Astrid; Orr-Weaver, Terry L

    2014-07-31

    The Shugoshin (Sgo) protein family helps to ensure proper chromosome segregation by protecting cohesion at the centromere by preventing cleavage of the cohesin complex. Some Sgo proteins also influence other aspects of kinetochore-microtubule attachments. Although many Sgo members require Aurora B kinase to localize to the centromere, factors controlling delocalization are poorly understood and diverse. Moreover, it is not clear how Sgo function is inactivated and whether this is distinct from delocalization. We investigated these questions in Drosophila melanogaster, an organism with superb chromosome cytology to monitor Sgo localization and quantitative assays to test its function in sister-chromatid segregation in meiosis. Previous research showed that in mitosis in cell culture, phosphorylation of the Drosophila Sgo, MEI-S332, by Aurora B promotes centromere localization, whereas Polo phosphorylation promotes delocalization. These studies also suggested that MEI-S332 can be inactivated independently of delocalization, a conclusion supported here by localization and function studies in meiosis. Phosphoresistant and phosphomimetic mutants for the Aurora B and Polo phosphorylation sites were examined for effects on MEI-S332 localization and chromosome segregation in meiosis. Strikingly, MEI-S332 with a phosphomimetic mutation in the Aurora B phosphorylation site prematurely dissociates from the centromeres in meiosis I. Despite the absence of MEI-S332 on meiosis II centromeres in male meiosis, sister chromatids segregate normally, demonstrating that detectable levels of this Sgo are not essential for chromosome congression, kinetochore biorientation, or spindle assembly.

  1. Meiosis gene inventory of four ciliates reveals the prevalence of a synaptonemal complex-independent crossover pathway.

    PubMed

    Chi, Jingyun; Mahé, Frédéric; Loidl, Josef; Logsdon, John; Dunthorn, Micah

    2014-03-01

    To establish which meiosis genes are present in ciliates, and to look for clues as to which recombination pathways may be treaded by them, four genomes were inventoried for 11 meiosis-specific and 40 meiosis-related genes. We found that the set of meiosis genes shared by Tetrahymena thermophila, Paramecium tetraurelia, Ichthyophthirius multifiliis, and Oxytricha trifallax is consistent with the prevalence of a Mus81-dependent class II crossover pathway that is considered secondary in most model eukaryotes. There is little evidence for a canonical class I crossover pathway that requires the formation of a synaptonemal complex (SC). This gene inventory suggests that meiotic processes in ciliates largely depend on mitotic repair proteins for executing meiotic recombination. We propose that class I crossovers and SCs were reduced sometime during the evolution of ciliates. Consistent with this reduction, we provide microscopic evidence for the presence only of degenerate SCs in Stylonychia mytilus. In addition, lower nonsynonymous to synonymous mutation rates of some of the meiosis genes suggest that, in contrast to most other nuclear genes analyzed so far, meiosis genes in ciliates are largely evolving at a slower rate than those genes in fungi and animals.

  2. OsSDS is essential for DSB formation in rice meiosis.

    PubMed

    Wu, Zhigang; Ji, Jianhui; Tang, Ding; Wang, Hongjun; Shen, Yi; Shi, Wenqing; Li, Yafei; Tan, Xuelin; Cheng, Zhukuan; Luo, Qiong

    2015-01-01

    SDS is a meiosis specific cyclin-like protein and required for DMC1 mediated double-strand break (DSB) repairing in Arabidopsis. Here, we found its rice homolog, OsSDS, is essential for meiotic DSB formation. The Ossds mutant is normal in vegetative growth but both male and female gametes are inviable. The Ossds meiocytes exhibit severe defects in homologous pairing and synapsis. No γH2AX immunosignals in Ossds meiocytes together with the suppression of chromosome fragmentation in Ossds-1 Osrad51c, both provide strong evidences that OsSDS is essential for meiotic DSB formation. Immunostaining investigations revealed that meiotic chromosome axes are normally formed but both SC installation and localization of recombination elements are failed in Ossds. We suspected that this cyclin protein has been differentiated pretty much between monocots and dicots on its function in meiosis.

  3. [Dynamics of cytoskeleton microtubules in higher plant meiosis. II. Perinuclear band formation].

    PubMed

    Shamina, N V; Dorogova, N V; Seriukova, E G

    2003-01-01

    Analyses of correspondent meiotic abnormalities is a good tool for studying cytoskeletal rearrangements during plant cell division. The paper reports on the wheat x wheatgrass F1 hybrids, showing various abnormalities during organization of the prophase perinuclear band of microtubules (PNB) in male meiosis. Based on these data, it may be concluded that the perinuclear system of microtubules (MT) in higher plant meiosis is formed from fibrils of the radial system as a result of their translocation in the cell cytoplasm space. According to our data, at this stage the radial MT arrays pass through the following consequence of events: separating from the nuclear envelope, 2) approaching, 3) tangential orientation to the nuclear surface, 4) bending, 5) co-orientation, lateral interaction. As a result, a flat ring of well organized concentric bent MT bundles encircling the nucleus meridionally is organized.

  4. Mitofusin 2 regulates the oocytes development and quality by modulating meiosis and mitochondrial function

    PubMed Central

    Liu, Qun; Kang, Lina; Wang, Lingjuan; Zhang, Ling; Xiang, Wenpei

    2016-01-01

    Mitofusin-2 (Mfn2), one of the mitochondrial dynamic proteins plays a key role in maintaining the integrity of mitochondrial morphology and function. However, it is unknown if Mfn2 influences the quality of oocytes in the process of development by modulating mitochondrial function in vitro. In this study, immature oocytes were transfected with Mfn2-siRNA for 16 h. We found that the expression level of the Mfn2 gene was significantly lower than those of the control group. The rates of maturation and fertility were also found to have declined. Moreover, mitochondrial structure and function, especially the morphogenesis of spindles, were observed as abnormal during meiosis. Thus, the above findings indicate that down-regulation of Mfn2 may have an impact on the maturation and fertilization of immature oocytes in vitro by modulating meiosis and mitochondrial function. PMID:27469431

  5. MicroRNAs and DNA methylation as epigenetic regulators of mitosis, meiosis and spermiogenesis.

    PubMed

    Yao, Chencheng; Liu, Yun; Sun, Min; Niu, Minghui; Yuan, Qingqing; Hai, Yanan; Guo, Ying; Chen, Zheng; Hou, Jingmei; Liu, Yang; He, Zuping

    2015-07-01

    Spermatogenesis is composed of three distinctive phases, which include self-renewal of spermatogonia via mitosis, spermatocytes undergoing meiosis I/II and post-meiotic development of haploid spermatids via spermiogenesis. Spermatogenesis also involves condensation of chromatin in the spermatid head before transformation of spermatids to spermatozoa. Epigenetic regulation refers to changes of heritably cellular and physiological traits not caused by modifications in the DNA sequences of the chromatin such as mutations. Major advances have been made in the epigenetic regulation of spermatogenesis. In this review, we address the roles and mechanisms of epigenetic regulators, with a focus on the role of microRNAs and DNA methylation during mitosis, meiosis and spermiogenesis. We also highlight issues that deserve attention for further investigation on the epigenetic regulation of spermatogenesis. More importantly, a thorough understanding of the epigenetic regulation in spermatogenesis will provide insightful information into the etiology of some unexplained infertility, offering new approaches for the treatment of male infertility.

  6. The roles of cohesins in mitosis, meiosis, and human health and disease.

    PubMed

    Brooker, Amanda S; Berkowitz, Karen M

    2014-01-01

    Mitosis and meiosis are essential processes that occur during development. Throughout these processes, cohesion is required to keep the sister chromatids together until their separation at anaphase. Cohesion is created by multiprotein subunit complexes called cohesins. Although the subunits differ slightly in mitosis and meiosis, the canonical cohesin complex is composed of four subunits that are quite diverse. The cohesin complexes are also important for DNA repair, gene expression, development, and genome integrity. Here we provide an overview of the roles of cohesins during these different events as well as their roles in human health and disease, including the cohesinopathies. Although the exact roles and mechanisms of these proteins are still being elucidated, this review serves as a guide for the current knowledge of cohesins.

  7. Molecular regulation of the mitosis/meiosis decision in multicellular organisms.

    PubMed

    Kimble, Judith

    2011-08-01

    A major step in the journey from germline stem cell to differentiated gamete is the decision to leave the mitotic cell cycle and begin progression through the meiotic cell cycle. Over the past decade, molecular regulators of the mitosis/meiosis decision have been discovered in most of the major model multicellular organisms. Historically, the mitosis/meiosis decision has been closely linked with controls of germline self-renewal and the sperm/egg decision, especially in nematodes and mice. Molecular explanations of those linkages clarify our understanding of this fundamental germ cell decision, and unifying themes have begun to emerge. Although the complete circuitry of the decision is not known in any organism, the recent advances promise to impact key issues in human reproduction and agriculture.

  8. The tricky path to recombining X and Y chromosomes in meiosis.

    PubMed

    Kauppi, Liisa; Jasin, Maria; Keeney, Scott

    2012-09-01

    Sex chromosomes are the Achilles' heel of male meiosis in mammals. Mis-segregation of the X and Y chromosomes leads to sex chromosome aneuploidies, with clinical outcomes such as infertility and Klinefelter syndrome. Successful meiotic divisions require that all chromosomes find their homologous partner and achieve recombination and pairing. Sex chromosomes in males of many species have only a small region of homology (the pseudoautosomal region, PAR) that enables pairing. Until recently, little was known about the dynamics of recombination and pairing within mammalian X and Y PARs. Here, we review our recent findings on PAR behavior in mouse meiosis. We uncovered unexpected differences between autosomal chromosomes and the X-Y chromosome pair, namely that PAR recombination and pairing occurs later, and is under different genetic control. These findings imply that spermatocytes have evolved distinct strategies that ensure successful X-Y recombination and chromosome segregation.

  9. Mesostoma ehrenbergii spermatocytes--a unique and advantageous cell for studying meiosis.

    PubMed

    Ferraro-Gideon, Jessica; Hoang, Carina; Forer, Arthur

    2013-09-01

    Mesostoma ehrenbergii have a unique male meiosis: their spermatocytes have three large bivalents that oscillate for 1-2 h before entering into anaphase without having formed a metaphase plate, have a precocious ('pre-anaphase') cleavage furrow, and have four univalents that segregate between spindle poles without physical interaction between them, that is via 'distance segregation'. These unique and unconventional features make Mesostoma spermatocytes an ideal organism for studying the force produced by the spindle to move chromosomes, and to study cleavage furrow control and 'distance segregation'. We review the literature on meiosis in Mesostoma spermatocytes and describe our current research with Mesostoma spermatocytes, rearing the animals in the laboratory using methods that described in our companion article [Hoang et al. (2013); Cell Biol Int].

  10. Chromosome or chromatin condensation leads to meiosis or apoptosis in stationary yeast (Saccharomyces cerevisiae) cells.

    PubMed

    Yang, Hui; Ren, Qun; Zhang, Zhaojie

    2006-12-01

    When starved of essential nutrients, yeast cells cease mitotic division and enter an alternative state called the 'stationary phase'. In this paper, we report that stationary cells enter two major pathways: meiosis and apoptosis. Using transmission electron microscopy, five types of cell were identified in the stationary phase: (1) cells with chromosome condensed nuclei; (2) cells with normal, homogeneously stained nuclei; (3) sporulated cells; (4) apoptotic cells, in which chromatin, but not individual chromosomes, was condensed; and (5) dead cells, in which nuclei and cytoplasm were degraded. Further evidence using live cell imaging and mutation analysis suggested that cells with condensed chromosomes underwent meiosis, whereas chromatin condensed cells underwent apoptotic cell death. Cells with homogeneous nuclei are believed to be in the true resting state and undergo cell death when starvation continues. Chromosome or chromatin condensation may serve as a hallmark of life or death for stationary cells.

  11. Did meiosis evolve before sex and the evolution of eukaryotic life cycles?

    PubMed

    Niklas, Karl J; Cobb, Edward D; Kutschera, Ulrich

    2014-11-01

    Biologists have long theorized about the evolution of life cycles, meiosis, and sexual reproduction. We revisit these topics and propose that the fundamental difference between life cycles is where and when multicellularity is expressed. We develop a scenario to explain the evolutionary transition from the life cycle of a unicellular organism to one in which multicellularity is expressed in either the haploid or diploid phase, or both. We propose further that meiosis might have evolved as a mechanism to correct for spontaneous whole-genome duplication (auto-polyploidy) and thus before the evolution of sexual reproduction sensu stricto (i.e. the formation of a diploid zygote via the fusion of haploid gametes) in the major eukaryotic clades. In addition, we propose, as others have, that sexual reproduction, which predominates in all eukaryotic clades, has many different advantages among which is that it produces variability among offspring and thus reduces sibling competition.

  12. Bilateral Simultaneous Tubal Ectopic Pregnancy: A Case Report, Review of Literature and a Proposed Management Algorithm

    PubMed Central

    Jena, Saubhagya Kumar; Nayak, Monalisha; Das, Leena; Senapati, Swagatika

    2016-01-01

    Bilateral simultaneous Tubal Ectopic Pregnancy (BTP) is the rarest form of ectopic pregnancy. The incidence is higher in women undergoing assisted reproductive techniques or ovulation induction. The clinical presentation is unpredictable and there are no unique features to distinguish it from unilateral ectopic pregnancy. BTP continues to be a clinician’s dilemma as pre-operative diagnosis is difficult and is commonly made during surgery. Treatment options are varied depending on site of ectopic pregnancy, extent of tubal damage and requirement of future fertility. We report a case of BTP which was diagnosed during surgery and propose an algorithm for management of such patients. PMID:27134950

  13. Ectopic eruption of maxillary central incisor through abnormally thickened labial frenum: An unusual presentation.

    PubMed

    Gugnani, Neeraj; Pandit, I K; Gupta, Monika; Gugnani, Shalini; Vishnoi, Ashmi; Sabharwal, Ozasvita; Manhas, Swati

    2017-01-01

    Ectopic eruption is a deviation from the normal eruption pattern, making the tooth erupt out of its normal position, and possibly causing resorption of adjacent primary teeth. A wide range of etiological factors may be responsible for ectopic eruption of the teeth, so their management depends on the correction of the established etiological factor. The present case report describes an unusual case of ectopically erupted central incisor encased within an abnormally thickened labial frenum, which was treated by orthodontic repositioning of the ectopically erupting tooth after frenectomy.

  14. Abdominal obesity: a marker of ectopic fat accumulation.

    PubMed

    Smith, Ulf

    2015-05-01

    In the early 1980s, we analyzed the metabolic profile of 930 men and women and concluded that an abdominal distribution of fat for a given BMI is associated with increased insulin resistance and risk of developing type 2 diabetes and cardiovascular disease. The correlation between abdominal fat and metabolic dysfunction has since been validated in many studies, and waist circumference is now a criterion for the diagnosis of metabolic syndrome. Several mechanisms for this relationship have been postulated; however, we now know that visceral fat is only one of many ectopic fat depots used when the subcutaneous adipose tissue cannot accommodate excess fat because of its limited expandability.

  15. Surgical Management of Ectopic Kidney with Bilateral Iliac Vein Invasion

    PubMed Central

    Tanwar, Harshwardhan V; Fernandes, Gwendolyn; Patil, Bhushan; Patwardhan, Sujata K

    2016-01-01

    Renal cell carcinoma (RCC) is a very rare phenomenon in an ectopic kidney. We come across a 61-year-old gentleman with a history of 2 months of gross, painless haematuria and palpable pelvic mass on examination. CT scan showed 6.5cm X 5.1cm X 5.8cm mass in pelvic kidney with bilateral iliac vein invasion. With the help of intra-operative ultra-sound, tumour thrombus was extracted from both iliac veins with en mass removal of tumour. Patient was well intraoperatively as well as in postoperatively. We also presented an elegant imaging for the case. PMID:27134940

  16. An Ectopic Case of Tunga spp. Infection in Peru

    PubMed Central

    Maco, Vicente; Maco, Vicente P.; Gotuzzo, Eduardo

    2010-01-01

    Tungiasis is a neglected ectoparasitism of impoverished areas in South America and sub-Saharan Africa. The sand flea Tunga spp. preferably infests the soles and the periungueal and interdigital regions of the feet. Ectopic tungiasis is rare, even in highly endemic areas. We describe a case of an indigenous patient in Peru who presented with a nodular lesion in the extensor aspect of the knee and whose biopsy was compatible with Tunga spp. This is the first documented case of knee tungiasis in an endemic country. The historical, clinical, histological, and current epidemiological aspects of tungiasis in Peru are discussed here. PMID:20519602

  17. Ectopic fat accumulation in patients with COPD: an ECLIPSE substudy

    PubMed Central

    Martin, Mickaël; Almeras, Natalie; Després, Jean-Pierre; Coxson, Harvey O; Washko, George R; Vivodtzev, Isabelle; Wouters, Emiel FM; Rutten, Erica; Williams, Michelle C; Murchison, John T; MacNee, William; Sin, Don D; Maltais, François

    2017-01-01

    Background Obesity is increasingly associated with COPD, but little is known about the prevalence of ectopic fat accumulation in COPD and whether this can possibly be associated with poor clinical outcomes and comorbidities. The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) substudy tested the hypothesis that COPD is associated with increased ectopic fat accumulation and that this would be associated with COPD-related outcomes and comorbidities. Methods Computed tomography (CT) images of the thorax obtained in ECLIPSE were used to quantify ectopic fat accumulation at L2–L3 (eg, cross-sectional area [CSA] of visceral adipose tissue [VAT] and muscle tissue [MT] attenuation, a reflection of muscle fat infiltration) and CSA of MT. A dose–response relationship between CSA of VAT, MT attenuation and CSA of MT and COPD-related outcomes (6-minute walking distance [6MWD], exacerbation rate, quality of life, and forced expiratory volume in 1 second [FEV1] decline) was addressed with the Cochran–Armitage trend test. Regression models were used to investigate possible relationships between CT body composition indices and comorbidities. Results From the entire ECLIPSE cohort, we identified 585 subjects with valid CT images at L2–L3 to assess body composition. CSA of VAT was increased (P<0.0001) and MT attenuation was reduced (indicating more muscle fat accumulation) in patients with COPD (P<0.002). Progressively increasing CSA of VAT was not associated with adverse clinical outcomes. The probability of exhibiting low 6MWD and accelerated FEV1 decline increased with progressively decreasing MT attenuation and CSA of MT. In COPD, the probability of having diabetes (P=0.024) and gastroesophageal reflux (P=0.0048) at baseline increased in parallel with VAT accumulation, while the predicted MT attenuation increased the probability of cardiovascular comorbidities (P=0.042). Body composition parameters did not correlate with coronary

  18. Effects of MAP kinase pathway and other factors on meiosis of Urechis unicinctus eggs.

    PubMed

    Tan, Xin; Wang, Yong-Chao; Sun, Qing-Yuan; Peng, An; Chen, Da-Yuan; Tang, Yong-Zheng

    2005-05-01

    The eggs of Urechis unicinctus Von Drasche, an echiuroid, are arrested at P-I stage in meiosis. The meiosis is reinitiated by fertilization. Immunoblotting analysis using anti-ERK2 and anti-phospho-MAPK antibodies revealed a 44 kDa MAP kinase species that was constantly expressed in U. unicinctus eggs, quickly phosphorylated after fertilization, and dephosphorylated slowly before the completion of meiosis I. Phosphorylation of the protein was not depressed by protein synthesis inhibitor Cycloheximide (CHX), but was depressed by the MEK1 inhibitor PD98059. Under PD98059 treatment, polar body extrusion was suppressed and the function of centrosome and spindle was abnormal though GVBD was not affected, indicating that MAP kinase cascade was important for meiotic division of U. unicinctus eggs. Other discovery includes: A23187 and OA could parthenogenetically activate U. unicinctus eggs and phosphorylated 44 kDa MAP kinase species, indicating that the effect of fertilization on reinitiating meiosis and phosphorylation of 44 kDa MAP kinase specie is mediated by raising intracellular free calcium and by phosphorylation of some proteins, and that phosphotase(s) sensitive to OA is responsible for arresting U. unicinctus eggs in prophase I. diC8, an activator of PKC, accelerated the process of U. unicinctus egg meiotic division after fertilization and accelerated the dephosphorylation of 44 kDa MAP kinase specie, which implied that the acceleration effect of PKC on meiotic division was mediated by inactivation of MAP kinase cascade. Elevating cAMP/PKA level in U. unicinctus eggs had no effect on meiotic division of the eggs.

  19. PGRMC1 participates in late events of bovine granulosa cells mitosis and oocyte meiosis.

    PubMed

    Terzaghi, L; Tessaro, I; Raucci, F; Merico, V; Mazzini, G; Garagna, S; Zuccotti, M; Franciosi, F; Lodde, V

    2016-08-02

    Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in both oocyte and ovarian somatic cells, where it is found in multiple cellular sub-compartments including the mitotic spindle apparatus. PGRMC1 localization in the maturing bovine oocytes mirrors its localization in mitotic cells, suggesting a possible common action in mitosis and meiosis. To test the hypothesis that altering PGRMC1 activity leads to similar defects in mitosis and meiosis, PGRMC1 function was perturbed in cultured bovine granulosa cells (bGC) and maturing oocytes and the effect on mitotic and meiotic progression assessed. RNA interference-mediated PGRMC1 silencing in bGC significantly reduced cell proliferation, with a concomitant increase in the percentage of cells arrested at G2/M phase, which is consistent with an arrested or prolonged M-phase. This observation was confirmed by time-lapse imaging that revealed defects in late karyokinesis. In agreement with a role during late mitotic events, a direct interaction between PGRMC1 and Aurora Kinase B (AURKB) was observed in the central spindle at of dividing cells. Similarly, treatment with the PGRMC1 inhibitor AG205 or PGRMC1 silencing in the oocyte impaired completion of meiosis I. Specifically the ability of the oocyte to extrude the first polar body was significantly impaired while meiotic figures aberration and chromatin scattering within the ooplasm increased. Finally, analysis of PGRMC1 and AURKB localization in AG205-treated oocytes confirmed an altered localization of both proteins when meiotic errors occur. The present findings demonstrate that PGRMC1 participates in late events of both mammalian mitosis and oocyte meiosis, consistent with PGRMC1's localization at the mid-zone and mid-body of the mitotic and meiotic spindle.

  20. Multiple Small Supernumerary Marker Chromosomes Resulting from Maternal Meiosis I or II Errors

    PubMed Central

    Hochstenbach, Ron; Nowakowska, Beata; Volleth, Marianne; Ummels, Amber; Kutkowska-Kaźmierczak, Anna; Obersztyn, Ewa; Ziemkiewicz, Kamila; Gerloff, Claudia; Schanze, Denny; Zenker, Martin; Muschke, Petra; Schanze, Ina; Poot, Martin; Liehr, Thomas

    2016-01-01

    We present 2 cases with multiple de novo supernumerary marker chromosomes (sSMCs), each derived from a different chromosome. In a prenatal case, we found mosaicism for an sSMC(4), sSMC(6), sSMC(9), sSMC(14) and sSMC(22), while a postnatal case had an sSMC(4), sSMC(8) and an sSMC(11). SNP-marker segregation indicated that the sSMC(4) resulted from a maternal meiosis II error in the prenatal case. Segregation of short tandem repeat markers on the sSMC(8) was consistent with a maternal meiosis I error in the postnatal case. In the latter, a boy with developmental/psychomotor delay, autism, hyperactivity, speech delay, and hypotonia, the sSMC(8) was present at the highest frequency in blood. By comparison to other patients with a corresponding duplication, a minimal region of overlap for the phenotype was identified, with CHRNB3 and CHRNA6 as dosage-sensitive candidate genes. These genes encode subunits of nicotinic acetylcholine receptors (nAChRs). We propose that overproduction of these subunits leads to perturbed component stoichiometries with dominant negative effects on the function of nAChRs, as was shown by others in vitro. With the limitation that in each case only one sSMC could be studied, our findings demonstrate that different meiotic errors lead to multiple sSMCs. We relate our findings to age-related aneuploidy in female meiosis and propose that predivision sister-chromatid separation during meiosis I or II, or both, may generate multiple sSMCs. PMID:26997941

  1. Role for rodent Smc6 in pericentromeric heterochromatin domains during spermatogonial differentiation and meiosis.

    PubMed

    Verver, D E; van Pelt, A M M; Repping, S; Hamer, G

    2013-08-01

    Chromatin structure and function are for a large part determined by the six members of the structural maintenance of chromosomes (SMC) protein family, which form three heterodimeric complexes: Smc1/3 (cohesin), Smc2/4 (condensin) and Smc5/6. Each complex has distinct and important roles in chromatin dynamics, gene expression and differentiation. In yeast and Drosophila, Smc6 is involved in recombinational repair, restarting collapsed replication forks and prevention of recombination in repetitive sequences such as rDNA and pericentromeric heterochromatin. Although such DNA damage control mechanisms, as well as highly dynamic changes in chromatin composition and function, are essential for gametogenesis, knowledge on Smc6 function in mammalian systems is limited. We therefore have investigated the role of Smc6 during mammalian spermatogonial differentiation, meiosis and subsequent spermiogenesis. We found that, during mouse spermatogenesis, Smc6 functions as part of meiotic pericentromeric heterochromatin domains that are initiated when differentiating spermatogonia become irreversibly committed toward meiosis. To our knowledge, we are the first to provide insight into how commitment toward meiosis alters chromatin structure and dynamics, thereby setting apart differentiating spermatogonia from the undifferentiated spermatogonia, including the spermatogonial stem cells. Interestingly, Smc6 is not essential for spermatogonial mitosis, whereas Smc6-negative meiotic cells appear unable to finish their first meiotic division. Importantly, during meiosis, we find that DNA repair or recombination sites, marked by γH2AX or Rad51 respectively, do not co-localize with the pericentromeric heterochromatin domains where Smc6 is located. Considering the repetitive nature of these domains and that Smc6 has been previously shown to prevent recombination in repetitive sequences, we hypothesize that Smc6 has a role in the prevention of aberrant recombination events between

  2. Distinct Roles of Meiosis-Specific Cohesin Complexes in Mammalian Spermatogenesis

    PubMed Central

    Biswas, Uddipta; Hempel, Kai; Llano, Elena; Pendas, Alberto; Jessberger, Rolf

    2016-01-01

    Mammalian meiocytes feature four meiosis-specific cohesin proteins in addition to ubiquitous ones, but the roles of the individual cohesin complexes are incompletely understood. To decipher the functions of the two meiosis-specific kleisins, REC8 or RAD21L, together with the only meiosis-specific SMC protein SMC1β, we generated Smc1β-/-Rec8-/- and Smc1β-/-Rad21L-/- mouse mutants. Analysis of spermatocyte chromosomes revealed that besides SMC1β complexes, SMC1α/RAD21 and to a small extent SMC1α/REC8 contribute to chromosome axis length. Removal of SMC1β and RAD21L almost completely abolishes all chromosome axes. The sex chromosomes do not pair in single or double mutants, and autosomal synapsis is impaired in all mutants. Super resolution microscopy revealed synapsis-associated SYCP1 aberrantly deposited between sister chromatids and on single chromatids in Smc1β-/-Rad21L-/- cells. All mutants show telomere length reduction and structural disruptions, while wild-type telomeres feature a circular TRF2 structure reminiscent of t-loops. There is no loss of centromeric cohesion in both double mutants at leptonema/early zygonema, indicating that, at least in the mutant backgrounds, an SMC1α/RAD21 complex provides centromeric cohesion at this early stage. Thus, in early prophase I the most prominent roles of the meiosis-specific cohesins are in axis-related features such as axis length, synapsis and telomere integrity rather than centromeric cohesion. PMID:27792785

  3. Residual recombination in Neurospora crassa spo11 deletion homozygotes occurs during meiosis.

    PubMed

    Bowring, F J; Yeadon, P J; Catcheside, D E A

    2013-09-01

    Spo11 is considered responsible for initiation of meiotic recombination in higher organisms, but previous analysis using spo11 (RIP) mutants suggests that the his-3 region of Neurospora crassa experiences spo11-independent recombination. However, despite possessing several stop codons, it is conceivable that the mutants are not completely null. Also, since lack of spo11 interferes with chromosomal pairing and proper segregation at Meiosis I, spores can be partially diploid for a period after meiosis. Thus, it is possible that the recombination observed could be an abnormal event, occurring during the period of aneuploidy rather than during meiosis. To test the former hypothesis, we generated spo11 deletion homozygotes. Using crosses heteroallelic for his-3 mutations, we showed that His(+) progeny are generated in spo11 deletion homozygotes at a frequency at least as high as in wild type and, as in the spo11 (RIP) mutants, local crossing over is not reduced. To test the latter hypothesis, we utilised mutations in either end of a histone H1-GFP fusion gene, inserted between the recombination hotspot cog and his-3, in which GFP(+) spores arise as a result of recombination in a cross between the two GFP alleles. In a control cross homozygous for spo11 (+), the frequency at which GFP(+) spores arise is comparable to the frequency of His(+) spores and glowing nuclei first appear during prophase, prior to metaphase I, as expected for a product of meiotic recombination. Similarly in spo11 deletion homozygotes, GFP(+) spores arise at high frequency and glowing nuclei are first seen before metaphase, indicating that allelic recombination occurs during meiosis in the absence of spo11. We have therefore shown that spo11 is not essential for either his-3 allelic recombination or crossing over in the vicinity of his-3, and that spo11-independent allelic recombination is meiotic, indicating that there is a spo11-independent mechanism for initiation of recombination in Neurospora.

  4. Bioinformatical analysis of eukaryotic shugoshins reveals meiosis-specific features of vertebrate shugoshins

    PubMed Central

    Kulichenko, Darya; Bogdanov, Yuri F.

    2016-01-01

    Background Shugoshins (SGOs) are proteins that protect cohesins located at the centromeres of sister chromatids from their early cleavage during mitosis and meiosis in plants, fungi, and animals. Their function is to prevent premature sister-chromatid disjunction and segregation. The study focused on the structural differences among SGOs acting during mitosis and meiosis that cause differences in chromosome behavior in these two types of cell division in different organisms. Methods A bioinformatical analysis of protein domains, conserved amino acid motifs, and physicochemical properties of 32 proteins from 25 species of plants, fungi, and animals was performed. Results We identified a C-terminal amino acid motif that is highly evolutionarily conserved among the SGOs protecting centromere cohesion of sister chromatids in meiotic anaphase I, but not among mitotic SGOs. This meiotic motif is arginine-rich in vertebrates. SGOs differ in different eukaryotic kingdoms by the sets and locations of amino acid motifs and the number of α-helical regions in the protein molecule. Discussion These structural differences between meiotic and mitotic SGOs probably could be responsible for the prolonged SGOs resistance to degradation during meiotic metaphase I and anaphase I. We suggest that the “arginine comb” in C-end meiotic motifs is capable of interaction by hydrogen bonds with guanine bases in the minor groove of DNA helix, thus protecting SGOs from hydrolysis. Our findings support independent evolution of meiosis in different lineages of multicellular organisms. PMID:27917322

  5. The role of OsMSH4 in male and female gamete development in rice meiosis

    PubMed Central

    Wang, Chaolong; Wang, Yang; Cheng, Zhijun; Zhao, Zhigang; Chen, Jun; Sheng, Peike; Yu, Yang; Ma, Weiwei; Duan, Erchao; Wu, Fuqing; Liu, Linglong; Qin, Ruizhen; Zhang, Xin; Guo, Xiuping; Wang, Jiulin; Jiang, Ling; Wan, Jianmin

    2016-01-01

    Meiosis is essential for gametogenesis in sexual reproduction in rice (Oryza sativa L.). We identified a MutS-homolog (MSH) family gene OsMSH4 in a trisomic plant. Cytological analysis showed that developments of both pollen and embryo sacs in an Osmsh4 mutant were blocked due to defective chromosome pairing. Compared with the wild type, the Osmsh4 mutant displayed a significant ~21.9% reduction in chiasma frequency, which followed a Poisson distribution, suggesting that class I crossover formation in the mutant was impaired. Temporal and spatial expression pattern analyses showed that OsMSH4 was preferentially expressed in meiocytes during their meiosis, indicating a critical role in gametogenesis. Subcellular localization showed that OsMSH4–green fluorescent protein was predominantly located in the nucleus. OsMSH4 could interact with another MSH member (OsMSH5) through the N-terminus and C-terminus, respectively. Direct physical interaction between OsMSH5, OsRPA1a, OsRPA2b, OsRPA1c, and OsRPA2c was identified by yeast two-hybrid assays and further validated by pull-down assays. Our results supported the conclusion that the OsMSH4/5 heterodimer plays a key role in regulation of crossover formation during rice meiosis by interaction with the RPA complex. PMID:26712826

  6. Efficacy of a Meiosis Learning Module Developed for the Virtual Cell Animation Collection.

    PubMed

    Goff, Eric E; Reindl, Katie M; Johnson, Christina; McClean, Phillip; Offerdahl, Erika G; Schroeder, Noah L; White, Alan R

    2017-01-01

    Recent reports calling for change in undergraduate biology education have resulted in the redesign of many introductory biology courses. Reports on one common change to course structure, the active-learning environment, have placed an emphasis on student preparation, noting that the positive outcomes of active learning in the classroom depend greatly on how well the student prepares before class. As a possible preparatory resource, we test the efficacy of a learning module developed for the Virtual Cell Animation Collection. This module presents the concepts of meiosis in an interactive, dynamic environment that has previously been shown to facilitate learning in introductory biology students. Participants (n = 534) were enrolled in an introductory biology course and were presented the concepts of meiosis in one of two treatments: the interactive-learning module or a traditional lecture session. Analysis of student achievement shows that students who viewed the learning module as their only means of conceptual presentation scored significantly higher (d = 0.40, p < 0.001) than students who only attended a traditional lecture on the topic. Our results show the animation-based learning module effectively conveyed meiosis conceptual understanding, which suggests that it may facilitate student learning outside the classroom. Moreover, these results have implications for instructors seeking to expand their arsenal of tools for "flipping" undergraduate biology courses.

  7. Transcription factor ZFP38 is essential for meiosis prophase I in male mice.

    PubMed

    Yan, Zechen; Fan, Dandan; Meng, Qingjun; Yang, Jinjian; Zhao, Wei; Guo, Fei; Song, Dongjian; Guo, Ruiming; Sun, Ke; Wang, Jiaxiang

    2016-11-01

    The production of haploid gametes by meiosis is a cornerstone of sexual reproduction and maintenance of genome integrity. Zfp38 mRNA is expressed in spermatocytes, indicating that transcription factor ZFP38 has the potential to regulate transcription during meiosis. In this study, we generated Zfp38 conditional knockout mice (Zfp38(flox/flox), Stra8-Cre, hereafter called Zfp38 cKO) and found that spermatogenesis did not progress beyond meiosis prophase I in Zfp38 cKO mice. Using a chromosomal spread technique, we observed that Zfp38 cKO spermatocytes exhibited a failure in chromosomal synapsis observed by SYCP1/SYCP3 double staining. Progression of DNA double-strand breaks (DSB) repair is disrupted in Zfp38 cKO spermatocytes, as revealed by γ-H2AX, RAD51 and MLH1 staining. Furthermore, the mRNA and protein levels of DSB repair enzymes and factors that guide their loading onto sites of DSBs, such as RAD51, DMC1, RAD51, TEX15 and PALB2, were significantly reduced in Zfp38 cKO spermatocytes. Taken together, our data suggest that ZFP38 is critical for the chromosomal synapsis and DSB repairs partially via its regulation of DSB repair-associated protein expression during meiotic progression in mouse.

  8. Emergence of apospory and bypass of meiosis via apomixis after sexual hybridisation and polyploidisation.

    PubMed

    Hojsgaard, Diego; Greilhuber, Johann; Pellino, Marco; Paun, Ovidiu; Sharbel, Timothy F; Hörandl, Elvira

    2014-12-01

    Hybridisation and polyploidy are major forces contributing to plant speciation. Homoploid (2x) and heteroploid (3x) hybrids, however, represent critical stages for evolution due to disturbed meiosis and reduced fertility. Apomixis--asexual reproduction via seeds--can overcome hybrid sterility, but requires several concerted alterations of developmental pathways to result in functional seed formation. Here, we analyse the reproductive behaviours of homo- and heteroploid synthetic hybrids from crosses between sexual diploid and tetraploid Ranunculus auricomus species to test the hypothesis that developmental asynchrony in hybrids triggers the shift to apomictic reproduction. Evaluation of male and female gametophyte development, viability and functionality of gametes shows developmental asynchrony, whereas seed set and germinability indicate reduced fitness in synthetic hybrids compared to sexual parents. We present the first experimental evidence for spontaneous apospory in most hybrids as an alternative pathway to meiosis, and the appearance of functional apomictic seeds in triploids. Bypassing meiosis permits these triploid genotypes to form viable seed and new polyploid progeny. Asynchronous development causes reduced sexual seed set and emergence of apospory in synthetic Ranunculus hybrids. Apomixis is functional in triploids and associated with drastic meiotic abnormalities. Selection acts to stabilise developmental patterns and to tolerate endosperm dosage balance shifts which facilitates successful seed set and establishment of apomictic lineages.

  9. A meiosis-specific Spt5 homolog involved in non-coding transcription.

    PubMed

    Gruchota, Julita; Denby Wilkes, Cyril; Arnaiz, Olivier; Sperling, Linda; Nowak, Jacek K

    2017-01-03

    Spt5 is a conserved and essential transcriptional regulator that binds directly to RNA polymerase and is involved in transcription elongation, polymerase pausing and various co-transcriptional processes. To investigate the role of Spt5 in non-coding transcription, we used the unicellular model Paramecium tetraurelia In this ciliate, development is controlled by epigenetic mechanisms that use different classes of non-coding RNAs to target DNA elimination. We identified two SPT5 genes. One (STP5v) is involved in vegetative growth, while the other (SPT5m) is essential for sexual reproduction. We focused our study on SPT5m, expressed at meiosis and associated with germline nuclei during sexual processes. Upon Spt5m depletion, we observed absence of scnRNAs, piRNA-like 25 nt small RNAs produced at meiosis. The scnRNAs are a temporal copy of the germline genome and play a key role in programming DNA elimination. Moreover, Spt5m depletion abolishes elimination of all germline-limited sequences, including sequences whose excision was previously shown to be scnRNA-independent. This suggests that in addition to scnRNA production, Spt5 is involved in setting some as yet uncharacterized epigenetic information at meiosis. Our study establishes that Spt5m is crucial for developmental genome rearrangements and necessary for scnRNA production.

  10. Ewing sarcoma gene EWS is essential for meiosis and B lymphocyte development

    PubMed Central

    Li, Hongjie; Watford, Wendy; Li, Cuiling; Parmelee, Alissa; Bryant, Mark A.; Deng, Chuxia; O’Shea, John; Lee, Sean Bong

    2007-01-01

    Ewing sarcoma gene EWS encodes a putative RNA-binding protein with proposed roles in transcription and splicing, but its physiological role in vivo remains undefined. Here, we have generated Ews-deficient mice and demonstrated that EWS is required for the completion of B cell development and meiosis. Analysis of Ews–/– lymphocytes revealed a cell-autonomous defect in precursor B lymphocyte (pre–B lymphocyte) development. During meiosis, Ews-null spermatocytes were deficient in XY bivalent formation and showed reduced meiotic recombination, resulting in massive apoptosis and complete arrest in gamete maturation. Inactivation of Ews in mouse embryonic fibroblasts resulted in premature cellular senescence, and the mutant animals showed hypersensitivity to ionizing radiation. Finally, we showed that EWS interacts with lamin A/C and that loss of EWS results in a reduced lamin A/C expression. Our findings reveal essential functions for EWS in pre–B cell development and meiosis, with proposed roles in DNA pairing and recombination/repair mechanisms. Furthermore, we demonstrate a novel role of EWS in cellular senescence, possibly through its interaction and modulation of lamin A/C. PMID:17415412

  11. Resolving complex chromosome structures during meiosis: versatile deployment of Smc5/6.

    PubMed

    Verver, Dideke E; Hwang, Grace H; Jordan, Philip W; Hamer, Geert

    2016-03-01

    The Smc5/6 complex, along with cohesin and condensin, is a member of the structural maintenance of chromosome (SMC) family, large ring-like protein complexes that are essential for chromatin structure and function. Thanks to numerous studies of the mitotic cell cycle, Smc5/6 has been implicated to have roles in homologous recombination, restart of stalled replication forks, maintenance of ribosomal DNA (rDNA) and heterochromatin, telomerase-independent telomere elongation, and regulation of chromosome topology. The nature of these functions implies that the Smc5/6 complex also contributes to the profound chromatin changes, including meiotic recombination, that characterize meiosis. Only recently, studies in diverse model organisms have focused on the potential meiotic roles of the Smc5/6 complex. Indeed, Smc5/6 appears to be essential for meiotic recombination. However, due to both the complexity of the process of meiosis and the versatility of the Smc5/6 complex, many additional meiotic functions have been described. In this review, we provide a clear overview of the multiple functions found so far for the Smc5/6 complex in meiosis. Additionally, we compare these meiotic functions with the known mitotic functions in an attempt to find a common denominator and thereby create clarity in the field of Smc5/6 research.

  12. Dgcr8 and Dicer are essential for sex chromosome integrity during meiosis in males.

    PubMed

    Modzelewski, Andrew J; Hilz, Stephanie; Crate, Elizabeth A; Schweidenback, Caterina T H; Fogarty, Elizabeth A; Grenier, Jennifer K; Freire, Raimundo; Cohen, Paula E; Grimson, Andrew

    2015-06-15

    Small RNAs play crucial roles in regulating gene expression during mammalian meiosis. To investigate the function of microRNAs (miRNAs) and small interfering RNAs (siRNAs) during meiosis in males, we generated germ-cell-specific conditional deletions of Dgcr8 and Dicer in mice. Analysis of spermatocytes from both conditional knockout lines revealed that there were frequent chromosomal fusions during meiosis, always involving one or both sex chromosomes. RNA sequencing indicates upregulation of Atm in spermatocytes from miRNA-deficient mice, and immunofluorescence imaging demonstrates an increased abundance of activated ATM kinase and mislocalization of phosphorylated MDC1, an ATM phosphorylation substrate. The Atm 3'UTR contains many potential microRNA target sites, and, notably, target sites for several miRNAs depleted in both conditional knockout mice were highly effective at promoting repression. RNF8, a telomere-associated protein whose localization is controlled by the MDC1-ATM kinase cascade, normally associates with the sex chromosomes during pachytene, but in both conditional knockouts redistributed to the autosomes. Taken together, these results suggest that Atm dysregulation in microRNA-deficient germ lines contributes to the redistribution of proteins involved in chromosomal stability from the sex chromosomes to the autosomes, resulting in sex chromosome fusions during meiotic prophase I.

  13. Anillin localization suggests distinct mechanisms of division plane specification in mouse oogenic meiosis I and II.

    PubMed

    Sharif, Bedra; Fadero, Tanner; Maddox, Amy Shaub

    2015-03-01

    Anillin is a conserved cytokinetic ring protein implicated in actomyosin cytoskeletal organization and cytoskeletal-membrane linkage. Here we explored anillin localization in the highly asymmetric divisions of the mouse oocyte that lead to the extrusion of two polar bodies. The purposes of polar body extrusion are to reduce the chromosome complement within the egg to haploid, and to retain the majority of the egg cytoplasm for embryonic development. Anillin's proposed roles in cytokinetic ring organization suggest that it plays important roles in achieving this asymmetric division. We report that during meiotic maturation, anillin mRNA is expressed and protein levels steadily rise. In meiosis I, anillin localizes to a cortical cap overlying metaphase I spindles, and a broad ring over anaphase spindles that are perpendicular to the cortex. Anillin is excluded from the cortex of the prospective first polar body, and highly enriched in the cytokinetic ring that severs the polar body from the oocyte. In meiosis II, anillin is enriched in a cortical stripe precisely coincident with and overlying the meiotic spindle midzone. These results suggest a model in which this cortical structure contributes to spindle re-alignment in meiosis II. Thus, localization of anillin as a conserved cytokinetic ring marker illustrates that the geometry of the cytokinetic ring is distinct between the two oogenic meiotic cytokineses in mammals.

  14. The key role of CYC2 during meiosis in Tetrahymena thermophila.

    PubMed

    Xu, Qianlan; Wang, Ruoyu; Ghanam, A R; Yan, Guanxiong; Miao, Wei; Song, Xiaoyuan

    2016-04-01

    Meiotic recombination is carried out through a specialized pathway for the formation and repair of DNA double-strand breaks (DSBs) made by the Spo11 protein. The present study shed light on the functional role of cyclin, CYC2, in Tetrahymena thermophila which has transcriptionally high expression level during meiosis process. Knocking out the CYC2 gene results in arrest of meiotic conjugation process at 2.5-3.5 h after conjugation initiation, before the meiosis division starts, and in company with the absence of DSBs. To investigate the underlying mechanism of this phenomenon, a complete transcriptome profile was performed between wild-type strain and CYC2 knock-out strain. Functional analysis of RNA-Seq results identifies related differentially expressed genes (DEGs) including SPO11 and these DEGs are enriched in DNA repair/mismatch repair (MMR) terms in homologous recombination (HR), which indicates that CYC2 could play a crucial role in meiosis by regulating SPO11 and participating in HR.

  15. Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling.

    PubMed

    Chen, Su-Ren; Liu, Yi-Xun

    2015-04-01

    Spermatogenesis is a continuous and productive process supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs), which arise from undifferentiated precursors known as gonocytes and are strictly controlled in a special 'niche' microenvironment in the seminiferous tubules. Sertoli cells, the only somatic cell type in the tubules, directly interact with SSCs to control their proliferation and differentiation through the secretion of specific factors. Spermatocyte meiosis is another key step of spermatogenesis, which is regulated by Sertoli cells on the luminal side of the blood-testis barrier through paracrine signaling. In this review, we mainly focus on the role of Sertoli cells in the regulation of SSC self-renewal and spermatocyte meiosis, with particular emphasis on paracrine and endocrine-mediated signaling pathways. Sertoli cell growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2), as well as Sertoli cell transcription factors, such as ETS variant 5 (ERM; also known as ETV5), nociceptin, neuregulin 1 (NRG1), and androgen receptor (AR), have been identified as the most important upstream factors that regulate SSC self-renewal and spermatocyte meiosis. Other transcription factors and signaling pathways (GDNF-RET-GFRA1 signaling, FGF2-MAP2K1 signaling, CXCL12-CXCR4 signaling, CCL9-CCR1 signaling, FSH-nociceptin/OPRL1, retinoic acid/FSH-NRG/ERBB4, and AR/RB-ARID4A/ARID4B) are also addressed.

  16. Widespread failure to complete meiosis does not impair fecundity in parthenogenetic whiptail lizards

    PubMed Central

    Newton, Aracely A.; Schnittker, Robert R.; Yu, Zulin; Munday, Sarah S.; Neaves, William B.; Baumann, Peter

    2016-01-01

    Parthenogenetic species of whiptail lizards in the genus Aspidoscelis constitute a striking example of speciation by hybridization, in which first-generation hybrids instantly attain reproductive isolation and procreate as clonal all-female lineages. Production of eggs containing a full complement of chromosomes in the absence of fertilization involves genome duplication prior to the meiotic divisions. In these pseudo-tetraploid oocytes, pairing and recombination occur exclusively between identical chromosomes instead of homologs; a deviation from the normal meiotic program that maintains heterozygosity. Whether pseudo-tetraploid cells arise early in germ cell development or just prior to meiosis has remained unclear. We now show that in the obligate parthenogenetic species A. neomexicana the vast majority of oocytes enter meiosis as diploid cells. Telomere bouquet formation is normal, but synapsis fails and oocytes accumulate in large numbers at the pairing stage. Pseudo-tetraploid cells are exceedingly rare in early meiotic prophase, but they are the only cells that progress into diplotene. Despite the widespread failure to increase ploidy prior to entering meiosis, the fecundity of parthenogenetic A. neomexicana is similar to that of A. inornata, one of its bisexual ancestors. PMID:27802173

  17. Dgcr8 and Dicer are essential for sex chromosome integrity during meiosis in males

    PubMed Central

    Modzelewski, Andrew J.; Hilz, Stephanie; Crate, Elizabeth A.; Schweidenback, Caterina T. H.; Fogarty, Elizabeth A.; Grenier, Jennifer K.; Freire, Raimundo; Cohen, Paula E.; Grimson, Andrew

    2015-01-01

    ABSTRACT Small RNAs play crucial roles in regulating gene expression during mammalian meiosis. To investigate the function of microRNAs (miRNAs) and small interfering RNAs (siRNAs) during meiosis in males, we generated germ-cell-specific conditional deletions of Dgcr8 and Dicer in mice. Analysis of spermatocytes from both conditional knockout lines revealed that there were frequent chromosomal fusions during meiosis, always involving one or both sex chromosomes. RNA sequencing indicates upregulation of Atm in spermatocytes from miRNA-deficient mice, and immunofluorescence imaging demonstrates an increased abundance of activated ATM kinase and mislocalization of phosphorylated MDC1, an ATM phosphorylation substrate. The Atm 3′UTR contains many potential microRNA target sites, and, notably, target sites for several miRNAs depleted in both conditional knockout mice were highly effective at promoting repression. RNF8, a telomere-associated protein whose localization is controlled by the MDC1–ATM kinase cascade, normally associates with the sex chromosomes during pachytene, but in both conditional knockouts redistributed to the autosomes. Taken together, these results suggest that Atm dysregulation in microRNA-deficient germ lines contributes to the redistribution of proteins involved in chromosomal stability from the sex chromosomes to the autosomes, resulting in sex chromosome fusions during meiotic prophase I. PMID:25934699

  18. Mps3 SUN domain is important for chromosome motion and juxtaposition of homologous chromosomes during meiosis.

    PubMed

    Rao, Hanumanthu B D Prasada; Shinohara, Miki; Shinohara, Akira

    2011-11-01

    In budding yeast, Mps3 is essential for duplicating the spindle pole body (SPB) and is critical for promoting chromosome motion during meiosis. It is a member of the SUN (Sad1-Unc-84) domain family of proteins that localizes to the inner nuclear envelope (NE) in many eukaryotic organisms and preferentially localizes to the SPB in vegetative growth; in meiotic prophase I, it redistributes to many sites within the NE. We constructed an mps3 mutant, mps3-sun, which completely lacks the SUN domain. Surprisingly, the mps3-sun mutation does not disrupt SPB duplication or Mps3 localization to the NE in meiosis. However, it confers several defects during meiotic prophase I including reduced chromosome motion, premature synapsis between homologous chromosomes, and reduced levels of closely juxtaposed homologous loci in pachytene. These findings suggest that in meiosis, the Mps3 SUN domain is important for modulating chromosome motion events that act in meiotic chromosome juxtaposition and by extension, promoting proper morphogenesis of the synaptonemal complex.

  19. Efficacy of a Meiosis Learning Module Developed for the Virtual Cell Animation Collection

    PubMed Central

    Goff, Eric E.; Reindl, Katie M.; Johnson, Christina; McClean, Phillip; Offerdahl, Erika G.; Schroeder, Noah L.; White, Alan R.

    2017-01-01

    Recent reports calling for change in undergraduate biology education have resulted in the redesign of many introductory biology courses. Reports on one common change to course structure, the active-learning environment, have placed an emphasis on student preparation, noting that the positive outcomes of active learning in the classroom depend greatly on how well the student prepares before class. As a possible preparatory resource, we test the efficacy of a learning module developed for the Virtual Cell Animation Collection. This module presents the concepts of meiosis in an interactive, dynamic environment that has previously been shown to facilitate learning in introductory biology students. Participants (n = 534) were enrolled in an introductory biology course and were presented the concepts of meiosis in one of two treatments: the interactive-learning module or a traditional lecture session. Analysis of student achievement shows that students who viewed the learning module as their only means of conceptual presentation scored significantly higher (d = 0.40, p < 0.001) than students who only attended a traditional lecture on the topic. Our results show the animation-based learning module effectively conveyed meiosis conceptual understanding, which suggests that it may facilitate student learning outside the classroom. Moreover, these results have implications for instructors seeking to expand their arsenal of tools for “flipping” undergraduate biology courses. PMID:28188282

  20. Mouse Tafazzin Is Required for Male Germ Cell Meiosis and Spermatogenesis.

    PubMed

    Cadalbert, Laurence C; Ghaffar, Farah Naz; Stevenson, David; Bryson, Sheila; Vaz, Frédéric M; Gottlieb, Eyal; Strathdee, Douglas

    2015-01-01

    Barth syndrome is an X-linked mitochondrial disease, symptoms of which include neutropenia and cardiac myopathy. These symptoms are the most significant clinical consequences of a disease, which is increasingly recognised to have a variable presentation. Mutation in the Taz gene in Xq28 is thought to be responsible for the condition, by altering mitochondrial lipid content and mitochondrial function. Male chimeras carrying a targeted mutation of Taz on their X-chromosome were infertile. Testes from the Taz knockout chimeras were smaller than their control counterparts and this was associated with a disruption of the progression of spermatocytes through meiosis to spermiogenesis. Taz knockout ES cells also showed a defect when differentiated to germ cells in vitro. Mutant spermatocytes failed to progress past the pachytene stage of meiosis and had higher levels of DNA double strand damage and increased levels of endogenous retrotransposon activity. Altogether these data revealed a novel role for Taz in helping to maintain genome integrity in meiosis and facilitating germ cell differentiation. We have unravelled a novel function for the Taz protein, which should contribute to an understanding of how a disruption of the Taz gene results in the complex symptoms underlying Barth Syndrome.