| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Jarvis, Erich D., et al.
(författare)
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Whole-genome analyses resolve early branches in the tree of life of modern birds
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
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Tidskriftsartikel (refereegranskat)abstract
- To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
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| 3. |
- Zhang, Hua, et al.
(författare)
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Life-long in vivo cell-lineage tracing shows that no oogenesis originates from putative germline stem cells in adult mice
- 2014
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Ingår i: Proceedings of the National Academy of Science of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:50, s. 17983-17988
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Tidskriftsartikel (refereegranskat)abstract
- Whether or not oocyte regeneration occurs in adult life has been the subject of much debate. In this study, we have traced germcell lineages over the life spans of three genetically modified mouse models and provide direct evidence that oogenesis does not originate from any germline stem cells (GSCs) in adult mice. By selective ablation of all existing oocytes in a Gdf9-Cre;iDTR mouse model, we have demonstrated that no new germ cells were ever regenerated under pathological conditions. By in vivo tracing of oocytes and follicles in the Sohlh1-CreERT2;R26R and Foxl2-CreERT2;mT/mG mouse models, respectively, we have shown that the initial pool of oocytes is the only source of germ cells throughout the life span of the mice and that no adult oogenesis ever occurs under physiological conditions. Our findings clearly show that there are no GSCs that contribute to adult oogenesis in mice and that the initial pool of oocytes formed in early life is the only source of germ cells throughout the entire reproductive life span.
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| 4. |
- Adhikari, Deepak, et al.
(författare)
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Cdk1, but not Cdk2, is the sole Cdk that is essential and sufficient to drive resumption of meiosis in mouse oocytes
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:11, s. 2476-2484
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Tidskriftsartikel (refereegranskat)abstract
- Mammalian oocytes are arrested at the prophase of meiosis I during fetal or postnatal development, and the meiosis is resumed by the preovulatory surge of luteinizing hormone. The in vivo functional roles of cyclin-dependent kinases (Cdks) during the resumption of meiosis in mammalian oocytes are largely unknown. Previous studies have shown that deletions of Cdk3, Cdk4 or Cdk6 in mice result in viable animals with normal oocyte maturation, indicating that these Cdks are not essential for the meiotic maturation of oocytes. In addition, conventional knockout of Cdk1 and Cdk2 leads to embryonic lethality and postnatal follicular depletion, respectively, making it impossible to study the functions of Cdk1 and Cdk2 in oocyte meiosis. In this study, we generated conditional knockout mice with oocyte-specific deletions of Cdk1 and Cdk2. We showed that the lack of Cdk1, but not of Cdk2, leads to female infertility due to a failure of the resumption of meiosis in the oocyte. Re-introduction of Cdk1 mRNA into Cdk1-null oocytes largely resumed meiosis. Thus, Cdk1 is the sole Cdk that is essential and sufficient to drive resumption of meiosis in mouse oocytes. We also found that Cdk1 maintains the phosphorylation status of protein phosphatase 1 and lamin A/C in oocytes in order for meiosis resumption to occur.
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| 5. |
- Adhikari, Deepak, et al.
(författare)
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Mastl is required for timely activation of APC/C in meiosis I and Cdk1 reactivation in meiosis II.
- 2014
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 206:7, s. 843-853
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
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| 7. |
- Adhikari, Deepak, et al.
(författare)
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Pharmacological Inhibition of mTORC1 Prevents Over-Activation of the Primordial Follicle Pool in Response to Elevated PI3K Signaling
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The majority of ovarian primordial follicles must be preserved in a quiescent state to allow for the regular production of gametes over the female reproductive lifespan. However, the molecular mechanism that maintains the long quiescence of primordial follicles is poorly understood. Under certain pathological conditions, the entire pool of primordial follicles matures simultaneously leading to an accelerated loss of primordial follicles and to premature ovarian failure (POF). We have previously shown that loss of Pten (phosphatase and tensin homolog deleted on chromosome ten) in mouse oocytes leads to premature activation of the entire pool of primordial follicles, subsequent follicular depletion in early adulthood, and the onset of POF. Lack of PTEN leads to increased phosphatidylinositol 3-kinase (PI3K)-Akt and mammalian target of rapamycin complex 1 (mTORC1) signaling in the oocytes. To study the functional and pathological roles of elevated mTORC1 signaling in the oocytes, we treated the Pten-mutant mice with the specific mTORC1 inhibitor rapamycin. When administered to Pten-deficient mice prior to the activation of the primordial follicles, rapamycin effectively prevented global follicular activation and preserved the ovarian reserve. These results provide a rationale for exploring the possible use of rapamycin as a drug for the preservation of the primordial follicle pool, and the possible prevention of POF.
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| 8. |
- Adhikari, Deepak, et al.
(författare)
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Regulation of quiescence and activation of oocyte growth in primordial follicles
- 2013
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Ingår i: Oogenesis. - London : Springer. - 9780857298263 - 9780857298256 ; , s. 49-62
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Bokkapitel (refereegranskat)abstract
- Once formed, the pool of dormant primordial follicles serves as the source of developing follicles and fertilizable ova for the duration of a female’s reproductive life. Depending upon the species, primordial follicles can remain quiescent for months, years, or even decades, and the highly regulated process of primordial follicle activation ensures the availability of growing follicles throughout the reproductive period. We have recently begun to elucidate the molecular mechanisms underlying the maintenance of follicular quiescence and the activation of primordial follicles, mainly through the use of genetically modified mouse models. Both overactivation as well as the failure of activation of primordial follicles can lead to pathological conditions such as premature ovarian failure (POF) in the experimental models. A thorough understanding of the underlying mechanisms that regulate quiescence and activation of oocyte growth in primordial follicles will have important biological and clinical implications. © Springer-Verlag London 2013.
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| 9. |
- Adhikari, Deepak, 1978-
(författare)
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Signaling pathways in the development of female germ cells
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Primordial follicles are the first small follicles to appear in the mammalian ovary. Women are born with a fixed number of primordial follicles in the ovaries. Once formed, the pool of primordial follicles serves as a source of developing follicles and oocytes. The first aim of this thesis was to investigate the functional role of the intra-oocyte signaling pathways, especially the phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin complex 1 (mTORC1) pathways in the regulation of primordial follicle activation and survival. We found that a primordial follicle remains dormant when the PI3K and mTORC1 signaling in its oocyte is activated to an appropriate level, which is just sufficient to maintain its survival, but not sufficient for its growth initiation. Hyperactivation of either of these signaling pathways causes global activation of the entire pool of primordial follicles leading to the exhaustion of all the follicles in young adulthood in mice. Mammalian oocytes, while growing within the follicles, remain arrested at prophase I of meiosis. Oocytes within the fully-grown antral follicles resume meiosis upon a preovulatory surge of leutinizing hormone (LH), which indicates that LH mediates the resumption of meiosis. The prophase I arrest in the follicle-enclosed oocyte is the result of low maturation promoting factor (MPF) activity, and resumption of meiosis upon the arrival of hormonal signals is mediated by activation of MPF. MPF is a complex of cyclin dependent kinase 1 (Cdk1) and cyclin B1, which is essential and sufficient for entry into mitosis. Although much of the mitotic cell cycle machinery is shared during meiosis, lack of Cdk2 in mice leads to a postnatal loss of all oocytes, indicating that Cdk2 is important for oocyte survival, and probably oocyte meiosis also. There have been conflicting results earlier about the role of Cdk2 in metaphase II arrest of Xenopus oocytes. Thus the second aim of the thesis was to identify the specific Cdk that is essential for mouse oocyte meiotic maturation. We generated mouse models with oocytespecific deletion of Cdk1 or Cdk2 and studied the specific requirements of Cdk1 and Cdk2 during resumption of oocyte meiosis. We found that only Cdk1 is essential and sufficient for the oocyte meiotic maturation. Cdk1 does not only phosphorylate the meiotic phosphoproteins during meiosis resumption but also phosphorylates and suppresses the downstream protein phosphatase 1, which is essential for protecting the Cdk1 substrates from dephosphorylation.
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| 10. |
- Adhikari, Deepak, et al.
(författare)
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The regulation of maturation promoting factor during prophase I arrest and meiotic entry in mammalian oocytes
- 2014
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207. ; 382:1, s. 480-487
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Tidskriftsartikel (refereegranskat)abstract
- Mammalian oocytes arrest at prophase of meiosis I at around birth and they remain arrested at this stage until puberty when the preovulatory surge of luteinizing hormone (LH) causes ovulation. Prophase I arrest in the immature oocyte results from the maintenance of low activity of maturation promoting factor (MPF), which consists of a catalytic subunit (CDK1) and regulatory subunit (cyclin B1). Phosphorylation-mediated inactivation of CDK1 and constant degradation of cyclin B1 keep MPF activity low during prophase I arrest. LH-mediated signaling manipulates a vast array of molecules to activate CDK1. Active CDK1 not only phosphorylates different meiotic phosphoproteins during the resumption of meiosis but also inhibits their rapid dephosphorylation by inhibiting the activities of CDK1 antagonizing protein phosphatases (PPs). In this way, CDK1 both phosphorylates its substrates and protects them from being dephosphorylated. Accumulating evidence suggests thatthe net MPF activity that drives the resumption of meiosis in oocytes depends on the activation status of CDK1 antagonizing PPs. This review aims to provide a summary of the current understanding of the signaling pathways involved in regulating MPF activity during prophase I arrest and reentry into meiosis of mammalian oocytes. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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| 11. |
- Adhikari, Deepak, et al.
(författare)
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The Safe Use of a PTEN Inhibitor for the Activation of Dormant Mouse Primordial Follicles and Generation of Fertilizable Eggs
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primordial ovarian follicles, which are often present in the ovaries of premature ovarian failure (POF) patients or are cryopreserved from the ovaries of young cancer patients who are undergoing gonadotoxic anticancer therapies, cannot be used to generate mature oocytes for in vitro fertilization (IVF). There has been very little success in triggering growth of primordial follicles to obtain fertilizable oocytes due to the poor understanding of the biology of primordial follicle activation. Methodology/Principal Findings: We have recently reported that PTEN (phosphatase and tensin homolog deleted on chromosome ten) prevents primordial follicle activation in mice, and deletion of Pten from the oocytes of primordial follicles leads to follicular activation. Consequently, the PTEN inhibitor has been successfully used in vitro to activate primordial follicles in both mouse and human ovaries. These results suggest that PTEN inhibitors could be used in ovarian culture medium to trigger the activation of primordial follicle. To study the safety and efficacy of the use of such inhibitors, we activated primordial follicles from neonatal mouse ovaries by transient treatment with a PTEN inhibitor bpV(HOpic). These ovaries were then transplanted under the kidney capsules of recipient mice to generate mature oocytes. The mature oocytes were fertilized in vitro and progeny mice were obtained after embryo transfer. Results and Conclusions: Long-term monitoring up to the second generation of progeny mice showed that the mice were reproductively active and were free from any overt signs or symptoms of chronic illnesses. Our results indicate that the use of PTEN inhibitors could be a safe and effective way of generating mature human oocytes for use in novel IVF techniques.
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| 12. |
- Adhikari, Deepak, et al.
(författare)
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Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:3, s. 397-410
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Tidskriftsartikel (refereegranskat)abstract
- To maintain the female reproductive lifespan, the majority of ovarian primordial follicles are preserved in a quiescent state in order to provide ova for later reproductive life. However, the molecular mechanism that maintains the long quiescence of primordial follicles is poorly understood. Here we provide genetic evidence to show that the tumor suppressor tuberous sclerosis complex 1 (Tsc1), which negatively regulates mammalian target of rapamycin complex 1 (mTORC1), functions in oocytes to maintain the quiescence of primordial follicles. In mutant mice lacking the Tsc1 gene in oocytes, the entire pool of primordial follicles is activated prematurely due to elevated mTORC1 activity in the oocyte, ending up with follicular depletion in early adulthood and causing premature ovarian failure (POF). We further show that maintenance of the quiescence of primordial follicles requires synergistic, collaborative functioning of both Tsc and PTEN (phosphatase and tensin homolog deleted on chromosome 10) and that these two molecules suppress follicular activation through distinct ways. Our results suggest that Tsc/mTORC1 signaling and PTEN/PI3K (phosphatidylinositol 3 kinase) signaling synergistically regulate the dormancy and activation of primordial follicles, and together ensure the proper length of female reproductive life. Deregulation of these signaling pathways in oocytes results in pathological conditions of the ovary, including POF and infertility.
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| 13. |
- Calounova, Gabriela, et al.
(författare)
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The Src homology 2 domain-containing adapter protein B (SHB) regulates mouse oocyte maturation
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:6, s. e11155-
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Tidskriftsartikel (refereegranskat)abstract
- SHB (Src homology 2 domain-containing adapter protein B) is involved in receptor tyrosine kinase signaling. Mice deficient in the Shb gene have been found to exhibit a transmission ratio distortion with respect to inheritance of the Shb null allele among offspring and this phenomenon was linked to female gamete production. Consequently, we postulated that Shb plays a role for oocyte biology and thus decided to investigate oocyte formation, meiotic maturation, and early embryo development in relation to absence of the Shb gene. Oogenesis was apparently accelerated judging from the stages of oocyte development on fetal day 18.5 and one week postnatally in Shb -/- mice; but in adulthood ovarian follicle maturation was impaired in these mice. Completion of meiosis I (first polar body extrusion) was less synchronized, with a fraction of oocytes showing premature polar body extrusion in the absence of Shb. In vitro fertilization of mature oocytes isolated from Shb +/+, +/- and -/- mice revealed impaired early embryo development in the -/- embryos. Moreover, the absence of Shb enhanced ERK (extracellular-signal regulated kinase) and RSK (ribosomal S6 kinase) signaling in oocytes and these effects were paralleled by an increased ribosomal protein S6 phosphorylation and activation. It is concluded that SHB regulates normal oocyte and follicle development and that perturbation of SHB signaling causes defective meiosis I and early embryo development.
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| 14. |
- Gorre, Nagaraju, et al.
(författare)
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mTORC1 Signaling in Oocytes Is Dispensable for the Survival of Primordial Follicles and for Female Fertility
- 2014
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- The molecular mechanisms underlying reproductive aging and menopausal age in female mammals are poorly understood. Mechanistic target of rapamycin complex 1 (mTORC1) is a central controller of cell growth and proliferation. To determine whether mTORC1 signaling in oocytes plays a direct role in physiological follicular development and fertility in female mice, we conditionally deleted the specific and essential mTORC1 component Rptor (regulatory-associated protein of mTORC1) from the oocytes of primordial follicles by using transgenic mice expressing growth differentiation factor 9 (Gdf-9) promoter-mediated Cre recombinase. We provide in vivo evidence that deletion of Rptor in the oocytes of both primordial and further-developed follicles leads to the loss of mTORC1 signaling in oocytes as indicated by loss of phosphorylation of S6K1 and 4e-bp1 at T389 and S65, respectively. However, the follicular development and fertility of mice lacking Rptor in oocytes were not affected. Mechanistically, the loss of mTORC1 signaling in Rptor-deleted mouse oocytes led to the elevation of phosphatidylinositol 3-kinase (PI3K) signaling that maintained normal follicular development and fertility. Therefore, this study shows that loss of mTORC1 signaling in oocytes triggers a compensatory activation of the PI3K signaling cascade that maintains normal ovarian follicular development and fertility.
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| 15. |
- Hyde, Kevin D., et al.
(författare)
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One stop shop: backbones trees for important phytopathogenic genera: I (2014)
- 2014
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Ingår i: Fungal diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 67:1, s. 21-125
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Tidskriftsartikel (refereegranskat)abstract
- Many fungi are pathogenic on plants and cause significant damage in agriculture and forestry. They are also part of the natural ecosystem and may play a role in regulating plant numbers/density. Morphological identification and analysis of plant pathogenic fungi, while important, is often hampered by the scarcity of discriminatory taxonomic characters and the endophytic or inconspicuous nature of these fungi. Molecular (DNA sequence) data for plant pathogenic fungi have emerged as key information for diagnostic and classification studies, although hampered in part by non-standard laboratory practices and analytical methods. To facilitate current and future research, this study provides phylogenetic synopses for 25 groups of plant pathogenic fungi in the Ascomycota, Basidiomycota, Mucormycotina (Fungi), and Oomycota, using recent molecular data, up-to-date names, and the latest taxonomic insights. Lineage-specific laboratory protocols together with advice on their application, as well as general observations, are also provided. We hope to maintain updated backbone trees of these fungal lineages over time and to publish them jointly as new data emerge. Researchers of plant pathogenic fungi not covered by the present study are invited to join this future effort. Bipolaris, Botryosphaeriaceae, Botryosphaeria, Botrytis, Choanephora, Colletotrichum, Curvularia, Diaporthe, Diplodia, Dothiorella, Fusarium, Gilbertella, Lasiodiplodia, Mucor, Neofusicoccum, Pestalotiopsis, Phyllosticta, Phytophthora, Puccinia, Pyrenophora, Pythium, Rhizopus, Stagonosporopsis, Ustilago and Verticillium are dealt with in this paper.
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| 16. |
- Jagarlamudi, Krishna, et al.
(författare)
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Genetically modified mouse models for premature ovarian failure (POF)
- 2010
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 315:1-2, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Premature ovarian failure (POF) is a complex disorder that affects approximately 1% of women. POF is characterized by the depletion of functional ovarian follicles before the age of 40 years, and clinically, patients may present with primary amenorrhea or secondary amenorrhea. Although some genes have been hypothesized to be candidates responsible for POF, the etiology of most of the cases is idiopathic, with the underlying causes still unidentified because of the heterogeneity of the disease. In this review, we consider some mutant mouse models that exhibit phenotypes which are comparable to human POF, and we suggest that the use of these mouse models may help us to gain a better understanding of the molecular mechanisms underlying POF in humans.
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| 17. |
- Nilsson, R. Henrik, 1976, et al.
(författare)
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Improving ITS sequence data for identification of plant pathogenic fungi
- 2014
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Ingår i: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 67:1, s. 11-19
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Tidskriftsartikel (refereegranskat)abstract
- Plant pathogenic fungi are a large and diverse assemblage of eukaryotes with substantial impacts on natural ecosystems and human endeavours. These taxa often have complex and poorly understood life cycles, lack observable, discriminatory morphological characters, and may not be amenable to in vitro culturing. As a result, species identification is frequently difficult. Molecular (DNA sequence) data have emerged as crucial information for the taxonomic identification of plant pathogenic fungi, with the nuclear ribosomal internal transcribed spacer (ITS) region being the most popular marker. However, international nucleotide sequence databases are accumulating numerous sequences of compromised or low-resolution taxonomic annotations and substandard technical quality, making their use in the molecular identification of plant pathogenic fungi problematic. Here we report on a concerted effort to identify high-quality reference sequences for various plant pathogenic fungi and to re-annotate incorrectly or insufficiently annotated public ITS sequences from these fungal lineages. A third objective was to enrich the sequences with geographical and ecological metadata. The results – a total of 31,954 changes – are incorporated in and made available through the UNITE database for molecular identification of fungi (http://unite.ut.ee), including standalone FASTA files of sequence data for local BLAST searches, use in the next-generation sequencing analysis platforms QIIME and mothur, and related applications. The present initiative is just a beginning to cover the wide spectrum of plant pathogenic fungi, and we invite all researchers with pertinent expertise to join the annotation effort.
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| 18. |
- Reddy, Pradeep, et al.
(författare)
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Mechanisms maintaining the dormancy and survival of mammalian primordial follicles
- 2010
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Ingår i: Trends in endocrinology and metabolism. - : Elsevier BV. - 1043-2760 .- 1879-3061. ; 21:2, s. 96-103
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Tidskriftsartikel (refereegranskat)abstract
- To preserve the length of a woman's reproductive life it is essential that the majority of her ovarian primordial follicles are maintained in a quiescent state to provide a reserve for continuous reproductive success. The mechanisms maintaining the dormancy and survival of primordial follicles have been a mystery for decades. In recent years information provided by genetically modified mouse models has revealed a number of molecules whose functions are indispensable for the maintenance of follicular quiescence (including PTEN, Tsc1, Tsc2, Foxo3a, p27) and survival (PI3K signaling). Here we summarize this updated information, which hopefully will lead to a better understanding of the pathophysiology of the human ovary and provide potential therapeutic options for some types of infertility.
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| 19. |
- Schoch, Conrad L., et al.
(författare)
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Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi
- 2014
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Ingår i: Database: The Journal of Biological Databases and Curation. - : Oxford University Press (OUP). - 1758-0463. ; 2014:bau061, s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi.
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| 20. |
- Sun, Yu-Ping, et al.
(författare)
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Propagation of a strong x-ray pulse : Pulse compression, stimulated Raman scattering, amplified spontaneous emission, lasing without inversion, and four-wave mixing
- 2010
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 81:1
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Tidskriftsartikel (refereegranskat)abstract
- We study the compression of strong x-ray pulses from x-ray free-electron lasers (XFELs) propagating through the resonant medium of atomic argon. The simulations are based on the three-level model with the frequency of the incident x-ray pulse tuned in the 2p(3/2)-4s resonance. The pulse propagation is accompanied by the self-seeded stimulated resonant Raman scattering (SRRS). The SRRS starts from two channels of amplified spontaneous emission (ASE), 4s-2p(3/2) and 3s-2p(3/2), which form the extensive ringing pattern and widen the power spectrum. The produced seed field triggers the Stokes ASE channel 3s-2p(3/2). The population inversion is quenched for longer propagation distances where the ASE is followed by the lasing without inversion (LWI), which amplifies the Stokes component. Both ASE and LWI reshape the input pulse: The compressed front part of the pulse (up to 100 as) is followed by the long tail of the ringing and beating between the pump and Stokes frequencies. The pump pulse also generates weaker Stokes and anti-Stokes fields caused by four-wave mixing. These four spectral bands have fine structures caused by the dynamical Stark effect. A slowdown of the XFEL pulse up to 78% of the speed of light in vacuum is found because of a large nonlinear refractive index.
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| 21. |
- Zhang, Hua, et al.
(författare)
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Combating ovarian aging depends on the use of existing ovarian follicles, not on putative oogonial stem cells
- 2013
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Ingår i: Reproduction. - : Bioscientifica. - 1470-1626 .- 1741-7899. ; 146:6
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian aging is characterized by both a reduction in egg quality and a drastic reduction in the number of ovarian follicles. It has been generally accepted for 60 years that a fixed population of primordial follicles is established in the ovaries during early life, and in most mammalian species, oocytes cannot renew themselves in postnatal or adult life. This dogma, however, has been challenged over the past decade. In this review, we summarize the recent studies on primordial follicles and putative oogonial stem cells and discuss what resources in the ovary might be more reliable and promising source tools for combating ovarian aging.
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| 22. |
- Zhang, Hua, et al.
(författare)
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Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 109:31, s. 12580-12585
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Tidskriftsartikel (refereegranskat)abstract
- It has been generally accepted for more than half a century that, in most mammalian species, oocytes cannot renew themselves in postnatal or adult life, and that the number of oocytes is already fixed in fetal or neonatal ovaries. This assumption, however, has been challenged over the past decade. In this study, we have taken an endogenous genetic approach to this question and generated a multiple fluorescent Rosa26(rbw/+); Ddx4-Cre germline reporter mouse model for in vivo and in vitro tracing of the development of female germline cell lineage. Through live cell imaging and de novo folliculogenesis experiments, we show that the Ddx4-expressing cells from postnatal mouse ovaries did not enter mitosis, nor did they contribute to oocytes during de novo folliculogenesis. Our results provide evidence that supports the traditional view that no postnatal follicular renewal occurs in mammals, and no mitotically active Ddx4-expressing female germline progenitors exist in postnatal mouse ovaries.
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| 23. |
- Zhang, Hua, et al.
(författare)
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Somatic Cells Initiate Primordial Follicle Activation and Govern the Development of Dormant Oocytes in Mice
- 2014
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822. ; 24:21, s. 2501-2508
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Tidskriftsartikel (refereegranskat)abstract
- Background: The majority of oocytes in the mammalian ovary are dormant oocytes that are enclosed in primordial follicles by several somatic cells, which we refer to as primordial follicle granulosa cells (pfGCs). Very little is known, however, about how the pfGCs control the activation of primordial follicles and the developmental fates of dormant oocytes. Results: By targeting molecules in pfGCs with several mutant mouse models, we demonstrate that the somatic pfGCs initiate the activation of primordial follicles and govern the quiescence or awakening of dormant oocytes. Inhibition of mTORC1 signaling in pfGCs prevents the differentiation of pfGCs into granulosa cells, and this arrests the dormant oocytes in their quiescent states, leading to oocyte death. Overactivation of mTORC1 signaling in pfGCs accelerates the differentiation of pfGCs into granulosa cells and causes premature activation of all dormant oocytes and primordial follicles. We further show that pfGCs trigger the awakening of dormant oocytes through KIT ligand (KITL), and we present an essential communication network between the somatic cells and germ cells that is based on signaling between the mTORC1-KITL cascade in pfGCs and KIT-PI3K signaling in oocytes. Conclusions: Our findings provide a relatively complete picture of how mammalian primordial follicles are activated. The microenvironment surrounding primordial follicles can activate mTORC1-KITL signaling in pfGCs, and these cells trigger the awakening of dormant oocytes and complete the process of follicular activation. Such communication between the microenvironment, somatic cells, and germ cells is essential to maintaining the proper reproductive lifespan in mammals.
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| 24. |
- Zhao, Ke, et al.
(författare)
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Effects of Structural Fluctuations on Two-Photon Absorption Activity of Interacting Dipolar Chromophores
- 2010
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 114:33, s. 10814-10820
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Tidskriftsartikel (refereegranskat)abstract
- One- and two-photon absorption properties of organic chromophores consisting of interacting dipolar branches have been studied using density functional response theory in combination with molecular dynamics simulation. Effects of dipole interaction on optical absorptions have been examined. The importance of solvent effects on optical properties of charge-transfer states is explored by means of polarizable continuum model. It is found that for the interacting dipolar molecule with flexible conformations in solutions, the structural fluctuations can result in new spectral features or significant broadening of one-photon absorption spectrum. Our study highlights again the usefulness of the combined quantum chemical and molecular dynamics approach for modeling two-photon absorption materials in solutions.
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| 25. |
- Zheng, Wenjing, et al.
(författare)
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Functional roles of the phosphatidylinositol 3-kinases (PI3Ks) signaling in the mammalian ovary
- 2012
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 356:1-2, s. 24-30
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Forskningsöversikt (refereegranskat)abstract
- Phosphatidylinositol 3-kinase (PI3K) signaling is a fundamental pathway for the regulation of cell proliferation, survival, migration, and metabolism in a variety of physiological and pathological processes. In recent years information provided by genetically modified mouse models has revealed that PI3K signaling plays vital roles in oogenesis, folliculogenesis, ovulation, and carcinogenesis in mouse ovary. In this review, we summarize (1) the physiological function of intra-oocyte PI3K signaling in regulation of primordial follicle survival and activation; (2) intra-granulosa cell PI3K signaling in regulation of cyclic follicular recruitment and ovulation; (3) intra-oocyte PI3K signaling in regulation of meiosis resumption and early embryogenesis; and also (4) the pathological function of PI3K signaling in ovarian diseases such as premature ovarian failure, granulosa cell tumors, and ovarian surface epithelium carcinomas. This updated info hopefully will lead to a better understanding of the human ovary and provide potential therapies for treating human infertility. © 2011.
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| 26. |
- Zheng, Wenjing, et al.
(författare)
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Maternal phosphatidylinositol 3-kinase signalling is crucial for embryonic genome activation and preimplantation embryogenesis
- 2010
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Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 11:11, s. 890-895
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Tidskriftsartikel (refereegranskat)abstract
- Maternal effect factors derived from oocytes are important for sustaining early embryonic development before the major wave of embryonic genome activation (EGA). In this study, we report a two-cell-stage arrest of embryos lacking maternal 3-phosphoinositide-dependent protein kinase 1 as a result of suppressed EGA. Concurrent deletion of maternal Pten completely rescued the suppressed EGA and embryonic progression through restored AKT signalling, which fully restored the fertility of double-mutant females. Our study identifies maternal phosphatidylinositol 3-kinase signalling as a new maternal effect factor that regulates EGA and preimplantation embryogenesis in mice.
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| 27. |
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| 28. |
- Zheng, Wenjing, et al.
(författare)
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The two classes of primordial follicles in the mouse ovary: their development, physiological functions and implications for future research
- 2014
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Ingår i: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 20:4, s. 286-292
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Forskningsöversikt (refereegranskat)abstract
- Ovarian follicles are the basic functional units in the mammalian ovary. This review summarizes early pioneering studies and focuses on recent progress that has shown that there are two distinct classes of primordial follicles in the ovary: the first wave of primordial follicles that are activated immediately after they are formed and the adult primordial follicles that are activated gradually in later life. These two separate classes have been proposed for two decades, but sufficient experimental evidence to support this hypothesis has only been obtained recently using newly developed follicular tracing techniques in genetically modified mouse models. These two follicle populations differ from each other primarily in terms of their developmental dynamics and their contributions to ovarian physiology. It is apparent now that these two follicle populations should be treated separately, and such knowledge will hopefully lead to a more in-depth understanding of how distinct types of primordial follicles contribute to physiologic and pathologic alterations of the mammalian ovary.
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| 29. |
- Zheng, Wenjing, et al.
(författare)
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Two classes of ovarian primordial follicles exhibit distinct developmental dynamics and physiological functions.
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:4, s. 920-928
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Tidskriftsartikel (refereegranskat)abstract
- In the mammalian ovary, progressive activation of primordial follicles serves as the source of fertilizable ova, and disorders in the development of primordial follicles lead to various ovarian diseases. However, very little is known about the developmental dynamics of primordial follicles under physiological conditions, and the fates of distinct populations of primordial follicles also remain unclear. In this study, by generating the Foxl2-CreERT2 and Sohlh1-CreERT2 inducible mouse models, we have specifically labeled and traced the in vivo development of two classes of primordial follicles, the first wave of simultaneously activated follicles after birth and the primordial follicles that are gradually activated in adulthood. Our results show that the first wave of follicles exists in the ovaries for ∼3 months and contributes to the onset of puberty and to early fertility. The primordial follicles at the ovarian cortex gradually replace the first wave of follicles and dominate the ovary after 3 months of age, providing fertility until the end of reproductive life. Moreover, by tracing the time periods needed for primordial follicles to reach various advanced stages in vivo, we were able to determine the exact developmental dynamics of the two classes of primordial follicles. We have now revealed the lifelong developmental dynamics of ovarian primordial follicles under physiological conditions and have clearly shown that two classes of primordial follicles follow distinct, age-dependent developmental paths and play different roles in the mammalian reproductive lifespan.
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