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[PMID]: 25319395
[Au] Autor:Wang S; Zhang R; Claret FX; Yang H
[Ad] Address:Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China. Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas....
[Ti] Title:Involvement of microRNA-24 and DNA Methylation in Resistance of Nasopharyngeal Carcinoma to Ionizing Radiation.
[So] Source:Mol Cancer Ther;13(12):3163-74, 2014 Dec.
[Is] ISSN:1538-8514
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Nasopharyngeal carcinoma (NPC) is a malignant tumor originating in the epithelium. Radiotherapy is the standard therapy, but tumor resistance to this treatment reduces the 5-year patient survival rate dramatically. Studies are urgently needed to elucidate the mechanism of NPC radioresistance. Epigenetics-particularly microRNAs (miRNA) and DNA methylation-plays an important role in carcinogenesis and oncotherapy. We used qRT-PCR analysis and identified an miRNA signature from differentially expressed miRNAs. Our objectives were to identify the role of miR24 in NPC tumorigenesis and radioresistance and to identify the mechanisms by which miR24 is regulated. We found that miR24 inhibited NPC cell growth, promoted cell apoptosis, and suppressed the growth of NPC xenografts. We showed that miR24 was significantly downregulated in recurrent NPC tissues. When combined with irradiation, miR24 acted as a radiosensitizer in NPC cells. One of the miR24 precursors was embedded in a CpG island. Aberrant DNA methylation was involved in NPC response to radiotherapy, which linked inactivation of miR24 through hypermethylation of its precursor promoter with NPC radioresistance. Treating NPC cells with the DNA-hypomethylating agent 5-aza-2'-deoxycytidine compensated for the reduced miR24 expression. Together, our findings showed that miR24 was negatively regulated by hypermethylation of its precursor promoter in NPC radioresistance. Our findings defined a central role for miR24 as a tumor-suppressive miRNA in NPC and suggested its use in novel strategies for treatment of this cancer. Mol Cancer Ther; 13(12); 3163-74. ©2014 AACR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1158/1535-7163.MCT-14-0317

  2 / 252291 MEDLINE  
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[PMID]: 25385821
[Au] Autor:Zhai SK; Volgina VV; Sethupathi P; Knight KL; Lanning DK
[Ad] Address:Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153....
[Ti] Title:Chemokine-Mediated B Cell Trafficking during Early Rabbit GALT Development.
[So] Source:J Immunol;193(12):5951-9, 2014 Dec 15.
[Is] ISSN:1550-6606
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Microbial and host cell interactions stimulate rabbit B cells to diversify the primary Ab repertoire in GALT. B cells at the base of appendix follicles begin proliferating and diversifying their V-(D)-J genes around 1 wk of age, ∼5 d after B cells first begin entering appendix follicles. To gain insight into the microbial and host cell interactions that stimulate B cells to diversify the primary Ab repertoire, we analyzed B cell trafficking within follicles during the first week of life. We visualized B cells, as well as chemokines that mediate B cell homing in lymphoid tissues, by in situ hybridization, and we examined B cell chemokine receptor expression by flow cytometry. We found that B cells were activated and began downregulating their BCRs well before a detectable B cell proliferative region appeared at the follicle base. The proliferative region was similar to germinal center dark zones, in that it exhibited elevated CXCL12 mRNA expression, and B cells that upregulated CXCR4 mRNA in response to signals acquired from selected intestinal commensals localized in this region. Our results suggest that after entering appendix follicles, B cells home sequentially to the follicle-associated epithelium, the follicular dendritic cell network, the B cell/T cell boundary, and, ultimately, the base of the follicle, where they enter a proliferative program and diversify the primary Ab repertoire.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.4049/jimmunol.1302575

  3 / 252291 MEDLINE  
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[PMID]: 24750037
[Au] Autor:Eidet JR; Utheim OA; Islam R; Lyberg T; Messelt EB; Dartt DA; Utheim TP
[Ad] Address:Unit of Regenerative Medicine, Department of Medical Biochemistry, Oslo University Hospital , Oslo , Norway .
[Ti] Title:The impact of storage temperature on the morphology, viability, cell number and metabolism of cultured human conjunctival epithelium.
[So] Source:Curr Eye Res;40(1):30-9, 2015 Jan.
[Is] ISSN:1460-2202
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:UNLABELLED: Abstract Purpose: To evaluate the effect of storage temperature on the morphology, viability, cell number and metabolism of cultured human conjunctival epithelial cells (HCjEs). MATERIALS AND METHODS: Three-day cultured HCjEs were stored at nine different temperatures between 4 °C and 37 °C for four and seven days. Phenotype was assessed by immunofluorescence microscopy, morphology by scanning electron microscopy, viability and cell number by a microplate fluorometer and glucose metabolism by a blood gas analyzer. RESULTS: Cultured cells not subjected to storage expressed the conjunctival cytokeratins 7 and 19 and the proliferation marker proliferating cell nuclear antigen. Cell morphology was best maintained following four-day storage between 12 °C and 28 °C and following 12 °C storage after seven days. Assessed by propidium iodide uptake, the percentage of viable cells after four-day storage was maintained only between 12 °C and 28 °C, whereas it had decreased in all other groups (p < 0.05; n = 4). After seven days this percentage was maintained in the 12 °C group, but it had decreased in all other groups, compared to the control (p < 0.05; n = 4). The total number of cells remaining in the cultures after four-day storage, compared to the control, had declined in all groups (p < 0.05; n = 4), except 12 °C and 20 °C groups. Following seven days this number had decreased in all groups (p < 0.01; n = 4), except 12 °C storage. Four-day storage at 12 °C demonstrated superior preservation of the number of calcein-stained viable cells (p < 0.05) and the least accumulation of ethidium homodimer 1-stained dead cells (p < 0.001), compared to storage at 4 °C and 24 °C (n = 6). The total metabolism of glucose to lactate after four-day storage was higher in the 24 °C group compared to 4 °C and 12 °C groups, as well as the control (p < 0.001; n = 3). CONCLUSIONS: Storage at 12 °C appears optimal for preserving the morphology, viability and total cell number in stored HCjE cultures. The superior cell preservation at 12 °C may be related to temperature-associated effects on cell metabolism.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3109/02713683.2014.909497

  4 / 252291 MEDLINE  
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[PMID]: 25473195
[Au] Autor:Ben Ari Z; Cohen-Ezra O; Weidenfeld J; Bradichevsky T; Weitzman E; Rimon U; Inbar Y; Amitai M; Bar-Zachai B; Eshkenazy R; Ariche A; Azoulay D
[Ad] Address:Ziv Ben Ari, Oranit Cohen-Ezra, Tania Bradichevsky, Ella Weitzman, Liver Disease Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, 52621 Tel Aviv, Israel....
[Ti] Title:Ciliated hepatic foregut cyst with high intra-cystic carbohydrate antigen 19-9 level.
[So] Source:World J Gastroenterol;20(43):16355-8, 2014 Nov 21.
[Is] ISSN:2219-2840
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:A ciliated hepatic foregut cyst (CHFC) is a rare foregut developmental malformation usually diagnosed in adulthood. Five percent of reported cases of CHFC transform into squamous cell carcinoma. We report the presentation, evaluation, and surgical management of a symptomatic 45-year-old male found to have a 6.2 cm CHFC. Contrast tomography-guided fine-needle aspiration demonstrated columnar, ciliated epithelium consistent with the histologic diagnosis of CHFC. The intracystic levels of carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) were extremely high (978118 U/mL and 973 µg/L, respectively). Histologically, the wall of the cyst showed characteristic pseudopapillae lined with a ciliated stratified columnar epithelium, underlying smooth muscle, an outer fibrous layer and no atypia. Immunohistochemistry for CA19-9 and CEA was positive. This is the first case report of a CHFC in which levels of CA 19-9 and CEA were measured. Our findings suggest that a large sized multilocular cyst and elevated cyst CA19-9 and CEA levels do not exclude a CHFC from consideration in the diagnosis. CHFCs should be included in the differential diagnosis of hepatic lesions. Accurate diagnosis of a CHFC is necessary given its potential for malignant transformation, and surgical excision is recommended.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3748/wjg.v20.i43.16355

  5 / 252291 MEDLINE  
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[PMID]: 25290952
[Au] Autor:Davis GS; Patel M; Hammond J; Zhang L; Dawid S; Marrs CF; Gilsdorf JR
[Ad] Address:Department of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA. Electronic address: gsdavis@gwu.edu....
[Ti] Title:Prevalence, distribution, and sequence diversity of hmwA among commensal and otitis media non-typeable Haemophilus influenzae.
[So] Source:Infect Genet Evol;28:223-32, 2014 Dec.
[Is] ISSN:1567-7257
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Nontypeable Haemophilus influenzae (NTHi) are Gram-negative coccobacilli that colonize the human pharynx, their only known natural reservoir. Adherence to the host epithelium facilitates NTHi colonization and marks one of the first steps in NTHi pathogenesis. Epithelial cell attachment is mediated, in part, by a pair of high molecular weight (HMW) adhesins that are highly immunogenic, antigenically diverse, and display a wide range of amino acid diversity both within and between isolates. In this study, the prevalence of hmwA, which encodes the HMW adhesin, was determined for a collection of 170 NTHi isolates recovered from the middle ears of children with otitis media (OM isolates) or throats or nasopharynges of healthy children (commensal isolates) from Finland, Israel, and the U.S. Overall, hmwA was detected in 61% of NTHi isolates and was significantly more prevalent (P=0.004) among OM isolates than among commensal isolates; the prevalence ratio comparing hmwA prevalence among ear isolates with that of commensal isolates was 1.47 (95% CI (1.12, 1.92)). Ninety-five percent (98/103) of the hmwA-positive NTHi isolates possessed two hmw loci. To advance our understanding of hmwA binding sequence diversity, we determined the DNA sequence of the hmwA binding region of 33 isolates from this collection. The average amino acid identity across all hmwA sequences was 62%. Phylogenetic analyses of the hmwA binding revealed four distinct sequence clusters, and the majority of hmwA sequences (83%) belonged to one of two dominant sequence clusters. hmwA sequences did not cluster by chromosomal location, geographic region, or disease status.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review

  6 / 252291 MEDLINE  
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[PMID]: 25464513
[Au] Autor:Ortín-Martínez A; Valiente-Soriano FJ; García-Ayuso D; Alarcón-Martínez L; Jiménez-López M; Bernal-Garro JM; Nieto-López L; Nadal-Nicolás FM; Villegas-Pérez MP; Wheeler LA; Vidal-Sanz M
[Ad] Address:Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain....
[Ti] Title:A Novel In Vivo Model of Focal Light Emitting Diode-Induced Cone-Photoreceptor Phototoxicity: Neuroprotection Afforded by Brimonidine, BDNF, PEDF or bFGF.
[So] Source:PLoS One;9(12):e113798, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:We have investigated the effects of light-emitting diode (LED)-induced phototoxicity (LIP) on cone-photoreceptors and their protection with brimonidine (BMD), brain-derived neurotrophic factor (BDNF), pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF) or basic fibroblast growth factor (bFGF). In anesthetized, dark adapted, adult albino rats a blue (400 nm) LED was placed perpendicular to the cornea (10 sec, 200 lux) and the effects were investigated using Spectral Domain Optical Coherence Tomography (SD-OCT) and/or analysing the retina in oriented cross-sections or wholemounts immune-labelled for L- and S-opsin and counterstained with the nuclear stain DAPI. The effects of topical BMD (1%) or, intravitreally injected BDNF (5 µg), PEDF (2 µg), CNTF (0.4 µg) or bFGF (1 µg) after LIP were examined on wholemounts at 7 days. SD-OCT showed damage in a circular region of the superotemporal retina, whose diameter varied from 1,842.4±84.5 µm (at 24 hours) to 1,407.7±52.8 µm (at 7 days). This region had a progressive thickness diminution from 183.4±5 µm (at 12 h) to 114.6±6 µm (at 7 d). Oriented cross-sections showed within the light-damaged region of the retina massive loss of rods and cone-photoreceptors. Wholemounts documented a circular region containing lower numbers of L- and S-cones. Within a circular area (1 mm or 1.3 mm radius, respectively) in the left and in its corresponding region of the contralateral-fellow-retina, total L- or S-cones were 7,118±842 or 661±125 for the LED exposed retinas (n = 7) and 14,040±1,860 or 2,255±193 for the fellow retinas (n = 7), respectively. BMD, BDNF, PEDF and bFGF but not CNTF showed significant neuroprotective effects on L- or S-cones. We conclude that LIP results in rod and cone-photoreceptor loss, and is a reliable, quantifiable model to study cone-photoreceptor degeneration. Intravitreal BDNF, PEDF or bFGF, or topical BMD afford significant cone neuroprotection in this model.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0113798

  7 / 252291 MEDLINE  
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[PMID]: 25460165
[Au] Autor:Snider AJ; Ali WH; Sticca JA; Coant N; Ghaleb AM; Kawamori T; Yang VW; Hannun YA; Obeid LM
[Ad] Address:Northport Veterans Affairs Medical Center, Northport, New York, United States of America; Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America; Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, United States of America....
[Ti] Title:Distinct roles for hematopoietic and extra-hematopoietic sphingosine kinase-1 in inflammatory bowel disease.
[So] Source:PLoS One;9(12):e113998, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Sphingosine kinase 1 (SK1), one of two SK enzymes, is highly regulated and has been shown to act as a focal point for the action of many growth factors and cytokines. SK1 leads to generation of sphingosine-1-phosphate (S1P) and potentially the activation of S1P receptors to mediate biologic effects. Our previous studies implicated SK1/S1P in the regulation of inflammatory processes, specifically in inflammatory bowel disease (IBD). These studies were conducted using a total body knockout mouse for SK1 and were unable to determine the source of SK1/S1P (hematopoietic or extra-hematopoietic) involved in the inflammatory responses. Therefore, bone marrow transplants were performed with wild-type (WT) and SK1-/- mice and colitis induced with dextran sulfate sodium (DSS). Irrespective of the source of SK1/S1P, bone marrow or tissue, DSS induced colitis in all mice; however, mice lacking SK1 in both hematopoietic and extra-hematopoietic compartments exhibited decreased crypt damage. Systemic inflammation was assessed, and mice with WT bone marrow demonstrated significant neutrophilia in response to DSS. In the local inflammatory response, mice lacking SK1/S1P in either bone marrow or tissue exhibited decreased induction of cytokines and less activation of STAT3 (signal transducer and activator of transcription 3). Interestingly, we determined that extra-hematopoietic SK1 is necessary for the induction of cyclooxygenase 2 (COX2) in colon epithelium in response to DSS-induced colitis. Taken together our data suggest that hematopoietic-derived SK1/S1P regulates specific aspects of the systemic inflammatory response, while extra-hematopoietic SK1 in the colon epithelium is necessary for the autocrine induction of COX2 in DSS-induced colitis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0113998

  8 / 252291 MEDLINE  
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[PMID]: 25460012
[Au] Autor:Weyler L; Engelbrecht M; Mata Forsberg M; Brehwens K; Vare D; Vielfort K; Wojcik A; Aro H
[Ad] Address:Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden....
[Ti] Title:Restriction Endonucleases from Invasive Neisseria gonorrhoeae Cause Double-Strand Breaks and Distort Mitosis in Epithelial Cells during Infection.
[So] Source:PLoS One;9(12):e114208, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The host epithelium is both a barrier against, and the target for microbial infections. Maintaining regulated cell growth ensures an intact protective layer towards microbial-induced cellular damage. Neisseria gonorrhoeae infections disrupt host cell cycle regulation machinery and the infection causes DNA double strand breaks that delay progression through the G2/M phase. We show that intracellular gonococci upregulate and release restriction endonucleases that enter the nucleus and damage human chromosomal DNA. Bacterial lysates containing restriction endonucleases were able to fragment genomic DNA as detected by PFGE. Lysates were also microinjected into the cytoplasm of cells in interphase and after 20 h, DNA double strand breaks were identified by 53BP1 staining. In addition, by using live-cell microscopy and NHS-ester stained live gonococci we visualized the subcellular location of the bacteria upon mitosis. Infected cells show dysregulation of the spindle assembly checkpoint proteins MAD1 and MAD2, impaired and prolonged M-phase, nuclear swelling, micronuclei formation and chromosomal instability. These data highlight basic molecular functions of how gonococcal infections affect host cell cycle regulation, cause DNA double strand breaks and predispose cellular malignancies.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0114208

  9 / 252291 MEDLINE  
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[PMID]: 25460003
[Au] Autor:Carter E; Miron-Buchacra G; Goldoni S; Danahay H; Westwick J; Watson ML; Tosh D; Ward SG
[Ad] Address:Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom; Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom....
[Ti] Title:Phosphoinositide 3-Kinase Alpha-Dependent Regulation of Branching Morphogenesis in Murine Embryonic Lung: Evidence for a Role in Determining Morphogenic Properties of FGF7.
[So] Source:PLoS One;9(12):e113555, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Branching morphogenesis is a critical step in the development of many epithelial organs. The phosphoinositide-3-kinase (PI3K) pathway has been identified as a central component of this process but the precise role has not been fully established. Herein we sought to determine the role of PI3K in murine lung branching using a series of pharmacological inhibitors directed at this pathway. The pan-class I PI3K inhibitor ZSTK474 greatly enhanced the branching potential of whole murine lung explants as measured by an increase in the number of terminal branches compared with controls over 48 hours. This enhancement of branching was also observed following inhibition of the downstream signalling components of PI3K, Akt and mTOR. Isoform selective inhibitors of PI3K identified that the alpha isoform of PI3K is a key driver in branching morphogenesis. To determine if the effect of PI3K inhibition on branching was specific to the lung epithelium or secondary to an effect on the mesenchyme we assessed the impact of PI3K inhibition in cultures of mesenchyme-free lung epithelium. Isolated lung epithelium cultured with FGF7 formed large cyst-like structures, whereas co-culture with FGF7 and ZSTK474 induced the formation of defined branches with an intact lumen. Together these data suggest a novel role for PI3K in the branching program of the murine embryonic lung contradictory to that reported in other branching organs. Our observations also point towards PI3K acting as a morphogenic switch for FGF7 signalling.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0113555

  10 / 252291 MEDLINE  
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[PMID]: 25426635
[Au] Autor:Irles P; Piulachs MD
[Ad] Address:Institut de Biologia Evolutiva (CSIC - Universitat Pompeu Fabra), Barcelona, Spain.
[Ti] Title:Unlike in Drosophila Meroistic Ovaries, Hippo Represses Notch in Blattella germanica Panoistic Ovaries, Triggering the Mitosis-Endocycle Switch in the Follicular Cells.
[So] Source:PLoS One;9(11):e113850, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:During insect oogenesis, the follicular epithelium undergoes both cell proliferation and apoptosis, thus modulating ovarian follicle growth. The Hippo pathway is key in these processes, and has been thoroughly studied in the meroistic ovaries of Drosophila melanogaster. However, nothing is known about the role of the Hippo pathway in primitive panoistic ovaries. This work examines the mRNA expression levels of the main components of the Hippo pathway in the panoistic ovary of the basal insect species Blattella germanica, and demonstrates the function of Hippo through RNAi. In Hippo-depleted specimens, the follicular cells of the basal ovarian follicles proliferate without arresting cytokinesis; the epithelium therefore becomes bilayered, impairing ovarian follicle growth. This phenotype is accompanied by long stalks between the ovarian follicles. In D. melanogaster loss of function of Notch determines that the stalk is not developed. With this in mind, we tested whether Hippo and Notch pathways are related in B. germanica. In Notch (only)-depleted females, no stalks were formed between the ovarian follicles. Simultaneous depletion of Hippo and Notch rescued partially the stalk to wild-type. Unlike in the meroistic ovaries of D. melanogaster, in panoistic ovaries the Hippo pathway appears to regulate follicular cell proliferation by acting as a repressor of Notch, triggering the switch from mitosis to the endocycle in the follicular cells. The phylogenetically basal position of B. germanica suggests that this might be the ancestral function of Hippo in insect ovaries.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1411
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0113850


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