264 research outputs found

    Phrenic Nerve Pacing: Current Concepts

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    Myocardial Echinococcosis: Rare Manifestation of a Common Parasitic Disease in Northern Tanzania

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    Hydatid (Echinococcal) disease often involves the liver and lungs but in sporadic cases, it can involve cardiac structures. A 24-year-old male was referred with symptoms of cough and shortness of breath and a provisional diagnosis of metastatic disease of unknown primary to the lung, which was based on a chest X-ray (CXR). Incidentally, on echocardiogram, he was found to have right ventricular (RV) and myocardial multiseptated cysts, which were compatible with cardiac echinococcosis, as the patient had multiple bilateral lung cysts as well. Imaging with ultrasound, computed tomography (CT) scan, and magnetic resonance imaging (MRI) has ameliorated the diagnosis of hydatid disease location in various body parts. However, for earlier and accurate diagnosis, a high index of suspicion is required in endemic areas, especially in vulnerable populations such as pastoralists

    Persepsi Masyarakat terhadap Rencana Pengembangan Kawasan Industri Sentolo di Kabupaten Kulon Progo

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    Rencana pengembangan Kawasan Industri Sentolo merupakan salah satu isu strategis yang dikeluarkan oleh pemerintah Kabupaten Kulon Progo. Namun, selain peran besar dari pemerintah, keterlibatan masyarakat tentu sangat dibutuhkan. Oleh karena itu, penelitian ini bertujuan untuk a) mengetahui sejauh mana realisasi pembangunan Kawasan Industri Sentolo, b) mengetahui persepsi masyarakat terhadap rencana pengembangan Kawasan Industri Sentolo, dan c) mengetahui peran rencana pengembangan kawasan industri terhadap kondisi sosial ekonomi masyarakat.Penelitian ini menggunakan pendekatan kualitatf dan kuantitatif. Pengambilan data secara in-depth interview terhadap 2 (dua) keyperson dan menggunakan kuesioner terhadap 95 responden. Data diolah menggunakan perangkat lunak SPSS.Hasil penelitian menunjukkan bahwa pengembangan kawasan industri pada tahap pengadaan lahan oleh Perusahaan pengelola kawasan industri. Persepsi masyarakat menunjukkan bahwa adanya dukungan dari masyarakat, namun masyarakat masih belum siap menghadapi kawasan industri dalam pengelolaan lingkungan dan pengalaman serta pendidikan masyarakat di bidang industri. Kawasan industri menurut masyarakat akan memberikan peran positif dan akan meningkatkan status sosial masyarakat

    Correlation effects during liquid infiltration into hydrophobic nanoporous mediums

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    Correlation effects arising during liquid infiltration into hydrophobic porous medium are considered. On the basis of these effects a mechanism of energy absorption at filling porous medium by nonwetting liquid is suggested. In accordance with this mechanism, the absorption of mechanical energy is a result expenditure of energy for the formation of menisci in the pores on the shell of the infinite cluster and expenditure of energy for the formation of liquid-porous medium interface in the pores belonging to the infinite cluster of filled pores. It was found that in dependences on the porosity and, consequently, in dependences on the number of filled pores neighbors, the thermal effect of filling can be either positive or negative and the cycle of infiltration-defiltration can be closed with full outflow of liquid. It can occur under certain relation between percolation properties of porous medium and the energy characteristics of the liquid-porous medium interface and the liquid-gas interface. It is shown that a consecutive account of these correlation effects and percolation properties of the pores space during infiltration allow to describe all experimental data under discussion

    A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development.

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    Resetting of the epigenome in human primordial germ cells (hPGCs) is critical for development. We show that the transcriptional program of hPGCs is distinct from that in mice, with co-expression of somatic specifiers and naive pluripotency genes TFCP2L1 and KLF4. This unique gene regulatory network, established by SOX17 and BLIMP1, drives comprehensive germline DNA demethylation by repressing DNA methylation pathways and activating TET-mediated hydroxymethylation. Base-resolution methylome analysis reveals progressive DNA demethylation to basal levels in week 5-7 in vivo hPGCs. Concurrently, hPGCs undergo chromatin reorganization, X reactivation, and imprint erasure. Despite global hypomethylation, evolutionarily young and potentially hazardous retroelements, like SVA, remain methylated. Remarkably, some loci associated with metabolic and neurological disorders are also resistant to DNA demethylation, revealing potential for transgenerational epigenetic inheritance that may have phenotypic consequences. We provide comprehensive insight on early human germline transcriptional network and epigenetic reprogramming that subsequently impacts human development and disease.W.C.C.T is supported by Croucher Foundation and Cambridge Trust. P.F.C.is a Wellcome Trust Senior Fellow in Clinical Science (101876/Z/13/Z), and a UK NIHR Senior Investigator with additional support from the Wellcome Trust Centre for Mitochondrial Research (096919Z/11/Z). M.A.S. is supported by HFSP and Wellcome Trust Investigator Award.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.cell.2015.04.05

    NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers.

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    Nanog, a core pluripotency factor in the inner cell mass of blastocysts, is also expressed in unipotent primordial germ cells (PGCs) in mice, where its precise role is yet unclear. We investigated this in an in vitro model, in which naive pluripotent embryonic stem (ES) cells cultured in basic fibroblast growth factor (bFGF) and activin A develop as epiblast-like cells (EpiLCs) and gain competence for a PGC-like fate. Consequently, bone morphogenetic protein 4 (BMP4), or ectopic expression of key germline transcription factors Prdm1, Prdm14 and Tfap2c, directly induce PGC-like cells (PGCLCs) in EpiLCs, but not in ES cells. Here we report an unexpected discovery that Nanog alone can induce PGCLCs in EpiLCs, independently of BMP4. We propose that after the dissolution of the naive ES-cell pluripotency network during establishment of EpiLCs, the epigenome is reset for cell fate determination. Indeed, we found genome-wide changes in NANOG-binding patterns between ES cells and EpiLCs, indicating epigenetic resetting of regulatory elements. Accordingly, we show that NANOG can bind and activate enhancers of Prdm1 and Prdm14 in EpiLCs in vitro; BLIMP1 (encoded by Prdm1) then directly induces Tfap2c. Furthermore, while SOX2 and NANOG promote the pluripotent state in ES cells, they show contrasting roles in EpiLCs, as Sox2 specifically represses PGCLC induction by Nanog. This study demonstrates a broadly applicable mechanistic principle for how cells acquire competence for cell fate determination, resulting in the context-dependent roles of key transcription factors during development.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature1648

    A Plant-Specific Transcription Factor IIB-Related Protein, pBRP2, Is Involved in Endosperm Growth Control

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    General transcription factor IIB (TFIIB) and TFIIB-related factor (BRF), are conserved RNA polymerase II/III (RNAPII/III) selectivity factors that are involved in polymerase recruitment and transcription initiation in eukaryotes. Recent findings have shown that plants have evolved a third type of B-factor, plant-specific TFIIB-related protein 1 (pBRP1), which seems to be involved in RNAPI transcription. Here, we extend the repertoire of B-factors in plants by reporting the characterization of a novel TFIIB-related protein, plant-specific TFIIB-related protein 2 (pBRP2), which is found to date only in the Brassicacea family. Unlike other B-factors that are ubiquitously expressed, PBRP2 expression is restricted to reproductive organs and seeds as shown by RT-PCR, immunofluorescence labelling and GUS staining experiments. Interestingly, pbrp2 loss-of-function specifically affects the development of the syncytial endosperm, with both parental contributions required for wild-type development. pBRP2, is the first B-factor to exhibit cell-specific expression and regulation in eukaryotes, and might play a role in enforcing bi-parental reproduction in angiosperms

    Principles of early human development and germ cell program from conserved model systems

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    Human primordial germ cells (hPGCs), the precursors of sperm and eggs, originate during week 2-3 of early postimplantation development(1). Using in vitro models of hPGC induction(2-4), recent studies suggest striking mechanistic differences in specification of human and mouse PGCs(5). This may partly be due to the divergence in their pluripotency networks, and early postimplantation development(6-8). Since early human embryos are inaccessible for direct studies, we considered alternatives, including porcine embryos that, as in humans, develop as bilaminar embryonic discs. Here we show that porcine PGCs (pPGCs) originate from the posterior pre-primitive streak competent epiblast by sequential upregulation of SOX17 and BLIMP1 in response to WNT and BMP signalling. Together with human and monkey in vitro models simulating peri-gastrulation development, we show conserved principles for epiblast development for competency for PGC fate, followed by initiation of the epigenetic program(9-11), regulated by a balanced SOX17–BLIMP1 gene dosage. Our combinatorial approach using human, porcine and monkey in vivo and in vitro models, provides synthetic insights on early human development

    Restricted Expression of Epstein-Barr Virus Latent Genes in Murine B Cells Derived from Embryonic Stem Cells

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    Background: Several human malignancies are associated with Epstein-Barr virus (EBV) and more than 95 % of the adult human population carries this virus lifelong. EBV efficiently infects human B cells and persists in this cellular compartment latently. EBV-infected B cells become activated and growth transformed, express a characteristic set of viral latent genes, and acquire the status of proliferating lymphoblastoid cell lines in vitro. Because EBV infects only primate cells, it has not been possible to establish a model of infection in immunocompetent rodents. Such a model would be most desirable in order to study EBV’s pathogenesis and latency in a suitable and amenable host. Methodology/Principal Findings: We stably introduced recombinant EBV genomes into mouse embryonic stem cells and induced their differentiation to B cells in vitro to develop the desired model. In vitro differentiated murine B cells maintained the EBV genomes but expression of viral genes was restricted to the latent membrane proteins (LMPs). In contrast to human B cells, EBV’s nuclear antigens (EBNAs) were not expressed detectably and growth transformed murine B cells did not arise in vitro. Aberrant splicing and premature termination of EBNA mRNAs most likely prevented the expression of EBNA genes required for B-cell transformation. Conclusions/Significance: Our findings indicate that fundamental differences in gene regulation between mouse and ma
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