Telomeric NAP1L4 and OSBPL5 of the KCNQ1 cluster, and the DECORIN gene are not imprinted in human trophoblast stem cells

Background: Genomic imprinting of the largest known cluster, the Kcnq1/KCNQ1 domain on mChr7/hChr11, displays significant differences between mouse and man. Of the fourteen transcripts in this cluster, imprinting of six is ubiquitous in mice and humans, however, imprinted expression of the other eight transcripts is only found in the mouse placenta. The human orthologues of the latter eight transcripts are biallelically expressed, at least from the first trimester onwards. However, as early development is less divergent between species, placental specific imprinting may be present in very early gestation in both mice and humans. Methodology/Principal Findings: Human embryonic stem (hES) cells can be differentiated to embryoid bodies and then to trophoblast stem (EB-TS) cells. Using EB-TS cells as a model of post-implantation invading cytotrophoblast, we analysed allelic expression of two telomeric transcripts whose imprinting is placental specific in the mouse, as well as the ncRNA KCNQ1OT1, whose imprinted expression is ubiquitous in early human and mouse development. KCNQ1OT1 expression was monoallelic in all samples but OSBPL5 and NAP1L4 expression was biallelic in EB-TS cells, as well as undifferentiated hES cells and first trimester human fetal placenta. DCN on hChr12, another gene imprinted in the mouse placenta only, was also biallelically expressed in EB-TS cells. The germline maternal methylation imprint at the KvDMR was maintained in both undifferentiated hES cells and EB-TS cells. Conclusions/Significance: The question of placental specific imprinting in the human has not been answered fully. Using a model of human trophoblast very early in gestation we show a lack of imprinting of two telomeric genes in the KCNQ1 region and of DCN, whose imprinted expression is placental specific in mice, providing further evidence to suggest that humans do not exhibit placental specific imprinting. The maintenance of both differential methylation of the KvDMR and monoallelic expression of KCNQ1OT1 indicates that the region is appropriately regulated epigenetically in vitro. Human gestational load is less than in the mouse, resulting in reduced need for maternal resource competition, and therefore maybe also a lack of placental specific imprinting. If genomic imprinting exists to control fetal acquisition of maternal resources driven by the placenta, placenta-specific imprinting may be less important in the human than the mouse

Spectrum of the Vortex Bound States of the Dirac and Schrodinger Hamiltonian in the presence of Superconducting Gaps

We investigate the vortex bound states both Schrodinger and Dirac Hamiltonian with the s-wave superconducting pairing gap by solving the mean-field Bogoliubov-de-Gennes equations. The exact vortex bound states spectrum is numerically determined by the integration method, and also accompanied by the quasi-classical analysis. It is found that the bound state energies is proportional to the vortex angular momentum when the chemical potential is large enough. By applying the external magnetic field, the vortex bound state energies of the Dirac Hamiltonian are almost unchanged; whereas the energy shift of the Schrodinger Hamiltonian is proportional to the magnetic field. These qualitative differences may serve as an indirect evidence of the existence of Majorana fermions in which the zero mode exists in the case of the Dirac Hamiltonian only.Comment: 8 pages, 9 figure

Precis of epistemic angst:Book Symposium: Duncan Pritchard, Epistemic Angst (Princeton University Press, 2015, xiii + 236 pages)

ABSTRACT This book symposium features three critical pieces dealing with Duncan Pritchard's book, 'Epistemic Angst'; the symposium also contains Pritchard's replies to his critics

Moorean Absurdities and the Nature of Assertion

10.1080/00048409612347111Australasian Journal of Philosophy741135-14

Extracellular vesicles derived from bone marrow mesenchymal stem cells enhance myelin maintenance after cortical injury in aged rhesus monkeys

Cortical injury, such as stroke, causes neurotoxic cascades that lead to rapid death and/or damage to neurons and glia. Axonal and myelin damage in particular, are critical factors that lead to neuronal dysfunction and impair recovery of function after injury. These factors can be exacerbated in the aged brain where white matter damage is prevalent. Therapies that can ameliorate myelin damage and promote repair by targeting oligodendroglia, the cells that produce and maintain myelin, may facilitate recovery after injury, especially in the aged brain where these processes are already compromised. We previously reported that a novel therapeutic, Mesenchymal Stem Cell derived extracellular vesicles (MSC-EVs), administered intravenously at both 24 h and 14 days after cortical injury, reduced microgliosis (Go et al. 2019), reduced neuronal pathology (Medalla et al. 2020), and improved motor recovery (Moore et al. 2019) in aged female rhesus monkeys. Here, we evaluated the effect of MSC-EV treatment on changes in oligodendrocyte maturation and associated myelin markers in the sublesional white matter using immunohistochemistry, confocal microscopy, stereology, qRT-PCR, and ELISA. Compared to vehicle control monkeys, EV-treated monkeys showed a reduction in the density of damaged oligodendrocytes. Further, EV-treatment was associated with enhanced myelin maintenance, evidenced by upregulation of myelin-related genes and increases in actively myelinating oligodendrocytes in sublesional white matter. These changes in myelination correlate with the rate of motor recovery, suggesting that improved myelin maintenance facilitates this recovery. Overall, our results suggest that EVs act on oligodendrocytes to support myelination and improves functional recovery after injury in the aged brain. SIGNIFICANCE: We previously reported that EVs facilitate recovery of function after cortical injury in the aged monkey brain, while also reducing neuronal pathology (Medalla et al. 2020) and microgliosis (Go et al. 2019). However, the effect of injury and EVs on oligodendrocytes and myelination has not been characterized in the primate brain (Dewar et al. 1999; Sozmen et al. 2012; Zhang et al. 2013). In the present study, we assessed changes in myelination after cortical injury in aged monkeys. Our results show, for the first time, that MSC-EVs support recovery of function after cortical injury by enhancing myelin maintenance in the aged primate brain

Iroa: the international register of open abdomen. an international effort to better understand the open abdomen: call for participants

Actually the most common indications for Open Abdomen (OA) are trauma, abdominal sepsis, severe acute pancreatitis and more in general all those situations in which an intra-abdominal hypertension condition is present, in order to prevent the development of an abdominal compartment syndrome. The mortality and morbidity rate in patients undergone to OA procedures is still high. At present many studies have been published about the OA management and the progresses in survival rate of critically ill trauma and septic surgical patients. However several issues are still unclear and need more extensive studies. The definitions of indications, applications and methods to close the OA are still matter of debate. To overcome this lack of high level of evidence data about the OA indications, management, definitive closure and follow-up, the World Society of Emergency Surgery (WSES) promoted the International Register of Open Abdomen (IROA). The register will be held on a web platform (Clinical Registers (R)) through a dedicated web site: www. clinicalregisters. org. This will allow to all surgeons and physicians to participate from all around the world only by having a computer and a web connection. The IROA protocol has been approved by the coordinating center Ethical Committee (Papa Giovanni XXIII hospital, Bergamo, Italy).Actually the most common indications for Open Abdomen (OA) are trauma, abdominal sepsis, severe acute pancreatitis and more in general all those situations in which an intra-abdominal hypertension condition is present, in order to prevent the development103713sem informaçãosem informaçã

Homologous Flares and Magnetic Field Topology in Active Region NOAA 10501 on 20 November 2003

We present and interpret observations of two morphologically homologous flares that occurred in active region (AR) NOAA 10501 on 20 November 2003. Both flares displayed four homologous H-alpha ribbons and were both accompanied by coronal mass ejections (CMEs). The central flare ribbons were located at the site of an emerging bipole in the center of the active region. The negative polarity of this bipole fragmented in two main pieces, one rotating around the positive polarity by ~ 110 deg within 32 hours. We model the coronal magnetic field and compute its topology, using as boundary condition the magnetogram closest in time to each flare. In particular, we calculate the location of quasiseparatrix layers (QSLs) in order to understand the connectivity between the flare ribbons. Though several polarities were present in AR 10501, the global magnetic field topology corresponds to a quadrupolar magnetic field distribution without magnetic null points. For both flares, the photospheric traces of QSLs are similar and match well the locations of the four H-alpha ribbons. This globally unchanged topology and the continuous shearing by the rotating bipole are two key factors responsible for the flare homology. However, our analyses also indicate that different magnetic connectivity domains of the quadrupolar configuration become unstable during each flare, so that magnetic reconnection proceeds differently in both events.Comment: 24 pages, 10 figures, Solar Physics (accepted