Efficient derivation of dopaminergic neurons from SOX1(-) floor plate cells under defined culture conditions.

BACKGROUND: Parkinson's disease (PD) is a severe neurodegenerative disease associated with loss of dopaminergic neurons. Derivation of dopaminergic neurons from human embryonic stem cells (hESCs) could provide new therapeutic options for PD therapy. Dopaminergic neurons are derived from SOX(-) floor plate (FP) cells during embryonic development in many species and in human cell culture in vitro. Early treatment with sonic hedgehog (Shh) has been reported to efficiently convert hESCs into FP lineages. METHODS: In this study, we attempted to utilize a Shh-free approach in deriving SOX1(-) FP cells from hESCs in vitro. Neuroectoderm conversion from hESCs was achieved with dual inhibition of the BMP4 (LDN193189) and TGF-β signaling pathways (SB431542) for 24 h under defined culture conditions. RESULTS: Following a further 5 days of treatment with LDN193189 or LDN193189 + SB431542, SOX1(-) FP cells constituted 70-80 % of the entire cell population. Upon treatment with Shh and FGF8, the SOX1(-) FP cells were efficiently converted to functional Nurr1(+) and TH(+) dopaminergic cells (patterning), which constituted more than 98 % of the entire cell population. However, when the same growth factors were applied to SOX1(+) cells, only less than 4 % of the cells became Nurr1(+), indicating that patterning was effective only if SOX1 expression was down-regulated. After transplanting the Nurr1(+) and TH(+) cells into a hemiparkinsonian rat model, significant improvements were observed in amphetamine induced ipslateral rotations, apomorphine induced contra-lateral rotations and Rota rod motor tests over a duration of 8 weeks. CONCLUSIONS: Our findings thus provide a convenient approach to FP development and functional dopaminergic neuron derivation.published_or_final_versio

Islamic perspectives on elective ovarian tissue freezing by single women for non-medical or social reasons

Non-medical or Social egg freezing (oocyte cryopreservation) is currently a controversial topic in Islam, with contradictory fatwas being issued in different Muslim countries. While Islamic authorities in Egypt permit the procedure, fatwas issued in Malaysia have banned single Muslim women from freezing their unfertilized eggs (vitrified oocytes) to be used later in marriage. The underlying principles of the Malaysian fatwas are that (i) sperm and egg cells produced before marriage, should not be used during marriage to conceive a child; (ii) extraction of mature egg cells from single women being unacceptable; and (iii) fertility preservation in anticipation of late marriage is a conjecture that has not yet occurred. Ovarian tissue freezing can potentially be a more Shariah-compliant alternative to social egg freezing, because once the frozen ovarian cortical tissue sections have been re-transplanted back into the woman, mature egg cells can readily be produced, collected, and fertilized by the husband’s sperm only during the period of marriage contract (′akd al-nikāḥ). Unlike accidental mix-ups with frozen eggs, muddling of lineage (nasab) would be automatically avoided in ovarian tissue freezing due to immunological rejection. However, upon critical analysis based on Qawā’id Fiqhiyyah (Islamic Legal Maxims), Maqāṣid-al-Shariah (Higher Objectives of Islamic Law), and Maslaḥah-Mafsadah (benefits versus harmful effects on society), elective ovarian tissue freezing by healthy single women for social reasons would likely be a highly contentious and controversial issue within Muslim communities that may conflict with conservative social-religious norms. This thus needs further debate among Islamic jurists in dialogue with medical doctors and biomedical scientists

Islamic viewpoints on opportunistic sex selection of IVF embryos upon doing preimplantation genetic testing for preventing genetic diseases

In recent years, preimplantation genetic testing (PGT) of IVF embryos have gained much traction in clinical assisted reproduction for preventing various genetic defects, including Down syndrome. However, such genetic tests inevitably reveal the sex of IVF embryos by identifying the sex (X and Y) chromosomes. In many countries with less stringent IVF regulations, information on the sex of embryos that are tested to be genetically normal is readily shared with patients. This would thus present Muslim patients with unintended opportunities for sex selection based on personal or social biases without any pressing need or valid medical reason. Additionally, there are other patients who claim using PGT for preventing genetic defects as a pretext or “convenient excuse,” with a secret intention to do sex selection when it is banned in their home country. Currently, non-medical sex selection is a highly-controversial and hotly debated issue in Islam, because there is generally a strong preference for having sons over daughters due to widespread cultural norms of elderly parents depending on their sons for financial support, as well as the need for male heirs to continue the family lineage within the backdrop of local patriarchal cultures. There is a risk of gender imbalance and social disequilibrium occurring in Islamic societies due to prevalent sex selection. Hence, the question is whether opportunistic sex selection with PGT would contravene Islamic ethics and principles, which will thus be discussed here

Differential resistance of human embryonic stem cells and somatic cell types to hydrogen peroxide-induced genotoxicity may be dependent on innate basal intracellular ROS levels

Previously, we demonstrated that undifferentiated human embryonic stem cells (hESC) displayed higher resistance to oxidative and genotoxic stress compared to somatic cells, but did not further probe the underlying mechanisms. Using H2O2-induced genotoxicity as a model, this study investigated whether higher resistance of hESC to oxidative and genotoxic stress could be due to lower innate basal intracellular levels of reactive oxygen species (ROS), as compared to their differentiated fibroblastic progenies (H1F) and two other somatic cell types — human embryonic palatal mesenchymal (HEPM) cells and peripheral blood lymphocytes (PBL). Comet assay demonstrated that undifferentiated hESC consistently sustained lower levels of DNA damage upon acute exposure to H2O2 for 30 min, compared to somatic cells. DCFDA and HE staining with flow cytometry showed that undifferentiated hESC had lower innate basal intracellular levels of reactive oxygen species compared to somatic cells, which could lead to their higher resistance to genotoxic stress upon acute exposure to H2O2

WASP-80b has a dayside within the T-dwarf range

AHMJT is a Swiss National Science Foundation (SNSF) fellow under grant number P300P2-147773. MG and EJ are Research Associates at the F.R.S-FNRS; LD received the support the support of the F.R.I.A. fund of the FNRS. DE, KH, and SU acknowledge the financial support of the SNSF in the frame of the National Centre for Competence in Research ‘PlanetS’. EH and IR acknowledge support from the Spanish Ministry of Economy and Competitiveness (MINECO) and the ‘Fondo Europeo de Desarrollo Regional’ (FEDER) through grants AYA2012-39612-C03-01 and ESP2013-48391-C4-1-R.WASP-80b is a missing link in the study of exo-atmospheres. It falls between the warm Neptunes and the hot Jupiters and is amenable for characterisation, thanks to its host star's properties. We observed the planet through transit and during occultation with Warm Spitzer. Combining our mid-infrared transits with optical time series, we find that the planet presents a transmission spectrum indistinguishable from a horizontal line. In emission, WASP-80b is the intrinsically faintest planet whose dayside flux has been detected in both the 3.6 and 4.5 $\mu$m Spitzer channels. The depths of the occultations reveal that WASP-80b is as bright and as red as a T4 dwarf, but that its temperature is cooler. If planets go through the equivalent of an L-T transition, our results would imply this happens at cooler temperatures than for brown dwarfs. Placing WASP-80b's dayside into a colour-magnitude diagram, it falls exactly at the junction between a blackbody model and the T-dwarf sequence; we cannot discern which of those two interpretations is the more likely. Flux measurements on other planets with similar equilibrium temperatures are required to establish whether irradiated gas giants, like brown dwarfs, transition between two spectral classes. An eventual detection of methane absorption in transmission would also help lift that degeneracy. We obtained a second series of high-resolution spectra during transit, using HARPS. We reanalyse the Rossiter-McLaughlin effect. The data now favour an aligned orbital solution and a stellar rotation nearly three times slower than stellar line broadening implies. A contribution to stellar line broadening, maybe macroturbulence, is likely to have been underestimated for cool stars, whose rotations have therefore been systematically overestimated. [abridged]Publisher PDFPeer reviewe

Pluripotent human embryonic stem cell derived neural lineages for in vitro modelling of enterovirus 71 infection and therapy

The incidence of neurological complications and fatalities associated with Hand, Foot & Mouth disease has increased over recent years, due to emergence of newly-evolved strains of Enterovirus 71 (EV71). In the search for new antiviral therapeutics against EV71, accurate and sensitive in vitro cellular models for preliminary studies of EV71 pathogenesis is an essential prerequisite, before progressing to expensive and time-consuming live animal studies and clinical trials. This study thus investigated whether neural lineages derived from pluripotent human embryonic stem cells (hESC) can fulfil this purpose. EV71 infection of hESC-derived neural stem cells (NSC) and mature neurons (MN) was carried out in vitro, in comparison with RD and SH-SY5Y cell lines. Results: Upon assessment of post-infection survivability and EV71 production by the various types, it was observed that NSC were significantly more susceptible to EV71 infection compared to MN, RD (rhabdomyosarcoma) and SHSY5Y cells, which was consistent with previous studies on mice. The SP81 peptide had significantly greater inhibitory effect on EV71 production by NSC and MN compared to the cancer-derived RD and SH-SY5Y cell lines. Hence, this study demonstrates that hESC-derived neural lineages can be utilized as in vitro models for studying EV71 pathogenesis and for screening of antiviral therapeutics

Using the raindrop size distribution to quantify the soil detachment rate at the laboratory scale

Rainfall simulators are beneficial tools for studying soil erosion processes and sediment transport for different circumstances and scales. They are useful to better understand soil erosion mechanisms and, therefore, to develop and validate process-based erosion models. Simulators permit experimental replicates for both simple and complex configurations. The 2 m × 6 m EPFL erosion flume is equipped with a hydraulic slope control and a sprinkling system located on oscillating bars 3 m above the surface. It provides a near-uniform spatial rainfall distribution. The intensity of the precipitation can be adjusted by changing the oscillation interval. The flume is filled to a depth of 0.32 m with an agricultural loamy soil. Raindrop detachment is an important process in interrill erosion, the latter varying with the soil properties as well as the raindrop size distribution and drop velocity. Since the soil detachment varies with the kinetic energy of raindrops, an accurate characterization of drop size distribution (DSD, measured, e.g., using a laser disdrometer) can potentially support erosion calculations. Here, a laser disdrometer was used at different rainfall intensities in the EPFL flume to quantify the rainfall event in terms of number of drops, diameter and velocity. At the same time, soil particle motion was measured locally using splash cups. These cups measured the detached material rates into upslope and downslope compartments. In contrast to previously reported splash cup experiments, the cups used in this study were equipped at the top with upside-down funnels, the upper part having the same diameter as the soil sampled at the bottom. This ensured that the soil detached and captured by the device was not re-exposed to rainfall. The experimental data were used to quantify the relationship between the raindrop distribution and the splash-driven sediment transport

The cooperative IGS RT-GIMs: a reliable estimation of the global ionospheric electron content distribution in real time

The Real-Time Working Group (RTWG) of the International GNSS Service (IGS) is dedicated to providing high-quality data and high-accuracy products for Global Navigation Satellite System (GNSS) positioning, navigation, timing and Earth observations. As one part of real-time products, the IGS combined Real-Time Global Ionosphere Map (RT-GIM) has been generated by the real-time weighting of the RT-GIMs from IGS real-time ionosphere centers including the Chinese Academy of Sciences (CAS), Centre National d'Etudes Spatiales (CNES), Universitat Politècnica de Catalunya (UPC) and Wuhan University (WHU). The performance of global vertical total electron content (VTEC) representation in all of the RT-GIMs has been assessed by VTEC from Jason-3 altimeter for 3 months over oceans and dSTEC-GPS technique with 2¿d observations over continental regions. According to the Jason-3 VTEC and dSTEC-GPS assessment, the real-time weighting technique is sensitive to the accuracy of RT-GIMs. Compared with the performance of post-processed rapid global ionosphere maps (GIMs) and IGS combined final GIM (igsg) during the testing period, the accuracy of UPC RT-GIM (after the improvement of the interpolation technique) and IGS combined RT-GIM (IRTG) is equivalent to the rapid GIMs and reaches around 2.7 and 3.0 TECU (TEC unit, 1016¿el¿m-2) over oceans and continental regions, respectively. The accuracy of CAS RT-GIM and CNES RT-GIM is slightly worse than the rapid GIMs, while WHU RT-GIM requires a further upgrade to obtain similar performance. In addition, a strong response to the recent geomagnetic storms has been found in the global electron content (GEC) of IGS RT-GIMs (especially UPC RT-GIM and IGS combined RT-GIM). The IGS RT-GIMs turn out to be reliable sources of real-time global VTEC information and have great potential for real-time applications including range error correction for transionospheric radio signals, the monitoring of space weather, and detection of natural hazards on a global scale. All the IGS combined RT-GIMs generated and analyzed during the testing period are available at https://doi.org/10.5281/zenodo.5042622 (Liu et al., 2021b).his research has been supported by the China Scholarship Council (CSC). The contribution from UPC- IonSAT authors was partially supported by the European Union- funded project PITHIA-NRF (grant no. 101007599) and by the ESSP/ICAO-funded project TEC4SpaW. The work of An- drzej Krankowski is supported by the National Centre for Research and Development, Poland, through grant ARTEMIS (grant nos. DWM/PL-CHN/97/2019 and WPC1/ARTEMIS/2019)Peer ReviewedPostprint (published version

WASP-80b has a dayside within the T-dwarf range

WASP-80b is a missing link in the study of exoatmospheres. It falls between the warm Neptunes and the hot Jupiters and is amenable for characterization, thanks to its host star's properties. We observed the planet through transit and during occultation with Warm Spitzer. Combining our mid-infrared transits with optical time series, we find that the planet presents a transmission spectrum indistinguishable from a horizontal line. In emission, WASP-80b is the intrinsically faintest planet whose dayside flux has been detected in both the 3.6 and 4.5 μm Spitzer channels. The depths of the occultations reveal that WASP-80b is as bright and as red as a T4 dwarf, but that its temperature is cooler. If planets go through the equivalent of an L-T transition, our results would imply that this happens at cooler temperatures than for brown dwarfs. Placing WASP-80b's dayside into a colour-magnitude diagram, it falls exactly at the junction between a blackbody model and the T-dwarf sequence; we cannot discern which of those two interpretations is the more likely. WASP-80b's flux density is as low as GJ436b at 3.6 μm; the planet's dayside is also fainter, but bluer than HD189733Ab's nightside (in the [3.6] and [4.5]Spitzer bands). Flux measurements on other planets with similar equilibrium temperatures are required to establish whether irradiated gas giants, such as brown dwarfs, transition between two spectral classes. An eventual detection of methane absorption in transmission would also help lift that degeneracy. We obtained a second series of high-resolution spectra during transit, using HARPS. We reanalyse the Rossiter-McLaughlin effect. The data now favour an aligned orbital solution and a stellar rotation nearly three times slower than stellar line broadening implies. A contribution to stellar line broadening, maybe macroturbulence, is likely to have been underestimated for cool stars, whose rotations have therefore been systematically overestimate

Characterization of the severe phenotype of pyruvate kinase deficiency

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162766/2/ajh25926.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162766/1/ajh25926_am.pd