miR-153 and miR-335, Ethanol Sensitive MicroRNAs, Control NSC/NPC Maturation during Fetal Brain Development

Maternal alcohol consumption during pregnancy, especially during the first and second trimester, can cause the wide range of severe birth defects classified as fetal alcohol spectrum disorder (FASD). FASD is a wide spectrum disease characterized by delayed fetal growth, facial abnormalities, and cognitive and behavioral deficits of the central nervous system. The cost of FASD to the U.S. healthcare system is estimated at more than $6 billion annually, suggesting the problem of maternal consumption is increasing through years. Previous research by Sathyan and his colleague has shown that only few miRNAs, miR-9, miR-21, miR-153, and miR-335, were able to mediate ethanol’s teratogenic effects through regulation neural stem/progenitor cell (NSC/NPC). However, the mechanisms whereby miRNAs mediate fetal neural stem cell (NSC) vulnerability and contribute to ethanol’s teratology are complex and still unclear. Therefore, the goal of my dissertation is to discover novel pathways of two miRNAs, miR-153 and miR-335, as key modulators of ethanol. Data from the miR-153 study identified NFIA (nuclear factor-1A) and its paralog, NFIB, as direct targets of miR-153 ex vivo as well as in vivo, and miR-153 overexpression prevented neuronal differentiation. MiR-153 functional analysis in neurospheres suggested that overexpression of this microRNA prevented, and partly reversed ethanol’s teratogenic effects on miR-153 target transcripts. This antagonistic effect was also found in the pharmacology studies using varenicline, a FDA-approved drug as a partial nicotinic acetylcholine receptor agonist, which increased miR-153 expression. These data collectively suggested a role for miR-153 in preventing NSCs/NPCs differentiation, and showed that direct or pharmacological manipulation of miRNAs in an ex vivo model have the potential capability to prevent or even reverse ethanol’s effects on fetal brain development. Data from miR-335 research presented show that miR-335 regulates NSCs/NPCs markers DCX, NeuroD1, and c-Kit, and that miR-335 dysregulation results in neuronal premature-maturation via increasing asymmetric cell divisions, driving neuronal early differentiation through inducing stem cell genes DCX and NeuroD1 in the ventricular zone (VZ) of the developing cortex. In sum, my data conclude that miR-335 and miR-153 act as molecular brakes to prevent NSCs/NPCs early maturation by regulating cell differentiation genes during the second trimester, and ethanol leads to organizational defects in the developing cerebral cortex through driving premature-maturation. In addition, preliminary data from miRNA functional studies indicate that misregulation of miRNA-regulated genes by ethanol exposure can be prevented or reversed in the presence of microRNAs or specific pharmaceuticals. This evidence explores the application of candidate miRNAs, as well as other medical drugs, as potential therapeutics to overcome ethanol’s teratology

Spin-orbit torques acting upon a perpendicularly-magnetized Py layer

We show that Py, a commonly-used soft ferromagnetic material with weak anisotropy, can become perpendicularly-magnetized while depositing on Ta buffer layer with Hf or Zr insertion layers (ILs) and MgO capping layer. By using two different approaches, namely harmonic voltage measurement and hysteresis loop shift measurement, the dampinglike spin-orbit torque (DL-SOT) efficiencies from Ta/IL/Py/IL/MgO magnetic heterostructures with perpendicular magnetic anisotropy are characterized. We find that though Ta has a significant spin Hall effect, the DL-SOT efficiencies are small in systems with the Ta/Py interface compared to that obtained from the control sample with the traditional Ta/CoFeB interface. Our results indicate that the spin transparency for the Ta/Py interface is much less than that for the Ta/CoFeB interface, which might be related to the variation of spin mixing conductance for different interfaces

Deep Learning for Spin-Orbit Torque Characterizations with a Projected Vector Field Magnet

Spin-orbit torque characterizations on magnetic heterostructures with perpendicular anisotropy are demonstrated on a projected vector field magnet via hysteresis loop shift measurement and harmonic Hall measurement with planar Hall correction. Accurate magnetic field calibration of the vector magnet is realized with the help of deep learning models, which are able to capture the nonlinear behavior between the generated magnetic field and the currents applied to the magnet. The trained models can successfully predict the applied current combinations under the circumstances of magnetic field scans, angle scans, and hysteresis loop shift measurements. The validity of the models is further verified, complemented by the comparison of the spin-orbit torque characterization results obtained from the deep-learning-trained vector magnet system with those obtained from a conventional setup comprised of two separated electromagnets. The damping-like spin-orbit torque (DL-SOT) efficiencies (|$\xi_{DL}$|) extracted from the vector magnet and the traditional measurement configuration are consistent, where |$\xi_{DL}$| $\approx$ 0.22 for amorphous W and |$\xi_{DL}$| $\approx$ 0.02 for $\alpha$-W. Our work provides an advanced method to meticulously control a vector magnet and to conveniently perform various spin-orbit torque characterizations

Helmet non-use by users of bikeshare programs, electric bicycles, racing bicycles, and personal bicycles: An observational study in Taipei, Taiwan.

The bikeshare program in Taipei City and New Taipei City, called U-bike, was launched in August 2012 and has more than 7500 bicycles operating out of 769 stations. Research has suggested that bicycle helmet use is a means of reducing morbidity and mortality among bike users. Helmets, however, are not available for rent when a U-bike is rented. The current research conducted an observational study to examine the prevalence of helmet non-use by users of the bikeshare program, electric bicycles, racing bicycles, and personal bicycles in Taipei City and New Taipei City. Trained observers using compact video cameras collected helmet non-use data during various times of the day and on different days of the week. Observers collected data on cyclist attributes, bicycle types, and helmet use at several selected locations within Taipei City and New Taipei City. U-bike users were found to be the least likely to wear helmets. Other noteworthy findings include that violations such as phone use, red-light violations, and travelling at ≥25 km/h were associated with riding without a helmet. Male users of racing bikes tended not to wear helmets, while female users of other bicycle types were less likely to use a helmet. Carrying passengers by users of electric bikes and personal bikes was a determinant of helmet non-use. This paper concludes with a discussion and recommendations for future research

MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells

Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The fetal neural stem cells (NSCs) that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expression in NSCs. To understand the role of miR-153 in the etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo, by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs and gene networks as important miR-153 targets. Moreover, miR-153 over-expression prevented neuronal differentiation without altering neuroepithelial cell survival or proliferation. Analysis of 3′UTRs and in utero over-expression of pre-miR-153 in fetal mouse brain identified Nfia (nuclear factor-1A) and its paralog, Nfib, as direct targets of miR-153. In utero ethanol exposure resulted in a predicted expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR-153 over-expression prevented, and partly reversed, the effects of ethanol exposure on miR-153 target transcripts. Varenicline, a partial nicotinic acetylcholine receptor agonist that, like nicotine, induces miR-153 expression, also prevented and reversed the effects of ethanol exposure. These data collectively provide evidence for a role for miR-153 in preventing premature NSC differentiation. Moreover, they provide the first evidence in a preclinical model that direct or pharmacological manipulation of miRNAs have the potential to prevent or even reverse effects of a teratogen like ethanol on fetal development

Publisher Correction: FGF signalling controls the specification of hair placode-derived SOX9 positive progenitors to Merkel cells.

The originally published version of this Article contained an error in Figure 2. In panel e, the blue bar was incorrectly labelled 'KRT8(+)/TOMATO(-)'. Furthermore, during the process of preparing a correction, the publication date of the Article was inadvertently changed to June 20th 2018. Both of these errors have been corrected in the PDF and HTML versions of the Article