Efficient and precise CRISPR/Cas9-mediated MECP2 modifications in human-induced pluripotent stem cells

Patients with Rett syndrome (RTT) have severe mental and physical disabilities. The majority of RTT patients carry a heterozygous mutation in methyl-CpG binding protein 2 (MECP2), an X-linked gene encoding an epigenetic factor crucial for normal nerve cell function. No curative therapy for RTT syndrome exists, and cellular mechanisms are incompletely understood. Here, we developed a CRISPR/Cas9-mediated system that targets and corrects the disease relevant regions of the MECP2 exon 4 coding sequence. We achieved homologous recombination (HR) efficiencies of 20% to 30% in human cell lines and iPSCs. Furthermore, we successfully introduced a MECP2(R270X) mutation into the MECP2 gene in human induced pluripotent stem cells (iPSCs). Consequently, using CRISPR/Cas9, we were able to repair such mutations with high efficiency in human mutant iPSCs. In summary, we provide a new strategy for MECP2 gene targeting that can be potentially translated into gene therapy or for iPSCs-based disease modeling of RTT syndrome

The predominance of seafood allergy in Vietnamese adults: results from the first population-based questionnaire survey

Background: Food allergy (FA) is a serious, costly and growing health problem worldwide. FA occurs in both children and adults; however, there is a paucity of information on FA prevalence and its clinical features in the adult population, especially in Asia. We sought to assess the prevalence of FAs in Vietnamese adults and the distribution of offending food items among different regions throughout Vietnam. Methods: A nationwide, cross-sectional, population-based survey was conducted among University students aged 16-50 years. We used a structured, anonymous questionnaire, which was modified from recently published FA epidemiologic studies and based on European Academy of Allergy and Clinical Immunology (EAACI) guidelines, to collect data on FA prevalence, clinical presentations, and implicated food groups. Statistical analysis was performed to generate the prevalence of self-reported and doctor-diagnosed FA and to examine the association of key environmental factors and FA incidence in this population. Results: Of the 14,500 surveys distributed, a total of 9,039 responses were returned, resulting in a response rate of 62.4%. Among participants who reported food-induced adverse reactions, 48.0% have repeated reactions. 18.0% of the participants perceived FA symptoms, but less than half of them sought medical services for confirmation (37.9%). Stratifying for true FA symptoms, the prevalence of self-reported FA was 11.8% and of doctor-diagnosed FA, 4.6%. The most common doctordiagnosed FA was to crustacean (3.0%; 95% CI, 2.6-3.3), followed by fish (1.6%; 95% CI, 1.3-1.8), mollusk (1.3%; 95% CI, 1.0-1.5) and beef (1.0%; 95% CI, 0.8-1.2). The prevalence of doctordiagnosed FA differed among participants living in urban (6.5%) and rural regions (4.9%) (P< 0.001). Atopic family history was the strongest predictor for FA(odds ratio 8.0; 95% CI, 6.2-10.4). Conclusions: Seafood allergy among adults is predominant in Vietnam, followed by beef, milk, and egg, while peanut, soy, and tree nut allergy are much less common. Populations in rural regions have considerably less FA; however, the protective environmental factors have yet to be identified

Chemical telemetry of OH observed to measure interstellar magnetic fields

We present models for the chemistry in gas moving towards the ionization front of an HII region. When it is far from the ionization front, the gas is highly depleted of elements more massive than helium. However, as it approaches the ionization front, ices are destroyed and species formed on the grain surfaces are injected into the gas phase. Photodissociation removes gas phase molecular species as the gas flows towards the ionization front. We identify models for which the OH column densities are comparable to those measured in observations undertaken to study the magnetic fields in star forming regions and give results for the column densities of other species that should be abundant if the observed OH arises through a combination of the liberation of H2O from surfaces and photodissociation. They include CH3OH, H2CO, and H2S. Observations of these other species may help establish the nature of the OH spatial distribution in the clouds, which is important for the interpretation of the magnetic field results.Comment: 11 pages, 2 figures, accepted by Astrophysics and Space Scienc

Using the Wigner-Ibach Surmise to Analyze Terrace-Width Distributions: History, User's Guide, and Advances

A history is given of the applications of the simple expression generalized from the surmise by Wigner and also by Ibach to extract the strength of the interaction between steps on a vicinal surface, via the terrace width distribution (TWD). A concise guide for use with experiments and a summary of some recent extensions are provided.Comment: 11 pages, 4 figures, reformatted (with revtex) version of refereed paper for special issue of Applied Physics A entitled "From Surface Science to Device Physics", in honor of the retirements of Prof. H. Ibach and Prof. H. L\"ut

Understanding the origin of the magnetic field morphology in the wide-binary protostellar system BHR 71

We present 1.3 mm Atacama Large Millimeter/submillimeter Array observations of polarized dust emission toward the wide-binary protostellar system BHR 71 IRS1 and IRS2. IRS1 features what appears to be a natal, hourglass-shaped magnetic field. In contrast, IRS2 exhibits a magnetic field that has been affected by its bipolar outflow. Toward IRS2, the polarization is confined mainly to the outflow cavity walls. Along the northern edge of the redshifted outflow cavity of IRS2, the polarized emission is sandwiched between the outflow and a filament of cold, dense gas traced by N2D+, toward which no dust polarization is detected. This suggests that the origin of the enhanced polarization in IRS2 is the irradiation of the outflow cavity walls, which enables the alignment of dust grains with respect to the magnetic field—but only to a depth of ~300 au, beyond which the dust is cold and unpolarized. However, in order to align grains deep enough in the cavity walls, and to produce the high polarization fraction seen in IRS2, the aligning photons are likely to be in the mid- to far-infrared range, which suggests a degree of grain growth beyond what is typically expected in very young, Class 0 sources. Finally, toward IRS1 we see a narrow, linear feature with a high (10%–20%) polarization fraction and a well-ordered magnetic field that is not associated with the bipolar outflow cavity. We speculate that this feature may be a magnetized accretion streamer; however, this has yet to be confirmed by kinematic observations of dense-gas tracers.Stars and planetary system

The BIOMASS level 2 prototype processor : design and experimental results of above-ground biomass estimation

BIOMASS is ESA’s seventh Earth Explorer mission, scheduled for launch in 2022. The satellite will be the first P-band SAR sensor in space and will be operated in fully polarimetric interferometric and tomographic modes. The mission aim is to map forest above-ground biomass (AGB), forest height (FH) and severe forest disturbance (FD) globally with a particular focus on tropical forests. This paper presents the algorithms developed to estimate these biophysical parameters from the BIOMASS level 1 SAR measurements and their implementation in the BIOMASS level 2 prototype processor with a focus on the AGB product. The AGB product retrieval uses a physically-based inversion model, using ground-canceled level 1 data as input. The FH product retrieval applies a classical PolInSAR inversion, based on the Random Volume over Ground Model (RVOG). The FD product will provide an indication of where significant changes occurred within the forest, based on the statistical properties of SAR data. We test the AGB retrieval using modified airborne P-Band data from the AfriSAR and TropiSAR campaigns together with reference data from LiDAR-based AGB maps and plot-based ground measurements. For AGB estimation based on data from a single heading, comparison with reference data yields relative Root Mean Square Difference (RMSD) values mostly between 20% and 30%. Combining different headings in the estimation process significantly improves the AGB retrieval to slightly less than 20%. The experimental results indicate that the implemented retrieval scheme provides robust results that are within mission requirements

Coherent matter wave inertial sensors for precision measurements in space

We analyze the advantages of using ultra-cold coherent sources of atoms for matter-wave interferometry in space. We present a proof-of-principle experiment that is based on an analysis of the results previously published in [Richard et al., Phys. Rev. Lett., 91, 010405 (2003)] from which we extract the ratio h/m for 87Rb. This measurement shows that a limitation in accuracy arises due to atomic interactions within the Bose-Einstein condensate

A new measurement of J/psi suppression in Pb-Pb collisions at 158 GeV per nucleon

We present a new measurement of J/psi production in Pb-Pb collisions at 158 GeV/nucleon, from the data sample collected in year 2000 by the NA50 Collaboration, under improved experimental conditions with respect to previous years. With the target system placed in vacuum, the setup was better adapted to study, in particular, the most peripheral nuclear collisions with unprecedented accuracy. The analysis of this data sample shows that the (J/psi)/Drell-Yan cross-sections ratio measured in the most peripheral Pb-Pb interactions is in good agreement with the nuclear absorption pattern extrapolated from the studies of proton-nucleus collisions. Furthermore, this new measurement confirms our previous observation that the (J/psi)/Drell-Yan cross-sections ratio departs from the normal nuclear absorption pattern for semi-central Pb-Pb collisions and that this ratio persistently decreases up to the most central collisions.Comment: 19 pages, 10 figures. Submitted to Eur. Phys. J.

Weight loss reversed obesity-induced HGF/c-Met pathway and basal-like breast cancer progression

Epidemiologic studies demonstrate that obesity is associated with an aggressive subtype of breast cancer called basal-like breast cancer (BBC). Using the C3(1)-TAg murine model of BBC, we previously demonstrated that mice displayed an early onset of tumors when fed obesogenic diets in the adult window of susceptibility. Obesity was also shown to elevate mammary gland expression and activation of hepatocyte growth factor (HGF)/c-Met compared to lean controls, a pro-tumorigenic pathway associated with BBC in patients. Epidemiologic studies estimate that weight loss could prevent a large proportion of BBC. We sought to investigate whether weight loss in adulthood prior to tumor onset would protect mice from accelerated tumorigenesis observed in obese mice. Using a life-long model of obesity, C3(1)-TAg mice were weaned onto and maintained on an obesogenic high-fat diet. Obese mice displayed significant elevations in tumor progression, but not latency or burden. Tumor progression was significantly reversed when obese mice were induced to lose weight by switching to a control low-fat diet prior to tumor onset compared to mice maintained on obesogenic diet. We investigated the HGF/c-Met pathway known to regulate tumorigenesis. Importantly, HGF/c-Met expression in normal mammary glands and c-Met in tumors was elevated with obesity and was significantly reversed with weight loss. Changes in tumor growth could not be explained by measures of HGF action including phospho-AKT or phospho-S6. Other mediators associated with oncogenesis such as hyperinsulinemia and a high leptin:adiponectin ratio were elevated by obesity and reduced with weight loss. In sum, weight loss significantly blunted the obesity-responsive pro-tumorigenic HGF/c-Met pathway and improved several metabolic risk factors associated with BBC, which together may have contributed to the dramatic reversal of obesity-driven tumor progression. Future research aims to evaluate the role of obesity and the HGF/c-Met pathway in basal-like breast cancer progression

Bottomonium and Drell-Yan production in p-A collisions at 450 GeV

The NA50 Collaboration has measured heavy-quarkonium production in p-A collisions at 450 GeV incident energy (sqrt(s) = 29.1 GeV). We report here results on the production of the Upsilon states and of high-mass Drell-Yan muon pairs (m > 6 GeV). The cross-section at midrapidity and the A-dependence of the measured yields are determined and compared with the results of other fixed-target experiments and with the available theoretical estimates. Finally, we also address some issues concerning the transverse momentum distributions of the measured dimuons.Comment: 18 pages, 9 figures, to be published in Phys. Lett.