Activin-A and Bmp4 Levels Modulate Cell Type Specification during CHIR-Induced Cardiomyogenesis

The use of human pluripotent cell progeny for cardiac disease modeling, drug testing and therapeutics requires the ability to efficiently induce pluripotent cells into the cardiomyogenic lineage. Although direct activation of the Activin-A and/or Bmp pathways with growth factors yields context-dependent success, recent studies have shown that induction of Wnt signaling using low molecular weight molecules such as CHIR, which in turn induces the Activin-A and Bmp pathways, is widely effective. To further enhance the reproducibility of CHIR-induced cardiomyogenesis, and to ultimately promote myocyte maturation, we are using exogenous growth factors to optimize cardiomyogenic signaling downstream of CHIR induction. As indicated by RNA-seq, induction with CHIR during Day 1 (Days 0–1) was followed by immediate expression of Nodal ligands and receptors, followed later by Bmp ligands and receptors. Co-induction with CHIR and high levels of the Nodal mimetic Activin-A (50–100 ng/ml) during Day 0–1 efficiently induced definitive endoderm, whereas CHIR supplemented with Activin-A at low levels (10 ng/ml) consistently improved cardiomyogenic efficiency, even when CHIR alone was ineffective. Moreover, co-induction using CHIR and low levels of Activin-A apparently increased the rate of cardiomyogenesis, as indicated by the initial appearance of rhythmically beating cells by Day 6 instead of Day 8. By contrast, co-induction with CHIR plus low levels (3–10 ng/ml) of Bmp4 during Day 0–1 consistently and strongly inhibited cardiomyogenesis. These findings, which demonstrate that cardiomyogenic efficacy is improved by optimizing levels of CHIR-induced growth factors when applied in accord with their sequence of endogenous expression, are consistent with the idea that Nodal (Activin-A) levels toggle the entry of cells into the endodermal or mesodermal lineages, while Bmp levels regulate subsequent allocation into mesodermal cell types

Critical Examinations of QSO Redshift Periodicities and Associations with Galaxies in Sloan Digital Sky Survey Data

We have used the publicly available data from the Sloan Digital Sky Survey and 2dF QSO Redshift Survey to test the hypothesis that QSOs are ejected from active galaxies with periodic non-cosmological redshifts. For two different intrinsic redshift models, namely the Karlsson $\log(1+z)$ model and Bell's decreasing intrinsic redshift (DIR) model, we do two tests respectively. First, using different criteria, we generate four sets of QSO-galaxy pairs and find there is no evidence for a periodicity at the predicted frequency in $\log(1+z)$, or at any other frequency. We then check the relationship between high redshift QSOs and nearby active galaxies, and we find the distribution of projected distance between high redshift QSOs and nearby active galaxies and the distribution of redshifts of those active galaxies are consistent with a distribution of simulated random pairs, completely different from Bell's previous conclusion. We also analyze the periodicity in redshifts of QSOs, and no periodicity is found in high completeness samples, contrary to the DIR model. These results support that QSOs are not ejected from active galaxies.Comment: 25 pages, 13 figures, accepted for publication in Ap

The Radio-to-Submm Spectral Index as a Redshift Indicator

We present models of the 1.4 GHz to 350 GHz spectral index, alpha(350/1.4), for starburst galaxies as a function of redshift. The models include a semi-analytic formulation, based on the well quantified radio-to-far infrared correlation for low redshift star forming galaxies, and an empirical formulation, based on the observed spectrum of the starburst galaxies M82 and Arp 220. We compare the models to the observed values of alpha(350/1.4) for starburst galaxies at low and high redshift. We find reasonable agreement between the models and the observations, and in particular, that an observed spectral index of alpha(350/1.4) > +0.5 indicates that the target source is likely to be at high redshift, z > 1. The evolution of alpha(350/1.4) with redshift is mainly due to the very steep rise in the Raleigh-Jeans portion of the thermal dust spectrum shifting into the 350 GHz band with increasing redshift. We also discuss situations where this relationship could be violated. We then apply our models to examine the putative identifications of submm sources in the Hubble Deep Field, and conclude that the submm sources reported by Hughes et al. are likely to be at high redshifts, z > 1.5.Comment: standard LATEX file plus 1 postscript figure. Added references and revised figure. second figure revision. Final Proof version. to appear in Astrophysical Journal Letter

Room-Temperature Superfluidity in Graphene Bilayers

Because graphene is an atomically two-dimensional gapless semiconductor with nearly identical conduction and valence bands, graphene-based bilayers are attractive candidates for high-temperature electron-hole pair condensation. We present estimates which suggest that the Kosterlitz-Thouless temperatures of these two-dimensional counterflow superfluids can approach room temperature.Comment: 5 pages, 3 figures; updated discussion and references; to appear in PRB Rapid Com

Impact of \u3cem\u3eMYH6\u3c/em\u3e Variants in Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Project. Damaging MYH6 variants, including novel, missense, in-frame deletion, premature stop, de novo, and compound heterozygous variants, were significantly enriched in HLHS cases (P \u3c 1 × 10−5). Clinical outcomes analysis showed reduced transplant-free survival in HLHS subjects with damaging MYH6 variants (P \u3c 1 × 10−2). Transcriptome and protein expression analyses with cardiac tissue revealed differential expression of cardiac contractility genes, notably upregulation of the β-myosin heavy chain (MYH7) gene in subjects with MYH6 variants (P \u3c 1 × 10−3). We subsequently used patient-specific induced pluripotent stem cells (iPSCs) to model HLHS in vitro. Early stages of in vitro cardiomyogenesis in iPSCs derived from two unrelated HLHS families mimicked the increased expression of MYH7 observed in vivo (P \u3c 1 × 10−2), while revealing defective cardiomyogenic differentiation. Rare, damaging variants in MYH6 are enriched in HLHS, affect molecular expression of contractility genes, and are predictive of poor outcome. These findings indicate that the etiology of MYH6-associated HLHS can be informed using iPSCs and suggest utility in future clinical applications

An integrative model for measuring graduates’ employability skills - A study in China

Employability is a key issue in graduates’ job-hunting, but little research has been done on that of the graduates in Chinese universities. These universities have been experiencing a decline in their graduate employment since the past decade. This paper attempts to tackle this issue. It reviews the relevant research on employability and develops a research-based theoretical framework to evaluate and analyze the graduates’ employability in China. It adopts multiple approaches to establish the skills that will enhance university students’ employability. Investigating around 100 employers and 200 undergraduates from the universities in Beijing, the paper explores the characteristics of and factors influencing the graduates’ employability. Subsequently, it proposes a qualitative model to measure graduates’ employability. Based on the findings, it discusses the theoretical and practical implications and provides advice for Chinese graduates to improve their employability

Bidirectional modulation of hyperalgesia via the specific control of excitatory and inhibitory neuronal activity in the ACC

Neurons in the anterior cingulate cortex (ACC) are assumed to play important roles in the perception of nociceptive signals and the associated emotional responses. However, the neuronal types within the ACC that mediate these functions are poorly understood. In the present study, we used optogenetic techniques to selectively modulate excitatory pyramidal neurons and inhibitory interneurons in the ACC and to assess their ability to modulate peripheral mechanical hypersensitivity in freely moving mice. We found that selective activation of pyramidal neurons rapidly and acutely reduced nociceptive thresholds and that this effect was occluded in animals made hypersensitive using Freund's Complete Adjuvant (CFA). Conversely, inhibition of ACC pyramidal neurons rapidly and acutely reduced hypersensitivity induced by CFA treatment. A similar analgesic effect was induced by activation of parvalbumin (PV) expressing interneurons, whereas activation of somatostatin (SOM) expressing interneurons had no effect on pain thresholds. Our results provide direct evidence of the pivotal role of ACC excitatory neurons, and their regulation by PV expressing interneurons, in nociception. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13041-015-0170-6) contains supplementary material, which is available to authorized users

Oil palm waste: An abundant and promising feedstock for microwave pyrolysis conversion into good quality biochar with potential multi-applications

Oil palm waste (OPW), comprising mainly of empty fruit bunch, mesocarp fiber, frond, trunk, and palm kernel shell generated from palm oil industry, was collected, characterized, and then pyrolyzed to evaluate their potential to be converted into biochar with desirable properties for use in multi-applications. The OPW was detected to have considerable amounts of carbon (43–51 wt%) and fixed carbon (30–39 wt%), showing potential to be converted into carbon-rich biochar. Microwave pyrolysis of palm kernel shell as the selected OPW produced a biochar with zero sulphur content and high heating value (23–26 MJ/kg) that is nearly comparable to conventional coal, thus indicating its potential as an eco-friendly solid fuel. The biochar obtained was also showed low moisture (<3 wt%) and ash (3 wt%), and a highly porous structure with high BET surface area (210 m2/g), indicating the presence of many adsorption sites and thus showing desirable characteristics for potential use as pollutant adsorbent in wastewater treatment, or bio-fertilizer to absorb nutrient and promote plant growth. Our results demonstrate that OPW is a biowaste that shows exceptional promise to be transformed into high-grade biochar rather than simply disposed by landfilling or burned as low-grade fuel in boiler

Ameliorating effects of Mango (Mangifera indica L.) fruit on plasma ethanol level in a mouse model assessed with 1H-NMR based metabolic profiling

The ameliorating effects of Mango (Mangifera indica L.) flesh and peel samples on plasma ethanol level were investigated using a mouse model. Mango fruit samples remarkably decreased mouse plasma ethanol levels and increased the activities of alcohol dehydrogenase and acetaldehyde dehydrogenase. The 1H-NMR-based metabolomic technique was employed to investigate the differences in metabolic profiles of mango fruits, and mouse plasma samples fed with mango fruit samples. The partial least squares-discriminate analysis of 1H-NMR spectral data of mouse plasma demonstrated that there were clear separations among plasma samples from mice fed with buffer, mango flesh and peel. A loading plot demonstrated that metabolites from mango fruit, such as fructose and aspartate, might stimulate alcohol degradation enzymes. This study suggests that mango flesh and peel could be used as resources for functional foods intended to decrease plasma ethanol level after ethanol uptake