Simultaneous profiling of transcriptome and DNA methylome from a single cell.

BackgroundSingle-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear.ResultsHere, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression.ConclusionsOur method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation

Efficient Algorithms for Generalized Linear Bandits with Heavy-tailed Rewards

This paper investigates the problem of generalized linear bandits with heavy-tailed rewards, whose $(1+\epsilon)$-th moment is bounded for some $\epsilon\in (0,1]$. Although there exist methods for generalized linear bandits, most of them focus on bounded or sub-Gaussian rewards and are not well-suited for many real-world scenarios, such as financial markets and web-advertising. To address this issue, we propose two novel algorithms based on truncation and mean of medians. These algorithms achieve an almost optimal regret bound of $\widetilde{O}(dT^{\frac{1}{1+\epsilon}})$, where $d$ is the dimension of contextual information and $T$ is the time horizon. Our truncation-based algorithm supports online learning, distinguishing it from existing truncation-based approaches. Additionally, our mean-of-medians-based algorithm requires only $O(\log T)$ rewards and one estimator per epoch, making it more practical. Moreover, our algorithms improve the regret bounds by a logarithmic factor compared to existing algorithms when $\epsilon=1$. Numerical experimental results confirm the merits of our algorithms

THE EXPRESSION OF INTERLEUKIN-1Β AND MIRNA-146A IN THE CEREBRAL CORTEX OF ACUTE ESCHERICHIA COLI MENINGITIS IMMATURE RAT MODEL

The main limitation to advances in treatment of bacterial meningitis and its complications is the incomplete knowledge of the pathogenesis and pathophysiology of this disease. The aim of this research is to detect the expression of interleukin (IL)-1β as pro-inflammatory cytokine and miRNA (miR)-146a as post transcriptional inflammation associated microRNA (miRNA) in the cerebral cortex of acute Escherichia coli (E. coli) meningitis immature rat model. Immature rats in the post natal day 11 (PN11) were used to construct a model of acute E. coli meningitis and served as controls. The expression of IL-1β and miR-146a were detected in the cerebral cortex by reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative PCR (qPCR) analysis respectively, 24 hours after bacterial inoculation. In the cerebral cortical tissue of acute E. coli meningitis immature rat model the IL-1β expression was significantly upregulated while the miR-146a expression was significantly downregulated. This study tried to add a new insight on the molecular basis of the E. coli meningitis pathogenesis at its very early stage through detecting the expression of IL-1β and miR-146a in the cerebral cortex of the infected immature rats. Consequently, modulation of the IL-1β- miR-146a axis may be a new target for treatment of acute E. coli meningitis

Quantum phase transition in magnetic nanographenes on a lead superconductor

Quantum spins, referred to the spin operator preserved by full SU(2) symmetry in the absence of the magnetic anistropy, have been proposed to host exotic interactions with superconductivity4. However, spin orbit coupling and crystal field splitting normally cause a significant magnetic anisotropy for d/f-shell spins on surfaces6,9, breaking SU(2) symmetry and fabricating the spins with Ising properties10. Recently, magnetic nanographenes have been proven to host intrinsic quantum magnetism due to their negligible spin orbital coupling and crystal field splitting. Here, we fabricate three atomically precise nanographenes with the same magnetic ground state of spin S=1/2 on Pb(111) through engineering sublattice imbalance in graphene honeycomb lattice. Scanning tunneling spectroscopy reveals the coexistence of magnetic bound states and Kondo screening in such hybridized system. Through engineering the magnetic exchange strength between the unpaired spin in nanographenes and cooper pairs, quantum phase transition from the singlet to the doublet state has been observed, in consistent with quantum models of spins on superconductors. Our work demonstrates delocalized graphene magnetism host highly tunable magnetic bound states with cooper pairs, which can be further developed to study the Majorana bound states and other rich quantum physics of low-dimensional quantum spins on superconductors.Comment: 13 pages, 4figure

Plasmonic organic solar cell and its absorption enhancement analysis using cylindrical Ag nano-particle model based on finite difference time domain (FDTD)

We report the plasmon-assisted photocurrent enhancement in Ag nanoparticles (NPs)-embedded PEDOT:PSS/P3HT:PCBM organic solar cells, and theoretically investigate the causes of the improved optical absorption based on a cylindrical Ag-NPs model which is simulated with a finite difference time domain (FDTD) method. The proposed cylindrical Ag-NPs model is able to explain the optical absorption enhancement by the localized surface plasmon resonance (LSPR) modes, and to provide a further understanding of Ag-NPs shape parameters which play an important role to determine the broadband absorption phenomena in plasmonic organic solar cells

Absorption and transport enhancement by Ag nanoparticle plasmonics for organic optoelectronics

The organic films such as P3HT/PCBM incorporating Ag metal nanoparticles are fabricated and experimentally characterized. Due to the excited surface plasma induced by Ag metal nanoparticles, the absorption of the active organic material layer is increased by around 30%. The broadened absorption spectrum to the 260-650nm wavelength range is also observed from our measurements because of the enhanced scattering cross section by Ag metal nanoparticles. Furthermore, by incorporating Ag nanoparticles into the active layer, the mobility have also been improved. Finite Difference Time Domain (FDTD) simulations confirm the increase in transmission of electromagnetic radiation at visible wavelength. The hopping model is proposed to explain the transport mechanism for the device operations. These observations suggest a variety of approaches for improving the performance of general organic optoelectronic devices

Biochemical and structural characterization of Cren7, a novel chromatin protein conserved among Crenarchaea

Archaea contain a variety of chromatin proteins consistent with the evolution of different genome packaging mechanisms. Among the two main kingdoms in the Archaea, Euryarchaeota synthesize histone homologs, whereas Crenarchaeota have not been shown to possess a chromatin protein conserved at the kingdom level. We report the identification of Cren7, a novel family of chromatin proteins highly conserved in the Crenarchaeota. A small, basic, methylated and abundant protein, Cren7 displays a higher affinity for double-stranded DNA than for single-stranded DNA, constrains negative DNA supercoils and is associated with genomic DNA in vivo. The solution structure and DNA-binding surface of Cren7 from the hyperthermophilic crenarchaeon Sulfolobus solfataricus were determined by NMR. The protein adopts an SH3-like fold. It interacts with duplex DNA through a β-sheet and a long flexible loop, presumably resulting in DNA distortions through intercalation of conserved hydrophobic residues into the DNA structure. These data suggest that the crenarchaeal kingdom in the Archaea shares a common strategy in chromatin organization

Targeting of the Human Coagulation Factor IX Gene at rDNA Locus of Human Embryonic Stem Cells

BACKGROUND: Genetic modification is a prerequisite to realizing the full potential of human embryonic stem cells (hESCs) in human genetic research and regenerative medicine. Unfortunately, the random integration methods that have been the primary techniques used keep creating problems, and the primary alternative method, gene targeting, has been effective in manipulating mouse embryonic stem cells (mESCs) but poorly in hESCs. METHODOLOGY/PRINCIPAL FINDINGS: Human ribosomal DNA (rDNA) repeats are clustered on the short arm of acrocentric chromosomes. They consist of approximately 400 copies of the 45S pre-RNA (rRNA) gene per haploid. In the present study, we targeted a physiological gene, human coagulation factor IX, into the rDNA locus of hESCs via homologous recombination. The relative gene targeting efficiency (>50%) and homologous recombination frequency (>10(-5)) were more than 10-fold higher than those of loci targeted in previous reports. Meanwhile, the targeted clones retained both a normal karyotype and the main characteristics of ES cells. The transgene was found to be stably and ectopically expressed in targeted hESCs. CONCLUSION/SIGNIFICANCE: This is the first targeting of a human physiological gene at a defined locus on the hESC genome. Our findings indicate that the rDNA locus may serve as an ideal harbor for transgenes in hESCs