Efficient Generation of Fully Reprogrammed Human iPS Cells via Polycistronic Retroviral Vector and a New Cocktail of Chemical Compounds

Direct reprogramming of human somatic cells into induced pluripotent stem (iPS) cells by defined transcription factors (TFs) provides great potential for regenerative medicine and biomedical research. This procedure has many challenges, including low reprogramming efficiency, many partially reprogrammed colonies, somatic coding mutations in the genome, etc. Here, we describe a simple approach for generating fully reprogrammed human iPS cells by using a single polycistronic retroviral vector expressing four human TFs in a single open reading frame (ORF), combined with a cocktail containing three small molecules (Sodium butyrate, SB431542, and PD0325901). Our results demonstrate that human iPS cells generated by this approach express human ES cells markers and exhibit pluripotency demonstrated by their abilities to differentiate into the three germ layers in vitro and in vivo. Notably, this approach not only provides a much faster reprogramming process but also significantly diminishes partially reprogrammed iPS cell colonies, thus facilitating efficient isolation of desired fully reprogrammed iPS cell colonies

A Neurotrophic Mechanism Directs Sensory Nerve Transit in Cranial Bone

The flat bones of the skull are densely innervated during development, but little is known regarding their role during repair. We describe a neurotrophic mechanism that directs sensory nerve transit in the mouse calvaria. Patent cranial suture mesenchyme represents an NGF (nerve growth factor)-rich domain, in which sensory nerves transit. Experimental calvarial injury upregulates Ngf in an IL-1 beta/TNF-alpha-rich defect niche, with consequent axonal ingrowth. In calvarial osteoblasts, IL-1 beta and TNF-alpha stimulate Ngf and downstream NF-kappa B signaling. Locoregional deletion of Ngf delays defect site re-innervation and blunted repair. Genetic disruption of Ngf among LysM-expressing macrophages phenocopies these observations, whereas conditional knockout of Ngf among Pdgfra-expressing cells does not. Finally, inhibition of TrkA catalytic activity similarly delays re-innervation and repair. These results demonstrate an essential role of NGF-TrkA signaling in bone healing and implicate macrophage-derived NGF-induced ingrowth of skeletal sensory nerves as an important mediator of this repair

Lysosomal protein surface expression discriminates fat- from bone-forming human mesenchymal precursor cells

Tissue resident mesenchymal stem/stromal cells (MSCs) occupy perivascular spaces. Profiling human adipose perivascular mesenchyme with antibody arrays identified 16 novel surface antigens, including endolysosomal protein CD107a. Surface CD107a expression segregates MSCs into functionally distinct subsets. In culture, CD107a(low) cells demonstrate high colony formation, osteoprogenitor cell frequency, and osteogenic potential. Conversely, CD107a(high) cells include almost exclusively adipocyte progenitor cells. Accordingly, human CD107a(low) cells drove dramatic bone formation after intramuscular transplantation in mice, and induced spine fusion in rats, whereas CD107a(high) cells did not. CD107a protein trafficking to the cell surface is associated with exocytosis during early adipogenic differentiation. RNA sequencing also suggested that CD107a(low) cells are precursors of CD107a(high) cells. These results document the molecular and functional diversity of perivascular regenerative cells, and show that relocation to cell surface of a lysosomal protein marks the transition from osteo- to adipogenic potential in native human MSCs, a population of substantial therapeutic interest

A Joint Detection and Decoding Scheme for PC-SCMA System Based on Pruning Iteration

Polar coding and sparse code multiple access (SCMA) are key technologies for 5G mobile communication, the joint design of them has a great significance to improve the overall performance of the transmitter-receiver symmetric wireless communication system. In this paper, we firstly propose a pruning iterative joint detection and decoding algorithm (PI-JDD) based on the confidence stability of resource nodes. Branches to be updated are dynamically pruned to avoid redundant iterative, which is able to reduce 24~50% complexity while achieving the approximate error performance of traditional serial joint iterative detection and decoding algorithm S-JIDD. Then, to further reduce the bit error rate (BER) of the receiver, a cyclic redundancy check (CRC) termination mechanism is added at the end of each joint iteration to avoid the convergence error caused by decoding deviation. Simulation results show that the addition of an early stopping criterion can achieve a remarkable performance gain compared with the S-JIDD algorithm. More importantly, the combined algorithm of the two proposed schemes can reduce the computational complexity while achieving better error performance

Phase field modeling of brittle fracture in an Euler–Bernoulli beam accounting for transverse part-through cracks

We present a phase field model to simulate brittle fracture in an initially straight Euler–Bernoulli beam, with generalization to curved beams. We start from formulating the problem with the principle of minimum potential energy in a 3D solid, with the displacement field and the phase field as primary arguments. We then select, for each cross section, representative fields that characterize the said cross section, including the beam deflection and rotation, and two independent ansatz variables within the cross section to represent the phase field. The problem then reduces to a minimization with only one-dimensional field variables. A feature of the proposed method is, without discretizing the phase field within the cross section, it can represent its variation within the cross section, allowing to simulate cracks partially going through the thickness due to bending as well as axial loads

Phase field modeling of brittle fracture in an Euler–Bernoulli beam accounting for transverse part-through cracks

© 2020 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/We present a phase field model to simulate brittle fracture in an initially straight Euler–Bernoulli beam, with generalization to curved beams. We start from formulating the problem with the principle of minimum potential energy in a 3D solid, with the displacement field and the phase field as primary arguments. We then select, for each cross section, representative fields that characterize the said cross section, including the beam deflection and rotation, and two independent ansatz variables within the cross section to represent the phase field. The problem then reduces to a minimization with only one-dimensional field variables. A feature of the proposed method is, without discretizing the phase field within the cross section, it can represent its variation within the cross section, allowing to simulate cracks partially going through the thickness due to bending as well as axial loads.Peer ReviewedPostprint (author's final draft

Transcriptome Profiles of Circular RNAs in Common Wheat during <i>Fusarium</i> Head Blight Disease

Circular RNAs (circRNAs) are covalently closed RNA molecules, and have been identified in many crops. However, there are few datasets for circRNA junctions from common wheat during Fusarium head blight disease. In the present study, we used RNA-seq to determine the changes in circRNAs among the control (CK) and 1, 3, and 5 days post-Fusarium graminearum inoculation (dpi) samples. More than one billion reads were produced from 12 libraries, and 99.99% of the reads were successfully mapped to a wheat reference genome. In total, 2091 high-confidence circRNAs—which had two or more junction reads and were supported by at least two circRNA identification algorithms—were detected. The completed expression profiling revealed a distinct expression pattern of circRNAs among the CK, 1dpi, 3dpi and 5dpi samples. This study provides a valuable resource for identifying F. graminearum infection-responsive circRNAs in wheat and for further functional characterization of circRNAs that participated in the Fusarium head blight disease response of wheat