BMP9 Induces Cord Blood-Derived Endothelial Progenitor Cell Differentiation and Ischemic Neovascularization via ALK1

Objective Modulating endothelial progenitor cells (EPCs) is essential for therapeutic angiogenesis, and thus various clinical trials involving EPCs are ongoing. However, the identification of environmental conditions and development of optimal methods are required to accelerate EPC-driven vasculogenesis. Approach and Results We evaluated gene expression profiles of cord blood-derived EPCs and endothelial cells to identify the key factors in EPCendothelial cell differentiation and to show that transforming growth factor- family members contribute to EPC differentiation. The expression levels of activin receptor-like kinase 1 (ALK1) and its high-affinity ligand, bone morphogenetic protein 9 (BMP9) were markedly changed in EPCendothelial cell differentiation. Interestingly, BMP9 induced EPCendothelial cell differentiation and EPC incorporation into vessel-like structures by acting on ALK1 expressed on EPCs in vitro. BMP9 also induced neovascularization in mice with hindlimb ischemia by increasing vessel formation and the incorporation of EPCs into vessels. Conversely, neovascularization was impaired when ALK1 signaling was blocked. Furthermore, EPCs exposed to either short- or long-term BMP9 stimulation demonstrated these functions in EPC-mediated neovascularization. Conclusions Collectively, our results indicated that BMP9/ALK1 augmented vasculogenesis and angiogenesis, and thereby enhanced neovascularization. Thus, we suggest that BMP9/ALK1 may improve the efficacy of EPC-based therapies for treating ischemic diseases.111212Ysciescopu

Facile Fabrication of Ultrafine Copper Nanoparticles in Organic Solvent

A facile chemical reduction method has been developed to fabricate ultrafine copper nanoparticles whose sizes can be controlled down to ca. 1 nm by using poly(N-vinylpyrrolidone) (PVP) as the stabilizer and sodium borohyrdride as the reducing agent in an alkaline ethylene glycol (EG) solvent. Transmission electron microscopy (TEM) results and UV–vis absorption spectra demonstrated that the as-prepared particles were well monodispersed, mostly composed of pure metallic Cu nanocrystals and extremely stable over extended period of simply sealed storage

Annexin A2 Binds RNA and Reduces the Frameshifting Efficiency of Infectious Bronchitis Virus

Annexin A2 (ANXA2) is a protein implicated in diverse cellular functions, including exocytosis, DNA synthesis and cell proliferation. It was recently proposed to be involved in RNA metabolism because it was shown to associate with some cellular mRNA. Here, we identified ANXA2 as a RNA binding protein (RBP) that binds IBV (Infectious Bronchitis Virus) pseudoknot RNA. We first confirmed the binding of ANXA2 to IBV pseudoknot RNA by ultraviolet crosslinking and showed its binding to RNA pseudoknot with ANXA2 protein in vitro and in the cells. Since the RNA pseudoknot located in the frameshifting region of IBV was used as bait for cellular RBPs, we tested whether ANXA2 could regulate the frameshfting of IBV pseudoknot RNA by dual luciferase assay. Overexpression of ANXA2 significantly reduced the frameshifting efficiency from IBV pseudoknot RNA and knockdown of the protein strikingly increased the frameshifting efficiency. The results suggest that ANXA2 is a cellular RBP that can modulate the frameshifting efficiency of viral RNA, enabling it to act as an anti-viral cellular protein, and hinting at roles in RNA metabolism for other cellular mRNAs

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

On Naturalness of the MSSM and NMSSM

With a bottom-up approach, we consider naturalness in the MSSM and NMSSM. Assuming the light stops, the LHC gluino search implies that the degree of fine tuning in both models is less than 2.5%. Taking the LHC hints for the SM-like Higgs boson mass m_h\sim125 GeV seriously, we find that naturalness will favor the NMSSM. We study the Higgs boson mass for several scenarios in the NMSSM: (1) A large \lambda and the doublet-singlet Higgs boson mixing effect pushing upward or pulling downward m_h. The former case can readily give the di-photon excess of the Higgs boson decay whereas the latter case can not. However, we point out that the former case has a new large fine-tuning related to strong \lambda-RGE running effect and vacuum stability. (2) A small \lambda and the mixing effect pushing m_h upward. Naturalness status becomes worse and no significant di-photon excess can be obtained. In these scenarios, the lightest supersymmetric particle (LSP) as a dark matter candidate is strongly disfavored by the XENON100 experiment. Even if the LSP can be a viable dark matter candidate, there does exist fine-tuning. The above naturalness evaluation is based on a high mediation scale for supersymmetry breaking, whereas for a low mediation scale, fine-tuning can be improved by about one order.Comment: JHEP version, adding some comments/references and improving Englis

Three-dimensional nitrogen-doped graphene supported molybdenum disulfide nanoparticles as an advanced catalyst for hydrogen evolution reaction

An efficient three-dimensional (3D) hybrid material of nitrogen-doped graphene sheets (N-RGO) supporting molybdenum disulfide (MoS2) nanoparticles with high-performance electrocatalytic activity for hydrogen evolution reaction (HER) is fabricated by using a facile hydrothermal route. Comprehensive microscopic and spectroscopic characterizations confirm the resulting hybrid material possesses a 3D crumpled few-layered graphene network structure decorated with MoS2 nanoparticles. Electrochemical characterization analysis reveals that the resulting hybrid material exhibits efficient electrocatalytic activity toward HER under acidic conditions with a low onset potential of 112 mV and a small Tafel slope of 44 mV per decade. The enhanced mechanism of electrocatalytic activity has been investigated in detail by controlling the elemental composition, electrical conductance and surface morphology of the 3D hybrid as well as Density Functional Theory (DFT) calculations. This demonstrates that the abundance of exposed active sulfur edge sites in the MoS2 and nitrogen active functional moieties in N-RGO are synergistically responsible for the catalytic activity, whilst the distinguished and coherent interface in MoS 2 /N-RGO facilitates the electron transfer during electrocatalysis. Our study gives insights into the physical/chemical mechanism of enhanced HER performance in MoS2/N-RGO hybrids and illustrates how to design and construct a 3D hybrid to maximize the catalytic efficiency

Deletion of the Huntingtin Polyglutamine Stretch Enhances Neuronal Autophagy and Longevity in Mice

Expansion of a stretch of polyglutamine in huntingtin (htt), the protein product of the IT15 gene, causes Huntington's disease (HD). Previous investigations into the role of the polyglutamine stretch (polyQ) in htt function have suggested that its length may modulate a normal htt function involved in regulating energy homeostasis. Here we show that expression of full-length htt lacking its polyglutamine stretch (ΔQ-htt) in a knockin mouse model for HD (Hdh140Q/ΔQ), reduces significantly neuropil mutant htt aggregates, ameliorates motor/behavioral deficits, and extends lifespan in comparison to the HD model mice (Hdh140Q/+). The rescue of HD model phenotypes is accompanied by the normalization of lipofuscin levels in the brain and an increase in the steady-state levels of the mammalian autophagy marker microtubule-associate protein 1 light chain 3-II (LC3-II). We also find that ΔQ-htt expression in vitro increases autophagosome synthesis and stimulates the Atg5-dependent clearance of truncated N-terminal htt aggregates. ΔQ-htt's effect on autophagy most likely represents a gain-of-function, as overexpression of full-length wild-type htt in vitro does not increase autophagosome synthesis. Moreover, HdhΔQ/ΔQ mice live significantly longer than wild-type mice, suggesting that autophagy upregulation may be beneficial both in diseases caused by toxic intracellular aggregate-prone proteins and also as a lifespan extender in normal mammals

CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism

In this study, we investigated the role of CD38 in a pristane-induced murine model of lupus. CD38-deficient (Cd38-/-) but not ART2-deficient (Art2-/-) mice developed less severe lupus compared to wild type (WT) mice, and their protective phenotype consisted of (i) decreased IFN-I-stimulated gene expression, (ii) decreased numbers of peritoneal CCR2hiLy6Chi inflammatory monocytes, TNF-α-producing Ly6G+ neutrophils and Ly6Clo monocytes/macrophages, (iii) decreased production of anti-single-stranded DNA and anti-nRNP autoantibodies, and (iv) ameliorated glomerulonephritis. Cd38-/- pristane-elicited peritoneal exudate cells had defective CCL2 and TNF-α secretion following TLR7 stimulation. However, Tnf-α and Cxcl12 gene expression in Cd38-/- bone marrow (BM) cells was intact, suggesting a CD38-independent TLR7/TNF-α/CXCL12 axis in the BM. Chemotactic responses of Cd38-/- Ly6Chi monocytes and Ly6G+ neutrophils were not impaired. However, Cd38-/- Ly6Chi monocytes and Ly6Clo monocytes/macrophages had defective apoptosis-mediated cell death. Importantly, mice lacking the cation channel TRPM2 (Trpm2-/-) exhibited very similar protection, with decreased numbers of PECs, and apoptotic Ly6Chi monocytes and Ly6Clo monocytes/macrophages compared to WT mice. These findings reveal a new role for CD38 in promoting aberrant inflammation and lupus-like autoimmunity via an apoptosis-driven mechanism. Furthermore, given the implications of CD38 in the activation of TRPM2, our data suggest that CD38 modulation of pristane-induced apoptosis is TRPM2-dependent.We would like to thank Dr. Yasuo Mori for providing the Tr pm 2−/− mice, Clara Sánchez for animal husbandry at the IPBLN-CSIC Animal Facility, and Thomas S. Simpler and Uma Mudunuru for animal husbandry at the University of Alabama at Birmingham (UAB). We would also like to thank Laura Montosa from the Centro de Instrumentación Cientifica (CIC) at the Universidad de Granada (UGR) for technical support with microscopy, as well as Mohamed Tassi and Ana Santos at CIC, UGR, and Sandra García-Jiménez, Victoria Romero-del-Amo, Gemma Palencia-López, and Samuel Ruiz-Santiago at Campus Formación Granada for tissue preparations, H&E staining, and other staining procedures. Work performed in the Sancho lab was supported in part by the European Commission in collaboration with the following Funding Agencies: (i) Junta de Andalucía (J.A.), Consejería Innovación Ciencia y Empresa y Consejería Educación y Ciencia, Project: PC08-CTS-04046 to J.S. and M.Z., and (ii) Ministerio de Economía y Competitividad (MINECO), Projects: SAF-2011-27261 to J.S. and M.Z. and SAF2014-55088-R to R.M. Work performed in the Lund lab was supported by funds provided by UAB.S