Age-associated epigenetic modifications in human DNA increase its immunogenicity

Chronic inflammation, increased reactivity to self-antigens and incidences of cancer are hallmarks of aging. However, the underlying mechanisms are not well understood. Age-associated alterations in the DNA either due to oxidative damage, defects in DNA repair or epigenetic modifications such as methylation that lead to mutations and changes in the expression of genes are thought to be partially responsible. Here we report that epigenetic modifications in aged DNA also increase its immunogenicity rendering it more reactive to innate immune system cells such as the dendritic cells. We observed increased upregulation of costimulatory molecules as well as enhanced secretion of IFN-α from dendritic cells in response to DNA from aged donors as compared to DNA from young donors when it was delivered intracellularly via Lipofectamine. Investigations into the mechanisms revealed that DNA from aged subjects is not degraded, neither is it more damaged compared to DNA from young subjects. However, there is significantly decreased global level of methylation suggesting that age-associated hypomethylation of the DNA may be the cause of its increased immunogenicity. Increased immunogenicity of self DNA may thus be another mechanism that may contribute to the increase in age-associated chronic inflammation, autoimmunity and cancer

Atomic-scale visualization of quasiparticle interference on a type-II Weyl semimetal surface

We combine quasiparticle interference simulation (theory) and atomic resolution scanning tunneling spectro-microscopy (experiment) to visualize the interference patterns on a type-II Weyl semimetal Mo$_{x}$W$_{1-x}$Te$_2$ for the first time. Our simulation based on first-principles band topology theoretically reveals the surface electron scattering behavior. We identify the topological Fermi arc states and reveal the scattering properties of the surface states in Mo$_{0.66}$W$_{0.34}$Te$_2$. In addition, our result reveals an experimental signature of the topology via the interconnectivity of bulk and surface states, which is essential for understanding the unusual nature of this material.Comment: To appear in Phys. Rev. Let

Ultraquantum magnetoresistance in Kramers Weyl semimetal candidate β\beta-Ag2Se

The topological semimetal $\beta$-Ag2Se features a Kramers Weyl node at the origin in momentum space and a quadruplet of spinless Weyl nodes, which are annihilated by spin-orbit coupling. We show that single crystalline $\beta$-Ag2Se manifests giant Shubnikov-de Haas oscillations in the longitudinal magnetoresistance which stem from a small electron pocket that can be driven beyond the quantum limit by a field less than 9 T. This small electron pocket is a remainder of the spin-orbit annihilatedWeyl nodes and thus encloses a Berry-phase structure. Moreover, we observed a negative longitudinal magnetoresistance when the magnetic field is beyond the quantum limit. Our experimental findings are complemented by thorough theoretical band structure analyses of this Kramers Weyl semimetal candidate, including first-principle calculations and an effective k*p model.Comment: A new version based on arXiv:1502.0232

Mirror protected Dirac fermions on a Weyl semimetal NbP surface

The first Weyl semimetal was recently discovered in the NbP class of compounds. Although the topology of these novel materials has been identified, the surface properties are not yet fully understood. By means of scanning tunneling spectroscopy, we find that NbPs (001) surface hosts a pair of Dirac cones protected by mirror symmetry. Through our high resolution spectroscopic measurements, we resolve the quantum interference patterns arising from these novel Dirac fermions, and reveal their electronic structure, including the linear dispersions. Our data, in agreement with our theoretical calculations, uncover further interesting features of the Weyl semimetal NbPs already exotic surface. Moreover, we discuss the similarities and distinctions between the Dirac fermions here and those in topological crystalline insulators in terms of symmetry protection and topology

Unconventional transformation of spin Dirac phase across a topological quantum phase transition

The topology of a topological material can be encoded in its surface states. These surface states can only be removed by a bulk topological quantum phase transition into a trivial phase. Here we use photoemission spectroscopy to image the formation of protected surface states in a topological insulator as we chemically tune the system through a topological transition. Surprisingly, we discover an exotic spin-momentum locked, gapped surface state in the trivial phase that shares many important properties with the actual topological surface state in anticipation of the change of topology. Using a spin-resolved measurement, we show that apart from a surface band-gap these states develop spin textures similar to the topological surface states well-before the transition. Our results offer a general paradigm for understanding how surface states in topological phases arise and are suggestive for future realizing Weyl arcs, condensed matter supersymmetry and other fascinating phenomena in the vicinity of topological quantum criticality.Comment: 20 pages, 5 Figures, Related papers at http://physics.princeton.edu/zahidhasangroup/index.html, Accepted for publication in Nature Commun.(2015