Long-term culture captures injury-repair cycles of colonic stem cells

The colonic epithelium can undergo multiple rounds of damage and repair, often in response to excessive inflammation. The responsive stem cell that mediates this process is unclear, in part because of a lack of in vitro models that recapitulate key epithelial changes that occur in vivo during damage and repair. Here, we identify a Hop

A Note on Temperature and Energy of 4-dimensional Black Holes from Entropic Force

We investigate the temperature and energy on holographic screens for 4-dimensional black holes with the entropic force idea proposed by Verlinde. We find that the "Unruh-Verlinde temperature" is equal to the Hawking temperature on the horizon and can be considered as a generalized Hawking temperature on the holographic screen outside the horizons. The energy on the holographic screen is not the black hole mass $M$ but the reduced mass $M_0$, which is related to the black hole parameters. With the replacement of the black hole mass $M$ by the reduced mass $M_0$, the entropic force can be written as $F=\frac{GmM_0}{r^2}$, which could be tested by experiments.Comment: V4: 13 pages, 4 figures, title changed, discussions for experiments added, accepted by CQ

Local density of states and scanning tunneling currents in graphene

We present exact analytical calculations of scanning tunneling currents in locally disordered graphene using a multimode description of the microscope tip. Analytical expressions for the local density of states (LDOS) are given for energies beyond the Dirac cone approximation. We show that the LDOS at the $A$ and $B$ sublattices of graphene are out of phase by $\pi$ implying that the averaged LDOS, as one moves away from the impurity, shows no trace of the $2q_F$ (with $q_F$ the Fermi momentum) Friedel modulation. This means that a STM experiment lacking atomic resolution at the sublattice level will not be able of detecting the presence of the Friedel oscillations [this seems to be the case in the experiments reported in Phys. Rev. Lett. {\bf 101}, 206802 (2008)]. The momentum maps of the LDOS for different types of impurities are given. In the case of the vacancy, $2q_F$ features are seen in these maps. In all momentum space maps, $K$ and $K+K^\prime$ features are seen. The $K+K^\prime$ features are different from what is seen around zero momentum. An interpretation for these features is given. The calculations reported here are valid for chemical substitution impurities, such as boron and nitrogen atoms, as well as for vacancies. It is shown that the density of states close to the impurity is very sensitive to type of disorder: diagonal, non-diagonal, or vacancies. In the case of weakly coupled (to the carbon atoms) impurities, the local density of states presents strong resonances at finite energies, which leads to steps in the scanning tunneling currents and to suppression of the Fano factor.Comment: 21 pages. Figures 6 and 7 are correctly displayed in this new versio

Next-to-leading order QCD predictions for Z0H0+jetZ^0 H^0 + {\rm jet} production at LHC

We calculate the complete next-to-leading order (NLO) QCD corrections to the $Z^0H^0$ production in association with a jet at the LHC. We study the impacts of the NLO QCD radiative corrections to the integrated and differential cross sections and the dependence of the cross section on the factorization/renormalization scale. We present the transverse momentum distributions of the final $Z^0$-, Higgs-boson and leading-jet. We find that the NLO QCD corrections significantly modify the physical observables, and obviously reduce the scale uncertainty of the LO cross section. The QCD K-factors can be 1.183 and 1.180 at the $\sqrt{s}=14 TeV$ and $\sqrt{s}=7 TeV$ LHC respectively, when we adopt the inclusive event selection scheme with $p_{T,j}^{cut}=50 GeV$, $m_H=120 GeV$ and $\mu=\mu_r=\mu_f=\mu_0 \equiv 1/2(m_Z+m_H)$. Furthermore, we make the comparison between the two scale choices, $\mu=\mu_0$ and $\mu=\mu_1=1/2(E_{T}^{Z}+E_{T}^{H}+ \sum_{j}E_{T}^{jet})$, and find the scale choice $\mu=\mu_1$ seems to be more appropriate than the fixed scale $\mu=\mu_0$.Comment: 18 pages, 7 figure

Investigation of radioactivity-induced backgrounds in EXO-200

The search for neutrinoless double-beta decay (0{\nu}{\beta}{\beta}) requires extremely low background and a good understanding of their sources and their influence on the rate in the region of parameter space relevant to the 0{\nu}{\beta}{\beta} signal. We report on studies of various {\beta}- and {\gamma}-backgrounds in the liquid- xenon-based EXO-200 0{\nu}{\beta}{\beta} experiment. With this work we try to better understand the location and strength of specific background sources and compare the conclusions to radioassay results taken before and during detector construction. Finally, we discuss the implications of these studies for EXO-200 as well as for the next-generation, tonne-scale nEXO detector.Comment: 9 pages, 7 figures, 3 table

Characterization of biological functions of human RNA-binding proteins in Poly(ADP-ribose) polymerase-1-regulated pathways

Poly(ADP-ribosy)lation (PARylation) can served as a scaffold for noncovalent interactions with various RNA binding proteins including helicases and ribosomal proteins, but many important questions remains regarding the molecular functions and biological roles through the interaction. Based on live-cell imaging assay, I found that DEAD-box helicase 18 (DDX18) and ribosomal protein S19 (RPS19) accumulated to DNA damage sites via PARP-1 activation, indicating their participation in PARP-1-dependent DNA damage repair. My results show that PARP-1 can mediate the association of DDX18 with R-loops thereby modulating R-loop homeostasis and R-loop-dependent DNA damage. DDX18 knockdown renders cells more sensitive to DNA damaging reagents. Furthermore, knockdown of DDX18 reduces R-loop-induced RPA32 and RAD51 foci formation in response to irradiation, and DDX18 depletion also leads to R-loop-induced γH2AX accumulation and genome instability. In addition, DDX18 knockdown abolishes DNA replication due to R-loop accumulation. Taken together, the data uncover new functions of PARP-1 mediated DDX18 in R-loop-mediated events. Here, I also identify RPS19 as a new regulator in DNA double-strand break (DSB) repair. RPS19 was recruited to the DNA damage regions through its putative PAR-binding motif, and the accumulation of RPS19 was PARP-1 dependent. In the absence of RPS19, cells showed reduced RAD51 foci formation, whereas γH2AX and RPA32 foci were increased. Furthermore, the accumulation of RPS19 at DNA damage sites were abolished during the treatment of ATR inhibitors but not ATM inhibitors. Upon X-ray irradiation, RPS19-knockdown cells also decreased phosphorylation of Chk1 at Ser345, which is the downstream of ATR. The results suggest the novel role of RPS19 in ATR pathway during DNA damage repair. In summary, these observations provide a further mechanistic understanding of RNA-binding proteins in PARP-1 mediated DNA damage responses.Biochemistr

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases