DamIP: A novel method to identify DNA binding sites in vivo

Identifying binding sites and target genes of transcription factors is a major biologic problem. The most commonly used current technique, chromatin immunoprecipitation (ChIP), is dependent on a high quality antibody for each protein of interest, which is not always available, and is also cumbersome, involving sequential cross-linking and reversal of cross-linking. We have developed a novel strategy to study protein DNA binding sites in vivo, which we term DamIP. By tethering a mutant form of E. coli DNA adenine methyltransferase to the target protein, the fusion protein introduces N-6-adenosine methylation to sequences proximal to the protein binding sites. DNA fragments with this modification, which is absent in eukaryotes, are detected using an antibody directed against methylated adenosine. For an initial test of the method we used human estrogen receptor α (hERα), one of the best studied transcription factors. We found that expression of Dam-hERα fusion proteins in MCF-7 cells introduces adenosine methylation near a series of known direct hERα binding sites. Specific methylation tags are also found at indirect hERα binding sites, including both primary binding sites for the ER interactors AP-1 and SP1, and promoters that are activated by upstream ER bound enhancers. DamIP provides a new tool for the study of DNA interacting protein function in vivo

Mechanical disruption of the blood-brain barrier following experimental concussion

Although concussion is now recognized as a major health issue, its non-lethal nature has limited characterization of the underlying pathophysiology. In particular, potential neuropathological changes have typically been inferred from non-invasive techniques or post-mortem examinations of severe traumatic brain injury (TBI). Here, we used a swine model of head rotational acceleration based on human concussion to examine blood–brain barrier (BBB) integrity after injury in association with diffuse axonal injury and glial responses. We then determined the potential clinical relevance of the swine concussion findings through comparisons with pathological changes in human severe TBI, where post-mortem examinations are possible. At 6–72 h post-injury in swine, we observed multifocal disruption of the BBB, demonstrated by extravasation of serum proteins, fibrinogen and immunoglobulin-G, in the absence of hemorrhage or other focal pathology. BBB disruption was observed in a stereotyped distribution consistent with biomechanical insult. Specifically, extravasated serum proteins were frequently observed at interfaces between regions of tissue with differing material properties, including the gray–white boundary, periventricular and subpial regions. In addition, there was substantial overlap of BBB disruption with regions of axonal pathology in the white matter. Acute perivascular cellular uptake of blood-borne proteins was observed to be prominent in astrocytes (GFAP-positive) and neurons (MAP-2-positive), but not microglia (IBA1-positive). Parallel examination of human severe TBI revealed similar patterns of serum extravasation and glial uptake of serum proteins, but to a much greater extent than in the swine model, attributed to the higher injury severity. These data suggest that BBB disruption represents a new and important pathological feature of concussion

Gold mineralized diorite beneath the Linglong ore field, North China craton: New insights into the origin of decratonization-related gold deposits

Gold deposits in Precambrian cratons were mostly generated during the formation and stabilization of the cratons, but the North China craton is unusual in that its gold deposits were mainly formed ∼1.7 b.y. after its stabilization. A magmatic-hydrothermal origin or mantle-derived fluid source has been proposed for the giant gold deposits of the Jiaodong District in the eastern North China craton, but direct evidence is sparse, and the mineralization processes remain controversial. Here, we present the results of a comprehensive geological, geochronological, and geochemical study of the gold mineralized Xiejia diorite beneath the Linglong ore field at Jiaodong to link the gold mineralization to underlying magmatism. Magmatic zircon and titanite grains from the Xiejia diorite have laser ablation−inductively coupled plasma−mass spectrometry (LA-ICP-MS) U-Pb ages of 121.3 ± 0.9 Ma to 120.8 ± 1.1 Ma and 121.7 ± 3.9 Ma, respectively, which are indistinguishable from the time of gold deposition throughout the Jiaodong District as constrained by previous studies. The diorite has a shoshonitic composition and is characterized by strong enrichment in large ion lithophile elements (LILEs) and light rare earth elements (LREEs) along with significant depletion in high field strength elements (HFSEs) and heavy rare earth elements (HREEs). Samples of the diorite have high initial 87Sr/86Sr ratios, but low εNd(t) and ɛHf(t) values and low Pb isotope ratios. These geochemical characteristics are akin to those of contemporaneous mafic dikes in most gold mines at Jiaodong, indicating that the Xiejia diorite was most likely derived from an enriched lithospheric mantle source. The upper part of the diorite intrusion is pervasively altered and mineralized, containing an average of 0.32 g/t Au, but locally up to 7.59 g/t. Hydrothermal titanite from the mineralized diorite has a LA-ICP-MS U-Pb age of 122.3 ± 4.3 Ma, which is consistent with the gold-bearing pyrite Re-Os isochron age of 122.5 ± 6.7 Ma. Ore-related sericite aggregates from the Dongfeng gold deposit above the Xiejia diorite have a 40Ar/39Ar plateau age of 122.6 ± 1.3 Ma. Pyrite from the mineralized diorite yielded δ34SCDT values of 2.1‰−9.7‰, which are comparable with those of pyrite (δ34SCDT = 5.8‰−8.1‰, where CDT indicates the Canyon Diablo troilite standard) from gold ores of Dongfeng. Pyrite grains from both groups also have similar Pb isotope compositions. The S and Pb isotope data are consistent with values of mafic dikes that are spatially and temporally associated with gold veins in the Linglong ore field. The results presented here thus indicate a possible genetic link between gold mineralization in the Xiejia diorite and underlying magma presumably represented by the Xiejia diorite. The auriferous fluids exsolved from that magma and migrated upward along the Potouqing fault to form the Dongfeng gold deposit above the Xiejia diorite. The mineralized diorite thus links shallow gold mineralization to deep-seated mantle-derived magmatism generated during the extensive destruction of the North China craton induced by the rollback of the subducted paleo-Pacific plate

Efficient and long-lived quantum memory with cold atoms inside a ring cavity

Quantum memories are regarded as one of the fundamental building blocks of linear-optical quantum computation and long-distance quantum communication. A long standing goal to realize scalable quantum information processing is to build a long-lived and efficient quantum memory. There have been significant efforts distributed towards this goal. However, either efficient but short-lived or long-lived but inefficient quantum memories have been demonstrated so far. Here we report a high-performance quantum memory in which long lifetime and high retrieval efficiency meet for the first time. By placing a ring cavity around an atomic ensemble, employing a pair of clock states, creating a long-wavelength spin wave, and arranging the setup in the gravitational direction, we realize a quantum memory with an intrinsic spin wave to photon conversion efficiency of 73(2)% together with a storage lifetime of 3.2(1) ms. This realization provides an essential tool towards scalable linear-optical quantum information processing.Comment: 6 pages, 4 figure

Revisiting the B {\to} {\pi} {\rho}, {\pi} {\omega} Decays in the Perturbative QCD Approach Beyond the Leading Order

We calculate the branching ratios and CP asymmetries of the $B \to \pi \rho$, $\pi\omega$ decays in the perturbative QCD factorization approach up to the next-to-leading-order contributions. We find that the next-to-leading-order contributions can interfere with the leading-order part constructively or destructively for different decay modes. Our numerical results have a much better agreement with current available data than previous leading-order calculations, e.g., the next-to-leading-order corrections enhance the $B^0\rightarrow \pi^0\rho^0$ branching ratios by a factor 2.5, which is helpful to narrow the gaps between theoretic predictions and experimental data. We also update the direct CP-violation parameters, the mixing-induced CP-violation parameters of these modes, which show a better agreement with experimental data than many of the other approaches.Comment: 23 pages, 4 figures, 4 table

Costs of screening children for hearing disorders and delivery of hearing aids in China

Contains fulltext : 79593.pdf (publisher's version ) (Open Access)BACKGROUND: The burden of disease of hearing disorders among children is high, but a large part goes undetected. School-based screening programs in combination with the delivery of hearing aids can alleviate this situation, but the costs of such programs are unknown. AIM: To evaluate the costs of a school-based screening program for hearing disorders, among approximately 216,000 school children, and the delivery of hearing aids to 206 children at three different care levels in China. METHODS: In a prospective study design, screening and hearing aid delivery costs were estimated on the basis of program records and an empirical assessment of health personnel time input. Household costs for seeking and undergoing hearing health care were collected with a questionnaire, administered to the parents of the child. Data were collected at three study sites representing primary, secondary and tertiary care levels. RESULTS: Total screening and hearing aid delivery costs ranged between RMB70,000 (US$9,000) and RMB133,000 (US$17,000) in the three study sites. Health care cost per child fitted ranged from RMB5,900 (US$760) at the primary care level, RMB7,200 (US$940) at the secondary care level, to RMB8,600 (US$1,120) at the tertiary care level. Household costs were only a small fraction of the overall costs. Cost per child fitted ranged between RMB1,608 and RMB2,812 (US$209-US$365), depending on perspective of analysis and study site. The program was always least costly in the primary care setting. CONCLUSION: Hearing screening and the delivery of hearing aids in China is least costly in a primary care setting. Important questions remain concerning its implementation

Parallel momentum distribution of the 28^{28}Si fragments from 29^{29}P

Distribution of the parallel momentum of $^{28}$Si fragments from the breakup of 30.7 MeV/nucleon $^{29}$P has been measured on C targets. The distribution has the FWHM with the value of 110.5 $\pm$ 23.5 MeV/c which is consistent quantitatively with Galuber model calculation assuming by a valence proton in $^{29}$P. The density distribution is also predicted by Skyrme-Hartree-Fock calculation. Results show that there might exist the proton-skin structure in $^{29}$P.Comment: 4 pages, 4 figure