CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention

The DNA-binding protein CCCTC-binding factor (CTCF) and the cohesin complex function together to shape chromatin architecture in mammalian cells, but the molecular details of this process remain unclear. Here, we demonstrate that a 79-aa region within the CTCF N terminus is essential for cohesin positioning at CTCF binding sites and chromatin loop formation. However, the N terminus of CTCF fused to artificial zinc fingers was not sufficient to redirect cohesin to non-CTCF binding sites, indicating a lack of an autonomously functioning domain in CTCF responsible for cohesin positioning. BORIS (CTCFL), a germline-specific paralog of CTCF, was unable to anchor cohesin to CTCF DNA binding sites. Furthermore, CTCF-BORIS chimeric constructs provided evidence that, besides the N terminus of CTCF, the first two CTCF zinc fingers, and likely the 3D geometry of CTCF-DNA complexes, are also involved in cohesin retention. Based on this knowledge, we were able to convert BORIS into CTCF with respect to cohesin positioning, thus providing additional molecular details of the ability of CTCF to retain cohesin. Taken together, our data provide insight into the process by which DNA-bound CTCF constrains cohesin movement to shape spatiotemporal genome organization

How to project a bipartite network?

The one-mode projecting is extensively used to compress the bipartite networks. Since the one-mode projection is always less informative than the bipartite representation, a proper weighting method is required to better retain the original information. In this article, inspired by the network-based resource-allocation dynamics, we raise a weighting method, which can be directly applied in extracting the hidden information of networks, with remarkably better performance than the widely used global ranking method as well as collaborative filtering. This work not only provides a creditable method in compressing bipartite networks, but also highlights a possible way for the better solution of a long-standing challenge in modern information science: How to do personal recommendation?Comment: 7 pages, 4 figure

High-Responsivity Graphene-Boron Nitride Photodetector and Autocorrelator in a Silicon Photonic Integrated Circuit

Graphene and other two-dimensional (2D) materials have emerged as promising materials for broadband and ultrafast photodetection and optical modulation. These optoelectronic capabilities can augment complementary metal-oxide-semiconductor (CMOS) devices for high-speed and low-power optical interconnects. Here, we demonstrate an on-chip ultrafast photodetector based on a two-dimensional heterostructure consisting of high-quality graphene encapsulated in hexagonal boron nitride. Coupled to the optical mode of a silicon waveguide, this 2D heterostructure-based photodetector exhibits a maximum responsivity of 0.36 A/W and high-speed operation with a 3 dB cut-off at 42 GHz. From photocurrent measurements as a function of the top-gate and source-drain voltages, we conclude that the photoresponse is consistent with hot electron mediated effects. At moderate peak powers above 50 mW, we observe a saturating photocurrent consistent with the mechanisms of electron-phonon supercollision cooling. This nonlinear photoresponse enables optical on-chip autocorrelation measurements with picosecond-scale timing resolution and exceptionally low peak powers

Fast Room-Temperature Detection of Terahertz Quantum Cascade Lasers with Graphene-Loaded Bow-Tie Plasmonic Antenna Arrays

We present a fast room-temperature terahertz detector based on interdigitated bow-tie antennas contacting graphene. Highly efficient photodetection was achieved by using two metals with different work functions as the arms of a bow-tie antenna contacting graphene. Arrays of the bow-ties were fabricated in order to enhance the responsivity and coupling of the incoming light to the detector, realizing an efficient imaging system. The device has been characterized and tested with a terahertz quantum cascade laser emitting in single frequency around 2 THz, yielding a responsivity of ∼34 μA/W and a noise-equivalent power of ∼1.5 × 10$^{-7}$ W/Hz$^{1/2}$.R.D., Y.R., and H.E.B. acknowledge financial support from the Engineering and Physical Sciences Research Council (Grant No. EP/J017671/1, Coherent Terahertz Systems). S.H. acknowledges funding from EPSRC (Grant No. EP/K016636/1, GRAPHTED). H.L. and J.A.Z. acknowledge financial support from the EPSRC (Grant No. EP/L019922/1). J.A.A.-W. acknowledges a Research Fellowship from Churchill College, Cambridge. H.J.J. thanks the Royal Commission for the Exhibition of 1851 for her Research Fellowship.This is the final version of the article. It first appeared from American Chemical Society via https://doi.org/10.1021/acsphotonics.6b0040

Atmospheric oxidation in the Mexico City Metropolitan Area (MCMA) during April 2003

International audienceThe Mexico City Metropolitan Area (MCMA) study in April 2003 had measurements of most atmospheric constituents including OH and HO2. It provided a unique opportunity to examine atmospheric oxidation in a megacity that has more pollution than typical US and European cities. OH typically reached 0.35 pptv (~7×106 cm?3), comparable to amounts observed in US cities, but HO2 reached 40 pptv in the early afternoon, more than observed in most US cities. A steady-state photochemical model simulated the measured OH and HO2 for day and night to within combined measurement and modeling uncertainties for 2/3 of the results. For OH, measured = 0.65 (modeled) + 0.026 pptv, with R2=0.80. For HO2, observed = 0.70 (modeled) + 3.4 pptv, with R2=0.64. Measurements tended to be higher during night and rush hour; the model was higher by ~30% during midday. With a large median measured OH reactivity of more than 120 s?1 during morning rush hour, median ozone production from observed HO2 reached 50 ppb hr?1; RO2 was calculated to have a similar ozone production rate. For both the HO2/OH ratio and the ozone production, the measured values have the essentially same dependence on NO as the modeled values. This similarity is unlike other urban studies in which the NO-dependence of the measured HO2/OH ratio was much less than the modeled ratio and the ozone production rate that was calculated from measured HO2 unexpectedly appeared to increase as a function of NO with no obvious peak

Sequential Alcohol Septal Ablation to Resolve LV Outflow Tract Obstruction After Transcatheter Mitral Valve Replacement

Left ventricular outflow tract obstruction (LVOTO) is a notorious complication of transcatheter mitral valve replacement (TMVR). Computed tomography–derived simulations can predict neo-LVOTO post-TMVR, whereas alcohol septal ablation can mitigate neo-LVOTO risk. We report a case of sequential alcohol septal ablation of 2 adjacent septal branches to resolve unexpected neo-LVOTO post-TMVR.</p

Hypomethylation and aberrant expression of the glioma pathogenesis-related 1 gene in Wilms tumors

Wilms tumors (WTs) have a complex etiology, displaying genetic and epigenetic changes, including loss of imprinting (LOI) and tumor suppressor gene silencing. To identify new regions of epigenetic perturbation in WTs, we screened kidney and tumor DNA using CpG island (CGI) tags associated with cancer-specific DNA methylation changes. One such tag corresponded to a paralog of the glioma pathogenesis-related 1/related to testis-specific, vespid, and pathogenesis proteins 1 (GLIPR1/RTVP-1) gene, previously reported to be a tumor-suppressor gene silenced by hypermethylation in prostate cancer. Here we report methylation analysis of the GLIPR1/RTVP-1 gene in WTs and normal fetal and pediatric kidneys. Hypomethylation of the GLIPR1/RTVP-1 5′-region in WTs relative to normal tissue is observed in 21/24 (87.5%) of WTs analyzed. Quantitative analysis of GLIPR1/RTVP-1 expression in 24 WTs showed elevated transcript levels in 16/24 WTs (67%), with 12 WTs displaying in excess of 20-fold overexpression relative to fetal kidney (FK) control samples. Immunohistochemical analysis of FK and WT corroborates the RNA expression data and reveals high GLIPR1/RTVP-1 in WT blastemal cells together with variable levels in stromal and epithelial components. Hypomethylation is also evident in the WT precursor lesions and nephrogenic rests (NRs), supporting a role for GLIPR1/RTVP-1 deregulation early in Wilms tumorigenesis. Our data show that, in addition to gene dosage changes arising from LOI and hypermethylation-induced gene silencing, gene activation resulting from hypomethylation is also prevalent in WTs. Copyright © 2007 Neoplasia Press, Inc. All rights reserved

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate &lt;0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P &lt; 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood