TFLink: an integrated gateway to access transcription factor-target gene interactions for multiple species

Analysis of transcriptional regulatory interactions and their comparisons across multiple species are crucial for progress in various fields in biology, from functional genomics to the evolution of signal transduction pathways. However, despite the rapidly growing body of data on regulatory interactions in several eukaryotes, no databases exist to provide curated high-quality information on transcription factor-target gene interactions for multiple species. Here, we address this gap by introducing the TFLink gateway, which uniquely provides experimentally explored and highly accurate information on transcription factor-target gene interactions (∼12 million), nucleotide sequences and genomic locations of transcription factor binding sites (∼9 million) for human and six model organisms: mouse, rat, zebrafish, fruit fly, worm and yeast by integrating 10 resources. TFLink provides user-friendly access to data on transcription factor-target gene interactions, interactive network visualizations and transcription factor binding sites, with cross-links to several other databases. Besides containing accurate information on transcription factors, with a clear labelling of the type/volume of the experiments (small-scale or high-throughput), the source database and the original publications, TFLink also provides a wealth of standardized regulatory data available for download in multiple formats. The database offers easy access to high-quality data for wet-lab researchers, supplies data for gene set enrichment analyses and facilitates systems biology and comparative gene regulation studies. Database URL https://tflink.net/

Bioinspired Precision Engineering of Three‐Dimensional Epithelial Stem Cell Microniches

Maintenance of the epithelium relies on stem cells residing within specialized microenvironments, known as epithelial crypts. Two‐photon polymerization (2PP) is a valuable tool for fabricating 3D micro/nanostructures for stem cell niche engineering applications. Herein, biomimetic gelatin methacrylate‐based constructs, replicating the precise geometry of the limbal epithelial crypt structures (limbal stem cell “microniches”) as an exemplar epithelial niche, are fabricated using 2PP. Human limbal epithelial stem cells (hLESCs) are seeded within the microniches in xeno‐free conditions to investigate their ability to repopulate the crypts and the expression of various differentiation markers. Cell proliferation and a zonation in cell phenotype along the z‐axis are observed without the use of exogenous signaling molecules. Significant differences in cell phenotype between cells located at the base of the microniche and those situated towards the rim are observed, demonstrating that stem cell fate is strongly influenced by its location within a niche and the geometrical details of where it resides. This study provides insight into the influence of the niche’s spatial geometry on hLESCs and demonstrates a flexible approach for the fabrication of biomimetic crypt‐like structures in epithelial tissues. This has significant implications for regenerative medicine applications and can ultimately lead to implantable synthetic “niche‐based” treatments

Large-scale Evolution of Seconds-long Relativistic Jets from Black Hole-Neutron Star Mergers

We present the first numerical simulations that track the evolution of a black hole-neutron star (BH-NS) merger from pre-merger to $r\gtrsim10^{11}\,{\rm cm}$. The disk that forms after a merger of mass ratio $q=2$ ejects massive disk winds ($3-5\times10^{-2}\,M_\odot$). We introduce various post-merger magnetic configurations, and find that initial poloidal fields lead to jet launching shortly after the merger. The jet maintains a constant power due to the constancy of the large-scale BH magnetic flux, until the disk becomes magnetically arrested (MAD), where the jet power falls off as $L_j\sim t^{-2}$. All jets inevitably exhibit either excessive luminosity due to rapid MAD activation when accretion rate is high, or excessive duration due to delayed MAD activation, compared to typical short gamma-ray burst (sGRBs). This provides a natural explanation to long sGRBs such as GRB 211211A, but also raises a fundamental challenge to our understanding of jet formation in binary mergers. One possible implication being the necessity of higher binary mass ratios or moderate BH spins to launch typical sGRB jets. For post-merger disks with a toroidal magnetic field, dynamo processes delay jet launching such that the jets break out of the disk winds after several seconds. We show for the first time that sGRB jets with initial magnetization $\sigma_0>100$ retain significant magnetization ($\sigma\gg1$) at $r>10^{10}\,{\rm cm}$, emphasizing the importance of magnetic processes in the prompt emission. The jet-wind interaction leads to a power-law angular energy distribution by inflating an energetic cocoon, whose emission is studied in a companion paper.Comment: For movies of the simulations, see https://oregottlieb.com/bhns.htm

Azimuthal anisotropy of neutral pion production in Au+Au collisions at sqrt(s_NN) = 200 GeV: Path-length dependence of jet quenching and the role of initial geometry

We have measured the azimuthal anisotropy of pi0's for 1 < pT < 18 GeV/c for Au+Au collisions at sqrt s_NN = 200 GeV. The observed anisotropy shows a gradual decrease in 3 < pT < 7 - 10 GeV/c, but remains positive beyond 10 GeV/c. The magnitude of this anisotropy is under-predicted, up to at least 10 GeV/c, by current perturbative QCD (pQCD) energy-loss model calculations. An estimate of the increase in anisotropy expected from initial-geometry modification due to gluon saturation effects and initial-geometry fluctuations is insufficient to account for this discrepancy. Calculations which implement a path length dependence steeper than what is implied by current pQCD energy-loss models, show reasonable agreement with the data.Comment: 384 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

The Polarised Valence Quark Distribution from semi-inclusive DIS

The semi-inclusive difference asymmetry A^{h^{+}-h^{-}} for hadrons of opposite charge has been measured by the COMPASS experiment at CERN. The data were collected in the years 2002-2004 using a 160 GeV polarised muon beam scattered off a large polarised ^6LiD target and cover the range 0.006 < x < 0.7 and 1 < Q^2 < 100 (GeV/c)^2. In leading order QCD (LO) the asymmetry A_d^{h^{+}-h^{-}} measures the valence quark polarisation and provides an evaluation of the first moment of Delta u_v + Delta d_v which is found to be equal to 0.40 +- 0.07 (stat.) +- 0.05 (syst.) over the measured range of x at Q^2 = 10 (GeV/c)^2. When combined with the first moment of g_1^d previously measured on the same data, this result favours a non-symmetric polarisation of light quarks Delta u-bar = - Delta d-bar at a confidence level of two standard deviations, in contrast to the often assumed symmetric scenario Delta u-bar = Delta d-bar = Delta s-bar = Delta s.Comment: 7 pages, 3 figures, COMPASS, revised: details added, author list update

Observation of a J^PC = 1-+ exotic resonance in diffractive dissociation of 190 GeV/c pi- into pi- pi- pi+

The COMPASS experiment at the CERN SPS has studied the diffractive dissociation of negative pions into the pi- pi- pi+ final state using a 190 GeV/c pion beam hitting a lead target. A partial wave analysis has been performed on a sample of 420000 events taken at values of the squared 4-momentum transfer t' between 0.1 and 1 GeV^2/c^2. The well-known resonances a1(1260), a2(1320), and pi2(1670) are clearly observed. In addition, the data show a significant natural parity exchange production of a resonance with spin-exotic quantum numbers J^PC = 1-+ at 1.66 GeV/c^2 decaying to rho pi. The resonant nature of this wave is evident from the mass-dependent phase differences to the J^PC = 2-+ and 1++ waves. From a mass-dependent fit a resonance mass of 1660 +- 10+0-64 MeV/c^2 and a width of 269+-21+42-64 MeV/c^2 is deduced.Comment: 7 page, 3 figures; version 2 gives some more details, data unchanged; version 3 updated authors, text shortened, data unchange

Measurement of the Longitudinal Spin Transfer to Lambda and Anti-Lambda Hyperons in Polarised Muon DIS

The longitudinal polarisation transfer from muons to lambda and anti-lambda hyperons, D_LL, has been studied in deep inelastic scattering off an unpolarised isoscalar target at the COMPASS experiment at CERN. The spin transfers to lambda and anti-lambda produced in the current fragmentation region exhibit different behaviours as a function of x and xF . The measured x and xF dependences of D^lambda_LL are compatible with zero, while D^anti-lambda_LL tends to increase with xF, reaching values of 0.4 - 0.5. The resulting average values are D^lambda_LL = -0.012 +- 0.047 +- 0.024 and D^anti-lambda_LL = 0.249 +- 0.056 +- 0.049. These results are discussed in the frame of recent model calculations.Comment: 13 pages, 7 figure