Developmental enhancers initiate transcription and are fundamental to our understanding of developmental networks, evolution and disease. Despite their importance, the properties governing ...enhancer-promoter interactions and their dynamics during embryogenesis remain unclear. At the β-globin locus, enhancer-promoter interactions appear dynamic and cell-type specific, whereas at the HoxD locus they are stable and ubiquitous, being present in tissues where the target genes are not expressed. The extent to which preformed enhancer-promoter conformations exist at other, more typical, loci and how transcription is eventually triggered is unclear. Here we generated a high-resolution map of enhancer three-dimensional contacts during Drosophila embryogenesis, covering two developmental stages and tissue contexts, at unprecedented resolution. Although local regulatory interactions are common, long-range interactions are highly prevalent within the compact Drosophila genome. Each enhancer contacts multiple enhancers, and promoters with similar expression, suggesting a role in their co-regulation. Notably, most interactions appear unchanged between tissue context and across development, arising before gene activation, and are frequently associated with paused RNA polymerase. Our results indicate that the general topology governing enhancer contacts is conserved from flies to humans and suggest that transcription initiates from preformed enhancer-promoter loops through release of paused polymerase.
Backward-angle meson electroproduction above the resonance region, which was previously ignored, is anticipated to offer unique access to the three quark plus sea component of the nucleon wave ...function. In this Letter, we present the first complete separation of the four electromagnetic structure functions above the resonance region in exclusive ω electroproduction off the proton, ep→e′pω, at central Q2 values of 1.60, 2.45 GeV2, at W=2.21 GeV. The results of our pioneering −u≈−umin study demonstrate the existence of a unanticipated backward-angle cross section peak and the feasibility of full L/T/LT/TT separations in this never explored kinematic territory. At Q2=2.45 GeV2, the observed dominance of σT over σL, is qualitatively consistent with the collinear QCD description in the near-backward regime, in which the scattering amplitude factorizes into a hard subprocess amplitude and baryon to meson transition distribution amplitudes: universal nonperturbative objects only accessible through backward-angle kinematics.
Abstract
Supernova (SN) 2021ocs was discovered in the galaxy NGC 7828 (
z
= 0.01911) within the interacting system Arp 144 and subsequently classified as a normal Type Ic SN around peak brightness. ...Very Large Telescope/FORS2 observations in the nebular phase at 148 days reveal that the spectrum is dominated by oxygen and magnesium emission lines of different transitions and ionization states: O
i
, O
i
, O
ii
, O
iii
, Mg
i
, and Mg
ii
. Such a spectrum has no counterpart in the literature, though it bears a few features similar to those of some interacting Type Ibn and Icn SNe. Additionally, SN 2021ocs showed a blue color, (
g
−
r
) ≲ −0.5 mag, after the peak and up to late phases, atypical for a Type Ic SN. Together with the nebular spectrum, this suggests that SN 2021ocs underwent late-time interaction with an H/He-poor circumstellar medium (CSM) resulting from the pre-SN progenitor mass loss during its final ∼1000 days. The strong O and Mg lines and the absence of strong C and He lines suggest that the progenitor star’s O–Mg layer is exposed, which places SN 2021ocs as the most extreme case of a massive progenitor star’s envelope stripping in interacting SNe, followed by Type Icn (stripped C–O layer) and Ibn (stripped He-rich layer) SNe. This is the first time such a case is reported in the literature. The SN 2021ocs emphasizes the importance of late-time spectroscopy of SNe, even for those classified as normal events, to reveal the inner ejecta and progenitor star’s CSM and mass loss.
Scanning nanoscale superconducting quantum interference devices (nanoSQUIDs) are of growing interest for highly sensitive quantitative imaging of magnetic, spintronic, and transport properties of ...low-dimensional systems. Utilizing specifically designed grooved quartz capillaries pulled into a sharp pipette, we have fabricated the smallest SQUID-on-tip (SOT) devices with effective diameters down to 39 nm. Integration of a resistive shunt in close proximity to the pipette apex combined with self-aligned deposition of In and Sn, has resulted in SOTs with a flux noise of 42 nΦ
Hz
, yielding a record low spin noise of 0.29 μ
Hz
. In addition, the new SOTs function at sub-Kelvin temperatures and in high magnetic fields of over 2.5 T. Integrating the SOTs into a scanning probe microscope allowed us to image the stray field of a single Fe
O
nanocube at 300 mK. Our results show that the easy magnetization axis direction undergoes a transition from the 〈111〉 direction at room temperature to an in-plane orientation, which could be attributed to the Verwey phase transition in Fe
O
.
We present the Pan-STARRS1 discovery of the long-lived and blue transient PS1-11af, which was also detected by Galaxy Evolution Explorer with coordinated observations in the near-ultraviolet (NUV) ...band. Four epochs of spectroscopy reveal a pair of transient broad absorption features in the UV on otherwise featureless spectra. Blackbody fits to the spectral energy distribution are inconsistent with the cooling, expanding ejecta of a SN, and the velocities of the absorption features are too high to represent material in homologous expansion near a SN photosphere. A full disruption model predicts higher bolometric luminosities, which would require most of the radiation to be emitted in a separate component at high energies where we lack observations. Three deep non-detections in the radio with the Very Large Array over the first two years after the event set strict limits on the production of any relativistic outflow comparable to Swift J1644+57, even if off-axis.
Summary The standard diagnostic technique for assessing osteoporosis is dual X-ray absorptiometry (DXA) measuring bone mass parameters. In this study, a combination of DXA and trabecular structure ...parameters (acquired by computed tomography CT) most accurately predicted the biomechanical strength of the proximal femur and allowed for a better prediction than DXA alone. Introduction An automated 3D segmentation algorithm was applied to determine specific structure parameters of the trabecular bone in CT images of the proximal femur. This was done to evaluate the ability of these parameters for predicting biomechanical femoral bone strength in comparison with bone mineral content (BMC) and bone mineral density (BMD) acquired by DXA as standard diagnostic technique. Methods One hundred eighty-seven proximal femur specimens were harvested from formalin-fixed human cadavers. BMC and BMD were determined by DXA. Structure parameters of the trabecular bone (i.e., morphometry, fuzzy logic, Minkowski functionals, and the scaling index method SIM) were computed from CT images. Absolute femoral bone strength was assessed with a biomechanical side-impact test measuring failure load (FL). Adjusted FL parameters for appraisal of relative bone strength were calculated by dividing FL by influencing variables such as body height, weight, or femoral head diameter. Results The best single parameter predicting FL and adjusted FL parameters was apparent trabecular separation (morphometry) or DXA-derived BMC or BMD with correlations up to r = 0.802. In combination with DXA, structure parameters (most notably the SIM and morphometry) added in linear regression models significant information in predicting FL and all adjusted FL parameters (up to R adj = 0.872) and allowed for a significant better prediction than DXA alone. Conclusion A combination of bone mass (DXA) and structure parameters of the trabecular bone (linear and nonlinear, global and local) most accurately predicted absolute and relative femoral bone strength.
The complement and neutrophil defence systems, as major components of innate immunity, are activated during inflammation and infection. For neutrophil migration to the inflamed region, we ...hypothesized that the complement activation product C5a induces significant changes in cellular morphology before chemotaxis. Exposure of human neutrophils to C5a dose‐ and time‐dependently resulted in a rapid C5a receptor‐1 (C5aR1)‐dependent shape change, indicated by enhanced flow cytometric forward‐scatter area values. Similar changes were observed after incubation with zymosan‐activated serum and in blood neutrophils during murine sepsis, but not in mice lacking the C5aR1. In human neutrophils, Amnis high‐resolution digital imaging revealed a C5a‐induced decrease in circularity and increase in the cellular length/width ratio. Biomechanically, microfluidic optical stretching experiments indicated significantly increased neutrophil deformability early after C5a stimulation. The C5a‐induced shape changes were inhibited by pharmacological blockade of either the Cl−/HCO3−‐exchanger or the Cl−‐channel. Furthermore, actin polymerization assays revealed that C5a exposure resulted in a significant polarization of the neutrophils. The functional polarization process triggered by ATP–P2X/Y‐purinoceptor interaction was also involved in the C5a‐induced shape changes, because pretreatment with suramin blocked not only the shape changes but also the subsequent C5a‐dependent chemotactic activity. In conclusion, the data suggest that the anaphylatoxin C5a regulates basic neutrophil cell processes by increasing the membrane elasticity and cell size as a consequence of actin‐cytoskeleton polymerization and reorganization, transforming the neutrophil into a migratory cell able to invade the inflammatory site and subsequently clear pathogens and molecular debris.
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