Mapping and Functional Characterisation of a CTCF-Dependent Insulator Element at the 3′ Border of the Murine Scl Transcriptional Domain

The Scl gene encodes a transcription factor essential for haematopoietic development. Scl transcription is regulated by a panel of cis-elements spread over 55 kb with the most distal 3′ element being located downstream of the neighbouring gene Map17, which is co-regulated with Scl in haematopoietic cells. The Scl/Map17 domain is flanked upstream by the ubiquitously expressed Sil gene and downstream by a cluster of Cyp genes active in liver, but the mechanisms responsible for delineating the domain boundaries remain unclear. Here we report identification of a DNaseI hypersensitive site at the 3′ end of the Scl/Map17 domain and 45 kb downstream of the Scl transcription start site. This element is located at the boundary of active and inactive chromatin, does not function as a classical tissue-specific enhancer, binds CTCF and is both necessary and sufficient for insulator function in haematopoietic cells in vitro. Moreover, in a transgenic reporter assay, tissue-specific expression of the Scl promoter in brain was increased by incorporation of 350 bp flanking fragments from the +45 element. Our data suggests that the +45 region functions as a boundary element that separates the Scl/Map17 and Cyp transcriptional domains, and raise the possibility that this element may be useful for improving tissue-specific expression of transgenic constructs

Congenital Hydrocephalus and Abnormal Subcommissural Organ Development in Sox3 Transgenic Mice

Congenital hydrocephalus (CH) is a life-threatening medical condition in which excessive accumulation of CSF leads to ventricular expansion and increased intracranial pressure. Stenosis (blockage) of the Sylvian aqueduct (Aq; the narrow passageway that connects the third and fourth ventricles) is a common form of CH in humans, although the genetic basis of this condition is unknown. Mouse models of CH indicate that Aq stenosis is associated with abnormal development of the subcommmissural organ (SCO) a small secretory organ located at the dorsal midline of the caudal diencephalon. Glycoproteins secreted by the SCO generate Reissner's fibre (RF), a thread-like structure that descends into the Aq and is thought to maintain its patency. However, despite the importance of SCO function in CSF homeostasis, the genetic program that controls SCO development is poorly understood. Here, we show that the X-linked transcription factor SOX3 is expressed in the murine SCO throughout its development and in the mature organ. Importantly, overexpression of Sox3 in the dorsal diencephalic midline of transgenic mice induces CH via a dose-dependent mechanism. Histological, gene expression and cellular proliferation studies indicate that Sox3 overexpression disrupts the development of the SCO primordium through inhibition of diencephalic roof plate identity without inducing programmed cell death. This study provides further evidence that SCO function is essential for the prevention of hydrocephalus and indicates that overexpression of Sox3 in the dorsal midline alters progenitor cell differentiation in a dose-dependent manner

Mouse hitchhiker mutants have spina bifida, dorso-ventral patterning defects and polydactyly: identification of Tulp3 as a novel negative regulator of the Sonic hedgehog pathway

The mammalian Sonic hedgehog (Shh) signalling pathway is essential for embryonic development and the patterning of multiple organs. Disruption or activation of Shh signalling leads to multiple birth defects, including holoprosencephaly, neural tube defects and polydactyly, and in adults results in tumours of the skin or central nervous system. Genetic approaches with model organisms continue to identify novel components of the pathway, including key molecules that function as positive or negative regulators of Shh signalling. Data presented here define Tulp3 as a novel negative regulator of the Shh pathway. We have identified a new mouse mutant that is a strongly hypomorphic allele of Tulp3 and which exhibits expansion of ventral markers in the caudal spinal cord, as well as neural tube defects and preaxial polydactyly, consistent with increased Shh signalling. We demonstrate that Tulp3 acts genetically downstream of Shh and Smoothened (Smo) in neural tube patterning and exhibits a genetic interaction with Gli3 in limb development. We show that Tulp3 does not appear to alter expression or processing of Gli3, and we demonstrate that transcriptional regulation of other negative regulators (Rab23, Fkbp8, Thm1, Sufu and PKA) is not affected. We discuss the possible mechanism of action of Tulp3 in Shh-mediated signalling in light of these new data

Angular analysis of B+→ρ+ρ0B^+ \to \rho^+\rho^0 decays reconstructed in 2019, 2020, and 2021 Belle II data

We report on a Belle II measurement of the branching fraction ($\mathcal{B}$), longitudinal polarization fraction ($f_L$), and CP asymmetry ($\mathcal{A}_{CP}$) of $B^+\to \rho^+\rho^0$ decays. We reconstruct $B^+\to \rho^+(\to \pi^+\pi^0(\to \gamma\gamma))\rho^0(\to \pi^+\pi^-)$ decays in a sample of SuperKEKB electron-positron collisions collected by the Belle II experiment in 2019, 2020, and 2021 at the $\Upsilon$(4S) resonance and corresponding to 190 fb$^{-1}$ of integrated luminosity. We fit the distributions of the difference between expected and observed $B$ candidate energy, continuum-suppression discriminant, dipion masses, and decay angles of the selected samples, to determine a signal yield of $345 \pm 31$ events. The signal yields are corrected for efficiencies determined from simulation and control data samples to obtain $\mathcal{B}(B^+ \to \rho^+\rho^0) = [23.2^{+\ 2.2}_{-\ 2.1} (\rm stat) \pm 2.7 (\rm syst)]\times 10^{-6}$,$f_L = 0.943 ^{+\ 0.035}_{-\ 0.033} (\rm stat)\pm 0.027(\rm syst)$, and$\mathcal{A}_{CP}=-0.069 \pm 0.068(\rm stat) \pm 0.060 (\rm syst)$. The results agree with previous measurements. This is the first measurement of$\mathcal{A}_{CP}$in$B^+\to \rho^+\rho^0$ decays reported by Belle II

Determination of ∣Vub∣|V_{ub}| from untagged B0→π−ℓ+νℓB^0\to\pi^- \ell^+ \nu_{\ell} decays using 2019-2021 Belle II data

We present an analysis of the charmless semileptonic decay $B^0\to\pi^- \ell^+ \nu_{\ell}$, where $\ell = e, \mu$, from 198.0 million pairs of $B\bar{B}$ mesons recorded by the Belle II detector at the SuperKEKB electron-positron collider. The decay is reconstructed without identifying the partner $B$ meson. The partial branching fractions are measured independently for $B^0\to\pi^- e^+ \nu_{e}$ and $B^0\to\pi^- \mu^+ \nu_{\mu}$ as functions of $q^{2}$ (momentum transfer squared), using 3896 $B^0\to\pi^- e^+ \nu_{e}$ and 5466 $B^0\to\pi^- \mu^+ \nu_{\mu}$ decays. The total branching fraction is found to be $(1.426 \pm 0.056 \pm 0.125) \times 10^{-4}$ for $B^0\to\pi^- \ell^+ \nu_{\ell}$ decays, where the uncertainties are statistical and systematic, respectively. By fitting the measured partial branching fractions as functions of $q^{2}$, together with constraints on the nonperturbative hadronic contribution from lattice QCD calculations, the magnitude of the Cabibbo-Kobayashi-Maskawa matrix element $V_{ub}$, $(3.55 \pm 0.12 \pm 0.13 \pm 0.17) \times 10^{-3}$, is extracted. Here, the first uncertainty is statistical, the second is systematic and the third is theoretical

Measurement of the branching fractions and CPCP asymmetries of B+→π+π0B^+ \rightarrow \pi^+ \pi^0 and B+→K+π0B^+ \rightarrow K^+ \pi^0 decays in 2019-2021 Belle II data

We determine the branching fractions ${\mathcal{B}}$ and $CP$ asymmetries ${\mathcal{A}_{{\it CP}}}$ of the decays $B^+ \rightarrow \pi^+ \pi^0$ and $B^+ \rightarrow K^+ \pi^0$. The results are based on a data set containing 198 million bottom-antibottom meson pairs corresponding to an integrated luminosity of $190\;\text{fb}^{-1}$ recorded by the Belle II detector in energy-asymmetric electron-positron collisions at the $\Upsilon (4S)$ resonance. We measure ${\mathcal{B}(B^+ \rightarrow \pi^+ \pi^0) = (6.12 \pm 0.53 \pm 0.53)\times 10^{-6}}$, ${\mathcal{B}(B^+ \rightarrow K^+ \pi^0) = (14.30 \pm 0.69 \pm 0.79)\times 10^{-6}}$, ${\mathcal{A}_{{\it CP}}(B^+ \rightarrow \pi^+ \pi^0) = -0.085 \pm 0.085 \pm 0.019}$, and ${\mathcal{A}_{{\it CP}}(B^+ \rightarrow K^+ \pi^0) = 0.014 \pm 0.047 \pm 0.010}$, where the first uncertainties are statistical and the second are systematic. These results improve a previous Belle II measurement and agree with the world averages

Measurement of the branching fraction for the decay B→K∗(892)ℓ+ℓ−B \to K^{\ast}(892)\ell^+\ell^- at Belle II

We report a measurement of the branching fraction of $B \to K^{\ast}(892)\ell^+\ell^-$ decays, where $\ell^+\ell^- = \mu^+\mu^-$ or $e^+e^-$, using electron-positron collisions recorded at an energy at or near the $\Upsilon(4S)$ mass and corresponding to an integrated luminosity of $189$ fb$^{-1}$. The data was collected during 2019--2021 by the Belle II experiment at the SuperKEKB $e^{+}e^{-}$ asymmetric-energy collider. We reconstruct $K^{\ast}(892)$ candidates in the $K^+\pi^-$, $K_{S}^{0}\pi^+$, and $K^+\pi^0$ final states. The signal yields with statistical uncertainties are $22\pm 6$, $18 \pm 6$, and $38 \pm 9$ for the decays $B \to K^{\ast}(892)\mu^+\mu^-$, $B \to K^{\ast}(892)e^+e^-$, and $B \to K^{\ast}(892)\ell^+\ell^-$, respectively. We measure the branching fractions of these decays for the entire range of the dilepton mass, excluding the very low mass region to suppress the $B \to K^{\ast}(892)\gamma(\to e^+e^-)$ background and regions compatible with decays of charmonium resonances, to be \begin{equation} {\cal B}(B \to K^{\ast}(892)\mu^+\mu^-) = (1.19 \pm 0.31 ^{+0.08}_{-0.07}) \times 10^{-6}, {\cal B}(B \to K^{\ast}(892)e^+e^-) = (1.42 \pm 0.48 \pm 0.09)\times 10^{-6}, {\cal B}(B \to K^{\ast}(892)\ell^+\ell^-) = (1.25 \pm 0.30 ^{+0.08}_{-0.07}) \times 10^{-6}, \end{equation} where the first and second uncertainties are statistical and systematic, respectively. These results, limited by sample size, are the first measurements of $B \to K^{\ast}(892)\ell^+\ell^-$ branching fractions from the Belle II experiment

The Belle II Physics Book

We present the physics program of the Belle II experiment, located on the intensity frontier SuperKEKB $e^+e^-$ collider. Belle II collected its first collisions in 2018, and is expected to operate for the next decade. It is anticipated to collect 50/ab of collision data over its lifetime. This book is the outcome of a joint effort of Belle II collaborators and theorists through the Belle II theory interface platform (B2TiP), an effort that commenced in 2014. The aim of B2TiP was to elucidate the potential impacts of the Belle II program, which includes a wide scope of physics topics: B physics, charm, tau, quarkonium, electroweak precision measurements and dark sector searches. It is composed of nine working groups (WGs), which are coordinated by teams of theorist and experimentalists conveners: Semileptonic and leptonic B decays, Radiative and Electroweak penguins, phi_1 and phi_2 (time-dependent CP violation) measurements, phi_3 measurements, Charmless hadronic B decay, Charm, Quarkonium(like), tau and low-multiplicity processes, new physics and global fit analyses. This book highlights "golden- and silver-channels", i.e. those that would have the highest potential impact in the field. Theorists scrutinised the role of those measurements and estimated the respective theoretical uncertainties, achievable now as well as prospects for the future. Experimentalists investigated the expected improvements with the large dataset expected from Belle II, taking into account improved performance from the upgraded detector.Comment: 689 page