Common Ownership and Corporate Social Responsibility

This paper studies the effect of common ownership on corporate social responsibility (CSR). We find that common ownership is positively associated with a firm's social performance. Additional tests strength the causal interpretation of the results. The empirical evidence is consistent with the predictions from a model in which CSR serves as a strategic tool for a firm to strengthen its product market position

Recurrence risk factors of intravitreal ranibizumab monotherapy in retinopathy of prematurity: a retrospective study at one center

AIM: To identify risk factors of recurrence of this disorder after intravitreal ranibizumab (IVR) monotherapy. METHODS: Totally 33 eyes of 19 patients who underwent initial IVR treatments for type 1 retinopathy of prematurity (ROP) at our center were retrospectively reviewed between April 1, 2016 and December 31, 2017. Patient demographics, the side of ROP, multiple gestations, Apgar scores, zone, stage, plus disease, postmenstrual age at injection, surfactant therapy, blood transfusion therapy, hemorrhage before IVR, hemorrhage after IVR, gestational diabetes mellitus, pregnancy-induced hypertension, anemia, intraventricular hemorrhage, sepsis, respiratory distress syndrome, carbohemia, and congenital heart defects were recorded. Adjusted hazard ratios (HRs) and 95% confidence intervals were determined after adjusting for potential confounders using multivariate proportional Cox regression. RESULTS: Of the 33 eyes, 12 (36.4%) had ROP recurrences 45.3 (5.1, 50.9)mo after initial IVR treatments. The independent risk factors for ROP recurrences were zone (¢ò vs ¢ñ, HR: 0.056, P=0.003) and gestational diabetes mellitus (no vs yes, HR: 0.095, P<0.001). The mean uncorrected visual acuity for four recurrence eyes was 0.46 logMAR (0.13, 0.70) at 55.0 (51.0, 58.9) mo after the initial IVR treatment. The mean uncorrected visual acuity for 10 eyes without recurrence was 0.46 logMAR (0.19, 0.63) at 48.0 (43.8, 58.4) mo after the initial IVR treatment. CONCLUSION: Two independent risk factors for type 1 ROP recurrence after IVR treatment involving zone¢ñand gestational diabetes mellitus are identified, and the mean uncorrected visual acuity is 0.46 logMAR at 51.0 (44.0, 58.9)mo. The findings of this study are important for follow-up management and for improving the visual function of ROP patients

Curing hemophilia A by NHEJ-mediated ectopic F8 insertion in the mouse

BACKGROUND: Hemophilia A, a bleeding disorder resulting from F8 mutations, can only be cured by gene therapy. A promising strategy is CRISPR-Cas9-mediated precise insertion of F8 in hepatocytes at highly expressed gene loci, such as albumin (Alb). Unfortunately, the precise in vivo integration efficiency of a long insert is very low (~ 0.1%). RESULTS: We report that the use of a double-cut donor leads to a 10- to 20-fold increase in liver editing efficiency, thereby completely reconstituting serum F8 activity in a mouse model of hemophilia A after hydrodynamic injection of Cas9-sgAlb and B domain-deleted (BDD) F8 donor plasmids. We find that the integration of a double-cut donor at the Alb locus in mouse liver is mainly through non-homologous end joining (NHEJ)-mediated knock-in. We then target BDDF8 to multiple sites on introns 11 and 13 and find that NHEJ-mediated insertion of BDDF8 restores hemostasis. Finally, using 3 AAV8 vectors to deliver genome editing components, including Cas9, sgRNA, and BDDF8 donor, we observe the same therapeutic effects. A follow-up of 100 mice over 1 year shows no adverse effects. CONCLUSIONS: These findings lay the foundation for curing hemophilia A by NHEJ knock-in of BDDF8 at Alb introns after AAV-mediated delivery of editing components

Rnd3/RhoE Modulates HIF1α/VEGF Signaling by Stabilizing HIF1α and Regulates Responsive Cardiac Angiogenesis

The insufficiency of compensatory angiogenesis in the heart of patients with hypertension contributes to heart failure transition. The hypoxia-inducible factor 1α-vascular endothelial growth factor (HIF1α-VEGF) signaling cascade controls responsive angiogenesis. One of the challenges in reprograming the insufficient angiogenesis is to achieve a sustainable tissue exposure to the proangiogenic factors, such as HIF1α stabilization. In this study, we identified Rnd3, a small Rho GTPase, as a proangiogenic factor participating in the regulation of the HIF1α-VEGF signaling cascade. Rnd3 physically interacted with and stabilized HIF1α, and consequently promoted VEGFA expression and endothelial cell tube formation. To demonstrate this proangiogenic role of Rnd3 in vivo, we generated Rnd3 knockout mice. Rnd3 haploinsufficient (Rnd3(+/-)) mice were viable, yet developed dilated cardiomyopathy with heart failure after transverse aortic constriction stress. The poststress Rnd3(+/-) hearts showed significantly impaired angiogenesis and decreased HIF1α and VEGFA expression. The angiogenesis defect and heart failure phenotype were partially rescued by cobalt chloride treatment, a HIF1α stabilizer, confirming a critical role of Rnd3 in stress-responsive angiogenesis. Furthermore, we generated Rnd3 transgenic mice and demonstrated that Rnd3 overexpression in heart had a cardioprotective effect through reserved cardiac function and preserved responsive angiogenesis after pressure overload. Finally, we assessed the expression levels of Rnd3 in the human heart and detected significant downregulation of Rnd3 in patients with end-stage heart failure. We concluded that Rnd3 acted as a novel proangiogenic factor involved in cardiac responsive angiogenesis through HIF1α-VEGFA signaling promotion. Rnd3 downregulation observed in patients with heart failure may explain the insufficient compensatory angiogenesis involved in the transition to heart failure

Association of genetic variants of TMEM135 and PEX5 in the peroxisome pathway with cutaneous melanoma-specific survival

Background: Peroxisomes are ubiquitous and dynamic organelles that are involved in the metabolism of reactive oxygen species (ROS) and lipids. However, whether genetic variants in the peroxisome pathway genes are associated with survival in patients with melanoma has not been established. Therefore, our aim was to identify additional genetic variants in the peroxisome pathway that may provide new prognostic biomarkers for cutaneous melanoma (CM). Methods: We assessed the associations between 8,397 common single-nucleotide polymorphisms (SNPs) in 88 peroxisome pathway genes and CM disease-specific survival (CMSS) in a two-stage analysis. For the discovery, we extracted the data from a published genome-wide association study from The University of Texas MD Anderson Cancer Center (MDACC). We then replicated the results in another dataset from the Nurse Health Study (NHS)/Health Professionals Follow-up Study (HPFS). Results: Overall, 95 (11.1%) patients in the MDACC dataset and 48 (11.7%) patients in the NHS/HPFS dataset died of CM. We found 27 significant SNPs in the peroxisome pathway genes to be associated with CMSS in both datasets after multiple comparison correction using the Bayesian false-discovery probability method. In stepwise Cox proportional hazards regression analysis, with adjustment for other covariates and previously published SNPs in the MDACC dataset, we identified 2 independent SNPs (TMEM135 rs567403 C>G and PEX5 rs7969508 A>G) that predicted CMSS (P=0.003 and 0.031, respectively, in an additive genetic model). The expression quantitative trait loci analysis further revealed that the TMEM135 rs567403 GG and PEX5 rs7969508 GG genotypes were associated with increased and decreased levels of mRNA expression of their genes, respectively. Conclusions: Once our findings are replicated by other investigators, these genetic variants may serve as novel biomarkers for the prediction of survival in patients with CM

Three-Dimensional Flat Bands and Dirac Cones in a Pyrochlore Superconductor

Emergent phases often appear when the electronic kinetic energy is comparable to the Coulomb interactions. One approach to seek material systems as hosts of such emergent phases is to realize localization of electronic wavefunctions due to the geometric frustration inherent in the crystal structure, resulting in flat electronic bands. Recently, such efforts have found a wide range of exotic phases in the two-dimensional kagome lattice, including magnetic order, time-reversal symmetry breaking charge order, nematicity, and superconductivity. However, the interlayer coupling of the kagome layers disrupts the destructive interference needed to completely quench the kinetic energy. Here we experimentally demonstrate that an interwoven kagome network--a pyrochlore lattice--can host a three dimensional (3D) localization of electron wavefunctions. In particular, through a combination of angle-resolved photoemission spectroscopy, fundamental lattice model and density functional theory (DFT) calculations, we present the novel electronic structure of a pyrochlore superconductor, CeRu$_2$. We find striking flat bands with bandwidths smaller than 0.03 eV in all directions--an order of magnitude smaller than that of kagome systems. We further find 3D gapless Dirac cones predicted originally by theory in the diamond lattice space group with nonsymmorphic symmetry. Our work establishes the pyrochlore structure as a promising lattice platform to realize and tune novel emergent phases intertwining topology and many-body interactions.Comment: 12 pages, 3 figure