Transplantation of human neural stem/progenitor cells overexpressing galectin-1 improves functional recovery from focal brain ischemia in the mongolian gerbil

Transplantation of human neural stem/progenitor cells (hNSPCs) is a promising method to regenerate tissue from damage and recover function in various neurological diseases including brain ischemia. Galectin-1(Gal1) is a lectin that is expressed in damaged brain areas after ischemia. Here, we characterized the detailed Gal1 expression pattern in an animal model of brain ischemia. After brain ischemia, Gal1 was expressed in reactive astrocytes within and around the infarcted region, and its expression diminished over time. Previously, we showed that infusion of human Gal1 protein (hGal1) resulted in functional recovery after brain ischemia but failed to reduce the volume of the ischemic region. This prompted us to examine whether the combination of hNSPCs-transplantation and stable delivery of hGal1 around the ischemic region could reduce the ischemic volume and promote better functional recovery after brain ischemia. In this study, we transplanted hNSPCs that stably overexpressed hGal1 (hGal1-hNSPCs) in a model of unilateral focal brain ischemia using Mongolian gerbils. Indeed, we found that transplantation of hGal1-hNSPCs both reduced the ischemic volume and improved deficits in motor function after brain ischemia to a greater extent than the transplantation of hNSPCs alone. This study provides evidence for a potential application of hGal1 with hNSPCs-transplantation in the treatment of brain ischemia

Human Hepatocyte Growth Factor Promotes Functional Recovery in Primates after Spinal Cord Injury

Many therapeutic interventions for spinal cord injury (SCI) using neurotrophic factors have focused on reducing the area damaged by secondary, post-injury degeneration, to promote functional recovery. Hepatocyte growth factor (HGF), which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We previously reported that introducing exogenous HGF into the injured rodent spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, that study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an original open field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. In vivo magnetic resonance imaging showed significant preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers compared to the control group, indicating that this treatment did not induce or exacerbate allodynia. This is the first study to report the efficacy of rhHGF for treating SCI in non-human primates. In addition, this is the first presentation of a novel scale for assessing neurological motor performance in non-human primates after contusive cervical SCI

Blue-emitting acridine-tagged silver(i)-bis-N-heterocyclic carbene

Herein, the photophysical properties of an acridine derivative of a bis-N-heterocyclic carbene silver complex were investigated. The HOMO and LUMO energy differences between 9-[(N-methyl imidazol-2-ylidene)]acridine and 4,5-bis[(N-methyl-imidazol-2-ylidene)methyl]acridine were theoretically compared. Based on the calculation, the 4,5-bis N-heterocyclic carbene-tethered acridine type of ligand was found to be a potential source for tuning the fluorescent nature of the resultant metal derivatives. Thus, a 4,5-bis N-heterocyclic carbene (NHC)-tethered acridine silver(I) salt was synthesized, and its photophysical properties were investigated. The 4,5-bis[(N-isopropylimidazol-2-ylidene)methyl]acridine silver(I) hexafluorophosphate complex was obtained from the reaction between [4,5-bis{(N-isopropylimidazolium)methyl}acridine] hexafluorophosphate and Ag2O in very good yield; this molecule was characterized by elemental analysis and FTIR, multinuclear (1H and 13C) NMR, UV-Vis, and fluorescence spectroscopic techniques. The molecular structure has been confirmed by single-crystal X-ray diffraction analysis, which has revealed that the complex is a homoleptic mononuclear silver(I) cationic solid. The charge of the Ag(I)–NHC cation is balanced by the hexafluorophosphate anion. The cationic moieties are closely packed in the chair and inverted chair forms where silver(I) possesses a quasi-linear geometry. Moreover, the silver complex provided blue emission from all the three excitations with good fluorescence quantum yield. The fluorescence lifetime of the silver(I) complex has been determined using the time-correlated single photon counting technique. Interestingly, the fluorescence decay pattern and the fluorescence lifetimes of the silver complex are largely different from those of the parent ligand acridine imidazolium salt. Moreover, the theoretical predictions have been found to be in good agreement with the experimental results

The Acyclic Retinoid Peretinoin Inhibits Hepatitis C Virus Replication and Infectious Virus Release in Vitro

Clinical studies suggest that the oral acyclic retinoid Peretinoin may reduce the recurrence of hepatocellular carcinoma (HCC) following surgical ablation of primary tumours. Since hepatitis C virus (HCV) infection is a major cause of HCC, we assessed whether Peretinoin and other retinoids have any effect on HCV infection. For this purpose, we measured the effects of several retinoids on the replication of genotype 1a, 1b, and 2a HCV in vitro. Peretinoin inhibited RNA replication for all genotypes and showed the strongest antiviral effect among the retinoids tested. Furthermore, it reduced infectious virus release by 80–90% without affecting virus assembly. These effects could be due to reduced signalling from lipid droplets, triglyceride abundance, and the expression of mature sterol regulatory element-binding protein 1c and fatty acid synthase. These negative effects of Peretinoin on HCV infection may be beneficial in addition to its potential for HCC chemoprevention in HCV-infected patients

The acyclic retinoid peretinoin inhibits hepatitis C virus replication and infectious virus release in vitro

Clinical studies suggest that the oral acyclic retinoid Peretinoin may reduce the recurrence of hepatocellular carcinoma (HCC) following surgical ablation of primary tumours. Since hepatitis C virus (HCV) infection is a major cause of HCC, we assessed whether Peretinoin and other retinoids have any effect on HCV infection. For this purpose, we measured the effects of several retinoids on the replication of genotype 1a, 1b, and 2a HCV in vitro. Peretinoin inhibited RNA replication for all genotypes and showed the strongest antiviral effect among the retinoids tested. Furthermore, it reduced infectious virus release by 80-90% without affecting virus assembly. These effects could be due to reduced signalling from lipid droplets, triglyceride abundance, and the expression of mature sterol regulatory element-binding protein 1c and fatty acid synthase. These negative effects of Peretinoin on HCV infection may be beneficial in addition to its potential for HCC chemoprevention in HCV-infected patients

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Bilingual Text Matching Using Bilingual Dictionary and Statistics

This paper describes a unified frmnework for bilingual text lnatching by combining existing hand-written bilingual dictionaries and statistical techniques. The process of bilingual text matching consists of two major steps: sentence alignment and structural matching of bilingual sentences. Statistical techniques are applied to estimate word correspondences not included in bilingual dictionaries. Estimateel word torrespore denccs are usetiff for improving both sentence align- ment and structural matching

Lincomycin Resistance Mutations in Two Regions Immediately Downstream of the −10 Region of lmr Promoter Cause Overexpression of a Putative Multidrug Efflux Pump in Bacillus subtilis Mutants

We isolated 19 lincomycin-resistant Bacillus subtilis mutants by expressing lmrB encoding a putative multidrug efflux protein. Eighteen of the mutants altered at two regions (−3 to −1 and +15) immediately downstream of the −10 region of the lmr promoter increased lmr transcription in vivo and in vitro