Synergistic effect of nogo-neutralizing antibody IN-1 and ciliary neurotrophic factor on axonal regeneration in adult rodent visual systems

The presence of Nogo axon regeneration inhibitory molecules in the central nervous system (CNS) and the counteracting effect of IN-1 antibodies have been widely reported. In this study, we examined the effect of IN-1-producing hybridoma cells on axon regeneration in adult rodent retinal ganglion cells (RGCs) after various types of optic nerve (ON) injury, evaluating therein whether ciliary neurotrophic factor (CNTF) potentiated the effect of IN-1. We found that application of IN-1 alone failed to enhance regeneration of intracranially or intraorbitally transected RGC axons in a peripheral nerve (PN) graft. IN-1 hybridoma cells also failed to significantly promote intraorbitally crushed ON axons to reenter the distal part of the ON. However, a combined application of IN-1 and CNTF had a synergistic effect in both intracranial PN and intraorbital ON crush paradigms. This study suggests that the action of IN-1 antibodies in promoting axon regeneration in the CNS could be more effective when coupled with other appropriate factors.published_or_final_versio

Fabrication of Coaxial Si1−xGex Heterostructure Nanowires by O2 Flow-Induced Bifurcate Reactions

We report on bifurcate reactions on the surface of well-aligned Si1−xGex nanowires that enable fabrication of two different coaxial heterostructure nanowires. The Si1−xGex nanowires were grown in a chemical vapor transport process using SiCl4 gas and Ge powder as a source. After the growth of nanowires, SiCl4 flow was terminated while O2 gas flow was introduced under vacuum. On the surface of nanowires was deposited Ge by the vapor from the Ge powder or oxidized into SiO2 by the O2 gas. The transition from deposition to oxidation occurred abruptly at 2 torr of O2 pressure without any intermediate region and enables selectively fabricated Ge/Si1−xGex or SiO2/Si1−xGex coaxial heterostructure nanowires. The rate of deposition and oxidation was dominated by interfacial reaction and diffusion of oxygen through the oxide layer, respectively

PuTmiR: A database for extracting neighboring transcription factors of human microRNAs

<p>Abstract</p> <p>Background</p> <p>Some of the recent investigations in systems biology have revealed the existence of a complex regulatory network between genes, microRNAs (miRNAs) and transcription factors (TFs). In this paper, we focus on TF to miRNA regulation and provide a novel interface for extracting the list of putative TFs for human miRNAs. A putative TF of an miRNA is considered here as those binding within the close genomic locality of that miRNA with respect to its starting or ending base pair on the chromosome. Recent studies suggest that these putative TFs are possible regulators of those miRNAs.</p> <p>Description</p> <p>The interface is built around two datasets that consist of the exhaustive lists of putative TFs binding respectively in the 10 kb upstream region (USR) and downstream region (DSR) of human miRNAs. A web server, named as PuTmiR, is designed. It provides an option for extracting the putative TFs for human miRNAs, as per the requirement of a user, based on genomic locality, i.e., any upstream or downstream region of interest less than 10 kb. The degree distributions of the number of putative TFs and miRNAs against each other for the 10 kb USR and DSR are analyzed from the data and they explore some interesting results. We also report about the finding of a significant regulatory activity of the YY1 protein over a set of oncomiRNAs related to the colon cancer.</p> <p>Conclusion</p> <p>The interface provided by the PuTmiR web server provides an important resource for analyzing the direct and indirect regulation of human miRNAs. While it is already an established fact that miRNAs are regulated by TFs binding to their USR, this database might possibly help to study whether an miRNA can also be regulated by the TFs binding to their DSR.</p

Byssinosis in Guangzhou, China

Objectives - To study the prevalence of byssinosis and other respiratory abnormalities in workers exposed to cotton dust in Guangzhou in two factories that processed purely cotton. Methods - All the 1320 workers exposed were included. The controls were 1306 workers with no history of occupational dust exposure. Total dust and inhalable dust were measured by Chinese total dust sampler and American vertical elutriator respectively. A World Health Organisation questionnaire was used. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV 1) were measured by a Vitalograph spirometer. Results - The median inhalable dust concentrations ranged from 0.41 to 1.51 mg/m 3 and median total dust concentrations from 3.04 to 12.32 mg/m. The prevalence of respiratory abnormalities in the cotton workers were (a) typical Monday symptoms 9.0%; (b) FEV 1 fall by ≥ 5% after a shift 16.8%; (c) FEV 1 fall by ≥ 10% after a shift 4.2%; (d) FEV'q < 80% predicted 6.1%; (e) FEV 1/FVC < 75% 4.0%; (f) cough or phlegm 18.2%; (g) chronic bronchitis 10-9%; and (h) byssinosis, defined by (a) plus (b) 1.7%. With the exception of (d), most of the prevalences increased with increasing age, duration of exposure, and cumulative inhalable dust exposure. No increasing trends of respiratory abnormalities were found for current total dust, inhalable dust, and cumulative total dust concentrations. Compared with controls, after adjustment for sex and smoking, with the exception of (d), all the pooled relative risks of respiratory abnormalities were raised for cotton exposure. Conclusions - It is concluded that cumulative inhalable cotton is likely to be the cause of byssinotic symptoms, acute lung function decrements, cough, or phlegm, and chronic bronchitis.published_or_final_versio

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib

BACKGROUND: Patients with metastatic pancreatic cancer (mPC) often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, Phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and mPC whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. PATIENTS AND METHODS: Patients were randomized to receive maintenance olaparib (300 mg bid; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥ 10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. RESULTS: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was less than 10 points in both arms and there was no significant between-group difference (-2.47; 95% CI - 7.27, 2.33; P=0.31). Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI - 8.75, -0.16; P=0.04). There was no difference in TSCMD for olaparib versus placebo for GHS (P=0.25; HR 0.72; 95% CI 0.41, 1.27) or physical functioning (P=0.32; HR 1.38; 95%CI 0.73, 2.63). CONCLUSIONS: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and mPC. CLINCALTRIALS.GOV NUMBER: NCT02184195

Biocompatibility of Graphene Oxide

Herein, we report the effects of graphene oxides on human fibroblast cells and mice with the aim of investigating graphene oxides' biocompatibility. The graphene oxides were prepared by the modified Hummers method and characterized by high-resolution transmission electron microscope and atomic force microscopy. The human fibroblast cells were cultured with different doses of graphene oxides for day 1 to day 5. Thirty mice divided into three test groups (low, middle, high dose) and one control group were injected with 0.1, 0.25, and 0.4 mg graphene oxides, respectively, and were raised for 1 day, 7 days, and 30 days, respectively. Results showed that the water-soluble graphene oxides were successfully prepared; graphene oxides with dose less than 20 μg/mL did not exhibit toxicity to human fibroblast cells, and the dose of more than 50 μg/mL exhibits obvious cytotoxicity such as decreasing cell adhesion, inducing cell apoptosis, entering into lysosomes, mitochondrion, endoplasm, and cell nucleus. Graphene oxides under low dose (0.1 mg) and middle dose (0.25 mg) did not exhibit obvious toxicity to mice and under high dose (0.4 mg) exhibited chronic toxicity, such as 4/9 mice death and lung granuloma formation, mainly located in lung, liver, spleen, and kidney, almost could not be cleaned by kidney. In conclusion, graphene oxides exhibit dose-dependent toxicity to cells and animals, such as inducing cell apoptosis and lung granuloma formation, and cannot be cleaned by kidney. When graphene oxides are explored for in vivo applications in animal or human body, its biocompatibility must be considered

Asymmetric Origin for Gravitino Relic Density in the Hybrid Gravity-Gauge Mediated Supersymmetry Breaking

We propose the hybrid gravity-gauge mediated supersymmetry breaking where the gravitino mass is about several GeV. The strong constraints on supersymmetry viable parameter space from the CMS and ATLAS experiments at the LHC can be relaxed due to the heavy colored supersymmetric particles, and it is consistent with null results in the dark matter (DM) direct search experiments such as XENON100. In particular, the possible maximal flavor and CP violations from the relatively small gravity mediation may naturally account for the recent LHCb anomaly. In addition, because the gravitino mass is around the asymmetric DM mass, we propose the asymmetric origin of the gravitino relic density and solve the cosmological coincident problem on the DM and baryon densities \Omega_{\rm DM}:\Omega_{B}\approx 5:1. The gravitino relic density arises from asymmetric metastable particle (AMP) late decay. However, we show that there is no AMP candidate in the minimal supersymmetric Standard Model (SM) due to the robust gaugino/Higgsino mediated wash-out effects. Interestingly, AMP can be realized in the well motivated supersymmetric SMs with vector-like particles or continuous U(1)_R symmetry. Especially, the lightest CP-even Higgs boson mass can be lifted in the supersymmetric SMs with vector-like particles.Comment: RevTex4, 21 pages, 1 figure, minor corrections, JHEP versio

Genome-wide enhancer maps link risk variants to disease genes

Genome-wide association studies (GWAS) have identified thousands of noncoding loci that are associated with human diseases and complextraits, each of which could reveal insights into the mechanisms of disease(1). Many ofthe underlying causal variants may affect enhancers(2,3), but we lack accurate maps of enhancers and their target genes to interpret such variants. We recently developed the activity-by-contact (ABC) model to predict which enhancers regulate which genes and validated the model using CRISPR perturbations in several cell types(4). Here we apply this ABC model to create enhancer-gene maps in 131 human cell types and tissues, and use these maps to interpret the functions of GWAS variants. Across 72 diseases and complex traits, ABC links 5,036 GWAS signals to 2,249 unique genes, including a class of 577genesthat appear to influence multiple phenotypes through variants in enhancers that act in different cell types. In inflammatory bowel disease (IBD), causal variants are enriched in predicted enhancers by more than 20-fold in particular cell types such as dendritic cells, and ABC achieves higher precision than other regulatory methods at connecting noncoding variants to target genes. These variant-to-function maps reveal an enhancer that contains an IBD risk variant and that regulates the expression of PPIF to alter the membrane potential of mitochondria in macrophages. Our study reveals principles of genome regulation, identifies genes that affect IBD and provides a resource and generalizable strategy to connect risk variants of common diseases to their molecular and cellular functions.Peer reviewe

Exsolution trends and co-segregation aspects of self-grown catalyst nanoparticles in perovskites

In perovskites, exsolution of transition metals has been proposed as a smart catalyst design for energy applications. Although there exist transition metals with superior catalytic activity, they are limited by their ability to exsolve under a reducing environment. When a doping element is present in the perovskite, it is often observed that the surface segregation of the doping element is changed by oxygen vacancies. However, the mechanism of co-segregation of doping element with oxygen vacancies is still an open question. Here we report trends in the exsolution of transition metal (Mn, Co, Ni and Fe) on the PrBaMn2O5+?? layered perovskite oxide related to the co-segregation energy. Transmission electron microscopic observations show that easily reducible cations (Mn, Co and Ni) are exsolved from the perovskite depending on the transition metal-perovskite reducibility. In addition, using density functional calculations we reveal that co-segregation of B-site dopant and oxygen vacancies plays a central role in the exsolution