Effect of hypoxia-inducible factor 1-alpha (HIF-1α) on proliferation and apoptosis of adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma cells

To understand whether hypoxia-inducible factor 1-alpha (HIF-1α) could protect AtT-20 cells from hypoxia induced apoptosis, we investigated the effects of HIF-1α on proliferation and apoptosis of adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma cells (AtT-20 cells). AtT-20 cells were treated with various concentrations of CoCl2 to induce hypoxia. 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide, a yellow tetrazole (MTT) was applied to detect the proliferation of these cells. Western blot assay and real time polymerase chain reaction (PCR) were used to determine the protein and mRNA expressions of HIF-1α, respectively. In addition, AtT-20 cells were transfected with siRNA targeting HIF-1α and treated with different concentrations of CoCl2. The transfection efficacy was assessed by real-time PCR and western blot assay. Apoptosis was measured by fluorescein isothiocyanate (FITC)-annexin V/ propidium iodide (PI) staining and TUNEL staining. The effect of CoCl2 on the proliferation of AtT-20 cells was in a concentration and time dependent manner. When the concentration of CoCl2 was ≤100 μM and/or duration of CoCl2 treatment was ≤48 h, CoCl2 triggered the proliferation of AtT-20 cells. Nevertheless, the apoptosis rate of cells transfected with HIF-1α-siRNA was markedly increased after CoCl2 treatment. These findings suggest that, HIF-1α can promote the proliferation of AtT-20 cells and exert anti-apoptotic effect under hypoxic condition.Key words: Hypoxia inducible factor–1α, cobalt chloride, apoptosis, pituitary adenom

The experience of long-term opiate maintenance treatment and reported barriers to recovery: A qualitative systematic review

Background/Aim: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. Methods: A qualitative systematic review. Results: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily ‘inward focused'. Conclusion: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery

Transmit Power Minimization for MIMO Systems of Exponential Average BER with Fixed Outage Probability

This document is the Accepted Manuscript version of the following article: Dian-Wu Yue, and Yichuang Sun, ‘Transmit Power Minimization for MIMO Systems of Exponential Average BER with Fixed Outage Probability’, Wireless Personal Communications, Vol. 90 (4): 1951-1970, first available online on 20 June 2016. Under embargo. Embargo end date: 20 June 2017. The final publication is available at Springer via https://link.springer.com/article/10.1007%2Fs11277-016-3432-4This paper is concerned with a wireless multiple-antenna system operating in multiple-input multiple-output (MIMO) fading channels with channel state information being known at both transmitter and receiver. By spatiotemporal subchannel selection and power control, it aims to minimize the average transmit power (ATP) of the MIMO system while achieving an exponential type of average bit error rate (BER) for each data stream. Under the constraints on each subchannel that individual outage probability and average BER are given, based on a traditional upper bound and a dynamic upper bound of Q function, two closed-form ATP expressions are derived, respectively, which can result in two different power allocation schemes. Numerical results are provided to validate the theoretical analysis, and show that the power allocation scheme with the dynamic upper bound can achieve more power savings than the one with the traditional upper bound.Peer reviewe

Construction of a Baculovirus-Silkworm Multigene Expression System and Its Application on Producing Virus-Like Particles

A new baculovirus-silkworm multigene expression system named Bombyx mori MultiBac is developed and described here, by which multiple expression cassettes can be introduced into the Bombyx mori nuclear polyhedrosis virus (BmNPV) genome efficiently. The system consists of three donor vectors (pCTdual, pRADM and pUCDMIG) and an invasive diaminopimelate (DAP) auxotrophic recipient E. coli containing BmNPV-Bacmid (BmBacmid) with a homologous recombination region, an attTn7 site and a loxp site. Two genes carried by pCTdual are firstly inserted into BmBacmid by homologous recombination, while the other eight genes in pRADM and pUCDMIG are introduced into BmBacmid through Tn7 transposition and cre-loxp recombination. Then the invasive and DAP auxotrophic E. coli carrying recombinant BmBacmid is directly injected into silkworm for expressing heterologous genes in larvae or pupae. Three structural genes of rotavirus and three fluorescent genes have been simultaneously expressed in silkworm larvae using our new system, resulting in the formation of virus-like particles (VLPs) of rotavirus and the color change of larvae. The VLPs were purified from hemolymph by ultracentrifugation using CsCl gradients, with a yield of 12.7 µg per larva. For the great capacity of foreign genes and the low cost of feeding silkworm, this high efficient BmMultiBac expression system provides a suitable platform to produce VLPs or protein complexes

Simple models of the chemical field around swimming plankton

Background. Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods. Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10−9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10−8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10−9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10−5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions. Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism

Graphene Photonics and Optoelectronics

The richness of optical and electronic properties of graphene attracts enormous interest. Graphene has high mobility and optical transparency, in addition to flexibility, robustness and environmental stability. So far, the main focus has been on fundamental physics and electronic devices. However, we believe its true potential to be in photonics and optoelectronics, where the combination of its unique optical and electronic properties can be fully exploited, even in the absence of a bandgap, and the linear dispersion of the Dirac electrons enables ultra-wide-band tunability. The rise of graphene in photonics and optoelectronics is shown by several recent results, ranging from solar cells and light emitting devices, to touch screens, photodetectors and ultrafast lasers. Here we review the state of the art in this emerging field.Comment: Review Nature Photonics, in pres

Safety of dabigatran etexilate for the secondary prevention of venous thromboembolism in children

This open-label, single-arm, prospective cohort trial is the first phase 3 safety study to describe outcomes in children treated with dabigatran etexilate for secondary venous thromboembolism (VTE) prevention. Eligible children aged 12 to <18 years (age stratum 1), 2 to <12 years (stratum 2), and >3 months to <2 years (stratum 3) had an objectively confirmed diagnosis of VTE treated with standard of care (SOC) for ‡3 months, or had completed dabigatran or SOC treatment in the DIVERSITY trial (NCT01895777) and had an unresolved clinical thrombosis risk factor requiring further anticoagulation. Children received dabigatran for up to 12 months, or less if the identified VTE clinical risk factor resolved. Primary end points included VTE recurrence, bleeding events, and mortality at 6 and 12 months. Overall, 203 children received dabigatran, with median exposure being 36.3 weeks (range, 0-57 weeks); 171 of 203 (84.2%) and 32 of 203 (15.8%) took capsules and pellets, respectively. Overall, 2 of 203 children (1.0%) experienced on-treatment VTE recurrence, and 3 of 203 (1.5%) experienced major bleeding events, with 2 (1.0%) reporting clinically relevant nonmajor bleeding events, and 37 (18.2%) minor bleeding events. There were no on-treatment deaths. On-treatment postthrombotic syndrome was reported for 2 of 162 children (1.2%) who had deep vein thrombosis or central-line thrombosis as their most recent VTE. Pharmacokinetic/pharmacodynamic relationships of dabigatran were similar to those in adult VTE patients. In summary, dabigatran showed a favorable safety profile for secondary VTE prevention in children aged from >3 months to <18 years with persistent VTE risk factor(s). This trial was registered at www.clinicaltrials.gov as #NCT02197416. (Blood. 2020;135(7):491-504

Protection of Hepatocytes from Cytotoxic T Cell Mediated Killing by Interferon-Alpha

<p>Background: Cellular immunity plays a key role in determining the outcome of hepatitis C virus (HCV) infection, although the majority of infections become persistent. The mechanisms behind persistence are still not clear; however, the primary site of infection, the liver, may be critical. We investigated the ability of CD8+ T-cells (CTL) to recognise and kill hepatocytes under cytokine stimulation.</p> <p>Methods/Principle Findings: Resting hepatocytes cell lines expressed low levels of MHC Class I, but remained susceptible to CTL cytotoxicity. IFN-α treatment, in vitro, markedly increased hepatocyte MHC Class I expression, however, reduced sensitivity to CTL cytotoxicity. IFN-α stimulated hepatocyte lines were still able to present antigen and induce IFN-γ expression in interacting CTL. Resistance to killing was not due to the inhibition of the FASL/FAS- pathway, as stimulated hepatocytes were still susceptible to FAS-mediated apoptosis. In vitro stimulation with IFN-α, or the introduction of a subgenomic HCV replicon into the HepG2 line, upregulated the expression of the granzyme-B inhibitor–proteinase inhibitor 9 (PI-9). PI-9 expression was also observed in liver tissue biopsies from patients with chronic HCV infection.</p> <p>Conclusion/Significance: IFN-α induces resistance in hepatocytes to perforin/granzyme mediate CTL killing pathways. One possible mechanism could be through the expression of the PI-9. Hindrance of CTL cytotoxicity could contribute to the chronicity of hepatic viral infections.</p&gt