Gene therapy for corneal dystrophies and disease, where are we?

We assess studies on vector systems for delivery of transgenes to the cornea that have been published over the last year, and summarise new work on the identification of specific transgenes for corneal diseases. Recent findings Adeno-associated viral vectors (AAV) are increasingly being successfully applied to the cornea, although transgene expression requires corneal epithelial debridement, or intrastromal injection of the vector. Gene delivery platforms based on nanoparticles of chitosan or gold also show promise. Over-expression of vasoinhibin-1 or decorin, or siRNA-mediated blockade of the cannabinoid receptor CB1, can all reduce corneal neovascularization. Over-expression of decorin or matrix metalloproteinase 14 can reduce corneal fibrosis and haze, while over-expression of c-Met accelerates epithelial wound healing. Induction of corneal endothelial cell replication by over-expression of E2F2, p16 or p21 can maintain or even increase corneal endothelial cell density in eye bank corneas. Over-expression of the anti-apoptotic transgenes Bcl-xL or p35 significantly enhances corneal endothelial cell survival and reduces apoptosis in stored human corneas. Summary Despite a wealth of information on methods for the delivery of nucleic acids to the human cornea, and ever-increasing information transgenes with substantial therapeutic potential, gene therapy for corneal disorders has yet to reach the clinic.KAW is supported by the National Health & Medical Research Council of Australia

Implementation of binary stochastic STDP learning using chalcogenide-based memristive devices

The emergence of nano-scale memristive devices encouraged many different research areas to exploit their use in multiple applications. One of the proposed applications was to implement synaptic connections in bio-inspired neuromorphic systems. Large-scale neuromorphic hardware platforms are being developed with increasing number of neurons and synapses, having a critical bottleneck in the online learning capabilities. Spike-timing-dependent plasticity (STDP) is a widely used learning mechanism inspired by biology which updates the synaptic weight as a function of the temporal correlation between pre- and post-synaptic spikes. In this work, we demonstrate experimentally that binary stochastic STDP learning can be obtained from a memristor when the appropriate pulses are applied at both sides of the device

On Modified Integral Inequalities for a Generalized Class of Convexity and Applications

In this paper, we concentrate on and investigate the idea of a novel family of modified p-convex functions. We elaborate on some of this newly proposed idea’s attractive algebraic characteristics to support it. This is used to study some novel integral inequalities in the frame of the Hermite–Hadamard type. A unique equality is established for differentiable mappings. The Hermite–Hadamard inequality is extended and estimated in a number of new ways with the help of this equality to strengthen the findings. Finally, we investigate and explore some applications for some special functions. We think the approach examined in this work will further pique the interest of curious researchers

Horizontal gene transfer, dispersal and haloarchaeal speciation

The Halobacteria are a well-studied archaeal class and numerous investigations are showing how their diversity is distributed amongst genomes and geographic locations. Evidence indicates that recombination between species continuously facilitates the arrival of new genes, and within species, it is frequent enough to spread acquired genes amongst all individuals in the population. To create permanent independent diversity and generate new species, barriers to recombination are probably required. The data support an interpretation that rates of evolution (e.g., horizontal gene transfer and mutation) are faster at creating geographically localized variation than dispersal and invasion are at homogenizing genetic differences between locations. Therefore, we suggest that recurrent episodes of dispersal followed by variable periods of endemism break the homogenizing forces of intrapopulation recombination and that this process might be the principal stimulus leading to divergence and speciation in Halobacteria

UJI TOKSISITAS AKUT EKSTRAK ETANOL KLIKA JAMBU MEDE (Anacardium occidentale L.) PADA MENCIT JANTAN (Mus musculus)

Research conducted acute toxicity test of ethanol extract of cashew Klika (Anacardium occidentale L.) in male mice (Mus musculus). This study aims to determine the ethanol extract LD50 Guava Klika Mede supply all oral and toxic symptoms were observed. This study used 25 male mice were divided into five treatment groups. The first group received 0.5% CMC-Na as the control group II, III, IV and V were given sample Klika cashew (Anacardium occidentale L.) with successive doses 40mg/20 gram BB mice, 80mg/20 gram BB mice, 160mg/20 gram BB mice and 320mg/20 gram BB mice. Prior to treatment, the mice were subjected to a prior fasting and received the test substance, in accordance with the calculated dose.The observations of toxic effects based on changes in the behavior of mice such as excessive salivation diarrhea, urinasi, decreased motor activity, aggressive behavior and respiratory changes with time of the successive observation 5, 10. 15, 30, 60, 120, 180 and 240 minutes. For the determination of LD50 values are based on the number of mice in each group died within 24 hours to 7 days. Analysis of data menuntukan toxic effects of the most dominant motion is the effect of the decrease in activity. The results of calculations using the LD50 values obtained Klika Thompson and Weil extract cashew (Anacardium occidentale L.) was 4923.45 mg / KgBB so that the level of toxicity in this category Lu "Toxic Medium"

The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.)

The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro) in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro), but not by mutant protein N(pro) C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro) inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro) and infection with Bovine Viral Diarrhea Virus (BVDV) prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro) and we show that, in common with many other viral proteins, N(pro) targets mitochondria to inhibit apoptosis in response to cell stress. N(pro) itself not only relocated to mitochondria but in addition, both N(pro) and IRF3 associated with peroxisomes, with over 85% of N(pro) puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro) and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro) accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro), and highlight the role of these organelles in the anti-viral pathway

Spectroscopic investigations of a Ti:Tm:LiNbO3 waveguide for photon-echo quantum memory

We report the fabrication and characterization of a Ti$^{4+}$:Tm$^{3+}$:LiNbO$_3$ optical waveguide in view of photon-echo quantum memory applications. In particular, we investigated room- and cryogenic-temperature properties via absorption, spectral hole burning, photon echo, and Stark spectroscopy. We found radiative lifetimes of 82 $\mu$s and 2.4 ms for the $^3$H$_4$ and $^3$F$_4$ levels, respectively, and a 44% branching ratio from the $^3$H$_{4}$ to the $^3$F$_4$ level. We also measured an optical coherence time of 1.6 $\mu$s for the $^3$H$_6\leftrightarrow{}^3$H$_4$, 795 nm wavelength transition, and investigated the limitation of spectral diffusion to spectral hole burning. Upon application of magnetic fields of a few hundred Gauss, we observed persistent spectral holes with lifetimes up to seconds. Furthermore, we measured a linear Stark shift of 25 kHz$\cdot$cm/V. Our results are promising for integrated, electro-optical, waveguide quantum memory for photons.Comment: 11 pages, 14 figure

Assessment of Chemical Inhibitor Addition to Improve the Gas Production from Biowaste

The coexistence of sulphate-reducing bacteria and methanogenic archaea in the reactors during the anaerobic digestion from sulphate-containing waste could favor the accumulation of sulfide on the biogas, and therefore reduce its quality. In this study, the effect of sulphate-reducing bacteria inhibitor (MoO−2 4 ) addition in a two phase system from sulphate-containing municipal solid waste to improve the quality of the biogas has been investigated. The results showed that although SRB and sulphide production decreased, the use of inhibitor was not effective to improve the anaerobic digestion in a two phase system from sulphate-containing waste, since a significant decrease on biogas and organic matter removal were observed. Before MoO−2 4 addition the average values of volatile solid were around 12 g/kg, after 5 days of inhibitor use, those values did exceed to 28 g/kg. Molybdate caused acidification in the reactor and it was according to decrease in the pH values. In relation to microbial consortia, the effect of inhibitor was a decrease in Bacteria (44%; 60% in sulphate-reducing bacteria) and Archaea (38%) population

Transcription factors NRF2 and HSF1 have opposing functions in autophagy

Abstract Autophagy plays a critical role in the maintenance of cellular homeostasis by degrading proteins, lipids and organelles. Autophagy is activated in response to stress, but its regulation in the context of other stress response pathways, such as those mediated by heat shock factor 1 (HSF1) and nuclear factor-erythroid 2 p45-related factor 2 (NRF2), is not well understood. We found that the Michael acceptor bis(2-hydoxybenzylidene)acetone (HBB2), a dual activator of NRF2 and HSF1, protects against the development of UV irradiation-mediated cutaneous squamous cell carcinoma in mice. We further show that HBB2 is an inducer of autophagy. In cells, HBB2 increases the levels of the autophagy-cargo protein p62/sequestosome 1, and the lipidated form of microtubule-associated protein light chain 3 isoform B. Activation of autophagy by HBB2 is impaired in NRF2-deficient cells, which have reduced autophagic flux and low basal and induced levels of p62. Conversely, HSF1-deficient cells have increased autophagic flux under both basal as well as HBB2-induced conditions, accompanied by increased p62 levels. Our findings suggest that NRF2 and HSF1 have opposing roles during autophagy, and illustrate the existence of tight mechanistic links between the cellular stress responses