A look into retinal organoids: methods, analytical techniques, and applications

Inherited retinal diseases (IRDs) cause progressive loss of light-sensitive photoreceptors in the eye and can lead to blindness. Gene-based therapies for IRDs have shown remarkable progress in the past decade, but the vast majority of forms remain untreatable. In the era of personalised medicine, induced pluripotent stem cells (iPSCs) emerge as a valuable system for cell replacement and to model IRD because they retain the specific patient genome and can differentiate into any adult cell type. Three-dimensional (3D) iPSCs-derived retina-like tissue called retinal organoid contains all major retina-specific cell types: amacrine, bipolar, horizontal, retinal ganglion cells, Müller glia, as well as rod and cone photoreceptors. Here, we describe the main applications of retinal organoids and provide a comprehensive overview of the state-of-art analysis methods that apply to this model system. Finally, we will discuss the outlook for improvements that would bring the cellular model a step closer to become an established system in research and treatment development of IRDs

Bacillus subtilis RarA Acts as a Positive RecA Accessory Protein

Ubiquitous RarA AAA+ ATPases play crucial roles in the cellular response to blocked replication forks in pro- and eukaryotes. Here, we provide evidence that RarA regulates the activity of the central player in homologous recombination (HR), RecA, in response to DNA damage. During unperturbed growth, absence of RarA reduced the viability of recA, recO and recF15 cells, and during repair of H2O2- or MMS-induced DNA damage, rarA was epistatic to recA, recO and recF. Conversely, the inactivation of rarA partially suppressed the HR defect of mutants lacking end-resection (addAB, recJ, recQ, recS) or branch migration (ruvAB, recG, radA) activity. RarA contributes to RecA thread formation, that are thought to be the active forms of RecA during homology search. The absence of RarA reduced RecA accumulation, and the formation of visible RecA threads in vivo upon DNA damage. When rarA was combined with mutations in genuine RecA accessory genes, RecA accumulation was further reduced in rarA recU and rarA recX double mutant cells, and was blocked in rarA recF15 cells. These results suggest that RarA contributes to the assembly of RecA nucleoprotein filaments onto single-stranded DNA (ssDNA), in concert with RecF, and possibly antagonizes RecA filament disassembly by RecX or RecU.Peer reviewe

A study of the selective hydroconversion of biocarboxylic acids to bioalcohols over novel indium-nickel/zeolite catalysts using octanoic acid as model reactant

Octanoic acid (OA) was hydrotreated in a flow-through reactor at 21 bar total pressure and 240-340 °C over supported metal catalysts prepared from Ni-zeolites (A, X, P) by indium modification. The Ni-zeolites were activated first in H2 flow at 21 bar and 450 °C. While a fraction of the nickel got fully reduced, the zeolite structure became partially destructed. However, some nickel cations remained unreduced, therefore a large fraction of the crystalline zeolite structure was retained. The indium modification of the reduced Ni-zeolites generated bimetallic NiIn/Ni,H-zeolite catalysts having higher stability, hydroconversion activity, octanol selectivity, and lower hydrodecarbonylation activity than the parent partially destructed Ni-zeolite and the Adkins-type catalysts, commercially applied for the conversion of fatty acids to alcohols. © 2013 Akadémiai Kiadó, Budapest, Hungary

Combining Static and Dynamic Contract Checking for Curry

Static type systems are usually not sufficient to express all requirements on function calls. Hence, contracts with pre- and postconditions can be used to express more complex constraints on operations. Contracts can be checked at run time to ensure that operations are only invoked with reasonable arguments and return intended results. Although such dynamic contract checking provides more reliable program execution, it requires execution time and could lead to program crashes that might be detected with more advanced methods at compile time. To improve this situation for declarative languages, we present an approach to combine static and dynamic contract checking for the functional logic language Curry. Based on a formal model of contract checking for functional logic programming, we propose an automatic method to verify contracts at compile time. If a contract is successfully verified, dynamic checking of it can be omitted. This method decreases execution time without degrading reliable program execution. In the best case, when all contracts are statically verified, it provides trust in the software since crashes due to contract violations cannot occur during program execution.Comment: Pre-proceedings paper presented at the 27th International Symposium on Logic-Based Program Synthesis and Transformation (LOPSTR 2017), Namur, Belgium, 10-12 October 2017 (arXiv:1708.07854

Effect of Gas Atmosphere on Catalytic Behaviour of Zirconia, Ceria and Ceria Zirconia Catalysts in Valeric Acid Ketonization

[EN] Ketonization of valeric acid, which can be obtained by lignocellulosic biomass conversion, was carried out in a fixed bed flow reactor over ZrO2, 5-20 % CeO2/ZrO2 and CeO2 both under hydrogen and nitrogen stream at 628 K and atmospheric pressure. Regardless gas-carrier 10 wt% CeO2/ZrO2 was found to show higher catalytic activity compared to zirconia per se as well as other ceria modified zirconia while ceria per se exhibited very low catalytic activity. All catalysts provided higher acid conversion in H-2 than in N-2 whereas selectivity to 5-nonanone was insensitive to gas atmosphere. XRD, FTIR, UV-Vis DRS, XPS, HRTEM methods were applied to characterize catalysts in reduced and unreduced states simulating corresponding reaction conditions during acid ketonization. XRD did not reveal any changes in zirconia and ceria/zirconia lattice parameters as well as crystalline phase depending on gas atmosphere while insertion of ceria in zirconia caused notable increase in lattice parameter indicating some distortion of crystalline structure. According to XPS, FTIR and UV-Vis methods, the carrier gas was found to affect catalyst surface composition leading to alteration in Lewis acid sites ratio. Appearance of Zr3+ cations was observed on the ZrO2 surface after hydrogen pretreatment whereas only Zr4+ cations were determined using nitrogen as a gas-carrier. These changes of catalyst's surface cation composition affected corresponding activity in ketonization probably being crucial for reaction mechanism involving metal cations catalytic centers for acid adsorption and COO- stabilization at the initial step.Financial support from the Russian Foundation of Basic Research (RFBR Grant No 11-03-94001-CSIC) is gratefully acknowledged. This work was supported by the Federal Program "Scientific and Educational Cadres of Russia'' (Grant No 2012-1.5-12-000-1013-002). The authors also wish to thank Dr. Evgeniy Gerasimov, Dr. Igor Prosvirin, Dr. Demid Demidov from the Department of Physicochemical Methods at the Boreskov Institute of Catalysis for TEM and XPS measurements.Zaytseva, YA.; Panchenko, VN.; Simonov, MN.; Shutilov, AA.; Zenkovets, GA.; Renz, M.; Simakova, IL.... (2013). Effect of Gas Atmosphere on Catalytic Behaviour of Zirconia, Ceria and Ceria Zirconia Catalysts in Valeric Acid Ketonization. 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The impact of contact tracing in clustered populations

The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections. Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn. We show that, when contact network structure is considered in addition to contact tracing, standard “mass action” models are generally inadequate. To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space. This result is sometimes reversed, however, for the case of highly effective contact tracing. We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks. In this way we contribute to the general theory of network-based interventions against infectious disease

The International-Trade Network: Gravity Equations and Topological Properties

This paper begins to explore the determinants of the topological properties of the international - trade network (ITN). We fit bilateral-trade flows using a standard gravity equation to build a "residual" ITN where trade-link weights are depurated from geographical distance, size, border effects, trade agreements, and so on. We then compare the topological properties of the original and residual ITNs. We find that the residual ITN displays, unlike the original one, marked signatures of a complex system, and is characterized by a very different topological architecture. Whereas the original ITN is geographically clustered and organized around a few large-sized hubs, the residual ITN displays many small-sized but trade-oriented countries that, independently of their geographical position, either play the role of local hubs or attract large and rich countries in relatively complex trade-interaction patterns

Scaling Laws in Human Language

Zipf's law on word frequency is observed in English, French, Spanish, Italian, and so on, yet it does not hold for Chinese, Japanese or Korean characters. A model for writing process is proposed to explain the above difference, which takes into account the effects of finite vocabulary size. Experiments, simulations and analytical solution agree well with each other. The results show that the frequency distribution follows a power law with exponent being equal to 1, at which the corresponding Zipf's exponent diverges. Actually, the distribution obeys exponential form in the Zipf's plot. Deviating from the Heaps' law, the number of distinct words grows with the text length in three stages: It grows linearly in the beginning, then turns to a logarithmical form, and eventually saturates. This work refines previous understanding about Zipf's law and Heaps' law in language systems.Comment: 6 pages, 4 figure