The Effects of Myocilin Expression on Functionally Relevant Trabecular Meshwork Genes: A Mini-Review

Myocilin is a secreted glaucoma-associated protein, specifically induced by dexamethasone in human trabecular meshwork cells, where it was discovered. Myocilin is expressed in several tissues of the body, but it causes disease only in the eye. The protein contains two domains: an N-terminal region with significant homologies to nonmuscle myosin, and a C-terminal region, which is similar to the olfactomedin proteins. Forty percent of myocilin undergoes an intracellular endoproteolytic cleavage by calpain II, a calcium-dependent cysteine protease, which releases the 2 domains. The protein is known to interact with intracellular and extracellular matrix proteins, and some is released into the extracellular space associated with exosomes. Myocilin mutations are linked to glaucoma and induce elevated intraocular pressure. Most of the glaucoma-causative mutations map to the olfactomedin domain, which appears to be a critical domain for the function of the protein. Myocilin mutants are misfolded, aggregate in the endoplasmic reticulum, and are not secreted. Overexpression of myocilin and of its mutants in primary human trabecular meshwork cells triggers changes in the expression of numerous genes, many of which have been known to be involved in mechanisms important for the physiology and pathology of the tissue. Here we review recent studies from our laboratory and those of others that deal with trabecular meshwork genes, which are altered by the overexpression of wild-type and glaucoma-causative mutant myocilin genes

Evidence for a calcification process in the trabecular meshwork

The human trabecular meshwork (TM) expresses many genes that have been associated with physiological (bone, cartilage, teeth) and pathological (vascular systems, kidney) calcification. In particular, the TM highly expresses the inhibitor of calcification Matrix Gla (MGP) gene, which encodes a vitamin K-dependent protein that requires post-translational activation to inhibit the formation of calcium precipitates. TM cells have high activity of the activating γ-carboxylase enzyme and produce active MGP. Silencing MGP increases the activity of alkaline phosphatase (ALP), an enzyme of the matrix vesicles and marker of calcification. Overexpressing MGP reduces the ALP activity induced by bone morphogenetic 2 (BMP2), a potent inducer of calcification. In this review we gathered evidence for the existence of a mineralization process in the TM. We selected twenty regulatory calcification genes, reviewed their functions in their original tissues and looked at their relative abundance in the TM by heat maps derived from existing microarrays. Although results are not yet fully conclusive and more experiments are needed, examining TM expression in the light of the calcification literature brings up many similarities. One such parallel is the role of mechanical forces in bone induction and the high levels of mineralization inhibitors found in the constantly mechanically stressed TM. During the next few years, examination of other calcification-related regulatory genes and pathways, as well as morphological examination of knockout animals would help elucidate the relevance of a calcification process to TM overall function

Experimental study of MIMO-OFDM transmissions at 94 GHz in indoor environments

Millimeter wave (mm-wave) frequencies have been proposed to achieve high capacity in 5G communications. Although meaningful research on the channel characteristics has been performed in the 28, 38and 60 GHz bands ─in both indoor and short-range scenarios─,only a small number of trials (experiments) have been carried out in other mm-wave bands. The objective of this work is to study the viability and evaluate the performance of the 94 GHz frequency band for MIMO-OFDM transmission in an indoor environment. Starting from a measurement campaign, the performance of MIMO algorithms is studied in terms of throughput for four different antenna configurations.This work was supported in part by the Ministerio de Economía y Competitividad MINECO, Spain under Grant TEC2016-78028-C3-2-P, and in part by the European FEDER funds

NEED en la Universidad

Onzenes Jornades de Foment de la Investigació de la FCHS (Any 2005-2006)Hemos considerado necesario realizar esta investigación porque después de consultar muchas y diversas fuentes, hemos podido observar que los estudios alrededor de este tema escasean, puesto que es un tema bastante reciente y hasta el momento se ha investigado bastante poco. Nuestra investigación se ha basado en el análisis de las actitudes tanto del profesorado como del alumnado de las tres facultades de la Universidad Jaume I de Castellón respecto a las Necesidades Educativas Especiales Derivadas de Discapacidad. Nuestro objetivo principal ha sido extraer conclusiones generales sobre éstas actitudes y verificar o desmentir la hipótesis de nuestra investigación, la cual planteaba que las actitudes del profesorado y del alumnado serán diferentes dependiendo si éstos han tenido o no alguna experiencia con personas con Necesidades Educativas Especiales Derivadas de Discapacidad, por lo tanto la variable dependiente será las actitudes de los profesores y de los alumnos y la variable independiente tener o no tener alguna experiencia con personas con NEEDD. Para obtener los datos utilizamos dos cuestionarios sobre actitudes, uno para el profesorado y otro para el alumnado. Los cuestionarios se pasaron a 150 alumnos y a 57 profesores. La conclusión de nuestra investigación, tras haber realizado los análisis pertinentes, es que no existen diferencias significativas en las actitudes del alumnado y del profesorado de la UJI respecto a los alumnos/as con NEEDD, es decir, nuestra hipótesis no se verifica.We have considered necessary to make this investigation because after consulting many and diverse sources, we have been able to observe that the studies around this subject are scarce, since is a quite recent subject and until the moment it has been investigated rather little. Our investigation has been based on the analysis of the attitudes as much of the teaching staff as of the pupils of the three faculties of the University Jaume I of Castellón with respect to the Special Educative Necessities Derived from Discapacidad. Our primary target has been to draw general conclusions on these attitudes and to verify or to deny the hypothesis of our investigation, which raised that the attitudes of the teaching staff and the pupils will be different depending if these have had or not some experience with people with Special Educative Necessities Derived from Discapacidad, therefore the dependent variable will be the attitudes of the professors and the students and the independent variable to have or not to have some experience with people with NEEDD. In order to collect the data we used two questionnaires on attitudes, one for the teaching staff and another one for the pupils. The questionnaires went to 150 students and 57 professors. The conclusion of our investigation, after to have made the pertinent analyses, is that significant differences in the attitudes of the pupils and the teaching staff of the UJI with respect to students with NEEDD do not exist, that is to say, our hypothesis is not verified

A Novel Mgp -Cre Knock-In Mouse Reveals an Anticalcification/Antistiffness Candidate Gene in the Trabecular Meshwork and Peripapillary Scleral Region

Soft tissue calcification is a pathological condition. Matrix Gla (MGP) is a potent mineralization inhibitor secreted by cartilage chondrocytes and arteries' vascular smooth muscle cells. Mgp knock-out mice die at 6 weeks due to massive arterial calcification. Arterial calcification results in arterial stiffness and higher systolic blood pressure. Intriguingly, MGP was highly abundant in trabecular meshwork (TM). Because tissue stiffness is relevant to glaucoma, we investigated which additional eye tissues use Mgp's function using knock-in mice

Development of a Model of Elevated Intraocular Pressure in Rats by Gene Transfer of Bone Morphogenetic Protein 2

To determine whether inducing calcification in the trabecular meshwork results in elevated IOP in living rats. To use this property to create an elevated IOP animal model by gene transfer of bone morphogenetic protein 2 (BMP2)

Prevention of Nocturnal Elevation of Intraocular Pressure by Gene Transfer of Dominant-Negative RhoA in Rats

We developed a gene transfer tool for the control of nocturnal elevated intraocular pressure (IOP)

Pesticide Inhalation Exposure of Applicators and Bystanders Using Conventional and Innovative Cropping Systems in the Valencian Region, Spain

This paper provides scientific results from a European LIFE project carried out in the Valencian region of Spain during the 2017 to 2018 time frame. In 2018, more than 60,000 tons of pesticides were commercialized in Spain, with approximately 15% destined for Valencian crops. In order to improve the air quality in the agricultural areas of this region, an innovative cropping system based on irrigation was developed and compared to conventional treatments based on hand-spray and turbo application. After applying conventional treatments to five types of crops (citrus, persimmon, nectarine, watermelon, and other stone fruits), a total of 13 active substances were detected in the air. The same active substances were applied to crops using the novel irrigation system, and no pesticide was detected in the air. Moreover, applicator and bystander populations in the region were assessed for their risk of inhalation exposure to pesticides, and no risk was found when either of the techniques, the innovative and the conventional agricultural one, were applied

Gas-phase and particulate products from the atmospheric degradation of the organothiophosphorus insecticide chlorpyrifos-methyl

The phosphorothioate structure is highly present in several organophosphorus pesticides. However, there is insufficient information about its degradation process after the release to the atmosphere and the secondary pollutants formed. Herein, the atmospheric reaction of chlorpyrifos-methyl (o,o-dimethyl o-(3,5,6-trichloropyridin-2-yl) phosphorothioate), is described for semi-urban or rural locations. The photo-oxidation under low NOx conditions (5-55 ppbV) was reproduced in a large outdoor simulation chamber, observing a rapid degradation (lifetime<3.5 h). The formation of gaseous products and particulate matter (aerosol yield 2-8%) was monitored. The chemical composition of minor products (gaseous and particulate) was studied, identifying 15 multi-oxygenated derivatives. The most abundant products were ring-retaining molecules such as o,o-dimethyl o-(3,5,6-trichloropyridin-2-yl) phosphorothioate, dimethyl 3,5,6-trichloropyridin-2-yl phosphate, o-methyl o-(3,5,6-trichloropyridin-2-yl) hydrogen phosphorothioate, 3,5,6-trichloropyridin-2-yl dihydrogen phosphate, 3,5,6-trichloropyridin-2-ol, and 3,5,6-trichloropyridine-2,4-diol. An atmospheric degradation mechanism has been proposed based on an oxidation started with OH-nucleophilic attack to P=S bond. The results have been extrapolated to other organothiophosphorus molecules, such as malathion, parathion, diazinon and methidathion, among many others, to estimate their photo-oxidative degradation and the expected products.The authors wish to thank the EUPHORE staff and J.T.B. The authors wish to acknowledge Ministerio de Economia y Competitividad for IMPLACAVELES (CGL2013-49093-C2-1-R) and IMPESTAT (CGL2010-18474/CLI) projects, and Generalitat Valenciana for the DESESTRES- Prometeo II project. The Fundacion CEAM is partly supported by Generalitat Valenciana - Spain. EUPHORE instrumentation is partly funded by MINECO - Spain, through INNPLANTA Project: PCT-440000-2010-003 and the projects FEDER CEAM10-3E-1301 and CEAM10-3E-1302.Borrás García, EM.; Tortajada-Genaro, LA.; Ródenas, M.; Vera, T.; Coscollá, C.; Yusá, V.; Muñoz, A. (2015). Gas-phase and particulate products from the atmospheric degradation of the organothiophosphorus insecticide chlorpyrifos-methyl. Chemosphere. 138:888-894. https://doi.org/10.1016/j.chemosphere.2014.11.067S88889413

Atmospheric degradation of two pesticides mixed with volatile organic compounds emitted by citrus trees. Ozone and secondary organic aerosol production

[EN] Once pesticides are released into the environment, their active ingredient and other formulation compounds, such as coadjuvants or solvents, may undergo biological and chemical degradation, and form a range of products that could be even more hazardous than their precursors. These degradation products may also interact with the natural biogenic compounds emitted by treated crops, which leads to secondary air pollutants, such as ozone (O3) or fine particulate matter, which directly affect human health and climate warming. This research provides evidence for the atmospheric process influencing the atmospheric and environmental fate of pesticides, active substance chloropicrin and commercially formulated chlorpyriphos, which interact with biogenic volatile organic compounds (alpha-pinene and a mixture of monoterpenes) simulating mixtures of terpenes emitted by orange trees at the large outdoor European PHOto-REactor (EUPHORE). Significant SOA formations were observed during the photolysis and/or ozonolysis of both pesticides in the presence of biogenic volatile organic com-pounds. For the photolysis of chloropicrin in the presence of alpha-pinene, the aerosol and O3 formation yields ranged from 6 to 16% and 167-338%, respectively, depending on the initial conditions. For the photolysis of commercial chlorpyrifos in the presence of a mixture of terpenes, the formed aerosol yield was 24%, higher than those obtained by the photolysis of the terpenes in the absence of pesticides. Both pesticides in combination with terpenes increased O3 formation. O3 reacted with those terpenes, which increased particulate matter formation and may pose atmospheric issues on local and global scales.This research has been partially supported by the European Commission LIFE Programme (PERFECT LIFE grant number LIFE17 ENV/ES/000205), by the Spanish Ministry of Science and Innovation (CGL2013-49093-C2-1-R) and by the Generalitat Valenciana (PROMETEO/2019/110). Fundacion CEAM is supported by the Generalitat Valenciana.Muñoz, A.; Borrás, E.; Vera, T.; Colmenar-González, I.; Ródenas, M.; Gimeno, C.; Fuentes, E.... (2023). Atmospheric degradation of two pesticides mixed with volatile organic compounds emitted by citrus trees. Ozone and secondary organic aerosol production. Atmospheric Environment. (295). https://doi.org/10.1016/j.atmosenv.2022.11954129