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Abstract This study compared the efficacy safety profiles of the Xen 63 and Preserflo MicroShunt devices, both standalone, in patients with primary open-angle glaucoma (POAG). It is a retrospective and single-center study conducted on consecutive on patients with medically uncontrolled POAG who underwent either a standalone Xen 63 or a standalone Preserflo and had a 12-month follow-up visit. The primary outcome was the mean IOP at month-12. Sixty eyes were included, 30 eyes in each Xen 63 and Preserflo groups, respectively. Preoperative IOP was significantly lowered from 20.8 ± 3.6 mmHg and 19.1 ± 3.8 mmHg to 14.2 ± 4.5 mmHg and 12.8 ± 2.3 mmHg in the Xen 63 and Preserflo groups, respectively (p

Fusarium head blight (FHB) is a devastating disease of wheat, causing yield losses, reduced grain quality, and mycotoxin contamination. Breeding can mitigate the severity of FHB epidemics, especially with genomics-assisted methods. The mechanisms underlying resistance to FHB in wheat have been extensively studied, including phenological traits and genome-wide markers associated with FHB severity. Here, we aimed to improve genomic prediction for FHB resistance across breeding programs by incorporating FHB-correlated traits and FHB-associated loci as model covariates. We combined phenotypic data on FHB severity, anthesis date, and plant height with genome-wide marker data from five Central European winter wheat breeding programs for genome-wide association studies (GWAS) and genomic prediction. Within all populations, FHB was correlated with anthesis date and/or plant height, and a marker linked to the semi-dwarfing locus Rht-D1 was detected with GWAS for FHB. Including the Rht-D1 marker, anthesis date, and/or plant height as covariates in genomic prediction modeling improved prediction accuracy not only within populations but also in cross-population scenarios.

Nowadays, it is possible to assert that the causality of environmental problems entails a complex social, economic, cultural and political background; faced with such a situation, it is essential to have an operational science that considers the human factor that is in constant interaction with the environment (socio-ecological systems), while seeking sustainable development. Because of that, it became necessary to join different disciplines in a construct called Environmental Sciences, whose main objective is to study and solve problems related to human-environment interactions. Endorsing the concept of exergy to an interdisciplinary science implies understanding how society satisfies its needs with the natural resources provided by the various ecosystems and how they sustain demand in the man-environment interaction cycle, starting from the development of structural and functional attributes in a dynamic flow of matter and energy. This can be addressed with the first and second laws of thermodynamics by allowing the use of holistic indicators in the Environmental Sciences; one such indicator is ecoexergy, which describes the state of an ecosystem based on the biomass content and genetic information. Thus, this work presents an outline of the incursion of exergy in the context of environmental sciences, which implies that the ecosystem is an open system whose behavior adheres to the laws of thermodynamics.

Background: Due to their high toxicity, cancer treatments produce multiple sequelae, including fatigue, which has a great impact on quality of life. Therefore, the aim of this study is to evaluate the efficacy on quality of life, fatigue, and functional capacity of a short-term exercise program combining aerobic exercise, resistance training, and stretching for 6 weeks in cancer patients. Methods: The design of the study was quasi-experimental, which included a group of 30 women who were receiving or had received in the last year chemotherapy, radiotherapy, or hormonal treatment. The exercise supervised program with vigorous intensity lasted for six weeks and consisted of three distinct blocks: aerobic exercise (25 min), resistance training (20 min), and stretching exercises (15 min). Before and after starting the exercise program quality of life (EORTC QLQ-C30 questionnaire), functional capacity [6 min Walking Test (6MWT), Handgrip Test (HGT), 30-Second Sit-to-Stand Test (30s-STST)], and fatigue (FACIT-F questionnaire) were measured. Results: In the EORTC QLQ-C30 questionnaire significantly higher scores were observed in the global health status scale (p < 0.05), as well as in the functional scale in the role functioning, emotional functioning, and cognitive functioning items (p < 0.05), indicating a higher quality of life and overall health level. There was also a reduction in fatigue (p < 0.05), obtaining higher scores on the FACIT-F questionnaire after the exercise program. Additionally significant improvements are observed in 6MWT, HGT, and 30s-STST following the implementation of the exercise program (p < 0.05). Conclusions: A 6-week exercise protocol, with a vigorous intensity, including resistance training, endurance, and stretching exercises can produce significant improvements in quality of life and reduction in fatigue, as well as improve muscle strength and functional capacity.

Abstract Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene mutations lead to fragile X syndrome, cognitive disorders, and, in some individuals, scoliosis and craniofacial abnormalities. Four-month-old (mo) male mice with deletion of the FMR1 gene exhibit a mild increase in cortical and cancellous femoral bone mass. However, consequences of absence of FMR1 in bone of young/aged male/female mice and the cellular basis of the skeletal phenotype remain unknown. We found that absence of FMR1 results in improved bone properties with higher bone mineral density in both sexes and in 2- and 9-mo mice. The cancellous bone mass is higher only in females, whereas, cortical bone mass is higher in 2- and 9-mo males, but higher in 2- and lower in 9-mo female FMR1-knockout mice. Furthermore, male bones show higher biomechanical properties at 2mo, and females at both ages. Absence of FMR1 increases osteoblast/mineralization/bone formation and osteocyte dendricity/gene expression in vivo/ex vivo/in vitro, without affecting osteoclasts in vivo/ex vivo. Thus, FMR1 is a novel osteoblast/osteocyte differentiation inhibitor, and its absence leads to age-, site- and sex-dependent higher bone mass/strength.

This research focuses on the potential for microbial treatment to stabilize compacted soils, which are often utilized in earthwork projects. A silt–clay sand was used to describe a particular kind of soil. The suggested remedy makes use of the soil’s naturally occurring urea and Ca2+, as well as microorganisms introduced to the compaction water. Two alternative initial water-content types were examined: those on the dry side and those close to the ideal Proctor conditions. Bacillaceae microorganisms were used to induce microbial CaCO3 precipitation and improve the hydraulic and mechanical properties of the compacted soil. The samples were biotreated and immediately compacted, so that the precipitation of calcium carbonate during the curing process took place in the contact areas between the particles (biocementation) and in the pore space (bioclogging). A set of techniques were used to study the ageing effects, such as the water-retention curve by dew-points psychrometer, mercury porosimetry intrusion, permeability, ultrasonic pulse velocity, resonant column, and unconfined and tensile-compression tests. During the ageing, it was observed that the bacterial activity consumed water for the hydrolysis of urea and other intermediate reactions to precipitate CaCO3. This process resulted in a retraction of the microstructure and a change in the macrostructure. The bioclogging phenomenon was more evident in the soil microstructure, while the biocementation process was easier to observe in the macrostructure. The suction’s effects on the soil stiffness were studied in detail, and a significant increase was detected. Despite these water-content losses, which caused soil stiffening by increasing the suction, it was still feasible to identify the gradual rise in small-strain stiffness throughout incubation. The unconfined and tensile-compression tests showed a similar progressive increase in terms of peak compressive and peak splitting strength during the incubation. These results are of interest when microbiological treatments are applied in soils to produce cementitious materials, with the present investigation demonstrating a complete study of their geotechnical behaviour.

The heterogenicity of antimicrobial resistance genes described in clinically significant bacterial isolates and their potential role in reducing the efficacy of classically effective antibiotics pose a major challenge for global healthcare, especially in infections caused by Gram-negative bacteria. We analyzed 112 multidrug-resistant (MDR) isolates from clinical samples in order to detect high resistance profiles, both phenotypically and genotypically, among four Gram-negative genera (Acinetobacter, Escherichia, Klebsiella, and Pseudomonas). We found that 9.8% of the total selected isolates were classified as extensively drug-resistant (XDR) (six isolates identified as A. baumannii and five among P. pneumoniae isolates). All other isolates were classified as MDR. Almost 100% of the isolates showed positive results for blaOXA-23 and blaNDM-1 genes among the A. baumannii samples, one resistance gene (blaCTX-M) among E. coli, and two genetic determinants (blaCTX-M and aac(6′)-Ib) among Klebsiella. In contrast, P. aeruginosa showed just one high-frequency antibiotic resistance gene (dfrA), which was present in 68.42% of the isolates studied. We also describe positive associations between ampicillin and cefotaxime resistance in A. baumannii and the presence of blaVEB and blaGES genes, as well as between the aztreonam resistance phenotype and the presence of blaGES gene in E. coli. These data may be useful in achieving a better control of infection strategies and antibiotic management in clinical scenarios where these multidrug-resistant Gram-negative pathogens cause higher morbidity and mortality.

Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis (T. vaginalis) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new therapeutic options against T. vaginalis infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC50 value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC50 values in the nanomolar range and AGR-2 being the most potent (IC50 400 nM). To gain insight into molecular events related to AGR-induced cell death in T. vaginalis, we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes (CK, PFK, TPI, and ENOL) and genes involved in metabolism (G6PD, TKT, TALDO, NADHOX, ACT, and TUB), suggesting that disturbing these key metabolic genes alters the survival of the T. vaginalis parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against T. vaginalis.

Several microaerophilic parasites such as Giardia lamblia, Trichomonas vaginalis, and Plasmodium falciparum are major disease-causing organisms and are responsible for spreading infections worldwide. Despite significant progress made in understanding the metabolism and molecular biology of microaerophilic parasites, chemotherapeutic treatment to control it has seen limited progress. A current proposed strategy for drug discovery against parasitic diseases is the identification of essential key enzymes of metabolic pathways associated with the parasite’s survival. In these organisms, glucose-6-phosphate dehydrogenase::6-phosphogluconolactonase (G6PD:: 6PGL), the first enzyme of the pentose phosphate pathway (PPP), is essential for its metabolism. Since G6PD:: 6PGL provides substrates for nucleotides synthesis and NADPH as a source of reducing equivalents, it could be considered an anti-parasite drug target. This review analyzes the anaerobic energy metabolism of G. lamblia, T. vaginalis, and P. falciparum, with a focus on glucose metabolism through the pentose phosphate pathway and the significance of the fused G6PD:: 6PGL enzyme as a therapeutic target in the search for new drugs.

Abstract Background Ocular surface disease in glaucoma patients is a significant ocular co-morbidity that can affect 40% to 59% of these patients worldwide. The current study was aimed at evaluating the potential clinical benefit of an intense pulsed light (IPL)-based treatment in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatments. To our knowledge, this is the first series analyzing the therapeutic effect of this treatment option in this type of patients. Methods This non-comparative prospective case series study enrolled a total of 30 glaucoma patients ranging in age from 57 to 94 years old and treated with hypotensive eyedrops for years with dry eye symptomatology. All patients received four sessions of IPL treatment using the Optima IPL system (Lumenis, Yokneam, Israel) adjusted to the official optimized Lumenis setting. Changes in symptomatology, corneal staining, conjunctival hyperemia, non-invasive break-up time (NIBUT), tear osmolarity, tear meniscus height (TMH), meiboscore and meibomian gland expressibility was analyzed after treatment. Results Statistically significant reductions were observed after IPL treatment in the symptomatology scores measured with different questionnaires [ocular surface disease index (OSDI), standard patient evaluation of eye dryness (SPEED) and symptom assessment questionnaire in dry eye (SANDE)] as well as with the visual analogue scale (P

Abstract Background Nitric oxide and GnRH are biological factors that participate in the regulation of reproductive functions. To our knowledge, there are no studies that link NO and GnRH in the sympathetic ganglia. Thus, the aim of the present work was to investigate the influence of NO on GnRH release from the coeliac ganglion and its effect on luteal regression at the end of pregnancy in the rat. Methods The ex vivo system composed by the coeliac ganglion, the superior ovarian nerve, and the ovary of rats on day 21 of pregnancy was incubated for 180 min with the addition, into the ganglionic compartment, of L-NG-nitro arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor. The control group consisted in untreated organ systems. Results The addition of L-NAME in the coeliac ganglion compartment decreased NO as well as GnRH release from the coeliac ganglion. In the ovarian compartment, and with respect to the control group, we observed a reduced release of GnRH, NO, and noradrenaline, but an increased production of progesterone, estradiol, and expression of their limiting biosynthetic enzymes, 3β-HSD and P450 aromatase, respectively. The inhibition of NO production by L-NAME in the coeliac ganglion compartment also reduced luteal apoptosis, lipid peroxidation, and nitrotyrosine, whereas it increased the total antioxidant capacity within the corpora lutea. Conclusion Collectively, the results indicate that NO production by the coeliac ganglion modulates the physiology of the ovary and luteal regression during late pregnancy in rats.

Purpose To investigate the possible risk factors for treatment failure in patients who had undergone Preserflo Microshunt (PMS) implantation, using anterior-segment optical coherence tomography (AS-OCT) to analyze the internal structures of the bleb. Methods The PMS blebs of 54 patients were evaluated with AS-OCT. A mathematical model was used to calculate the total filtering surface of the episcleral fluid cavity (EFC) and the hydraulic conductivity (HC) of the bleb wall. Complete and qualified success were defined as IOP between 6 and 17 mmHg with or without glaucoma medication. The relation between baseline characteristics and probability of bleb success was analyzed by bivariate and multivariate logistic regression. The main outcome measures were mean bleb wall thickness (BWT), reflectivity (BWR), HC, mean horizontal and vertical diameter and total filtering surface (TFS) of the EFC. Results Blebs from 74% patients were considered as complete success and 26% as failure. BWR and BWT increased linearly up to the first year in both groups. BWR was higher in the group failure (p = 0.02) and BWT in the group success (pConclusions AS-OCT revealed that successful PMS blebs could show either thick hyporreflective walls or wide filtering surfaces with thin capsules. A higher baseline IOP increased the probability of surgical success.

Aun teniendo gran relevancia el concepto de calidad de vida en el ámbito de la discapacidad intelectual (DI), existe escasa investigación acerca de su aplicación en jóvenes con trastorno del espectro del autismo (TEA), especialmente acerca de la dimensión derechos, área que ha cobrado especial importancia en los últimos años con la ratificación de la Convención de los Derechos de las Personas con Discapacidad de Naciones Unidas. Este estudio se centra en la evaluación de derechos en jóvenes con TEA y DI, comparando sus resultados con dos grupos de jóvenes que presentan DI y otra condición comórbida: síndrome de Down y parálisis cerebral. Para ello, se utilizó la subescala derechos de la versión piloto de la Escala KidsLife en una muestra de 153 participantes con DI entre 4 y 21 años (TEA = 51; síndrome de Down = 51; parálisis cerebral = 51). En el grupo con TEA, el género, el tipo de escolarización, el nivel de DI y de necesidades de apoyo dieron lugar a diferencias significativas. Los tres grupos obtuvieron resultados positivos, aunque los jóvenes con síndrome de Down obtienen resultados significativamente superiores a los obtenidos por jóvenes con TEA.

Abstract To assess the effectiveness and safety of the Preserflo Microshunt (PMS) implantation combined with cataract surgery in open-angle glaucoma (OAG) patients. Retrospective, open-label study conducted on insufficiently controlled OAG patients, who underwent a PMS implant procedure with mitomycin-C 0.2%, either alone or in combination with cataract surgery, and were followed for at least 12 months. Success was defined as an intraocular pressure (IOP) ≤ 18 mmHg and a reduction of at least 20% without (complete) or with (qualified) hypotensive medication. Fifty-eight eyes were included in the study, 35 eyes underwent PMS alone and 23 underwent PMS + Phaco. In the overall study sample, mean IOP was significantly lowered from 21.5 ± 3.3 mmHg at baseline to 14.6 ± 3.5 mmHg at month 12 (p

Contextualización: El agua es el recurso natural de mayor importancia. No obstante, su aprovechamiento es limitado, ya que sólo el 1% del agua del planeta es potencialmente apto para el consumo humano. En áreas rurales los sistemas de abastecimiento y conducción de aguas residuales pueden ser considerados artesanales o rudimentarios, lo cual no garantiza el flujo constante del recurso ni la calidad óptima para el consumo humano. Además, tiene efectos negativos para la salud pública y genera afectación a los recursos naturales. Vacío de conocimiento: En este sentido, este tipo de trabajos cobran importancia al describir los mecanismos asociados al recurso hídrico con los que cuentan las comunidades rurales, para que esta información, a su vez, contribuya en la formulación de propuestas desde los grupos de interés. Propósito: El presente estudio tuvo como objetivo principal identificar los sistemas de abastecimiento de agua y sistemas de disposición de aguas residuales de la comunidad rural de la vereda Barcelona, en el municipio de Villavicencio (Meta). Metodología: La información analizada se obtuvo por medio de encuestas semiestructuradas que fueron realizadas de manera aleatoria en distintos sectores de la vereda. Resultados y conclusiones: Entre los principales resultados se encontró que la comunidad se abastece de agua por medio de aljibes (100 %) y realiza la disposición de aguas residuales mediante cuatro sistemas: pozo séptico propio (44 %); pozo séptico comunitario (20 %); pozo séptico propio y campo abierto (28 %); pozo séptico comunitario y campo abierto (8 %). Adicionalmente, la percepción de la calidad del agua varío de acuerdo con el género. El 100 % de las mujeres identificaron como de baja calidad el agua para consumo humano, y en razón de esto se abastecen de fuentes seguras para su consumo y preparación de alimentos; mientras que los hombres la identificaron como regular y el 37% la consumen directamente. Finalmente, se evidenció que el actual mecanismo de limpieza de los sistemas de disposición de aguas residuales puede convertirse en un factor de riesgo de contaminación y afectación a la salud pública.

Protozoan parasites, such as Giardia lamblia and Trichomonas vaginalis, cause the most prevalent infections in humans in developing countries and provoke significant morbidity and mortality in endemic countries. Despite its side-effects, metronidazole is still the drug of choice as a giardiacidal and trichomonacidal tissue-active agent. However, the emergence of metronidazole resistance and its evolved strategies of parasites to evade innate host defenses have hindered the identification and development of new therapeutic strategies against these parasites. Here, we tested five synthesized benzimidazole derivatives as possible drugs for treating giardiasis and trichomoniasis, probing the bifunctional enzyme glucose 6-phosphate dehydrogenase::6-phosphogluconolactone from G. lamblia (GlG6PD::6PGL) and T. vaginalis (TvG6PD::6PGL) as a drug target. The investigated benzimidazole derivatives were H-B2M1, H-B2M2, H2N-BZM6, O2N-BZM7, and O2N-BZM9. The recombinant enzymes were used in inhibition assays, and in silico computational predictions and spectroscopic studies were applied to follow the structural alteration of the enzymes and identify the possible mechanism of inhibition. We identified two potent benzimidazole compounds (O2N-BZM7 and O2N-BZM9), which are capable of inhibiting both protozoan G6PD::6PGL enzymes and in vitro assays with these parasites, showing that these compounds also affect their viability. These results demonstrate that other therapeutic targets of the compounds are the enzymes GlG6PD::6PGL and TvG6PD::6PGL, which contribute to their antiparasitic effect and their possible use in antigiardial and trichomonacidal therapies.

Helicobacter pylori (H. pylori) has been proposed as the foremost risk factor for the development of gastric cancer. We found that H. pylori express the enzyme glucose-6-phosphate dehydrogenase (HpG6PD), which participates in glucose metabolism via the pentose phosphate pathway. Thus, we hypothesized that if the biochemical and physicochemical characteristics of HpG6PD contrast with the host G6PD (human G6PD, HsG6PD), HpG6PD becomes a potential target for novel drugs against H. pylori. In this work, we characterized the biochemical properties of the HpG6PD from the H.pylori strain 29CaP and expressed the active recombinant protein, to analyze its steady-state kinetics, thermostability, and biophysical aspects. In addition, we analyzed the HpG6PD in silico structural properties to compare them with those of the HsG6PD. The optimal pH for enzyme activity was 7.5, with a T1/2 of 46.6 °C, at an optimum stability temperature of 37 °C. The apparent Km values calculated for G6P and NADP+ were 75.0 and 12.8 µM, respectively. G6P does not protect HpG6PD from trypsin digestion, but NADP+ does protect the enzyme from trypsin and guanidine hydrochloride (Gdn-HCl). The biochemical characterization of HpG6PD contributes to knowledge regarding H. pylori metabolism and opens up the possibility of using this enzyme as a potential target for specific and efficient treatment against this pathogen; structural alignment indicates that the three-dimensional (3D) homodimer model of the G6PD protein from H. pylori is different from the 3D G6PD of Homo sapiens.

Potassium (K+) and nitrogen (N) are essential nutrients, and their absorption and distribution within the plant must be coordinated for optimal growth and development. Potassium is involved in charge balance of inorganic and organic anions and macromolecules, control of membrane electrical potential, pH homeostasis and the regulation of cell osmotic pressure, whereas nitrogen is an essential component of amino acids, proteins, and nucleic acids. Nitrate (NO3–) is often the primary nitrogen source, but it also serves as a signaling molecule to the plant. Nitrate regulates root architecture, stimulates shoot growth, delays flowering, regulates abscisic acid-independent stomata opening, and relieves seed dormancy. Plants can sense K+/NO3– levels in soils and adjust accordingly the uptake and root-to-shoot transport to balance the distribution of these ions between organs. On the other hand, in small amounts sodium (Na+) is categorized as a “beneficial element” for plants, mainly as a “cheap” osmolyte. However, at high concentrations in the soil, Na+ can inhibit various physiological processes impairing plant growth. Hence, plants have developed specific mechanisms to transport, sense, and respond to a variety of Na+ conditions. Sodium is taken up by many K+ transporters, and a large proportion of Na+ ions accumulated in shoots appear to be loaded into the xylem by systems that show nitrate dependence. Thus, an adequate supply of mineral nutrients is paramount to reduce the noxious effects of salts and to sustain crop productivity under salt stress. In this review, we will focus on recent research unraveling the mechanisms that coordinate the K+-NO3–; Na+-NO3–, and K+-Na+ transports, and the regulators controlling their uptake and allocation.

Trichomoniasis is a sexually transmitted disease with a high incidence worldwide, affecting 270 million people. Despite the existence of a catalog of available drugs to combat this infection, their extensive use promotes the appearance of resistant Trichomonas vaginalis (T. vaginalis), and some side effects in treated people, which are reasons why it is necessary to find new alternatives to combat this infection. In this study, we investigated the impact of an in-house library comprising 55 compounds on the activity of the fused T. vaginalis G6PD::6PGL (TvG6PD::6PGL) protein, a protein mediating the first reaction step of the pentose phosphate pathway (PPP), a crucial pathway involved in the parasite’s energy production. We found four compounds: JMM-3, CNZ-3, CNZ-17, and MCC-7, which inhibited the TvG6PD::6PGL protein by more than 50%. Furthermore, we determined the IC50, the inactivation constants, and the type of inhibition. Our results showed that these inhibitors induced catalytic function loss of the TvG6PD::6PGL enzyme by altering its secondary and tertiary structures. Finally, molecular docking was performed for the best inhibitors, JMM-3 and MCC-7. All our findings demonstrate the potential role of these selected hit compounds as TvG6PD::6PGL enzyme selective inhibitors.

AIM: To determine the effects of peripheral corneal thickness (PCT) on dynamic contour tonometry(DCT) and Goldmann applanation tonometry (GAT). METHODS: A cross-sectional study. We created a software which calculates the corneal contour (CC) as a function of the radius from the corneal apex to each pixel of the contour. The software generates a central circumference with a radius of 1 mm and the remainder of the cornea is segmented in 5 rings concentric with corneal apex being its diameter not constant around the corneal circumference as a consequence of the irregular CC but keeping constant the diameter of each ring in each direction of the contour. PCT was determined as the mean thickness of the most eccentric ring. Locally weighted scatterplot smoothing (LOWESS) regression was used to determine the pattern of the relationship between PCT and both DCT and GAT respectively. Thereafter, two multivariable linear regression models were constructed. In each of them, the dependant variable was intraocular pressure (IOP) as determined using GAT and DCT respectively. In both of the models the predictive variable was PCT though LOWESS regression pattern was used to model the relationship between the dependant variables and the predictor one. Age and sex were also introduced control variables along with their first-degree interactions with PCT. Main outcome measures include amount of IOP variation explained through regression models (R2) and regression coefficients (B). RESULTS: Subjects included 109 eyes of 109 healthy individuals. LOWESS regression suggested that a 2nd-degree polynomial would be suitable to model the relationship between both DCT and GAT with PCT. Hence PCT was introduced in both models as a linear and quadratic term. Neither age nor sex nor interactions were statistically significant in both models. For GAT model, R2 was 17.14% (F=9.02; P=0.0002), PCT linear term B was -1.163 (95% CI: -1.163, -0.617). PCT quadratic term B was 0.00081 (95% CI: 0.00043, 0.00118). For DCT model R2 was 14.28% (F=9.29; P=0.0002), PCT linear term B was -0.712 (95% CI: -1.052, -0.372), PCT quadratic term was B=0.0005 (95% CI: 0.0003, 0.0007). CONCLUSION: DCT and GAT measurements are conditioned by PCT though this effect, rather than linear, follows a 2nd-degree polynomial pattern.

Abstract The impact of organic pollutants on oceanic ecosystem functioning is largely unknown. Prochlorococcus, the most abundant known photosynthetic organism on Earth, has been suggested to be especially sensible to exposure to organic pollutants, but the sub-lethal effects of organic pollutants on its photosynthetic function at environmentally relevant concentrations and mixtures remain unexplored. Here we show the modulation of the expression of two photosynthetic genes, rbcL (RuBisCO large subunit) and psbA (PSII D1 protein), of oceanic populations of Prochlorococcus from the Atlantic, Indian and Pacific Oceans when exposed to mixtures of organic pollutants consisting of the non-polar fraction of a seawater extract. This mixture included most persistent organic pollutants, semivolatile aromatic-like compounds, and the unresolved complex mixture of hydrocarbons. Prochlorococcus populations in the controls showed the expected diel cycle variations in expression of photosynthetic genes. However, exposure to a complex mixture at concentrations only 2-fold above the environmental levels resulted in a decrease of expression of both genes, suggesting an effect on the photosynthetic function. While organic pollutant effects on marine phytoplankton have been already demonstrated at the cellular level, this is the first field study showing alterations at the molecular level of the photosynthetic function due to organic pollutants.

Este artículo aborda el estudio sobre los Trabajos Prácticos de Laboratorio elaborados por un grupo de futuros docentes en Física y en Química de la provincia de San Juan, en la República Argentina. El objetivo del mismo consiste en analizar las propuestas presentadas por estos estudiantes en el marco de un taller extracurricular. Este taller fue desarrollado para identificar fortalezas y debilidades a fin de proponer acciones para el mejoramiento del futuro desempeño docente. Analizamos los protocolos propuestos, basándonos en categorías previamente diseñadas. Los resultados obtenidos evidencian distintos elementos que podrían resultar facilitadores u obstaculizadores del desempeño exitoso en la futura práctica docente en Ciencias Naturales. Entre los elementos facilitadores, encontramos la presencia de situaciones contextualizadas y la adecuación al nivel escolar de los alumnos. Mientras entre los elementos obstaculizadores se destaca la ausencia de actividades que medien el tránsito de las observaciones a las interpretaciones. Por todo esto, sería recomendable formar a los futuros docentes en la revisión de sus diseños experimentales, de modo que consideren las observaciones, incorporen análisis que conduzcan a interpretaciones, y finalmente, propongan actividades tendientes a movilizar estos nuevos aprendizajes para aplicar en el análisis y resolución de situaciones cotidianas.

Giardia lamblia is a single-celled eukaryotic parasite with a small genome and is considered an early divergent eukaryote. The pentose phosphate pathway (PPP) plays an essential role in the oxidative stress defense of the parasite and the production of ribose-5-phosphate. In this parasite, the glucose-6-phosphate dehydrogenase (G6PD) is fused with the 6-phosphogluconolactonase (6PGL) enzyme, generating the enzyme named G6PD::6PGL that catalyzes the first two steps of the PPP. Here, we report that the G6PD::6PGL is a bifunctional enzyme with two catalytically active sites. We performed the kinetic characterization of both domains in the fused G6PD::6PGL enzyme, as well as the individual cloned G6PD. The results suggest that the catalytic activity of G6PD and 6PGL domains in the G6PD::6PGL enzyme are more efficient than the individual proteins. Additionally, using enzymatic and mass spectrometry assays, we found that the final metabolites of the catalytic reaction of the G6PD::6PGL are 6-phosphoglucono-δ-lactone and 6-phosphogluconate. Finally, we propose the reaction mechanism in which the G6PD domain performs the catalysis, releasing 6-phosphoglucono-δ-lactone to the reaction medium. Then, this metabolite binds to the 6PGL domain catalyzing the hydrolysis reaction and generating 6-phosphogluconate. The structural difference between the G. lamblia fused enzyme G6PD::6PGL with the human G6PD indicate that the G6PD::6PGL is a potential drug target for the rational synthesis of novels anti-Giardia drugs.

Helicobacter pylori (H. pylori) is a pathogen that can remain in the stomach of an infected person for their entire life. As a result, this leads to the development of severe gastric diseases such as gastric cancer. In addition, current therapies have several problems including antibiotics resistance. Therefore, new practical options to eliminate this bacterium, and its induced affections, are required to avoid morbidity and mortality worldwide. One strategy in the search for new drugs is to detect compounds that inhibit a limiting step in a central metabolic pathway of the pathogen of interest. In this work, we tested 55 compounds to gain insights into their possible use as new inhibitory drugs of H. pylori glucose-6-phosphate dehydrogenase (HpG6PD) activity. The compounds YGC-1; MGD-1, MGD-2; TDA-1; and JMM-3 with their respective scaffold 1,3-thiazolidine-2,4-dione; 1H-benzimidazole; 1,3-benzoxazole, morpholine, and biphenylcarbonitrile showed the best inhibitory activity (IC50 = 310, 465, 340, 204 and 304 μM, respectively). We then modeled the HpG6PD protein by homology modeling to conduct an in silico study of the chemical compounds and discovers its possible interactions with the HpG6PD enzyme. We found that compounds can be internalized at the NADP+ catalytic binding site. Hence, they probably exert a competitive inhibitory effect with NADP+ and a non-competitive or uncompetitive effect with G6P, that of the compounds binding far from the enzyme’s active site. Based on these findings, the tested compounds inhibiting HpG6PD represent promising novel drug candidates against H. pylori.

In this paper we reflect on the interaction between didactics of science as an academic discipline and the regulations on compulsory science education in Argentina. Recent contributions from didactical research are reviewed, particularly those related to the notion of school science, which has influence on problems such as currículum development, classroom communication and science teacher education. We start from the hypothesis that the model of school science permits greater integration between didactical innovation and real classroom practice.

Congenital glaucoma (CG) is a severe and inherited childhood optical neuropathy that leads to irreversible visual loss and blindness in children. CG pathogenesis remains largely unexplained in most patients. Herein we have extended our previous studies to evaluate the role of FOXC2 and PITX2 variants in CG. Variants of the proximal promoter and transcribed sequence of these two genes were analyzed by Sanger sequencing in a cohort of 133 CG families. To investigate possible oligogenic inheritance involving FOXC2 or PITX2 and CYP1B1, we also analyzed FOXC2 and PITX2 variants in a group of 25 CG cases who were known to carry CYP1B1 glaucoma-associated genotypes. The functional effect of three identified variants was assessed by transactivation luciferase reporter assays, protein stability and subcellular localization analyses. We found eight probands (6.0%) who carried four rare FOXC2 variants in the heterozygous state. In addition, we found an elevated frequency (8%) of heterozygous and rare PITX2 variants in the group of CG cases who were known to carry CYP1B1 glaucoma-associated genotypes, and one of these PITX2 variants arose de novo. To the best of our knowledge, two of the identified variants (FOXC2: c.1183C>A, p.(H395N); and PITX2: c.535C>A, p.(P179T)) have not been previously identified. Examination of the genotype-phenotype correlation in this group suggests that the presence of the infrequent PITX2 variants increase the severity of the phenotype. Transactivation reporter analyses showed partial functional alteration of three identified amino acid substitutions (FOXC2: p.(C498R) and p.(H395N); PITX2: p.(P179T)). In summary, the increased frequency in PCG patients of rare FOXC2 and PITX2 variants with mild functional alterations, suggests they play a role as putative modifier factors in this disease further supporting that CG is not a simple monogenic disease and provides novel insights into the complex pathological mechanisms that underlie CG.

En los últimos veinte años, las sociedades de España e Italia han experimentado un cambio demográfico muy notable debido a flujos migratorios de alta intensidad. Desde principios de la década de 1990, la población extranjera se multiplicó por cinco en ambos países y en 2010 alcanzó el 12 y el 6 por ciento, respectivamente, del conjunto poblacional (INE, 2015; ISTAT, 2015). En ambos casos, dicho fenómeno migratorio plantea nuevos desafíos de representación democrática, dado que, en un periodo muy corto de tiempo, ha generado un gran caudal de nuevos residentes con expectativas legítimas de hacer oír su voz en el proceso de toma de decisiones. Sin embargo, el aumento del número de inmigrantes residentes en España e Italia también coincidió con un período en el que la opinión pública empezó a mostrar mayor preocupación por la inmigración, lo que provocó actitudes negativas cada vez más visibles hacia los colectivos inmigrantes en ambos países. Este artículo analiza en qué medida la presión migratoria y el cambio actitudinal hacia los inmigrantes en España e Italia pueden ayudarnos a comprender mejor las estrategias de los partidos a la hora de facilitar el acceso de este colectivo a cargos electos en los parlamentos nacionales. Haciendo uso de una base de datos única que incluye información sobre el perfil sociodemográfico y político de todos los diputados y diputadas en ambos países desde 1990 hasta la actualidad, nuestro estudio contribuye a avanzar en el conocimiento sobre las dinámicas que favorecen y que dificultan la representación política de los inmigrantes en estos dos países del sur de Europa.

Los bosques de Polylepis, endémicos de las montañas de Sudamérica, suelen estar asociados con sitios relativamente inaccesibles como quebradas, roquedales o laderas empinadas. Las hipótesis más discutidas que explican esta asociación son: 1) factores abióticos como la humedad, la temperatura o el viento, ó 2) factores antropogénicos como la protección del ramoneo por ganado doméstico, la tala o los fuegos iniciados por el ser humano. Para resumir el estado de avance en el conocimiento, realizamos una revisión cuantitativa sobre los estudios de ecología y conservación de bosques de Polylepis a lo largo de toda su distribución. Identificamos 139 publicaciones relevantes, de las que el 36% estuvo concentrado en la Argentina. Las publicaciones incluyen 20 de las ~27 especies existentes, de las cuales las más estudiadas son P. australis y P. tarapacana, con 45 y 21 publicaciones, respectivamente. En el otro extremo, hay 7 especies no representadas en publicaciones. Las disciplinas más populares fueron la ecología de poblaciones (35%) y los estudios sobre biodiversidad y comunidades (18%). Muy pocos estudios se repiten de una región a la otra. Los estudios que intentan comprender la contribución relativa de factores abióticos vs. antropogénicos para explicar la asociación de los bosques con lugares relativamente inaccesibles señalan una contribución mayor de los factores antrópicos, aunque todos están concentrados en el extremo sur de la distribución de Polylepis en la Argentina. Sugerimos áreas de vacancia en estudios y posibles mejoras en la producción de nuevas publicaciones y en la red de interacciones entre investigadores interesados en los ecosistemas de Polylepis. https://doi.org/10.25260/EA.18.28.1.1.522

AIM: To correlate corneal variables (determined using the Pentacam) with optic nerve head (ONH) variables determined using the Heidelberg retina tomograph (HRT) in healthy subjects and patients diagnosed with primary open angle glaucoma (POAG). METHODS: Measurements were made in 75 healthy eyes and 73 eyes with POAG and correlations examined through Pearson correlation coefficients between the two sets of variables in the two subject groups. The corneal variables determined were corneal volume (CVol), central corneal thickness (CCT), overall corneal thickness (OvCT), the mean thickness of a circular zone centered at the corneal apex of 1 mm radius (zone I) and the mean thickness of several concentric rings, also centered at the apex until the limbus, each of 1 mm width (zones II to VI respectively). The ONH variables were determined using the HRT. RESULTS: The following pairs of variables were correlated in the control group: CCT-disc area (DAr) (-0.48; P

To examine differences in individual retinal layer thicknesses measured by spectral domain optical coherence tomography (SD-OCT) (Spectralis®) produced with age and according to sex.Cross-sectional, observational study.The study was conducted in 297 eyes of 297 healthy subjects aged 18 to 87 years. In one randomly selected eye of each participant the volume and mean thicknesses of the different macular layers were measured by SD-OCT using the instrument's macular segmentation software.Volume and mean thickness of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigmentary epithelium (RPE) and photoreceptor layer (PR).Retinal thickness was reduced by 0.24 μm for every one year of age. Age adjusted linear regression analysis revealed mean GCL, IPL, ONL and PR thickness reductions and a mean OPL thickness increase with age. Women had significantly lower mean GCL, IPL, INL, ONL and PR thicknesses and volumes and a significantly greater mRNFL volume than men.The thickness of most retinal layers varies both with age and according to sex. Longitudinal studies are needed to determine the rate of layer thinning produced with age.

AIM: To anatomically locate the points of minimum corneal thickness and central corneal thickness (pupil center) in relation to the corneal apex.METHODS: Observational, cross-sectional study, 299 healthy volunteers. Thickness at the corneal apex (AT), minimum corneal thickness (MT) and corneal thickness at the pupil center (PT) were determined using the pentacam. Distances from the corneal apex to MT (MD) and PT (PD) were calculated and their quadrant position (taking the corneal apex as the reference) determined:point of minimum thickness (MC) and point of central thickness (PC) depending on the quadrant position. Two multivariate linear regression models were constructed to examine the influence of age, gender, power of the flattest and steepest corneal axes, position of the flattest axis, corneal volume (determined using the Pentacam) and PT on MD and PD. The effects of these variables on MC and PC were also determined in two multinomial regression models.RESULTS: MT was located at a mean distance of 0.909 mm from the apex (79.4% in the inferior-temporal quadrant). PT was located at a mean distance of 0.156 mm from the apex. The linear regression model for MD indicated it was significantly influenced by corneal volume (B=-0.024; 95%CI:-0.043 to -0.004). No significant relations were identified in the linear regression model for PD or the multinomial logistic regressions for MC and PC.CONCLUSION: MT was typically located at the inferior-temporal quadrant of the cornea and its distance to the corneal apex tended to decrease with the increment of corneal volume.

Giardia lambia is a flagellated protozoan parasite that lives in the small intestine and is the causal agent of giardiasis. It has been reported that G. lamblia exhibits glucose-6-phosphate dehydrogenase (G6PD), the first enzyme in the pentose phosphate pathway (PPP). Our group work demonstrated that the g6pd and 6pgl genes are present in the open frame that gives rise to the fused G6PD::6PGL protein; where the G6PD region is similar to the 3D structure of G6PD in Homo sapiens. The objective of the present work was to show the presence of the structural NADP+ binding site on the fused G6PD::6PGL protein and evaluate the effect of the NADP+ molecule on protein stability using biochemical and computational analysis. A protective effect was observed on the thermal inactivation, thermal stability, and trypsin digestions assays when the protein was incubated with NADP+. By molecular docking, we determined the possible structural-NADP+ binding site, which is located between the Rossmann fold of G6PD and 6PGL. Finally, molecular dynamic (MD) simulation was used to test the stability of this complex; it was determined that the presence of both NADP+ structural and cofactor increased the stability of the enzyme, which is in agreement with our experimental results.

Objetivo: Identificar los conocimientos y prácticas sexuales en la población de adolescentes de los grados 8 a 11 de una institución educativa de la ciudad de Manizales (Caldas, Colombia). Materiales y métodos: Estudio de corte transversal; la población estuvo conformada por 170 adolescentes de 14 a 21 años, matriculados en los grados 8 a 11 de Básica Secundaria de una institución educativa de la ciudad de Manizales, de estratos medio y bajo. Se realizó por el método de encuesta. Se tomaron diferentes variables sobre conocimientos sexuales, prácticas sexuales y factores de riesgo para embarazo y enfermedades de transmisión sexual. Resultados: El promedio de edad fue de 16,31 años, de género masculino en un 56,5 %. Presentaron un promedio de 2,9 (sobre 5) de conocimientos en educación sexual, 1,8 en métodos anticonceptivos, 2,4 en embarazo, 3,5 en enfermedades de transmisión sexual, para un promedio total de 2,7. El 91,8 % ha tenido experiencias sexuales, 70,1 % con penetración; 46,6 % no emplea métodos anticonceptivos; 5 % de las mujeres manifestó que había tenido embarazos; 4,2 % dijo que no ha tenido enfermedades de transmisión sexual. El bajo puntaje de conocimientos correlaciona significativamente con incomodidad en el empleo de métodos anticonceptivos (p=0.018), desconocimiento de para qué se emplean (p=0.019), no empleo de ellos (p=0,007). Conclusiones: Debido al bajo conocimiento en temas de sexualidad y la intensa práctica sexual, esta población se convierte en población de alta riesgo para presencia de embarazos no deseados, de abortos inducidos y de enfermedades de transmisión sexual.

Algunos investigadores han alertado de que los ciudadanos occidentales participan cadavez menos en los asuntos públicos, a pesar del aumento en los niveles educativos y enlas habilidades y recursos de que disponen estos mismos ciudadanos. Esta crisis participativase manifestaría a través del declive en los niveles de participación electoral yen una menor participación en la política convencional.En el caso español, la creencia común es que, tras un breve período de amplia movilizacióny participación ciudadana durante la transición a la democracia, los ciudadanos españolesson cada vez más reticentes a participar en la esfera pública.Este artículo contradice esta descripción de la realidad española mediante el análisis delas pautas longitudinales y generacionales de participación política y asociacionismo enEspaña desde comienzos de los años ochenta, gracias a los datos de encuesta disponibles.La existencia de información sobre una amplia variedad de formas de participación políticapermite contrastar la evolución de la acción política convencional y no convencional enEspaña. Con ello se obtiene una imagen más clara de hasta qué punto los españolesparticipan ahora más o menos que hace dos décadas.

Develop the first normative database of the thickness of every inner retinal layer in the macular area in a healthy, Caucasian population between 18 to 87 years old, using Spectralis Optical Coherence Tomography (OCT).On this transversal, observational study, 300 patients between 18 to 87 years old and without an ophthalmological condition were recruited. Macular OCT scans were performed on all patients (Spectralis OCT, Heidelberg Engineering). An axial length measurement, and keratometry were performed using an optical biometer. The volume and thickness of the different macular sectors of the inner retinal layers (retinal nerve fiber layer (RNFL), ganglion cells layer (CGL) and inner plexiform layer (IPL)) were analyzed with the Spectralis OCT segmentation software. An eye was randomly selected for each patient.297 patients (179 females and 118 males) were included in the study. The mean age was 56.07 years (range: 40.50-72). The multivariate analysis showed a positive correlation between the RNFL thickness and the axial length (p < 0.001). The mean central retinal thickness was 278.2 μm (range: 266-291), the mean central RNFL thickness was 12.61 μm (range: 11-14), the mean central CGL thickness was 17.63 μm (range: 14-21) and the mean central IPL thickness was 22.02 μm (range: 20-25). The multivariate analysis showed a negative correlation between age and CGL thickness and inner IPL thickness (p< 0.001).This study provides a normative database of the volume of each of the inner retinal layers on a Caucasian population.

La enfermedad hepática inducida por fármacos (DILI) es una condición poco frecuente; sin embargo, explica el 40%-50% de las insuficiencias hepáticas agudas. Su patrón es colestásico en un 20%-40%, causado por la inhibición de los transportadores que regulan la síntesis biliar; esta reducción en la actividad es mediada directa o indirectamente por los medicamentos y sus metabolitos, por polimorfismos genéticos y otros factores de riesgo del paciente. Sus manifestaciones van desde las alteraciones bioquímicas en ausencia de síntomas, hasta la insuficiencia hepática aguda y el daño hepático crónico. Aunque no existe un examen o marcador que indique el diagnóstico absoluto de la enfermedad, se han desarrollado escalas y algoritmos que permiten valorar la probabilidad de DILI colestásica, y otras pruebas que por su complejidad y costo no son de uso rutinario. Por lo anterior, es principalmente un diagnóstico de exclusión basado en evidencia circunstancial. El patrón colestásico de DILI presenta una mejor tasa de supervivencia general pero un mayor riesgo de desarrollo de enfermedad hepática crónica. En la mayoría de los casos, el cuadro del paciente mejora con el retiro del medicamento responsable del daño; la hemodiálisis y el trasplante deben considerarse solo para casos selectos. No se ha probado la eficacia de otras terapias. En este artículo se profundizará en la fisiopatología, la presentación clínica, bioquímica e histopatológica, además del diagnóstico, manejo y pronóstico de este tipo de colestasis.

The fungus Fusarium verticillioides can infect maize ears, causing Fusarium ear rot (FER) and contaminating the grain with fumonisins (FUM), which are harmful to humans and animals. Breeding for resistance to FER and FUM and post-harvest sorting of grain are two strategies for reducing FUM in the food system. Kernel and cob tissues have been previously associated with differential FER and FUM. Four recombinant inbred line families from the maize nested associated mapping population were grown and inoculated with F. verticillioides across four environments, and we evaluated the kernels for external and internal infection severity as well as FUM contamination. We also employed publicly available phenotypes on innate ear morphology to explore genetic relationships between ear architecture and resistance to FER and FUM. The four families revealed wide variation in external symptomatology at the phenotypic level. Kernel bulk density under inoculation was an accurate indicator of FUM levels. Genotypes with lower kernel density—under both inoculated and uninoculated conditions—and larger cobs were more susceptible to infection and FUM contamination. Quantitative trait locus (QTL) intervals could be classified as putatively resistance-specific and putatively shared for ear and resistance traits. Both types of QTL mapped in this study had substantial overlap with previously reported loci for resistance to FER and FUM. Ear morphology may be a component of resistance to F. verticillioides infection and FUM accumulation.

El análisis de los datos de la tercera ola de la Encuesta Social Europea en España y su comparación con los de las dos olas precedentes permiten descubrir los factores que más han incidido en la mejora de los resultados y cuál es el perfil de las personas sobre las que es más rentable concentrar los esfuerzos de localización y de conversión de negativas, siendo las localizaciones y las conversiones las que, en definitiva, han constituido las principales claves del éxito. El trabajo muestra que el aumento de la tasa de respuesta de la tercera ola con respecto de las dos olas precedentes fue debido esencialmente a un mayor y mejor control de los procesos de campo, a un incremento de los incentivos a los entrevistadores y a un mayor esfuerzo de localización y conversión de negativas en horarios fuera de la jornada laboral habitual.

The molecular mechanisms regulating the accuracy of gene expression are still not fully understood. Among these mechanisms, Nonsense-mediated Decay (NMD) is a quality control process that detects post-transcriptionally abnormal transcripts and leads them to degradation. The UPF1 protein lays at the heart of NMD as shown by several structural and functional features reported for this factor mainly for Homo sapiens and Saccharomyces cerevisiae. This process is highly conserved in eukaryotes but functional diversity can be observed in various species. Ustilago maydis is a basidiomycete and the best-known smut, which has become a model to study molecular and cellular eukaryotic mechanisms. In this study, we performed in silico analysis to investigate the structural and biochemical properties of the putative UPF1 homolog in Ustilago maydis. The putative homolog for UPF1 was recognized in the annotated genome for the basidiomycete, exhibiting 66% identity with its human counterpart at the protein level. The known structural and functional domains characteristic of UPF1 homologs were also found. Based on the crystal structures available for UPF1, we constructed different three-dimensional models for umUPF1 in order to analyze the secondary and tertiary structural features of this factor. Using these models, we studied the spatial arrangement of umUPF1 and its capability to interact with UPF2. Moreover, we identified the critical amino acids that mediate the interaction of umUPF1 with UPF2, ATP, RNA and with UPF1 itself. Mutating these amino acids in silico showed an important effect over the native structure. Finally, we performed molecular dynamic simulations for UPF1 proteins from H. sapiens and U. maydis and the results obtained show a similar behavior and physicochemical properties for the protein in both organisms. Overall, our results indicate that the putative UPF1 identified in U. maydis shows a very similar sequence, structural organization, mechanical stability, physicochemical properties and spatial organization in comparison to the NMD factor depicted for Homo sapiens. These observations strongly support the notion that human and fungal UPF1 could perform equivalent biological activities.

Purpose. To evaluate the long-term efficacy and safety of the iStent inject device (Glaukos Corporation, Laguna Hills, CA) combined with phacoemulsification in patients with coexistent cataract and open-angle glaucoma or ocular hypertension (OHT). Methods. A prospective, uncontrolled, nonrandomized, interventional case series study was conducted in patients with both mild or moderate open-angle glaucoma or OHT and cataract. Patients underwent cataract surgery along with the implant of two iStent inject devices. Outcome measures were intraocular pressure (IOP), topical hypotensive medications required, and best-corrected visual acuity (BCVA). Results. 20 patients were enrolled. Mean follow-up was 47.4±18.46 months. Mean baseline IOP was 19.95±3.71 mmHg with medication and 26±3.11 mmHg after washout. Mean end-follow-up IOP was 16.25±1.99 mmHg, representing an IOP decrease of 36.92%, 9.74±3.14 mmHg (P

Dominant glaucoma, a heterogeneous, infrequent and irreversible optic neuropathy, is often associated with elevated intraocular pressure and early-onset. The role of FOXC1 in this type of glaucoma was investigated in twelve Spanish probands via nucleotide variation screening of its proximal promoter and unique exon. Functional evaluations of the identified variants included analyses of the transcriptional activity, protein stability, DNA binding ability and subcellular localization. Four different mutations that were identified in four probands (33.3%) were associated with remarkable phenotypic variability and were functionally classified as either hypermorphic (p.Y47X, p.Q106X and p.G447_G448insDG) or hypomorphic (p.I126S) alleles. To the best of our knowledge, three of the variants are novel (p.Y47X, p.I126S and p.G447_G448insDG) and, in addition, hypermorphic FOXC1 mutations are reported herein for the first time. The presence of an intact N-terminal activation domain in the truncated proteins p.Y47X and p.Q106X may underlie their associated transactivation hyperactivity by a gain-of-function mechanism involving dysregulated protein-protein interactions. Similarly, altered molecular interactions may also lead to increased p.G447_G448insDG activity. In contrast, the partial loss-of-function associated with p.I126S was due to impaired protein stability, DNA binding, protein phosphorylation and subcellular distribution. These results support that moderate and variable FOXC1 transactivation changes are associated with moderate goniodysgenesis, dominant glaucoma and remarkable phenotypic variability.

Objective: To describe the inheritance pattern and clinical variability of primary congenital glaucoma (PCG) in a family with two affected siblings. Materials and Methods: Two sisters diagnosed at birth with bilateral PCG, whose father had bilateral PCG and mother had bilateral microphthalmus, were subjected to a familial genetic study and ophthalmologic follow-up including intraocular pressure (IOP) measurement, and collection of biometric and cup-to-disc ratio data. Results: The inheritance pattern was autosomal recessive in compound heterozygosis. The sisters were found to be carriers of three pathogenic allele variants of the CYP1B1 gene: c.317C>A (p.Ala106Asp) and c.1345delG (p.Asp449MetfsTer8) in one patient (10 years) and c.1345delG (p.Asp449MetfsTer8) and c.202_209delCAGGCGGC (p.Gln68Serfs153Ter) in her older sister (12 years). Surgical histories included: three goniotomies and two Ahmed valves in each eye, and two trabeculectomies and a pupilloplasty in the right eye in the 10-year old; and one goniotomy, trabeculectomy and three Ahmed valves in each eye in the older sister. Currently, both sisters have a controlled intraocular pressure of 18–20 mmHg in both eyes. The father is blind in both eyes and carries two variants c.317C>A (p.Ala106Asp) and c.202_209delCAGGCGGC (p.Gln68Serfs153Ter). The mother with a single variant c.1345delG (p.Asp440MetfsTer8) has a prosthetic right eye and microphthalmus left eye. Conclusions: The sisters were found to show two different allelic CYP1B1 variants (compound heterozygosis) with different repercussions on the clinical severity of PCG. These findings highlight the importance of genetic screening of affected families. [ABSTRACT FROM AUTHOR]

Summary: Diatoms are a highly successful group of phytoplankton, well adapted also to oligotrophic environments and capable of handling nutrient fluctuations in the ocean, particularly nitrate. The presence of a large vacuole is an important trait contributing to their adaptive features. It confers diatoms the ability to accumulate and store nutrients, such as nitrate, when they are abundant outside and then to reallocate them into the cytosol to meet deficiencies, in a process called luxury uptake.The molecular mechanisms that regulate these nitrate fluxes are still not known in diatoms. In this work, we provide new insights into the function of Phaeodactylum tricornutum NPF1, a putative low‐affinity nitrate transporter. To accomplish this, we generated overexpressing strains and CRISPR/Cas9 loss‐of‐function mutants.Microscopy observations confirmed predictions that PtNPF1 is localized on the vacuole membrane. Furthermore, functional characterizations performed on knock‐out mutants revealed a transient growth delay phenotype linked to altered nitrate uptake.Together, these results allowed us to hypothesize that PtNPF1 is presumably involved in modulating intracellular nitrogen fluxes, managing intracellular nutrient availability. This ability might allow diatoms to fine‐tune the assimilation, storage and reallocation of nitrate, conferring them a strong advantage in oligotrophic environments. [ABSTRACT FROM AUTHOR]