Effectiveness and safety of fluocinolone acetonide intravitreal implant in diabetic macular edema patients considered insufficiently responsive to available therapies (REACT): a prospective, non-randomized, and multicenter study.

OBJECTIVE: To assess the effectiveness and safety of the intravitreal fluocinolone-acetonide implant (FAc-i) in patients with chronic diabetic macular edema who did not sufficiently respond to other available therapies. METHODS: This was a multicenter, prospective, non-randomized, and phase-IV observational study conducted on patients with recurrent-DME who were insufficient responders to currently available therapies (REACT-Study). The primary end-point was the mean change in best-corrected-visual-acuity from baseline to month-24 values. RESULTS: Thirty-one eyes from 31 patients were included in the study. Mean age was 68.0 ± 7.7 years, and 10 (32.3%) were women. Study patients had received 5.3 ± 7.3 previous DME treatments before starting the study. In the overall study sample, BCVA improved from 56.1 ± 12.3 letters at baseline to 62.4 ± 17.0 letters at month-24 (p = 0.0510). The eyes with a baseline BCVA < 70 ETDRS letters had a significant improvement in BCVA from 53.2 ± 10.2 letters at baseline to 61.5 ± 17.9 letters at month-24 (p = 0.0165). In the overall study population, central-subfoveal-thickness (CST) was significantly reduced from 474.0 ± 135.1 µm at baseline to 333.4 ± 135.6 at month-24 (p < 0.0001). Similarly, macular-volume (MV) was significantly reduced from 10.7 ± 2.7 mm3 at baseline to 9.6 ± 2.9 mm3 (p = 0.0027) at month-24. Among the 31 study eyes, 19 (61.3%) required an additional treatment for DME. Throughout the study, 9 (29.0%) eyes required ocular hypotensive medication for controlling their intraocular-pressure and 5 (16.1%) eyes underwent cataract surgery. CONCLUSIONS: In DME eyes who did not sufficiently respond to previous therapies, the FAc-i was associated with an improvement in visual and anatomic outcomes. There were no unexpected adverse-events. TRIAL REGISTRATION NUMBER: EudraCT identifier: 2016-001680-37.

Molecular Responses of Red Ripe Tomato Fruit to Copper Deficiency Stress.

Fruit nutritional value, plant growth, and yield can be compromised by deficient copper (Cu) bioavailability, which often appears in arable lands. This condition causes low Cu content and modifications in the ripening-associated processes in tomato fruit. This research studies the transcriptomic changes that occur in red ripe tomato fruit grown under suboptimal Cu conditions to shed light on the molecular mechanisms underlying this stress. Comparative RNA-sequencing and functional analyses revealed that Cu deficiency during cultivation activates signals for metal ion transport, cellular redox homeostasis, pyridoxal phosphate binding, and amino acid metabolism while repressing the response to phosphate starvation in harvested fruit. Transcriptomic analyses highlighted a number of novel Cu stress-responsive genes of unknown function and indicated that Cu homeostasis regulation in tomato fruit may involve additional components than those described in model plants. It also studied the regulation of high-affinity Cu transporters and a number of well-known Cu stress-responsive genes during tomato fruit ripening depending on Cu availability, which allowed potential candidates to be targeted for biotechnological improvements in reproductive tissues. We provide the first study characterizing the molecular responses of fruit to Cu deficiency stress for any fruit crop.

Deficient copper availability on organoleptic and nutritional quality of tomato fruit.

Copper (Cu) is an essential micronutrient for plants because it functions as a redox-active cofactor in vital processes inside the cells. Arable lands are often deficient in micronutrient contents and require the application of enriched fertilisers, whose overuse poses a high risk for human health, the environment and the food safety. Here, we aimed to decipher the effects of Cu deficiency during fruit growth on Cu and other micronutrients contents and on the fruit nutritional value and quality of tomato, the most consumed fruit worldwide, throughout the maturation process. Changes in the contents of important micronutrients for fruit physiology and human health, such as Fe and Mn, occurred in response to Cu deficient growing conditions at different fruit ripening stages, while lower Cu levels were detected in those fruit along the whole maturation process. Cu deficiency delayed changes in lycopene content and fruit colour, but increased acidity, and advanced the rise in antioxidant capacity and vitamin C content during fruit colour change from green to light red in the Moneymaker tomato; although this time lag eventually caught up in the most mature fruit stage. Cu deficiency also increased total phenolic and flavonoid contents only in green fruit.

The Role of ABA in the Interaction between Citrus Fruit and Penicillium digitatum.

Abscisic acid (ABA) protects citrus fruit against Penicillium digitatum infection. The global mechanisms involved in the role of ABA in the P. digitatum-citrus fruit interaction are unknown. Here, we determine the transcriptome differences between the Navelate (Citrus sinensis (L.) Osbeck) orange and its ABA-deficient mutant Pinalate, which is less resistant to infection. Low ABA levels may affect both the constitutive mechanisms that protect citrus fruit against P. digitatum and early responses to infection. The repression of terpenoid, phenylpropanoid and glutation metabolism; of oxidation-reduction processes; and of processes related to the defense response to fungus and plant hormone signal transduction may be one part of the constitutive defense reduced in the mutant against P. digitatum. Our results also provide potential targets for developing P. digitatum-citrus fruit-resistant varieties. Of those up-regulated by ABA, a thaumatin protein and a bifunctional inhibitor/LTP, which are relevant in plant immunity, were particularly remarkable. It is also worth highlighting chlorophyllase 1 (CLH1), induced by infection in Pinalate, and the OXS3 gene, which was down-regulated by ABA, because the absence of OXS3 activates ABA-responsive genes in plants.

Ethylene-driven changes in epicuticular wax metabolism in citrus fruit.

Epicuticular waxes are important natural compounds that influence cuticle properties and can protect fruit from factors that harm its external quality. We demonstrated that, at a dose that reduces postharvest citrus fruit quality loss (4 d 2 µL L-1), ethylene redirected epicuticular wax metabolism towards the synthesis of primary alcohols, mostly behenyl alcohol, by favouring the acyl-reduction pathway. This treatment also reduced the synthesis of terpenoids by redirecting the mevalonate pathway towards farnesol accumulation to the detriment of the accumulation of most triterpenoids, but not of their precursor squalene. Moreover, the 4 d ethylene treatment sharply increased the synthesis of docosane and lignoceric acid and lowered that of cerotic acid. Longer ethylene exposure (8 d) reversed some of these effects by lowering the contents of most alcohols, lignoceric acid and squalene, while increasing that of its derivative sitosterol. The 8 d ethylene treatment also increased farnesol and docosane contents.

Relative humidity regimes modify epicuticular wax metabolism and fruit properties during Navelate orange conservation in an ABA-dependent manner.

Relative humidity (RH) during conservation and the chemical composition of epicuticular wax layer are factors that determine fruit quality and weight loss. This study investigates the influence of RH on the epicuticular wax metabolism during citrus fruit storage, and how it is affected by abscisic acid (ABA). Low RH conditions increased alcohols and fatty acids abundance, mainly due to accumulation of docosanol and lignoceric and cerotic acids. Low RH also decreased terpenoids and nonacosane and hentriacontane contents, the most abundant alkanes. Consequently, the alkane/terpenoid ratio was decreased concomitantly with fruit weight loss and cuticle permeability increments. ABA treatment differently mediated wax compositional changes at high or low RH. At low RH, ABA attenuated the increase in fatty acids and enhanced the decrease in alcohols and the accumulation of terpenoids, mainly affecting lignoceric and cerotic acids, docosanol, α-amyrin, sitosterol, friedelin and friedelanone contents. These trends were inversed under high RH conditions.

The Combination of Abscisic Acid (ABA) and Water Stress Regulates the Epicuticular Wax Metabolism and Cuticle Properties of Detached Citrus Fruit.

The phytohormone abscisic acid (ABA) is a major regulator of fruit response to water stress, and may influence cuticle properties and wax layer composition during fruit ripening. This study investigates the effects of ABA on epicuticular wax metabolism regulation in a citrus fruit cultivar with low ABA levels, called Pinalate (Citrus sinensis L. Osbeck), and how this relationship is influenced by water stress after detachment. Harvested ABA-treated fruit were exposed to water stress by storing them at low (30-35%) relative humidity. The total epicuticular wax load rose after fruit detachment, which ABA application decreased earlier and more markedly during fruit-dehydrating storage. ABA treatment changed the abundance of the separated wax fractions and the contents of most individual components, which reveals dependence on the exposure to postharvest water stress and different trends depending on storage duration. A correlation analysis supported these responses, which mostly fitted the expression patterns of the key genes involved in wax biosynthesis and transport. A cluster analysis indicated that storage duration is an important factor for the exogenous ABA influence and the postharvest environment on epicuticular wax composition, cuticle properties and fruit physiology. Dynamic ABA-mediated reconfiguration of wax metabolism is influenced by fruit exposure to water stress conditions.

Identification and molecular characterization of the high-affinity copper transporters family in Solanum lycopersicum.

Copper (Cu) plays a key role as cofactor in the plant proteins participating in essential cellular processes, such as electron transport and free radical scavenging. Despite high-affinity Cu transporters (COPTs) being key participants in Cu homeostasis maintenance, very little is known about COPTs in tomato (Solanum lycopersicum) even though it is the most consumed fruit worldwide and this crop is susceptible to suboptimal Cu conditions. In this study, a six-member family of COPT (SlCOPT1-6) was identified and characterized. SlCOPTs have a conserved architecture consisting of three transmembrane domains and ß-strains. However, the presence of essential methionine residues, a methionine-enriched amino-terminal region, an Mx3Mx12Gx3G Cu-binding motif and a cysteine rich carboxy-terminal region, all required for their functionality, is more variable among members. Accordingly, functional complementation assays in yeast indicate that SlCOPT1 and SlCOPT2 are able to transport Cu inside the cell, while SlCOPT3 and SlCOPT5 are only partially functional. In addition, protein interaction network analyses reveal the connection between SlCOPTs and Cu PIB-type ATPases, other metal transporters, and proteins related to the peroxisome. Gene expression analyses uncover organ-dependency, fruit vasculature tissue specialization and ripening-dependent gene expression profiles, as well as different response to Cu deficiency or toxicity in an organ-dependent manner.

Differential Transcriptomic Regulation in Sweet Orange Fruit (Citrus sinensis L. Osbeck) Following Dehydration and Rehydration Conditions Leading to Peel Damage.

Water stress is the most important environmental agent that contributes to the crop productivity and quality losses globally. In citrus, water stress is the main driver of the fruit peel disorders that impact the quality and market ability. An increasingly present post-harvest peel disorder is non-chilling peel pitting (NCPP). Non-chilling peel pitting is manifested as collapsed areas of flavedo randomly scattered on the fruit and its incidence increases due to abrupt increases in the environmental relative humidity (RH) during post-harvest fruit manipulation. In this study, we have used a custom-made cDNA microarray containing 44k unigenes from Citrus sinensis (L. Osbeck), covering for the first time the whole genome from this species, to study transcriptomic responses of mature citrus fruit to water stress. In the study, the global gene expression profiles of flavedo from Navelate oranges subjected to severe water stress are compared with those fruits subjected to rehydration stress provoked by changes in the RH during post-harvest, which enhances the development of NCPP. The study results show that NCPP is a complex physiological process that shares molecular responses with those from prolonged dehydration in fruit, but the damage associated with NCPP may be explained by unique features of rehydration stress at the molecular level, such as membrane disorganization, cell wall modification, and proteolysis.

Albedo- and Flavedo-Specific Transcriptome Profiling Related to Penicillium digitatum Infection in Citrus Fruit.

Penicillium digitatum is the main postharvest pathogen of citrus fruit. Although the inner fruit peel part (albedo) is less resistant than the outer part (flavedo) to P. digitatum, the global mechanisms involved in their different susceptibility remain unknown. Here, we examine transcriptome differences between both tissues at fruit harvest and in their early responses to infection. At harvest, not only was secondary metabolism, involving phenylpropanoids, waxes, and terpenoids, generally induced in flavedo vs. albedo, but also energy metabolism, transcription factors (TFs), and biotic stress-related hormones and proteins too. Flavedo-specific induced responses to infection might be regulated in part by ERF1 TF, and are related to structural plant cell wall reinforcement. Other induced responses may be related to H2O2, the synthesis of phenylpropanoids, and the stress-related proteins required to maintain basal defense responses against virulent pathogens, whereas P. digitatum represses some hydrolase-encoding genes that play different functions and auxin-responsive genes in this peel tissue. In infected albedo, the repression of transport and signal transduction prevail, as does the induction of not only the processes related to the synthesis of flavonoids, indole glucosinolates, cutin, and oxylipins, but also the specific genes that elicit plant immunity against pathogens.

Antioxidant Activity and Neuroprotective Role of Docosahexaenoic Acid (DHA) Supplementation in Eye Diseases That Can Lead to Blindness: A Narrative Review.

The objective of this narrative review is to provide updated evidence, based on data from experimental and clinical studies, of the prominent role of omega-3 polyunsaturated fatty acids (n-3 PUFAs) for a number of crucial mechanisms involved in counteracting cell damage induced by oxidative stress in eye diseases. This article is focused on the antioxidant and neuroprotective effects of docosahexaenoic acid (DHA), which have been assessed in different experimental models and clinical studies, particularly in proliferative diabetic retinopathy, age-related macular degeneration and glaucoma that are the most common eye diseases leading to severe vision loss. The mechanisms involved in the role of DHA in protecting human retinal pigment epithelial cells from oxidative stress as well as the interaction with glutathione (GSH) are also described. The review is intended to provide novel and salient findings supporting the rationale of the use of dietary supplementation with high-dose DHA (1050 mg/day) in the form of triglyceride as a potent antioxidant compound for improving the eye health. However, the overall clinical evidence for the use of dietary strategies based on supplementation with n-3 PUFAs in eye diseases linked to oxidative stress other than high-dose DHA triglyceride is both limited and inconsistent.

Coordinated activation of the metabolic pathways induced by LED blue light in citrus fruit.

The biochemical changes induced by LED Blue Light (LBL) (450 nm) in Lane Late oranges were investigated. The selected quantum flux (60 µmol m-2 s-1, 2 days) was associated with resistance against Penicillium digitatum, the main postharvest pathogen of citrus fruit. A holistic overview was obtained by a comparative transcriptome profile analysis, which revealed that LBL favored energy metabolism and redirected metabolic pathways toward the synthesis of diverse primary and secondary metabolism products. LBL favored reactive oxygen species homeostasis and metabolic activities involving lipid metabolism, specifically the synthesis of pigments and oxylipins, and the metabolism of carbohydrates, amino acids and indol- and alkaloid-derivatives. LBL also repressed limonene catabolism and triggered phenylpropanoid derivatives-related changes, which increased content in total flavonoids. Transferring fruit from LBL to darkness favored those processes involving amino acids, different phenylpropanoid, alkaloid and terpenoid classes, and ferrochelatase activity.

Abscisic Acid Deficiency Alters Epicuticular Wax Metabolism and Morphology That Leads to Increased Cuticle Permeability During Sweet Orange (Citrus sinensis) Fruit Ripening.

Citrus fruit ripening is coupled with the synthesis and deposition of epicuticular waxes, which reduces water loss during fruit postharvest storage. Although abscisic acid (ABA) is a major regulator of citrus fruit ripening, whether ABA mediates epicuticular wax formation during this process remains poorly understood. We investigated the implication of ABA in cuticle properties and epicuticular wax metabolism, composition, and morphology by comparing the Navelate orange [Citrus sinensis (L.) Osbeck] and its ABA biosynthesis-impaired mutant Pinalate in four ripening stages. ABA deficiency had minor effects on cuticle thickness and epicuticular wax load, but correlated with cuticle permeability. ABA content aligned with mostly fatty acids accumulation in both cultivars, and also with specific alkane, terpenoid, and aldehyde constituents in the parental fruit. In turn, cuticle permeability correlated with the fatty acid profile during fruit ripening in the Navelate and Pinalate, and with primary alcohols, terpenoids, and aldehydes, but only in the mutant fruit. Low ABA levels increased the susceptibility of waxes to crack and were lost from the epicuticular layer. The RNA-seq analysis highlighted the differential regulation of a list of 87 cuticle-related genes between genotypes and ripening stages. Changes in the gene expression of the selected genes in both cultivars were consistent with the content of the aliphatics and terpenoid fractions during ripening. The results suggest a role for ABA in the regulation of fatty acid content and primary alcohol composition, and point out the importance of alkane and triterpenoid for controlling water permeance through fruit cuticles.

Design and tests of prospective property predictions for novel antimalarial 2-aminopropylaminoquinolones.

There is a pressing need to improve the efficiency of drug development, and nowhere is that need more clear than in the case of neglected diseases like malaria. The peculiarities of pyrimidine metabolism in Plasmodium species make inhibition of dihydroorotate dehydrogenase (DHODH) an attractive target for antimalarial drug design. By applying a pair of complementary quantitative structure-activity relationships derived for inhibition of a truncated, soluble form of the enzyme from Plasmodium falciparum (s-PfDHODH) to data from a large-scale phenotypic screen against cultured parasites, we were able to identify a class of antimalarial leads that inhibit the enzyme and abolish parasite growth in blood culture. Novel analogs extending that class were designed and synthesized with a goal of improving potency as well as the general pharmacokinetic and toxicological profiles. Their synthesis also represented an opportunity to prospectively validate our in silico property predictions. The seven analogs synthesized exhibited physicochemical properties in good agreement with prediction, and five of them were more active against P. falciparum growing in blood culture than any of the compounds in the published lead series. The particular analogs prepared did not inhibit s-PfDHODH in vitro, but advanced biological assays indicated that other examples from the class did inhibit intact PfDHODH bound to the mitochondrial membrane. The new analogs, however, killed the parasites by acting through some other, unidentified mechanism 24-48 h before PfDHODH inhibition would be expected to do so.

Insights into the regulation of molecular mechanisms involved in energy shortage in detached citrus fruit.

Harvested fruit undergo carbon and energy deprivation. However, the events underlying this energy-related stress in detached fruit and their involvement in cell damage have not yet been elucidated. We showed that supplementing detached sweet oranges with additional carbon or energy sources reduced peel damage, while inhibitors of energy metabolism increased it. We investigated the effect of an exogenous source of carbon (glycerol), energy (ATP), and an inhibitor of energy metabolism 2-deoxy-D-glucose (DeOGlc) + sodium iodoacetate (IAc), on the transcriptome of harvested fruit flavedo (outer peel part). ATP and Gly induced common, but also specific, alternative modes of energy metabolism by reducing the stress caused by energy shortage. They also induced shifts in energy metabolism that led to the production of the intermediates required for plant defense secondary metabolites to form. ATP and Gly triggered changes in the expression of the genes involved in cell lesion containment through a defined pathway involving hormones and redox-mediated signaling. DeOGlc + IAc had a contrasting effect on some of these mechanisms. These chemicals altered the biological processes related to membrane integrity and molecular mechanisms involving reactive oxygen species (ROS) production, and lipid and protein degradation.

A sweet orange mutant impaired in carotenoid biosynthesis and reduced ABA levels results in altered molecular responses along peel ripening.

Citrus fruit ripening is a complex process involving biochemical, physiological and molecular events that differ between the flesh and the peel of the fruit. We characterized sweet orange peel maturation by means of a comparative transcriptomic analysis between Navelate orange (Citrus sinensis L. Osbeck) and its mutant fruit Pinalate, which presents a severe blockage at early steps of the carotenoid biosynthetic pathway and consequently reduced ABA levels. Peel ripening involved the decrease of the photosynthetic activity and the transmembrane transport processes, as well as the buildup of starch and cuticular waxes and the cell wall modification. In addition, a number of biotic and abiotic stress responses, including the defense response, and the response to blue light, water deprivation and abscisic acid stimulus were modulated in a ripening-stage specific manner. The regulation of energy-related processes and secondary metabolism pathways was attenuated in Pinalate, while the molecular mechanisms underlying stress responses displayed dependency on ABA levels. These results indicate that ABA is a key signal inducing stress responses along orange peel ripening, which might determine the fruit postharvest performance.

THREE-YEAR OUTCOMES IN A RANDOMIZED SINGLE-BLIND CONTROLLED TRIAL OF INTRAVITREAL RANIBIZUMAB AND ORAL SUPPLEMENTATION WITH DOCOSAHEXAENOIC ACID AND ANTIOXIDANTS FOR DIABETIC MACULAR EDEMA.

PURPOSE: To report 3-year results of a randomized single-blind controlled trial of intravitreal ranibizumab combined with oral docosahexaenoic acid (DHA) supplementation versus ranibizumab alone in patients with diabetic macular edema. METHODS: There were 26 patients (31 eyes) in the DHA group and 29 (38 eyes) in the control group. Ranibizumab (0.5 mg) was administered monthly for the first 4 months followed by a pro re nata (PRN) regimen. In the experimental group, patients received oral DHA supplementation (1,050 mg/day) (Brudyretina 1.5 g). RESULTS: At 36 months, mean decrease of central subfield macular thickness was higher in the DHA-supplementation group than in controls (275 ± 50 µm vs. 310 ± 97 µm) with significant differences at Months 25, 30, 33, and 34. Between-group differences in best-corrected visual acuity were not found, but the percentages of ETRDS gains >5 and >10 letters were higher in the DHA-supplementation group. Differences serum HbA1c, plasma total antioxidant capacity values, erythrocyte DHA content, and serum IL-6 levels were all significant in favor of the DHA-supplementation group. CONCLUSION: The addition of a high-rich DHA dietary supplement to intravitreal ranibizumab was effective to achieve better sustained improvement of central subfield macular thickness outcomes after 3 years of follow-up as compared with intravitreal ranibizumab alone.

Remisión espontánea a largo plazo de la forma congénita de la taquicardia ectópica de la unión / Long-term Spontaneous Remission of Congenital Junctional Ectopic Tachycardia

RESUMEN Introducción: La forma congénita de la taquicardia ectópica de la unión (junctional ectopic tachycardia, JET) es una taquicardia supraventricular poco común, con alta morbimortalidad. Su tratamiento requiere, frecuentemente, el uso de múltiples fármacos durante períodos prolongados. En algunos casos se necesita, además, realizar un procedimiento invasivo, como la crioablación. Algunos estudios han demostrados la existencia de casos de remisión espontánea de la arritmia a largo plazo (con la reversión a ritmo sinusal o a un ritmo nodal acelerado), sin requerimiento de fármacos y sin mediar intervención alguna. Objetivos: Evaluar la incidencia de remisión espontanea de la JET congénita en una población pediátrica en el seguimiento a largo plazo. Material y métodos: Se incluyeron 23 pacientes consecutivos con JET congénita evaluados en el Hospital J.P. Garrahan y en el Hospital Italiano de Buenos Aires, entre los años 1999 y 2017, con un seguimiento medio de 8,8 años (rango intercuartil, RIC: 5,5-14,1). Se evaluó a largo plazo la incidencia de remisión espontánea de la arritmia. Resultados: La mediana para la edad de presentación fue 2 meses (RIC: 0,625-3); 15 pacientes (62,5%) presentaron signos de insuficiencia cardíaca y 11 pacientes (45,8%), taquicardiomiopatía. A 2 pacientes se les realizó una crioablación en forma exitosa. La tasa de remisión espontánea fue del 52%. En aquellos pacientes con un seguimiento mayor a 10 años (15 sujetos), la remisión fue del 62,5%. La media para edad de remisión fue 9,6 años. Conclusiones: La JET congénita es una taquicardia potencialmente grave en los primeros meses de vida, pero con alta tasa de remisión espontánea a largo plazo.

ABSTRACT Background: The congenital form of junctional ectopic tachycardia (JET) is a rare supraventricular tachycardia with high morbidity and mortality. Its treatment frequently requires the prolonged use of multiple drugs and, in some cases, an inva-sive procedure, such as cryoablation, is necessary. Some studies have demonstrated the existence of spontaneous remission of arrhythmia in the long term (with reversal to sinus rhythm or to an accelerated nodal rhythm), without need of drugs or any other form of intervention. Objectives: The aim of this study was to evaluate the long-term incidence of spontaneous remission of congenital JET in a pediatric population. Methods: Twenty-three consecutive patients with congenital JET were evaluated at Hospital J.P. Garrahan and Hospital Italiano de Buenos Aires, between 1999 and 2017, with a mean follow-up of 8.8 years interquartile range (IQR): 5.5-14.1). The incidence of spontaneous arrhythmia remission was evaluated in the long term. Results: Median presentation age was 2 months (IQR: 0.625-3); 15 patients (62.5%) presented signs of heart failure and 11 patients (45.8%) tachycardiomyopathy. Two patients underwent successful cryoablation. The spontaneous remission rate was 52%. In patients with follow-up above 10 years (15 subjects), remission was 62.5%. Mean remission age was 9.6 years. Conclusions: Congenital JET is a potentially severe tachycardia in the first months of life, but with a high rate of long-term spontaneous remission.

A Dynamic Chemical Network for Cystinuria Diagnosis.

The study of molecular networks represents a conceptual revolution in chemistry. Building on previous knowledge and after understanding the rules of non-covalent interactions, the design of stimulus-responsive chemical systems is possible. Herein we report a new strategy, based on the reorganization of a dynamic chemical network that generates new fluorescent associations in the presence of cysteine or cystine. The binding and sensing units are encoded in the components that dynamically assemble and disassemble responding to external stimuli as a successful tool to detect both cysteine and cystine in aqueous media. Moreover, the dynamic sensing system works in human urine, as a prospective application for cystinuria diagnosis.

Light-emitting Diode Blue Light Alters the Ability of Penicillium digitatum to Infect Citrus Fruits.

Penicillium digitatum (Pers.:Fr.) Sacc. is the main fungus causing postharvest losses in citrus fruits. Previous work showed the potential of LED blue light (LBL) in controlling P. digitatum growth. Here, we have investigated whether LBL alters the ability of this fungus to infect citrus fruits. Before fruit infection, Petri plates inoculated with the same conidia concentration were held under darkness (control) or LBL (100 µmol m-2 s-1 ) for 8 d (continuous light), or were treated with the same LBL for 3 d and then shifted to darkness for 5 d (non-continuous light). Spores from cultures exposed to continuous light showed very low capacity to germinate (1.8% respect to control) but a high viability and a similar morphology and ability to infect the fruits than spores from control cultures. The number of spores produced in plates exposed to non-continuous light was slightly lower than in control plates, but they showed much lower viability and lower capacity to infect the fruits. This effect was more likely related to aberrant morphology of spores, which formed aggregates, than to its metabolic activity or its ability to produce ethylene that might contribute to destroy natural defense barriers from the fruit.