Perfectionism and Emotional Intelligence: A Person-Centered Approach.

This study examined the relationship between perfectionistic concerns (PC) and perfectionistic strivings (PS) with the subcomponents of emotional intelligence (EI) through a latent class person-centered approach. A sample of 1582 Ecuadorian adolescents (619 females) aged from 12 to 18 was employed. The trait meta-mood scale-24 (TMMS-24) and the child and adolescent perfectionism scale (CAPS) were used, respectively, for assessing three subcomponents of EI (i.e., emotional attention, emotional clarity, and mood repair) and two perfectionist dimensions (PC and PS). A three-class solution (High perfectionism, moderate perfectionism, and nonperfectionism) was identified by using latent class analysis. High perfectionism significantly scored higher on emotional attention in comparison with the moderate and nonperfectionism classes, with small and moderate effect sizes. Overall, results suggest that people with high perfectionism might be at greater risk of developing maladaptive emotional self-regulation strategies, such as rumination, because of their tendency to excessively attend their negative mood states.

Factor Invariance of the Trait Meta-Mood Scale-24 in a Sample of Chilean Adolescents.

The purpose of this study is to adapt the Trait Meta-Mood Scale-24 (TMMS-24; Fernández-Berrocal, Extremera, & Ramos, 2004, Spanish short version of the TMMS, Salovey, Mayer, Goldman, Turvey, & Palfai, 1995) to the Chilean adolescent population (13-17 years), analyzing the psychometric properties of the instrument through confirmatory factor analyses, factor invariance analysis, and latent mean differences. For this purpose, a sample of 3,255 secondary and high school students, between 12 and 18 years old (M = 15.28, SD = 1.24), were recruited. The results confirm the measurement invariance and structure of TMMS-24 scores by sex and age. The results of the latent mean analysis show the existence of significant differences associated with sex and age in the TMMS-24 attention to feelings factor. The adequate psychometric properties of the TMMS-24 show that it is valid for the Chilean adolescent population, thus covering the existing gap in this context.

Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis.

Small interfering ribonucleic acid (siRNA) has the potential to revolutionize therapeutics since it can knockdown very efficiently the target protein. It is starting to be widely used to interfere with cell infection by HIV. However, naked siRNAs are unable to get into the cell, requiring the use of carriers to protect them from degradation and transporting them across the cell membrane. There is no information about which is the most efficient endocytosis route for high siRNA transfection efficiency. One of the most promising carriers to efficiently deliver siRNA are cyclodextrin derivatives. We have used nanocomplexes composed of siRNA and a ß-cyclodextrin derivative, AMC6, with a very high transfection efficiency to selectively knockdown clathrin heavy chain, caveolin 1, and p21 Activated Kinase 1 to specifically block clathrin-mediated, caveolin-mediated and macropinocytosis endocytic pathways. The main objective was to identify whether there is a preferential endocytic pathway associated with high siRNA transfection efficiency. We have found that macropinocytosis is the preferential entry pathway for the nanoparticle and its associated siRNA cargo. However, blockade of macropinocytosis does not affect AMC6-mediated transfection efficiency, suggesting that macropinocytosis blockade can be functionally compensated by an increase in clathrin- and caveolin-mediated endocytosis.

Potent Glycosidase Inhibition with Heterovalent Fullerenes: Unveiling the Binding Modes Triggering Multivalent Inhibition.

Glycosidases are key enzymes in metabolism, pathogenic/antipathogenic mechanisms and normal cellular functions. Recently, a novel approach for glycosidase inhibition that conveys multivalent glycomimetic conjugates has emerged. Many questions regarding the mechanism(s) of multivalent enzyme inhibition remain unanswered. Herein we report the synthesis of a collection of novel homo- and heterovalent glyco(mimetic)-fullerenes purposely conceived for probing the contribution of non-catalytic pockets in glysosidases to the multivalent inhibitory effect. Their affinities towards selected glycosidases were compared with data from homovalent fullerene conjugates. An original competitive glycosidase-lectin binding assay demonstrated that the multivalent derivatives and the substrate compete for low affinity non-glycone binding sites of the enzyme, leading to inhibition by a "recognition and blockage" mechanism. Most notably, this work provides evidence for enzyme inhibition by multivalent glycosystems, which will likely have a strong impact in the glycosciences given the utmost relevance of multivalency in Nature.

Prochlorococcus can use the Pro1404 transporter to take up glucose at nanomolar concentrations in the Atlantic Ocean.

Prochlorococcus is responsible for a significant part of CO2 fixation in the ocean. Although it was long considered an autotrophic cyanobacterium, the uptake of organic compounds has been reported, assuming they were sources of limited biogenic elements. We have shown in laboratory experiments that Prochlorococcus can take up glucose. However, the mechanisms of glucose uptake and its occurrence in the ocean have not been shown. Here, we report that the gene Pro1404 confers capability for glucose uptake in Prochlorococcus marinus SS120. We used a cyanobacterium unable to take up glucose to engineer strains that express the Pro1404 gene. These recombinant strains were capable of specific glucose uptake over a wide range of glucose concentrations, showing multiphasic transport kinetics. The Ks constant of the high affinity phase was in the nanomolar range, consistent with the average concentration of glucose in the ocean. Furthermore, we were able to observe glucose uptake by Prochlorococcus in the central Atlantic Ocean, where glucose concentrations were 0.5-2.7 nM. Our results suggest that Prochlorococcus are primary producers capable of tuning their metabolism to energetically benefit from environmental conditions, taking up not only organic compounds with key limiting elements in the ocean, but also molecules devoid of such elements, like glucose.

Neuronopathic Gaucher's disease: induced pluripotent stem cells for disease modelling and testing chaperone activity of small compounds.

Gaucher's disease (GD) is caused by mutations in the GBA1 gene, which encodes acid-ß-glucosidase, an enzyme involved in the degradation of complex sphingolipids. While the non-neuronopathic aspects of the disease can be treated with enzyme replacement therapy (ERT), the early-onset neuronopathic form currently lacks therapeutic options and is lethal. We have developed an induced pluripotent stem cell (iPSc) model of neuronopathic GD. Dermal fibroblasts of a patient with a P.[LEU444PRO];[GLY202ARG] genotype were transfected with a loxP-flanked polycistronic reprogramming cassette consisting of Oct4, Sox2, Klf4 and c-Myc and iPSc lines derived. A non-integrative lentiviral vector expressing Cre recombinase was used to eliminate the reprogramming cassette from the reprogrammed cells. Our GD iPSc express pluripotent markers, differentiate into the three germ layers, form teratomas, have a normal karyotype and show the same mutations and low acid-ß-glucosidase activity as the original fibroblasts they were derived from. We have differentiated them efficiently into neurons and also into macrophages without observing deleterious effects of the mutations on the differentiation process. Using our system as a platform to test chemical compounds capable of increasing acid-ß-glucosidase activity, we confirm that two nojirimycin analogues can rescue protein levels and enzyme activity in the cells affected by the disease.

pH-Responsive Pharmacological Chaperones for Rescuing Mutant Glycosidases.

A general approach is reported for the design of small-molecule competitive inhibitors of lysosomal glycosidases programmed to 1) promote correct folding of mutant enzymes at the endoplasmic reticulum, 2) facilitate trafficking, and 3) undergo dissociation and self-inactivation at the lysosome. The strategy is based on the incorporation of an orthoester segment into iminosugar conjugates to switch the nature of the aglycone moiety from hydrophobic to hydrophilic in the pH 7 to pH 5 window, which has a dramatic effect on the enzyme binding affinity. As a proof of concept, new highly pH-responsive glycomimetics targeting human glucocerebrosidase or α-galactosidase with strong potential as pharmacological chaperones for Gaucher or Fabry disease, respectively, were developed.

Mixotrophy in cyanobacteria.

Cyanobacteria evolved the oxygenic photosynthesis to generate organic matter from CO2 and sunlight, and they were responsible for the production of oxygen in the Earth's atmosphere. This made them a model for photosynthetic organisms, since they are easier to study than higher plants. Early studies suggested that only a minority among cyanobacteria might assimilate organic compounds, being considered mostly autotrophic for decades. However, compelling evidence from marine and freshwater cyanobacteria, including toxic strains, in the laboratory and in the field, has been obtained in the last decades: by using physiological and omics approaches, mixotrophy has been found to be a more widespread feature than initially believed. Furthermore, dominant clades of marine cyanobacteria can take up organic compounds, and mixotrophy is critical for their survival in deep waters with very low light. Hence, mixotrophy seems to be an essential trait in the metabolism of most cyanobacteria, which can be exploited for biotechnological purposes.

Direct interaction between marine cyanobacteria mediated by nanotubes.

Microbial associations and interactions drive and regulate nutrient fluxes in the ocean. However, physical contact between cells of marine cyanobacteria has not been studied thus far. Here, we show a mechanism of direct interaction between the marine cyanobacteria Prochlorococcus and Synechococcus, the intercellular membrane nanotubes. We present evidence of inter- and intra-genus exchange of cytoplasmic material between neighboring and distant cells of cyanobacteria mediated by nanotubes. We visualized and measured these structures in xenic and axenic cultures and in natural samples. We show that nanotubes are produced between living cells, suggesting that this is a relevant system of exchange material in vivo. The discovery of nanotubes acting as exchange bridges in the most abundant photosynthetic organisms in the ocean may have important implications for their interactions with other organisms and their population dynamics.

Probing the nature of the cluster effect observed with synthetic multivalent galactosides and peanut agglutinin lectin.

We designed a set of multi-galactosides with valencies ranging from one to seven and different spacer-arm lengths. The compounds display a high structural homology for a strict assessment of multivalent phenomena. The multimers were first evaluated by an enzyme-linked lectin assay (ELLA) toward the peanut agglutinin (PNA). The binding affinity was shown to be dependent on the spacer-arm length, and cluster effects were observed for the galactosides bearing the shortest and the longest linkers. The latter compounds were shown to be much more potent PNA cross-linkers in a "sandwich assay". Dynamic light scattering (DLS) experiments also revealed the formation of soluble aggregates between heptavalent derivatives with medium or long linkers and the labeled PNA. ELLA experiments performed with valency-controlled clusters and labeled lectins are therefore not always devoid from aggregative processes. The precise nature of the multivalent interaction observed by ELLA for the compounds bearing the shortest linkers, which are unable to form PNA aggregates, was further investigated by atomic force microscopy (AFM). The galactosides were grafted onto the tip of a cantilever and the PNA lectin onto a gold surface. Similar unbinding forces were registered when the valency of the ligands was increased, thus showing that the multimers cannot interact more strongly with PNA. Multiple binding events to the PNA were also never observed, thus confirming that a chelate binding mode does not operate with the multivalent galactosides, probably because the linkers are too short. Altogether, these results suggest that the cluster effect that operates in ELLA with the multimers is not related to additional PNA stabilizations and can be ascribed to local concentration effects that favor a dynamic turnover of the tethered galactosides in the PNA binding sites.

Integrated Proteomic and Metabolomic Analyses Show Differential Effects of Glucose Availability in Marine Synechococcus and Prochlorococcus.

We compared changes induced by the addition of 100 nM and 5 mM glucose on the proteome and metabolome complements in Synechococcus sp. strains WH8102, WH7803, and BL107 and Prochlorococcus sp. strains MED4, SS120, and MIT9313, grown either under standard light conditions or in darkness. Our results suggested that glucose is metabolized by these cyanobacteria, using primarily the oxidative pentoses and Calvin pathways, while no proof was found for the involvement of the Entner-Doudoroff pathway in this process. We observed differences in the effects of glucose availability, both between genera and between Prochlorococcus MED4 and SS120 strains, which might be related to their specific adaptations to the environment. We found evidence for fermentation in Prochlorococcus sp. strain SS120 and Synechococcus sp. strain WH8102 after 5 mM glucose addition. Our results additionally suggested that marine cyanobacteria can detect nanomolar glucose concentrations in the environment and that glucose might be used to sustain metabolism under darkness. Furthermore, the KaiB and KaiC proteins were also affected in Synechococcus sp. WH8102, pointing to a direct link between glucose assimilation and circadian rhythms in marine cyanobacteria. In conclusion, our study provides a wide overview on the metabolic effects induced by glucose availability in representative strains of the diverse marine picocyanobacteria, providing further evidence for the importance of mixotrophy in marine picocyanobacteria. IMPORTANCE Glucose uptake by marine picocyanobacteria has been previously described and strongly suggests they are mixotrophic organisms (capable of using energy from the sun to make organic matter, but also to directly use organic matter from the environment when available). However, a detailed analysis of the effects of glucose addition on the proteome and metabolome of these microorganisms had not been carried out. Here, we analyzed three Prochlorococcus sp. and three Synechococcus sp. strains which were representative of several marine picocyanobacterial clades. We observed differential features in the effects of glucose availability, depending on both the genus and strain; our study illuminated the strategies utilized by these organisms to metabolize glucose and showed unexpected links to other pathways, such as circadian regulation. Furthermore, we found glucose addition had profound effects in the microbiome, favoring the growth of coexisting heterotrophic bacteria.

Profiles of Perfectionistic Automatic Thoughts and Aggression.

In recent years, the study of perfectionistic automatic thoughts (PAT) has increased given its maladaptive nature since it is link to numerous psychological disorders. From our knowledge, no previous research has addressed the relationship between PAT and the four components of aggressive behavior (anger, hostility, verbal aggression, and physical aggression). This study had a double goal. The first aim was to identify distinct profiles of PAT in a sample of 3060 Ecuadorian undergraduates (Mage = 22.7, SD = 2.46). The second aim of this study was to determine whether or not statistically significant differences exist between these profiles, based on the four components of aggressive behavior. The Perfectionism Cognitions Inventory (PCI) and the Aggression Questionnaire (AQ) were used. Five profiles with different intensities in the dimensions of perfectionistic automatic thoughts were identified by Latent Class Analysis ((1) No-Perfectionistic Automatic Thoughts, (2) Low Perfectionistic Automatic Thoughts, (3) High Perfectionistic Demands, (4) Moderate Perfectionistic Automatic Thoughts, and (5) High Perfectionistic Automatic Thoughts). The moderate and high perfectionistic automatic thoughts profiles obtained the highest mean scores for all components of aggressive behavior (i.e., the four factors that make up AQ: Physical Aggression, Verbal Aggression, Anger, and Hostility), while the No-perfectionistic automatic thoughts and Low perfectionistic automatic thoughts profiles had the lowest mean scores. These results provide new knowledge about the prevalence of PAT in the context of Ecuador. Also, they suggest further research on the topic given the positive relationship of PAT and aggressive behavior.

Emotional Profiles of Anxiety, Depression, and Stress: Differences in School Anxiety.

INTRODUCTION: This study aims to confirm the existence of profiles according to the combinations of anxiety, depression, and stress, and looks to examine the differences between profiles according to the mean scores obtained in school anxiety. METHODS: A total of 1,234 Spanish students at the secondary education level with an age range of 13-16 years old (M = 14.52; SD = 1.24) participated in the study by completing the abbreviated version of the Depression, Anxiety, and Stress Scale (DASS-21) and the School Anxiety Inventory. RESULTS: The results showed positive, statistically significant, and moderate-sized correlations between all the variables analyzed. The Latent Profile Analysis identified four distinct profiles of depression, anxiety, and stress: Low DAS, Moderate DAS, High DAS, and Very High DAS. The results of the MANOVA showed statistically significant differences between these profiles regarding the school anxiety dimensions, with the profiles Very High DAS and Low DAS being the ones that reported, respectively, the highest and lowest levels in all the school anxiety components. Post hoc analyses revealed significant differences for the large part of profile comparisons, with there being large and moderate differences observed in the majority of cases (d = .30 and 1.66). CONCLUSIONS: The results show the importance of considering social anxiety as a construct that is strongly associated with emotional problems such as depression, anxiety, and stress when developing effective actions to detect them and intervene with adolescents.

Production, homology modeling and mutagenesis studies on GlcH glucose transporter from Prochlorococcus sp. strain SS120.

The marine cyanobacterium Prochlorococcus is one of the main primary producers on Earth, which can take up glucose by using the high affinity, multiphasic transporter GlcH. We report here the overexpression of glcH from Prochlorococcus marinus strain SS120 in Escherichia coli. Modeling studies of GlcH using the homologous MelB melibiose transporter from Salmonella enterica serovar Typhimurium showed high conservation at the overall fold. We observed that an important structural interaction, mediated by a strong hydrogen bond between D8 and R141, is conserved in Prochlorococcus, although the corresponding amino acids in MelB from Salmonella are different. Biased docking studies suggested that when glucose reaches the pocket of the transporter and interacts with D8 and R141, the hydrogen bond network in which these residues are involved could be disrupted, favoring a conformational change with the subsequent translocation of the glucose molecule towards the cytoplasmic region of the pmGlcH structure. Based on these theoretical predictions and on the conservation of N117 and W348 in other MelB structures, D8, N117, R141 and W348 were mutated to glycine residues. Their key role in glucose transport was evaluated by glucose uptake assays. N117G and W348G mutations led to 17 % decrease in glucose uptake, while D8G and R141G decreased the glucose transport by 66 % and 92 % respectively. Overall, our studies provide insights into the Prochlorococcus 3D-structure of GlcH, paving the way for further analysis to understand the features which are involved in the high affinity and multiphasic kinetics of this transporter.

Fluoro-labelled sp2-iminoglycolipids with immunomodulatory properties.

The unique electronic properties of the fluorine atom make its strategic incorporation into a bioactive compound a very useful tool in the design of drugs with optimized pharmacological properties. In the field of the carbohydrates, its selective installation at C2 position has proven particularly interesting, some 2-deoxy-2-fluorosugar derivatives being currently in the market. We have now transferred this feature into immunoregulatory glycolipid mimetics that contain a sp2-iminosugar moiety, namely sp2-iminoglycolipids (sp2-IGLs). The synthesis of two epimeric series of 2-deoxy-2-fluoro-sp2-IGLs, structurally related to nojirimycin and mannonojirimycin, has been accomplished by sequential Selectfluor-mediated fluorination and thioglycosidation of sp2-iminoglycals. Exclusively the α-anomer is obtained regardless of the configurational profile of the sp2-IGL (d-gluco or d-manno), highlighting the overwhelming anomeric effect in these prototypes. Notably, the combination of a fluorine atom at C2 and an α-oriented sulfonyl dodecyl lipid moiety in compound 11 led to remarkable anti-proliferative properties, featuring similar GI50 values than the chemotherapy drug Cisplatin against several tumor cell lines and better selectivity. The biochemical data further evidence a strong reduction of the number of tumor cell colonies and apoptosis induction. Mechanistic investigations revealed that this fluoro-sp2-IGL induces the non-canonical activation mode of the mitogen-activated protein kinase signaling pathway, causing p38α autoactivation under an inflammatory context.

Microwave-assisted synthesis of prebiotic di-D-fructose dianhydride-enriched caramels.

The synthesis of prebiotic caramels involving the use of microwaves as the activating/heating source has been achieved. The yields in di-fructose dianhydrides (DFAs) in caramels were measured. The aim of this study was twofold: first to check the feasibility of the process, and second to determine the conditions to obtain an optimum response with microwave heating. The study showed that it was possible to obtain a yield of almost 50% of DFAs in a reaction time that was 10 times shorter than a previous study; i.e. 5-10 min for microwave activation compared to 60-120 min for conventional heating. It was shown that the radiation time and the radiation power were linked. The simultaneous determination of the values of these two factors was therefore necessary to obtain significant yields. This technique demonstrates the advantage of activation for mixtures such as caramels.

School anxiety profiles in Spanish adolescents and their differences in psychopathological symptoms.

School anxiety and psychopathological symptoms tend to co-occur across development and persist in adulthood. The present study aimed to determine school anxiety profiles based on Lang's model of the triple response system (cognitive anxiety, psychophysiological anxiety, and behavioral anxiety) and to identify possible differences between these profiles in psychopathological symptoms (depression, hostility, interpersonal sensitivity, somatization, anxiety, psychoticism, obsessive-compulsive, phobic anxiety, and paranoid ideation). The School Anxiety Inventory (SAI) and the Symptom Assessment-45 Questionnaire (SA-45) were administered to 1525 Spanish students (49% girls) between 15 and 18 years old (M = 16.36, SD = 1.04). Latent Profile Analysis identified four school anxiety profiles: Low School Anxiety, Average School Anxiety, High School Anxiety, and Excessive School Anxiety. A multivariate analysis of variance revealed statistically significant differences among the school anxiety profiles in all the psychopathological symptoms examined. Specifically, adolescents with Excessive School Anxiety showed significantly higher levels of the nine psychopathological symptoms than their peers with Average School Anxiety and Low School Anxiety. In addition, the Excessive School Anxiety profile scored significantly higher in phobic anxiety than the High School Anxiety group. These findings allow to conclude that it is necessary enhance well-being and reduce psychopathology of those adolescents who manifest high and very high reactivity in cognitive, psychophysiological, and behavioral anxiety.

Marine Synechococcus sp. Strain WH7803 Shows Specific Adaptative Responses to Assimilate Nanomolar Concentrations of Nitrate.

Marine Synechococcus, together with Prochlorococcus, contribute to a significant proportion of the primary production on Earth. The spatial distribution of these two groups of marine picocyanobacteria depends on different factors such as nutrient availability and temperature. Some Synechococcus ecotypes thrive in mesotrophic and moderately oligotrophic waters, where they exploit both oxidized and reduced forms of nitrogen. Here, we present a comprehensive study, which includes transcriptomic and proteomic analyses of the response of Synechococcus sp. strain WH7803 to nanomolar concentrations of nitrate, compared to micromolar ammonium or nitrogen starvation. We found that Synechococcus has a specific response to a nanomolar nitrate concentration that differs from the response shown under nitrogen starvation or the presence of standard concentrations of either ammonium or nitrate. This fact suggests that the particular response to the uptake of nanomolar concentrations of nitrate could be an evolutionary advantage for marine Synechococcus against Prochlorococcus in the natural environment. IMPORTANCE Marine Synechococcus are a very abundant group of photosynthetic organisms on our planet. Previous studies have shown blooms of these organisms when nanomolar concentrations of nitrate become available. We have assessed the effect of nanomolar nitrate concentrations by studying the transcriptome and proteome of Synechococcus sp. WH7803, together with some physiological parameters. We found evidence that Synechococcus sp. strain WH7803 does sense and react to nanomolar concentrations of nitrate, suggesting the occurrence of specific adaptive mechanisms to allow their utilization. Thus, very low concentrations of nitrate in the ocean seem to be a significant nitrogen source for marine picocyanobacteria.

Stereoselective Synthesis of Nojirimycin α-C-Glycosides from a Bicyclic Acyliminium Intermediate: A Convenient Entry to N,C-Biantennary Glycomimetics.

A simple and efficient method for the stereoselective synthesis of nojirimycin α-C-glycoside derivatives has been developed using a bicyclic carbamate-type sp2-iminosugar, whose preparation on a gram scale has been optimized, as the starting material. sp2-iminosugar O-glycosides or anomeric esters serve as excellent precursors of acyliminium cations, which can add nucleophiles, including C-nucleophiles. The stereochemical outcome of the reaction is governed by stereoelectronic effects, affording the target α-anomer with total stereoselectivity. Thus, the judicious combination of C-allylation, carbamate hydrolysis, cross-metathesis, and hydrogenation reactions provides a very convenient entry to iminosugar α-C-glycosides, which have been transformed into N,C-biantennary derivatives by reductive amination or thiourea-forming reactions. The thiourea adducts undergo intramolecular cyclization to bicyclic iminooxazolidine iminosugar α-C-glycosides upon acid treatment, broadening the opportunities for molecular diversity. A preliminary evaluation against a panel of commercial glycosidases validates the approach for finely tuning the inhibitory profile of glycomimetics.

Functional Glyconanomaterials.

Nanotechnology provides a new array of techniques and platforms to study biological processes including glycosystems [...].