α-GalCer sp-iminoglycolipid analogs as CD1d-dependent iNKT modulators: Evaluation of their immunotherapeutic potential in murine models of asthma and autoimmune hepatitis.

Invariant natural killer T (iNKT) cells are a subset of innate T cells displaying powerful immunomodulatory functions. Despite extensive preclinical research on the use of iNKT agonist and antagonist for various diseases, translating these findings into successful clinical applications has proven challenging, leaving no approved treatments to date. Efforts to optimize therapeutic outcomes by developing alternative glycolipids to α-galactosylceramide (α-GalCer or KRN7000), the prototypical iNKT antigen, have shown improved preclinical results.

β-Cyclodextrin-based geometrically frustrated amphiphiles as one-component, cell-specific and organ-specific nucleic acid delivery systems.

We introduce an innovative β-cyclodextrin (βCD)-prototype for delivering nucleic acids: "geometrically frustrated amphiphiles (GFAs)." GFAs are designed with cationic centers evenly distributed across the primary O6 and secondary O2 positions of the βCD scaffold, while hydrophobic tails are anchored at the seven O3 positions. Such distribution of functional elements differs from Janus-type architectures and enlarges the capacity for accessing strictly monodisperse variants.

Does school climate affect student well-being? Anxiety in school situations as a predictor of stress in high-school students.

Background: When the school climate is not ideal and coping skills for school situations are not strengthened in adolescents, school anxiety and stress may be manifested, potentially harming development and mental health during adulthood. This study aimed to analyze the predictive ability of school anxiety on elevated levels of stress in high-school students.

Materials And Methods: This cross-sectional predictive study was conducted with 1588 students aged 12-18 (M = 14.

Social Anxiety Profiles and Psychopathological Symptom Differences in Spanish Adolescents.

Research on social anxiety (SA) over the years has revealed its associations with different psychopathological symptoms. This study aims to characterize SA profiles in a sample of Spanish adolescents and explore their differences in psychopathological symptoms. Data from 1,288 Spanish students in the 15 to 18 age range (M = 16.

sp-Iminosugar azobenzene O-glycosides: Light-sensitive glycosidase inhibitors with unprecedented tunability and switching factors.

The conventional approach to developing light-sensitive glycosidase activity regulators, involving the combination of a glycomimetic moiety and a photoactive azobenzene module, results in conjugates with differences in glycosidase inhibitory activity between the interchangeable E and Z-isomers at the azo group that are generally below one-order of magnitude. In this study, we have exploited the chemical mimic character of sp-iminosugars to access photoswitchable p- and o-azobenzene α-O-glycosides based on the gluco-configured representative ONJ. Notably, we achieved remarkably high switching factors for glycosidase inhibition, favoring either the E- or Z-isomer depending on the aglycone structure.

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 and , the intercellular membrane nanotubes.

Trehalose-polyamine/DNA nanocomplexes: impact of vector architecture on cell and organ transfection selectivity.

A novel family of precision-engineered gene vectors with well-defined structures built on trehalose and trehalose-based macrocycles (cyclotrehalans) comprising linear or cyclic polyamine heads have been synthesized through procedures that exploit click chemistry reactions. The strategy was conceived to enable systematic structural variations and, at the same time, ensuring that enantiomerically pure vectors are obtained. Notably, changes in the molecular architecture translated into topological differences at the nanoscale upon co-assembly with plasmid DNA, especially regarding the presence of regions with short- or long-range internal order as observed by TEM.

Mixotrophy in cyanobacteria.

Cyanobacteria evolved the oxygenic photosynthesis to generate organic matter from CO 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.

High-Mannose Oligosaccharide Hemimimetics that Recapitulate the Conformation and Binding Mode to Concanavalin A, DC-SIGN and Langerin.

The "carbohydrate chemical mimicry" exhibited by sp -iminosugars has been utilized to develop practical syntheses for analogs of the branched high-mannose-type oligosaccharides (HMOs) Man and Man . In these compounds, the terminal nonreducing Man residues have been substituted with 5,6-oxomethylidenemannonojirimycin (OMJ) motifs. The resulting oligomannoside hemimimetic accurately reproduce the structure, configuration, and conformational behavior of the original mannooligosaccharides, as confirmed by NMR and computational techniques.

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 ( = 14.52; = 1.

A bibliometric analysis on adolescent social anxiety and psychoeducational variables in Web of Science 2002-2021.

The aim of this bibliometric analysis was to analyze the scientific output on adolescent social anxiety and its relationship with 15 psychoeducational variables in peer-reviewed journals during the period 2002-2021. The goal was to provide a comprehensive overview of the state of the art on adolescent social anxiety and academic/school achievement, performance, self-concept, self-esteem, self-efficacy, self-attributions, goals, attachment, adjustment, engagement, refusal, absenteeism, anxiety, learning strategies, and self-regulated learning. A search of scientific literature was conducted using Web of Science, and 157 empirical studies were identified.

Potent and Selective Cell-Active Iminosugar Inhibitors of Human α-N-Acetylgalactosaminidase (α-NAGAL).

Glycoside hydrolases (GHs) are a class of enzymes with emerging roles in a range of disease. Selective GH inhibitors are sought to better understand their functions and assess the therapeutic potential of modulating their activities. Iminosugars are a promising class of GH inhibitors but typically lack the selectivity required to accurately perturb biological systems.

Fluoro-labelled sp-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 sp-iminosugar moiety, namely sp-iminoglycolipids (sp-IGLs).

Serine-/Cysteine-Based sp-Iminoglycolipids as Novel TLR4 Agonists: Evaluation of Their Adjuvancy and Immunotherapeutic Properties in a Murine Model of Asthma.

Glycolipids with TLR4 agonistic properties can serve either as therapeutic agents or as vaccine adjuvants by stimulating the development of proinflammatory responses. Translating them to the clinical setting is hampered by synthetic difficulties, the lack of stability in biological media, and/or a suboptimal profile of balanced immune mediator secretion. Here, we show that replacement of the sugar fragment by an sp-iminosugar moiety in a prototypic TLR4 agonist, , yields iminoglycolipid analogues that retain or improve their biological activity in vitro and in vivo and can be accessed through scalable protocols with total stereoselectivity.

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.

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.

Mannobioside biomimetics that trigger DC-SIGN binding selectivity.

Selective DC-SIGN targeting . langerin might lead to anti-infective agents, given their counteracting effects upon infection by some pathogens. Here we show that multivalent sp-iminosugar-containing mannobioside analogs can achieve total DC-SIGN selectivity by levering the canonic binding mode towards high-mannose oligosaccharide ligands, behaving as factual biomimics.

Differential Timing for Glucose Assimilation in and Coexistent Microbial Populations in the North Pacific Subtropical Gyre.

The marine cyanobacterium can utilize glucose as a source of carbon. However, the relative importance of inorganic and organic carbon assimilation and the timing of glucose assimilation are still poorly understood in these numerically dominant cyanobacteria. Here, we investigated whole microbial community and group-specific primary production and glucose assimilation using incubations with radioisotopes combined with flow cytometry cell sorting.

Unravelling the Inflammatory Processes in the Early Stages of Diabetic Nephropathy and the Potential Effect of ()-DS-ONJ.

Inflammatory processes play a central role in the pathogenesis of diabetic nephropathy (DN) in the early stages of the disease. The authors demonstrate that the glycolipid mimetic ()-DS-ONJ is able to abolish inflammation via the induction of autophagy flux and provokes the inhibition of inflammasome complex in ex vivo and in vitro models, using adult kidney explants from BB rats. The contribution of ()-DS-ONJ to reducing inflammatory events is mediated by the inhibition of classical stress kinase pathways and the blocking of inflammasome complex activation.

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

Marine , together with , 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 ecotypes thrive in mesotrophic and moderately oligotrophic waters, where they exploit both oxidized and reduced forms of nitrogen.

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

A simple and efficient method for the stereoselective synthesis of nojirimycin α--glycoside derivatives has been developed using a bicyclic carbamate-type sp-iminosugar, whose preparation on a gram scale has been optimized, as the starting material. sp-iminosugar -glycosides or anomeric esters serve as excellent precursors of acyliminium cations, which can add nucleophiles, including -nucleophiles. The stereochemical outcome of the reaction is governed by stereoelectronic effects, affording the target α-anomer with total stereoselectivity.

sp-Iminosugars targeting human lysosomal β-hexosaminidase as pharmacological chaperone candidates for late-onset Tay-Sachs disease.

The late-onset form of Tay-Sachs disease displays when the activity levels of human β-hexosaminidase A (HexA) fall below 10% of normal, due to mutations that destabilise the native folded form of the enzyme and impair its trafficking to the lysosome. Competitive inhibitors of HexA can rescue disease-causative mutant HexA, bearing potential as pharmacological chaperones, but often also inhibit the enzyme O-glucosaminidase (GlcNAcase; OGA), a serious drawback for translation into the clinic. We have designed sp-iminosugar glycomimetics related to GalNAc that feature a neutral piperidine-derived thiourea or a basic piperidine-thiazolidine bicyclic core and behave as selective nanomolar competitive inhibitors of human Hex A at pH 7 with a ten-fold lower inhibitory potency at pH 5, a good indication for pharmacological chaperoning.