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.

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.

An in-depth physicochemical investigation of drug-loaded core-shell UiO66 nanoMOFs.

Nanosized UiO66 are among the most studied MOF materials. They have been extensively applied in various areas, such as catalysis, gas absorption, electrochemistry, chemical sensing, and biomedical applications. However, the preparation of stable nano-sized UiO66 for drug delivery applications is challenging because of the high tendency of UiO66 to aggregate during storage. To address this issue, we coated UiO66 with oligomers made of crosslinked cyclodextrins. The coated UiO66 exhibited a good stability upon storage for more than three weeks, even for low quantities of coating materials. The resulting core-shell UiO66 were characterized using a set of complementary methods including microscopies, spectroscopies, X-ray diffraction, and thermogravimetric investigations. Size distribution was assessed by orthogonal methods. Cisplatin was loaded in the core-shell nanoparticles, followed by an in-depth analysis by asymmetric flow field-flow fractionation (AF4) hyphenated with inductively coupled plasma-mass spectrometry (ICP-MS). This method combines the extremely high elemental selectivity and ultratrace detection limits of mass spectrometry with the capacity of AF4 to differentiate the diverse populations present in the sample. Free cisplatin and UiO66-associated cisplatin could be well separated by AF4. AF4-ICP-MS/MS analysis provided the exact drug loading, without the need of separating the nanoparticles from their suspension media. These data suggest the potential of AF4-ICP-MS/MS in the optimization of drug delivery systems.

The Phenotypic Spectrum of Spinocerebellar Ataxia Type 19 in a Series of Latin American Patients.

Spinocerebellar ataxia 19 (SCA19) represents a rare autosomal dominant genetic disorder resulting in progressive ataxia and cerebellar atrophy. SCA19 is caused by variants in the KCND3 gene, which encodes a voltage-gated potassium channel subunit essential for cerebellar Purkinje cell function. We describe six cases from Chile and Mexico, representing the largest report on SCA19 in Latin America. These cases encompass a range of clinical presentations, highlighting the phenotypic variability within SCA19 from an early-onset, severe disease to a late-onset, slowly progressive condition with normal lifespan. While some patients present with pure ataxia, others also show cognitive impairment, dystonia, and other neurological symptoms. The correlations between specific KCND3 variants and phenotypic outcomes are complex and warrant further investigation. As the genomic landscape of spinocerebellar ataxias evolves, comprehensive genetic testing is becoming pivotal in improving diagnostic accuracy. This study contributes to a better understanding of the clinical spectrum of SCA19, laying the groundwork for further genotype-phenotype correlations and functional studies to elucidate the underlying pathophysiology.

Human occupations of upland and cold environments in inland Spain during the Last Glacial Maximum and Heinrich Stadial 1: The new Magdalenian sequence of Charco Verde II.

The settlement of cold and arid environments by Pleistocene hunter-gatherers has been a heated topic in Paleolithic Archaeology and the Quaternary Sciences for years. In the Iberian Peninsula, a key area for studying human adaptations to such environments is composed by the large interior and upland regions of the northern and southern plateaus (Mesetas) and bordering areas. As, traditionally, these regions have been relatively under-investigated compared to the ecologically more favored coastal areas of the peninsula, our knowledge of the human settlement of the whole Iberian hinterland remains scarce for the Last Glacial. In this paper we present the discovery and first geoarcheological, paleoenvironmental and chronometric evidence obtained at Charco Verde II, a new site close to the southwestern foothills of the Iberian system range (Guadalajara province, Spain), bearing a sequence of Magdalenian human occupations starting at least at 20.8-21.4 ka cal BP during the Last Glacial Maximum, and covering Greenland Stadial 2 until ∼15.1-16.6 ka cal BP, including Heinrich stadial 1. As this site is located in an upland region which today faces one of the harshest climates in Iberia, such occupation sequence, occurred during some of the coldest and most arid phases of the Last Glacial, has relevant implications for our understanding of human-environment-climate interactions and population dynamics in Iberia and Western Europe. These findings support the hypothesis that the Iberian hinterland was not avoided by Upper Paleolithic hunter-gatherers due to ecological constraints, but it hosted a complex and relatively dense settlement at least in some areas, even during cold periods. This suggest, one more time, that the historical scarcity of Upper Paleolithic sites in inland Iberia is, to a significant extent, an artifact of research bias.

Mousterian human fossils from El Castillo cave (Puente Viesgo, Cantabria, Spain).

El Castillo cave is a well-known site because of its Paleolithic archaeology and parietal rock art. This paper is focused on the human remains found by V. Cabrera in the Mousterian Unit XX assigned to MIS 4 and early MIS 3. The fossils consist of one upper left second premolar (ULP4), one incomplete proximal hand phalanx, and one partial femoral head. The tooth and the phalanx were assigned to adults, whereas the femoral head belonged to an immature individual due to the absence of fusion traces to the metaphyseal surface. The external morphology and metrical characterization of the Castillo-1466 (ULP4) tooth crown was quantified and compared to the variability of other Neanderthal dental remains and a sample of modern human populations. We also quantified its 3D enamel thickness distribution, its roots morphology, as well as the presence of chipping, and their possible relation to masticatory or paramasticatory activities. Castillo-1466 shows crown dimensions compatible with middle-sized Neanderthal teeth, but with a remarkably thicker enamel than other Neanderthal premolars, such as Marillac 13. The femoral head and the hand phalanx fragment are compared to published values for Neanderthals, although both partial fossils lack diagnostic features precluding any clear taxonomic diagnostic. Therefore, their attribution to Neanderthals is assumed based on the dating of the layers in which they were discovered. El Castillo cave Mousterian fossils represent another contribution to the knowledge of the Middle Paleolithic populations of Northern Spain, where different sites along the Cantabrian mountains yielded several human remains assigned to MIS 4 and early MIS 3.

MNAzymes and gold nanoparticles as isothermal signal amplification strategy for visual detection of miRNA.

MicroRNAs (miRNAs) represent a class of small noncoding RNAs that are considered a novel emerging class of disease biomarkers in a variety of afflictions. Sensitive detection of miRNA is typically achieved using hybridization-based methods coupled with genetic amplification techniques. Although their sensitivity has improved, amplification techniques often present erroneous results due to their complexity. In addition, the use of these techniques is usually linked to the application of protein enzymes, the activity of which is dependent on the temperature and pH of the medium. To address these drawbacks, an alternative genetic enzyme for the highly sensitive detection of miRNAs is proposed in this work. Multicomponent nucleic acid enzymes (MNAzymes), coupled with the use of DNA-functionalized gold nanoparticles (AuNPs), were used in this study to develop an isothermal signal amplification strategy for visual genetic detection. miR146a, a biomarker of bovine mastitis present in milk, was selected as a model analyte. The developed methodology is easily carried out in 80 min at 50 °C, generating a low visual limit of detection of 250 pM based on the observation of a color change. The methodology was successfully applied to the detection of miR146a in raw cow milk samples.

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.

Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.

Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.

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.

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.

Ulnar nerve thickness at the elbow on longitudinal ultrasound view in control subjects.

INTRODUCTION: Ulnar mononeuropathy at the elbow is the second most frequent neuropathy in humans. Diagnosis is based on clinical and electrophysiological criteria and, more recently, also on ultrasound. Cross-sectional ultrasound is currently the most valued, although longitudinal ultrasound allows assessment of the entire affected trajectory of the nerve in a single view, but always in a straight line with no changes in direction, as in the extended elbow. The main aim of this work is to propose normative values ​​for longitudinal ultrasound of the ulnar nerve at the elbow. METHODS: The neurological exploration of upper extremity, and electrophysiological and ultrasound parameters at the elbow of ulnar nerve were evaluated in 76 limbs from 38 asymptomatic subjects. RESULTS: The diameters of the nerve as well as the distal and proximal areas were larger at the proximal region of the ulnar groove, and even more so in older individuals. In most of these elderly subjects, we found a small, non-significant slowdown in motor conduction velocity at the elbow with respect to the forearm (less than 5 m/s). CONCLUSIONS: We observed a good correlation between the longitudinal and cross-sectional ultrasounds of the ulnar nerve at the elbow. Longitudinal ultrasound proved to be sensitive, reliable, simple and rapid, but its greatest contribution was allowing the visualization of the entire nerve trajectory in an integrated way, providing an image with good definition of the outline, proportions and intraneural characteristics of the nerve.

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.

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.

Working capital management, financial constraints and exports: evidence from European and US manufacturers.

This paper investigates the effect of firms' working capital management, measured by the cash conversion cycle (CCC) on exports, on both the intensive and extensive margins. By using Heckman's two-stage model for the treatment of sample selection bias, we find that the longer the CCC, the lower firms' likelihood of exporting and the lower the volume of their exports. This phenomenon is economically more relevant for financially constrained firms than for unconstrained firms. The results are robust to the propensity score matching, the transition sample and the placebo analyses. Finally, these results can be extrapolated in the context of the COVID-19 crisis because of the decline in trading conditions and firms' shortage of liquidity.

Perfectionistic Self-Presentation Scale in Ecuador: psychometric properties and latent mean differences across genders / Escala de Autopresentación Perfeccionista en Ecuador: propiedades psicométricas y diferencias de medias latentes en función del género

Abstract Introduction: This paper aims to examine the psychometric properties, i.e., validity, reliability, factorial invariance, and latent mean differences based on gender, of the Perfectionistic Self-Presentation Scale, PSPS, in the Ecuadorian context. Method: A sample consisting of 597 Ecuadorian undergraduates participated in the study. Results: Confirmatory Factor Analysis supported a 14-item and three-dimensional model of the scale: Perfectionistic Self-Promotion, Nondisplay of Imperfection, and Nondisclosure of Imperfection. This model presented configural; measurement, i.e., metric, strong, and strict; as well as structural invariance across genders. Discriminant validity was observed by analysing correlations between PSPS factors and perfectionism traits. Males exhibited higher latent means of Perfectionistic Self-Promotion and also Nondisplay of Imperfection than females. Conclusions: The Spanish-translated and brief version of the PSPS represents a reliable and valid tool for assessing perfectionistic self-presentation in Ecuador.

Resumen Introducción: Este artículo tiene como objetivo examinar las propiedades psicométricas, i.e., validez, fiabilidad, invarianza factorial y diferencias de medias latentes en función del género, de la Escala de Autopresentación Perfeccionista, PSPS, en el contexto de Ecuador. Método: La muestra se compuso de 597 universitarios ecuatorianos. Resultados: El análisis factorial confirmatorio apoyó una estructura de la escala compuesta por 14 ítems y tres dimensiones: autopromoción perfeccionista, no-divulgación de la imperfección, y no-verbalización de la imperfección. Este modelo mostró invarianza configural; de medida, métrica, escalar y estricta; y estructural a través del género. El análisis de correlaciones entre los factores de la PSPS y los rasgos perfeccionistas evidenció la validez discriminante de la escala. Los hombres obtuvieron medias latentes significativamente más altas en comparación con las mujeres en los factores autopromoción perfeccionista y no-divulgación de la imperfección. Conclusiones: La versión de la PSPS abreviada y traducida al español representa una medida fiable y válida para evaluar la autopresentación perfeccionista en Ecuador.

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.

A ß-Cyclodextrin-Based Nanoparticle with Very High Transfection Efficiency Unveils siRNA-Activated TLR3 Responses in Human Prostate Cancer Cells.

Synthetic double-stranded small interfering RNAs (siRNAs) mimic interference RNAs (RNAi) and can bind target mRNAs with a high degree of specificity, leading to selective knockdown of the proteins they encode. However, siRNAs are very labile and must be both protected and transported by nanoparticles to be efficiently delivered into cells. In this work, we used a Janus-type polycationic amphiphilic ß-cyclodextrin derivative to efficiently transfect siRNAs targeting mRNAs encoding mitogen-activated protein kinase (p42-MAPK) or Ras homolog enriched in brain (Rheb) into different cancer cell lines as well as astrocytes. We took advantage of this high transfection efficiency to simultaneously knock down p42-MAPK and Rheb to boost docetaxel (DTX)-mediated toxicity in two human prostate cancer cell lines (LNCaP and PC3). We found that double knockdown of p42-MAPK and Rheb increased DTX-toxicity in LNCaP but not in PC3 cells. However, we also observed the same effect when scramble siRNA was used, therefore pointing to an off-target effect. Indeed, we found that the siRNA we used in this work induced toll-like receptor 3 activation, leading to ß-interferon production and caspase activation. We believe that this mechanism could be very useful as a general strategy to elicit an immune response against prostate cancer cells.

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.