Synthetic Receptors for the High-Affinity Recognition of O-GlcNAc Derivatives

The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water-soluble carbohydrate receptors ("synthetic lectins"). Both systems show outstanding affinities for derivatives of N-acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc-β-OMe with Ka ≈20,000 m(-1), whereas the other one binds an O-GlcNAcylated peptide with Ka ≈70,000 m(-1). These values substantially exceed those usually measured for GlcNAc-binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl-peptide complex can be explained by extra-cavity interactions, raising the possibility of a family of complementary receptors for O-GlcNAc in different contexts

The perception of patients, mothers and healthcare professionals regarding introduction of home visits for adolescents with type 1 diabetes

Background and Objectives: Despite advancements in diabetes management, a subgroup of patients does not achieve an acceptable level of metabolic control. To achieve treatment goals for high-risk patients, a higher frequency of contact with healthcare professionals is essential. However, socioeconomic challenges often lead to nonattendance at the outpatient clinic. Therefore, home visits were introduced as a supplement/an alternative to consultations at the paediatric diabetes clinic. The aim of this study was to uncover the perception of patients, mothers and healthcare professionals regarding home visits versus consultations at the outpatient clinic in order to being able to improve the services offered. Methods: Semistructured interviews with patients, mothers and healthcare professionals were conducted to explore the experiences and perspectives of the concept at two paediatric diabetes clinics in Denmark. Paired t tests were used to compare the glycated hemoglobin A1c (HbA1c) levels at the start of the intervention with HbA1c 1 year before and HbA1c at the end of the intervention. Results: Both patients, mothers and healthcare professionals found consultations in familiar surroundings to result in stronger relationships between healthcare professionals and families, creating greater opportunities to discuss personal issues aimed at improving the outcome of diabetes. Furthermore, home visits facilitated finding alternative methods of helping patients and the families integrating diabetes into everyday life. Conclusion: Overall, home visits were found to contribute toward creating a more constructive relationship. However, it was still a challenge to keep the scheduled appointments, and during this short study, no improvement in metabolic control could be observed.</p

Marine nature-based solutions: Where societal challenges and ecosystem requirements meet the potential of our oceans

Nature-Based Solutions (NbS), a concept introduced in the late 2000s, has developed rapidly during the last years and is now frequently appearing in a broad spectrum of policies developed within the European Union. Its role in marine policies and research programmes is however still limited, but is likely to increase as NbS are adopted as key terminology in both biodiversity strategies and the EU taxonomy for sustainable financing. This will enhance the need for scientific advisory institutions to provide evidence-based advice on potential impacts of various combinations of marine NbS. To facilitate a critical debate about the prospects and pitfalls related to the operationalisation of marine NbS in an EU context, this paper provides an analysis of core definitions, potential categories of marine NBS and a suite of case studies. Coastal waters, shelf and open oceans present multiple options for testing new and scaling up known NbS, which could support both environmental restoration simultaneously with addressing multiple societal challenges, paving the way for a new level of ecosystem-based management. However, as the acceptance of NbS types will depend on ecosystem state and thus history, it will be a significant task to consistently communicate why some solutions may count as a NbS in some areas, while not in others. To conclude, the paper therefore raises a set of research priorities and policy advice aimed at ensuring the successful advice and deployment of marine NBS in support of multiple societal goals

Applications of isothermal titration calorimetry - the research and technical developments from 2011 to 2015

Isothermal titration calorimetry is a widely used biophysical technique for studying the formation or dissociation of molecular complexes. Over the last 5years, much work has been published on the interpretation of isothermal titration calorimetry (ITC) data for single binding and multiple binding sites. As over 80% of ITC papers are on macromolecules of biological origin, this interpretation is challenging. Some researchers have attempted to link the thermodynamics constants to events at the molecular level. This review highlights work carried out using binding sites characterized using x-ray crystallography techniques that allow speculation about individual bond formation and the displacement of individual water molecules during ligand binding and link these events to the thermodynamic constants for binding. The review also considers research conducted with synthetic binding partners where specific binding events like anion-π and π-π interactions were studied. The revival of assays that enable both thermodynamic and kinetic information to be collected from ITC data is highlighted. Lastly, published criticism of ITC research from a physical chemistry perspective is appraised and practical advice provided for researchers unfamiliar with thermodynamics and its interpretation

Acute hypoxia increases the cerebral metabolic rate:a magnetic resonance imaging study

The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O(2) hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% ([Formula: see text]), glutamate increased by 4.7% ([Formula: see text]) and creatine and phosphocreatine decreased by 15.2% (p [Formula: see text]). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia

Differential Responses of Calcifying and Non-Calcifying Epibionts of a Brown Macroalga to Present-Day and Future Upwelling pCO2

Seaweeds are key species of the Baltic Sea benthic ecosystems. They are the substratum of numerous fouling epibionts like bryozoans and tubeworms. Several of these epibionts bear calcified structures and could be impacted by the high pCO2 events of the late summer upwellings in the Baltic nearshores. Those events are expected to increase in strength and duration with global change and ocean acidification. If calcifying epibionts are impacted by transient acidification as driven by upwelling events, their increasing prevalence could cause a shift of the fouling communities toward fleshy species. The aim of the present study was to test the sensitivity of selected seaweed macrofoulers to transient elevation of pCO2 in their natural microenvironment, i.e. the boundary layer covering the thallus surface of brown seaweeds. Fragments of the macroalga Fucus serratus bearing an epibiotic community composed of the calcifiers Spirorbis spirorbis (Annelida) and Electra pilosa (Bryozoa) and the non-calcifier Alcyonidium hirsutum (Bryozoa) were maintained for 30 days under three pCO2 conditions: natural 460±59 µatm, present-day upwelling1193±166 µatm and future upwelling 3150±446 µatm. Only the highest pCO2 caused a significant reduction of growth rates and settlement of S. spirorbis individuals. Additionally, S. spirorbis settled juveniles exhibited enhanced calcification of 40% during daylight hours compared to dark hours, possibly reflecting a day-night alternation of an acidification-modulating effect by algal photosynthesis as opposed to an acidification-enhancing effect of algal respiration. E. pilosa colonies showed significantly increased growth rates at intermediate pCO2 (1193 µatm) but no response to higher pCO2. No effect of acidification on A. hirsutum colonies growth rates was observed. The results suggest a remarkable resistance of the algal macro-epibionts to levels of acidification occurring at present day upwellings in the Baltic. Only extreme future upwelling conditions impacted the tubeworm S. spirorbis, but not the bryozoans