Amorphous Solid Forms of Ranolazine and Tryptophan and Their Relaxation to Metastable Polymorphs.

Different methods were explored for the amorphization of ranolazine, a sparingly soluble anti-anginal drug, such as mechanochemistry, quench-cooling, and solvent evaporation from solutions. Amorphous phases, with Tg values lower than room temperature, were obtained by cryo-milling and quench-cooling. New forms of ranolazine, named II and III, were identified from the relaxation of the ranolazine amorphous phase produced by cryo-milling, which takes place within several hours after grinding. At room temperature, these metastable polymorphs relax to the lower energy polymorph I, whose crystal structure was solved in this work for the first time. A binary co-amorphous mixture of ranolazine and tryptophan was produced, with three important advantages: higher glass transition temperature, increased kinetic stability preventing relaxation of the amorphous to crystalline phases for at least two months, and improved aqueous solubility. Concomitantly, the thermal behavior of amorphous tryptophan obtained by cryo-milling was studied by DSC. Depending on experimental conditions, it was possible to observe relaxation directly to the lower energy form or by an intermediate metastable crystalline phase and the serendipitous production of the neutral form of this amino acid in the pure solid phase.

Introduction to Pharmaceutical Co-amorphous Systems Using a Green Co-milling Technique.

The concept of co-amorphous systems is introduced in an integrated laboratory experiment, designed for advanced chemistry students, using solvent-free, environmentally friendly mechanochemistry. The dual-drug naproxen-cimetidine co-amorphous system (NPX-CIM) is investigated as an example of the emergent field of medicinal mechanochemistry. Students are trained in solid-state characterization techniques including X-ray powder diffraction, Fourier-transform infrared spectroscopy, and thermal analysis by differential scanning calorimetry. This lab experiment also provides an opportunity to discuss the relevance of different solid forms of pharmaceutics, emphasizing particular properties of disordered materials. This experiment can easily fit the curriculum of any Chemistry or Pharmacy master level degree in courses dealing with instrumental analysis, solid state chemistry, or green chemistry, for classes of 6 to 18 students, in a 5-h lab session. Suggestions to adapt it to the use of a single characterization technique are provided.

Sustainability issues along the coffee chain: From the field to the cup.

The coffee industry is one of the most important commercial value chains worldwide. Nonetheless, it is also associated to several social, economic, and environmental concerns that impair its sustainability. The present review is focused on these main sustainability concerns from the field to the coffee cup, as well as on the strategies that are being developed and/or implemented to attain sustainability and circular economy principles in the different chain segments. In this context, distinct approaches have been applied, such as sustainable certifications (e.g., voluntary sustainability standards), corporate sustainability initiatives, direct trade, relationship coffee concepts, geographical indication, legislations, waste management, and byproducts valorization, among others. These strategies are addressed and discussed throughout this review, as well as their recognized advantages and limitations. Overall, there is still a long way to go to attain the much-desired sustainability in the coffee chain, being essential to join the efforts of all actors and entities directly or indirectly involved, namely, producers, retailers, roasters, governments, educational institutions (such as universities and scientific research institutes), and organizations.

Supramolecular ultra-short carboxybenzyl-protected dehydropeptide-based hydrogels for drug delivery.

Self-assembled peptide-based hydrogels are promising materials for biomedical research owing to biocompatibility and similarity to the extracellular matrix, amenable synthesis and functionalization and structural tailoring of the rheological properties. Wider developments of self-assembled peptide-based hydrogels in biomedical research and clinical translation are hampered by limited commercial availability allied to prohibitive costs. In this work a focused library of Cbz-protected dehydrodipeptides Cbz-L-Xaa-Z-ΔPhe-OH (Xaa= Met, Phe, Tyr, Ala, Gly) was synthesised and evaluated as minimalist hydrogels. The Cbz-L-Met-Z-ΔPhe-OH and Cbz-L-Phe-Z-ΔPhe-OH hydrogelators were comprehensively evaluated regarding molecular aggregation and self-assembly, gelation, biocompatibility and as drug carriers for delivery of the natural compound curcumin and the clinically important antitumor drug doxorubicin. Drug release profiles and FRET studies of drug transport into small unilamellar vesicles (as biomembrane models) demonstrated that the Cbz-protected dehydropeptide hydrogels are effective nanocarriers for drug delivery. The expedite and scalable synthesis (in 3 steps), using commercially available reagents and amenable reaction conditions, makes Cbz-protected dehydrodipeptide hydrogels, widely available at affordable cost to the research community.

Impact of Citrate and Lipid-Functionalized Magnetic Nanoparticles in Dehydropeptide Supramolecular Magnetogels: Properties, Design and Drug Release.

Currently, the nanoparticle functionalization effect on supramolecular peptide-based hydrogels remains undescribed, but is expected to affect the hydrogels' self-assembly and final magnetic gel properties. Herein, two different functionalized nanoparticles: citrate-stabilized (14.4 ± 2.6 nm) and lipid-coated (8.9 ± 2.1 nm) magnetic nanoparticles, were used for the formation of dehydropeptide-based supramolecular magnetogels consisting of the ultra-short hydrogelator Cbz-L-Met-Z-ΔPhe-OH, with an assessment of their effect over gel properties. The lipid-coated nanoparticles were distributed along the hydrogel fibers, while citrate-stabilized nanoparticles were aggregated upon gelation, which resulted into a heating efficiency improvement and decrease, respectively. Further, the lipid-coated nanoparticles did not affect drug encapsulation and displayed improved drug release reproducibility compared to citrate-stabilized nanoparticles, despite the latter attaining a stronger AMF-trigger. This report points out that adsorption of nanoparticles to hydrogel fibers, which display domains that improve or do not affect drug encapsulation, can be explored as a means to optimize the development of supramolecular magnetogels to advance theranostic applications.

Horizontal and vertical movements of starry smooth-hound Mustelus asterias in the northeast Atlantic.

Commercial landings of starry smooth-hound Mustelus asterias in northern European seas are increasing, whilst our knowledge of their ecology, behaviour and population structure remains limited. M. asterias is a widely distributed demersal shark, occupying the waters of the southern North Sea and Irish Sea in the north, to at least the southern Bay of Biscay in the south, and is seasonally abundant in UK waters. There are no species-specific management measures for the northeast Atlantic stock, and the complexity of its population structure is not yet fully understood. To address this issue, we deployed both mark-recapture and electronic tags on M. asterias to gain novel insights into its horizontal and vertical movements. Our data suggest that the habitat use of M. asterias changes on a seasonal basis, with associated changes in geographical distribution, depth utilisation and experienced temperature. We report the first direct evidence of philopatry for this species, and also provide initial evidence of sex-biased dispersal and potential metapopulation-like stock structuring either side of the UK continental shelf. Investigations of finer-scale vertical movements revealed clear diel variation in vertical activity. The illustrated patterns of seasonal space-use and behaviour will provide important information to support the stock assessment process and will help inform any future management options.

Bycatch and discarding patterns of dogfish and sharks taken in English and Welsh commercial fisheries.

At-sea observer programmes can provide spatio-temporal data on the sizes and quantities of fish being either discarded or retained, including for species and size categories that may not be sampled effectively during scientific surveys. Such data were analysed for English and Welsh fisheries operating on the continental shelf of the North Sea ecoregion (ICES Divisions 4a-c and 7d) and Celtic Seas ecoregion (ICES Divisions 6a, 7a-c, e-k) for the period (2002-2016). These data were collated for four main gear types: beamtrawl, nephrops and otter trawls, and nets (including gillnets, tangle nets and trammel nets). Beamtrawlers caught proportionally more smaller individuals than otter trawlers, whilst nets were the most size-selective gear for larger sharks. Size-related discarding was observed, with smaller spurdog Squalus acanthias and starry smooth-hound Mustelus asterias (< 60 cm total length, LT ) usually being discarded. Such size-based selection was not evident for lesser-spotted dogfish Scyliorhinus canicula, which was generally landed as bait. Temporal changes in the discard-retention patterns were evident for S. acanthias and porbeagle Lamna nasus, with increased regulatory discarding as management measures became restrictive. A corresponding increase in the proportion of the non-quota M. asterias retained was also observed over the study period. Knowledge of the size-based discard-retention patterns by métier can also help inform on where future studies on discard survival could usefully be undertaken.

Organohalogen contaminants and trace metals in North-East Atlantic porbeagle shark (Lamna nasus).

The North-East Atlantic porbeagle (Lamna nasus) population has declined dramatically over the last few decades and is currently classified as 'Critically Endangered'. As long-lived, apex predators, they may be vulnerable to bioaccumulation of contaminants. In this study organohalogen compounds and trace elements were analysed in 12 specimens caught as incidental bycatch in commercial gillnet fisheries in the Celtic Sea in 2011. Levels of organohalogen contaminants were low or undetectable (summed CB and BDE concentrations 0.04-0.85 mg kg(-1)wet weight). A notably high Cd concentration (7.2 mg kg(-1)wet weight) was observed in one mature male, whereas the range observed in the other samples was much lower (0.04-0.26 mg kg(-1)wet weight). Hg and Pb concentrations were detected only in single animals, at 0.34 and 0.08 mg kg(-1)wet weight, respectively. These contaminant levels were low in comparison to other published studies for shark species.

Fighting zebrafish: characterization of aggressive behavior and winner-loser effects.

Aggression is a key component of the behavioral repertoire of animals that impacts on their Darwinian fitness. The available genetic tools in zebrafish make this species a promising vertebrate neurogenetic model for the study of neural circuits underlying aggressive behavior. For this purpose, a detailed characterization of the aggressive behavior and its behavioral consequences is first needed. In this article we establish a simple protocol that reliably elicits the expression of fighting behavior in zebrafish dyads and characterized it. The agonistic behavior expressed during dyadic fighting behavior has a temporal structure, indicating the existence of an underlying architecture prone to genetic manipulation. Social interactions have consequences for subsequent behavior with a potential fitness impact, which stresses the validity of this species for the study of aggression. These effects of experience seem to be mediated by different mechanisms in winners and losers. Winners increase the probability of winning subsequent fights without changing their fighting behavior, suggesting the existence of social status cues. On the other hand, losers decrease the probability of winning subsequent fights by decreasing their motivation to escalate fights. Together, these results are a first step to the development of a quantitative framework for the study of aggressive behavior in zebrafish.