Alignment of multiple glial cell populations in 3D nanofiber scaffolds: toward the development of multicellular implantable scaffolds for repair of neural injury

Non-neuronal cells of the central nervous system (CNS), termed "neuroglia," play critical roles in neural regeneration; therefore, replacement of glial populations via implantable nanofabricated devices (providing a growth-permissive niche) is a promising strategy to enhance repair. Most constructs developed to date have lacked three-dimensionality, multiple glial populations and control over spatial orientations, limiting their ability to mimic in vivo neurocytoarchitecture. We describe a facile technique to incorporate multiple glial cell populations [astrocytes, oligodendrocyte precursor cells (OPCs) and oligodendrocytes] within a three-dimensional (3D) nanofabricated construct. Highly aligned nanofibers could induce elongation of astrocytes, while OPC survival, elongation and maturation required pre-aligned astrocytes. The potential to scale-up the numbers of constituent nanofiber layers is demonstrated with astrocytes. Such complex implantable constructs with multiple glial sub-populations in defined 3D orientations could represent an effective approach to reconstruct glial circuitry in neural injury sites

Long-term modifications of coastal defences enhance marine biodiversity

Realization that hard coastal infrastructures support lower biodiversity than natural habitats has prompted a wealth of research seeking to identify design enhancements offering ecological benefits. Some studies showed that artificial structures could be modified to increase levels of diversity. Most studies, however, only considered the short-term ecological effects of such modifications, even though reliance on results from short-term studies may lead to serious misjudgements in conservation. In this study, a seven-year experiment examined how the addition of small pits to otherwise featureless seawalls may enhance the stocks of a highly-exploited limpet. Modified areas of the seawall supported enhanced stocks of limpets seven years after the addition of pits. Modified areas of the seawall also supported a community that differed in the abundance of littorinids, barnacles and macroalgae compared to the controls. Responses to different treatments (numbers and size of pits) were species-specific and, while some species responded directly to differences among treatments, others might have responded indirectly via changes in the distribution of competing species. This type of habitat enhancement can have positive long-lasting effects on the ecology of urban seascapes. Understanding of species interactions could be used to develop a rule-based approach to enhance biodiversity

Physico-Chemically Distinct Nanomaterials Synthesized from Derivates of a Poly(Anhydride) Diversify the Spectrum of Loadable Antibiotics

Recent advances in the field of nanotechnology such as nanoencapsulation offer new biomedical applications, potentially increasing the scope and efficacy of therapeutic drug delivery. In addition, the discovery and development of novel biocompatible polymers increases the versatility of these encapsulating nanostructures, enabling chemical properties of the cargo and vehicle to be adapted to specific physiological requirements. Here, we evaluate the capacity of various polymeric nanostructures to encapsulate various antibiotics of different classes, with differing chemical structure. Polymers were sourced from two separate derivatives of poly(methyl vinyl ether-alt-maleic anhydride) (PMVE/MA): an acid (PMVE/MA-Ac) and a monoethyl ester (PMVE/MA-Es). Nanoencapsulation of antibiotics was attempted through electrospinning, and nanoparticle synthesis through solvent displacement, for both polymers. Solvent incompatibilities prevented the nanoencapsulation of amikacin, neomycin and ciprofloxacin in PMVE/MA-Es nanofibers. However, all compounds were successfully loaded into PMVE/MA-Es nanoparticles. Encapsulation efficiencies in nanofibers reached approximately 100% in all compatible systems; however, efficiencies varied substantially in nanoparticles systems, depending on the tested compound (14%–69%). Finally, it was confirmed that both these encapsulation processes did not alter the antimicrobial activity of any tested antibiotic against Staphylococcus aureus and Escherichia coli, supporting the viability of these approaches for nanoscale delivery of antibioticsThis research was funded by the Spanish Ministerio de Economía y Competitividad, grant numbers MAT-2017-86805-R and MAT-2014-53282-R,and Spanish Ministerio de Ciencia e Innovación (MCI)—Agencia Estatal de Investigación (AEI)/Fondo Europeo de Desarrollo Regional (FEDER), grant number RTI2018-101969-J-I0

Identifying the cellular targets of drug action in the central nervous system following corticosteroid therapy

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical Neuroscience, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/cn400167nCorticosteroid (CS) therapy is used widely in the treatment of a range of pathologies, but can delay production of myelin, the insulating sheath around central nervous system nerve fibers. The cellular targets of CS action are not fully understood, that is, "direct" action on cells involved in myelin genesis [oligodendrocytes and their progenitors the oligodendrocyte precursor cells (OPCs)] versus "indirect" action on other neural cells. We evaluated the effects of the widely used CS dexamethasone (DEX) on purified OPCs and oligodendrocytes, employing complementary histological and transcriptional analyses. Histological assessments showed no DEX effects on OPC proliferation or oligodendrocyte genesis/maturation (key processes underpinning myelin genesis). Immunostaining and RT-PCR analyses show that both cell types express glucocorticoid receptor (GR; the target for DEX action), ruling out receptor expression as a causal factor in the lack of DEX-responsiveness. GRs function as ligand-activated transcription factors, so we simultaneously analyzed DEX-induced transcriptional responses using microarray analyses; these substantiated the histological findings, with limited gene expression changes in DEX-treated OPCs and oligodendrocytes. With identical treatment, microglial cells showed profound and global changes post-DEX addition; an unexpected finding was the identification of the transcription factor Olig1, a master regulator of myelination, as a DEX responsive gene in microglia. Our data indicate that CS-induced myelination delays are unlikely to be due to direct drug action on OPCs or oligodendrocytes, and may occur secondary to alterations in other neural cells, such as the immune component. To the best of our knowledge, this is the first comparative molecular and cellular analysis of CS effects in glial cells, to investigate the targets of this major class of anti-inflammatory drugs as a basis for myelination deficits.British Neuro-pathological Society, North Staffordshire Medical Institute, and The University of Nottingham

Race and sex: teachers' views on who gets ahead in schools?

The research reported here was part of a large study of the impact of age, disability, race and sex on the teaching profession in England. The basic question asked in this research was how do these factors interact with career aspirations and achievements of classteachers, promoted teachers and headteachers? There were three different data sources: a large postal survey drawn from diverse geographic regions across England with over 2000 respondents; face‐to‐face individual interviews with over 100 teachers in 18 case study schools from across all of the main regions of England; discussions with special interest groups of teachers. Not surprisingly, the answer to the above question was complex. Nonetheless, the paper's conclusion highlights some of the noteworthy themes across this broad sample of teachers from primary, secondary and special schools

'Stealth' nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics

Surface engineering to control cell behavior is of high interest across the chemical engineering, drug delivery and biomaterial communities. Defined chemical strategies are necessary to tailor nanoscale protein interactions/adsorption, enabling control of cell behaviors for development of novel therapeutic strategies. Nanoparticle-based therapies benefit from such strategies but particle targeting to sites of neurological injury remains challenging due to circulatory immune clearance. As a strategy to overcome this barrier, the use of stealth coatings can reduce immune clearance and prolong circulatory times, thereby enhancing therapeutic capacity. Polyethylene glycol (PEG) is the most widely-used stealth coating and facilitates particle accumulation in the brain. However, once within the brain, the mode of handling of PEGylated particles by the resident immune cells of the brain itself (the ‘microglia’) is unknown. This is a critical question as it is well established that microglia avidly sequester nanoparticles, limiting their bioavailability and posing a major translational barrier. If PEGylation can be proved to promote evasion of microglia, then this information will be of high value in developing tailored nanoparticle-based therapies for neurological applications. Here, we have conducted the first comparative study of uptake of PEGylated particles by all the major (immune and non-immune) brain cell types. We prove for the first time that PEGylated nanoparticles evade major brain cell populations — a phenomenon which will enhance extracellular bioavailability. We demonstrate changes in protein coronas around these particles within biological media, and discuss how surface chemistry presentation may affect this process and subsequent cellular interactions

The early career researcher's toolkit: translating tissue engineering, regenerative medicine and cell therapy products

Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization

Recruitment of the exotic weakfish at its southernmost limit in Europe: a preliminary assessment.

Since its first record in Europe as an exotic species back in 2009 at the Schelde estuary (Belgium), the weakfish Cynoscion regalis -native from North America East coast- has increased its presence in the Iberian Peninsula waters. Identified for the first time in the Guadalquivir River estuary (2011) and later in the Sado estuary (2014), C. regalis population is increasing in the Gulf of Cadiz and is becoming a fisheries resource. Its introduction into Europe probably occurred through maritime transatlantic trade. Morais et al (2017) suggested that weakfish could have been introduced through multiple independent ballast water release events. The Guadalquivir, Sado and Schelde estuaries show similar transoceanic ship traffic to upstream important commercial ports, supporting multiple direct or secondary transatlantic introductions among European ports. The first genetic studies suggest that C. regalis populations in southern European estuaries are connected and come from a single transoceanic commercial route. Currently, the Gulf of Cadiz maintains a well-established population with frequent catches by artisanal fishing, especially in coastal waters and the estuary, where it is sold in local markets of the surrounding cities. The population in the area is constituted by mature specimens (ranging from 234 to 453 mm) that are using the estuary as a spawning area, where larvae and juvenile have also been found. In recent years, an increase in the abundance of larvae and juvenile has been observed through monthly samplings in the estuary, which indicates the culmination of the complete life cycle in the Gulf of Cadiz. These findings represent new evidence that the Guadalquivir estuary constitutes a remarkable nursery habitat for this species. This could have effects on native fauna and the ecosystem, which is why it is currently under study and evaluation (EcoInvadiz project) for helping the local Administration to establish, if needed, an appropriate management program

The early career researcher's toolkit:translating tissue engineering, regenerative medicine and cell therapy products

Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization