Influence of Liposomes’ and Lipoplexes’ Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta

Pregnant women are still considered as drug orphans. Developing new medications for pregnancy complications is an urgent need. Nanomedicines seem to be a promising approach to control the biodistribution of drugs to ensure both the mother’s and the fetus’ safety. Understanding the interaction between nanoparticles and the placental barrier is a key factor to the success of the development of nanomedicines for pregnant women. In this study, we evaluated the behavior of fluorescent PEGylated liposomes and lipoplexes in human placental tissue using in vitro and ex vivo models, BeWo cell culture and suspended villous placental explants, respectively. Fluorescent based analytical tools such as Fluorescence activated cells sorting (FACS), confocal microscopy and HPLC coupled to fluorescence detection were used to assess liposomes penetration and their endocytosis mechanisms in the placenta. First, no influence of the PEGylation density was observed on the cellular internalization of liposomal formulations using both models. The comparison between neutral and cationic liposomes exhibits a significant higher internalization of the cationic formulation compared to the neutral ones. In addition, the HPLC quantification of the fluorescent liposomes in human villous explants demonstrated an increase of cationic liposomes uptake with increasing incubation concentrations. Similar uptake of cationic liposomes and lipoplexes, containing the same cationic lipid, the DMAPAP but with an overall neutral surface charge, was observed and evidenced the higher effect of composition than charge surface on trophoblast penetration. Moreover, both cationic liposomes and lipoplexes exhibited an endocytosis mechanism of internalization via pathways implicating dynamin. These data highlight the key role of the liposome’s lipid composition and the possibility to modulate their internalization in the placenta by adjusting their design.     

Identification of 8-Hydroxyquinoline Derivatives That Decrease Cystathionine Beta Synthase (CBS) Activity

CBS encodes a pyridoxal 5′-phosphate-dependent enzyme that catalyses the condensation of homocysteine and serine to form cystathionine. Due to its implication in some cancers and in the cognitive pathophysiology of Down syndrome, the identification of pharmacological inhibitors of this enzyme is urgently required. However, thus far, attempts to identify such molecules have only led to the identification of compounds with low potency and limited selectivity. We consequently developed an original, yeast-based screening method that identified three FDA-approved drugs of the 8-hydroxyquinoline family: clioquinol, chloroxine and nitroxoline. These molecules reduce CBS enzymatic activity in different cellular models, proving that the molecular mechanisms involved in yeast phenotypic rescue are conserved in mammalian cells. A combination of genetic and chemical biology approaches also revealed the importance of copper and zinc intracellular levels in the regulation of CBS enzymatic activity—copper promoting CBS activity and zinc inhibiting its activity. Taken together, these results indicate that our effective screening approach identified three new potent CBS inhibitors and provides new findings for the regulation of CBS activity, which is crucial to develop new therapies for CBS-related human disorders.     

Reconciled freshwater flux into the Godthåbsfjord system from satellite and airborne remote sensing

As the rapid reduction in ice volume of the Greenland ice sheet (GrIS) continues, increased melt water flux from the GrIS enters the deep Greenlandic fjords. This increased freshwater flux may change the salinity and eventually the ecology of the fjords. Here, we present a case study in which we, from various remote-sensing data sets, estimate the freshwater flux from the GrIS into a specific fjord system, the Godthåbsfjord, in southwest Greenland. The area of the GrIS draining into Godthåbsfjord covers approximately 36,700 km². The large areal extent and the multiple outlets from the GrIS hamper in situ observations. Here, we evaluate available data from remote sensing and find a drainage basin in rapid change. An analysis of data from the Gravity Recovery and Climate Experiment (GRACE) satellites shows a mean seasonal freshwater flux into Godthåbsfjord of 18.2 ± 1.2 Gt, in addition to an imbalance in the mass balance of the drainage basin from 2003 to 2013 of 14.4 ± 0.2 Gt year^?1. Altimetry data from air and spaceborne missions also suggest rapid changes in the outlet glacier dynamics. We find that only applying data from the Ice, Cloud, and land Elevation Satellite (ICESat) mission the mass change of the Godthåbsfjord drainage basin is significantly underestimated. When including additional laser-altimetry surveys, to account for changes in the outlet glaciers elevation, not captured by ICESat, the altimetry data were able to reconcile the basin mass balance with the gravimetric estimate and provide a higher spatial resolution of the mass changes.     

Investigation of LSPR Coupling Effects toward the Rational Design of CsxWO3–δ Based Solar NIR Filtering Coatings

The optical range of localized surface plasmon resonance (LSPR) is extended into the infrared region, thanks to the development of highly doped semiconductor nanocrystals. Particularly, the near-infrared (NIR) range holds a significant interest in managing solar radiation. However, practical applications necessitate the arrangement of particles, which is known to possibly impact their optical properties through LSPR coupling effects. How such coupling modifies the LSPR response in semiconductor hosts remains largely unexplored. In this study, a protocol for producing composite coatings composed of cesium-doped tungsten bronze nanocrystals embedded in a silica matrix is presented. Achieving individual dispersion of nanocrystals is made possible through careful selection of a surface polyglycerol ligand exchange. This allows to tune the interparticle distance by adjusting the nanocrystal volume fraction in the composite. The findings demonstrate that LSPR coupling effects significantly influence the LSPR intensity of nanocrystals in the composite when the nanocrystal-to-nanocrystal distance matches their size. Beyond elucidating the LSPR coupling effect, this study provides insights into the potential use of Cs-HTB nanocrystals for solar control applications. Through the optimization of morphology and film structure, remarkable selectivity is obtained in terms of maintaining good transparency in the visible range while achieving high absorption in the NIR.     

Responsive Spiral Photonic Structures for Visible Vapor Sensing,Pattern Transformation and Encryption

Two photon polymerisation using direct laser writing is a burgeoning field of research, with recent focus being placed on bringing added value to microstructures, by incorporating soft, responsive polymers. Moving to the micron-scale can have a profound impact on such stimuli-responsive materials, whose speed of actuation can be increased many-fold compared to their mm-scale counterparts. Here, the fabrication of submicron 2D photonic structures, based on a vapor-responsive photoresist with a refractive index <1.55, in the visible wavelength range. The fabricated concentric spiral arrays are evaluated for their feasibility as vapor sensors by testing spectral and structural color reproducibility and reversibility under water, ethanol, isopropanol, and acetone vapors. This approach allows for the realization of predictable uniform color displays that can be modulated upon stimuli response. The transmitted colour in the dry and hydrated states can be accurately modelled. This knowledge is used to design and demonstrate structures for cloaking and image transformation. Such capability can be used for encryption and anti-counterfeiting applications.     

Inclusive recovery planning for incremental systemic change: A methodology,early outcomes,and limitations from the Falkland Islands' Covid-19 recovery planning experience

Crises do not affect populations equally but expose and exacerbate long-standing vulnerabilities and inequalities. Recovery language such as ‘build back better’, or ‘bounce forward’ has been criticised for neglecting underlying inequalities. This paper reports on the process and early outcomes of an inclusive Community Recovery Planning process for the Falkland Islands, in response to Covid-19. The Falkland Islands is home to a complex community, with close ties and short power distances (due to its small size and remoteness), with differences institutionalised in citizenship statuses and entitlements, and shaped by geopolitical tensions. We aimed to use the ‘pandemic as a portal’, seeking out previously ‘less heard’ voices, to make visible previously hidden impacts, and initiate incremental systemic change to tackle them. Community Impact Assessments evidenced specific areas of vulnerability (e.g., housing and income insecurity) and inequalities, largely shaped by differing citizenship status. In tandem with other government currents, the Community Recovery Planning process has contributed to progressive policy changes in Equalities legislation and Income Support. We offer this paper as a demonstration of our methodology for inclusive recovery planning that could be adapted elsewhere. We argue that the inclusion of previously unheard voices contributed to incremental systemic change to reduce inequalities.     

Organizational unlearning: A risky food safety strategy?

Strategically unlearning specific knowledge, behaviors, and practices facilitates product and process innovation, business model evolution, and new market opportunities and is essential to meet emergent supply chain and customer requirements. Indeed, addressing societal concerns such as climate change and net zero means elements of contemporary practice in food supply chains need to be unlearned to ensure new practices are adopted. However, unlearning is a risky process if crucial knowledge is lost, for example, if knowledge is situated in the supply base not the organization itself, or there is insufficient organizational food safety knowledge generation, curation, and management when new practices/processes are designed and implemented. An exploratory, critical review of management and food safety academic and gray literature is undertaken that aims to consider the cycle of unlearning, learning, and relearning in food organizations and supply chains with particular emphasis on organizational innovation, inertia, and the impact on food safety management systems and food safety performance. Findings demonstrate it is critical with food safety practices, such as duration date coding or refrigeration practices, that organizations “unlearn” in a way that does not increase organizational, food safety, or public health risk. This paper contributes to extant literature by highlighting the organizational vulnerabilities that can arise when strategically unlearning to promote sustainability in a food supply context. Mitigating such organizational, food safety, and public health risk means organizations must simultaneously drive unlearning, learning, and relearning as a dynamic integrated knowledge acquisition and management approach. The research implications are of value to academics, business managers, and wider industry.     

Solid-State Catalytic Hydrogen Sponge Effects in BaInO2.5 Epitaxial Films

Gas sponges capable of absorbing, storing, and releasing ions in a reversible manner are in high demand for advanced electronics, energy devices, and sensors. Here, it is shown that brownmillerite BaInO_2.5 epitaxial films exhibit the capability to act as solid-state catalytic hydrogen sponges at a remarkably low temperature (≈100 °C). Compared to sintered pellets with random crystallographic orientations and many defects, BaInO_2.5 epitaxial films give three orders of magnitude higher conductivity of hydrogen ions, which can be linked to the presence of well-ordered 1D channels and lack of grain boundaries and other defects. Using scanning transmission electron microscopy, it is shown that hydrogen ions can be stored near InO₄ tetrahedral layers of brownmillerite without destroying the parent framework. The high performance and reproducibility of the BaInO_2.5 epitaxial films coupled with ultralow power consumption make them ideal candidates for neuromorphic devices and beyond.     

Group processes and interoperability: A longitudinal case study analysis of the UK's civil contingency response to Covid-19

Our case study explored a Local Resilience Forum's (LRF) civil contingency response to COVID-19 in the United Kingdom. We undertook 19 semistructured ethnographic longitudinal interviews, between March 25, 2020 and February 17, 2021, with a Director of a Civil Contingencies Unit and a Chief Fire Officer who both played key roles within their LRF. Within these interviews, we focused on their strategic level decision-making and how their relationship with national government impacted on local processes and outcomes. Using a form of grounded theory, our data describe the chronological evolution of an increasingly effective localized approach toward outbreak control and a growing resilience in dealing with concurrent emergency incidents. However, we also highlight how national government organizations imposed central control on aspects of the response in ways that undermined or misaligned with local preparedness. Thus, during emergencies, central governments can undermine the principle of subsidiarity and damage the ways in which LRFs can help scaffold local resilience. Our work contributes to the theoretical understanding of the social psychological factors that can shape the behaviour of responder agencies during a prolonged crisis. In particular, the implications of our analysis for advancing our conceptual understanding of strategic decision-making during emergencies are discussed.