Air–Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects

Reliable and predictive in vitro assays for hazard assessments of manufactured nanomaterials (MNMs) are still limited. Specifically, exposure systems which more realistically recapitulate the physiological conditions in the lung are needed to predict pulmonary toxicity. To this end, air-liquid interface (ALI) systems have been developed in recent years which might be better suited than conventional submerged exposure assays. However, there is still a need for rigorous side-by-side comparisons of the results obtained with the two different exposure methods considering numerous parameters, such as different MNMs, cell culture models and read outs. In this study, human A549 lung epithelial cells and differentiated THP-1 macrophages were exposed under submerged conditions to two abundant types of MNMs i.e., ceria and titania nanoparticles (NPs). Membrane integrity, metabolic activity as well as pro-inflammatory responses were recorded. For comparison, A549 monocultures were also exposed at the ALI to the same MNMs. In the case of titania NPs, genotoxicity was also investigated. In general, cells were more sensitive at the ALI compared to under classical submerged conditions. Whereas ceria NPs triggered only moderate effects, titania NPs clearly initiated cytotoxicity, pro-inflammatory gene expression and genotoxicity. Interestingly, low doses of NPs deposited at the ALI were sufficient to drive adverse outcomes, as also documented in rodent experiments. Therefore, further development of ALI systems seems promising to refine, reduce or even replace acute pulmonary toxicity studies in animals

Love is the triumph of the imagination: daydreams about significant others are associated with increased happiness, love and connection

Social relationships and interactions contribute to daily emotional well-being. The emotional benefits that come from engaging with others are known to arise from real events, but do they also come from the imagination during daydreaming activity? Using experience sampling methodology with 101 participants, we obtained 371 reports of naturally occurring daydreams with social and non-social content and self-reported feelings before and after daydreaming. Social, but not non-social, daydreams were associated with increased happiness, love and connection and this effect was not solely attributable to the emotional content of the daydreams. These effects were only present when participants were lacking in these feelings before daydreaming and when the daydream involved imagining others with whom the daydreamer had a high quality relationship. Findings are consistent with the idea that social daydreams may function to regulate emotion: imagining close others may serve the current emotional needs of daydreamers by increasing positive feelings towards themselves and others

A roadmap towards safe and sustainable by design nanotechnology: implementation for nano-silver-based antimicrobial textile coatings production by ASINA project

This report demonstrates a case study within the ASINA project, aimed at instantiating a roadmap with quantitative metrics for Safe(r) and (more) Sustainable by Design (SSbD) options. We begin with a description of ASINA’s methodology across the product lifecycle, outlining the quantitative elements within: Physical-Chemical Features (PCFs), Key Decision Factors (KDFs), and Key Performance Indicators (KPIs). Subsequently, we delve in a proposed decision support tool for implementing the SSbD objectives across various dimensions—functionality, cost, environment, and human health safety—within a broader European context. We then provide an overview of the technical processes involved, including design rationales, experimental procedures, and tools/models developed within ASINA in delivering nano-silver-based antimicrobial textile coatings. The result is pragmatic, actionable metrics intended to be estimated and assessed in future SSbD applications and to be adopted in a common SSbD roadmap aligned with the EU’s Green Deal objectives. The methodological approach is transparently and thoroughly described to inform similar projects through the integration of KPIs into SSbD and foster data-driven decision-making. Specific results and project data are beyond this work’s scope, which is to demonstrate the ASINA roadmap and thus foster SSbD-oriented innovation in nanotechnology

UNBOUND

Featured here, are the extraordinary works of our graduating Fashion Design class. This accomplishment is truly a celebration of the tree years of passion, hard work, and dedication of our students. It\u27s our hope that the fashion industry will partake in the creative endeavors of the emerging designers from the Fashion Design program at Fanshawe College in London, Ontario.https://first.fanshawec.ca/famd_design_fashiondesign_unbound/1002/thumbnail.jp

Disrupted lymph node and splenic stroma in mice with induced inflammatory melanomas is associated with impaired recruitment of T and dendritic cells

International audienceMigration of dendritic cells (DC) from the tumor environment to the T cell cortex in tumor-draining lymph nodes (TDLN) is essential for priming naïve T lymphocytes (TL) to tumor antigen (Ag). We used a mouse model of induced melanoma in which similar oncogenic events generate two phenotypically distinct melanomas to study the influence of tumor-associated inflammation on secondary lymphoid organ (SLO) organization. One tumor promotes inflammatory cytokines, leading to mobilization of immature myeloid cells (iMC) to the tumor and SLO; the other does not. We report that inflammatory tumors induced alterations of the stromal cell network of SLO, profoundly altering the distribution of TL and the capacity of skin-derived DC and TL to migrate or home to TDLN. These defects, which did not require tumor invasion, correlated with loss of fibroblastic reticular cells in T cell zones and in impaired production of CCL21. Infiltrating iMC accumulated in the TDLN medulla and the splenic red pulp. We propose that impaired function of the stromal cell network during chronic inflammation induced by some tumors renders spleens non-receptive to TL and TDLN non-receptive to TL and migratory DC, while the entry of iMC into these perturbed SLO is enhanced. This could constitute a mechanism by which inflammatory tumors escape immune control. If our results apply to inflammatory tumors in general, the demonstration that SLO are poorly receptive to CCR7-dependent migration of skin-derived DC and naïve TL may constitute an obstacle for proposed vaccination or adoptive TL therapies of their hosts

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

BACKGROUND: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence

Background: Osteosarcoma is the most common malignant primary bone tumour in young adult treated by neo adjuvant chemotherapy, surgical tumor removal and adjuvant multidrug chemotherapy. For correction of soft tissue defect consecutive to surgery and/or tumor treatment, autologous fat graft has been proposed in plastic and reconstructive surgery. Principal Findings: We report here a case of a late local recurrence of osteosarcoma which occurred 13 years after the initial pathology and 18 months after a lipofilling procedure. Because such recurrence was highly unexpected, we investigated the possible relationship of tumor growth with fat injections and with mesenchymal stem/stromal cell like cells which are largely found in fatty tissue. Results obtained in osteosarcoma pre-clinical models show that fat grafts or progenitor cells promoted tumor growth. Significance: These observations and results raise the question of whether autologous fat grafting is a safe reconstructive procedure in a known post neoplasic context

Conception, characterization and application of glyconanoparticles in (bio)electrochemistry

Cette thèse effectuée, en collaboration entre le Département de Chimie Moléculaire (DCM), et le Centre de Recherches sur les Macromolécules Végétales (CERMAV) est dédiée à la conception de nouvelles glyconanoparticules (GNPs) rédox obtenues par auto assemblage de deux copolymères amphiphiles selon un procédé de nanoprécipitation: le polystyrène-bloc-cyclodextrine (PS-b-CD) et le polystyrène-bloc-maltoheptaose (PS-b-MH) ou d’un mélange en différentes proportions de ces deux copolymères. La morphologie et la taille nanométrique des GNPs ont pu être déterminées grâce à des caractérisations par diffusion dynamique de la lumière, microscopie électronique à transmission et à balayage. Selon la nature du composé rédox choisi, la fonctionnalisation des GNPs a été réalisée pendant leur formation ou après l’auto-assemblage de celles-ci en utilisant les propriétés d’inclusion des cyclodextrines. Un axe abordé pendant la thèse est l’étude des propriétés électrochimiques des glyconanoparticules rédox en solution ainsi que la transposition de leurs propriétés rédox sur support carboné. Afin de mieux appréhender les propriétés électrochimiques des glyconanoparticules, une étude en amont des propriétés électrochimiques des composés rédox en solution comme pour l’entité viologène substituée par le groupement adamantane ou pyrène a été réalisée. Un dernier volet exploré est l'utilisation des glyconanoparticules en bioélectrochimie pour la réalisation de biocathodes enzymatiques et de biocapteurs enzymatiques à glucose, ce dernier étant choisi comme preuve de concept.This thesis, carried out in collaboration between the Département de Chimie Moléculaire (DCM), and Centre de Recherches sur les Macromolécules Végétales (CERMAV) is dedicated to the conception of new redox glyconanoparticles (GNPs). They are obtained by self-assembly of amphiphilic block copolymer systems using nanoprecipitation technique: polystyrene-block-cyclodextrin (PS-b-CD) and polystyrene-block-maltoheptaose (PS-b-MH) or a mixture of these 2 copolymers in different proportions. The morphology and the nanometric size of the GNPs were determined thanks to characterizations by dynamic light scattering, transmission and scanning electron microscopy. Depending on the nature of the chosen redox compound, the GNPs functionalization was carried out during their formation or after self-assembly using the inclusion properties of cyclodextrins. Another approach of the thesis is the study of the electrochemical properties of these redox glyconanoparticles in solution as well as their electrochemical transposition on carbon electrode. For a better understanding of the electrochemical properties of modified glyconanoparticles, a study of the electrochemical properties of redox compounds in solution, as for the viologen entity substituted by the adamantane or pyrene group, was carried out. A final aspect explored is the use of glyconanoparticles in bioelectrochemistry for the elaboration of enzymatic biocathodes and enzymatic glucose biosensors, this latter being chosen as proof of concept

Lessons Learned From the YTSA Open Custom Adoption Program

Following a historic meeting of staff with Alberta Children's Services and the Yellowhead Tribal Services Agency (YTSA) a pilot program, the YTSA Open Custom Adoption Program was developed. The agency initially researched existing adoption models in the Northwest Territories, British Columbia and the Cheyenne Nation in the United States. An advisory committee comprised of one Elder from each member First Nation community was struck to provide guidance and direction throughout the project. From 2000 to 2010 YTSA placed over a hundred children in adoptive homes and there were no adoption breakdowns (Aski Awasis Children of the Earth, p.79). Although the agency has now closed its doors there are lessons to be learned from the YTSA Open Custom Adoption program which is still viewed as an advanced model of adoption service inspired by traditional First Nation teachings and child caring. This article is a review of lessons learned from this agency. What remains for me is the importance of connectedness to family, culture, community and nationhood for Indigenous children and adoption