Normality in terms of distances and contractions

The main purpose of this paper is to explore normality in terms of distances between points and sets. We prove some important consequences on realvalued contractions, i.e. functions not enlarging the distance, showing that as in the classical context of closures and continuous maps, normality in terms of distances based on an appropriate numerical notion of $\gamma$-separation of sets, has far reaching consequences on real valued contractive maps, where the real line is endowed with the Euclidean metric. We show that normality is equivalent to (1) separation of $\gamma$-separated sets by some Urysohn contractive map, (2) to Kat\v{e}tov-Tong's interpolation, stating that for bounded positive realvalued functions, between an upper and a larger lower regular function, there exists a contractive interpolating map and (3) to Tietze's extension theorem stating that certain contractions defined on a subspace can be contractively extended to the whole space. The appropriate setting for these investigations is the category of approach spaces, but the results have (quasi)-metric counterparts in terms of non-expansive maps. Moreover when restricted to topological spaces, classical normality and its equivalence to separation by a Urysohn continuous map, to Kat\v{e}tov-Tong's interpolation for semicontinuous maps and to Tietze's extension theorem for continuous maps are recovered

Genetic analysis of seed traits in \u3ci\u3eSorghum bicolor\u3c/i\u3e that affect the human gut microbiome

Prebiotic fibers, polyphenols and other molecular components of food crops significantly affect the composition and function of the human gut microbiome and human health. The abundance of these, frequently uncharacterized, microbiome-active components vary within individual crop species. Here, we employ high throughput in vitro fermentations of pre-digested grain using a human microbiome to identify segregating genetic loci in a food crop, sorghum, that alter the composition and function of human gut microbes. Evaluating grain produced by 294 sorghum recombinant inbreds identifies 10 loci in the sorghum genome associated with variation in the abundance of microbial taxa and/or microbial metabolites. Two loci co-localize with sorghum genes regulating the biosynthesis of condensed tannins. We validate that condensed tannins stimulate the growth of microbes associated with these two loci. Our work illustrates the potential for genetic analysis to systematically discover and characterize molecular components of food crops that influence the human gut microbiome

Functionalized iron oxide nanoparticles for controlling the movement of immune cells

Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed “cell box” was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain

Carbohydrate utilization by the gut microbiome determines host health responsiveness to whole grain type and processing methods

Little is known about how interactions among grain processing, grain type, and carbohydrate utilization (CU) by the microbiome influence the health benefits of whole grains. Therefore, two whole grains – brown rice and whole wheat – and two processing methods – boiling (porridge) and extrusion – were studied for their effects on host metabolic outcomes in mice harboring human microbiomes previously shown in vitro to have high or low CU. Mice carrying either microbiome experienced increases in body weight and glycemia when consuming Western diets supplemented with extruded grains versus porridge. However, mice with the high but not low CU microbiome also gained more weight and fat over time and were less glucose tolerant when consuming extruded grain diets. In high CU microbiome mice, the exacerbated negative health outcomes associated with extrusion were related to altered abundances of Lachnospiraceae and Ruminococcaceae as well as elevated sugar degradation and colonic acetate production. The amplicon sequence variants (ASVs) associated with extruded and porridge diets in this in vivo study were not the same as those identified in our prior in vitro study; however, the predicted functions were highly correlated. In conclusion, mice harboring both high and low CU microbiomes responded to the whole grain diets similarly, except the high CU microbiome mice exhibited exacerbated effects due to excessive acetate production, indicating that CU by the microbiome is linked to host metabolic health outcomes. Our work demonstrates that a greater understanding of food processing effects on the microbiome is necessary for developing foods that promote rather than diminish host health

The waxy mutation in sorghum and other cereal grains reshapes the gut microbiome by reducing levels of multiple beneficial species

Waxy starches from cereal grains contain \u3e90% amylopectin due to naturally occurring mutations that block amylose biosynthesis. Waxy starches have unique organoleptic characteristics (e.g. sticky rice) as well as desirable physicochemical properties for food processing. Using isogenic pairs of wild type sorghum lines and their waxy derivatives, we studied the effects of waxy starches in the whole grain context on the human gut microbiome. In vitro fermentations with human stool microbiomes show that beneficial taxonomic and metabolic signatures driven by grain from wild type parental lines are lost in fermentations of grain from the waxy derivatives and the beneficial signatures can be restored by addition of resistant starch. These undesirable effects are conserved in fermentations of waxy maize, wheat, rice and millet. We also demonstrate that humanized gnotobiotic mice fed low fiber diets supplemented with 20% grain from isogenic pairs of waxy vs. wild type parental sorghum have significant differences in microbiome composition and show increased weight gain. We conclude that the benefits of waxy starches on food functionality can have unintended tradeoff effects on the gut microbiome and host physiology that could be particularly relevant in human populations consuming large amounts of waxy grains

Een 18de-eeuwse wraksite op de Buiten Ratel-zandbank (Belgische territoriale wateren): 1. Multidisciplinair onderzoek van het vondstenmateriaal

In 1996 werd op de Buiten Ratel-zandbank, op 9 mijl van de kust, ter hoogte van Koksijde, een houten scheepswrak gelokaliseerd. Het werd onderzocht door een groep sportduikers, met de naam NATA. Jarenlange verkenning van de wraksite leverde talrijke vondsten op. In 2003 zochten de duikers steun bij het toenmalige IAP (Instituut voor het Archeologisch Patrimonium), nu Vlaams Instituut voor het Onroerend Erfgoed (VIOE), om het onderzoek en de conservatie op wetenschappelijke basis verder te zetten. Het VIOE ontfermde zich over het onderzoek van de tot nu toe geborgen materiële resten van de wraksite. Het eerste hoofdstuk van het artikel geeft een overzicht van de observaties van de wraksite via duikonderzoek en via gespecialiseerde technieken vanop een onderzoeksschip. In hoofdstuk 2 worden de objecten beschreven, hun betekenis aan boord van het schip besproken, evenals hun datering en herkomst. Hoofdstuk 3 brengt alle informatie samen en geeft aan wat er in de toekomst nog aan onderzoek kan gebeuren

ATP13A2 deficiency disrupts lysosomal polyamine export

ATP13A2 (PARK9) is a late endolysosomal transporter that is genetically implicated in a spectrum of neurodegenerative disorders, including Kufor-Rakeb syndrome—a parkinsonism with dementia1—and early-onset Parkinson’s disease2. ATP13A2 offers protection against genetic and environmental risk factors of Parkinson’s disease, whereas loss of ATP13A2 compromises lysosomes3. However, the transport function of ATP13A2 in lysosomes remains unclear. Here we establish ATP13A2 as a lysosomal polyamine exporter that shows the highest affinity for spermine among the polyamines examined. Polyamines stimulate the activity of purified ATP13A2, whereas ATP13A2 mutants that are implicated in disease are functionally impaired to a degree that correlates with the disease phenotype. ATP13A2 promotes the cellular uptake of polyamines by endocytosis and transports them into the cytosol, highlighting a role for endolysosomes in the uptake of polyamines into cells. At high concentrations polyamines induce cell toxicity, which is exacerbated by ATP13A2 loss due to lysosomal dysfunction, lysosomal rupture and cathepsin B activation. This phenotype is recapitulated in neurons and nematodes with impaired expression of ATP13A2 or its orthologues. We present defective lysosomal polyamine export as a mechanism for lysosome-dependent cell death that may be implicated in neurodegeneration, and shed light on the molecular identity of the mammalian polyamine transport system

Modulation of aberrant CDK5 signaling rescues impaired neurogenesis in models of Alzheimer's disease

Recent studies show that in Alzheimer's disease (AD), alterations in neurogenesis contribute to the neurodegenerative process. Neurodegeneration in AD has been associated with aberrant signaling through the cyclin-dependent kinase-5 (CDK5) pathway via its activators p35/p25; however, the role of CDK5 in the mechanisms of defective adult neurogenesis in AD is unknown. First, to study AD-like abnormal activation of CDK5 signaling in an in vitro model of neurogenesis, neuronal progenitor cells (NPCs) were infected with a viral vector expressing p35, and exposed to amyloid-β protein (Aβ1−42). These conditions resulted in impaired maturation and neurite outgrowth in vitro, and these effects were reversed by pharmacological or genetic inhibition of CDK5. Similarly, neurogenesis was impaired in a transgenic mouse model of AD that expresses high levels of amyloid precursor protein (APP), and this effect was reversed in transgenic mice crossed with a CDK5 heterozygous-deficient mouse line. A similar rescue effect was observed in APP transgenic mice treated with Roscovitine, a pharmacological inhibitor of CDK5. Taken together, these data suggest that the CDK5 signaling pathway has a critical role in maintaining the integrity of NPCs and neuronal maturation in the adult hippocampus. Moreover, potential therapeutic approaches could focus on modulating the aberrant activity of CDK5 to target the neurogenic and neurodegenerative alterations in AD

Party rules, party resources, and the politics of parliamentary democracies: how parties organize in the 21st Century

This article introduces the first findings of the Political Party Database (PPDB) project, a major survey of party organizations in parliamentary and semi-presidential democracies. The project’s first round of data covers 122 parties in 19 countries. In this paper we describe the scope of the database, then investigate what it tells us about contemporary party organization in these countries, focussing on parties’ resources, structures and internal decision-making. We examine organizational patterns by country and party family, and where possible we make temporal comparisons with older datasets. Our analyses suggest a remarkable coexistence of uniformity and diversity. In terms of the major organizational resources on which parties can draw, such as members, staff and finance, the new evidence largely confirms the continuation of trends identified in previous research: i.e., declining membership, but enhanced financial resources and more paid staff. We also find remarkable uniformity regarding the core architecture of party organizations. At the same time, however, we find substantial variation between countries and party families in terms of their internal processes, with particular regard to how internally democratic they are, and in the forms that this democratization takes