Evaluation of the effect of probiotic cultures added to commercial yogurt over a known population of Listeria monocytogenes and Escherichia coli O157:H7

The effect of probiotic cultures over Listeria monocytogenes and Escherichia coli O157:H7 during yogurt storage was evaluated. Two different yogurt brands, one with additional probiotic cultures (Lactobacillus casei and L. acidophilus) were inoculated with known populations (106 UFC/g) of either L. monocytogenes or E. coli O157:H7 in three different times and stored for 32 days at 5 degrees C. Every four days the count of lactic bacteria, the added pathogens and pH was evaluated, according to the methodology described in the Bacteriological Analytical Manual. The pH and lactic bacteria population were constant during the testing period. Yogurt with additional probiotic cultures reduced the population of L. monocytogenes in 8 days, the population of E. coli O157:H7 in 16; yogurt with no additional probiotics took 20 days to reduce L. monocytogenes to non-detectable levels and even after 28 days of storage, E. coli O157:H7 was cultured. In this work, the beneficial effects of additional probiotic cultures in yogurt is confirmed again.     

Removal of dichloromethane from waste gases in one- and two-liquid-phase stirred tank bioreactors and biotrickling filters

The removal of dichloromethane (DCM) from polluted air was studied both in biotrickling filters and in continuous stirred tank bioreactors, using either a single-liquid aqueous phase or a combination of an aqueous-organic liquid phase. The presence of the organic phase, i.e. silicone oil, at a volume ratio of 10% of the liquid phase, increased the maximum EC by about 25% in the BTF, reaching 200 g m³/h, and by as much as 300% in the CSTB, reaching 350 g m³/h. Based on data of chloride release in the aqueous phase and carbon dioxide production in the gas phase, complete dechlorination and mineralization of the pollutant could be confirmed. When applying shock loads, a more stable behaviour was observed in the presence of the organic phase. Generally, the completely mixed reactors were also more stable than the plug-flow biotrickling filters, irrespective of the presence of the organic phase. The use of molecular techniques allowed showing that the originally inoculated DCM-degrading Hyphomicrobium strains remained present, although not dominant, after long-term bioreactor operation. Different new bacterial populations did also appear in the systems, some of which were unable to degrade DCM.     

Thermal control of the liquid lithium divertor for NSTX

The liquid lithium divertor (LLD) to be installed in NSTX has four toroidal panels, each a conical section inclined at 22° like the previous graphite divertor tiles. Each LLD panel is a copper plate clad with 0.25 mm of stainless steel (SS) and a surface layer of flame sprayed molybdenum (Mo) that will host lithium deposited from an evaporator. LITER (evaporators) already used in NSTX will be upgraded for the LLD. Each has twelve 500 W cartridge heaters with thermocouples, 16 other thermocouples, and a channel for helium cooling. During LLD experiments, the LLD will be heated so that the lithium is just above its melting temperature. The length of each shot will be preset to prevent excessive evaporation of lithium from the LLD. This duration depends on the heat load and is likely to be in the range of less than a second to several seconds. Careful thermal control of the LLD is important to maximize the shot times and to guide operation of the LLD. This paper describes the layout of the LLD, its expected thermal performance, the control system, and supporting experiments and analysis. A companion paper in this conference, “Physics design requirements for the national spherical torus experiment liquid lithium divertor,” provides other information.     

A Modular Composite Device of Poly(Ethylene Oxide)/Poly(Butylene Terephthalate) (PEOT/PBT) Nanofibers and Gelatin as a Dual Drug Delivery System for Local Therapy of Soft Tissue Tumors

In the clinical management of solid tumors, the possibility to successfully couple the regeneration of injured tissues with the elimination of residual tumor cells left after surgery could open doors to new therapeutic strategies. In this work, we present a composite hydrogel–electrospun nanofiber scaffold, showing a modular architecture for the delivery of two pharmaceutics with distinct release profiles, that is potentially suitable for local therapy and post-surgical treatment of solid soft tumors. The composite was obtained by coupling gelatin hydrogels to poly(ethylene oxide)/poly(butylene terephthalate) block copolymer nanofibers. Results of the scaffolds’ characterization, together with the analysis of gelatin and drug release kinetics, displayed the possibility to modulate the device architecture to control the release kinetics of the drugs, also providing evidence of their activity. In vitro analyses were also performed using a human epithelioid sarcoma cell line. Furthermore, publicly available expression datasets were interrogated. Confocal imaging showcased the nontoxicity of these devices in vitro. ELISA assays confirmed a modulation of IL-10 inflammation-related cytokine supporting the role of this device in tissue repair. In silico analysis confirmed the role of IL-10 in solid tumors including 262 patients affected by sarcoma as a negative prognostic marker for overall survival. In conclusion, the developed modular composite device may provide a key-enabling technology for the treatment of soft tissue sarcoma.     

ICA1L Is Associated with Small Vessel Disease: A Proteome-Wide Association Study in Small Vessel Stroke and Intracerebral Haemorrhage

Small vessel strokes (SVS) and intracerebral haemorrhages (ICH) are acute outcomes of cerebral small vessel disease (SVD). Genetic studies combining both phenotypes have identified three loci associated with both traits. However, the genetic cis-regulation at the protein level associated with SVD has not been studied before. We performed a proteome-wide association study (PWAS) using FUSION to integrate a genome-wide association study (GWAS) and brain proteomic data to discover the common mechanisms regulating both SVS and ICH. Dorsolateral prefrontal cortex (dPFC) brain proteomes from the ROS/MAP study (N = 376 subjects and 1443 proteins) and the summary statistics for the SVS GWAS from the MEGASTROKE study (N = 237,511) and multi-trait analysis of GWAS (MTAG)-ICH–SVS from Chung et al. (N = 240,269) were selected. We performed PWAS and then a co-localization analysis with COLOC. The significant and nominal results were validated using a replication dPFC proteome (N = 152). The replicated results (q-value < 0.05) were further investigated for the causality relationship using summary data-based Mendelian randomization (SMR). One protein (ICA1L) was significantly associated with SVS (z-score = −4.42 and p-value = 9.6 × 10⁻⁶) and non-lobar ICH (z-score = −4.8 and p-value = 1.58 × 10⁻⁶) in the discovery PWAS, with a high co-localization posterior probability of 4. In the validation PWAS, ICA1L remained significantly associated with both traits. The SMR results for ICA1L indicated a causal association of protein expression levels in the brain with SVS (p-value = 3.66 × 10⁻⁵) and non-lobar ICH (p-value = 1.81 × 10⁻⁵). Our results show that the association of ICA1L with SVS and non-lobar ICH is conditioned by the cis-regulation of its protein levels in the brain.     

An Experimental Model of Neuro–Immune Interactions in the Eye: Corneal Sensory Nerves and Resident Dendritic Cells

The cornea is an avascular connective tissue that is crucial, not only as the primary barrier of the eye but also as a proper transparent refractive structure. Corneal transparency is necessary for vision and is the result of several factors, including its highly organized structure, the physiology of its few cellular components, the lack of myelinated nerves (although it is extremely innervated), the tightly controlled hydration state, and the absence of blood and lymphatic vessels in healthy conditions, among others. The avascular, immune-privileged tissue of the cornea is an ideal model to study the interactions between its well-characterized and dense sensory nerves (easily accessible for both focal electrophysiological recording and morphological studies) and the low number of resident immune cell types, distinguished from those cells migrating from blood vessels. This paper presents an overview of the corneal structure and innervation, the resident dendritic cell (DC) subpopulations present in the cornea, their distribution in relation to corneal nerves, and their role in ocular inflammatory diseases. A mouse model in which sensory axons are constitutively labeled with tdTomato and DCs with green fluorescent protein (GFP) allows further analysis of the neuro-immune crosstalk under inflammatory and steady-state conditions of the eye.     

Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer

Based on the rapid increase in incidence of inflammatory bowel disease (IBD), the identification of susceptibility genes and cell populations contributing to this condition is essential. Previous studies suggested multiple genes associated with the susceptibility of IBD; however, due to the analysis of whole-tissue samples, the contribution of individual cell populations remains widely unresolved. Single-cell RNA sequencing (scRNA-seq) provides the opportunity to identify underlying cellular populations. We determined the enrichment of Crohn’s disease (CD)-induced genes in a publicly available Crohn’s disease scRNA-seq dataset and detected the strongest induction of these genes in innate lymphoid cells (ILC1), highly activated T cells and dendritic cells, pericytes and activated fibroblasts, as well as epithelial cells. Notably, these genes were highly enriched in IBD-associated neoplasia, as well as sporadic colorectal cancer (CRC). Indeed, the same six cell populations displayed an upregulation of CD-induced genes in a CRC scRNA-seq dataset. Finally, after integrating and harmonizing the CD and CRC scRNA-seq data, we demonstrated that these six cell types display a gradual increase in gene expression levels from a healthy state to an inflammatory and tumorous state. Together, we identified cell populations that specifically upregulate CD-induced genes in CD and CRC patients and could, therefore, contribute to inflammation-associated tumor development.     

Phenolic Composition and Antioxidant Capacity of Bilberry (<Emphasis Type="Italic">Vaccinium myrtillus</Emphasis>) Leaves in Northern Europe Following Foliar Development and Along Environmental Gradients

Bilberry is a characteristic field layer species in the boreal forests and is an important forage plant for herbivores of the North European ecosystem. Bilberry leaves contain high levels of phenolic compounds, especially hydroxycinnamic acids, flavonols, catechins, and proanthocyanidins. We investigated the phenolic composition of bilberry leaves in two studies, one following foliar development in forest and open areas, and the other along a wide geographical gradient from south to north boreal forests in Finland. An analysis of bilberry leaves collected in open and forest areas showed that major phenolic changes appeared in the first stages of leaf development, but, most importantly, synthesis and accumulation of flavonoids was delayed in the forest compared to the high light sites. Sampling along a geographical gradient in the boreal zone indicated that leaves from higher latitudes and higher altitudes had greater soluble phenolic and flavonol levels, higher antioxidant capacity, and lower contents of chlorogenic acid derivatives. The ecological significance of the results is discussed.     

Linearization through state immersion of nonlinear systems admitting Lie symmetries

In this paper, it is shown that if a nonlinear system admits a Lie symmetry that can be transformed into its Poincaré-Dulac normal form by a state diffeomorphism, then, under some technical conditions, such a nonlinear system can be immersed into a linear one. This allows us to compute in closed-form the flow, all algebraic invariant curves (through semi-invariants) of the nonlinear system, and Lyapunov functions to study stability properties.     

Investigation of Trypanothione Reductase as a Drug Target in Trypanosoma brucei

There is an urgent need for new drugs for the treatment of tropical parasitic diseases such as human African trypanosomiasis, which is caused by Trypanosoma brucei. The enzyme trypanothione reductase (TryR) is a potential drug target within these organisms. Herein we report the screening of a 62 000 compound library against T. brucei TryR. Further work was undertaken to optimise potency and selectivity of two novel‐compound series arising from the enzymatic and whole parasite screens and mammalian cell counterscreens. Both of these series, containing either a quinoline or pyrimidinopyrazine scaffold, yielded low micromolar inhibitors of the enzyme and growth of the parasite. The challenges of inhibiting TryR with druglike molecules is discussed.