Foleysmed0914

Leptospirosis, the most common zoonotic infection worldwide, is a multi-system disorder affecting the kidney, liver, and lungs. Infections can be asymptomatic, self-limiting or progress to multi-organ system failure and pulmonary hemorrhage. The incidence of canine and human leptospirosis is steadily increasing worldwide. At least sixty-four Leptospira species and several hundred lipopolysaccharide-based serovars have been defined. Preventive vaccines are available for use in veterinary medicine and limited use in humans in some countries. All commercially available vaccines are bacterin formulations that consist of a combination of laboratory cultivated strains of different lipopolysaccharide serotypes. The development of a broadly protective subunit vaccine would represent a significant step forward in efforts to combat leptospirosis in humans, livestock, and companion animals worldwide. Here we investigate the potential of General secretory protein D (GspD; LIC11570), a secretin, to serve as a possible antigen in a multi-valent vaccine formulation. GspD is conserved, expressed in vitro, antigenic during infection and elicits antibody with complement independent bactericidal activity. Importantly, antibody to GspD is bactericidal against diverse Leptospira species of the P1 subclade. Epitope mapping localized the bactericidal epitopes to the N-terminal N0 domain of GspD. Selleck Setanaxib The data within support further exploration of GspD as a candidate for inclusion in a next generation multi-protein subunit vaccine.Exploiting metal-organic frameworks (MOFs) as selectively permeable shelters for encapsulating engineered cells to form hybrid living materials has attracted increasing attention in recent years. Optimizing the synthesis process to improve encapsulation efficiency (EE) is critical for further technological development and applications. Here, using ZIF-90 and genetically engineered Escherichia coli (E. coli) as a demo, we fabricated E. coli@ZIF-90 living composites in which E. coli cells were encapsulated in ZIF-90 crystals. We illustrated that ZIF-90 could serve as a protective porous cage for cells to shield against toxic bactericides including benzaldehyde, cinnamaldehyde, and kanamycin. Notably, the E. coli cells remained alive and could self-reproduce after removing the ZIF-90 crystal cages in ethylenediaminetetraacetic acid, suggesting a feasible route for protecting and prolonging the lifespan of bacterial cells. Moreover, an aqueous multiple-step deposition approach was developed to improve EE of the E. coli@ZIF-90 composites the EE increased to 61.9 ± 5.2%, in contrast with the efficiency of the traditional method (21.3 ± 4.4%) prepared with PBS buffer. In short, we develop a simple yet viable strategy to manufacture MOF-based living hybrid materials that promise new applications across diverse fields.

In our recent study using [U-

C

]glycerol, a small subset of hamsters showed an unusual profile of glycerol metabolism negligible gluconeogenesis from glycerol plus conversion of glycerol to 1,3-propanediol (1,3PDO) and 3-hydroxypropionate (3HP) which were detected in the liver and blood. The purpose of the current study is to evaluate the association of these unusual glycerol products with other biochemical processes in the liver.

Fasted hamsters received acetaminophen (400mg/kg; n=16) or saline (n=10) intraperitoneally. After waiting 2h, all the animals received [U-

C

]glycerol intraperitoneally. Liver and blood were harvested 1h after the glycerol injection for NMR analysis and gene expression assays.

1,3PDO and 3HP derived from [U-

C

]glycerol were detected in the liver and plasma of eight hamsters (two controls and six hamsters with acetaminophen treatment). Glycerol metabolism in the liver of these animals differed substantially from conventional metabolic pathways. [U-

C

]glycerol was metRare Earth Elements (REEs) are used in increasing amounts in technical applications and consumer products. However, to date, the contribution of industrial sources to the loads of individual REEs in wastewater streams have not been quantified. Here, we determine the REE contents in sludge collected from 63 wastewater treatment plants (WWTPs) across Switzerland. To quantify the industrial fraction of individual REEs in the sewage sludge, we develop two complementary approaches, based on REE ratios and REE pattern fitting. Unspecific (background) inputs, with REE patterns similar to the averaged REE pattern of soils collected across Switzerland, dominate the REE budget of most WWTPs. A few WWTPs receive significant REE inputs from specific industrial sources. Based on population equivalents of Switzerland, we estimate a total annual load of 4200 kg Cerium (Ce, 0.5 g Ce year-1 capita-1), with an industrial contribution of 2000 kg year-1. The latter agrees with estimates of probabilistic mass flow models for engineered nanoscale CeO2 particles discharged to the sewer network. About 7 kg year-1 of Samarium (Sm,total for Switzerland 184 kg year-1 or 0.02 g Sm year-1 capita-1) and 3 kg year-1 of Europium (Eu,total for Switzerland 44 kg year-1 or 0.005 g Eu year-1 capita-1) are assigned to industrial inputs from single WWTPs. Gadolinium (Gd) is used in the form of a stable complex as contrast agent in magnetic resonance imaging. Assuming 10% removal of Gd during wastewater treatment, we calculate an annual discharge of 90 kg of Gd from one individual WWTP to surface waters. WWTPs with exceptionally high industrial inputs of specific REEs warrant detailed investigations to identify the respective sources and to assess whether REE concentrations in effluents are elevated to the same degree.

Development of new and more effective therapies against hepatitis B virus (HBV) is limited by the lack of suitable small animal models. The HBV transgenic mouse model containing an integrated overlength 1.3-mer construct has yielded crucial insights, but this model unfortunately lacks covalently closed circular DNA (cccDNA), the episomal HBV transcriptional template, and cannot be cured given that HBV is integrated in every cell.

To solve these 2 problems, we generated a novel transgenic mouse (HBV1.1X), which generates an excisable circular HBV genome using Cre/LoxP technology. This model possesses a HBV1.1-mer cassette knocked into the

locus and is designed for stable expression of viral proteins from birth, like the current HBV transgenic mouse model, before genomic excision with the introduction of Cre recombinase.

We demonstrated induction of recombinant cccDNA (rcccDNA) formation via viral or transgenic Cre expression in HBV1.1X mice, and the ability to regulate HBsAg and HBc expression with Crmice, enabling curative therapies to be tested in this new mouse model.

Hepatitis B virus (HBV) can only naturally infect humans and chimpanzees. Mouse models have been developed with the HBV genome integrated into mouse chromosomes, but this prevents mice from being cured. We developed a new transgenic mouse model that allows for HBV to be excised from mouse chromosomes to form a recombinant circular DNA molecule resembling the natural circular HBV genome. HBV expression could be reduced in these mice, enabling curative therapies to be tested in this new mouse model.

Non-alcoholic fatty liver disease (NAFLD), which is closely associated with obesity, metabolic syndrome, and diabetes, is a highly prevalent emerging condition that can be optimally managed through a multidisciplinary patient-centred approach. National preparedness to address NAFLD is essential to ensure that health systems can deliver effective care. We present a NAFLD Preparedness Index for Europe.

In June 2019, data were extracted by expert groups from 29 countries to complete a 41-item questionnaire about NAFLD. Questions were classified into 4 categories policies/civil society (9 questions), guidelines (16 questions), epidemiology (4 questions), and care management (12 questions). Based on the responses, national preparedness for each indicator was classified into low, middle, or high-levels. We then applied a multiple correspondence analysis to obtain a standardised preparedness score for each country ranging from 0 to100.

The analysis estimated a summary factor that explained 71.3% of the variaticies and civil society engagement, guidelines, epidemiology, and care management. NAFLD preparedness was found to be deficient in all 29 countries studied, with great variation among the countries and the 4 categories studied.Pain is a negative affective state arising from tissue damage or inflammation. Because pain is aversive and its relief is innately rewarding, animals may learn to avoid a context in which pain is experienced and prefer one where pain relief occurs. It is generally accepted that vertebrate animals experience pain; however, there is currently inconclusive evidence that the affective component of pain occurs in any invertebrate. Here, we show that octopuses, the most neurologically complex invertebrates, exhibit cognitive and spontaneous behaviors indicative of affective pain experience. In conditioned place preference assays, octopuses avoided contexts in which pain was experienced, preferred a location in which they experienced relief from pain, and showed no conditioned preference in the absence of pain. Injection site grooming occurred in all animals receiving acetic acid injections, but this was abolished by local anesthesia. Thus, octopuses are likely to experience the affective component of pain.Antibiotics have been considered as effective weapons against bacterial infections since they were discovered. However, antibiotic resistance caused by overuse and abuse of antibiotics is an emerging public health threat nowadays. Fully defeating bacterial infections has become a tough challenge. In this work, cerium oxide was fabricated on medical titanium by thermolysis of cerium-containing metal-organic framework (Ce-BTC). Regulation of Ce (Ⅲ)/Ce (Ⅳ) ratios was realized by pyrolysis of Ce-BTC in different gas environment, and the antibacterial properties were studied. The results indicated that, in acidic conditions, ceria with a high Ce (Ⅲ)/Ce (Ⅳ) ratio owned high oxidase-like activity which could produce reactive oxygen species. Moreover, ceria with high Ce (Ⅲ) content possessed strong ATP deprivation capacity which could cut off the energy supply of bacteria. Based on this, ceria with a high Ce (Ⅲ)/Ce (Ⅳ) ratio exhibited superior antibacterial activity.Electrochemical oxygen reduction reaction (ORR) is an important energy-related process requiring alternative catalysts to expensive platinum-based ones. Although recently some advancements in carbon catalysts have been reported, there is still a lack of understanding which surface features might enhance their efficiency for ORR. Through a detailed study of oxygen adsorption on carbon molecular sieves and using inelastic neutron scattering, we demonstrated here that the extent of oxygen adsorption/interactions with surface is an important parameter affecting ORR. It was found that both the strength of O2 physical adsorption in small pores and its specific interactions with surface ether functionalities in the proximity of pores positively influence the ORR efficiency. We have shown that ultramicropores and hydrophobic surface rich in ether-based groups and/or electrons enhance ORR on carbon electrocatalysts and the performance parameters are similar to those measured on Pt/C with the number of electron transfer equal to 4.