Propositionalism without propositions, objectualism without objects

Propositionalism is the view that all intentional states are propositional states, which are states with a propositional content, while objectualism is the view that at least some intentional states are objectual states, which are states with objectual contents, such as objects, properties, and kinds. This paper argues that there are two distinct ways of understanding propositionalism and objectualism: (1) as views about the deep nature of the contents of intentional states, and (2) as views about the superficial character of the contents of intentional states. I argue that we should understand the views in the second way. I also argue that the propositionalism debate is fairly independent from debates over the deep nature of intentionality, and that this has implications for arguments for propositionalism and objectualism from claims about the nature of intentional content. I close with a short discussion of how related points apply to the debate over singular content

Antigen Diversity in the Parasitic Bacterium Anaplasma phagocytophilum Arises from Selectively-Represented, Spatially Clustered Functional Pseudogenes

Anaplasma phagocytophilum is a tick-transmitted bacterial pathogen of humans and other animals, and is an obligate intracellular parasite. Throughout the course of infection, hosts acquire temporary resistance to granulocytic anaplasmosis as they develop immunity specific for the major antigen, major surface protein 2 (Msp2). However, the bacterium then utilizes a novel recombination mechanism shuffling functional pseudogenes sequentially into an expression cassette with conserved 5′ and 3′ ends, bypassing host immunity. Approximately 100 pseudogenes are present in the only fully sequenced human-origin HZ genome, representing the possibility for almost unlimited antigenic diversity. In the present study, we identified a select group of 20% of the A. phagocytophilum HZ msp2 pseudogenes that have matched preferentially to human, canine, and equine expression cassettes. Pseudogenes cluster predominantly in one spatial run limited to a single genomic island in less than 50% of the genome but phylogenetically related pseudogenes are neither necessarily located in close proximity on the genome nor share similar percent identity with expression cassettes. Pseudogenes near the expression cassette (and the origin) are more likely to be expressed than those farther away. Taken together, these findings suggest that there may be natural selection pressure to retain pseudogenes in one cluster near the putative origin of replication, even though global recombination shuffles pseudogenes around the genome, separating pseudogenes that share genetic origins as well as those with similar identities

Contribution of water-limited ecoregions to their own supply of rainfall

The occurrence of wet and dry growing seasons in water-limited regions remains poorly understood, partly due to the complex role that these regions play in the genesis of their own rainfall. This limits the predictability of global carbon and water budgets, and hinders the regional management of naturalresources. Using novel satellite observations and atmospheric trajectory modelling, we unravel the origin and immediate drivers of growing-season precipitation, and the extent to which ecoregions themselves contribute to their own supply of rainfall. Results show that persistent anomalies in growing-season precipitation—and subsequent biomass anomalies—are caused by a complex interplay of land and ocean evaporation, air circulation and local atmospheric stability changes. For regions such as the Kalahari and Australia, the volumes of moisture recycling decline in dry years, providing a positive feedback that intensifies dry conditions. However, recycling ratios increase up to40%, pointing to the crucial role of these regions in generating their own supply of rainfall; transpiration in periods of water stress allows vegetation to partly offset the decrease in regional precipitation. Findings highlight the need to adequately represent vegetation–atmosphere feedbacks in models to predict biomass changes and to simulate the fate of water-limited regions in our warming climate

Dogs are more permissive than cats or guinea pigs to experimental infection with a human isolate of Bartonella rochalimae

Bartonella rochalimae was first isolated from the blood of a human who traveled to Peru and was exposed to multiple insect bites. Foxes and dogs are likely natural reservoirs for this bacterium. We report the results of experimental inoculation of two dogs, five cats and six guinea pigs with the only human isolate of this new Bartonella species. Both dogs became bacteremic for 5–7 weeks, with a peak of 103–104 colony forming units (CFU)/mL blood. Three cats had low bacteremia levels (< 200 CFU/mL) of 6–8 weeks’ duration. One cat that remained seronegative had two bacterial colonies isolated at a single culture time point. A fifth cat never became bacteremic, but seroconverted. None of the guinea pigs became bacteremic, but five seroconverted. These results suggest that dogs could be a reservoir of this strain of B. rochalimae, in contrast to cats and guinea pigs

Design method for estimation of unit value of extrication works after an accident using selected special technologies for removing the traffic obstacle on a motorway

Abstrakt Tato diplomová práce je dílčí součástí celkového projektu na stanovení všeobecné metodiky výpočtu nákladů na vyproštění nákladního automobilu. Zabývá se legislativou související s vyproštěním nákladních vozidel, analýzou nákladů a vyčíslení nákladů v důsledku odtahů u vybrané speciální techniky po nehodě. Práce je vodítkem pro znalce z ústavu soudního inženýrství, kteří na základě podkladů mohou snadněji stanovit postup a jednotkovou cenu vyprošťovacích prací po nehodě. Poté se zrychlí určování této ceny např. při soudních jednání a vyplacení zisků odtahovým firmám.Abstract (example) This thesis is a minor part of the overall project on the establishment of a general methodology of calculation of the cost of rescuing a lorry. It deals with legislation related to goods vehicle extrication, analysis of costs and costs as a result of exhausts for selected special equipment after an accident. The work is a guide for experts from the Institute of forensic engineering, on the basis of who can more easily establish a procedure and the unit price recovery work after the accident. Then speeds up determining the prices for example during the court proceedings and the payment of the profits of a business.

Fetal Demise and Failed Antibody Therapy During Zika Virus Infection of Pregnant Macaques

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission

Rebalancing of mitochondrial homeostasis through an NAD+-SIRT1 pathway preserves intestinal barrier function in severe malnutrition.

BACKGROUND: The intestine of children with severe malnutrition (SM) shows structural and functional changes that are linked to increased infection and mortality. SM dysregulates the tryptophan-kynurenine pathway, which may impact processes such as SIRT1- and mTORC1-mediated autophagy and mitochondrial homeostasis. Using a mouse and organoid model of SM, we studied the repercussions of these dysregulations on malnutrition enteropathy and the protective capacity of maintaining autophagy activity and mitochondrial health. METHODS: SM was induced through feeding male weanling C57BL/6 mice a low protein diet (LPD) for 14-days. Mice were either treated with the NAD +-precursor, nicotinamide; an mTORC1-inhibitor, rapamycin; a SIRT1-activator, resveratrol; or SIRT1-inhibitor, EX-527. Malnutrition enteropathy was induced in enteric organoids through amino-acid deprivation. Features of and pathways to malnutrition enteropathy were examined, including paracellular permeability, nutrient absorption, and autophagic, mitochondrial, and reactive-oxygen-species (ROS) abnormalities. FINDINGS: LPD-feeding and ensuing low-tryptophan availability led to villus atrophy, nutrient malabsorption, and intestinal barrier dysfunction. In LPD-fed mice, nicotinamide-supplementation was linked to SIRT1-mediated activation of mitophagy, which reduced damaged mitochondria, and improved intestinal barrier function. Inhibition of mTORC1 reduced intestinal barrier dysfunction and nutrient malabsorption. Findings were validated and extended using an organoid model, demonstrating that resolution of mitochondrial ROS resolved barrier dysfunction. INTERPRETATION: Malnutrition enteropathy arises from a dysregulation of the SIRT1 and mTORC1 pathways, leading to disrupted autophagy, mitochondrial homeostasis, and ROS. Whether nicotinamide-supplementation in children with SM could ameliorate malnutrition enteropathy should be explored in clinical trials. FUNDING: This work was supported by the Bill and Melinda Gates Foundation, the Sickkids Research Institute, the Canadian Institutes of Health Research, and the University Medical Center Groningen