The Role of Phagocytes in Immunity to Candida albicans

Body clearance of fungi such as Candida albicans involves phagocytosis by fixed tissue macrophages as well as infiltrating monocytes and neutrophils. Through phagocytosis, the fungi are confined and killed by the oxidative and non-oxidative anti-microbial systems. These include oxygen derived reactive species, generated from the activation of the NADPH oxidase complex and granule constituents. These same mechanisms are responsible for the damage to hyphal forms of C. albicans. Complement promotes phagocytosis, through their interaction with a series of complement receptors including the recently described complement receptor immunoglobulin. However, it is also evident that under other conditions, the killing of yeast and hyphal forms can occur in a complement-independent manner. Phagocytosis and killing of Candida is enhanced by the cytokine network, such as tumour necrosis factor and interferon gamma. Patients with primary immunodeficiency diseases who have phagocytic deficiencies, such as those with defects in the NADPH oxidase complex are predisposed to fungal infections, providing evidence for the critical role of phagocytes in anti-fungal immunity. Secondary immunodeficiencies can arise as a result of treatment with anti-cancer or other immunosuppressive drugs. These agents may also predispose patients to fungal infections due to their ability to compromise the anti-microbial activity of phagocytes

A new foundational crisis in mathematics, is it really happening?

The article reconsiders the position of the foundations of mathematics after the discovery of HoTT. Discussion that this discovery has generated in the community of mathematicians, philosophers and computer scientists might indicate a new crisis in the foundation of mathematics. By examining the mathematical facts behind HoTT and their relation with the existing foundations, we conclude that the present crisis is not one. We reiterate a pluralist vision of the foundations of mathematics. The article contains a short survey of the mathematical and historical background needed to understand the main tenets of the foundational issues.Comment: Final versio

An order-theoretic characterization of the Howard-Bachmann-hierarchy

In this article we provide an intrinsic characterization of the famous Howard-Bachmann ordinal in terms of a natural well-partial-ordering by showing that this ordinal can be realized as a maximal order type of a class of generalized trees with respect to a homeomorphic embeddability relation. We use our calculations to draw some conclusions about some corresponding subsystems of second order arithmetic. All these subsystems deal with versions of light-face Π₁¹-comprehension

The cell adhesion molecule L1 regulates the expression of choline acetyltransferase and the development of septal cholinergic neurons

Mutations in the L1 gene cause severe brain malformations and mental retardation. We investigated the potential roles of L1 in the regulation of choline acetyltransferase (ChAT) and in the development of septal cholinergic neurons, which are known to project to the hippocampus and play key roles in cognitive functions. Using stereological approaches, we detected significantly fewer ChAT-positive cholinergic neurons in the medial septum and vertical limb of the diagonal band of Broca (MS/VDB) of 2-week-old L1-deficient mice compared to wild-type littermates (1644 ± 137 vs. 2051 ± 165, P = 0.038). ChAT protein levels in the septum were 53% lower in 2-week-old L1-deficient mice compared to wild-type littermates. ChAT activity in the septum was significantly reduced in L1-deficient mice compared to wild-type littermates at 1 (34%) and 2 (40%) weeks of age. In vitro, increasing doses of L1-Fc induced ChAT activity in septal neurons with a significant linear trend (*P = 0.0065). At 4 weeks of age in the septum and at all time points investigated in the caudate-putamen (CPu), the number of ChAT-positive neurons and the levels of ChAT activity were not statistically different between L1-deficient mice and wild-type littermates. The total number of cells positive for the neuronal nuclear antigen (NeuN) in the MS/VDB and CPu was not statistically different in L1-deficient mice compared to wild-type littermates, and comparable expression of the cell cycle marker Ki67 was observed. Our results indicate that L1 is required for the timely maturation of septal cholinergic neurons and that L1 promotes the expression and activity of ChAT in septal neurons

The tomato Prf complex is a molecular trap for bacterial effectors based on Pto transphosphorylation

The bacteria Pseudomonas syringae is a pathogen of many crop species and one of the model pathogens for studying plant and bacterial arms race coevolution. In the current model, plants perceive bacteria pathogens via plasma membrane receptors, and recognition leads to the activation of general defenses. In turn, bacteria inject proteins called effectors into the plant cell to prevent the activation of immune responses. AvrPto and AvrPtoB are two such proteins that inhibit multiple plant kinases. The tomato plant has reacted to these effectors by the evolution of a cytoplasmic resistance complex. This complex is compromised of two proteins, Prf and Pto kinase, and is capable of recognizing the effector proteins. How the Pto kinase is able to avoid inhibition by the effector proteins is currently unknown. Our data shows how the tomato plant utilizes dimerization of resistance proteins to gain advantage over the faster evolving bacterial pathogen. Here we illustrate that oligomerisation of Prf brings into proximity two Pto kinases allowing them to avoid inhibition by the effectors by transphosphorylation and to activate immune responses

On Relating Theories: Proof-Theoretical Reduction

The notion of proof-theoretical or finitistic reduction of one theory to another has a long tradition. Feferman and Sieg (Buchholz et al., Iterated inductive definitions and subsystems of analysis. Springer, Berlin, 1981, Chap. 1) and Feferman in (J Symbol Logic 53:364–384, 1988) made first steps to delineate it in more formal terms. The first goal of this paper is to corroborate their view that this notion has the greatest explanatory reach and is superior to others, especially in the context of foundational theories, i.e., theories devised for the purpose of formalizing and presenting various chunks of mathematics. A second goal is to address a certain puzzlement that was expressed in Feferman’s title of his Clermont-Ferrand lectures at the Logic Colloquium 1994: “How is it that finitary proof theory became infinitary?” Hilbert’s aim was to use proof theory as a tool in his finitary consistency program to eliminate the actual infinite in mathematics from proofs of real statements. Beginning in the 1950s, however, proof theory began to employ infinitary methods. Infinitary rules and concepts, such as ordinals, entered the stage. In general, the more that such infinitary methods were employed, the farther did proof theory depart from its initial aims and methods, and the closer did it come instead to ongoing developments in recursion theory, particularly as generalized to admissible sets; in both one makes use of analogues of regular cardinals, as well as “large” cardinals (inaccessible, Mahlo, etc.). (Feferman 1994). The current paper aims to explain how these infinitary tools, despite appearances to the contrary, can be formalized in an intuitionistic theory that is finitistically reducible to (actually Π02 -conservative over) intuitionistic first order arithmetic, also known as Heyting arithmetic. Thus we have a beautiful example of Hilbert’s program at work, exemplifying the Hilbertian goal of moving from the ideal to the real by eliminating ideal elements

Ordinal notation systems corresponding to Friedman's linearized well-partial-orders with gap-condition

In this article we investigate whether the following conjecture is true or not: does the addition-free theta functions form a canonical notation system for the linear versions of Friedman’s well-partial-orders with the so-called gap-condition over a finite set of n labels. Rather surprisingly, we can show this is the case for two labels, but not for more than two labels. To this end, we determine the order type of the notation systems for addition-free theta functions in terms of ordinals less than ε0ε0 . We further show that the maximal order type of the Friedman ordering can be obtained by a certain ordinal notation system which is based on specific binary theta functions

Mol Vis

PURPOSE: To analyze in vivo the function of chicken acidic leucine-rich epidermal growth factor-like domain containing brain protein/Neuroglycan C (gene symbol: Cspg5) during retinal degeneration in the Rpe65(-)/(-) mouse model of Leber congenital amaurosis. METHODS: We resorted to mice with targeted deletions in the Cspg5 and retinal pigment epithelium protein of 65 kDa (Rpe65) genes (Cspg5(-)/(-)/Rpe65(-)/(-)). Cone degeneration was assessed with cone-specific peanut agglutinin staining. Transcriptional expression of rhodopsin (Rho), S-opsin (Opn1sw), M-opsin (Opn1mw), rod transducin alpha subunit (Gnat1), and cone transducin alpha subunit (Gnat2) genes was assessed with quantitative PCR from 2 weeks to 12 months. The retinal pigment epithelium (RPE) was analyzed at P14 with immunodetection of the retinol-binding protein membrane receptor Stra6. RESULTS: No differences in the progression of retinal degeneration were observed between the Rpe65(-)/(-) and Cspg5(-)/(-)/Rpe65(-)/(-) mice. No retinal phenotype was detected in the late postnatal and adult Cspg5(-)/(-) mice, when compared to the wild-type mice. CONCLUSIONS: Despite the previously reported upregulation of Cspg5 during retinal degeneration in Rpe65(-)/(-) mice, no protective effect or any involvement of Cspg5 in disease progression was identified

Collection Principles in Dependent Type Theory

We introduce logic-enriched intuitionistic type theories, that extend intuitionistic dependent type theories with primitive judgements to express logic. By adding type theoretic rules that correspond to the collection axiom schemes of the constructive set theory CZF we obtain a generalisation of the type theoretic interpretation of CZF. Suitable logic-enriched type theories allow also the study of reinterpretations of logic. We end the paper with an application to the double-negation in- terpretation