How to master the host immune system? Leishmania parasites have the solutions!

Infection by protozoan parasites of the genus Leishmania results in the development of leishmaniasis, an increasingly prevalent group of diseases affecting over 12 million people worldwide. Leishmaniasis can have very different outcomes ranging from cutaneous lesions, mucosal lesions to visceralization depending on the species of the infecting parasite and on the immune response developed by the host. As an obligate intracellular parasite, residing within macrophages, Leishmania evolved in strict contact with the host immune system, developing different mechanisms to evade or modulate the immune response. Various types of immune responses are observed during different Leishmania spp. infections, resulting in parasite clearance but also contributing to the pathogenesis, thus increasing the complexity of the course of the disease. Interestingly, depending on the type of leishmaniasis developed, opposite treatment strategies, which either boost or inhibit the inflammatory response, have shown efficacy. In this review, we summarize the contribution of different immune cell types to the development of the anti-leishmanial immune response and the parasite strategies to evade and modulate host immunity. Further, we discuss the involvement of co-infecting pathogens in the determination of the outcome of leishmaniasis and on the effectiveness of treatment and the implication of the immune response for treatment and vaccine development

The criminal association of Leishmania parasites and viruses.

In nature, humans infected with protozoan parasites can encounter viruses, which could alter their host immune response. The impact of viruses on human parasitic diseases remains largely unexplored due to the highly sterilized environment in experimental studies and the difficulty to draw a correlation between co-infection and pathology. Recent studies show that viral infections exacerbate pathology and promote dissemination of some Leishmania infections, based on a hyper-inflammatory reaction driven by type I interferons. Thus, not only the infecting parasite species, but also bystander viral infections could be a major determinant of the outcome of Leishmania infection. In this review, we focus on the contribution of viral co-infection to the exacerbation of leishmaniasis's pathology and its possible impact on treatment and vaccination strategies

An explicit KO-degree map and applications

The goal of this note is to study the analog in unstable ${{\mathbb A}^1}$-homotopy theory of the unit map from the motivic sphere spectrum to the Hermitian K-theory spectrum, i.e., the degree map in Hermitian K-theory. We show that "Suslin matrices", which are explicit maps from odd dimensional split smooth affine quadrics to geometric models of the spaces appearing in Bott periodicity in Hermitian K-theory, stabilize in a suitable sense to the unit map. As applications, we deduce that $K^{MW}_i(F) = GW^i_i(F)$ for $i \leq 3$, which can be thought of as an extension of Matsumoto's celebrated theorem describing $K_2$ of a field. These results provide the first step in a program aimed at computing the sheaf $\pi_{n}^{{\mathbb A}^1}({\mathbb A}^n \setminus 0)$ for $n \geq 4$.Comment: 36 Pages, Final version, to appear Journal of Topolog

The relative importance of personal beliefs, meta-stereotypes and societal stereotypes of age for the wellbeing of older people

Negative images of old age can harm older individuals' cognitive and physical functioning and health. Yet, older people may be confronted with age stereotypes that are inconsistent with their own personal beliefs. We examine the implications for older people's wellbeing of three distinct elements of age stereotypes: their personal beliefs about their age group, their perception about how others generally perceive older people (i.e. their meta-stereotypes) and the societal age stereotypes that are empirically widely shared in society. Using measures from the Stereotype Content Model and survey data of older people from the United Kingdom (UK) (Study 1, N = 171), we found only partial overlap between older people's personal beliefs and their meta-stereotypes. Personal beliefs were unrelated to wellbeing, but positive meta-stereotypes of older people's competence were linked to higher wellbeing. These findings were largely replicated with a sample of baby-boomers from Switzerland (Study 2, N = 400) controlling for socio-demographics. Study 3 used representative survey data (N = 10,803) across 29 European countries, to test and confirm that the link between positive competence meta-stereotypes and wellbeing can be generalised to different cultures, and that positive warmth meta-stereotypes were an additional predictor. At the country level, societal age stereotypes about competence were positively related to the wellbeing of older people, but only in countries that provide greater opportunities for competence attainment.info:eu-repo/semantics/acceptedVersio

The path to fusion power†

The promise, status and challenges of developing fusion power are outlined. The key physics and engineering principles are described and recent progress quantified. As the successful demonstration of 16 MW of fusion in 1997 in the Joint European Torus showed, fusion works. The central issue is therefore to make it work reliably and economically on the scale of a power station. We argue that to meet this challenge in 30 years we must follow the aggressive programme known as the ‘Fast Track to Fusion’. This programme is described in some detail

Caspase-mediated cleavage of raptor participates in the inactivation of mTORC1 during cell death.

The mammalian target of rapamycin complex 1 (mTORC1) is a highly conserved protein complex regulating key pathways in cell growth. Hyperactivation of mTORC1 is implicated in numerous cancers, thus making it a potential broad-spectrum chemotherapeutic target. Here, we characterized how mTORC1 responds to cell death induced by various anticancer drugs such rapamycin, etoposide, cisplatin, curcumin, staurosporine and Fas ligand. All treatments induced cleavage in the mTORC1 component, raptor, resulting in decreased raptor-mTOR interaction and subsequent inhibition of the mTORC1-mediated phosphorylation of downstream substrates (S6K and 4E-BP1). The cleavage was primarily mediated by caspase-6 and occurred at two sites. Mutagenesis at one of these sites, conferred resistance to cell death, indicating that raptor cleavage is important in chemotherapeutic apoptosis