Interferon-Gamma Release Assay (Modified QuantiFERON) as a Potential Marker of Infection for Leishmania donovani, a Proof of Concept Study

Visceral leishmaniasis is caused by a parasite of the Leishmania species, but infection does not always lead to overt clinical disease. To detect infection, the Montenegro test or Leishmanin Skin Test (LST) is used along with serological markers. The LST is a test of the delayed-type hypersensitivity response read 48–72 hours after intradermal injection of leishmanin antigen. LST has many drawbacks, as complex administration and reading, boosting of anamnestic immune responses and difficult sourcing of GMP-compliant product and alternative tools for epidemiological research are badly needed. We evaluated whether a Interferon-γ Release Assay based on the QuantiFERON-TB test format, which was approved by the Food and Drug Administration (FDA) as a test for detecting latent Mycobacterium tuberculosis infection, could become an in vitro diagnostic aid for the measurement of cell-mediated immune reactivity against L.donovani. We obtained good results with one of five of the antigens we evaluated and confirm the potential of this assay

Austerity urbanism and Olympic counter-legacies: gendering, defending and expanding the urban commons in East London

This article reflects on an occupation led by single mothers to contest the destruction of social housing in post-Olympics East London. In the process, it argues for a more gendered theorisation of the urban commons. Drawing on auto-ethnography, participant observation and qualitative interviews, the article argues three central points: First, that the occupation demonstrates the gendered nature of the urban commons and the leadership of women in defending them from enclosure; second that the defence of an existing urban commons enabled the creation of a new temporary commons characterised by the collectivisation of gendered socially reproductive activities; and third that this commoning has had a lasting impact on housing activism at the city scale and beyond. This impact is conceptualised as an ‘Olympic counter-legacy’ that is characterised by the forging of new relationships and affinities, the strengthening of networked activism and circulation of tactics between campaign groups

Plastic possibilities: Contrasting the uses of plastic ‘waste’ in India

This is the final version. Available on open access from Wiley via the DOI in this recordThis article draws on examples of inventive plastic reuse from India and personal anecdotes of elders as an anthropological reflection on possible plastic futures. It sketches the large-scale governmental reforms in the domain of municipal solid waste management, or MSWM (which, by legal definition in India, includes plastic waste). In this regard, it draws out some of the problematic socio-political and environmental implications of Prime Minister Narendra Modi's ‘Clean India’ campaign, whose technocratic policy orientations towards standardized centralized MSWM echo his cultural nationalist agenda. These reforms contrast with home-based re-engineering methods and the redeploying of plastic discards (thereby making them notuner moton (‘like new again’), and their localized circulation through relatively local but uneven reputational and economic networks. Clean India sequesters and processes vast quantities of plastics through the wide-ranging adoption of a waste-to-energy techno-fix (in which plastics are incinerated). In contrast, the authors illustrate routine practices and relations whereby people reuse, repurpose and recycle plastics. While Clean India can detract from and disrupt these mundane practices and everyday relations, these are suggestive of alternative plastic futures – both socio-material and environmental

Measurement of Recent Exposure to Phlebotomus argentipes, the Vector of Indian Visceral Leishmaniasis, by Using Human Antibody Responses to Sand Fly Saliva

Antibody (IgG) responses to the saliva of Phlebotomus argentipes were investigated using serum samples from regions of India endemic and non-endemic for visceral leishmaniasis (VL). By pre-adsorbing the sera against the saliva of the competing human-biting but non-VL vector P. papatasi, we significantly improved the specificity of a P. argentipes saliva enzyme-linked immunosorbent assay. Using this method, we observed a statistically significant correlation between antibodies to P. argenitpes saliva and the average indoor density of female sand flies. Additionally, the method was able to detect recent changes in vector exposure when sera from VL patients were assayed before, during, and after hospitalization and protected from sand fly bites under untreated bed nets. Collectively, these results highlight the utility of antibodies to P. argentipes saliva as an important tool to evaluate VL vector control programs

Decommissioning care: The need for rigorous multifaceted evaluations of decisions to withdraw health services

In this Perspective on the two clinical trials of Terry Haines and colleagues that incrementally removed and reinstated allied healthcare services, Aziz Sheikh discusses the evidence base for the routine provision of such services

A Nanoparticle-Based Approach for the Detection of Extracellular Vesicles

The analysis of extracellular vesicles (EVs) typically requires tedious and time-consuming isolation process from bio-fluids. We developed a nanoparticle-based time resolved fluorescence immunoassay (NP-TRFIA) that uses biotinylated antibodies against the proteins of tetraspanin family and tumor-associated antigens for capturing EVs from urine samples and cell culture supernatants without the need for isolation. The captured-EVs were detected either with Eu3+-chelate or Eu3+-doped nanoparticle-based labels conjugated either to antibodies against the tetraspanins or lectins targeting the glycan moieties on EVs surface. The NP-TRFIA demonstrated specific capturing and detection of EVs by antibodies and lectins. Lectin-nanoparticle based assays showed 2–10 fold higher signal-to-background ratio compared with lectin-chelate assays. The nanoparticle assay concept allowed surface glycosylation profiling of the urine derived-EVs with lectins. It was also applied to establish an assay showing differential expression of tumor-associated proteins on more aggressive (higher ITGA3 on DU145- and PC3-EVs) compared to less aggressive (higher EpCAM on LNCaP-EVs) PCa- cell lines derived-EVs. This NP-TRFIA can be used as a simple tool for analysis and characterization of EVs in urine and cell culture supernatants. Such approach could be useful in identification of disease-specific markers on the surface of patient-derived urinary EVs

Marriage and the crisis of peasant society in Gujarat, India

This contribution takes marriage as the example of a crisis of production and reproduction in rural India. Through the juxtaposition of ethnography separated by six decades, we detail a shift away from land and agriculture as the primary markers of status among the Patidars of central Gujarat, western India, in favour of a hierarchical understanding of international migration. The paper discusses the disconnect between a cultural revolution in favour of migration, and the failure of many to live up to their own cultural standards. More broadly, we reflect on the forces that simultaneously strengthen and dissolve caste inequality in the context of India's uneven growth

Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth

Targeted cancer therapies, which act on specific cancer-associated molecular targets, are predominantly inhibitors of oncogenic kinases. While these drugs have achieved some clinical success, the inactivation of kinase signaling via stimulation of endogenous phosphatases has received minimal attention as an alternative targeted approach. Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. Our group previously developed a series of orally bioavailable small molecule activators of PP2A, termed SMAPs. We now report that SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse xenografts and transgenic models. Mechanistically, we found that SMAPs act by binding to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. These results show that PP2A can be activated in cancer cells to inhibit proliferation. Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins