Fine-tuning of Substrate Affinity Leads to Alternative Roles of Mycobacterium tuberculosis Fe2+-ATPases

Little is known about iron efflux transporters within bacterial systems. Recently, the participation of Bacillus subtilis PfeT, a P1B4-ATPase, in cytoplasmic Fe(2+) efflux has been proposed. We report here the distinct roles of mycobacterial P1B4-ATPases in the homeostasis of Co(2+) and Fe(2+) Mutation of Mycobacterium smegmatis ctpJ affects the homeostasis of both ions. Alternatively, an M. tuberculosis ctpJ mutant is more sensitive to Co(2+) than Fe(2+), whereas mutation of the homologous M. tuberculosis ctpD leads to Fe(2+) sensitivity but no alterations in Co(2+) homeostasis. In vitro, the three enzymes are activated by both Fe(2+) and Co(2+) and bind 1 eq of either ion at their transport site. However, equilibrium binding affinities and activity kinetics show that M. tuberculosis CtpD has higher affinity for Fe(2+) and twice the Fe(2+)-stimulated activity than the CtpJs. These parameters are paralleled by a lower activation and affinity for Co(2+) Analysis of Fe(2+) and Co(2+) binding to CtpD by x-ray absorption spectroscopy shows that both ions are five- to six-coordinate, constrained within oxygen/nitrogen environments with similar geometries. Mutagenesis studies suggest the involvement of invariant Ser, His, and Glu residues in metal coordination. Interestingly, replacement of the conserved Cys at the metal binding pocket leads to a large reduction in Fe(2+) but not Co(2+) binding affinity. We propose that CtpJ ATPases participate in the control of steady state Fe(2+) levels. CtpD, required for M. tuberculosis virulence, is a high affinity Fe(2+) transporter involved in the rapid response to iron dyshomeostasis generated upon redox stress

Downgrading – An overlooked reality in African cities: Reflections from an indigenous neighborhood of Accra, Ghana

African cities contain a range of low-income ethnic and cultural enclaves that defy conventional ‘slum’ typecasts and intervention guidelines. Further, new forms of urbanization (e.g. gated communities and informal settlements) have received heavy emphasis in recent urban geographic research. Such research emphases have many unintended consequences; one of which is that traditional indigenous neighborhoods in the older city are glossed over. This paper focuses on urban downgrading in Korle Gonno, a prominent and established indigenous community in Accra, Ghana. Using mixed-method data (including surveys), the results illustrate that a traditional neighborhood encounters many of the same dimensions of urban poverty as the more famed slums in the city, yet it experiences different poverty trajectories. We argue that the prevailing slum profiling techniques fall short of capturing these trajectories; more nuanced approaches that capture continuity and discontinuity with past and present socioeconomic processes are necessary. Attention must be rebalanced toward understanding the deterioration of these neighborhoods if policymakers, planners and urban theorists are to obtain a comprehensive picture of poverty dynamics and appropriate interventions in African cities. ► Downgrading traditional neighborhoods in African cities are understudied. ► Korle Gonno's residents face similar poverty dimensions as those in informal slums do. ► The magnitude and scale of urban poverty in Accra reaches beyond informal slums. ► Quantitative indicators alone do not capture full extent of urban poverty in Africa. ► City authorities in African cities need more nuanced poverty analysis techniques

Crowdsourcing interactions: using crowdsourcing for evaluating interactive information retrieval systems

In the field of information retrieval (IR), researchers and practitioners are often faced with a demand for valid approaches to evaluate the performance of retrieval systems. The Cranfield experiment paradigm has been dominant for the in-vitro evaluation of IR systems. Alternative to this paradigm, laboratory-based user studies have been widely used to evaluate interactive information retrieval (IIR) systems, and at the same time investigate users’ information searching behaviours. Major drawbacks of laboratory-based user studies for evaluating IIR systems include the high monetary and temporal costs involved in setting up and running those experiments, the lack of heterogeneity amongst the user population and the limited scale of the experiments, which usually involve a relatively restricted set of users. In this paper, we propose an alternative experimental methodology to laboratory-based user studies. Our novel experimental methodology uses a crowdsourcing platform as a means of engaging study participants. Through crowdsourcing, our experimental methodology can capture user interactions and searching behaviours at a lower cost, with more data, and within a shorter period than traditional laboratory-based user studies, and therefore can be used to assess the performances of IIR systems. In this article, we show the characteristic differences of our approach with respect to traditional IIR experimental and evaluation procedures. We also perform a use case study comparing crowdsourcing-based evaluation with laboratory-based evaluation of IIR systems, which can serve as a tutorial for setting up crowdsourcing-based IIR evaluations

Kaplan-Meier plot showing the proportion of participants reporting arthralgia over time in years in Managua, Nicaragua (2014–2018).

A Kaplan-Meier graph plotting the proportion of participants not reporting arthralgia (y-axis) against days since fever onset (x-axis). Ticks correspond to censoring events. Panels show the distribution of participants beginning 10 days post-fever onset and ending at the last reported data point based on the exclusion criteria (< 625 days post-fever onset), stratified by age range (A) and sex (B). The p-values were calculated using the log-rank test.</p

Reported polyarthralgia beyond the acute phase of chikungunya associated-arthralgia by body part and age in year in Managua, Nicaragua (2014–2018).

Cluster dendrogram depicting the relationship between occurrence of polyarthralgia across the different body parts, with the y-axis representing the underlying cluster distance calculated using the Manhattan distance method. The cophenetic distance correlation coefficient is 0.95; the higher the cophenetic distance correlation coefficient is, the more appropriately the dendrogram represents a hierarchical structure present in the original data (A). Age trends of the prevalence of arthralgia among clustered body groups (B) and individual body parts (C), including the 95% confidence intervals, visualized using shading corresponding to each respective color group and depicted using a generalized additive model.</p

Prevalence of post-acute polyarthralgia by age and body part in Managua, Nicaragua (2014–2018).

Prevalence of post-acute polyarthralgia by age and body part in Managua, Nicaragua (2014–2018).</p

Risk factors for acute chikungunya-associated arthralgia in Managua, Nicaragua (2014–2018).

Risk factors for acute chikungunya-associated arthralgia in Managua, Nicaragua (2014–2018).</p

Odds of progressing to chronic chikungunya-associated arthralgia after an initial presentation with only acute or interim chikungunya-associated arthralgia in Managua, Nicaragua (2014–2018).

Odds of progressing to chronic chikungunya-associated arthralgia after an initial presentation with only acute or interim chikungunya-associated arthralgia in Managua, Nicaragua (2014–2018).</p

Density plot of participants stratified by age range in years in Managua, Nicaragua (2014–2018).

The percent of participants in this study across age are depicted using an age-density plot. Colors correspond to the age-ranges defined within the study (0–4, 5–9, 10–15, and 16+ years old). (TIF)</p

Prevalence of reports of arthralgia in the acute and post-acute phase in Managua, Nicaragua (2014–2018).

Prevalence of reports of arthralgia in the acute and post-acute phase in Managua, Nicaragua (2014–2018).</p