Modelling a silent epidemic:A review of the in vitro models of latent tuberculosis

Tuberculosis (TB) is the primary cause of death by a single infectious agent; responsible for around two million deaths in 2016. A major virulence factor of TB is the ability to enter a latent or Non-Replicating Persistent (NRP) state which is presumed untreatable. Approximately 1.7 billion people are latently infected with TB and on reactivation many of these infections are drug resistant. As the current treatment is ineffective and diagnosis remains poor, millions of people have the potential to reactivate into active TB disease. The immune system seeks to control the TB infection by containing the bacteria in a granuloma, where it is exposed to stressful anaerobic and nutrient deprived conditions. It is thought to be these environmental conditions that trigger the NRP state. A number of in vitro models have been developed that mimic conditions within the granuloma to a lesser or greater extent. These different models have all been utilised for the research of different characteristics of NRP Mycobacterium tuberculosis, however their disparity in approach and physiological relevance often results in inconsistencies and a lack of consensus between studies. This review provides a summation of the different NRP models and a critical analysis of their respective advantages and disadvantages relating to their physiological relevance

Effective Occupational Therapy Interventions to Decrease Picky Eating in Children: A Systematic Review

PURPOSE: Picky eating is related to the lack of consumption in food variety by children when shown different foods (Wolstenholme et al., 2020). A 2015 study reported that almost half of children experience a period of picky eating at some point during early childhood, including almost 15% of children for whom picky eating does not resolve by age 6 (Cardona et al., 2015). The purpose of this systematic review is to identify interventions within the scope of occupational therapy that increase food acceptance in children under the age of seven years who demonstrate picky eating characteristics and who have no underlying health conditions. DESIGN: This systematic review included articles relevant to children under the age of 7 with no underlying health conditions, addressed unfamiliar food introductions or picky eating interventions, and assessed food consumption and variety. Level I evidence published in 2012 to 2023 in peer-reviewed journals was included. METHOD: We reviewed the title and abstract of 738 articles from four different literature databases; each title and abstract was reviewed by two researchers to build consensus about which articles would be considered for full-text review. Then we reviewed the full text of 102 articles that appeared to meet or might meet the study’s inclusion criteria, all of which were reviewed by at least two researchers. Twelve articles met the inclusion criteria of this study. We used the U.S. Preventive Services Task Force levels of certainty and grade definition to describe the strength of evidence across these 12 studies. RESULTS: We categorized articles into three different themes: taste exposure, nutrition education, and flavor change. Nine articles provided strong support for occupation-based interventions involving taste exposure for improving food acceptance and variety. These interventions consisted of screen-based modeling, offering unfamiliar food at snack times, making the foods into small pieces to eat, and using rewards or praise. There was moderate evidence supporting nutrition education and flavor change; these interventions included picture books, school based nutritional education, flavor change of vegetables, and changing the form of vegetables, respectively. CONCLUSION: Overall, this systematic review identifies several strategies within the scope of occupational therapy practice that may improve food consumption and variety in picky eaters aged seven and under. Eating is a chief activity of daily living and essential to life, and occupational therapy services can address picky eating by using interventions tailored to the individual. Occupational therapy practitioners can use taste exposure to effectively increase food consumption. Since there is moderate evidence to support interventions involving nutrition education and flavor change, practitioners should consider recommending these interventions on a routine basis. Future research could refine protocols’ intervention activities, frequency, and duration. Cardona Cano, S., Tiemeier, H., Van Hoeken, D., Tharner, A., Jaddoe, V. W., Hofman, A., Verhulst, F. C., & Hoek, H. W. (2015). Trajectories of picky eating during childhood: A general population study. The International Journal of Eating Disorders, 48(6), 570–579. https://doi.org/10.1002/eat.22384 Wolstenholme, H., Kelly, C., Hennessy, M., & Heary, C. (2020). Childhood fussy/picky eating behaviours: A systematic review and synthesis of qualitative studies. International Journal of Behavioral Nutrition and Physical Activity, 17(2), p.1-2. [CJ1] [JL2] https://doi.org/10.1186/s12966-019-0899-xhttps://digitalcommons.unmc.edu/cahp_ot_sysrev/1004/thumbnail.jp

Cholesterol-dependent activity of dapsone against non-replicating persistent mycobacteria

One-third of the world’s population is estimated to be latently infected with Mycobacterium tuberculosis . This reservoir of bacteria is largely resistant to antimicrobial treatment that often only targets actively replicating mycobacteria, with current treatment for latent infection revolving around inhibiting the resuscitation event rather than preventing or treating latent infection. As a result, antimicrobials that target latent infection often have little to no activity in vivo. Here we report a method of in vitro analysis of physiologically relevant non-replicating persistence (NRP) utilizing cholesterol as the sole carbon source, alongside hypoxia as a driver of Mycobacterium bovis BCG into the NRP state. Using the minimal cholesterol media NRP assay, we observed an increased state of in vitro resistance to front-line anti-tubercular compounds. However, following a phenotypic screen of an approved-drug library, we identified dapsone as a bactericidal active molecule against cholesterol-dependent NRP M. bovis BCG. Through an overexpression trial of probable antimicrobial target enzymes, we further identified FolP2, a non-functional dihydropteroate synthase homologue, as the likely target of dapsone under cholesterol-NRP due to a significant increase in bacterial resistance when overexpressed. These results highlight the possible reason for little in vivo activity seen for current front-line anti-NRP drugs, and we introduce a new methodology for future drug screening as well as a potential role for dapsone inclusion within the current treatment regime

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Global Finance and Urban Adaptation: Governing Climate Risk in Miami, Florida

In recent years, a growing chorus of policymakers, scholars, and activists has begun to suggest that financial markets will play important roles in urban climate adaptation. By pricing future climate risks into existing risk rating and investment-making practices, working with city officials to assess local climate risks and beneficial courses of action, and more, these individuals have stressed that financial markets will greatly shape which cities can (and cannot) adapt to climate change, how cities adapt to climate change, and who benefits from adaptive infrastructure in cities. These are significant claims, with significant implications for climate justice: they speak to key distributional questions of how climate risk and security are distributed across space and time in cities, and who has the authority to make those distributional calls.With these concerns and claims in mind, this study examines how finance is beginning to shape urban adaptation and resilience pathways through the exemplary case of Miami, Florida. I focus the analysis on three large-scale adaptation and resilience measures that are already underway in the highly climate vulnerable, financialized, and unequal city: the $400 million Miami Forever Bond, the Miami Forever Climate Ready Strategy, and the Resilient305 regional resilience plan. Across the measures, I explore how climate-linked investment concerns and shifts in practices of valuation among bond rating agencies, real estate and bond market investors, and (re)insurance companies are beginning to shape the what, when, and where of urban adaptation in Miami: that is, what urban adaptation practically consists of; how far into the future urban adaptation measures are meant to extend, and where urban adaptation measures are sited within the city. I use ethnographic research methods, such as extended interviews with city officials, financial experts, and climate activists; participant observation of financial industry, local government, and activist meetings, conferences, and workshops; and media analysis of climate-linked shifts in financial practice, ongoing and planned adaptation measures in Miami, and local responses to these adaptation measures. Study findings are as follows. First, I find that local adaptation and resilience measures are key terrains where the significance of climate change for financial markets—and the significance of finance-driven adaptation for local climate outcomes—are being forged and negotiated. Second, in the absence of pre-baked consensus on how to act locally on climate risk, I observe that finance-driven adaptation and resilience measures in Miami multiply, rather than foreclose, sites of political contestation over the city’s future and present-day adaptation and resilience decision-making processes. Third, and finally, I find that local investments in adaptation and resilience are unpredictable: insofar as Miami officials direct resilience and adaptation dollars to projects that support existing patterns of urban accumulation, they also make significant investments in anti-displacement measures, confounding critical accounts which have often reduced adaptation and resilience to the latest iteration of urban growth machine politics.The study makes three important contributions to the disciplines of urban planning and human geography. First, at a topical level the research encourages planning scholars to direct their attention to the highly consequential, yet still relatively understudied, field of finance when it comes to conducting inquiry on the politics and uneven outcomes of urban adaptation planning. Second, the research offers a novel way to analyze finance in relation to urban adaptation and resilience. Bringing literatures from the interdisciplinary field of the Social Studies of Finance to bear to the case of finance-driven adaptation in Miami, the analytical approach developed and deployed across the dissertation enables researchers to account for the geographically-contingent ensemble of power struggles, social relations, and expert practices that help shape (and reshape) what finance-driven adaptation measures, and urban adaptation and resilience more broadly, ultimately do and spell for urban climate futures. Third, and finally, by incorporating the practices and strategies of local climate justice activists into my account of finance-driven adaptation, the dissertation contributes to an emergent research agenda within financial geography which calls for tracing the work of activist movements as they attempt to rework the means of public finance toward more transformative ends

Feasting on the Riches of His Grace

Photograph of Savannah Lee Coxhttps://scholarsjunction.msstate.edu/cht-sheet-music/11823/thumbnail.jp

Arsenic Exposure Causes Global Changes in the Metalloproteome of Escherichia coli

Arsenic is a toxic metalloid with differential biological effects, depending on speciation and concentration. Trivalent arsenic (arsenite, AsIII) is more toxic at lower concentrations than the pentavalent form (arsenate, AsV). In E. coli, the proteins encoded by the arsRBC operon are the major arsenic detoxification mechanism. Our previous transcriptional analyses indicate broad changes in metal uptake and regulation upon arsenic exposure. Currently, it is not known how arsenic exposure impacts the cellular distribution of other metals. This study examines the metalloproteome of E. coli strains with and without the arsRBC operon in response to sublethal doses of AsIII and AsV. Size exclusion chromatography coupled with inductively coupled plasma mass spectrometry (SEC-ICPMS) was used to investigate the distribution of five metals (56Fe, 24Mg, 66Zn, 75As, and 63Cu) in proteins and protein complexes under native conditions. Parallel analysis by SEC-UV-Vis spectroscopy monitored the presence of protein cofactors. Together, these data reveal global changes in the metalloproteome, proteome, protein cofactors, and soluble intracellular metal pools in response to arsenic stress in E. coli. This work brings to light one outcome of metal exposure and suggests that metal toxicity on the cellular level arises from direct and indirect effects

Arsenic Exposure Causes Global Changes in the Metalloproteome of <i>Escherichia coli</i>

Arsenic is a toxic metalloid with differential biological effects, depending on speciation and concentration. Trivalent arsenic (arsenite, AsIII) is more toxic at lower concentrations than the pentavalent form (arsenate, AsV). In E. coli, the proteins encoded by the arsRBC operon are the major arsenic detoxification mechanism. Our previous transcriptional analyses indicate broad changes in metal uptake and regulation upon arsenic exposure. Currently, it is not known how arsenic exposure impacts the cellular distribution of other metals. This study examines the metalloproteome of E. coli strains with and without the arsRBC operon in response to sublethal doses of AsIII and AsV. Size exclusion chromatography coupled with inductively coupled plasma mass spectrometry (SEC-ICPMS) was used to investigate the distribution of five metals (56Fe, 24Mg, 66Zn, 75As, and 63Cu) in proteins and protein complexes under native conditions. Parallel analysis by SEC-UV-Vis spectroscopy monitored the presence of protein cofactors. Together, these data reveal global changes in the metalloproteome, proteome, protein cofactors, and soluble intracellular metal pools in response to arsenic stress in E. coli. This work brings to light one outcome of metal exposure and suggests that metal toxicity on the cellular level arises from direct and indirect effects

Interrupted rhythms and uncertain futures: Mortgage finance and the (spatio-) temporalities of climate breakdown

As intensifying climate-related disasters strike cities across the United States, they are provoking rising concern for the stability of the U.S. housing market and broader financial system. How homeowners, mortgage lenders, federal institutions/regulators, and investors will variously encounter and manage climate risk is an urgent question for urban scholars, as is who might bear the costs of restabilizing mortgage finance under new breakdowns. This paper’s multi-scalar intervention draws on financial “following” methods to explore how climate risks are being experienced and governed at multiple illustrative moments of U.S. mortgage finance: (1) working households at the front line of urban climate impacts, (2) mortgage professionals brokering loans to them, (3) government-sponsored enterprises (GSEs) negotiating incoming federal climate risk disclosure requirements, and (4) capital markets off-taking GSE risks through financial derivatives like credit risk transfers. Emerging concerns include ruptures between household risks and financial system-preserving responses and new dangers of “climate redlining.”.Urban Development Managemen

Bookbinding for Puerto Rico: Culture, Food, Folklore

Eight advanced printmaking students will exhibit their artist books and conduct a hands on bookbinding workshop at Southern Graphics Council International in Puerto Rico, demonstrating the book structures they created. Under the mentorship of Professor Nicole Hand, the students will work in pairs and design four different book structures that they will exhibit and demonstrate, while participants learn how to create their own. The design and content of each book will be based on the groups research on culture, food, and folklore in Puerto Rico. This project is part of the community outreach and humanitarian efforts the Southern Graphics Council International has adapted for this conference due to the loss the community has experienced after several natural disasters