Rewriting the History of the Native Mounted Police in Queensland

The Archaeology of the Native Mounted Police in Queensland project, jointly led by Nulungu research fellow Dr Lynley Wallis, is a long-overdue exploration into the nature of frontier invasion. Several of our team members have worked in Queensland for many decades and, in every Aboriginal community in which we’ve worked, stories are told about the ‘killing times’ or the ‘war’, as community members call the period when the Native Mounted Police (NMP, also referred to as the ‘Native Police’) were operating. Many community members have asked us over the years to record their stories about the massacres that took place, or have shown us places associated with the police camps or the massacre sites, and often told us that they would like to know more about what happened. These requests eventually led to the archaeologists on this project coming together, talking with key Aboriginal people and communities, and developing a research project to address their interests — the project described in this paper is the result.https://researchonline.nd.edu.au/nulungu_insights/1000/thumbnail.jp

The characterization, management, and future considerations for ErbB-family TKI-associated diarrhea.

PurposeDiarrhea is recognized as a common adverse event associated with tyrosine kinase inhibitors (TKIs), with those targeting the ErbB family of receptors being associated with the highest rate of diarrhea.MethodsThis paper reviews data on the incidence, timing, and duration of diarrhea associated with US Food and Drug Administration-approved ErbB family-targeted TKIs from the published literature, and sets forth recommendations for management.ResultsIn the absence of anti-diarrheal prophylaxis the incidence of any-grade diarrhea varies and typically occurs early during the course of treatment. Although it is difficult to determine if the incidence and severity of diarrhea is related to inhibition of a particular kinase target because of the multi-targeted and overlapping activity of many agents, evidence suggests that second-generation TKIs with broader target profiles (i.e., afatinib, lapatinib, neratinib) result in a higher incidence of diarrhea compared with highly specific first- (erlotinib, gefitinib) or third- (osimertinib) generation agents. The mechanisms responsible for TKI-associated diarrhea are not fully understood and are likely multi-factorial, involving dysregulated ion transport, inflammation, and mucosal injury. Management strategies have been developed-and continue to be refined-to prevent and reduce the severity and duration of TKI-associated diarrhea. For agents associated with more significant symptoms, anti-diarrheal prophylaxis reduces the incidence and severity of diarrhea, and ongoing studies are evaluating specific strategies to further reduce incidence and duration of TKI-associated diarrhea.ConclusionsContinued investigations into risk factors and pharmacogenomic markers for diarrhea may further improve management of this common toxicity

The Discipline of Dress: Uniform Buttons and Accoutrements of the Native Mounted Police in Queensland, Australia

Clothing is capable of providing a range of insights into aspects of identity, authority, power, and hierarchy. Here we present the results of an analysis of an assemblage of uniform buttons and accoutrements from seven 19th-century Native Mounted Police (NMP) camps in Queensland, Australia. As part of wider colonial structures of discipline and expropriation, the NMP uniform was a powerful symbol of control: over troopers’ bodies, over NMP detachments by officers, and over “wild” and “savage” Indigenous peoples by the NMP. Exploring the history and development of the NMP uniform, its intent in constructing officers and particularly troopers, the indexical qualities it acquired as a symbol of violence and fear amongst Indigenous people, and some of the alternative ways in which uniforms could be worn provides a variety of insights into the role, nature, and experience of the Queensland NMP. La ropa es puede proporcionar una variedad de conocimientos sobre aspectos de identidad, autoridad, poder y jerarquía. Aquí presentamos los resultados de un análisis de un conjunto de pertrechos y botones de uniformes de siete campamentos de la Policía Montada Nativa (NMP, por sus siglas en inglés) del siglo XIX en Queensland, Australia. Como parte de estructuras coloniales más amplias de disciplina y expropiación, el uniforme de la NMP era un poderoso símbolo de control: sobre los cuerpos de los soldados, sobre los destacamentos de la NMP por parte de los ofciales y sobre los pueblos indígenas “salvajes” y “descontrolados” por parte de la NMP. Explorar la historia y el desarrollo del uniforme de la NMP, su intención de construir ofciales y, en particular, soldados, las cualidades indexadas que adquirió como símbolo de violencia y miedo entre los pueblos indígenas, y algunas de las formas alternativas en que se pueden usar los uniformes, proporciona una variedad de ideas sobre el papel, la naturaleza y la experiencia de la NMP de Queensland. Les vêtements ont le potentiel d’apporter une variété d’éclairages sur les aspects liés à l’identité, l’autorité, le pouvoir et la hiérarchie. Nous présentons ici les résultats d’une analyse d’un assemblage de boutons d’uniforme et d’habits provenant de sept camps de la Police montée (Native Mounted Police—NMP) du 19ème siècle dans le Queensland en Australie. S’inscrivant dans les structures coloniales plus vastes de la discipline et de l’expropriation, l’uniforme NMP était un symbole puissant de contrôle, à savoir sur les corps de ses membres, sur les détachements NMP par les ofciers et enfn sur les peuples indigènes «sans retenue » et « sauvages » par le NMP. L’étude de l’histoire et du développement de l’uniforme NMP, de son intention quant à la construction d’ofciers et particulièrement de membres de la police montée, des qualités indexicales dont il a été investi en tant que symbole de violence et de peur parmi les peuples indigènes, de même que certaines des manières alternatives dont ces uniformes pouvaient être portés, fournit une variété d’éclairages sur le rôle, la nature et l’expérience de la NMP du Queensland

Effects of increasing the affinity of CarD for RNA polymerase on Mycobacterium tuberculosis growth, rRNA transcription, and virulence

CarD is an essential RNA polymerase (RNAP) interacting protein in Mycobacterium tuberculosis that stimulates formation of RNAP-promoter open complexes. CarD plays a complex role in M. tuberculosis growth and virulence that is not fully understood. Therefore, to gain further insight into the role of CarD in M. tuberculosis growth and virulence, we determined the effect of increasing the affinity of CarD for RNAP. Using site-directed mutagenesis guided by crystal structures of CarD bound to RNAP, we identified amino acid substitutions that increase the affinity of CarD for RNAP. Using these substitutions, we show that increasing the affinity of CarD for RNAP increases the stability of the CarD protein in M. tuberculosis. In addition, we show that increasing the affinity of CarD for RNAP increases the growth rate in M. tuberculosis without affecting 16S rRNA levels. We further show that increasing the affinity of CarD for RNAP reduces M. tuberculosis virulence in a mouse model of infection despite the improved growth rate in vitro. Our findings suggest that the CarD-RNAP interaction protects CarD from proteolytic degradation in M. tuberculosis, establish that growth rate and rRNA levels can be uncoupled in M. tuberculosis and demonstrate that the strength of the CarD-RNAP interaction has been finely tuned to optimize virulence. IMPORTANCE Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a major global health problem. In order to develop new strategies to battle this pathogen, we must gain a better understanding of the molecular processes involved in its survival and pathogenesis. We have previously identified CarD as an essential transcriptional regulator in mycobacteria. In this study, we detail the effects of increasing the affinity of CarD for RNAP on transcriptional regulation, CarD protein stability, and virulence. These studies expand our understanding of the global transcription regulator CarD, provide insight into how CarD activity is regulated, and broaden our understanding of prokaryotic transcription

Interaction of CarD with RNA polymerase mediates Mycobacterium tuberculosis viability, rifampin resistance, and pathogenesis

Mycobacterium tuberculosis infection continues to cause substantial human suffering. New chemotherapeutic strategies, which require insight into the pathways essential for M. tuberculosis pathogenesis, are imperative. We previously reported that depletion of the CarD protein in mycobacteria compromises viability, resistance to oxidative stress and fluoroquinolones, and pathogenesis. CarD associates with the RNA polymerase (RNAP), but it has been unknown which of the diverse functions of CarD are mediated through the RNAP; this question must be answered to understand the CarD mechanism of action. Herein, we describe the interaction between the M. tuberculosis CarD and the RNAP β subunit and identify point mutations that weaken this interaction. The characterization of mycobacterial strains with attenuated CarD/RNAP β interactions demonstrates that the CarD/RNAP β association is required for viability and resistance to oxidative stress but not for fluoroquinolone resistance. Weakening the CarD/RNAP β interaction also increases the sensitivity of mycobacteria to rifampin and streptomycin. Surprisingly, depletion of the CarD protein did not affect sensitivity to rifampin. These findings define the CarD/RNAP interaction as a new target for chemotherapeutic intervention that could also improve the efficacy of rifampin treatment of tuberculosis. In addition, our data demonstrate that weakening the CarD/RNAP β interaction does not completely phenocopy the depletion of CarD and support the existence of functions for CarD independent of direct RNAP binding

Longitudinal associations among asthma control, sleep problems, and health-related quality of life in children with asthma: a report from the PROMIS® Pediatric Asthma Study

Few studies have investigated the complex relationship among asthma control, sleep problems, and health-related quality of life (HRQOL) among children with asthma. This study aimed to test the longitudinal effect of asthma control status on asthma-specific HRQOL through the mechanism of nighttime sleep quality and daytime sleepiness

C/EBPβ-1 promotes transformation and chemoresistance in Ewing sarcoma cells.

CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Overexpression of C/EBPβ-1, the largest of the three C/EBPβ isoforms, led to a significant increase in colony formation when cells were grown in soft agar compared to empty vector transduced cells. In addition, depletion of C/EBPβ decreased colony formation, and re-expression of either C/EBPβ-1 or C/EBPβ-2 rescued the phenotype. We identified the cancer stem cell marker ALDH1A1 as a target of C/EBPβ in Ewing sarcoma. Furthermore, increased expression of C/EBPβ led to resistance to chemotherapeutic agents. In summary, we have identified CEBPB as an oncogene in Ewing sarcoma. Overexpression of C/EBPβ-1 increases transformation, upregulates expression of the cancer stem cell marker ALDH1A1, and leads to chemoresistance

A climate analog approach to evaluate seed transfer and vegetation transitions

IntroductionThere is growing recognition that restoring species diversity is crucial to maintaining ecological functions and services. Increasing the diversity of species used in restoration programs has placed greater emphasis on determining the seed transfer needs for a wider array of plants. However, many plants, outside of commercial forestry, lack information that would provide guidance on seed transfer for current or future climates. Generalized seed transfer approaches use climate partitioning to approximate adaptive differentiation among populations and provide an estimation of seed transfer distance for such species.MethodsHerein, we describe a generalized seed transfer approach that uses Euclidean distance of 19 climate variables within North America (from northern Honduras to the Arctic). Euclidean distances are used to identify climate analogs from vegetation databases of about 685,000 plots, an average density of 1 plot per 32 km2. Analogs are classified into three thresholds (strong, moderate, and weak) that correspond to altitudinal climate gradients and are guided by the scientific literature of observed adaptive variation of natural tree populations and seed transfer limits.ResultsFor strong threshold observations, about 97% of the analogs had climate distances equivalent to ≤300 m elevation, whereas for the weak threshold observations, 53% had an elevation equivalence of ≤300 m. On average 120, 267, and 293 m elevation separated two points under strong, moderate, and weak thresholds, respectively. In total, threshold classification errors were low at 13.9%.DiscussionWe use examples of plot data identified from a reference period (1961–1990) and mid-century (2056–2065) analogs across North American biomes to compare and illustrate the outcomes of projected vegetation change and seed transfer. These examples showcase that mid-century analogs may be located in any cardinal direction and vary greatly in spatial distance and abundance from no analog to hundreds depending on the site. The projected vegetative transitions will have substantial impacts on conservation programs and ecosystem services. Our approach highlights the complexity that climate change presents to managing ecosystems, and the need for predictive tools in guiding land management decisions to mitigate future impacts caused by climate change

Sexual Satisfaction and the Importance of Sexual Health to Quality of Life Throughout the Life Course of U.S. Adults

Discussions about sexual health are uncommon in clinical encounters, despite the sexual dysfunction associated with many common health conditions. Understanding of the importance of sexual health and sexual satisfaction among US adults is limited