Internet All Nation Breath of life (I-ANBL) a Tribal College Student Engaged Development of an Internet-based Smoking Cessation Intervention

Background: Compared to non-Hispanic white college students, American Indian (AI) tribal college students have the highest smoking prevalence in the U.S. (~34%). Culturally-tailored smoking cessation programs have proven to be successful in reducing smoking rates but may require new methods to reach college students. Currently, there is little documentation on the development and success of Internet-based smoking interventions for AI tribal college students. Objectives: To develop an Internet-based smoking cessation program (Internet-All Nations Breath of Life or I-ANBL) with tribal college students. Methods: We conducted six focus groups (n=41) at a tribal college. Focus groups included tribal college students who smoked and groups were stratified by sex. Transcripts were analyzed using insider and outsider perspectives. After analysis, an Internet-based smoking cessation program was developed, based on insight gained. Results: Numerous suggestions for creating the program were offered. There was consensus on the need for a variety of visuals including cultural images, videos, and interactive content. The students also suggested the integration of familiar platforms such as FacebookTM. Conclusion: When culturally tailoring a web-based smoking cessation program for tribal college students, it is important to incorporate cultural aspects and recognize gender differences. One important aspect is to recognize that for many AI, tobacco is a sacred plant and images of tobacco should be respectful. Now that this intervention has been developed, next we will test it for efficacy in a randomized controlled trial. Keywords: American Indians, tribal college, tobacco, program development, smoking cessation, community-based participatory researc

Ensuring Healthy American Indian Generations for Tomorrow through Safe and Healthy Indoor Environments

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.American Indians (AI) have the highest rate of severe physical housing problems in the U.S. (3.9%). Little information exists about the environmental hazards in AI homes. The purposes of this paper are to discuss challenges that were encountered when recruiting AI for a home-and employment-based environmental health assessments, highlight major successes, and propose recommendations for future indoor environmental health studies. The Center for American Indian Community Health (CAICH) and Children’s Mercy Hospital’s Center for Environmental Health and Allergy and Immunology Research Lab collaborated to provide educational sessions and healthy home assessments for AI. Through educational trainings, more than 240 AI were trained on the primary causes of health problems in homes. A total of 72 homes and places of employment were assessed by AI environmental health specialists. The top three categories with the most concerns observed in the homes/places of employment were allergens/dust (98%), safety/injury (89%) and chemical exposure (82%). While some information on smoking inside the home was collected, these numbers may have been underreported due to stigma. This was CAICH’s first endeavor in environmental health and although challenges arose, many more successes were achieved

Thermal Stability of the Human Immunodeficiency Virus Type 1 (HIV-1) Receptors, CD4 and CXCR4, Reconstituted in Proteoliposomes

Background: The entry of human immunodeficiency virus (HIV-1) into host cells involves the interaction of the viral exterior envelope glycoprotein, gp120, and receptors on the target cell. The HIV-1 receptors are CD4 and one of two chemokine receptors, CCR5 or CXCR4. Methodology/Principal Findings: We created proteoliposomes that contain CD4, the primary HIV-1 receptor, and one of the coreceptors, CXCR4. Antibodies against CD4 and CXCR4 specifically bound the proteoliposomes. CXCL12, the natural ligand for CXCR4, and the small-molecule CXCR4 antagonist, AMD3100, bound the proteoliposomes with affinities close to those associated with the binding of these molecules to cells expressing CXCR4 and CD4. The HIV-1 gp120 exterior envelope glycoprotein bound tightly to proteoliposomes expressing only CD4 and, in the presence of soluble CD4, bound weakly to proteoliposomes expressing only CXCR4. The thermal stability of CD4 and CXCR4 inserted into liposomes was examined. Thermal denaturation of CXCR4 followed second-order kinetics, with an activation energy (E$_a$) of 269 kJ/mol (64.3 kcal/mol) and an inactivation temperature (T$_i$) of 56°C. Thermal inactivation of CD4 exhibited a reaction order of 1.3, an E$_a$ of 278 kJ/mol (66.5 kcal/mol), and a T$_i$ of 52.2°C. The second-order denaturation kinetics of CXCR4 is unusual among G protein-coupled receptors, and may result from dimeric interactions between CXCR4 molecules. Conclusions/Significance: Our studies with proteoliposomes containing the native HIV-1 receptors allowed an examination of the binding of biologically important ligands and revealed the higher-order denaturation kinetics of these receptors. CD4/CXCR4-proteoliposomes may be useful for the study of virus-target cell interactions and for the identification of inhibitors

Removing or truncating connexin 43 in murine osteocytes alters cortical geometry, nanoscale morphology, and tissue mechanics in the tibia

Gap junctions are formed from ubiquitously expressed proteins called connexins that allow the transfer of small signaling molecules between adjacent cells. Gap junctions are especially important for signaling between osteocytes and other bone cell types. The most abundant type of connexin in bone is connexin 43 (Cx43). The C-terminal domain of Cx43 is thought to be an important modulator of gap junction function but the role that this domain plays in regulating tissue-level mechanics is largely unknown. We hypothesized that the lack of the C-terminal domain of Cx43 would cause morphological and compositional changes as well as differences in how bone responds to reference point indentation (RPI) and fracture toughness testing. The effects of the C-terminal domain of Cx43 in osteocytes and other cell types were assessed in a murine model (C57BL/6 background). Mice with endogenous Cx43 in their osteocytes removed via a Cre-loxP system were crossed with knock-in mice which expressed Cx43 that lacked the C-terminal domain in all cell types due to the insertion of a truncated allele to produce the four groups used in the study. The main effect of removing the C-terminal domain from osteocytic Cx43 increased cortical mineral crystallinity (p=0.036) and decreased fracture toughness (p=0.017). The main effect of the presence of the C-terminal domain in other cell types increased trabecular thickness (p<0.001), cortical thickness (p=0.008), and average RPI unloading slope (p=0.004). Collagen morphology was altered when either osteocytes lacked Cx43 (p=0.008) or some truncated Cx43 was expressed in all cell types (p<0.001) compared to controls but not when only the truncated form of Cx43 was expressed in osteocytes (p=0.641). In conclusion, the presence of the C-terminal domain of Cx43 in osteocytes and other cell types is important to maintain normal structure and mechanical integrity of bone

American Indian Knowledge, Attitudes, and Beliefs About Smokeless Tobacco: A Comparison of Two Focus Group Studies

The final publication is available at Springer via http://doi.org/10.1007/s10900-017-0362-3.Though smokeless tobacco (SLT) use has decreased in many communities, concern for American Indian (AI) SLT use remains, as this population continues to be disproportionally affected by SLT-related diseases. Tobacco has cultural significance to many AI tribes, therefore tobacco cessation messages portraying tobacco as entirely negative may be ineffective. As a part of our formative research for an SLT cessation intervention, we sought to gain a better understanding of the knowledge, attitudes, and beliefs about SLT among AI community members. We describe two independent focus group studies conducted in Montana (ten focus groups, 54 participants) and Kansas (six focus groups, 27 participants). Predominant themes emerged from three major topic areas (SLT use, program development, and recreational SLT use) during the discussions from both studies. The formative approach and data from these studies will allow us to more appropriately address SLT-related health disparities across multiple AI communities

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases

A transcriptomics-based drug repositioning approach to identify drugs with similar activities for the treatment of muscle pathologies in spinal muscular atrophy (SMA) models

© 2023 The Author(s). Published by Oxford University Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by the reduction of survival of motor neuron (SMN) protein levels. Although three SMN-augmentation therapies are clinically approved that significantly slow down disease progression, they are unfortunately not cures. Thus, complementary SMN-independent therapies that can target key SMA pathologies and that can support the clinically approved SMN-dependent drugs are the forefront of therapeutic development. We have previously demonstrated that prednisolone, a synthetic glucocorticoid (GC) improved muscle health and survival in severe Smn-/-;SMN2 and intermediate Smn2B/- SMA mice. However, long-term administration of prednisolone can promote myopathy. We thus wanted to identify genes and pathways targeted by prednisolone in skeletal muscle to discover clinically approved drugs that are predicted to emulate prednisolone's activities. Using an RNA-sequencing, bioinformatics, and drug repositioning pipeline on skeletal muscle from symptomatic prednisolone-treated and untreated Smn-/-; SMN2 SMA and Smn+/-; SMN2 healthy mice, we identified molecular targets linked to prednisolone's ameliorative effects and a list of 580 drug candidates with similar predicted activities. Two of these candidates, metformin and oxandrolone, were further investigated in SMA cellular and animal models, which highlighted that these compounds do not have the same ameliorative effects on SMA phenotypes as prednisolone; however, a number of other important drug targets remain. Overall, our work further supports the usefulness of prednisolone's potential as a second-generation therapy for SMA, identifies a list of potential SMA drug treatments and highlights improvements for future transcriptomic-based drug repositioning studies in SMA.Peer reviewe

Age- and sex-dependent role of osteocytic pannexin1 on bone and muscle mass and strength

Pannexins (Panxs), glycoproteins that oligomerize to form hemichannels on the cell membrane, are topologically similar to connexins, but do not form cell-to-cell gap junction channels. There are 3 members of the family, 1-3, with Panx1 being the most abundant. All Panxs are expressed in bone, but their role in bone cell biology is not completely understood. We now report that osteocytic Panx1 deletion (Panx1Δot) alters bone mass and strength in female mice. Bone mineral density after reaching skeletal maturity is higher in female Panx1Δot mice than in control Panx1fl/fl mice. Further, osteocytic Panx1 deletion partially prevented aging effects on cortical bone structure and mechanical properties. Young 4-month-old female Panx1Δot mice exhibited increased lean body mass, even though pannexin levels in skeletal muscle were not affected; whereas no difference in lean body mass was detected in male mice. Furthermore, female Panx1-deficient mice exhibited increased muscle mass without changes in strength, whereas Panx1Δot males showed unchanged muscle mass and decreased in vivo maximum plantarflexion torque, indicating reduced muscle strength. Our results suggest that osteocytic Panx1 deletion increases bone mass in young and old female mice and muscle mass in young female mice, but has deleterious effects on muscle strength only in males

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Incipient Cognition Solves the Spatial Reciprocity Conundrum of Cooperation

Background: From the simplest living organisms to human societies, cooperation among individuals emerges as a paradox difficult to explain and describe mathematically, although very often observed in reality. Evolutionary game theory offers an excellent toolbar to investigate this issue. Spatial structure has been one of the first mechanisms promoting cooperation; however, alone it only opens a narrow window of viability. Methodology/Principal Findings: Here we equip individuals with incipient cognitive abilities, and investigate the evolution of cooperation in a spatial world where retaliation, forgiveness, treason and mutualism may coexist, as individuals engage in Prisoner’s Dilemma games. In the model, individuals are able to distinguish their partners and act towards them based on previous interactions. We show how the simplest level of cognition, alone, can lead to the emergence of cooperation. Conclusions/Significance: Despite the incipient nature of the individuals ’ cognitive abilities, cooperation emerges for unprecedented values of the temptation to cheat, being also robust to invasion by cheaters, errors in decision making an