The New Minnesotans: Profile of West Central Minnesota

In 2005, The Center for Small towns, together with the University of Minnesota West Central Regional Sustainable Development Partnership, began the New Minnesotans project that aimed to help identify underrepresented racial and ethnic groups who are new residents of West Central Minnesota. The project\u27s goal was to find ways to support the needs of these groups and to encourage their abilities. Twelve counties were involved in the study done for the project: Big Stone,Chippewa, Douglas, Grant, Kandiyohi, Lac qui Parle, Pope, Renville, Stevens, Swift, Traverse, and Yellow Medicine.https://digitalcommons.morris.umn.edu/cst/1001/thumbnail.jp

Economic outcomes associated with deep surgical site infection in patients with an open fracture of the lower limb

Aims The aim of this study was to estimate economic outcomes associated with deep surgical site infection (SSI) in patients with an open fracture of the lower limb. Patients and Methods A total of 460 patients were recruited from 24 specialist trauma hospitals in the United Kingdom Major Trauma Network. Preference-based health-related quality-of-life outcomes, assessed using the EuroQol EQ-5D-3L and the 6-Item Short-Form Health Survey questionnaire (SF-6D), and economic costs (£, 2014/2015 prices) were measured using participant-completed questionnaires over the 12 months following injury. Descriptive statistics and multivariate regression analysis were used to explore the relationship between deep SSI and health utility scores, quality-adjusted life-years (QALYs), and health and personal social service (PSS) costs. Results Deep SSI was associated with lower EQ-5D-3L derived QALYs (adjusted mean difference -0.102, 95% confidence interval (CI) -0.202 to 0.001, p = 0.047) and increased health and social care costs (adjusted mean difference £1950; 95% CI £1383 to £5285, p = 0.250) versus patients without deep SSI over the 12 months following injury. Conclusion Deep SSI may lead to significantly impaired health-related quality of life and increased economic costs. Our economic estimates can be used to inform clinical and budgetary service planning and can act as reference data for future economic evaluations of preventive or treatment interventions

Synthesis of Rhamnosylated Arginine Glycopeptides and Determination of the Glycosidic Linkage in Bacterial Elongation Factor P

A new class of N-linked protein glycosylation – arginine rhamnosylation – has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). Herein, we describe the synthesis of suitably protected α- and β-rhamnosylated arginine amino acid “cassettes” that can be directly installed into rhamnosylated peptides. Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies

Quantitative proteomic characterization of cellular pathways associated with altered insulin sensitivity in skeletal muscle following high-fat diet feeding and exercise training

Regular exercise elicits advantageous metabolic adaptations in skeletal muscle, such as improved insulin sensitivity. However, the underpinning molecular mechanisms and the effect of diet on muscle exercise training benefits are unclear. We therefore characterized the skeletal muscle proteome following exercise training (ET) in mice fed chow or high-fat diet (HFD). ET increased exercise performance, lowered body-weight, decreased fat mass and improved muscle insulin action in chow-and HFD-fed mice. At the molecular level, ET regulated 170 muscle proteins in chow-fed mice, but only 29 proteins in HFD-fed mice. HFD per se altered 56 proteins, most of which were regulated in a similar direction by ET. To identify proteins that might have particular health-related bearing on skeletal muscle metabolism, we filtered for differentially regulated proteins in response to ET and HFD. This yielded 15 proteins, including the major urinary protein 1 (MUP1), which was the protein most decreased after HFD, but increased with ET. The ET-induced Mup1 expression was absent in mouse muscle lacking functional AMPK. MUP1 also potentiated insulin-stimulated GLUT4 translocation in cultured muscle cells. Collectively, we provide a resource of ET-regulated proteins in insulin-sensitive and insulin-resistant skeletal muscle. The identification of MUP1 as a diet-, ET-and AMPK-regulated skeletal muscle protein that improves insulin sensitivity in muscle cells demonstrates the usefulness of these data

The intrahepatic signalling niche of hedgehog is defined by primary cilia positive cells during chronic liver injury

Background & Aims: In vertebrates, canonical Hedgehog (Hh) pathway activation requires Smoothened (SMO) translocation to the primary cilium (Pc), followed by a GLI-mediated transcriptional response. In addition, a similar gene regulation occurs in response to growth factors/cytokines, although independently of SMO signalling. The Hh pathway plays a critical role in liver fibrosis/regeneration; however, the mechanism of activation in chronic liver injury is poorly understood. This study aimed to characterise Hh pathway activation upon thioacetamide (TAA)- induced chronic liver injury in vivo by defining Hh-responsive cells, namely cells harbouring Pc and Pc-localised SMO. Methods: C57BL/6 mice (wild-type or Ptc1+/_) were TAA-treated. Liver injury and Hh ligand/pathway mRNA and protein expression were assessed in vivo. SMO/GLI manipulation and SMO dependent/ independent activation of GLI-mediated transcriptional response in Pc-positive (Pc+) cells were studied in vitro. Results: In vivo, Hh activation was progressively induced following TAA. At the epithelial-mesenchymal interface, injured hepatocytes produced Hh ligands. Progenitors, myofibroblasts, leukocytes and hepatocytes were GLI2+. Pc+ cells increased following TAA, but only EpCAM+/GLI2+ progenitors were Pc+/SMO+. In vitro, SMO knockdown/hGli3-R overexpression reduced proliferation/viability in Pc+ progenitors, whilst increased proliferation occurred with hGli1 overexpression. HGF induced GLI transcriptional activity independently of Pc/SMO. Ptc1+/_ mice exhibited increased progenitor, myofibroblast and fibrosis responses. Conclusions: In chronic liver injury, Pc+ progenitors receive Hh ligand signals and process it through Pc/SMO-dependent activation of GLI-mediated transcriptional response. Pc/SMO-independent GLI activation likely occurs in Pc_/GLI2+ cells. Increased fibrosis in Hh gain-of-function mice likely occurs by primary progenitor expansion/proliferation and secondary fibrotic myofibroblast expansion, in close contact with progenitors

Can we save large carnivores without losing large carnivore science?

Large carnivores are depicted to shape entire ecosystems through top-down processes. Studies describing these processes are often used to support interventionist wildlife management practices, including carnivore reintroduction or lethal control programs. Unfortunately, there is an increasing tendency to ignore, disregard or devalue fundamental principles of the scientific method when communicating the reliability of current evidence for the ecological roles that large carnivores may play, eroding public confidence in large carnivore science and scientists. Here, we discuss six interrelated issues that currently undermine the reliability of the available literature on the ecological roles of large carnivores: (1) the overall paucity of available data, (2) reliability of carnivore population sampling techniques, (3) general disregard for alternative hypotheses to top-down forcing, (4) lack of applied science studies, (5) frequent use of logical fallacies, and (6) generalisation of results from relatively pristine systems to those substantially altered by humans. We first describe how widespread these issues are, and given this, show, for example, that evidence for the roles of wolves (Canis lupus) and dingoes (Canis lupus dingo) in initiating trophic cascades is not as strong as is often claimed. Managers and policy makers should exercise caution when relying on this literature to inform wildlife management decisions. We emphasise the value of manipulative experiments, and discuss the role of scientific knowledge in the decision-making process. We hope that the issues we raise here prompt deeper consideration of actual evidence, leading towards an improvement in both the rigour and communication of large carnivore science

Structural basis for phosphorylation and lysine acetylation cross-talk in a kinase motif associated with myocardial ischemia and cardioprotection

Myocardial ischemia and cardioprotection by ischemic pre-conditioning induce signal networks aimed at survival or cell death if the ischemic period is prolonged. These pathways are mediated by protein post-translational modifications that are hypothesized to cross-talk with and regulate each other. Phosphopeptides and lysine-acetylated peptides were quantified in isolated rat hearts subjected to ischemia or ischemic pre-conditioning, with and without splitomicin inhibition of lysine deacetylation. We show lysine acetylation (acetyl-Lys)-dependent activation of AMP-activated protein kinase, AKT, and PKA kinases during ischemia. Phosphorylation and acetyl-Lys sites mapped onto tertiary structures were proximal in >50% of proteins investigated, yet they were mutually exclusive in 50 ischemic pre-conditioning- and/or ischemia-associated peptides containing the KXXS basophilic protein kinase consensus motif. Modifications in this motif were modeled in the C terminus of muscle-type creatine kinase. Acetyl-Lys increased proximal dephosphorylation by 10-fold. Structural analysis of modified muscle-type creatine kinase peptide variants by two-dimensional NMR revealed stabilization via a lysine-phosphate salt bridge, which was disrupted by acetyl-Lys resulting in backbone flexibility and increased phosphatase accessibility

Verification of a Fully Implicit Particle-in-Cell Method for the v∥v_\parallel Formalism of Electromagnetic Gyrokinetics in the XGC Code

A fully implicit particle-in-cell method for handling the $v_\parallel$-formalism of electromagnetic gyrokinetics has been implemented in XGC. By choosing the $v_\parallel$-formalism, we avoid introducing the non-physical skin terms in Amp\`{e}re's law, which are responsible for the well-known ``cancellation problem" in the $p_\parallel$-formalism. The $v_\parallel$-formalism, however, is known to suffer from a numerical instability when explicit time integration schemes are used due to the appearance of a time derivative in the particle equations of motion from the inductive component of the electric field. Here, using the conventional $\delta f$ scheme, we demonstrate that our implicitly discretized algorithm can provide numerically stable simulation results with accurate dispersive properties. We verify the algorithm using a test case for shear Alfv\'{e}n wave propagation in addition to a case demonstrating the ITG-KBM transition. The ITG-KBM transition case is compared to results obtained from other $\delta f$ gyrokinetic codes/schemes, whose verification has already been archived in the literature

Large carnivore science: non-experimental studies are useful, but experiments are better

1. Response to Bruskotter and colleagues We recently described the following six interrelated issues that justify questioning some of the discourse about the reliability of the literature on the ecological roles of large carnivores (Allen et al., in press): 1. The overall paucity of available data, 2. The reliability of carnivore population sampling techniques, 3. The general disregard for alternative hypotheses to top-down forcing, 4. The lack of applied science studies, 5. The frequent use of logical fallacies, 6. The generalisation of results from relatively pristine systems to those substantially altered by humans. We thank Bruskotter et al. (2017) for responding to our concerns and engaging with this important issue. We agree completely that nonexperimental studies can and do often have great value, and we recognize that in many (most) cases these types of studies may provide the only data that are available. We acknowledge the many challenges of working on large, cryptic, dangerous, and highly-mobile animals in the wild. However, the absence of more robust data and the reality of these challenges do not excuse weak inference or overstating conclusions – a practice apparent in many studies (and communication of those studies) adopting only observational or correlative methods to infer the roles of large carnivores (reviewed in Allen et al., in press)