TREM1/3 deficiency impairs tissue repair after acute kidney injury and mitochondrial metabolic flexibility in tubular epithelial cells

Long-term sequelae of acute kidney injury (AKI) are associated with incomplete recovery of renal function and the development of chronic kidney disease (CKD), which can be mediated by aberrant innate immune activation, mitochondrial pathology, and accumulation of senescent tubular epithelial cells (TECs). Herein, we show that the innate immune receptor Triggering receptor expressed on myeloid cells-1 (TREM-1) links mitochondrial metabolism to tubular epithelial senescence. TREM-1 is expressed by inflammatory and epithelial cells, both players in renal repair after ischemia/reperfusion (IR)-induced AKI. Hence, we subjected WT and TREM1/3 KO mice to different models of renal IR. TREM1/3 KO mice displayed no major differences during the acute phase of injury, but increased mortality was observed in the recovery phase. This detrimental effect was associated with maladaptive repair, characterized by persistent tubular damage, inflammation, fibrosis, and TEC senescence. In vitro, we observed an altered mitochondrial homeostasis and cellular metabolism in TREM1/3 KO primary TECs. This was associated with G2/M arrest and increased ROS accumulation. Further exposure of cells to ROS-generating triggers drove the cells into a stress-induced senescent state, resulting in decreased wound healing capacity. Treatment with a mitochondria anti-oxidant partly prevented the senescent phenotype, suggesting a role for mitochondria herein. In summary, we have unraveled a novel (metabolic) mechanism by which TREM1/3 deficiency drives senescence in TECs. This involves redox imbalance, mitochondrial dysfunction and a decline in cellular metabolic activities. These finding suggest a novel role for TREM-1 in maintaining tubular homeostasis through regulation of mitochondrial metabolic flexibility

The impacts of hydraulic clamming in shallow water and the importance of incorporating anthropogenic disturbances into habitat assessments

Hydraulic dredging for shellfish is known to create some of the highest levels of disturbance, affecting the benthic microfaunal community and the physical characteristics of the substrate. Properly conducted benthic habitat assessments are complex and time consuming, resulting in assessments not being conducted increasing the uncertainty in post impact studies. Hydraulic dredging for Atlantic surfclams (Spisula soldidissima) took place at Herring Cove, Massachusetts in the winter of 2014–2015 resulting in areas of high impact disturbance of the seafloor. Surveys conducted in the summer of 2015 included hydroacoustics, benthic invertebrate sampling, video, and grain size analysis for the creation of a habitat map of Herring Cove. The four habitats (A–D) identified were a mix of sand, shell, cobble, algae, and eelgrass. Habitat type “D” is a mix of sand, algae and cobble material and occurred at 12 of 18 stations. These 12 stations were distributed across areas of “high” (n = 4), “low” (n = 2), and “no” (n = 6) hydraulic dredge disturbance. Once habitat was accounted for, benthic invertebrate community structure varied significantly (Analysis of similarity; significance level of sample statistic: 0.3%) between areas of “high”, “low” to “no” disturbance. Areas of “low” to “no” dredge track coverage contained high abundances of bivalves, echinoderms, and isopods, whereas highly disturbed areas had highest abundances of polychaetes and oligochaetes. Future mapping efforts, especially surveys with biological components, need to include and quantify the level, type and spatial distribution of anthropogenic alterations. More attention should be given to “reference maps” instead of “baseline maps”. The latter of which omits to acknowledge pre-existing anthropogenic disturbances and has the potential to skew monitoring of restoration and management efforts

Spiritual Formation Training in the George Fox University Graduate Department of Clinical Psychology

Spiritual formation training in the George Fox University Graduate Department of Clinical Psychology is described. An evangelical Quaker institution, the ethos of George Fox University is intended to foster experiential spiritual development and reflective self-awareness. In a 2008 curriculum revision the faculty attempted to strengthen the experiential dimensions of spiritual formation training even at the risk of reducing training in more academic dimensions of theology and integration. A 2013 program evaluation solicited student and alumni perspectives on the effectiveness of the spiritual formation training they received. Results of the program evaluation suggest areas for future development

A novel multiparametric approach to 3D quantitative MRI of the brain

Magnetic Resonance properties of tissues can be quantified in several respects: relaxation processes, density of imaged nuclei, magnetism of environmental molecules, etc. In this paper, we propose a new comprehensive approach to obtain 3D high resolution quantitative maps of arbitrary body districts, mainly focusing on the brain. The theory presented makes it possible to map longitudinal (R1), pure transverse (R2) and free induction decay (R2 ) rates, along with proton density (PD) and magnetic susceptibility (χ), from a set of fast acquisition sequences in steady-state that are highly insensitive to flow phenomena. A novel denoising scheme is described and applied to the acquired datasets to enhance the signal to noise ratio of the derived maps and an information theory approach compensates for biases from radio frequency (RF) inhomogeneities, if no direct measure of the RF field is available. Finally, the results obtained on sample brain scans of healthy controls and multiple sclerosis patients are presented and discussed

Selection on stability across ecological scales

Much of the focus in evolutionary biology has been on the adaptive differentiation among organisms. It is equally important to understand the processes that result in similarities of structure among systems. Here, we discuss examples of similarities occurring at different ecological scales, from predator–prey relations (attack rates and handling times) through communities (food-web structures) to ecosystem properties. Selection among systemic configurations or patterns that differ in their intrinsic stability should lead generally to increased representation of relatively stable structures. Such nonadaptive, but selective processes that shape ecological communities offer an enticing mechanism for generating widely observed similarities, and have sparked new interest in stability properties. This nonadaptive systemic selection operates not in opposition to, but in parallel with, adaptive evolution

Feasibility of Harbor-wide Barrier Systems: Preliminary Analysis for Boston Harbor

The aim of this study is to provide the City of Boston with a preliminary assessment of the feasibilities and potential benefits, costs, and environmental impacts of three harborwide barrier configurations. While this study is not comprehensive, and there are many ways that further research could refine and extend its findings, those findings were clear enough to justify making recommendations for next steps. The authors recommend that the City continue to focus its climate resilience strategy for the next several decades on the shore-based multi-layered approach described in Climate Ready Boston. Shore-based solutions would provide flood management more quickly at a lower cost, offer several key advantages over a harbor-wide barrier, and provide more flexibility in adapting and responding to changing conditions, technological innovations, and new information about global sea level rise. These shore-based solutions would be needed in any case over the next few decades to manage coastal flooding during the design and construction period of a harbor-wide barrier if a decision was made to build one in the future

The unexpected resurgence of Weyl geometry in late 20-th century physics

Weyl's original scale geometry of 1918 ("purely infinitesimal geometry") was withdrawn by its author from physical theorizing in the early 1920s. It had a comeback in the last third of the 20th century in different contexts: scalar tensor theories of gravity, foundations of gravity, foundations of quantum mechanics, elementary particle physics, and cosmology. It seems that Weyl geometry continues to offer an open research potential for the foundations of physics even after the turn to the new millennium.Comment: Completely rewritten conference paper 'Beyond Einstein', Mainz Sep 2008. Preprint ELHC (Epistemology of the LHC) 2017-02, 92 pages, 1 figur

Chinese medicine treatment for menopausal symptoms in the UK health service: Is a clinical trial warranted?

Objectives The aims of this pilot study were to evaluate treatment effects, ascertain safety and formulate best practice Chinese medicine protocols relevant for London women suffering from menopausal symptoms. Study design This clinical pilot study employed a case series design within a wider action-based research project. 117 perimenopausal women between 45 and 55 years of age recruited from the general population were treated for menopausal symptoms by six experienced practitioners of Chinese medicine at the Polyclinic of the University of Westminster. Practitioners were instructed to treat as near to their usual practice style as possible. This involved using Chinese herbal medicine and/or acupuncture along with dietary and lifestyle advice. A maximum of 12 treatments over 6 months was allowed per patient. Outcome measures The menopause specific quality of life questionnaire (MenQoL), the Greene climacteric scale, and flushing diaries were used to evaluate treatment outcomes. Liver and kidney function tests were carried out at intake and after 1, 6 and 12 treatments to evaluate the safety particularly in relation to the use of herbal medicines. Results Patients showed significant improvement across all domains measured by the MenQoL and Greene climacteric scales. Reduction on the MenQoL scale between first and last visit was from 4.31 to 3.27 (p < 0.001) and on the Green climacteric scale from 21.01 to 13.00 (p < 0.001). Study participants did not reliably complete their flushing diaries. No adverse events or abnormal liver or kidney function values were observed during the course of the study. Conclusions Further research that seeks to investigate the effects observed in more detail and to evaluate them against other forms of treatment and/or no-treatment controls is warranted. This could be achieved by way of a pragmatic randomized controlled trial that evaluated Chinese medicine against orthodox medical care

Should I and Can I?: a mixed methods study of clinician beliefs and attitudes in the management of lifestyle risk factors in primary health care

BackgroundPrimary health care (PHC) clinicians have an important role to play in addressing lifestyle risk factors for chronic diseases. However they intervene only rarely, despite the opportunities that arise within their routine clinical practice. Beliefs and attitudes have been shown to be associated with risk factor management practices, but little is known about this for PHC clinicians working outside general practice. The aim of this study was to explore the beliefs and attitudes of PHC clinicians about incorporating lifestyle risk factor management into their routine care and to examine whether these varied according to their self reported level of risk factor management.MethodsA cross sectional survey was undertaken with PHC clinicians (n = 59) in three community health teams. Clinicians\u27 beliefs and attitudes were also explored through qualitative interviews with a purposeful sample of 22 clinicians from the teams. Mixed methods analysis was used to compare beliefs and attitudes for those with high and low levels of self reported risk factor management.ResultsRole congruence, perceived client acceptability, beliefs about capabilities, perceived effectiveness and clinicians\u27 own lifestyle were key themes related to risk factor management practices. Those reporting high levels of risk factor screening and intervention had different beliefs and attitudes to those PHC clinicians who reported lower levels.ConclusionPHC clinicians\u27 level of involvement in risk factor management reflects their beliefs and attitudes about it. This provides insights into ways of intervening to improve the integration of behavioural risk factor management into routine practice