PPARα contributes to protection against metabolic and inflammatory derangements associated with acute kidney injury in experimental sepsis

Abstract Sepsis‐associated acute kidney injury (AKI) is a significant problem in critically ill children and adults resulting in increased morbidity and mortality. Fundamental mechanisms contributing to sepsis‐associated AKI are poorly understood. Previous research has demonstrated that peroxisome proliferator‐activated receptor α (PPARα) expression is associated with reduced organ system failure in sepsis. Using an experimental model of polymicrobial sepsis, we demonstrate that mice deficient in PPARα have worse kidney function, which is likely related to reduced fatty acid oxidation and increased inflammation. Ultrastructural evaluation with electron microscopy reveals that the proximal convoluted tubule is specifically injured in septic PPARα deficient mice. In this experimental group, serum metabolomic analysis reveals unanticipated metabolic derangements in tryptophan‐kynurenine‐NAD+ and pantothenate pathways. We also show that a subgroup of children with sepsis whose genome‐wide expression profiles are characterized by repression of the PPARα signaling pathway has increased incidence of severe AKI. These findings point toward interesting associations between sepsis‐associated AKI and PPARα‐driven fatty acid metabolism that merit further investigation

Accessing Nuclear Structure for Field Emission, in Lens, Scanning Electron Microscopy (FEISEM)

Scanning electron microscopy (SEM) has had a shorter time course in biology than conventional transmission electron microscopy (TEM) but has nevertheless produced a wealth of images that have significantly complemented our perception of biological structure and function from TEM information. By its nature, SEM is a surface imaging technology, and its impact at the subcellular level has been restricted by the considerably reduced resolution in conventional SEM in comparison to TEM. This restriction has been removed by the recent advent of high-brightness sources used in lensfield emission instruments (FEISEM) which have produced resolution of around 1 nanometre, which is not usually a limiting figure for biological material. This communication reviews our findings in the use of FEISEM in the imaging of nuclear surfaces, then associated structures, such as nuclear pore complexes, and the relationships of these structures with cytoplasmic and nucleoplasmic elements. High resolution SEM allows the structurally orientated cell biologist to visualise, directly and in three dimensions, subcellular structure and its modulation with a view to understanding its functional significance. Clearly, intracellular surfaces require separation from surrounding structural elements in vivo to allow surface imaging, and we review a combination of biochemical and mechanical isolation methods for nuclear surfaces

Using novel palaeolimnological techniques to define lake conservation objectives for three Cheshire meres

This is the final report to Natural England on the project „Using novel palaeolimnological techniques to define lake conservation objectives for three Cheshire meres‟: Melchett Mere, Tatton Mere and Comber Mere. The aim is to use existing and recently developed palaeoecological techniques to define reference conditions and assess the condition of selected Sites of Special Scientific Interest (SSSIs) in the Cheshire meres, and thereby assist in the setting of conservation objectives and management goals

Sedimentary macrofossil records reveal ecological change in English lakes: implications for conservation

Aquatic macrophytes play a key role in providing habitat, refuge and food for a range of biota in shallow lakes. However, many shallow lakes have experienced declines in macrophyte vegetation in recent decades, principally due to eutrophication. As changes in macrophyte composition and abundance can affect overall ecological structure and function of a lake, an assessment of the timing and nature of such changes is crucial to our understanding of the wider lake ecosystem. In the typical absence of historical plant records, the macro-remains of macrophytes preserved in lake sediments can be used to assess long-term changes in aquatic vegetation. We generated recent (150–200 years) plant macrofossil records for six English lakes subject to conservation protection to define past macrophyte communities, assess trajectories of ecological change and consider the implications of our findings for conservation targets and strategies. The data for all six lakes reveal a diverse submerged macrophyte community, with charophytes as a key component, in the early part of the sedimentary records. The stratigraphies indicate considerable change to the aquatic vegetation over the last two centuries with a general shift towards species more typically associated with eutrophic conditions. A common feature is the decline in abundance of low-growing charophytes and an increase in tall canopy-forming angiosperms such as fine-leaved Potamogeton species, Zannichellia palustris and Callitriche species. We hypothesise, based on findings from long-term datasets and palaeoecological records from enriched shallow lakes where plants are now absent, that the observed shifts provide a warning to managers that the lakes are on a pathway to complete macrophyte loss such that nutrient load reduction is urgently needed. It is the sound understanding of present-day plant ecology that affords such reliable interpretation of the fossil data which, in turn, provide valuable context for current conservation decisions

Evaluation and Comparison of a Habitat Suitability Model for Postdrift Larval Lake Sturgeon in the St. Clair and Detroit Rivers

We evaluated composition and spatial distribution of riverine nursery habitat for larval Lake Sturgeon Acipenser fulvescens in the Middle Channel of the St. Clair River, Michigan, and Fighting Island Channel of the Detroit River, Ontario, using a habitat suitability model (HSM) and fish collections. Although model outputs indicated similar portions of high‐quality habitat in the Middle Channel (16.9%) and Fighting Island Channel (15.7%), larval abundance and dispersal patterns varied between these systems. Analysis with Akaike’s information criterion indicated that a regression model using sand–silt substrate performed best at predicting the observed water‐volume‐standardized CPUE (number of larvae·h−1·m−3) in the Middle Channel. Of 93 larvae that were collected in the Middle Channel, most were found to cluster at three distinct areas of high‐ and moderate‐quality habitat, which was composed predominately of sand–silt substrate. Lengths of larvae varied by as much as 9 mm, and the degree of yolk sac absorption also varied, indicating that larvae in the Middle Channel remained within the channel after a short drift downstream. Of the 25 larvae that were collected in Fighting Island Channel, distribution was sporadic, and occurrence did not significantly correlate with measured habitat variables. Larvae were relatively homogeneous in size and yolk sac stage, indicating that newly emerged larvae did not utilize available habitat in Fighting Island Channel but instead drifted into the main channel of the Detroit River. Dispersal patterns indicate variability in young Lake Sturgeon ecology, which is dependent on local habitat conditions—most notably, substrate composition. Furthermore, modeled larval–habitat associations found in this study were compared to a similar study on larval Lake Sturgeon from the North Channel of the St. Clair River. Model outputs from all three systems accurately accounted for observed larval dispersal patterns among both rivers. This supports the transferability of an HSM parameterized for Lake Sturgeon from individual river reaches within two large river systems.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146299/1/nafm10217.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146299/2/nafm10217_am.pd

STING gain-of-function disrupts lymph node organogenesis and innate lymphoid cell development in mice

STING gain-of-function causes autoimmunity and immunodeficiency in mice and STING-associated vasculopathy with onset in infancy (SAVI) in humans. Here, we report that STING gain-of-function in mice prevents development of lymph nodes and Peyer\u27s patches. We show that the absence of secondary lymphoid organs is associated with diminished numbers of innate lymphoid cells (ILCs), including lymphoid tissue inducer (LTi) cells. Although wild-type (WT) α4β

Psychological impact of anti-VEGF treatments for wet macular degeneration-a review.

To review the current literature on the psychological impact of anti-VEGF treatments for wet age-related macular degeneration (wAMD), in terms of patients' experiences of receiving these treatments, and the impact of these treatments for patients' mental health and quality of life.We critically analyzed current literature evaluating psychological impact of anti-VEGF treatments for wAMD. Primary searches of PubMed, Science Direct, and Web of Science were conducted in July and August of 2015. We reviewed all papers on the topic published until August 5, 2015.Our literature search found 14 papers addressing the psychological impact of anti-VEGF treatments for wAMD. Results highlighted potential anxieties and experiences of pain caused by receiving regular intravitreal injections. A positive visual outcome of anti-VEGF therapy is associated with positive vision-related QOL outcomes, although such association seems to be dependent on improvements on visual acuity. In the literature reviewed, patients receiving anti-VEGF treatments showed a prevalence rate of depression between 20 and 26 %.Although anti-VEGF treatments can cause some anxiety and being experienced as a stressful event, especially in the beginning of the treatment, preliminary findings suggest a potential benefit for long-term vision-related quality of life. Further longitudinal and qualitative research should bring more evidence on the positive and negative effects of these treatments on patients' long-term mental health

Advice about diet and smoking for people with or at risk of age-related macular degeneration: a cross-sectional survey of eye care professionals in the UK.

BACKGROUND: In the absence of a cure, there has been considerable interest in attempts to prevent or reduce the progression of age-related macular degeneration (AMD) by targeting particular modifiable risk factors. The aim of this study was to conduct a cross-sectional survey of the current practice of UK eye care professionals in relation to advice given on diet and other lifestyle modifications for patients with or at risk of AMD. METHODS: Optometrists and ophthalmologists on the membership databases of professional organisations for the two professions were invited to participate in an online survey. The survey was open for 12 weeks between July and September 2012. RESULTS: A total of 1,468 responses were received (96.3% from optometrists and 3.7% from ophthalmologists). The response rate of those receiving the invitation was 16.2% (1,414/8735) for optometrists and 6% (54/1460) for ophthalmologists. A majority of respondents reported that they frequently provide dietary advice to patients with established AMD (67.9%) and those at risk of AMD (53.6%). Typical advice consisted of a recommendation to eat plenty of leafy green vegetables and eat more oily fish. The decision to recommend nutritional supplements was based on the risk of progression to advanced AMD, with approximately 93% of respondents recommending supplementation in a patient with advanced AMD in one eye. However for the majority, the type of supplement recommended did not comply with current best research evidence, based on the findings of the Age-related Eye Disease Study (AREDS). Only one in three optometrists regularly assessed smoking status and advised on smoking cessation. CONCLUSIONS: Within a large sample of eye care professionals, consisting predominantly of optometrists, who responded to a cross-sectional survey, there was active engagement in providing nutritional advice to patients with or at risk of AMD. However, the results demonstrate a need to raise awareness of the evidence underpinning the use of nutritional supplements together with an increased involvement in targeted smoking cessation

Defining Chlorophyll-a Reference Conditions in European Lakes

The concept of “reference conditions” describes the benchmark against which current conditions are compared when assessing the status of water bodies. In this paper we focus on the establishment of reference conditions for European lakes according to a phytoplankton biomass indicator—the concentration of chlorophyll-a. A mostly spatial approach (selection of existing lakes with no or minor human impact) was used to set the reference conditions for chlorophyll-a values, supplemented by historical data, paleolimnological investigations and modelling. The work resulted in definition of reference conditions and the boundary between “high” and “good” status for 15 main lake types and five ecoregions of Europe: Alpine, Atlantic, Central/Baltic, Mediterranean, and Northern. Additionally, empirical models were developed for estimating site-specific reference chlorophyll-a concentrations from a set of potential predictor variables. The results were recently formulated into the EU legislation, marking the first attempt in international water policy to move from chemical quality standards to ecological quality targets