Enhancement of the Enzymatic Biosensor Response through Targeted Electrode Surface Roughness

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An investigation on the ability of Nanofibrillated cellulose to enhance the environmental sustainability of paper product manufacture

There are a number of products which are manufactured at a very large scale globally which are both energy and materials use intensive. In the case of paper and board manufacture, paper pulp (a mixture of cellulose, water and additives such as TiO2) require large quantities of cellulose, principally from trees and plant sources with the corresponding addition addition and removal of water by mechanical or thermal means.The objective of the study was to investigate the potential benefit if using a nanofibrillated form of cellulose (NFC) to reduce the total paper pulp quantities used while retaining paper mechanical and printing performance of the paper stock produced

A flexible and efficient Bayesian implementation of point process models for spatial capture‐recapture data

Spatial capture–recapture (SCR) is now routinely used for estimating abundance and density of wildlife populations. A standard SCR model includes sub-models for the distribution of individual activity centers (ACs) and for individual detections conditional on the locations of these ACs. Both sub-models can be expressed as point processes taking place in continuous space, but there is a lack of accessible and efficient tools to fit such models in a Bayesian paradigm. Here, we describe a set of custom functions and distributions to achieve this. Our work allows for more efficient model fitting with spatial covariates on population density, offers the option to fit SCR models using the semi-complete data likelihood (SCDL) approach instead of data augmentation, and better reflects the spatially continuous detection process in SCR studies that use area searches. In addition, the SCDL approach is more efficient than data augmentation for simple SCR models while losing its advantages for more complicated models that account for spatial variation in either population density or detection. We present the model formulation, test it with simulations, quantify computational efficiency gains, and conclude with a real-life example using non-invasive genetic sampling data for an elusive large carnivore, the wolverine (Gulo gulo) in Norway. area search, binomial point process, continuous sampling, NIMBLE, non-invasive genetic sampling, Poisson point process, spatial capture–recapture, wolverinepublishedVersio

An evaluation of nest predator impacts and the efficacy of plastic meshing on marine turtle nests on the western Cape York Peninsula, Australia

Nest predation is considered to be one of the most significant biotic threats to marine turtle populations globally. The introduction of feral predators to nesting beaches has dramatically increased nest predation, reaching near total egg loss in some regions. We monitored a 48 km stretch of beach along western Cape York Peninsula, Australia, from June – November 2018. We recorded a total of 360 nests comprising 117 flatback and 243 olive ridley nests. We installed plastic meshing (90 cm × 100 cm) on 110 olive ridley nests (45.2% of total olive ridley clutches laid) within the study area. We classified all nest predation attempts into three categories: complete, partial, or failed predation events. In total, 109 (30.2%) of all marine turtle nests were depredated by a variety of predators, including feral pigs, dingoes, goannas, and humans. The addition of plastic meshing reduced the likelihood of dingoes gaining access to eggs, but not goannas or feral pigs. Further, we found no difference in the proportion of hatchling emergence between meshed and un-meshed nests. Additionally, while hatchling emergence was reduced in nests that had been partially depredated, these nests still produced live hatchlings and contributed to recruitment. The success of particular predator control methods is often predator, and/or regionally, specific. Our findings highlight a thorough understanding of predator guilds and their relative impacts is required to deploy targeted and predator-specific strategies to maximize conservation results. We present a strong case for data-driven adaptive management that has implications for designing optimal predator management plans

Systemic inflammation associates with and precedes cord atrophy in progressive multiple sclerosis

In preclinical models of multiple sclerosis, systemic inflammation has an impact on the compartmentalised inflammatory process within the central nervous system and results in axonal loss. It remains to be shown whether this is the case in humans, specifically whether systemic inflammation contributes to spinal cord or brain atrophy in multiple sclerosis. Hence, an observational longitudinal study was conducted to delineate the relationship between systemic inflammation and atrophy using magnetic resonance imaging: the SIMS (Systemic Inflammation in Multiple Sclerosis) study. Systemic inflammation and progression were assessed in people with progressive multiple sclerosis (n = 50) over two and a half years. Eligibility criteria included: (1) primary or secondary progressive multiple sclerosis, (2) age ≤70, and (3) Expanded Disability Status Scale ≤6.5. First morning urine was collected weekly to quantify systemic inflammation by measuring the urinary neopterin-to-creatinine ratio using a validated ultra-performance liquid chromatography mass spectrometry technique. The urinary neopterin-to-creatinine ratio temporal profile was characterised by short-term responses overlaid on a background level of inflammation, so these two distinct processes were considered as separate variables: background inflammation and inflammatory response. In preclinical models, the effects of a systemic inflammatory challenge on tissue injury depended on prior exposure to inflammation. Participants underwent MRI at the start and end of the study, to measure cervical spinal cord and brain atrophy. Brain and cervical cord atrophy occurred on the study, but the most striking change was seen in the cervical spinal cord, in keeping with the corticospinal tract involvement that is typical of progressive disease. Systemic inflammation predicted cervical cord atrophy. An association with brain atrophy was not observed in this cohort. A time lag between systemic inflammation and cord atrophy was evident, suggesting but not proving causation. The association of the inflammatory response with cord atrophy depended on the level of background inflammation, in keeping with experimental data in preclinical models. A higher inflammatory response was associated with accelerated cord atrophy in the presence of background systemic inflammation below the median for the study population. Higher background inflammation, while associated with cervical cord atrophy itself, subdued the association of the inflammatory response with cord atrophy. Findings were robust to sensitivity analyses adjusting for potential confounders and excluding cases with new lesion formation. In conclusion, systemic inflammation associates with, and precedes, multiple sclerosis progression. Further work is needed to prove causation since targeting systemic inflammation may offer novel treatment strategies for slowing neurodegeneration in multiple sclerosis

A school-based intervention to promote physical activity among adolescent girls: Rationale, design, and baseline data from the Girls in Sport group randomised controlled trial

Background: Physical activity levels decline markedly among girls during adolescence. School-based interventions that are multi-component in nature, simultaneously targeting curricular, school environment and policy, and community links, are a promising approach for promoting physical activity. This report describes the rationale, design and baseline data from the Girls in Sport group randomised trial, which aims to prevent the decline in moderate-to-vigorous intensity physical activity (MVPA) among adolescent girls. Methods/design: A community-based participatory research approach and action learning framework are used with measurements at baseline and 18-month follow-up. Within each intervention school, a committee develops an action plan aimed at meeting the primary objective (preventing the decline in accelerometer-derived MVPA). Academic partners and the State Department of Education and Training act as critical friends. Control schools continue with their usual school programming. 24 schools were matched then randomized into intervention (n = 12) and control (n = 12) groups. A total of 1518 girls (771 intervention and 747 control) completed baseline assessments (86% response rate). Useable accelerometer data (≥ 10 hrs/day on at least 3 days) were obtained from 79% of this sample (n = 1199). Randomisation resulted in no differences between intervention and control groups on any of the outcomes. The mean age (SE) of the sample was 13.6 (± 0.02) years and they spent less than 5% of their waking hours in MVPA (4.85 ± 0.06). Discussion: Girls in Sport will test the effectiveness of schools working towards the same goal, but developing individual, targeted interventions that bring about changes in curriculum, school environment and policy, and community links. By using community-based participatory research and an action learning framework in a secondary school setting, it aims to add to the body of literature on effective school-based interventions through promoting and sustaining increased physical activity participation among adolescent girls

The pedagogy and principles of teaching therapeutic practice with children and young people.

Technical approaches suggesting that systematically produced, generalized, and scientific knowledge are the most solid foundations for practice present significant challenges for the social work profession, in which the decisions faced often are not technical but rather moral, requiring the application of ethically based and intuitive skills. Meanwhile, the command, control, and measurement of outcomes in social work practice also present significant conundrums for the delivery of relational person-centered social work and social care. With a focus too often on efficiency rather than on effectiveness, this managerialistic approach frequently fails to acknowledge the complexity inherent in the act of caring. In this context and framework, teaching therapeutic practice with children draws a balance between traditional systematic teaching methods and use of creative media including art, play, and music. This article outlines the positive contribution to professional social work practice that the teaching of therapeutic approaches to child care can make

Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15–17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype–phenotype map than previously anticipated

Metabolic State Determines Sensitivity to Cellular Stress in Huntington Disease: Normalization by Activation of PPARγ

Impairments in mitochondria and transcription are important factors in the pathogenesis of Huntington disease (HD), a neurodegenerative disease caused by a polyglutamine expansion in the huntingtin protein. This study investigated the effect of different metabolic states and peroxisome proliferator-activated receptor γ (PPARγ) activation on sensitivity to cellular stressors such as H2O2 or thapsigargin in HD. Striatal precursor cells expressing wild type (STHdhQ7) or mutant huntingtin (STHdhQ111) were prepared in different metabolic conditions (glucose vs. pyruvate). Due to the fact that STHdhQ111 cells exhibit mitochondrial deficits, we expected that in the pyruvate condition, where ATP is generated primarily by the mitochondria, there would be greater differences in cell death between the two cell types compared to the glucose condition. Intriguingly, it was the glucose condition that gave rise to greater differences in cell death. In the glucose condition, thapsigargin treatment resulted in a more rapid loss of mitochondrial membrane potential (ΔΨm), a greater activation of caspases (3, 8, and 9), and a significant increase in superoxide/reactive oxygen species (ROS) in STHdhQ111 compared to STHdhQ7, while both cell types showed similar kinetics of ΔΨm-loss and similar levels of superoxide/ROS in the pyruvate condition. This suggests that bioenergetic deficiencies are not the primary contributor to the enhanced sensitivity of STHdhQ111 cells to stressors compared to the STHdhQ7 cells. PPARγ activation significantly attenuated thapsigargin-induced cell death, concomitant with an inhibition of caspase activation, a delay in ΔΨm loss, and a reduction of superoxide/ROS generation in STHdhQ111 cells. Expression of mutant huntingtin in primary neurons induced superoxide/ROS, an effect that was significantly reduced by constitutively active PPARγ. These results provide significant insight into the bioenergetic disturbances in HD with PPARγ being a potential therapeutic target for HD

p53 Transactivation and the Impact of Mutations, Cofactors and Small Molecules Using a Simplified Yeast-Based Screening System

The p53 tumor suppressor, which is altered in most cancers, is a sequence-specific transcription factor that is able to modulate the expression of many target genes and influence a variety of cellular pathways. Inactivation of the p53 pathway in cancer frequently occurs through the expression of mutant p53 protein. In tumors that retain wild type p53, the pathway can be altered by upstream modulators, particularly the p53 negative regulators MDM2 and MDM4. promoter, ii) single copy, chromosomally located p53-responsive and control luminescence reporters, iii) enhanced chemical uptake using modified ABC-transporters, iv) small-volume formats for treatment and dual-luciferase assays, and v) opportunities to co-express p53 with other cofactor proteins. This robust system can distinguish different levels of expression of WT and mutant p53 as well as interactions with MDM2 or 53BP1.We found that the small molecules Nutlin and RITA could both relieve the MDM2-dependent inhibition of WT p53 transactivation function, while only RITA could impact p53/53BP1 functional interactions. PRIMA-1 was ineffective in modifying the transactivation capacity of WT p53 and missense p53 mutations. This dual-luciferase assay can, therefore, provide a high-throughput assessment tool for investigating a matrix of factors that can influence the p53 network, including the effectiveness of newly developed small molecules, on WT and tumor-associated p53 mutants as well as interacting proteins