Pattern recognition receptors in antifungal immunity

We thank the Wellcome Trust for funding this study.Peer reviewedPublisher PD

Comparative review of the effects of organic farming on biodiversity (OF0149)

This is the final report of Defra project OF0149 1. The report reviews the impact of different farming regimes and makes a comparative study of their influence on the biodiversity of arable farmland. 2. Within this review, the evaluation of impacts on biodiversity focuses on species and habitats, and includes both the number, abundance and activity of species (section 1.3). 3. Five farming regimes are defined and discussed, namely Conventional Arable, Conventional Mixed Lowland, Organic and two integrated production regimes - LEAF (Linking Environment and Farming) and IFS-Experimental regimes The main differences between the regimes in relation to the use of external inputs and other agricultural practices are discussed. The review draws on both UK and European information (section 1.4). 4. The effect of each farming regime on biodiversity is assessed according to the agricultural practices adopted and to the occurrence and management of uncropped land present. Agricultural practices are reviewed within the following categories: cultivation, crop production, crop protection and post-cropping practice (section 2.1). 5. Among the agricultural practices examined, those associated with crop protection and the artificial inputs associated with crop production were seen as the most adverse for biodiversity. Several practices were seen to benefit the biodiversity of arable land. These included set-aside, crop rotations with grass leys, spring sowing, permanent pasture, green manuring and intercropping (section 2.7). 6. Uncropped areas, such as sown grass strips (beetle banks), grass margins and conservation headlands, were seen as critical for the maintenance of biodiversity on arable farmland. Changes in the balance of cropped to uncropped land within some farming regimes, linked to increase in field size, have had a major impact on the diversity of flora and fauna associated with those regimes (section 3.4). 7. Based on the evaluation of agricultural practices used, the occurrence of uncropped land and the extent of the farming regime within England and Wales, it was concluded that Conventional Arable regimes act effectively to maintain the impoverished status of biodiversity on arable land. Extreme examples can be found of intensively managed farms that further deplete biodiversity and sympathetically managed farms that try to enhance it. Increased adoption of agricultural practices such as direct drilling, use of farmyard manure, set-aside, use of crop rotations with leys, or an increase in the incidence and sympathetic management of uncropped areas may well assist biodiversity on farms within this regime (sections 4.3 & 4.4) 8. Organic regimes were shown to have an overall benefit for biodiversity at the farm level, both in terms of the agricultural practices adopted and in the occurrence and management of uncropped areas (sections 4.3 & 4.4). 9. Conventional Mixed Lowland and LEAF regimes were both seen to have the potential for enhancing biodiversity on arable land. Here, adverse impacts associated with crop protection and crop production may be mitigated by beneficial effects associated with post-cropping practices, the occurrence of permanent pasture and uncropped land. At present, the extent to which enhancement may be achieved, may well depend on the extent, condition and management of uncropped land present within these regimes (sections 4.3 & 4.4). 10. IFS-experimental regimes were seen to have a beneficial effect on biodiversity, due to the stringent procedures used for targeting herbicides and pesticides and for establishing and managing uncropped areas. At present these regimes occupy a tiny area of the national resource of arable land and thus their impact on national biodiversity is likely to be insignificant at the present time (sections 4.3 & 4.4). 11. A number of areas are highlighted for further consideration. These include: • monitoring of biodiversity on farms pre- and post- conversion to organic farming, • comparative studies that focus on the effectiveness of different regimes or agricultural practices in enhancing biodiversity on species-impoverished intensively managed arable land, • manipulative experiments to determine the optimal balance of cropped to uncropped areas for enhancing biodiversity, • manipulative experiments to examine the separate impacts of rotational regimes and agricultural inputs on biodiversity, • an economic assessment of the costs and benefits in both production and biodiversity terms, of conversion to organic, integrated production or uptake of available agri-environment schemes

Conjugation of an oligonucleotide to Tat, a cell penetrating peptide, via click chemistry

Uptake of diagnostic and therapeutic oligonucleotides that specifically target disease can be enhanced by attachment of a cell penetrating peptide. Here we describe the covalent attachment of an oligonucleotide to Tat, a biologically important cell-penetrating peptide, via click chemistry

Facilitating goal-oriented behaviour in the Stroop task: when executive control is influenced by automatic processing.

A portion of Stroop interference is thought to arise from a failure to maintain goal-oriented behaviour (or goal neglect). The aim of the present study was to investigate whether goal- relevant primes could enhance goal maintenance and reduce the Stroop interference effect. Here it is shown that primes related to the goal of responding quickly in the Stroop task (e.g. fast, quick, hurry) substantially reduced Stroop interference by reducing reaction times to incongruent trials but increasing reaction times to congruent and neutral trials. No effects of the primes were observed on errors. The effects on incongruent, congruent and neutral trials are explained in terms of the influence of the primes on goal maintenance. The results show that goal priming can facilitate goal-oriented behaviour and indicate that automatic processing can modulate executive control

The Spirit-Murdering of Black Students from White Educators

In this collection of autoethnographies, four researchers explored our deeply personal experiences and encounters with racialized oppression in the form of spirit-murder. Using Critical Race Theory (CRT) and Critical Whiteness Studies, this dissertation explores how two white educators have committed spirit-murder against Black students and how two Black educators have both experienced spirit-murder as students and have spirit-murdered their Black and Brown students as classroom teachers. We wanted to elevate our voices using counter-stories as a tenet of CRT and examples of our teaching practices. We aimed to elicit relatable suggestions to combat spirit-murdering from white educators toward Black students during their grade school and college experiences. All four educators hoped that by sharing, we exposed not only the existence and effects of spirit-murder and ways we were working to eliminate these unfair acts and practices but also ways to better support Black children in classrooms where racist school systems still exist. We reflected on the personal damage caused to us as Black children and created by us towards Black children as white and Black educators. We analyzed the importance and value of a person’s spirit, the term “murder,” and the phrase “spirit-murder,” as they related to our experiences. We shared encounters from grade school to college classrooms in public, private, urban, and suburban settings. Our cohort dissertation group consists of a Black male who is an assistant principal, a white male who is a former visual arts teacher and is now an athletic director, a white female who is a high school English teacher, and a Black female who is a district culture and climate coordinator

Drug Discovery Opportunities and Challenges at G Protein Coupled Receptors for Long Chain Free Fatty Acids

Discovery of G protein coupled receptors for long chain free fatty acids (FFAs), FFA1 (GPR40) and GPR120, has expanded our understanding of these nutrients as signaling molecules. These receptors have emerged as important sensors for FFA levels in the circulation or the gut lumen, based on evidence from in vitro and rodent models, and an increasing number of human studies. Here we consider their promise as therapeutic targets for metabolic disease, including type 2 diabetes and obesity. FFA1 directly mediates acute FFA-induced glucose-stimulated insulin secretion in pancreatic beta-cells, while GPR120 and FFA1 trigger release of incretins from intestinal endocrine cells, and so indirectly enhance insulin secretion and promote satiety. GPR120 signaling in adipocytes and macrophages also results in insulin sensitizing and beneficial anti-inflammatory effects. Drug discovery has focused on agonists to replicate acute benefits of FFA receptor signaling, with promising early results for FFA1 agonists in man. Controversy surrounding chronic effects of FFA1 on beta-cells illustrates that long term benefits of antagonists also need exploring. It has proved challenging to generate highly selective potent ligands for FFA1 or GPR120 subtypes, given that both receptors have hydrophobic orthosteric binding sites, which are not completely defined and have modest ligand affinity. Structure activity relationships are also reliant on functional read outs, in the absence of robust binding assays to provide direct affinity estimates. Nevertheless synthetic ligands have already helped dissect specific contributions of FFA1 and GPR120 signaling from the many possible cellular effects of FFAs. Approaches including use of fluorescent ligand binding assays, and targeting allosteric receptor sites, may improve further pre-clinical ligand development at these receptors, to exploit their unique potential to target multiple facets of diabetes

Solution structure of a bacterial microcompartment targeting peptide and its application in the construction of an ethanol bioreactor

Targeting of proteins to bacterial microcompartments (BMCs) is mediated by an 18-amino-acid peptide sequence. Herein, we report the solution structure of the N-terminal targeting peptide (P18) of PduP, the aldehyde dehydrogenase associated with the 1,2-propanediol utilization metabolosome from Citrobacter freundii. The solution structure reveals the peptide to have a well-defined helical conformation along its whole length. Saturation transfer difference and transferred NOE NMR has highlighted the observed interaction surface on the peptide with its main interacting shell protein, PduK. By tagging both a pyruvate decarboxylase and an alcohol dehydrogenase with targeting peptides, it has been possible to direct these enzymes to empty BMCs in vivo and to generate an ethanol bioreactor. Not only are the purified, redesigned BMCs able to transform pyruvate into ethanol efficiently, but the strains containing the modified BMCs produce elevated levels of alcohol

Fonsecaea pedrosoi-induced Th17-cell differentiation in mice is fostered by Dectin-2 and suppressed by Mincle recognition

Funded by NIH. Grant Number: R01 AI093553 Wellcome TrustPeer reviewedPublisher PD

Mental Health Functioning in the Human Rights Field: Findings from an International Internet-Based Survey

Human rights advocates play a critical role in promoting respect for human rights world-wide, and engage in a broad range of strategies, including documentation of rights violations, monitoring, press work and report-writing, advocacy, and litigation. However, little is known about the impact of human rights work on the mental health of human rights advocates. This study examined the mental health profile of human rights advocates and risk factors associated with their psychological functioning. 346 individuals currently or previously working in the field of human rights completed an internet-based survey regarding trauma exposure, depression, posttraumatic stress disorder (PTSD), resilience and occupational burnout. PTSD was measured with the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) and depression was measured with the Patient History Questionnaire-9 (PHQ-9). These findings revealed that among human rights advocates that completed the survey, 19.4% met criteria for PTSD, 18.8% met criteria for subthreshold PTSD, and 14.7% met criteria for depression. Multiple linear regressions revealed that after controlling for symptoms of depression, PTSD symptom severity was predicted by human rights-related trauma exposure, perfectionism and negative self-appraisals about human rights work. In addition, after controlling for symptoms of PTSD, depressive symptoms were predicted by perfectionism and lower levels of self-efficacy. Survey responses also wuggested high levels of resilience: 43% of responders reported minimal symptoms of PTSD. Although survey responses suggest that many human rights workers are resilient, they also suggest that human rights work is associated with elevated rates of PTSD and depression. The field of human rights would benefit from further empirical research, as well as additional education and training programs in the workplace about enhancing resilience in the context of human rights work

Newcomer families' experiences with programs and services to support early childhood development in Canada: A scoping review

It can be difficult for families with young children to navigate early childhood development supports. In particular, newcomer families often encounter additional barriers and require resources, programs, and services that are tailored to their unique assets, experiences, and needs. We conducted a scoping review of the literature published between 2000 and 2019 to explore what is known about newcomer families’ experiences with programs and services to support early childhood development in Canada. We searched 12 databases, screened 2390 articles, and included 34 articles for synthesis and analysis. Three common and connected themes were identified: 1) effective intercultural understanding, responsiveness, and communication are critical to ensuring full access to meaningful programs and services; 2) some newcomer families face systemic barriers exacerbated by their immigration status, and; 3) feelings and perceptions of families and service providers, as well as social supports, networks, and relationships influence how programs and services are accessed and experienced. Our review identifies the requirement for additional, participatory research that centres the voices and perspectives of newcomer children and their families and the need to expand that research to less populated and rural areas of the country to inform meaningful and culturally relevant policies, programs, and services for newcomer families to support their children’s well-being