Comparison of Organic and Integrated Nutrient Management Strategies for Reducing Soil N\u3csub\u3e2\u3c/sub\u3eO Emissions

To prevent nutrient limitations to crop growth, nitrogen is often applied in agricultural systems in the form of organic inputs (e.g., crop residues, manure, compost, etc.) or inorganic fertilizer. Inorganic nitrogen fertilizer has large environmental and economic costs, particularly for low-input smallholder farming systems. The concept of combining organic, inorganic, and biological nutrient sources through Integrated Nutrient Management (INM) is increasingly promoted as a means of improving nutrient use efficiency by matching soil nutrient availability with crop demand. While the majority of previous research on INM has focused on soil quality and yield, potential climate change impacts have rarely been assessed. In particular, it remains unclear whether INM increases or decreases soil nitrous oxide (N2O) emissions compared to organic nitrogen inputs, which may represent an overlooked environmental tradeoff. The objectives of this review were to (i) summarize the mechanisms influencing N2O emissions in response to organic and inorganic nitrogen (N) fertilizer sources, (ii) synthesize findings from the limited number of field experiments that have directly compared N2O emissions for organic N inputs vs. INM treatments, (iii) develop a hypothesis for conditions under which INM reduces N2O emissions and (iv) identify key knowledge gaps to address in future research. In general, INM treatments having low carbon to nitrogen ratio C:N (2O emissions

A Comparison of Nucleosome Organization in \u3cem\u3eDrosophila\u3c/em\u3e Cell Lines

Changes in the distribution of nucleosomes along the genome influence chromatin structure and impact gene expression by modulating the accessibility of DNA to transcriptional machinery. However, the role of genome-wide nucleosome positioning in gene expression and in maintaining differentiated cell states remains poorly understood. Drosophila melanogastercell lines represent distinct tissue types and exhibit cell-type specific gene expression profiles. They thus could provide a useful tool for investigating cell-type specific nucleosome organization of an organism’s genome. To evaluate this possibility, we compared genome-wide nucleosome positioning and occupancy in five different Drosophila tissue-specific cell lines, and in reconstituted chromatin, and then tested for correlations between nucleosome positioning, transcription factor binding motifs, and gene expression. Nucleosomes in all cell lines were positioned in accordance with previously known DNA-nucleosome interactions, with helically repeating A/T di-nucleotide pairs arranged within nucleosomal DNAs and AT-rich pentamers generally excluded from nucleosomal DNA. Nucleosome organization in all cell lines differed markedly from in vitro reconstituted chromatin, with highly expressed genes showing strong nucleosome organization around transcriptional start sites. Importantly, comparative analysis identified genomic regions that exhibited cell line-specific nucleosome enrichment or depletion. Further analysis of these regions identified 91 out of 16,384 possible heptamer sequences that showed differential nucleosomal occupation between cell lines, and 49 of the heptamers matched one or more known transcription factor binding sites. These results demonstrate that there is differential nucleosome positioning between these Drosophila cell lines and therefore identify a system that could be used to investigate the functional significance of differential nucleosomal positioning in cell type specification

Socioeconomic status, mental wellbeing and transition to secondary school: analysis of the School Health Research Network/Health Behaviour in School-aged Children survey in Wales

Young people’s wellbeing is often lowest where they assume a relatively low position within their school’s socioeconomic hierarchy, for example, among poorer children attending more affluent schools. Transition to secondary school is a period during which young people typically enter an environment which is more socio-economically diverse than their primary school. Young people joining a school with a higher socioeconomic status intake relative to their primary school may assume a relatively lowered position within their schools’ socioeconomic hierarchy, experiencing a detriment to their wellbeing as a consequence. This paper draws on data from 45,055 pupils in Years 7 and 8, from 193 secondary schools in Wales, who completed the 2017 Student Health Research Network (SHRN) Student Health and Wellbeing (SHW) Survey. Pupils reported which primary school they previously attended, and survey data on wellbeing were linked to publicly available data on the Free School Meal entitlement of schools attended. In cross-classified linear mixed-effects models, with primary and secondary school as levels, mental wellbeing varied significantly according to both primary and secondary school attended. A higher school-level deprivation was associated with worse mental wellbeing in both cases. Mental wellbeing was significantly predicted by the relative affluence of a child’s primary and secondary school, with movement to a secondary school of higher overall socioeconomic status associated with lowered wellbeing. These findings highlight transition to secondary school as a key point in which socioeconomic inequality in wellbeing ma

What’s coming for health science and policy in 2018? Global experts look ahead in their field

In PLOS Medicine\u27s first editorial of 2018, editorial board members and other leading researchers share their hopes, pleas, concerns, and expectations for this year in health research and policy

Animals can assign novel odours to a known category

The ability to identify a novel stimulus as a member of a known category allows an organism torespond appropriately towards it. Categorisation is thus a fundamental component of cognition andan essential tool for processing and responding to unknown stimuli. Therefore, one might expectto observe it throughout the animal kingdom and across sensory domains. There is much evidenceof visual categorisation in non-human animals, but we currently know little about this process inother modalities. In this experiment, we investigated categorisation in the olfactory domain. Dogswere trained to discriminate between 40 odours; the presence or absence of accelerants formed thecategorical rule. Those in the experimental group were rewarded for responding to substrates withaccelerants (either burnt or un-burnt) and inhibit responses to the same substrates (either burnt or unburnt)without accelerants (S+ counterbalanced). The pseudocategory control group was trained onthe same stimuli without the categorical rule. The experimental group learned the discrimination andanimals were able to generalise to novel stimuli from the same category. None of the control animalswere able to learn the discrimination within the maximum number of trials. This study provides the firstevidence that non-human animals can learn to categorise non-biologically relevant odour information

Breast cancer metastasis suppressor 1 (BRMS1) inhibits osteopontin transcription by abrogating NF-κB activation

BACKGROUND: Osteopontin (OPN), a secreted phosphoglycoprotein, has been strongly associated with tumor progression and aggressive cancers. MDA-MB-435 cells secrete very high levels of OPN. However metastasis-suppressed MDA-MB-435 cells, which were transfected with breast cancer metastasis suppressor 1 (BRMS1), expressed significantly less OPN. BRMS1 is a member of mSin3-HDAC transcription co-repressor complex and has been shown to suppress the metastasis of breast cancer and melanoma cells in animal models. Hence we hypothesized that BRMS1 regulates OPN expression. RESULTS: The search for a BRMS1-regulated site on the OPN promoter, using luciferase reporter assays of the promoter deletions, identified a novel NF-κB site (OPN/NF-κB). Electrophoretic mobility shift assays and chromatin immunoprecipitations (ChIP) confirmed this site to be an NF-κB-binding site. We also show a role of HDAC3 in suppression of OPN via OPN/NF-κB. CONCLUSION: Our results show that BRMS1 regulates OPN transcription by abrogating NF-κB activation. Thus, we identify OPN, a tumor-metastasis activator, as a crucial downstream target of BRMS1. Suppression of OPN may be one of the possible underlying mechanisms of BRMS1-dependent suppression of tumor metastasis

Narrative writing, reading and cognitive processes in middle childhood: what are the links?

This study investigated the relationship between measures of reading and writing, and explored whether cognitive measures known to be related to reading ability were also associated with writing performance in middle childhood. Sixty-Four children, aged between 8 years 9 months and 11 years 9 months, took part in a battery of writing, reading, and cognitive ability tasks. Reading fluency emerged as having a strong relationship to written language performance, after controlling for age and verbal reasoning. While children with reading difficulties were weak at spelling accuracy, they were otherwise found to produce written compositions of similar quality to typical readers. Boys produced less written text than girls, but did not demonstrate weaker written language abilities. Collectively the results demonstrate that writing skills can be separated into transcription and composition processes, and highlight the need for further research on the relationship between reading fluency and children’s writing

Targeting quiescent leukemic stem cells using second generation autophagy inhibitors

In chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) treatment induces autophagy that promotes survival and TKI-resistance in leukemic stem cells (LSCs). In clinical studies hydroxychloroquine (HCQ), the only clinically approved autophagy inhibitor, does not consistently inhibit autophagy in cancer patients, so more potent autophagy inhibitors are needed. We generated a murine model of CML in which autophagic flux can be measured in bone marrow-located LSCs. In parallel, we use cell division tracing, phenotyping of primary CML cells, and a robust xenotransplantation model of human CML, to investigate the effect of Lys05, a highly potent lysosomotropic agent, and PIK-III, a selective inhibitor of VPS34, on the survival and function of LSCs. We demonstrate that long-term haematopoietic stem cells (LT-HSCs: Lin−Sca-1+c-kit+CD48−CD150+) isolated from leukemic mice have higher basal autophagy levels compared with non-leukemic LT-HSCs and more mature leukemic cells. Additionally, we present that while HCQ is ineffective, Lys05-mediated autophagy inhibition reduces LSCs quiescence and drives myeloid cell expansion. Furthermore, Lys05 and PIK-III reduced the number of primary CML LSCs and target xenografted LSCs when used in combination with TKI treatment, providing a strong rationale for clinical use of second generation autophagy inhibitors as a novel treatment for CML patients with LSC persistence

Evaluation of Molecularly Imprinted Polymers as Synthetic Virus Neutralizing Antibody Mimics

Rapid development of antibody-based therapeutics are crucial to the agenda of innovative manufacturing of macromolecular therapies to combat emergent diseases. Although highly specific, antibody therapies are costly to produce. Molecularly-imprinted polymers (MIPs) constitute a rapidly-evolving class of antigen-recognition materials that act as synthetic antibodies. We report here on the virus neutralizing capacity of hydrogel-based MIPs. We produced MIPs using porcine reproductive and respiratory syndrome virus (PRRSV-1), as a model mammalian virus. Assays were performed to evaluate the specificity of virus neutralization, the effect of incubation time and MIP concentration. Polyacrylamide and N-hydroxymethylacrylamide based MIPs produced a highly significant reduction in infectious viral titer recovered after treatment, reducing it to the limit of detection of the assay. MIP specificity was tested by comparing their neutralizing effects on PRRSV-1 to the effects on the unrelated bovine viral diarrhea virus-1; no significant cross-reactivity was observed. The MIPs demonstrated effective virus neutralization in just 2.5 minutes and their effect was concentration dependent. These data support the further evaluation of MIPs as synthetic antibodies as a novel approach to the treatment of viral infection

Costs and Cost-Effectiveness of Biomedical, Non-Surgical HIV Prevention Interventions: A Systematic Literature Review.

BACKGROUND: Considerable evidence on the costs and cost-effectiveness of biomedical, non-surgical interventions to prevent human immunodeficiency virus (HIV) transmission has been generated over the last decade. This study aims to synthesize findings and identify remaining knowledge gaps to suggest future research priorities. METHODS: A systematic literature review was carried out in August 2020 using the MEDLINE, Embase, Global Health and EconLit databases to retrieve economic evaluations and costing studies of oral pre-exposure prophylaxis (PrEP), injectable long-acting PrEP, vaginal microbicide rings and gels, HIV vaccines and broadly neutralizing antibodies. Studies reporting costs from the provider or societal perspective were included in the analysis. Those reporting on behavioural methods of prevention, condoms and surgical approaches (voluntary medical male circumcision) were excluded. The quality of reporting of the included studies was assessed using published checklists. RESULTS: We identified 3007 citations, of which 87 studies were retained. Most were set in low- and middle-income countries (LMICs; n = 53) and focused on the costs and/or cost-effectiveness of oral PrEP regimens (n = 70). Model-based economic evaluations were the most frequent study design; only two trial-based cost-effectiveness analyses and nine costing studies were found. Less than half of the studies provided practical details on how the intervention would be delivered by the health system, and only three of these, all in LMICs, explicitly focused on service integration and its implication for delivery costs. 'Real-world' programme delivery mechanisms and costs of intervention delivery were rarely considered. PrEP technologies were generally found to be cost-effective only when targeting high-risk subpopulations. Single-dose HIV vaccines are expected to be cost-effective for all groups despite substantial uncertainty around pricing. CONCLUSIONS: A lack of primary, detailed and updated cost data, including above-service level costs, from a variety of settings makes it difficult to evaluate the cost-effectiveness of specific delivery modes at scale, or to evaluate strategies for services integration. Closing this evidence gap around real-world implementation is vital, not least because the strategies targeting high-risk groups that are recommended by PrEP models may incur substantially higher costs and be of limited practical feasibility in some settings