Effects of Degraded Optical Conditions on Behavioural Responses to Alarm Cues in a Freshwater Fish

Prey organisms often use multiple sensory cues to gain reliable information about imminent predation threat. In this study we test if a freshwater fish increases the reliance on supplementary cues when the reliability of the primary cue is reduced. Fish commonly use vision to evaluate predation threat, but may also use chemical cues from predators or injured conspecifics. Environmental changes, such as increasing turbidity or water colour, may compromise the use of vision through changes in the optical properties of water. In an experiment we tested if changes in optical conditions have any effects on how crucian carp respond to chemical predator cues. In turbidity treatments we added either clay or algae, and in a brown water colour treatment we added water with a high humic content. We found that carp reduced activity in response to predator cues, but only in the turbidity treatments (clay, algae), whereas the response in the brown water treatment was intermediate, and not significantly different from, clear and turbid water treatments. The increased reliance on chemical cues indicates that crucian carp can compensate for the reduced information content from vision in waters where optical conditions are degraded. The lower effect in brown water may be due to the reduction in light intensity, changes in the spectral composition (reduction of UV light) or to a change in chemical properties of the cue in humic waters

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses.

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Birds in the playground: Evaluating the effectiveness of an urban environmental education project in enhancing school children's awareness, knowledge and attitudes towards local wildlife.

Children nowadays, particularly in urban areas, are more disconnected from nature than ever before, leading to a large-scale "extinction of experience" with the natural world. Yet there are many potential benefits from children interacting with nature first-hand, including via outdoor learning opportunities. Urban environmental education programmes typically aim to increase awareness and knowledge of local biodiversity and to promote positive attitudes and behaviour towards the environment. However, limited research has been conducted evaluating to what extent these interventions achieve their goals. Here, we explore and assess the influence of a six-week bird-feeding and monitoring project conducted within school grounds ("Bird Buddies") on individual awareness, knowledge and attitudes towards birds by primary school children. This initiative was conducted across eight (sub-)urban primary schools within Brighton and Hove (UK), with 220 participating children (aged 7 to 10). Via pre- and post-project questionnaires, we found evidence for enhanced awareness of local biodiversity, alongside significant gains in both bird identification knowledge and attitudes, which were greatest for children with little prior exposure to nature. Many children expressed a keenness to continue improving the environmental value of their school grounds and to apply elements of the project at home. Student project evaluation scores were consistently positive. Mirroring this, participating teachers endorsed the project as a positive learning experience for their students. One year after the project, several schools were continuing to feed and watch birds. Collectively, the findings from this study highlight the multiple benefits that can be derived from engagement with a relatively short outdoor environmental activity. We therefore believe that such interventions, if repeated locally/longer term, could enhance children's experience with nature in urban settings with combined positive environmental impact

Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol

The interstitium in cardiac repair: role of the immune-stromal cell interplay

Cardiac regeneration, that is, restoration of the original structure and function in a damaged heart, differs from tissue repair, in which collagen deposition and scar formation often lead to functional impairment. In both scenarios, the early-onset inflammatory response is essential to clear damaged cardiac cells and initiate organ repair, but the quality and extent of the immune response vary. Immune cells embedded in the damaged heart tissue sense and modulate inflammation through a dynamic interplay with stromal cells in the cardiac interstitium, which either leads to recapitulation of cardiac morphology by rebuilding functional scaffolds to support muscle regrowth in regenerative organisms or fails to resolve the inflammatory response and produces fibrotic scar tissue in adult mammals. Current investigation into the mechanistic basis of homeostasis and restoration of cardiac function has increasingly shifted focus away from stem cell-mediated cardiac repair towards a dynamic interplay of cells composing the less-studied interstitial compartment of the heart, offering unexpected insights into the immunoregulatory functions of cardiac interstitial components and the complex network of cell interactions that must be considered for clinical intervention in heart diseases