Variation in Isoprene Emission from Quercus rubra: Sources, Causes, and Consequences for Estimating Fluxes

Isoprene is the dominant volatile organic compound produced in many forest systems. Uncertainty in estimates of leaf level isoprene emission rate stems from an insufficient understanding of the patterns and processes controlling isoprene emission capacity in plant leaves. Previous studies suggest that variation in isoprene emission capacity is substantial; however, it is not known at what scale emission capacity is the most variable. Identifying the sources of variation in emission capacity has implications for conducting measurements and for model development, which will ultimately improve emission estimates and models of tropospheric chemistry. In addition, understanding the sources of variation will help to develop a comprehensive understanding of the physiological controls over isoprene emission. This study applied a variance partitioning approach to identify the major sources of variation in isoprene emission capacity from two populations of northern red oak (Quercus rubra) over three growing seasons. Specifically, we evaluated variation due to climate, populations, trees, branches, leaves, seasons, and years. Overall, the dominant source of variation was the effect of a moderate drought event. In the years without drought events, variation among individual trees (intraspecific) explained approximately 60% of the total variance. Within the midseason, isoprene emission capacity of sun leaves varied by a factor of 2 among trees. During the third year a moderate 20-day drought event caused isoprene emission capacity to decrease fourfold, and the relative importance of intraspecific variation was reduced to 24% of total variance. Overall, ambient temperature, light, and a drought index were poor predictors of isoprene emission capacity over a 0 to 14-day period across growing seasons. The drought event captured in this study emphasizes the need to incorporate environmental influences into leaf level emission models

A robust prognostic signature for hormone-positive node-negative breast cancer

BACKGROUND: Systemic chemotherapy in the adjuvant setting can cure breast cancer in some patients that would otherwise recur with incurable, metastatic disease. However, since only a fraction of patients would have recurrence after surgery alone, the challenge is to stratify high-risk patients (who stand to benefit from systemic chemotherapy) from low-risk patients (who can safely be spared treatment related toxicities and costs). METHODS: We focus here on risk stratification in node-negative, ER-positive, HER2-negative breast cancer. We use a large database of publicly available microarray datasets to build a random forests classifier and develop a robust multi-gene mRNA transcription-based predictor of relapse free survival at 10 years, which we call the Random Forests Relapse Score (RFRS). Performance was assessed by internal cross-validation, multiple independent data sets, and comparison to existing algorithms using receiver-operating characteristic and Kaplan-Meier survival analysis. Internal redundancy of features was determined using k-means clustering to define optimal signatures with smaller numbers of primary genes, each with multiple alternates. RESULTS: Internal OOB cross-validation for the initial (full-gene-set) model on training data reported an ROC AUC of 0.704, which was comparable to or better than those reported previously or obtained by applying existing methods to our dataset. Three risk groups with probability cutoffs for low, intermediate, and high-risk were defined. Survival analysis determined a highly significant difference in relapse rate between these risk groups. Validation of the models against independent test datasets showed highly similar results. Smaller 17-gene and 8-gene optimized models were also developed with minimal reduction in performance. Furthermore, the signature was shown to be almost equally effective on both hormone-treated and untreated patients. CONCLUSIONS: RFRS allows flexibility in both the number and identity of genes utilized from thousands to as few as 17 or eight genes, each with multiple alternatives. The RFRS reports a probability score strongly correlated with risk of relapse. This score could therefore be used to assign systemic chemotherapy specifically to those high-risk patients most likely to benefit from further treatment

CD4-Transgenic Zebrafish Reveal Tissue-Resident Th2- and Regulatory T Cell-like Populations and Diverse Mononuclear Phagocytes.

CD4+ T cells are at the nexus of the innate and adaptive arms of the immune system. However, little is known about the evolutionary history of CD4+ T cells, and it is unclear whether their differentiation into specialized subsets is conserved in early vertebrates. In this study, we have created transgenic zebrafish with vibrantly labeled CD4+ cells allowing us to scrutinize the development and specialization of teleost CD4+ leukocytes in vivo. We provide further evidence that CD4+ macrophages have an ancient origin and had already emerged in bony fish. We demonstrate the utility of this zebrafish resource for interrogating the complex behavior of immune cells at cellular resolution by the imaging of intimate contacts between teleost CD4+ T cells and mononuclear phagocytes. Most importantly, we reveal the conserved subspecialization of teleost CD4+ T cells in vivo. We demonstrate that the ancient and specialized tissues of the gills contain a resident population of il-4/13b-expressing Th2-like cells, which do not coexpress il-4/13a Additionally, we identify a contrasting population of regulatory T cell-like cells resident in the zebrafish gut mucosa, in marked similarity to that found in the intestine of mammals. Finally, we show that, as in mammals, zebrafish CD4+ T cells will infiltrate melanoma tumors and obtain a phenotype consistent with a type 2 immune microenvironment. We anticipate that this unique resource will prove invaluable for future investigation of T cell function in biomedical research, the development of vaccination and health management in aquaculture, and for further research into the evolution of adaptive immunity.European Research Council (Grant IDs: ERC-2011-StG-282059 (PROMINENT), 677501 (ZF_Blood)), Biotechnology and Biological Sciences Research Council (Grant ID: BB/L007401/1), Dowager Countess Eleanor Peel Trust (Grant ID: TH-PRCL.FID2228), Medical Research Council, Department for International Development (Career Development Award Fellowship MR/J009156/1), Medical Research Foundation (Grant ID: R/140419), Cancer Research UK (Grant ID: C45041/A14953), Wellcome Trust and Medical Research Council to the Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute (core support grant)This is the final version of the article. It first appeared from The American Association of Immunologists via https://doi.org/10.4049/​jimmunol.160095

A Qualitative Analysis of Factors Influencing HPV Vaccine Uptake in Soweto, South Africa among Adolescents and Their Caregivers

Background: In South Africa, the prevalence of oncogenic Human Papillomavirus (HPV) may be as high as 64%, and cervical cancer is the leading cause of cancer-related death among women. The development of efficacious prophylactic vaccines has provided an opportunity for primary prevention. Given the importance of psycho-social forces in vaccine uptake, we sought to elucidate factors influencing HPV vaccination among a sample of low-income South African adolescents receiving the vaccine for the first time in Soweto. Methods: The HPV vaccine was introduced to adolescents in low-income townships throughout South Africa as part of a nationwide trial to understand adolescent involvement in future vaccine research targeting human immunodeficiency virus (HIV). We performed in-depth semi-structured interviews with purposively-sampled adolescents and their care providers to understand what forces shaped HPV vaccine uptake. Interviews were recorded, transcribed, translated, and examined using thematic analysis. Results: Of 224 adolescents recruited, 201 initiated the vaccine; 192 (95.5%) received a second immunization; and 164 (81.6%) completed three doses. In our qualitative study of 39 adolescent-caregiver dyads, we found that factors driving vaccine uptake reflected a socio-cultural backdrop of high HIV endemnicity, sexual violence, poverty, and an abundance of female-headed households. Adolescents exercised a high level of autonomy and often initiated decision-making. Healthcare providers and peers provided support and guidance that was absent at home. The impact of the HIV epidemic on decision-making was substantial, leading participants to mistakenly conflate HPV and HIV. Conclusions: In a setting of perceived rampant sexual violence and epidemic levels of HIV, adolescents and caregivers sought to decrease harm by seeking a vaccine targeting a sexually transmitted infection (STI). Despite careful consenting, there was confusion regarding the vaccine’s target. Future interventions promoting STI vaccines will need to provide substantial information for participants, particularly adolescents who may exercise a significant level of autonomy in decision-making

Embodied Knowledge: Writing Researchers’ Bodies Into Qualitative Health Research

After more than a decade of postpositivist health care research and an increase in narrative writing practices, social scientific, qualitative health research remains largely disembodied. The erasure of researchers’ bodies from conventional accounts of research obscures the complexities of knowledge production and yields deceptively tidy accounts of research. Qualitative health research could benefit significantly from embodied writing that explores the discursive relationship between the body and the self and the semantic challenges of writing the body by incorporating bodily details and experiences into research accounts. Researchers can represent their bodies by incorporating autoethnographic narratives, drawing on all of their senses, interrogating the connections between their bodily signifiers and research processes, and experimenting with the semantics of self and body. The author illustrates opportunities for embodiment with excerpts from an ethnography of a geriatric oncology team and explores implications of embodied writing for the practice of qualitative health research

Tumor Cell-Surface Binding of Immune Stimulating Polymeric Glyco-Adjuvant via Cysteine-Reactive Pyridyl Disulfide Promotes Antitumor Immunity

Immune stimulating agents like Toll-like receptor 7 (TLR7) agonists induce potent antitumor immunity but are limited in their therapeutic window due to off-target immune activation. Here, we developed a polymeric delivery platform that binds excess unpaired cysteines on tumor cell surfaces and debris to adjuvant tumor neoantigens as an in situ vaccine. The metabolic and enzymatic dysregulation in the tumor microenvironment produces these exofacial free thiols, which can undergo efficient disulfide exchange with thiol-reactive pyridyl disulfide moieties upon intratumoral injection. These functional monomers are incorporated into a copolymer with pendant mannose groups and TLR7 agonists to target both antigen and adjuvant to antigen presenting cells. When tethered in the tumor, the polymeric glyco-adjuvant induces a robust antitumor response and prolongs survival of tumor-bearing mice, including in checkpoint-resistant B16F10 melanoma. The construct additionally reduces systemic toxicity associated with clinically relevant small molecule TLR7 agonists

A combinatorial TIR1/AFB–Aux/IAA co-receptor system for differential sensing of auxin

The plant hormone auxin regulates virtually every aspect of plant growth and development. Auxin acts by binding the F-box protein transport inhibitor response 1 (TIR1) and promotes the degradation of the AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) transcriptional repressors. Here we show that efficient auxin binding requires assembly of an auxin co-receptor complex consisting of TIR1 and an Aux/IAA protein. Heterologous experiments in yeast and quantitative IAA binding assays using purified proteins showed that different combinations of TIR1 and Aux/IAA proteins form co-receptor complexes with a wide range of auxin-binding affinities. Auxin affinity seems to be largely determined by the Aux/IAA. As there are 6 TIR1/AUXIN SIGNALING F-BOX proteins (AFBs) and 29 Aux/IAA proteins in Arabidopsis thaliana, combinatorial interactions may result in many co-receptors with distinct auxin-sensing properties. We also demonstrate that the AFB5–Aux/IAA co-receptor selectively binds the auxinic herbicide picloram. This co-receptor system broadens the effective concentration range of the hormone and may contribute to the complexity of auxin response

Development of an Interactive Lifestyle Programme for Adolescents at Risk of Developing Type 2 Diabetes: PRE-STARt

Background: Type 2 diabetes (T2D) is increasing in young people. Reporting on the processes used when developing prevention interventions is needed. We present the development of a family-based interactive lifestyle intervention for adolescents with risk factors for T2D in the future. Method: A multidisciplinary team in the UK site led the intervention development process with sites in Portugal, Greece, Germany and Spain. Potential programme topics and underpinning theory were gathered from literature and stakeholders. A theoretical framework based on self-efficacy theory and the COM-B (capability, opportunity, motivation, behaviour) model was developed. Sessions and supporting resources were developed and refined via two iterative cycles of session and resource piloting, feedback, reflection and refinement. Decision on delivery and content were made by stakeholders (young people, teachers, parents, paediatricians) and all sites. Materials were translated to local languages. Site-specific adaptations to the language, content and supporting resources were made. Results: The “PRE-STARt” programme is eight 90-min interactive sessions with supporting curriculum and resources. Iterative development work provided valuable feedback on programme content and delivery. Conclusion: Reporting on the intervention development process, which includes stakeholder input, could yield a flexible approach for use in this emerging ‘at risk’ groups and their families

Unraveling the effects of the Ebola experience on behavior choices during COVID-19 in Liberia: a mixed-methods study across successive outbreaks

Background: The burden of the COVID-19 pandemic in terms of morbidity and mortality differentially affected populations. Between and within populations, behavior change was likewise heterogeneous. Factors influencing precautionary behavior adoption during COVID-19 have been associated with multidimensional aspects of risk perception; however, the influence of lived experiences during other recent outbreaks on behavior change during COVID-19 has been less studied. Methods: To consider how the direct disease experience (“near misses”) and behavior change during the 2014–2016 Ebola virus disease (EVD) outbreak may have impacted behavior change during the early waves of the COVID-19 outbreak in West Africa, we analyzed data from a mixed-methods study that included a phone-based survey and in-depth interviews among vaccinated Liberian adults. Logistic regression via generalized estimating equations with quasi-likelihood information criterion (QIC)-based model selection was conducted to evaluate the influence of the interaction between and individual effects of the outbreak (EVD and COVID-19) and the “near-miss” experience on adoption of individual precautionary behaviors. Thematic analysis of interview transcripts explored reasons for differential behavior adoption between the two outbreaks. Results: At the population level, being a “near miss” was not associated with significantly different behavior during COVID-19 versus Ebola; however, overall, people had lower odds of adopting precautionary behaviors during COVID-19 relative to during Ebola. Participants who report near miss experiences during Ebola were significantly more likely to report having a household member test positive for COVID-19 (p<0.001). Qualitatively, participants often reflected on themes around more proximal and personal experiences with Ebola than with COVID-19; they also commented on how EVD led to better preparedness at the systems level and within communities for how to behave during an outbreak, despite such awareness not necessarily translating into action during COVID-19. Conclusions: The results suggest that perceived proximity and intensity to disease threats in space and time affect behavioral decisions. For successive disease threats, comparisons of the present outbreak to past outbreaks compound those effects, regardless of whether individuals were directly impacted via a “near-miss” experience. Measures, such as risk communication and community engagement efforts, that gauge and reflect comparisons with previous outbreaks should be considered in response strategies to enhance the adoption of precautionary behavior