80 research outputs found

    Darwin's "Abominable Mystery": the role of RNA interference in the evolution of flowering plants

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    Darwin was famously concerned that the sudden appearance and rapid diversification of flowering plants in the mid-Cretaceous could not have occurred by gradual change. Here, we review our attempts to resolve the relationships among the major seed plant groups, i.e., cycads, ginkgo, conifers, gnetophytes, and flowering plants, and to provide a pipeline in which these relationships can be used as a platform for identifying genes of functional importance in plant diversification. Using complete gene sets and unigenes from 16 plant species, genes with positive partitioned Bremer support at major nodes were used to identify overrepresented gene ontology (GO) terms. Posttranscriptional silencing via RNA interference (RNAi) was overrepresented at several major nodes, including between monocots and dicots during early angiosperm divergence. One of these genes, RNA-dependent RNA polymerase 6, is required for the biogenesis of trans-acting small interfering RNA (tasiRNA), confers heteroblasty and organ polarity, and restricts maternal specification of the germline. Processing of small RNA and transfer between neighboring cells underlies these roles and may have contributed to distinct mutant phenotypes in plants, and in particular in the early split of the monocots and eudicots

    Catalysis study for space shuttle vehicle thermal protection systems

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    Experimental results on the problem of reducing aerodynamic heating on space shuttle orbiter surfaces are presented. Data include: (1) development of a laboratory flow reactor technique for measuring gamma sub O and gamma sub N on candidate materials at surfaces, T sub w, in the nominal range 1000 to 2000, (2) measurements of gamma sub O and gamma sub N above 1000 K for both the glass coating of a reusable surface insulation material and the siliconized surface of a reinforced pyrolyzed plastic material, (3) measurement of the ablation behavior of the coated RPP material at T sub w is greater than or equal to 2150 K, (4) X-ray photoelectron spectral studies of the chemical constituents on these surfaces before and after dissociated gas exposure, (5) scanning electron micrograph examination of as-received and reacted specimens, and (6) development and exploitation of a method of predicting the aerodynamic heating consquences of these gamma sub O(T sub w) and gamma sub N(T sub w) measurements for critical locations on a radiation cooled orbiter vehicle

    Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies

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    Age Factors; Anal human papillomavirus infection; SexualityFactores de edad; Infección anal por virus del papiloma humano; SexualidadFactors d'edat; Infecció anal pel virus del papil·loma humà; SexualitatBackground Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. Methods We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. Findings The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15–18 years and 28·8% (141 of 490) among those age 23–24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25–34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15–18 and 13·9% (166 of 1192) among those age 23–24 years (ptrend=0·0076); the prevalence plateaued thereafter (ptrend=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36–1·73), HPV16-positive HSIL+ (1·66, 1·36–2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04–1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. Interpretation High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+.International Agency for Research on Cancer

    IL-23 signaling regulation of pro-inflammatory T-cell migration uncovered by phosphoproteomics

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    Interleukin 23 (IL-23) triggers pathogenic features in pro-inflammatory, IL-17-secreting T cells (Th17 and Tγδ17) that play a key role in the development of inflammatory diseases. However, the IL-23 signaling cascade remains largely undefined. Here, we used quantitative phosphoproteomics to characterize IL-23 signaling in primary murine Th17 cells. We quantified 6,888 phosphorylation sites in Th17 cells and found 168 phosphorylations regulated upon IL-23 stimulation. IL-23 increased the phosphorylation of the myosin regulatory light chain (RLC), an actomyosin contractibility marker, in Th17 and Tγδ17 cells. IL-23-induced RLC phosphorylation required Janus kinase 2 (JAK2) and Rho-associated protein kinase (ROCK) catalytic activity, and further study of the IL-23/ROCK connection revealed an unexpected role of IL-23 in the migration of Tγδ17 and Th17 cells through ROCK activation. In addition, pharmacological inhibition of ROCK reduced Tγδ17 recruitment to inflamed skin upon challenge with inflammatory agent Imiquimod. This work (i) provides new insights into phosphorylation networks that control Th17 cells, (ii) widely expands the current knowledge on IL-23 signaling, and (iii) contributes to the increasing list of immune cells subsets characterized by global phosphoproteomic approachesThis work was supported by grants from the Spanish Goverment (Ministry of Economy and Competitiveness). M.N.N, C.A-S, G.P-F, I.R.M and J.P are funded by grants SAF2013-43833-R, SAF2016-78180-R and RYC-2012-10252 to M.N.N. R.C-G and D.C are funded by SAF2014-55579-R to Prof. Sánchez-Madri

    When Worlds Collide: Boundary Management of Adolescent and Young Adult Childhood Cancer Survivors and Caregivers

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    Adolescent and young adult childhood cancer survivors experience health complications, late or long-term biomedical complications, as well as economic and psychosocial challenges that can have a lifelong impact on their quality-of-life. As childhood cancer survivors transition into adulthood, they must learn to balance their identity development with demands of everyday life and the near- and long-term consequences of their cancer experience, all of which have implications for the ways they use existing technologies and the design of novel technologies. In this study, we interviewed 24 childhood cancer survivors and six caregivers about their cancer survivorship experiences. The results of our analysis indicate that the challenges of transitioning to adulthood as a cancer survivor necessitate the development and management of multiple societal, relational, and personal boundaries, processes that social computing technologies can help or hinder. This paper contributes to the empirical understanding of adolescent and young adult cancer survivors’ social experiences. We further contribute sociotechnical design provocations for researchers, designers, and community members to support survivors

    Parents’ Perspectives on a Smartwatch Intervention for Children with ADHD: Rapid Deployment and Feasibility Evaluation of a Pilot Intervention to Support Distance Learning During COVID-19

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    Distance learning in response to the COVID-19 pandemic presented tremendous challenges for many families. Parents were expected to support children’s learning, often while also working from home. Students with Attention Deficit Hyperactivity Disorder (ADHD) are at particularly high risk for setbacks due to difficulties with organization and increased risk of not participating in scheduled online learning. This paper explores how smartwatch technology, including timing notifications, can support children with ADHD during distance learning due to COVID-19. We implemented a 6-week pilot study of a Digital Health Intervention (DHI) with ten families. The DHI included a smartwatch and a smartphone. Google calendars were synchronized across devices to guide children through daily schedules. After the sixth week, we conducted parent interviews to understand the use of smartwatches and the impact on children’s functioning, and we collected physiological data directly from the smartwatch. Our results demonstrated that children successfully adopted the use of the smartwatch, and parents believed the intervention was helpful, especially in supporting the development of organizational skills in their children. Overall, we illustrate how even simple DHIs, such as using smartwatches to promote daily organization and task completion, have the potential to support children and families, particularly during periods of distance learning. We include practical suggestions to help professionals teach children with ADHD to use smartwatches to improve organization and task completion, especially as it applies to supporting remote instruction

    Characteristic function of impulse responses in churches

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    The tool presented enables the sound behaviour of a room to be objectified on the basis of the representation of the characteristic function (CF) of said room.In this paper, we study characteristic functions, defined from the impulsive responses measured at different points in the room, that are obtained in churchesand cathedrals. These CFs show a variation that correlates with the distance from the point of measurement and the source. An analysis is carried out on the relationship between this variation with those acoustic parameters that depend on the distance to the source: C50, C80,and G. In addition, the differentiating features between these types of spaces are shown,therebyallowing the characteristic function to offer an overall assessment of the room, which in turnenables the classification of similar sound space

    Single cell analysis of kynurenine and System L amino acid transport in T cells

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    Acknowledgements We thank Cantrell group members for their critical discussion of the data, the Biological Resources unit, Sarah Thomson (for rLM work) and the Flow Cytometry facility (A. Whigham and R. Clarke) at the University of Dundee. This work was supported by the Wellcome Trust (Principal Research Fellowship to D.A.C. 097418/Z/11/Z and 205023/Z/16/Z, and Wellcome Trust Equipment Award 202950/Z/16/Z).Peer reviewedPublisher PD
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