158,166 research outputs found

    Contemporary Issues in Global Criminal Justice

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    An in situ hybridization approach distinguishes <i>M-opsin</i> and <i>L-opsin</i> mRNA.

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    (A) Alignment of human M-opsin and L-opsin mRNA. Green bar = nucleotide difference. Horizontal pink and blue lines = location of in situ hybridization probes. (B) Alignment of portions of exon 5 from M- and L-opsin. In situ hybridization probes target mRNA sequences, indicated by blue (M-opsin) and pink (L-opsin) boxes. Green arrowheads indicate 8 nucleotide differences. Dots indicate nucleotide alignment between the opsins. (C–H) HEK293 cells probed for M-opsin mRNA (blue) and L-opsin mRNA (pink). Insets = schematic of transfected plasmid. Cells that did not express M-opsin mRNA or L-opsin mRNA were not quantified. (C) Quantification of transfected HEK293 cells expressing M-opsin mRNA only, L-opsin mRNA only, or M-opsin mRNA and L-opsin mRNA for the conditions in (D–H). (D–H) Brightfield images of cells with: (D) No plasmid transfected. (E) Transfection of a plasmid driving M-opsin. (F) Transfection of a plasmid driving L-opsin. (G) Transfection of either a plasmid driving M-opsin or a plasmid driving L-opsin independently and then the cells were mixed. (H) Transfection of both a plasmid driving M-opsin and a plasmid driving L-opsin. (I) Visualization of M-opsin mRNA, L-opsin mRNA, and M-/L-opsin protein (black) in HEK293 cells transfected with both a plasmid driving M-opsin and a plasmid driving L-opsin. M-opsin (blue) and L-opsin (pink). Blue arrow indicates a cell expressing M-opsin mRNA only. Pink arrows indicate cells expressing L-opsin mRNA only. Purple arrow indicates a cell expressing both M-opsin mRNA and L-opsin mRNA. Black arrow indicates an untransfected cell. Cells were identified based on nuclear Hoechst staining (S1A Fig). With this combined RNA in situ hybridization/immunohistochemistry approach, the mRNA signal was reduced, when compared to the mRNA signal observed when RNA in situ hybridization was conducted alone (Fig 1H). (J) Quantification of M-/L-opsin mRNA and M/L-opsin protein expression in transfected HEK293 cells (I). Original data sets are in S1 Data. (K) Quantification of M-/L-opsin mRNA and M/L-opsin protein expression in adult human retina (L). Original data sets are in S1 Data. (L) Visualization of M-opsin mRNA, L-opsin mRNA, and M-/L-opsin protein in cone cells in an adult human retina. M-opsin (blue) and L-opsin (pink). No cones co-expressed M-opsin mRNA and L-opsin mRNA. ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer. Cell boundaries were determined by identifying layers from a nuclear Hoechst stain (S1B Fig) and analyzing opsin protein immunohistochemistry signal from the ONL to the OPL.</p

    RA signaling induces <i>M-opsin</i> and inhibits <i>L-opsin</i> early in human retinal organoids.

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    (A–C) Expression of ALDH1A1, ALDH1A2, and ALDH1A3 in fetal human retinas by day of gestation and retinal region. CPM, log counts per million. Analyzed from [16]. Error bars for the 2 samples from fetal day 94 indicate SEM. Original data sets are in S3 Data. (A) Whole retina. (B) Central retina. (C) Periphery. (D) Black bars indicate temporal windows of 1.0 μm RA addition during retinal organoid culture. (E) Quantification of M and L cone ratios for RA treatments. For “No RA,” N = 3; for “RA to day 60,” N = 6; for “RA to day 130,” N = 3; and for “Late RA,” N = 5. One-way ANOVA with Dunnett’s multiple comparisons test: “No RA” L-opsin versus “RA to day 60” L-opsin, p L-opsin versus “RA to day 130” L-opsin p L-opsin versus “Late RA” L-opsin p = 0.9635. Error bars indicate SEM. * Indicates p p (F–I) M-opsin (blue) and L-opsin (pink) expression in organoids grown in different RA conditions (D), quantified in (E). White dotted outlines indicate M- or L-opsin-expressing cells. White lines indicate the edge of the organoid. (F) No RA. (G) RA to day 60. (H) RA to day 130. (I) Late RA.</p

    Expression of <i>NR2F2</i> and <i>NR2F2-AS1</i> during development.

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    The rs372754794 SNP at the NR2F2/NR2F2-AS1 locus lies in a putative regulatory region. (A) Expression of NR2F2 and NR2F2-AS1 in human fetal retinas, analyzed from [16]. Original data sets are in S3 Data. (B) Expression of NR2F2 and NR2F2-AS1 in human retinal organoids, analyzed from [15]. Original data sets are in S6 Data. (C) ReMap ChIP-seq database [52] shows that the rs372754794 SNP lies in an enhancer based on transcription factor binding. Each colored line indicates ChIP-seq binding data for a different transcriptional regulator. The ReMap density shows the density of the peaks overlap. (D) GeneHancer database [53] shows that the rs372754794 SNP neighbors a region predicted to physically interact and regulate NR2F2 and/or NR2F2-AS1. (PDF)</p

    Antibody-Conjugated Polymersomes with Encapsulated Indocyanine Green J‑Aggregates and High Near-Infrared Absorption for Molecular Photoacoustic Cancer Imaging

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    Imaging plays a critical role in all stages of cancer care from early detection to diagnosis, prognosis, and therapy monitoring. Recently, photoacoustic imaging (PAI) has started to emerge into the clinical realm due to its high sensitivity and ability to penetrate tissues up to several centimeters deep. Herein, we encapsulated indocyanine green J (ICGJ) aggregate, one of the only FDA-approved organic exogenous contrast agents that absorbs in the near-infrared range, at high loadings up to ∼40% w/w within biodegradable polymersomes (ICGJ-Ps) composed of poly(lactide-co-glycolide-b-polyethylene glycol) (PLGA-b-PEG). The small Ps hydrodynamic diameter of 80 nm is advantageous for in vivo applications, while directional conjugation with epidermal growth factor receptor (EGFR) targeting cetuximab antibodies renders molecular specificity. Even when exposed to serum, the ∼11 nm-thick membrane of the Ps prevents dissociation of the encapsulated ICGJ for at least 48 h with a high ratio of ICGJ to monomeric ICG absorbances (i.e., I895/I780 ratio) of approximately 5.0 that enables generation of a strong NIR photoacoustic (PA) signal. The PA signal of polymersome-labeled breast cancer cells is proportional to the level of cellular EGFR expression, indicating the feasibility of molecular PAI with antibody-conjugated ICGJ-Ps. Furthermore, the labeled cells were successfully detected with PAI in highly turbid tissue-mimicking phantoms up to a depth of 5 mm with the PA signal proportional to the amount of cells. These data show the potential of molecular PAI with ICGJ-Ps for clinical applications such as tumor margin detection, evaluation of lymph nodes for the presence of micrometastasis, and laparoscopic imaging procedures

    Designing, developing and evaluating integrated STEM activities for junior science

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    Science and mathematics are closely related in the physical world, yet as school subjects they can be quite separate, even where they share overlapping content. Science and mathematics integration has been recommended as a way to increase student conceptual understanding of, interest in, and motivation to learn both subject (Czerniak 2007). Moreover, STEM education (involving the purposeful integration of science, technology, engineering and mathematics) is receiving increasing emphasis in Ireland and elsewhere (Breiner et al. 2012). In this research the STEM focus has been into the design and development and evaluation of a model that will permit teachers to assist students to transfer their mathematical knowledge and skills into Junior Science. This resulted in a CISA (Critical Integrated Skills and Activities) Model for developing context-appropriate integrated materials. The model consists of a Syllabus Map of the overlapping content on the Junior Cycle science and mathematics curricula, a Teaching and Learning Sequence for overlapping science and mathematics content and skills, a CISA lesson template for developing integrated lessons, and three exemplar CISA lesson packs. The Syllabus Map and Sequence were evaluated in an earlier stage of the research and one outcome was the need to provide flexibility in the Model so that teachers could adapt it to their local situation and to their students’ learning needs. Instead of prescribing the science and mathematics topics that should be integrated, teachers can use the Map, Sequence, lesson template and exemplar lessons to identify critical skills that they may adapt to activities suitable for their science teaching. This paper reports on the design of the CISA exemplar lessons, and of the subsequent evaluation of both the lessons and of the overarching CISA Model, by subject matter experts and by teachers.</p

    Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma

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    Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10-6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10-8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10-6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control

    Examining the acceptability and feasibility of the Compassionate Mindful Resilience (CMR) programme in adult patients with chronic kidney disease: the COSMIC Study

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    People with chronic kidney disease often experience challenging physical and psychological symptoms and are at an increased risk of anxiety and depression. Mindfulness Interventions have the potential to improve mental wellbeing of people living with chronic illness.The COSMIC study explored the feasibility and acceptability of the four-week Compassionate Mindful Resilience (CMR) programme for patients living with stage 4 and 5 kidney disease and those who have received a kidney transplant. The study was supported by Kidney Care UK, and utilised a single-group multi-methods approach.The CMR programme can be considered acceptable and feasible for individuals living with kidney disease. The improvements in clinical outcome measures and qualitative analysis suggest that the mindfulness intervention has the potential to support the mental health and wellbeing of this patient population.<br/