InCoB2013 introduces Systems Biology as a major conference theme

10.1186/1752-0509-7-S3-S1BMC Systems Biology7SUPPL.3

Hard and soft news: A review of concepts, operationalizations and key findings

Over 30 years, a large body of research on what is often called ‘hard’ and ‘soft news’ has accumulated in communication studies. However, there is no consensus about what hard and soft news exactly is, or how it should be defined or measured. Moreover, the concept has not been clearly differentiated from or systematically related to concepts addressing very similar phenomena – tabloidization and ‘infotainment’. Consequently, the results of various studies are hard to compare and different scientific discourses on related issues remain unconnected. Against this backdrop, this article offers a conceptual analysis of the concept based on studies in English and other languages. We identify key dimensions of the concept and make suggestions for a standardized definition and multi-dimensional measurement of harder and softer news. In doing so, we propose to distinguish thematic, focus and style features as basic dimensions that – in their combination – make up harder and softer types of news

Faster Sensitivity Loss around Dense Scotomas than for Overall Macular Sensitivity in Stargardt Disease: ProgStar Report No. 14

Purpose: Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS. Design: Multicenter, international, prospective cohort study: ProgStar Study. Methods: Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS). Results: Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β = −1.33; P < .001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β = .09; P = .461). Conclusions: In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts

Shaping public opinion about regional integration: the rhetoric of justification and party cues

The article investigates how justifications used by politicians to explain their positions on policies of regional integration shape public opinion about these policies. I argue that support for a policy position increases when politicians tailor their justifications to the expectations of their audience; and I suggest that this happens even when party cues offer a less effortful way of forming opinions. I test my theoretical expectations in laboratory experiments with diverse samples, which manipulate party cues and justifications for a policy of European integration. I find that citizens use justifications and cues to form opinions. The relative importance of the two factors depends on individual dispositions and political context. In a non-competitive context (study 1), politically invested citizens use cues, while uninvested citizens use justifications. In a competitive context (study 2), the opinions of politically invested citizens are shaped by both factors, while the opinions of uninvested citizens become erratic

MAGE I Transcription Factors Regulate KAP1 and KRAB Domain Zinc Finger Transcription Factor Mediated Gene Repression

Class I MAGE proteins (MAGE I) are normally expressed only in developing germ cells but are aberrantly expressed in many cancers. They have been shown to promote tumor survival, aggressive growth, and chemoresistance but the underlying mechanisms and MAGE I functions have not been fully elucidated. KRAB domain zinc finger transcription factors (KZNFs) are the largest group of vertebrate transcription factors and regulate neoplastic transformation, tumor suppression, cellular proliferation, and apoptosis. KZNFs bind the KAP1 protein and direct KAP1 to specific DNA sequences where it suppresses gene expression by inducing localized heterochromatin characterized by histone 3 lysine 9 trimethylation (H3me3K9). Discovery that MAGE I proteins also bind to KAP1 prompted us to investigate whether MAGE I can affect KZNF and KAP1 mediated gene regulation. We found that expression of MAGE I proteins, MAGE-A3 or MAGE-C2, relieved repression of a reporter gene by ZNF382, a KZNF with tumor suppressor activity. ChIP of MAGE I (-) HEK293T cells showed KAP1 and H3me3K9 are normally bound to the ID1 gene, a target of ZNF382, but that binding is greatly reduced in the presence of MAGE I proteins. MAGE I expression relieved KAP1 mediated ID1 repression, causing increased expression of ID1 mRNA and ID1 chromatin relaxation characterized by loss of H3me3K9. MAGE I binding to KAP1 also induced ZNF382 poly-ubiquitination and degradation, consistent with loss of ZNF382 leading to decreased KAP1 binding to ID1. In contrast, MAGE I expression caused increased KAP1 binding to Ki67, another KAP1 target gene, with increased H3me3K9 and decreased Ki67 mRNA expression. Since KZNFs are required to direct KAP1 to specific genes, these results show that MAGE I proteins can differentially regulate members of the KZNF family and KAP1 mediated gene repression

Mice and Men: Their Promoter Properties

Using the two largest collections of Mus musculus and Homo sapiens transcription start sites (TSSs) determined based on CAGE tags, ditags, full-length cDNAs, and other transcript data, we describe the compositional landscape surrounding TSSs with the aim of gaining better insight into the properties of mammalian promoters. We classified TSSs into four types based on compositional properties of regions immediately surrounding them. These properties highlighted distinctive features in the extended core promoters that helped us delineate boundaries of the transcription initiation domain space for both species. The TSS types were analyzed for associations with initiating dinucleotides, CpG islands, TATA boxes, and an extensive collection of statistically significant cis-elements in mouse and human. We found that different TSS types show preferences for different sets of initiating dinucleotides and cis-elements. Through Gene Ontology and eVOC categories and tissue expression libraries we linked TSS characteristics to expression. Moreover, we show a link of TSS characteristics to very specific genomic organization in an example of immune-response-related genes (GO:0006955). Our results shed light on the global properties of the two transcriptomes not revealed before and therefore provide the framework for better understanding of the transcriptional mechanisms in the two species, as well as a framework for development of new and more efficient promoter- and gene-finding tools

The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1)

BACKGROUND/AIMS: To describe the design and baseline characteristics of patients enrolled in the multicenter, prospective natural history study of Stargardt disease type 4. METHODS: Fifteen eligible patients aged 6 years and older at baseline, harboring disease-causing variants in the PROM1 gene, and with specified ocular lesions were enrolled. They were examined at baseline using a standard protocol, with 6 monthly follow-up visits for a 2-year period including best-corrected ETDRS visual acuity, spectral-domain optical coherence tomography, fundus autofluorescence (FAF), mesopic and scotopic microperimetry (MP). Areas of definitely decreased FAF (DDAF) and questionably decreased FAF were outlined and quantified on FAF images. RESULTS: Amongst the 15 patients (29 eyes) that were enrolled at 5 centers in the USA and Europe, 10 eyes (34.5%) had areas of DDAF with an average lesion area of 3.2 ± 3.5 mm2 (range 0.36-10.39 mm2) at baseline. The mean retinal sensitivity of the posterior pole derived from mesopic MP was 8.8 ± 5.8 dB. CONCLUSIONS: Data on disease progression in PROM1-related retinopathy from this study will contribute to the characterization of the natural history of disease and the exploration of the utility of several modalities to track progression and therefore to potentially be used in future interventional clinical trials

Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) Study: Design and Baseline Characteristics (Report No. 1)

PURPOSE: To describe the study design and characteristics at first visit of participants in the longitudinal Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) study. METHODS: Scotopic microperimetry (sMP) was performed in one designated study eye in a subset of participants with molecularly proven ABCA4-associated Stargardt disease (STGD1) enrolled in a multicenter natural history study (ProgStar). Study visits were every 6 months over a period ranging from 6 to 24 months, and also included fundus autofluorescence (FAF). RESULTS: SMART enrolled 118 participants (118 eyes). At the first visit of SMART, the mean sensitivity in mesopic microperimetry was 11.48 (±5.05; range 0.00-19.88) dB and in sMP 11.25 (±5.26; 0-19.25) dB. For FAF, all eyes had a lesion of decreased autofluorescence (mean lesion size 3.62 [±3.48; 0.10-21.46] mm2), and a total of 76 eyes (65.5%) had a lesion of definitely decreased autofluorescence with a mean lesion size of 3.46 (±3.60; 0.21-21.46) mm2. CONCLUSIONS: Rod function is impaired in STGD1 and can be assessed by sMP. Testing rod function may serve as a potential outcome measure for future clinical treatment trials. This is evaluated in the SMART study

Progression of Visual Acuity and Fundus Autofluorescence in Recent-Onset Stargardt Disease: ProgStar Study Report #4

PURPOSE: To investigate the impact of areas of decreased fundus autofluorescence (AF) on visual acuity (VA) in molecularly confirmed Stargardt disease (STGD1) with recent symptom onset, and investigate the association between these structural and functional measures over time. DESIGN: Prospective, international, multicenter observational study of Stargardt disease. PARTICIPANTS: Sixty-four patients (124 eyes) aged ≥6 years at first study visit, with onset of symptoms ≤2 years before the first visit. METHODS: AF images were graded for the presence and areas of definitely decreased AF (DDAF), questionably decreased AF (QDAF), and total decreased AF (DAF). First-visit images were also graded for presence of these lesions and for the presence of increased AF in the fovea. VA was measured as best-corrected or presenting acuity and converted to logarithm of the minimum angle of resolution (logMAR). Cross-sectional associations were measured using linear models with generalized estimating equations. Longitudinal linear mixed effects models were used to estimate yearly progression rates of VA and AF lesion areas. Main outcome measures were rate of change in VA and rate of change of decreased AF area. RESULTS: In cross-sectional analyses at baseline, VA was not significantly associated with area of DDAF (P = 0.86), or QDAF (P = 0.11), but was significantly associated with lesion involvement in the fovea (P < 0.001). The VA change rate was 0.054 logMAR/year (P < 0.001) and depended on initial level of VA (faster loss was observed in those with 20/30 to 20/70 at first visit, 0.114 logMAR/year, 95% confidence interval = 0.090-0.138). Growth of DDAF depended on the size of the lesion at first visit, with larger DDAF having faster growth. Regression of QDAF area over time was associated with significantly larger growth in DDAF (P < 0.001), suggesting that QDAF areas may lose further AF signal over time. The increase in area of DDAF, or total decreased AF, was not associated with change in VA (P = 0.62, and P = 0.27, respectively). CONCLUSIONS: In recent-onset STGD1, the rate of VA loss was not significantly associated with the rate of increase in area of DDAF, QDAF, or DAF. For DDAF, the growth rate depended on the initial size of the lesion, a finding that will be helpful in stratifying these patients for intervention