Vortices in polariton OPO superfluids

This chapter reviews the occurrence of quantised vortices in polariton fluids, primarily when polaritons are driven in the optical parametric oscillator (OPO) regime. We first review the OPO physics, together with both its analytical and numerical modelling, the latter being necessary for the description of finite size systems. Pattern formation is typical in systems driven away from equilibrium. Similarly, we find that uniform OPO solutions can be unstable to the spontaneous formation of quantised vortices. However, metastable vortices can only be injected externally into an otherwise stable symmetric state, and their persistence is due to the OPO superfluid properties. We discuss how the currents charactering an OPO play a crucial role in the occurrence and dynamics of both metastable and spontaneous vortices.Comment: 40 pages, 16 figure

Drosophila Argonaute-1 is critical for transcriptional cosuppression and heterochromatin formation

Argonaute-1 (Ago-1) plays a crucial role in gene regulation and genome stability via biogenesis of small non-coding RNAs. Two “Argonaute” family genes, piwi and Ago-2 in Drosophila are involved in multiple silencing mechanisms in the nucleus, transgene cosuppression, long-distant chromosome interaction, nuclear organization and heterochromatin formation. To investigate whether Ago-1 also plays a similar role, we have generated a series of Ago-1 mutations by excising P element, inserted in the Ago-1 promoter (Ago-1k08121). AGO-1 protein is distributed uniformly in the nucleus and cytosol in early embryos but accumulated predominantly in the cytoplasm during the gastrulation stage. Repeat induced silencing produced by the mini-white (mw) array and transcriptional cosuppression of non-homologous transgenes Adh-w/w-Adh was disrupted by Ago-1 mutation. These effects of Ago-1 are distict from its role in microRNA processing because Dicer-1, a critical enzyme for miRNA biogenesis, has no role on the above silencing. Reduction of AGO-1 protein dislodged the POLYCOMB, EZ (enhancer of zeste) and H3me3K27 binding at the cosuppressed Adh-w transgene insertion sites suggesting its role in Polycomb dependent cosuppression. An overall reduction of methylated histone H3me2K9 and H3me3K27 from the polytene nuclei precisely from the mw promoters was also found that leads to concomitant changes in the chromatin structure. These results suggest a prominent role of Ago-1 in chromatin organization and transgene silencing and demonstrate a critical link between transcriptional transgene cosuppression, heterochromatin formation and chromatin organization. We propose Drosophila Ago-1 as a multifunctional RNAi component that interconnects at least two unrelated events, chromatin organization in the nucleus and microRNA processing in the cytoplasm, which may be extended to the other systems

End-stage extension of the knee and its influence on tibial tuberosity-trochlear groove distance (TTTG) in asymptomatic volunteers

PURPOSE: Increased tibial tuberosity-trochlear groove distance (TTTG) is one potential correcting parameter in patients suffering from lateral patellar instability. It was hypothesized that end-stage extension of the knee might influence the TTTG distance on MR images. METHODS: Transverse T1-weighted MR images of the knee were acquired at full extension, 15° and 30° flexion of the knee in 30 asymptomatic volunteers. MRI parameters: slice thickness: 3 mm, matrix: 256 × 384, FOV: 150 × 150 mm. Two observers independently measured the TTTG at all positions. RESULTS: Mean TTTG for observer 1 was 15.1 ± 3.2 mm at full extension, 10.0 ± 3.5 mm at 15° flexion and 8.1 ± 3.4 mm at 30° flexion. Mean TTTG for observer 2: 14.8 ± 3.3 mm at full extension, 9.4 ± 3.0 mm at 15° flexion, 8.6 ± 3.4 mm at 30° flexion. Mean values were significantly different (p < 0.001) between full extension and 15° as well as 30° flexion for both observers. Mean values were significantly different (p < 0.001) between 15° and 30° for observer 1, but not for observer 2 (n.s.). Interobserver agreement was very good (intraclass correlation coefficient: 0.87-0.88; p < 0.001). CONCLUSIONS: The TTTG increases significantly at the end-stage extension of the knee. Therefore, the comparability of published TTTG values measured on radiographs, CT and MRI at various flexion/extension angles of the knee are limited. LEVEL OF EVIDENCE: Development of diagnostic criteria in a consecutive series of patients and a universally applied 'gold' standard, Level II

Inhibitors of MyD88-Dependent Proinflammatory Cytokine Production Identified Utilizing a Novel RNA Interference Screening Approach

The events required to initiate host defenses against invading pathogens involve complex signaling cascades comprised of numerous adaptor molecules, kinases, and transcriptional elements, ultimately leading to the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha). How these signaling cascades are regulated, and the proteins and regulatory elements participating are still poorly understood.We report here the development a completely random short-hairpin RNA (shRNA) library coupled with a novel forward genetic screening strategy to identify inhibitors of Toll-like receptor (TLR) dependent proinflammatory responses. We developed a murine macrophage reporter cell line stably transfected with a construct expressing diphtheria toxin-A (DT-A) under the control of the TNF-alpha-promoter. Stimulation of the reporter cell line with the TLR ligand lipopolysaccharide (LPS) resulted in DT-A induced cell death, which could be prevented by the addition of an shRNA targeting the TLR adaptor molecule MyD88. Utilizing this cell line, we screened a completely random lentiviral short hairpin RNA (shRNA) library for sequences that inhibited TLR-mediated TNF-alpha production. Recovery of shRNA sequences from surviving cells led to the identification of unique shRNA sequences that significantly inhibited TLR4-dependent TNF-alpha gene expression. Furthermore, these shRNA sequences specifically blocked TLR2 but not TLR3-dependent TNF-alpha production.Thus, we describe the generation of novel tools to facilitate large-scale forward genetic screens in mammalian cells and the identification of potent shRNA inhibitors of TLR2 and TLR4- dependent proinflammatory responses

Multimorbidity prevalence and patterns across socioeconomic determinants: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Studies on the prevalence of multimorbidity, defined as having two or more chronic conditions, have predominantly focused on the elderly. We estimated the prevalence and specific patterns of multimorbidity across different adult age groups. Furthermore, we examined the associations of multimorbidity with socio-demographic factors.</p> <p>Methods</p> <p>Using data from the Health Quality Council of Alberta (HQCA) 2010 Patient Experience Survey, the prevalence of self reported multimorbidity was assessed by telephone interview among a sample of 5010 adults (18 years and over) from the general population. Logistic regression analyses were performed to determine the association between a range of socio-demographic factors and multimorbidity.</p> <p>Results</p> <p>The overall age- and sex-standardized prevalence of multimorbidity was 19.0% in the surveyed general population. Of those with multimorbidity, 70.2% were aged less than 65 years. The most common pairing of chronic conditions was chronic pain and arthritis. Age, sex, income and family structure were independently associated with multimorbidity.</p> <p>Conclusions</p> <p>Multimorbidity is a common occurrence in the general adult population, and is not limited to the elderly. Future prevention programs and practice guidelines should take into account the common patterns of multimorbidity.</p

Chromatin structure characteristics of pre-miRNA genomic sequences

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are non-coding RNAs with important roles in regulating gene expression. Recent studies indicate that transcription and cleavage of miRNA are coupled, and that chromatin structure may influence miRNA transcription. However, little is known about the relationship between the chromatin structure and cleavage of pre-miRNA from pri-miRNA.</p> <p>Results</p> <p>By analysis of genome-wide nucleosome positioning data sets from human and <it>Caenorhabditis elegans </it>(<it>C. elegans</it>), we found an enrichment of positioned nucleosome on pre-miRNA genomic sequences, which is highly correlated with GC content within pre-miRNA. In addition, obvious enrichments of three histone modifications (H2BK5me1, H3K36me3 and H4K20me1) as well as RNA Polymerase II (RNAPII) were observed on pre-miRNA genomic sequences corresponding to the active-promoter miRNAs and expressed miRNAs.</p> <p>Conclusion</p> <p>Our results revealed the chromatin structure characteristics of pre-miRNA genomic sequences, and implied potential mechanisms that can recognize these characteristics, thus improving pre-miRNA cleavage.</p

Comparative Structural Analysis of Human DEAD-Box RNA Helicases

DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA remodeling is unknown. We present crystal structures of the isolated DEAD-domains of human DDX2A/eIF4A1, DDX2B/eIF4A2, DDX5, DDX10/DBP4, DDX18/myc-regulated DEAD-box protein, DDX20, DDX47, DDX52/ROK1, and DDX53/CAGE, and of the helicase domains of DDX25 and DDX41. Together with prior knowledge this enables a family-wide comparative structural analysis. We propose a general mechanism for opening of the RNA binding site. This analysis also provides insights into the diversity of DExD/H- proteins, with implications for understanding the functions of individual family members