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12 microRNA expression profiling platforms are compared for their reproducibility, sensitivity, accuracy and specificity, and the strengths and weaknesses of each platform are discussed. MicroRNAs are important negative regulators of protein-coding gene expression and have been studied intensively over the past years. Several measurement platforms have been developed to determine relative miRNA abundance in biological samples using different technologies such as small RNA sequencing, reverse transcription–quantitative PCR (RT-qPCR) and (microarray) hybridization. In this study, we systematically compared 12 commercially available platforms for analysis of microRNA expression. We measured an identical set of 20 standardized positive and negative control samples, including human universal reference RNA, human brain RNA and titrations thereof, human serum samples and synthetic spikes from microRNA family members with varying homology. We developed robust quality metrics to objectively assess platform performance in terms of reproducibility, sensitivity, accuracy, specificity and concordance of differential expression. The results indicate that each method has its strengths and weaknesses, which help to guide informed selection of a quantitative microRNA gene expression platform for particular study goals.

ObjectivesTo investigate current patterns of work-related injuries sustained by foreign workers in Singapore and compare them to a decade ago. Secondary aim to analyse usefulness of selected trauma scores in this context.DesignRetrospective review of trauma registry of a single centre, from 1 April to 30 June 2015. Data compared with those from similar study performed at same centre in 2004.SettingEmergency department (ED) of 1500-bedded acute urban public hospital in Singapore.Participants1094 foreign workers with work-related injuries were included. Tourists, foreign students, non-work-related injuries, re-attendances for the same condition were excluded.ResultsMean age of participants was 32.8 years (SD 7.8), 90.0% were men. ED attendance was lowest on Sundays. Mechanism of injury: blunt (78.2%), penetrating (19.2%), burns (2.6%). Compared to 2004, 5% of foreign workers required admission (vs 19.6% in 2004, p≤0.0001), 8.0% underwent day or inpatient surgical procedures (vs 13.2% in 2004, p≤0.0001), 41.6% were referred to specialist outpatient clinics (vs 27.6% in 2004, p≤0.0001), 12.5% were referred to primary care follow-up (vs 29.9% in 2004, p≤0.0001). Mean duration of sick days was 4.3 (vs 5.1 in 2004, p≤0.0001). Of admitted patients, 49.1% had extremity injuries and 36.3% had head and neck injuries. Mean Injury Severity Score (ISS) for admitted patients was 3.64 (SD 3.1) (vs 4.3 (SD 5.5) in 2004, p=0.39). Mean Revised Trauma Score (RTS) for admitted patients was 7.74 (SD 0.39) (vs 7.8 (SD 0.2) in 2004, p=0.07). Of discharged patients, 48.9% had extremity injuries and 48.9% had external injuries. There was no death.ConclusionCompared to 2004, there were fewer major/fatal work-related injuries and an increased proportion of minor injuries. ISS and RTSs were of limited use in this setting.

The law on sedition in India has been employed as a tool of harassment to curb free speech. This has resulted in widespread demands to repeal the provisions regarding sedition as it is seen as an archaic law that was meant to serve the colonial interests. In this paper, the researcher explores the law on sedition under section 124A of the Indian Penal Code, 1860. The researcher seeks to propose an amendment to section 124A, by devising Austin’s Speech Acts Theory, Sorial’s exposition based on Austin’s theory and by accommodating the prevalent judicial interpretation into the existing provision.

Certain concepts concerning EPO/EPOR action modes have been challenged by in vivo studies: Bcl-x levels are elevated in maturing erythroblasts, but not in their progenitors; truncated EPOR alleles that lack a major p85/PI3K recruitment site nonetheless promote polycythemia; and Erk1 disruption unexpectedly bolsters erythropoiesis. To discover novel EPO/EPOR action routes, global transcriptome analyses presently are applied to interrogate EPO/EPOR effects on primary bone marrow-derived CFUe-like progenitors. Overall, 160 EPO/EPOR target transcripts were significantly modulated 2-to 21.8-fold. A unique set of EPO-regulated survival factors included Lyl1, Gas5, Pim3, Pim1, Bim, Trib3 and Serpina 3g. EPO/EPOR-modulated cell cycle mediators included Cdc25a, Btg3, Cyclin-d2, p27-kip1, Cyclin-g2 and CyclinB1-IP-1. EPO regulation of signal transduction factors was also interestingly complex. For example, not only Socs3 plus Socs2 but also Spred2, Spred1 and Eaf1 were EPO-induced as negative-feedback components. Socs2, plus five additional targets, further proved to comprise new EPOR/Jak2/Stat5 response genes (which are important for erythropoiesis during anemia). Among receptors, an atypical TNF-receptor Tnfr-sf13c was up-modulated >5-fold by EPO. Functionally, Tnfr-sf13c ligation proved to both promote proerythroblast survival, and substantially enhance erythroblast formation. The EPOR therefore engages a sophisticated set of transcriptome response circuits, with Tnfr-sf13c deployed as one novel positive regulator of proerythroblast formation.

Cerebellar dizziness is a common clinical sign in patients with cerebellar dysfunction with several multifaceted consequences in the life of an individual. The clinical diagnosis of this type of dizziness is delayed or overlooked as its frequency is underestimated. Inaccurate examination of the vestibular or ocular motor systems contributes to this effect. However, with expansion of use of ocular vestibular evoked myogenic potentials (oVEMPs) in the diagnosis of central disorders, makes it an important tool used in routine practice. The present study shows that oVEMP is majorly affected in various cerebellar disorders, making it a sensitive test to be used in suspected patients. Based on the vestibular evoked myogenic potential results and complete audiological profile in the patients with cerebellar demyelination and cerebellar atrophy, medical team was able to arrive at a diagnosis when the radiological findings were inconclusive. This study shows that oVEMPs are neurological responses, sensitive to cerebellar dysfunction.

Nat. Methods 11, 809–815 (2014); published online 29 June 2014; corrected after print 30 July 2014 In the version of this article initially published, the author Linda Wong was omitted from the author list. The error has been corrected in the HTML and PDF versions of the article.

PARP-14, a member of the poly ADP-ribose polymerase super family, promotes T helper cell 2 (Th2) differentiation by regulating interleukin-4 (IL-4) and STAT6-dependent transcription. Yet, whether PARP-14 globally impacts gene regulation has not been determined. In this report, using an RNA pol II ChIP-seq approach, we identify genes in Th2 cells that are regulated by PARP-14, and either dependent or independent of ADP-ribosyltransferase catalytic activity. Our data demonstrate that PARP-14 enhances the expression of Th2 genes as it represses the expression of Th1-associated genes. Among the relevant targets are Signal Transducer and Activator of Transcription genes required for polarizing Th1 and Th2 cells. To define a mechanism for PARP-14 function, we use an informatics approach to identify putative PARP-14 DNA binding sites. Two putative PARP-14 binding motifs are identified in multiple Th2 cytokine genes, and we demonstrate that PARP-14 interacts with each motif using in vitro binding assays. Taken together our results indicate that PARP-14 is an important factor for T helper cell differentiation and it binds to specific DNA sequences to mediate its function.