miR-CATCH: microRNA capture affinity technology.

Several experimental methods exist to explore the microRNA (miRNA) regulome. These methods almost exclusively focus on multiple targets bound to a single, or perhaps a few miRNAs of interest. Here, we describe a microRNA capture affinity technology (miR-CATCH) which uses an affinity capture oligonucleotide to co-purify a single target messenger RNA (mRNA) together with all its endogenously bound miRNAs. This bench-top method is similar to RNA immunoprecipitation (RIP) and provides an experimental alternative to computational miRNA target prediction

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Socio-cognitive scaffolding with collaboration scripts: a meta-analysis

Scripts for computer-supported collaborative learning (CSCL) offer socio-cognitive scaffolding for learners to engage in collaborative activities that are considered beneficial for learning. Yet, CSCL scripts are often criticized for hampering naturally emerging collaboration. Research on the effectiveness of CSCL scripts has shown divergent results. This article reports a meta-analysis about the effects of CSCL scripts on domain-specific knowledge and collaboration skills. Results indicate that CSCL scripts as a kind of socio-cognitive scaffolding can enhance learning outcomes substantially. Learning with CSCL scripts leads to a small positive effect on domain-specific knowledge (d = 0.20) and a large positive effect on collaboration skills (d = 0.95) compared to unstructured CSCL. Further analyses reveal that CSCL scripts are particularly effective for domain-specific learning when they prompt transactive activities (i.e., activities in which a learner’s reasoning builds on the contribution of a learning partner) and when they are combined with additional content-specific scaffolding (worked examples, concept maps, etc.). Future research on CSCL scripts should include measures of learners’ internal scripts (i.e., prior collaboration skills) and the transactivity of the actual learning process

Longest property-preserved common factor

In this paper we introduce a new family of string processing problems. We are given two or more strings and we are asked to compute a factor common to all strings that preserves a specific property and has maximal length. Here we consider two fundamental string properties: square-free factors and periodic factors under two different settings, one per property. In the first setting, we are given a string x and we are asked to construct a data structure over x answering the following type of on-line queries: given string y, find a longest square-free factor common to x and y. In the second setting, we are given k strings and an integer 1 < k’ ≤ k and we are asked to find a longest periodic factor common to at least k’ strings. We present linear-time solutions for both settings. We anticipate that our paradigm can be extended to other string properties

Measurement of the Branching Fraction of J/psi --> pi+ pi- pi0

Using 58 million J/psi and 14 million psi' decays obtained by the BESII experiment, the branching fraction of J/psi --> pi+ pi- pi0 is determined. The result is (2.10+/-0.12)X10^{-2}, which is significantly higher than previous measurements.Comment: 9 pages, 8 figures, RevTex

First observation of psi(2S)-->K_S K_L

The decay psi(2S)-->K_S K_L is observed for the first time using psi(2S) data collected with the Beijing Spectrometer (BESII) at the Beijing Electron Positron Collider (BEPC); the branching ratio is determined to be B(psi(2S)-->K_S K_L) = (5.24\pm 0.47 \pm 0.48)\times 10^{-5}. Compared with J/psi-->K_S K_L, the psi(2S) branching ratio is enhanced relative to the prediction of the perturbative QCD ``12%'' rule. The result, together with the branching ratios of psi(2S) decays to other pseudoscalar meson pairs (\pi^+\pi^- and K^+K^-), is used to investigate the relative phase between the three-gluon and the one-photon annihilation amplitudes of psi(2S) decays.Comment: 5 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let

Plant expression, lyophilisation and storage of HBV medium and large surface antigens for a prototype oral vaccine formulation

Current immunisation programmes against hepatitis B virus (HBV) increasingly often involve novel tri-component vaccines containing—together with the small (S-HBsAg)—also medium and large surface antigens of HBV (M- and L-HBsAg). Plants producing all HBsAg proteins can be a source of components for a potential oral ‘triple’ anti-HBV vaccine. The objective of the presented research was to study the potential of M/L-HBsAg expression in leaf tissue and conditions of its processing for a prototype oral vaccine. Tobacco and lettuce carrying M- or L-HBsAg genes and resistant to the herbicide glufosinate were engineered and integration of the transgenes was verified by PCR and Southern hybridizations. M- and L-HBsAg expression was confirmed by Western blot and assayed by ELISA at the level of micrograms per g of fresh weight. The antigens displayed a common S domain and characteristic domains preS2 and preS1 and were assembled into virus-like particles (VLPs). Leaf tissues containing M- and L-HBsAg were lyophilised to produce a starting material of an orally administered vaccine formula. The antigens were distinctly sensitive to freeze-drying conditions and storage temperature, in the aspect of stability of S and preS domains and formation of multimeric particles. Efficiency of lyophilisation and storage depended also on the initial antigen content in plant tissue, yet M-HBsAg appeared to be approximately 1.5–2 times more stable than L-HBsAg. The results of the study provide indications concerning the preparation of two other constituents, next to S-HBsAg, for a plant-derived prototype oral tri-component vaccine against hepatitis B

An exploration of secondary students' mental states when learning about acids and bases

This study explored factors of students’ mental states, including emotion, intention, internal mental representation, and external mental representation, which can affect their learning performance. In evaluating students’ mental states during the science learning process and the relationship between mental states and learning achievement, valid, reliable, and scalable measures of students’ mental states and learning achievement are needed. This paper presents the development of the Mental State Conceptual Learning Inventory (MSCLI) to identify students’ mental states before and after learning about acids and bases. This instrument is time efficient and convenient and can be administered to large student samples so that teachers and researchers can gain profound insights into their students’ learning of acids and bases in science class. The results of this study indicate that students’ mental states are highly correlated with their achievement. As a whole, low-achieving students tended to have negative emotions and low intentions, were not good at internal visualization, and were unable to interpret graphics and draw pictures. In contrast, high-achieving students had positive emotions and intentions when learning life-related topics about acids and bases, and were good at internal visualization and drawing and interpreting graphics

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Estimation of progression of multi-state chronic disease using the Markov model and prevalence pool concept

<p>Abstract</p> <p>Background</p> <p>We propose a simple new method for estimating progression of a chronic disease with multi-state properties by unifying the prevalence pool concept with the Markov process model.</p> <p>Methods</p> <p>Estimation of progression rates in the multi-state model is performed using the E-M algorithm. This approach is applied to data on Type 2 diabetes screening.</p> <p>Results</p> <p>Good convergence of estimations is demonstrated. In contrast to previous Markov models, the major advantage of our proposed method is that integrating the prevalence pool equation (that the numbers entering the prevalence pool is equal to the number leaving it) into the likelihood function not only simplifies the likelihood function but makes estimation of parameters stable.</p> <p>Conclusion</p> <p>This approach may be useful in quantifying the progression of a variety of chronic diseases.</p