A mutate-and-map protocol for inferring base pairs in structured RNA

Chemical mapping is a widespread technique for structural analysis of nucleic acids in which a molecule's reactivity to different probes is quantified at single-nucleotide resolution and used to constrain structural modeling. This experimental framework has been extensively revisited in the past decade with new strategies for high-throughput read-outs, chemical modification, and rapid data analysis. Recently, we have coupled the technique to high-throughput mutagenesis. Point mutations of a base-paired nucleotide can lead to exposure of not only that nucleotide but also its interaction partner. Carrying out the mutation and mapping for the entire system gives an experimental approximation of the molecules contact map. Here, we give our in-house protocol for this mutate-and-map strategy, based on 96-well capillary electrophoresis, and we provide practical tips on interpreting the data to infer nucleic acid structure.Comment: 22 pages, 5 figure

RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

Giant Electroresistance in Edge Metal-Insulator-Metal Tunnel Junctions Induced by Ferroelectric Fringe Fields

An enormous amount of research activities has been devoted to developing new types of non-volatile memory devices as the potential replacements of current flash memory devices. Theoretical device modeling was performed to demonstrate that a huge change of tunnel resistance in an Edge Metal-Insulator-Metal (EMIM) junction of metal crossbar structure can be induced by the modulation of electric fringe field, associated with the polarization reversal of an underlying ferroelectric layer. It is demonstrated that single three-terminal EMIM/Ferroelectric structure could form an active memory cell without any additional selection devices. This new structure can open up a way of fabricating all-thin-film-based, high-density, high-speed, and low-power non-volatile memory devices that are stackable to realize 3D memory architectureope

From research to practice: Lay adherence counsellors' fidelity to an evidence-based intervention for promoting adherence to antiretroviral treatment in the Western Cape, South Africa

In the Western Cape, lay counsellors are tasked with supporting antiretroviral (ARV) adherence in public healthcare clinics. Thirty-nine counsellors in 21 Cape Town clinics were trained in Options for Health (Options), an evidence-based intervention based on motivational interviewing (MI). We evaluated counsellors’ ability to deliver Options for addressing poor adherence following 5 days training. Audio-recordings of counselling sessions collected following training were transcribed and translated into English. Thirty-five transcripts of sessions conducted by 35 counsellors were analysed for fidelity to the Options protocol, and using the Motivational Interviewing Treatment and Integrity (MITI) code. Counsellors struggled with some of the strategies associated with MI, such as assessing readiness-to-change and facilitating change talk. Overall, counsellors failed to achieve proficiency in the approach of MI according to the MITI. Counsellors were able to negotiate realistic plans for addressing patients’ barriers to adherence. Further efforts aimed at strengthening the ARV adherence counselling programme are needed.Department of HE and Training approved lis

Right and left prefrontal transcranial magnetic stimulation at 1 Hz does not affect mood in healthy volunteers

Background: Prefrontal repetitive transcranial magnetic stimulation (rTMS) has been used to induce side-specific mood changes in volunteers and patients. To clarify inconsistencies between reports that used different stimulation frequencies, we conducted a controlled study with a low (1 Hz) frequency, comparing left with right-sided stimulation. Methods: Nineteen healthy volunteers received randomised left or right prefrontal rTMS at a frequency of 1 Hz and 100% of motor threshold in two sessions two weeks apart. Results: There were significant improvements with TMS for performance in the digit symbol substitution and verbal fluency tests, but no change of mood on a number of measures. There was also a reduction of pulse rate after TMS. The only side-specific TMS-effect was on mean arterial pressure, which decreased pressure after left, but not after right prefrontal TMS. Conclusions: Apart from the unexpected and so far unreplicated effect on mean arterial pressure, there were no side-specific effects on mood in volunteers. It is unlikely that a simple laterality model of mood together with the assumed activating effect of higher and 'quenching' effect of lower stimulation frequency can account for the effects of TMS on mood

The effects of juvenile stress on anxiety, cognitive bias and decision making in adulthood:a rat model

Stress experienced in childhood is associated with an increased risk of developing psychiatric disorders in adulthood. These disorders are particularly characterized by disturbances to emotional and cognitive processes, which are not currently fully modeled in animals. Assays of cognitive bias have recently been used with animals to give an indication of their emotional/cognitive state. We used a cognitive bias test, alongside a traditional measure of anxiety (elevated plus maze), to investigate the effects of juvenile stress (JS) on adulthood behaviour using a rodent model. During the cognitive bias test, animals were trained to discriminate between two reward bowls based on a stimulus (rough/smooth sandpaper) encountered before they reached the bowls. One stimulus (e.g. rough) was associated with a lower value reward than the other (e.g. smooth). Once rats were trained, their cognitive bias was explored through the presentation of an ambiguous stimulus (intermediate grade sandpaper): a rat was classed as optimistic if it chose the bowl ordinarily associated with the high value reward. JS animals were lighter than controls, exhibited increased anxiety-like behaviour in the elevated plus maze and were more optimistic in the cognitive bias test. This increased optimism may represent an optimal foraging strategy for these underweight animals. JS animals were also faster than controls to make a decision when presented with an ambiguous stimulus, suggesting altered decision making. These results demonstrate that stress in the juvenile phase can increase anxiety-like behaviour and alter cognitive bias and decision making in adulthood in a rat model

The Herschel-SPIRE Legacy Survey (HSLS): the scientific goals of a shallow and wide submillimeter imaging survey with SPIRE

A large sub-mm survey with Herschel will enable many exciting science opportunities, especially in an era of wide-field optical and radio surveys and high resolution cosmic microwave background experiments. The Herschel-SPIRE Legacy Survey (HSLS), will lead to imaging data over 4000 sq. degrees at 250, 350, and 500 micron. Major Goals of HSLS are: (a) produce a catalog of 2.5 to 3 million galaxies down to 26, 27 and 33 mJy (50% completeness; 5 sigma confusion noise) at 250, 350 and 500 micron, respectively, in the southern hemisphere (3000 sq. degrees) and in an equatorial strip (1000 sq. degrees), areas which have extensive multi-wavelength coverage and are easily accessible from ALMA. Two thirds of the of the sources are expected to be at z > 1, one third at z > 2 and about a 1000 at z > 5. (b) Remove point source confusion in secondary anisotropy studies with Planck and ground-based CMB data. (c) Find at least 1200 strongly lensed bright sub-mm sources leading to a 2% test of general relativity. (d) Identify 200 proto-cluster regions at z of 2 and perform an unbiased study of the environmental dependence of star formation. (e) Perform an unbiased survey for star formation and dust at high Galactic latitude and make a census of debris disks and dust around AGB stars and white dwarfs

Exploring new physics frontiers through numerical relativity

The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology

Combining sequence-based prediction methods and circular dichroism and infrared spectroscopic data to improve protein secondary structure determinations

<p>Abstract</p> <p>Background</p> <p>A number of sequence-based methods exist for protein secondary structure prediction. Protein secondary structures can also be determined experimentally from circular dichroism, and infrared spectroscopic data using empirical analysis methods. It has been proposed that comparable accuracy can be obtained from sequence-based predictions as from these biophysical measurements. Here we have examined the secondary structure determination accuracies of sequence prediction methods with the empirically determined values from the spectroscopic data on datasets of proteins for which both crystal structures and spectroscopic data are available.</p> <p>Results</p> <p>In this study we show that the sequence prediction methods have accuracies nearly comparable to those of spectroscopic methods. However, we also demonstrate that combining the spectroscopic and sequences techniques produces significant overall improvements in secondary structure determinations. In addition, combining the extra information content available from synchrotron radiation circular dichroism data with sequence methods also shows improvements.</p> <p>Conclusion</p> <p>Combining sequence prediction with experimentally determined spectroscopic methods for protein secondary structure content significantly enhances the accuracy of the overall results obtained.</p

Changes to the law on consent in South Africa: implications for school-based adolescent sexual and reproductive health research

BACKGROUND:The National Health Act, No 61, 2003 in South Africa is the first effort made by the government to protect health-related research participants under law. Implemented on March 1, 2012, the law mandates active consent from a parent or legal guardian for all research conducted with research participants under the age of 18 years. This paper focuses on the Act's implications for school-based adolescent sexual and reproductive health research.DISCUSSION:Although well intentioned, the added legal protections in the National Health Act may have the unintended consequence of reducing participation rates in school-based adolescent sexual and reproductive health research, thereby excluding the most at-risk students. The Act may also compromise adolescents' right to dignity and privacy, especially considering the personal nature of research on sex and sexuality. Devolved, discretionary decision-making, which empowers local human research ethics committees to permit a wider range of protective measures, including passive consent, independent adolescent consent or community consultation ought to be considered. The continued and direct involvement of young people in their sexual and reproductive health and well-being is an important principle to uphold.SUMMARY:This paper calls for a re-examination of section 71's ethical guidelines relating to informed consent in the National Health Act, No 61, 2003 in South Africa in order to better serve the interests of South African adolescents in sexual and reproductive health research