A Variable Polyglutamine Repeat Affects Subcellular Localization and Regulatory Activity of a Populus ANGUSTIFOLIA Protein.

Polyglutamine (polyQ) stretches have been reported to occur in proteins across many organisms including animals, fungi and plants. Expansion of these repeats has attracted much attention due their associations with numerous human diseases including Huntington's and other neurological maladies. This suggests that the relative length of polyQ stretches is an important modulator of their function. Here, we report the identification of a Populus C-terminus binding protein (CtBP) ANGUSTIFOLIA (PtAN1) which contains a polyQ stretch whose functional relevance had not been established. Analysis of 917 resequenced Populus trichocarpa genotypes revealed three allelic variants at this locus encoding 11-, 13- and 15-glutamine residues. Transient expression assays using Populus leaf mesophyll protoplasts revealed that the 11Q variant exhibited strong nuclear localization whereas the 15Q variant was only found in the cytosol, with the 13Q variant exhibiting localization in both subcellular compartments. We assessed functional implications by evaluating expression changes of putative PtAN1 targets in response to overexpression of the three allelic variants and observed allele-specific differences in expression levels of putative targets. Our results provide evidence that variation in polyQ length modulates PtAN1 function by altering subcellular localization

Sequence Dependence of Transcription Factor-Mediated DNA Looping

DNA is subject to large deformations in a wide range of biological processes. Two key examples illustrate how such deformations influence the readout of the genetic information: the sequestering of eukaryotic genes by nucleosomes, and DNA looping in transcriptional regulation in both prokaryotes and eukaryotes. These kinds of regulatory problems are now becoming amenable to systematic quantitative dissection with a powerful dialogue between theory and experiment. Here we use a single-molecule experiment in conjunction with a statistical mechanical model to test quantitative predictions for the behavior of DNA looping at short length scales, and to determine how DNA sequence affects looping at these lengths. We calculate and measure how such looping depends upon four key biological parameters: the strength of the transcription factor binding sites, the concentration of the transcription factor, and the length and sequence of the DNA loop. Our studies lead to the surprising insight that sequences that are thought to be especially favorable for nucleosome formation because of high flexibility lead to no systematically detectable effect of sequence on looping, and begin to provide a picture of the distinctions between the short length scale mechanics of nucleosome formation and looping.Comment: Nucleic Acids Research (2012); Published version available at http://nar.oxfordjournals.org/cgi/content/abstract/gks473? ijkey=6m5pPVJgsmNmbof&keytype=re

The effect of sodium tetradecyl sulphate on coagulation and endothelium.

A thesis submitted to the Faculty of Medicine, University of the Witwatersrand, for the degree of Doctor of Philosophy in Medicine.Despite having been initially described more than fifty years ago, sclerotherapy of oesophageal varices has only relatively recently became regarded as one of the primary modalities both to control bleeding oesophageal varices and to prevent recurrent bleeding. Sclerotherapy, however, ts associated with numerous complications and its exact mechanism of action, particularly that pertaining to its effect on haemostasis, has to date been poorly documented. One of the problems of comparing the various trials has been the diversity of both the technique and the type and concentration of the sclerosants used. (Abbreviation abstract)Andrew Chakane 201

Redshift-independent Distances in the NASA/IPAC Extragalactic Database: Methodology, Content, and Use of NED-D

Estimates of galaxy distances based on indicators that are independent of cosmological redshift are fundamental to astrophysics. Researchers use them to establish the extragalactic distance scale, to underpin estimates of the Hubble constant, and to study peculiar velocities induced by gravitational attractions that perturb the motions of galaxies with respect to the "Hubble flow" of universal expansion. In 2006 the NASA/IPAC Extragalactic Database (NED) began making available a comprehensive compilation of redshift-independent extragalactic distance estimates. A decade later, this compendium of distances (NED-D) now contains more than 100,000 individual estimates based on primary and secondary indicators, available for more than 28,000 galaxies, and compiled from over 2000 references in the refereed astronomical literature. This paper describes the methodology, content, and use of NED-D, and addresses challenges to be overcome in compiling such distances. Currently, 75 different distance indicators are in use. We include a figure that facilitates comparison of the indicators with significant numbers of estimates in terms of the minimum, 25th percentile, median, 75th percentile, and maximum distances spanned. Brief descriptions of the indicators, including examples of their use in the database, are given in an appendix

Evaluation of a retrospective diary for peri-conceptual and mid-pregnancy drinking in Scotland:a cross-sectional study

Introduction: Heavy episodic (“binge”) drinking among women in Scotland is commonplace; prepregnancy drinking is associated with continued antenatal drinking. Evidence for effectiveness of standardized antenatal alcohol assessment is lacking. Alcohol-exposed pregnancies may be missed. We assessed peri-conceptual and mid-pregnancy consumption using a week-long retrospective diary and standard alcohol questionnaires, and evaluated the agreement between these instruments. Material and methods: Cross-sectional study in two Scottish health board areas involving 510 women attending mid-pregnancy ultrasound scan clinics. Face-to-face administration of alcohol retrospective diary and AUDIT or AUDIT-C assessed weekly and daily alcohol consumption levels and patterns. Depression-Anxiety-Stress Scale (DASS-21) assessed maternal wellbeing. A sub-sample (n=30) provided hair for alcohol metabolite analysis. Pearson's correlation coefficient investigated associations between questionnaires and alcohol metabolite data. Results: The response rate was 73.8%. The retrospective diary correlated moderately with AUDIT-C and AUDIT but elicited reports of significantly higher peri-conceptual consumption, (median unit consumption on “drinking days” 6.8; range 0.4–63.8). Additional “special occasions” consumption ranged from 1 to 125 units per week. Correlations between DASS-21 and retrospective diary were weak. Biomarker analysis identified three instances of hazardous peri-conceptual drinking. Conclusions: Women reported higher consumption levels when completing the retrospective diary, especially regarding peri-conceptual “binge” drinking. Routine clinical practice methods may not capture potentially harmful or irregular drinking patterns. Given the association between prepregnancy and antenatal drinking, and alcohol's known teratogenic effects, particularly in the first trimester, the retrospective diary may be a useful low-tech tool to gather information on alcohol intake patterns and levels

Combined-channel instantaneous frequency analysis for audio source separation based on comodulation

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2008.Includes bibliographical references (p. 295-303).Normal human listeners have a remarkable ability to focus on a single sound or speaker of interest and to block out competing sound sources. Individuals with hearing impairments, on the other hand, often experience great difficulty in noisy environments. The goal of our research is to develop novel signal processing methods inspired by neural auditory processing that can improve current speech separation systems. These could potentially be of use as assistive devices for the hearing impaired, and in many other communications applications. Our focus is the monaural case where spatial information is not available. Much perceptual evidence indicates that detecting common amplitude and frequency variation in acoustic signals plays an important role in the separation process. The physical mechanisms of sound generation in many sources cause common onsets/offsets and correlated increases/decreases in both amplitude and frequency among the spectral components of an individual source, which can potentially serve as a distinct signature. However, harnessing these common modulation patterns is difficult because when spectral components of competing sources overlap within the bandwidth of a single auditory filter, the modulation envelope of the resultant waveform resembles that of neither source. To overcome this, for the coherent, constant-frequency AM case, we derive a set of matrix equations which describes the mixture, and we prove that there exists a unique factorization under certain constraints. These constraints provide insight into the importance of onset cues in source separation. We develop algorithms for solving the system in those cases in which a unique solution exists. This work has direct bearing on the general theory of non-negative matrix factorization which has recently been applied to various problems in biology and learning. For the general, incoherent, AM and FM case, the situation is far more complex because constructive and destructive interference between sources causes amplitude fluctuations within channels that obscures the modulation patterns of individual sources.(cont.) Motivated by the importance of temporal processing in the auditory system, and specifically, the use of extrema, we explore novel methods for estimating instantaneous amplitude, frequency, and phase of mixtures of sinusoids by comparing the location of local maxima of waveforms from various frequency channels. By using an overlapping exponential filter bank model with properties resembling the cochlea, and combining information from multiple frequency bands, we are able to achieve extremely high frequency and time resolution. This allows us to isolate and track the behavior of individual spectral components which can be compared and grouped with others of like type. Our work includes both computational and analytic approaches to the general problem. Two suites of tests were performed. The first were comparative evaluations of three filter-bank-based algorithms on sets of harmonic-like signals with constant frequencies. One of these algorithms was selected for further performance tests on more complex waveforms, including AM and FM signals of various types, harmonic sets in noise, and actual recordings of male and female speakers, both individual and mixed. For the frequency-varying case, initial results of signal analysis with our methods appear to resolve individual sidebands of single harmonics on short time scales, and raise interesting conceptual questions on how to define, use and interpret the concept of instantaneous frequency. Based on our results, we revisit a number of questions in current auditory research, including the need for both rate and place coding, the asymmetrical shapes of auditory filters, and a possible explanation for the deficit of the hearing impaired in noise.by Barry David Jacobson.Ph.D

Visual Dependency and Dizziness after Vestibular Neuritis

Symptomatic recovery after acute vestibular neuritis (VN) is variable, with around 50% of patients reporting long term vestibular symptoms; hence, it is essential to identify factors related to poor clinical outcome. Here we investigated whether excessive reliance on visual input for spatial orientation (visual dependence) was associated with long term vestibular symptoms following acute VN. Twenty-eight patients with VN and 25 normal control subjects were included. Patients were enrolled at least 6 months after acute illness. Recovery status was not a criterion for study entry, allowing recruitment of patients with a full range of persistent symptoms. We measured visual dependence with a laptop-based Rod-and-Disk Test and severity of symptoms with the Dizziness Handicap Inventory (DHI). The third of patients showing the worst clinical outcomes (mean DHI score 36–80) had significantly greater visual dependence than normal subjects (6.35° error vs. 3.39° respectively, p = 0.03). Asymptomatic patients and those with minor residual symptoms did not differ from controls. Visual dependence was associated with high levels of persistent vestibular symptoms after acute VN. Over-reliance on visual information for spatial orientation is one characteristic of poorly recovered vestibular neuritis patients. The finding may be clinically useful given that visual dependence may be modified through rehabilitation desensitization techniques