Detection of changes in gene regulatory patterns, elicited by perturbations of the Hsp90 molecular chaperone complex, by visualizing multiple experiments with an animation

<p>Abstract</p> <p>Background</p> <p>To make sense out of gene expression profiles, such analyses must be pushed beyond the mere listing of affected genes. For example, if a group of genes persistently display similar changes in expression levels under particular experimental conditions, and the proteins encoded by these genes interact and function in the same cellular compartments, this could be taken as very strong indicators for co-regulated protein complexes. One of the key requirements is having appropriate tools to detect such regulatory patterns.</p> <p>Results</p> <p>We have analyzed the global adaptations in gene expression patterns in the budding yeast when the Hsp90 molecular chaperone complex is perturbed either pharmacologically or genetically. We integrated these results with publicly accessible expression, protein-protein interaction and intracellular localization data. But most importantly, all experimental conditions were simultaneously and dynamically visualized with an animation. This critically facilitated the detection of patterns of gene expression changes that suggested underlying regulatory networks that a standard analysis by pairwise comparison and clustering could not have revealed.</p> <p>Conclusions</p> <p>The results of the animation-assisted detection of changes in gene regulatory patterns make predictions about the potential roles of Hsp90 and its co-chaperone p23 in regulating whole sets of genes. The simultaneous dynamic visualization of microarray experiments, represented in networks built by integrating one's own experimental with publicly accessible data, represents a powerful discovery tool that allows the generation of new interpretations and hypotheses.</p

Singularities of the Magnon Boundstate S-Matrix

We study the conjectured exact S-matrix for the scattering of BPS magnon boundstates in the spin-chain description of planar N=4 SUSY Yang-Mills. The conjectured S-matrix exhibits both simple and double poles at complex momenta. Some of these poles lie parametrically close to the real axis in momentum space on the branch where particle energies are positive. We show that all such poles are precisely accounted for by physical processes involving one or more on-shell intermediate particles belonging to the known BPS spectrum.Comment: 32 pages, 9 figure

Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease

Keratin 9 was recently identified as an important component of a biomarker panel which demonstrated a high diagnostic accuracy (87%) for Alzheimer’s disease (AD). Understanding how a protein which is predominantly expressed in palmoplantar epidermis is implicated in AD may shed new light on the mechanisms underlying the disease. Here we use immunoassays to examine blood plasma expression patterns of Keratin 9 and its relationship to other AD-associated proteins. We correlate this with the use of an in silico analysis tool VisANT to elucidate possible pathways through which the involvement of Keratin 9 may take place. We identify possible links with Dickkopf-1, a negative regulator of the wnt pathway, and propose that the abnormal expression of Keratin 9 in AD blood and cerebrospinal fluid may be a result of blood brain barrier dysregulation and disruption of the ubiquitin proteasome system. Our findings suggest that dysregulated Keratin 9 expression is a consequence of AD pathology but, as it interacts with a broad range of proteins, it may have other, as yet uncharacterized, downstream effects which could contribute to AD onset and progression

Power efficiency of outer hair cell somatic electromotility

© 2009 Rabbitt et al. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS Computational Biology 5 (2009): e1000444, doi:10.1371/journal.pcbi.1000444.Cochlear outer hair cells (OHCs) are fast biological motors that serve to enhance the vibration of the organ of Corti and increase the sensitivity of the inner ear to sound. Exactly how OHCs produce useful mechanical power at auditory frequencies, given their intrinsic biophysical properties, has been a subject of considerable debate. To address this we formulated a mathematical model of the OHC based on first principles and analyzed the power conversion efficiency in the frequency domain. The model includes a mixture-composite constitutive model of the active lateral wall and spatially distributed electro-mechanical fields. The analysis predicts that: 1) the peak power efficiency is likely to be tuned to a specific frequency, dependent upon OHC length, and this tuning may contribute to the place principle and frequency selectivity in the cochlea; 2) the OHC power output can be detuned and attenuated by increasing the basal conductance of the cell, a parameter likely controlled by the brain via the efferent system; and 3) power output efficiency is limited by mechanical properties of the load, thus suggesting that impedance of the organ of Corti may be matched regionally to the OHC. The high power efficiency, tuning, and efferent control of outer hair cells are the direct result of biophysical properties of the cells, thus providing the physical basis for the remarkable sensitivity and selectivity of hearing.This work was supported by NIDCD R01 DC04928 (Rabbitt), NIDCD R01 DC00384 (Brownell) and NASA Ames GSRA56000135 (Breneman)

Interactions between canopy structure and herbaceous biomass along environmental gradients in moist forest and dry miombo woodland of Tanzania

We have limited understanding of how tropical canopy foliage varies along environmental gradients, and how this may in turn affect forest processes and functions. Here, we analyse the relationships between canopy leaf area index (LAI) and above ground herbaceous biomass (AGBH) along environmental gradients in a moist forest and miombo woodland in Tanzania. We recorded canopy structure and herbaceous biomass in 100 permanent vegetation plots (20 m × 40 m), stratified by elevation. We quantified tree species richness, evenness, Shannon diversity and predominant height as measures of structural variability, and disturbance (tree stumps), soil nutrients and elevation as indicators of environmental variability. Moist forest and miombo woodland differed substantially with respect to nearly all variables tested. Both structural and environmental variables were found to affect LAI and AGBH, the latter being additionally dependent on LAI in moist forest but not in miombo, where other factors are limiting. Combining structural and environmental predictors yielded the most powerful models. In moist forest, they explained 76% and 25% of deviance in LAI and AGBH, respectively. In miombo woodland, they explained 82% and 45% of deviance in LAI and AGBH. In moist forest, LAI increased non-linearly with predominant height and linearly with tree richness, and decreased with soil nitrogen except under high disturbance. Miombo woodland LAI increased linearly with stem density, soil phosphorous and nitrogen, and decreased linearly with tree species evenness. AGBH in moist forest decreased with LAI at lower elevations whilst increasing slightly at higher elevations. AGBH in miombo woodland increased linearly with soil nitrogen and soil pH. Overall, moist forest plots had denser canopies and lower AGBH compared with miombo plots. Further field studies are encouraged, to disentangle the direct influence of LAI on AGBH from complex interrelationships between stand structure, environmental gradients and disturbance in African forests and woodlands

Laboratory evaluation of methanolic extract of Atlantia monophylla (Family: Rutaceae) against immature stages of mosquitoes and non-target organisms

Methanolic extracts of the leaves of Atlantia monophylla (Rutaceae) were evaluated for mosquitocidal activity against immature stages of three mosquito species, Culex quinquefasciatus, Anopheles stephensi, and Aedes aegypti in the laboratory.Larvae of Cx. quinquefasciatus and pupae of An. stephensi were found more susceptible, with LC50 values of 0.14 mg/l and 0.05 mg/l, respectively. Insect growth regulating activity of this extract was more pronounced against Ae. aegypti, with EI50 value 0.002 mg/l. The extract was found safe to aquatic mosquito predators Gambusia affinis, Poecilia reticulata, and Diplonychus indicus, with the respective LC50 values of 23.4, 21.3, and 5.7 mg/l. The results indicate that the mosquitocidal effects of the extract of this plant were comparable to neem extract and certain synthetic chemical larvicides like fenthion, methoprene, etc

Oncoplastic Breast Surgery: A Global Perspective on Practice, Availability, and Training

Based on a BSI symposium, ISW 2007, Montreal, Canada.Oncoplastic surgery is the seamless joining of the extirpative and reconstructive aspects of breast surgery that is performed by a single surgeon. A symposium was held at ISW 2007 in Montreal with a prearranged aim to publish an article on the current and historical record of the developing specialty of oncoplastic breast surgery. The presenters and authors are well-known breast surgeons from Australia, Croatia, India, Sweden, and South Africa.Peter L. Malycha, Ian R. Gough, Marko Margaritoni, S. V. S. Deo, Kerstin Sandelin, Ines Buccimazza, Gaurav Agarwa