Positional dependence of transcriptional inhibition by DNA torsional stress in yeast chromosomes

How DNA helical tension is constrained along the linear chromosomes of eukaryotic cells is poorly understood. In this study, we induced the accumulation of DNA (+) helical tension in Saccharomyces cerevisiae cells and examined how DNA transcription was affected along yeast chromosomes. The results revealed that, whereas the overwinding of DNA produced a general impairment of transcription initiation, genes situated at <100 kb from the chromosomal ends gradually escaped from the transcription stall. This novel positional effect seemed to be a simple function of the gene distance to the telomere: It occurred evenly in all 32 chromosome extremities and was independent of the atypical structure and transcription activity of subtelomeric chromatin. These results suggest that DNA helical tension dissipates at chromosomal ends and, therefore, provides a functional indication that yeast chromosome extremities are topologically open. The gradual escape from the transcription stall along the chromosomal flanks also indicates that friction restrictions to DNA twist diffusion, rather than tight topological boundaries, might suffice to confine DNA helical tension along eukaryotic chromatin

MRI plaque imaging and its role in population-based studies

Noninvasive direct vessel wall (plaque) imaging may provide a good opportunity to study unique aspects of atherosclerotic lesions in different populations. The article published by Esposito et al. provides new insights into our understanding of diabetic atherosclerotic vascular disease by using direct plaque imaging techniques. The findings from this article call for attention to more in vivo imaging to understand the nature of high-risk atherosclerosis, especially in prospective studies in diabetic patients

Strongly magnetized pulsars: explosive events and evolution

Well before the radio discovery of pulsars offered the first observational confirmation for their existence (Hewish et al., 1968), it had been suggested that neutron stars might be endowed with very strong magnetic fields of $10^{10}$-$10^{14}$G (Hoyle et al., 1964; Pacini, 1967). It is because of their magnetic fields that these otherwise small ed inert, cooling dead stars emit radio pulses and shine in various part of the electromagnetic spectrum. But the presence of a strong magnetic field has more subtle and sometimes dramatic consequences: In the last decades of observations indeed, evidence mounted that it is likely the magnetic field that makes of an isolated neutron star what it is among the different observational manifestations in which they come. The contribution of the magnetic field to the energy budget of the neutron star can be comparable or even exceed the available kinetic energy. The most magnetised neutron stars in particular, the magnetars, exhibit an amazing assortment of explosive events, underlining the importance of their magnetic field in their lives. In this chapter we review the recent observational and theoretical achievements, which not only confirmed the importance of the magnetic field in the evolution of neutron stars, but also provide a promising unification scheme for the different observational manifestations in which they appear. We focus on the role of their magnetic field as an energy source behind their persistent emission, but also its critical role in explosive events.Comment: Review commissioned for publication in the White Book of "NewCompStar" European COST Action MP1304, 43 pages, 8 figure

Interfacility Helicopter Ambulance Transport of Neurosurgical Patients: Observations, Utilization, and Outcomes from a Quaternary Level Care Hospital

The clinical benefit of helicopter transport over ground transportation for interfacility transport is unproven. We sought to determine actual practice patterns, utilization, and outcomes of patients undergoing interfacility transport for neurosurgical conditions.We retrospectively examined all interfacility helicopter transfers to a single trauma center during 2008. We restricted our analysis to those transfers leading either to admission to the neurosurgical service or to formal consultation upon arrival. Major exclusion criteria included transport from the scene, death during transport, and transport to any area of the hospital other than the emergency department. The primary outcome was time interval to invasive intervention. Secondary outcomes were estimated ground transportation times from the referring hospital, admitting disposition, and discharge disposition. Of 526 candidate interfacility helicopter transfers to our emergency department in 2008, we identified 167 meeting study criteria. Seventy-five (45%) of these patients underwent neurosurgical intervention. The median time to neurosurgical intervention ranged from 1.0 to 117.8 hours, varying depending on the diagnosis. For 101 (60%) of the patients, estimated driving time from the referring institution was less than one hour. Four patients (2%) expired in the emergency department, and 34 patients (20%) were admitted to a non-ICU setting. Six patients were discharged home within 24 hours. For those admitted, in-hospital mortality was 28%.Many patients undergoing interfacility transfer for neurosurgical evaluation are inappropriately triaged to helicopter transport, as evidenced by actual times to intervention at the accepting institution and estimated ground transportation times from the referring institution. In a time when there is growing interest in health care cost containment, practitioners must exercise discretion in the selection of patients for air ambulance transport--particularly when it may not bear influence on clinical outcome. Neurosurgical evaluation via telemedicine may be one strategy for improving air transport triage

Traditional management of ear, nose and throat (ENT) diseases in Central Kenya

Diseases of ear, nose and throat (ENT) often have serious consequences including hearing impairment, and emotional strain that lower the quality of life of patients. In Kenya, upper respiratory infections are among the most common infections encountered in outpatient facilities. Some of these infections are becoming difficult to control because some of the causing microorganisms have acquired antibiotic resistance and hence the need to develop new drugs with higher efficacy. Ethnobotanical studies have now been found to be instrumental in improving chances of discovering plants with antimicrobial activity in new drug development. In Kenya the majority of local people are turning to herbal remedies for primary health care needs. In most cases the sources of these remedies are undocumented and the knowledge about them passed orally form generation to generation, hence under threat of disappearing with current rates of modernisation. This study explored the traditional remedies used in managing various ENT diseases in seven districts of the Central Province of Kenya. The most common ENT conditions managed using traditional therapies include: common cold, cough, tonsillitis, otitis-media, chest pains and asthma. The results indicate that 67 species belonging to 36 plant families were utilized in this region. These plants were of varying habits; herbs (37.3%), shrubs (34.4%), trees (25.4%) as well as some grasses and sedges (3%). The traditional preparations were found to be made mainly from leaves (49%), roots (20.5%) and barks (12.5%). For each of the ENT conditions multiple species are utilized mainly as individual preparations but occasionally as polyherbal concoctions. In the case of common cold for example, 30 different species are used. Plants reported in this survey are important candidates for antimicrobial tests against ENT disease causing micro-organisms, especially those with antibiotic resistance

Common variants in the regulative regions of GRIA1 and GRIA3 receptor genes are associated with migraine susceptibility

<p>Abstract</p> <p>Background</p> <p>Glutamate is the principal excitatory neurotransmitter in the central nervous system which acts by the activation of either ionotropic (AMPA, NMDA and kainate receptors) or G-protein coupled metabotropic receptors. Glutamate is widely accepted to play a major role in the path physiology of migraine as implicated by data from animal and human studies. Genes involved in synthesis, metabolism and regulation of both glutamate and its receptors could be, therefore, considered as potential candidates for causing/predisposing to migraine when mutated.</p> <p>Methods</p> <p>The association of polymorphic variants of <it>GRIA1</it>-<it>GRIA4 </it>genes which encode for the four subunits (GluR1-GluR4) of the alpha-amino-3- hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor for glutamate was tested in migraineurs with and without aura (MA and MO) and healthy controls.</p> <p>Results</p> <p>Two variants in the regulative regions of <it>GRIA1 </it>(rs2195450) and <it>GRIA3 </it>(rs3761555) genes resulted strongly associated with MA (P = 0.00002 and P = 0.0001, respectively), but not associated with MO, suggesting their role in cortical spreading depression. Whereas the rs548294 variant in <it>GRIA1 </it>gene showed association primarily with MO phenotype, supporting the hypothesis that MA and MO phenotypes could be genetically related. These variants modify binding sites for transcription factors altering the expression of <it>GRIA1 </it>and <it>GRIA3 </it>genes in different conditions.</p> <p>Conclusions</p> <p>This study represents the first genetic evidence of a link between glutamate receptors and migraine.</p

Thermotolerance and molecular chaperone function of the small heat shock protein HSP20 from hyperthermophilic archaeon, Sulfolobus solfataricus P2

Small heat shock proteins are ubiquitous in all three domains (Archaea, Bacteria and Eukarya) and possess molecular chaperone activity by binding to unfolded polypeptides and preventing aggregation of proteins in vitro. The functions of a small heat shock protein (S.so-HSP20) from the hyperthermophilic archaeon, Sulfolobus solfataricus P2 have not been described. In the present study, we used real-time polymerase chain reaction analysis to measure mRNA expression of S.so-HSP20 in S. solfataricus P2 and found that it was induced by temperatures that were substantially lower (60°C) or higher (80°C) than the optimal temperature for S. solfataricus P2 (75°C). The expression of S.so-HSP20 mRNA was also up-regulated by cold shock (4°C). Escherichia coli cells expressing S.so-HSP20 showed greater thermotolerance in response to temperature shock (50°C, 4°C). By assaying enzyme activities, S.so-HSP20 was found to promote the proper folding of thermo-denatured citrate synthase and insulin B chain. These results suggest that S.so-HSP20 promotes thermotolerance and engages in chaperone-like activity during the stress response

An Empirical Comparison of Information-Theoretic Criteria in Estimating the Number of Independent Components of fMRI Data

BACKGROUND: Independent Component Analysis (ICA) has been widely applied to the analysis of fMRI data. Accurate estimation of the number of independent components of fMRI data is critical to reduce over/under fitting. Although various methods based on Information Theoretic Criteria (ITC) have been used to estimate the intrinsic dimension of fMRI data, the relative performance of different ITC in the context of the ICA model hasn't been fully investigated, especially considering the properties of fMRI data. The present study explores and evaluates the performance of various ITC for the fMRI data with varied white noise levels, colored noise levels, temporal data sizes and spatial smoothness degrees. METHODOLOGY: Both simulated data and real fMRI data with varied Gaussian white noise levels, first-order auto-regressive (AR(1)) noise levels, temporal data sizes and spatial smoothness degrees were carried out to deeply explore and evaluate the performance of different traditional ITC. PRINCIPAL FINDINGS: Results indicate that the performance of ITCs depends on the noise level, temporal data size and spatial smoothness of fMRI data. 1) High white noise levels may lead to underestimation of all criteria and MDL/BIC has the severest underestimation at the higher Gaussian white noise level. 2) Colored noise may result in overestimation that can be intensified by the increase of AR(1) coefficient rather than the SD of AR(1) noise and MDL/BIC shows the least overestimation. 3) Larger temporal data size will be better for estimation for the model of white noise but tends to cause severer overestimation for the model of AR(1) noise. 4) Spatial smoothing will result in overestimation in both noise models. CONCLUSIONS: 1) None of ITC is perfect for all fMRI data due to its complicated noise structure. 2) If there is only white noise in data, AIC is preferred when the noise level is high and otherwise, Laplace approximation is a better choice. 3) When colored noise exists in data, MDL/BIC outperforms the other criteria