Linear Discriminant Functions in Connection with the micro-RNA Diagnosis of Colon Cancer

Early detection (localized stage) of colon cancer is associated with a five-year survival rate of 91%. Only 39% of colon cancers, however, are diagnosed at that early stage. Early and accurate diagnosis, therefore, constitutes a critical need and a decisive factor in the clinical treatment of colon cancer and its success. In this study, using supervised linear discriminant analysis, we have developed three diagnostic biomarker models that—based on global micro-RNA expression analysis of colonic tissue collected during surgery—can discriminate with a perfect accuracy between subjects with colon cancer (stages II–IV) and normal healthy subjects. We developed our three diagnostic biomarker models with 57 subjects [40 with colon cancer (stages II–IV) and 17 normal], and we validated them with 39 unknown (new and different) subjects [28 with colon cancer (stages II–IV) and 11 normal]. For all three diagnostic models, both the overall sensitivity and specificity were 100%. The nine most significant micro-RNAs identified, which comprise the input variables to the three linear discriminant functions, are associated with genes that regulate oncogenesis, and they play a paramount role in the development of colon cancer, as evidenced in the tumor tissue itself. This could have a significant impact in the fight against this disease, in that it may lead to the development of an early serum or blood diagnostic test based on the detection of those nine key micro-RNAs

Distinct patterns of fiber type adaptation in rat hindlimb muscles 4 weeks After hemorrhagic stroke

This is a pre-copy-editing, author-produced PDF of an article accepted for publication following peer review. This accepted manuscript is being archived under the conditions specified in the BU OA policy.OBJECTIVE: The aim of this study was to evaluate adaptations in soleus and tibialis anterior muscles in a rat model 4 wks after hemorrhagic stroke. DESIGN: Young adult Sprague Dawley rats were randomly assigned to two groups: stroke and control, with eight soleus and eight tibialis anterior muscles per group. Hemorrhagic stroke was induced in the right caudoputamen of the stroke rats. Control rats had no intervention. Neurologic status was evaluated in both groups before stroke and 4 wks after stroke. Muscles were harvested after poststroke neurologic testing. Muscle fiber types and cross-sectional areas were determined in soleus and tibialis anterior using immunohistochemical labeling for myosin heavy chain. RESULTS: No generalized fiber atrophy was found in any of the muscles. Fiber types shifted from faster to slower in the tibialis anterior of the stroke group, but no fiber type shifts occurred in the soleus muscles of stroke animals. CONCLUSIONS: Because slower myosin heavy chain fiber types are associated with weaker contractile force and slower contractile speed, this faster to slower fiber type shift in tibialis anterior muscles may contribute to weaker and slower muscle contraction in this muscle after stroke. This finding may indicate potential therapeutic benefit from treatments known to influence fiber type plasticity.Accepted manuscrip

Field-potential evidence for extrasynaptic alterations in the hippocampal CA1 pyramidal cell population during paired-pulse potentiation

The mechanisms of paired-pulse potentiation of the CA1 pyramidal cell population were examined by determining input-output relations for control and potentiated responses originating from the activation of radiatum fibers in the hippocampal slice preparation. Two types of potentiation for synchronously discharging pyramidal cells (population spike) were observed. In the first type, the potentiation of the population spike was found to be a combination of synaptic and extrasynaptic factors. This form of potentiation was observed in 16 of 28 slices. In the second type, the potentiation of the population spike was attributed entirely to the potentiation of summated dendritic depolarizations (population EPSP). This synaptic process of potentiation was observed in 12 of 28 slices. The involvement of only extrasynaptic mechanisms in the paired-pulse potentiation of the population spike was not observed. For the potentiation originating from a combination of synaptic and extrasynaptic mechanisms, 60% of the potentiation of the population spike was a result of synaptic factors and 40% could be attributed to extrasynaptic factors. These results support the concept that alterations in the excitability of postsynaptic neurons serve as a component of the mechanisms of paired-pulse potentiation in the radiatum fiber-CA1 pyramidal cell system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25247/1/0000689.pd

Three-dimensional modeling of the HI kinematics of NGC 2915

The nearby blue compact dwarf, NGC 2915, has its stellar disc embedded in a large, extended (~ 22 B-band scale-lengths) HI disc. New high-resolution HI synthesis observations of NGC 2915 have been obtained with the Australia Telescope Compact Array. These observations provide evidence of extremely complex HI kinematics within the immediate vicinity of the galaxy's star-forming core. We identify and quantify double-peaked HI line profiles near the centre of the galaxy and show that the HI energetics can be accounted for by the mechanical energy output of the central high-mass stellar population within time-scales of 10^6-10^7 yr. Full three-dimensional models of the HI data cube are generated and compared to the observations to test various physical scenarios associated with the high-mass star-forming core of NGC 2915. Purely circular HI kinematics are ruled out together with the possibility of a high-velocity-dispersion inter-stellar medium at inner radii. Radial velocities of ~ 30 km/s are required to describe the central-most HI kinematics of the system. Our results lend themselves to the simple physical scenario in which the young stellar core of the galaxy expels the gas outwards from the centre of the disc, thereby creating a central HI under-density. These kinematics should be thought of as being linked to a central HI outflow rather than a large-scale galactic blow-out or wind.Comment: 11 pages, 6 figures, accepted for publication in MNRA

The M81 Group Dwarf Irregular Galaxy DDO 165. II. Connecting Recent Star Formation with ISM Structures and Kinematics

We compare the stellar populations and complex neutral gas dynamics of the M81 group dIrr galaxy DDO 165 using data from the HST and the VLA. Paper I identified two kinematically distinct HI components, multiple localized high velocity gas features, and eight HI holes and shells (the largest of which spans ~2.2x1.1 kpc). Using the spatial and temporal information from the stellar populations in DDO 165, we compare the patterns of star formation over the past 500 Myr with the HI dynamics. We extract localized star formation histories within 6 of the 8 HI holes identified in Paper I, as well as 23 other regions that sample a range of stellar densities and neutral gas properties. From population synthesis modeling, we derive the energy outputs (from stellar winds and supernovae) of the stellar populations within these regions over the last 100 Myr, and compare with refined estimates of the energies required to create the HI holes. In all cases, we find that "feedback" is energetically capable of creating the observed structures in the ISM. Numerous regions with significant energy inputs from feedback lack coherent HI structures but show prominent localized high velocity gas features; this feedback signature is a natural product of temporally and spatially distributed star formation. In DDO 165, the extended period of heightened star formation activity (lasting more than 1 Gyr) is energetically capable of creating the observed holes and high velocity gas features in the neutral ISM.Comment: The Astrophysical Journal, in press. Full-resolution version available on request from the first autho

The M81 Group Dwarf Irregular Galaxy DDO 165. I. High Velocity Neutral Gas in a Post-Starburst System

We present new multi-configuration VLA HI spectral line observations of the M81 group dIrr post-starburst galaxy DDO 165. The HI morphology is complex, with multiple column density peaks surrounding a large region of very low HI surface density that is offset from the center of the stellar distribution. The bulk of the neutral gas is associated with the southern section of the galaxy; a secondary peak in the north contains ~15% of the total HI mass. These components appear to be kinematically distinct, suggesting that either tidal processes or large-scale blowout have recently shaped the ISM of DDO 165. Using spatially-resolved position-velocity maps, we find multiple localized high-velocity gas features. Cross-correlating with radius-velocity analyses, we identify eight shell/hole structures in the ISM with a range of sizes (~400-900 pc) and expansion velocities (~7-11 km/s). These structures are compared with narrow- and broad-band imaging from KPNO and HST. Using the latter data, recent works have shown that DDO 165's previous "burst" phase was extended temporally (>1 Gyr). We thus interpret the high-velocity gas features, HI holes, and kinematically distinct components of the galaxy in the context of the immediate effects of "feedback" from recent star formation. In addition to creating HI holes and shells, extended star formation events are capable of creating localized high velocity motion of the surrounding interstellar material. A companion paper connects the energetics from the HI and HST data.Comment: The Astrophysical Journal, in press. Full-resolution version available on request from the first autho

Apoptosis-associated microRNAs are modulated in mouse, rat and human neural differentiation

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRs or miRNAs) regulate several biological processes in the cell. However, evidence for miRNAs that control the differentiation program of specific neural cell types has been elusive. Recently, we have shown that apoptosis-associated factors, such as p53 and caspases participate in the differentiation process of mouse neural stem (NS) cells. To identify apoptosis-associated miRNAs that might play a role in neuronal development, we performed global miRNA expression profiling experiments in NS cells. Next, we characterized the expression of proapoptotic miRNAs, including miR-16, let-7a and miR-34a in distinct models of neural differentiation, including mouse embryonic stem cells, PC12 and NT2N cells. In addition, the expression of antiapoptotic miR-19a and 20a was also evaluated.</p> <p>Results</p> <p>The expression of miR-16, let-7a and miR-34a was consistently upregulated in neural differentiation models. In contrast, expression of miR-19a and miR-20a was downregulated in mouse NS cell differentiation. Importantly, differential expression of specific apoptosis-related miRNAs was not associated with increased cell death. Overexpression of miR-34a increased the proportion of postmitotic neurons of mouse NS cells.</p> <p>Conclusions</p> <p>In conclusion, the identification of miR-16, let-7a and miR-34a, whose expression patterns are conserved in mouse, rat and human neural differentiation, implicates these specific miRNAs in mammalian neuronal development. The results provide new insights into the regulation of neuronal differentiation by apoptosis-associated miRNAs.</p

Highly resolved in vivo 1H NMR spectroscopy of the mouse brain at 9.4 T

An efficient shim system and an optimized localization sequence were used to measure in vivo 1H NMR spectra from cerebral cortex, hippocampus, striatum, and cerebellum of C57BL/6 mice at 9.4 T. The combination of automatic first- and second-order shimming (FASTMAP) with strong custom-designed second-order shim coils (shim strength up to 0.04 mT/cm2) was crucial to achieve high spectral resolution (water line width of 11-14 Hz). Requirements for second-order shim strengths to compensate field inhomogeneities in the mouse brain at 9.4 T were assessed. The achieved spectral quality (resolution, S/N, water suppression, localization performance) allowed reliable quantification of 16 brain metabolites (LCModel analysis) from 5-10-microL brain volumes. Significant regional differences (up to 2-fold, P < 0.05) were found for all quantified metabolites but Asp, Glc, and Gln. In contrast, 1H NMR spectra measured from the striatum of C57BL/6, CBA, and CBA/BL6 mice revealed only small (<13%, P < 0.05) interstrain differences in Gln, Glu, Ins, Lac, NAAG, and PE. It is concluded that 1H NMR spectroscopy at 9.4 T can provide precise biochemical information from distinct regions of the mouse brain noninvasively that can be used for monitoring of disease progression and treatment as well as phenotyping in transgenic mice models

Extended Scaling in High Dimensions

We apply and test the recently proposed "extended scaling" scheme in an analysis of the magnetic susceptibility of Ising systems above the upper critical dimension. The data are obtained by Monte Carlo simulations using both the conventional Wolff cluster algorithm and the Prokof'ev-Svistunov worm algorithm. As already observed for other models, extended scaling is shown to extend the high-temperature critical scaling regime over a range of temperatures much wider than that achieved conventionally. It allows for an accurate determination of leading and sub-leading scaling indices, critical temperatures and amplitudes of the confluent corrections.Comment: 16 pages, 8 figures. Improved version to appear in JSTA