MF890

Edward P. Call & James R. Dunham, A guide to successful AI, Kansas State University, September 1992

Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDNA and no differences in heteroplasmic mtDNA mutation abundance

Abstract Background Sporadic Parkinson's disease (sPD) is a nervous system-wide disease that presents with a bradykinetic movement disorder and is frequently complicated by depression and cognitive impairment. sPD likely has multiple interacting causes that include increased oxidative stress damage to mitochondrial components and reduced mitochondrial bioenergetic capacity. We analyzed mitochondria from postmortem sPD and CTL brains for evidence of oxidative damage to mitochondrial DNA (mtDNA), heteroplasmic mtDNA point mutations and levels of electron transport chain proteins. We sought to determine if sPD brains possess any mtDNA genotype-respiratory phenotype relationships. Results Treatment of sPD brain mtDNA with the mitochondrial base-excision repair enzyme 8-oxyguanosine glycosylase-1 (hOGG1) inhibited, in an age-dependent manner, qPCR amplification of overlapping ~2 kbase products; amplification of CTL brain mtDNA showed moderate sensitivity to hOGG1 not dependent on donor age. hOGG1 mRNA expression was not different between sPD and CTL brains. Heteroplasmy analysis of brain mtDNA using Surveyor nuclease® showed asymmetric distributions and levels of heteroplasmic mutations across mtDNA but no patterns that statistically distinguished sPD from CTL. sPD brain mitochondria displayed reductions of nine respirasome proteins (respiratory complexes I-V). Reduced levels of sPD brain mitochondrial complex II, III and V, but not complex I or IV proteins, correlated closely with rates of NADH-driven electron flow. mtDNA levels and PGC-1α expression did not differ between sPD and CTL brains. Conclusion PD brain mitochondria have reduced mitochondrial respiratory protein levels in complexes I-V, implying a generalized defect in respirasome assembly. These deficiencies do not appear to arise from altered point mutational burden in mtDNA or reduction of nuclear signaling for mitochondrial biogenesis, implying downstream etiologies. The origin of age-related increases in distribution of oxidative mtDNA damage in sPD but not CTL brains is not clear, tracks with but does not determine the sPD phenotype, and may indicate a unique consequence of aging present in sPD that could contribute to mtDNA deletion generation in addition to mtDNA replication, transcription and sequencing errors. sPD frontal cortex experiences a generalized bioenergetic deficiency above and beyond aging that could contribute to mood disorders and cognitive impairments.</p

The Bolocam Galactic Plane Survey IX: Data Release 2 and Outer Galaxy Extension

We present a re-reduction and expansion of the Bolocam Galactic Plane Survey, first presented by Aguirre et al. (2011) and Rosolowsky et al. (2010). The BGPS is a 1.1 mm survey of dust emission in the Northern galactic plane, covering longitudes -10 < \ell < 90 and latitudes |b| < 0.5 with a typical 1-\sigma RMS sensitivity of 30-100 mJy in a 33" beam. Version 2 of the survey includes an additional 20 square degrees of coverage in the 3rd and 4th quadrants and 2 square degrees in the 1st quadrant. The new data release has improved angular recovery, with complete recovery out to 80" and partial recovery to 300", and reduced negative bowls around bright sources resulting from the atmospheric subtraction process. We resolve the factor of 1.5 flux calibration offset between the v1.0 data release and other data sets and determine that there is no offset between v2.0 and other data sets. The v2.0 pointing accuracy is tested against other surveys and demonstrated to be accurate and an improvement over v1.0. We present simulations and tests of the pipeline and its properties, including measurements of the pipeline's angular transfer function. The Bolocat cataloging tool was used to extract a new catalog, which includes 8594 sources, with 591 in the expanded regions. We have demonstrated that the Bolocat 40" and 80" apertures are accurate even in the presence of strong extended background emission. The number of sources is lower than in v1.0, but the amount of flux and area included in identified sources is larger.Comment: 36 pages, 16 figures, accepted to ApJS. Data available from http://irsa.ipac.caltech.edu/data/BOLOCAM_GPS

A Mid-Infrared Census of Star Formation Activity in Bolocam Galactic Plane Survey Sources

We present the results of a search for mid-infrared signs of star formation activity in the 1.1 mm sources in the Bolocam Galactic Plane Survey (BGPS). We have correlated the BGPS catalog with available mid-IR Galactic plane catalogs based on the Spitzer Space Telescope GLIMPSE legacy survey and the Midcourse Space Experiment (MSX) Galactic plane survey. We find that 44% (3,712 of 8,358) of the BGPS sources contain at least one mid-IR source, including 2,457 of 5,067 (49%) within the area where all surveys overlap (10 deg < l < 65 deg). Accounting for chance alignments between the BGPS and mid-IR sources, we conservatively estimate that 20% of the BPGS sources within the area where all surveys overlap show signs of active star formation. We separate the BGPS sources into four groups based on their probability of star formation activity. Extended Green Objects (EGOs) and Red MSX Sources (RMS) make up the highest probability group, while the lowest probability group is comprised of "starless" BGPS sources which were not matched to any mid-IR sources. The mean 1.1 mm flux of each group increases with increasing probability of active star formation. We also find that the "starless" BGPS sources are the most compact, while the sources with the highest probability of star formation activity are on average more extended with large skirts of emission. A subsample of 280 BGPS sources with known distances demonstrates that mass and mean H_2 column density also increase with probability of star formation activity.Comment: 20 pages, 12 figures, 3 tables. Accepted for publication in ApJ. Full Table 2 will be available online through Ap

The Bolocam Galactic Plane Survey: Survey Description and Data Reduction

We present the Bolocam Galactic Plane Survey (BGPS), a 1.1 mm continuum survey at 33" effective resolution of 170 square degrees of the Galactic Plane visible from the northern hemisphere. The survey is contiguous over the range -10.5 < l < 90.5, |b| < 0.5 and encompasses 133 square degrees, including some extended regions |b| < 1.5. In addition to the contiguous region, four targeted regions in the outer Galaxy were observed: IC1396, a region towards the Perseus Arm, W3/4/5, and Gem OB1. The BGPS has detected approximately 8400 clumps over the entire area to a limiting non-uniform 1-sigma noise level in the range 11 to 53 mJy/beam in the inner Galaxy. The BGPS source catalog is presented in a companion paper (Rosolowsky et al. 2010). This paper details the survey observations and data reduction methods for the images. We discuss in detail the determination of astrometric and flux density calibration uncertainties and compare our results to the literature. Data processing algorithms that separate astronomical signals from time-variable atmospheric fluctuations in the data time-stream are presented. These algorithms reproduce the structure of the astronomical sky over a limited range of angular scales and produce artifacts in the vicinity of bright sources. Based on simulations, we find that extended emission on scales larger than about 5.9' is nearly completely attenuated (> 90%) and the linear scale at which the attenuation reaches 50% is 3.8'. Comparison with other millimeter-wave data sets implies a possible systematic offset in flux calibration, for which no cause has been discovered. This presentation serves as a companion and guide to the public data release through NASA's Infrared Processing and Analysis Center (IPAC) Infrared Science Archive (IRSA). New data releases will be provided through IPAC IRSA with any future improvements in the reduction.Comment: Accepted for publication in Astrophysical Journal Supplemen

Pleiotropic effects of simvastatin and losartan in preclinical models of post-traumatic elbow contracture

Elbow trauma can lead to post-traumatic joint contracture (PTJC), which is characterized by loss of motion associated with capsule/ligament fibrosis and cartilage damage. Unfortunately, current therapies are often unsuccessful or cause complications. This study aimed to determine the effects of prophylactically administered simvastatin (SV) and losartan (LS) in two preclinical models of elbow PTJC: a

Phenoscape: Identifying Candidate Genes for Evolutionary Phenotypes

Phenotypes resulting from mutations in genetic model organisms can help reveal candidate genes for evolutionarily important phenotypic changes in related taxa. Although testing candidate gene hypotheses experimentally in nonmodel organisms is typically difficult, ontology-driven information systems can help generate testable hypotheses about developmental processes in experimentally tractable organisms. Here, we tested candidate gene hypotheses suggested by expert use of the Phenoscape Knowledgebase, specifically looking for genes that are candidates responsible for evolutionarily interesting phenotypes in the ostariophysan fishes that bear resemblance to mutant phenotypes in zebrafish. For this, we searched ZFIN for genetic perturbations that result in either loss of basihyal element or loss of scales phenotypes, because these are the ancestral phenotypes observed in catfishes (Siluriformes). We tested the identified candidate genes by examining their endogenous expression patterns in the channel catfish, Ictalurus punctatus. The experimental results were consistent with the hypotheses that these features evolved through disruption in developmental pathways at, or upstream of, brpf1 and eda/edar for the ancestral losses of basihyal element and scales, respectively. These results demonstrate that ontological annotations of the phenotypic effects of genetic alterations in model organisms, when aggregated within a knowledgebase, can be used effectively to generate testable, and useful, hypotheses about evolutionary changes in morphology

A novel method for delivering ramped cooling reveals rat behaviours at innocuous and noxious temperatures: a comparative study of human psychophysics and rat behaviour

Background: Thermal sensory testing in rodents informs human pain research. There are important differences in the methodology for delivering thermal stimuli to humans and rodents. This is particularly true in cold pain research. These differences confound extrapolation and de-value nociceptive tests in rodents. New method: We investigated cooling-induced behaviours in rats and psychophysical thresholds in humans using ramped cooling stimulation protocols. A Peltier device mounted upon force transducers simultaneously applied a ramped cooling stimulus whilst measuring contact with rat hind paw or human finger pad. Rat withdrawals and human detection, discomfort and pain thresholds were measured. Results: Ramped cooling of a rat hind paw revealed two distinct responses: Brief paw removal followed by paw replacement, usually with more weight borne than prior to the removal (temperature inter-quartile range: 19.1 °C to 2.8 °C). Full withdrawal was evoked at colder temperatures (inter quartile range: −11.3 °C to −11.8 °C). The profile of human cool detection threshold and cold pain threshold were remarkably similar to that of the rat withdrawals behaviours. Comparison: Previous rat cold evoked behaviours utilise static temperature stimuli. By utilising ramped cold stimuli this novel methodology better reflects thermal testing in patients. Conclusion: Brief paw removal in the rat is driven by non-nociceptive afferents, as is the perception of cooling in humans. This is in contrast to the nociceptor-driven withdrawal from colder temperatures. These findings have important implications for the interpretation of data generated in older cold pain models and consequently our understanding of cold perception and pain

A genome annotation-driven approach to cloning the human ORFeome.

We have developed a systematic approach to generating cDNA clones containing full-length open reading frames (ORFs), exploiting knowledge of gene structure from genomic sequence. Each ORF was amplified by PCR from a pool of primary cDNAs, cloned and confirmed by sequencing. We obtained clones representing 70% of genes on human chromosome 22, whereas searching available cDNA clone collections found at best 48% from a single collection and 60% for all collections combined.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The Bolocam Galactic Plane Survey: II. Catalog of The Image Data

We present a catalog of 8358 sources extracted from images produced by the Bolocam Galactic Plane Survey (BGPS). The BGPS is a survey of the millimeter dust continuum emission from the northern Galactic plane. The catalog sources are extracted using a custom algorithm, Bolocat, which was designed specifically to identify and characterize objects in the large-area maps generated from the Bolocam instrument. The catalog products are designed to facilitate follow-up observations of these relatively unstudied objects. The catalog is 98% complete from 0.4 Jy to 60 Jy over all object sizes for which the survey is sensitive ( \u3c 3\u27.5). We find that the sources extracted can best be described as molecular clumps-large dense regions in molecular clouds linked to cluster formation. We find that the flux density distribution of sources follows a power law with dN/dS alpha S(-2.4+/-0.1) and that the mean Galactic latitude for sources is significantly below the midplane: \u3c b \u3e = (-0 degrees.095 +/- 0 degrees.001)