The Origin of OB Clusters: From 10 pc to 0.1 pc

We observe the 1.2 mm continuum emission around the OB cluster forming region G10.6-0.4, using the IRAM 30m telescope MAMBO-2 bolometer array and the Submillimeter array. Comparison of the Spitzer 24 $\mu$m and 8 $\mu$m images with our 1.2 mm continuum maps reveals the ionization front of an HII region, the photon-dominated layer, and several 5 pc scale filaments following the outer edge of the photon-dominated layer. The filaments, which are resolved in the MAMBO-2 observations, show regularly spaced parsec-scale molecular clumps, embedded with a cluster of submillimeter molecular cores as shown in the SMA 0.87 mm observations. Toward the center of the G10.6-0.4 region, the combined SMA+IRAM 30m continuum image reveals several, parsec-scale protrusions. They may continue down to within 0.1 pc of the geometric center of a dense 3 pc size structure, where a 200 M$_{\odot}$ OB cluster resides. The observed filaments may facilitate mass accretion onto the central cluster--forming region in the presence of strong radiative and mechanical stellar feedbacks. Their filamentary geometry may also facilitate fragmentation. We did not detect any significant polarized emission at 0.87 mm in the inner 1 pc region with the SMA.Comment: 32 pages, 10 figures, Accepted by ApJ on 2011.October

The Cyprinodon variegatus genome reveals gene expression changes underlying differences in skull morphology among closely related species

Genes in durophage intersection set at 15 dpf. This is a comma separated table of the genes in the 15 dpf durophage intersection set. Given are edgeR results for each pairwise comparison. Columns indicating whether a gene is included in the intersection set at a threshold of 1.5 or 2 fold are provided. (CSV 13 kb

Validation of the Chronic Pain Acceptance Questionnaire-8 in an Australian pain clinic sample

Background: Recently, an 8-item short-form version of the Chronic Pain Acceptance Questionnaire (CPAQ-8) was developed predominantly in an internet sample. Further investigation of the factor structure in a multidisciplinary pain clinic sample is required. Investigation of the concurrent validity of the CPAQ-8 after accounting for the effects of variables commonly measured in the pain clinic setting is also necessary. Purpose: This study examines the factor structure and concurrent validity of the CPAQ-8 in a sample of treatmentseeking patients who attended a multidisciplinary pain clinic. Methods: Participants were 334 patients who attended an Australian multidisciplinary pain service. Participants completed the CPAQ, a demographic questionnaire, and measures of patient adjustment and functioning. Results: Confirmatory factor analysis identified a two-factor 8-item model consisting of Activity Engagement and Pain Willingness factors (SRMR=0.039, RMSEA=0.063, CFI=0.973, TLI=0.960) was superior to both the CPAQ and CPAQ with an item removed. The CPAQ and CPAQ-8 total scores were highly correlated (r=0.93). After accounting for pain intensity, the CPAQ-8 was a significant predictor of depression, anxiety, stress, and disability. The subscales of the CPAQ-8 were both unique contributors to depression and disability in regression analyses, after accounting for pain intensity and kinesiophobia, and after accounting for pain intensity and catastrophizing. Conclusions: The CPAQ-8 has a sound factor structure and similar psychometric properties to the CPAQ; it may have clinical utility as a measure of pain acceptance in treatmentseeking, chronic pain patients

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Identification and classification of high risk groups for Coal Workers' Pneumoconiosis using an artificial neural network based on occupational histories: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Coal workers' pneumoconiosis (CWP) is a preventable, but not fully curable occupational lung disease. More and more coal miners are likely to be at risk of developing CWP owing to an increase in coal production and utilization, especially in developing countries. Coal miners with different occupational categories and durations of dust exposure may be at different levels of risk for CWP. It is necessary to identify and classify different levels of risk for CWP in coal miners with different work histories. In this way, we can recommend different intervals for medical examinations according to different levels of risk for CWP. Our findings may provide a basis for further emending the measures of CWP prevention and control.</p> <p>Methods</p> <p>The study was performed using longitudinal retrospective data in the Tiefa Colliery in China. A three-layer artificial neural network with 6 input variables, 15 neurons in the hidden layer, and 1 output neuron was developed in conjunction with coal miners' occupational exposure data. Sensitivity and ROC analyses were adapted to explain the importance of input variables and the performance of the neural network. The occupational characteristics and the probability values predicted were used to categorize coal miners for their levels of risk for CWP.</p> <p>Results</p> <p>The sensitivity analysis showed that influence of the duration of dust exposure and occupational category on CWP was 65% and 67%, respectively. The area under the ROC in 3 sets was 0.981, 0.969, and 0.992. There were 7959 coal miners with a probability value < 0.001. The average duration of dust exposure was 15.35 years. The average duration of ex-dust exposure was 0.69 years. Of the coal miners, 79.27% worked in helping and mining. Most of the coal miners were born after 1950 and were first exposed to dust after 1970. One hundred forty-four coal miners had a probability value ≥0.1. The average durations of dust exposure and ex-dust exposure were 25.70 and 16.30 years, respectively. Most of the coal miners were born before 1950 and began to be exposed to dust before 1980. Of the coal miners, 90.28% worked in tunneling.</p> <p>Conclusion</p> <p>The duration of dust exposure and occupational category were the two most important factors for CWP. Coal miners at different levels of risk for CWP could be classified by the three-layer neural network analysis based on occupational history.</p

Identification of the risk for liver fibrosis on CHB patients using an artificial neural network based on routine and serum markers

<p>Abstract</p> <p>Background</p> <p>Liver fibrosis progression is commonly found in patients with CHB. Liver biopsy is a gold standard for identifying the extent of liver fibrosis, but has many draw-backs. It is essential to construct a noninvasive model to predict the levels of risk for liver fibrosis. It would provide very useful information to help reduce the number of liver biopsies of CHB patients.</p> <p>Methods</p> <p>339 chronic hepatitis B patients with HBsAg-positive were investigated retrospectively, and divided at random into 2 subsets with twice as many patients in the training set as in the validation set; 116 additional patients were consequently enrolled in the study as the testing set. A three-layer artificial neural network was developed using a Bayesian learning algorithm. Sensitivity and ROC analysis were performed to explain the importance of input variables and the performance of the neural network.</p> <p>Results</p> <p>There were 329 patients without significant fibrosis and 126 with significant fibrosis in the study. All markers except gender, HB, ALP and TP were found to be statistically significant factors associated with significant fibrosis. The sensitivity analysis showed that the most important factors in the predictive model were age, AST, platelet, and GGT, and the influence on the output variable among coal miners were 22.3-24.6%. The AUROC in 3 sets was 0.883, 0.884, and 0.920. In the testing set, for a decision threshold of 0.33, sensitivity and negative predictive values were 100% and all CHB patients with significant fibrosis would be identified.</p> <p>Conclusions</p> <p>The artificial neural network model based on routine and serum markers would predict the risk for liver fibrosis with a high accuracy. 47.4% of CHB patients at a decision threshold of 0.33 would be free of liver biopsy and wouldn't be missed.</p

Nicotine up-regulates α4β2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning

The up-regulation of α4β2* nicotinic acetylcholine receptors (nAChRs) by chronic nicotine is a cell-delimited process and may be necessary and sufficient for the initial events of nicotine dependence. Clinical literature documents an inverse relationship between a person’s history of tobacco use and his or her susceptibility to Parkinson’s disease; this may also result from up-regulation. This study visualizes and quantifies the subcellular mechanisms involved in nicotine-induced nAChR up-regulation by using transfected fluorescent protein (FP)-tagged α4 nAChR subunits and an FP-tagged Sec24D endoplasmic reticulum (ER) exit site marker. Total internal reflection fluorescence microscopy shows that nicotine (0.1 µM for 48 h) up-regulates α4β2 nAChRs at the plasma membrane (PM), despite increasing the fraction of α4β2 nAChRs that remain in near-PM ER. Pixel-resolved normalized Förster resonance energy transfer microscopy between α4-FP subunits shows that nicotine stabilizes the (α4)2(β2)3 stoichiometry before the nAChRs reach the trans-Golgi apparatus. Nicotine also induces the formation of additional ER exit sites (ERES). To aid in the mechanistic analysis of these phenomena, we generated a β2enhanced-ER-export mutant subunit that mimics two regions of the β4 subunit sequence: the presence of an ER export motif and the absence of an ER retention/retrieval motif. The α4β2enhanced-ER-export nAChR resembles nicotine-exposed nAChRs with regard to stoichiometry, intracellular mobility, ERES enhancement, and PM localization. Nicotine produces only small additional PM up-regulation of α4β2enhanced-ER-export receptors. The experimental data are simulated with a model incorporating two mechanisms: (1) nicotine acts as a stabilizing pharmacological chaperone for nascent α4β2 nAChRs in the ER, eventually increasing PM receptors despite a bottleneck(s) in ER export; and (2) removal of the bottleneck (e.g., by expression of the β2enhanced-ER-export subunit) is sufficient to increase PM nAChR numbers, even without nicotine. The data also suggest that pharmacological chaperoning of nAChRs by nicotine can alter the physiology of ER processes

ASPM and microcephalin expression in epithelial ovarian cancer correlates with tumour grade and survival

BACKGROUND: The clinico-pathological and molecular heterogeneity of epithelial ovarian cancer (EOC) complicates its early diagnosis and successful treatment. Highly aneuploid tumours and the presence of ascitic fluids are hallmarks of EOC. Two microcephalyassociated proteins, abnormal spindle-like microcephaly-associated protein (ASPM) and microcephalin, are involved in mitosis and DNA damage repair. Their expression is deregulated at the RNA level in EOC. Here, ASPM and microcephalin protein expression in primary cultures established from the ascites of patients with EOC was determined and correlated with clinical data to assess their suitability as biomarkers. METHODS: Five established ovarian cancer cell lines, cells derived from two benign ovarian ascites samples and 40 primary cultures of EOC derived from ovarian ascites samples were analysed by protein slot blotting and/or immunofluorescence to determine ASPM and microcephalin protein levels and their cellular localisation. Results were correlated with clinico-pathological data. RESULTS: A statistically significant correlation was identified for ASPM localisation and tumour grade, with high levels of cytoplasmic ASPM correlating with grade 1 tumours. Conversely, cytoplasmic microcephalin was only identified in high-grade tumours. Furthermore, low levels of nuclear microcephalin correlated with reduced patient survival. CONCLUSION: Our results suggest that ASPM and microcephalin have the potential to be biomarkers in ovarian cance

Differences in lateral gene transfer in hypersaline versus thermal environments

<p>Abstract</p> <p>Background</p> <p>The role of lateral gene transfer (LGT) in the evolution of microorganisms is only beginning to be understood. While most LGT events occur between closely related individuals, inter-phylum and inter-domain LGT events are not uncommon. These distant transfer events offer potentially greater fitness advantages and it is for this reason that these "long distance" LGT events may have significantly impacted the evolution of microbes. One mechanism driving distant LGT events is microbial transformation. Theoretically, transformative events can occur between any two species provided that the DNA of one enters the habitat of the other. Two categories of microorganisms that are well-known for LGT are the thermophiles and halophiles.</p> <p>Results</p> <p>We identified potential inter-class LGT events into both a thermophilic class of Archaea (Thermoprotei) and a halophilic class of Archaea (Halobacteria). We then categorized these LGT genes as originating in thermophiles and halophiles respectively. While more than 68% of transfer events into Thermoprotei taxa originated in other thermophiles, less than 11% of transfer events into Halobacteria taxa originated in other halophiles.</p> <p>Conclusions</p> <p>Our results suggest that there is a fundamental difference between LGT in thermophiles and halophiles. We theorize that the difference lies in the different natures of the environments. While DNA degrades rapidly in thermal environments due to temperature-driven denaturization, hypersaline environments are adept at preserving DNA. Furthermore, most hypersaline environments, as topographical minima, are natural collectors of cellular debris. Thus halophiles would in theory be exposed to a greater diversity and quantity of extracellular DNA than thermophiles.</p

Characterization of the Fecal Microbiome from Non-Human Wild Primates Reveals Species Specific Microbial Communities

BACKGROUND: Host-associated microbes comprise an integral part of animal digestive systems and these interactions have a long evolutionary history. It has been hypothesized that the gastrointestinal microbiome of humans and other non-human primates may have played significant roles in host evolution by facilitating a range of dietary adaptations. We have undertaken a comparative sequencing survey of the gastrointestinal microbiomes of several non-human primate species, with the goal of better understanding how these microbiomes relate to the evolution of non-human primate diversity. Here we present a comparative analysis of gastrointestinal microbial communities from three different species of Old World wild monkeys. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed fecal samples from three different wild non-human primate species (black-and-white colobus [Colubus guereza], red colobus [Piliocolobus tephrosceles], and red-tailed guenon [Cercopithecus ascanius]). Three samples from each species were subjected to small subunit rRNA tag pyrosequencing. Firmicutes comprised the vast majority of the phyla in each sample. Other phyla represented were Bacterioidetes, Proteobacteria, Spirochaetes, Actinobacteria, Verrucomicrobia, Lentisphaerae, Tenericutes, Planctomycetes, Fibrobacateres, and TM7. Bray-Curtis similarity analysis of these microbiomes indicated that microbial community composition within the same primate species are more similar to each other than to those of different primate species. Comparison of fecal microbiota from non-human primates with microbiota of human stool samples obtained in previous studies revealed that the gut microbiota of these primates are distinct and reflect host phylogeny. CONCLUSION/SIGNIFICANCE: Our analysis provides evidence that the fecal microbiomes of wild primates co-vary with their hosts, and that this is manifested in higher intraspecies similarity among wild primate species, perhaps reflecting species specificity of the microbiome in addition to dietary influences. These results contribute to the limited body of primate microbiome studies and provide a framework for comparative microbiome analysis between human and non-human primates as well as a comparative evolutionary understanding of the human microbiome