Towards Constraining Glacial Isostatic Adjustment in Greenland Using ICESat and GPS Observations

Constraining glacial isostatic adjustment (GIA) i.e. the Earth’s viscoelastic response to past ice changes, is an important task, because GIA is a significant correction in gravity-based ice sheet mass balance estimates. Here, we investigate how temporal variations in the observed and modeled crustal displacements due to the Earth’s response to ongoing ice mass changes can contribute to the process of constraining GIA. We use mass change grids of the Greenland ice sheet (GrIS) derived from NASA’s high resolution Ice, Cloud and land Elevation Satellite (ICESat) data in three overlapping time spans covering the period 2004–2009 to estimate temporal variations in the elastic response due to present day ice mass loss. The modeled crustal displacements (elastic + GIA) are compared with GPS time series from five permanent sites (KELY, KULU, QAQ1, THU2, and SCOR). We find, that the modeled pattern of elastic crustal displacements shows pronounced variation during the observation period, where an increase in elastic displacement is found at the northwest coast of Greenland, while a decrease is found at the southeast coast. This pattern of temporal changes is supported by the GPS observations. We find, that the temporal behavior of the ICESat-based modeled elastic response agrees well with the GPS observations at the sites KELY, QAQ1, and SCOR. This suggests, that our elastic models are able to resolve the temporal changes in the observed uplift, which indicates that the elastic uplift models are reliable at these sites. Therefore, we conclude that these sites are useful for constraining GIA

Expressed sequence tag analysis of khat (Catha edulis) provides a putative molecular biochemical basis for the biosynthesis of phenylpropylamino alkaloids

Khat (Catha edulis Forsk.) is a flowering perennial shrub cultivated for its neurostimulant properties resulting mainly from the occurrence of (S)-cathinone in young leaves. The biosynthesis of (S)-cathinone and the related phenylpropylamino alkaloids (1S,2S)-cathine and (1R,2S)-norephedrine is not well characterized in plants. We prepared a cDNA library from young khat leaves and sequenced 4,896 random clones, generating an expressed sequence tag (EST) library of 3,293 unigenes. Putative functions were assigned to > 98% of the ESTs, providing a key resource for gene discovery. Candidates potentially involved at various stages of phenylpropylamino alkaloid biosynthesis from L-phenylalanine to (1S,2S)-cathine were identified

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

Evolution of Streptococcus pneumoniae and Its Close Commensal Relatives

Streptococcus pneumoniae is a member of the Mitis group of streptococci which, according to 16S rRNA-sequence based phylogenetic reconstruction, includes 12 species. While other species of this group are considered prototypes of commensal bacteria, S. pneumoniae is among the most frequent microbial killers worldwide. Population genetic analysis of 118 strains, supported by demonstration of a distinct cell wall carbohydrate structure and competence pheromone sequence signature, shows that S. pneumoniae is one of several hundred evolutionary lineages forming a cluster separate from Streptococcus oralis and Streptococcus infantis. The remaining lineages of this distinct cluster are commensals previously collectively referred to as Streptococcus mitis and each represent separate species by traditional taxonomic standard. Virulence genes including the operon for capsule polysaccharide synthesis and genes encoding IgA1 protease, pneumolysin, and autolysin were randomly distributed among S. mitis lineages. Estimates of the evolutionary age of the lineages, the identical location of remnants of virulence genes in the genomes of commensal strains, the pattern of genome reductions, and the proportion of unique genes and their origin support the model that the entire cluster of S. pneumoniae, S. pseudopneumoniae, and S. mitis lineages evolved from pneumococcus-like bacteria presumably pathogenic to the common immediate ancestor of hominoids. During their adaptation to a commensal life style, most of the lineages gradually lost the majority of genes determining virulence and became genetically distinct due to sexual isolation in their respective hosts

Efficacy of a referral and physical activity program for survivors of prostate cancer [ENGAGE]: Rationale and design for a cluster randomised controlled trial

Background: Despite evidence that physical activity improves the health and well-being of prostate cancer survivors, many men do not engage in sufficient levels of activity. The primary aim of this study (ENGAGE) is to determine the efficacy of a referral and physical activity program among survivors of prostate cancer, in terms of increasing participation in physical activity. Secondary aims are to determine the effects of the physical activity program on psychological well-being, quality of life and objective physical functioning. The influence of individual and environmental mediators on participation in physical activity will also be determined.Methods/Design: This study is a cluster randomised controlled trial. Clinicians of prostate cancer survivors will be randomised into either the intervention or control condition. Clinicians in the intervention condition will refer eligible patients (n = 110) to participate in an exercise program, comprising 12 weeks of supervised exercise sessions and unsupervised physical activity. Clinicians allocated to the control condition will provide usual care to eligible patients (n = 110), which does not involve the recommendation of the physical activity program. Participants will be assessed at baseline, 12 weeks, 6 months, and 12 months on physical activity, quality of life, anxiety, depression, self-efficacy, outcome expectations, goals, and socio-structural factors.Discussion: The findings of this study have implications for clinicians and patients with different cancer types or other chronic health conditions. It will contribute to our understanding on the potential impact of clinicians promoting physical activity to patients and the long term health benefits of participating in physical activity programs.<br /

In vivo Identification and Specificity assessment of mRNA markers of hypoxia in human and mouse tumors

<p>Abstract</p> <p>Background</p> <p>Tumor hypoxia is linked to poor prognosis, but identification and quantification of tissue hypoxia remains a challenge. The hypoxia-specificity of HIF-1α target genes in vivo has been questioned due to the confounding influence of other microenvironmental abnormalities known to affect gene expression (e.g., low pH). Here we describe a new technique that by exploiting intratumoral oxygenation heterogeneity allows us to identify and objectively rank the most robust mRNA hypoxia biomarkers.</p> <p>Methods</p> <p>Mice carrying human (FaDu_dd) or murine (SCCVII) tumors were injected with the PET hypoxia tracer FAZA. Four hours post-injection tumors were removed, frozen, and crushed into milligram-sized fragments, which were transferred individually to pre-weighed tubes containing RNAlater and then weighed. For each fragment radioactivity per tissue mass and expression patterns of selected mRNA biomarkers were analyzed and compared.</p> <p>Results</p> <p>In both tumour models, fragmentation into pieces weighing 10 to 60 mg resulted in tissue fragments with highly variable relative content of hypoxic cells as evidenced by an up to 13-fold variation in FAZA radioactivity per mass of tissue. Linear regression analysis comparing FAZA retention with patterns of gene expression in individual tissue fragments revealed that CA9, GLUT1 and LOX mRNA levels were equally and strongly correlated to hypoxic extent in FaDu_dd. The same link between hypoxia and gene expression profile was observed for CA9 and GLUT1, but not LOX, in SCCVII tumors. Apparent in vivo hypoxia-specificity for other putative molecular markers of tissue hypoxia was considerably weaker.</p> <p>Conclusions</p> <p>The portrayed technique allows multiple pairwise measurements of mRNA transcript levels and extent of hypoxia in individual tumors at a smallest possible volumetric scale which (by limiting averaging effects inherent to whole-tumor analysis) strengthen the conclusiveness on true hypoxia-specificity of candidate genes while limiting the required number of tumors. Among tested genes, our study identified CA9, GLUT1 and possibly LOX as highly specific biomarkers of tumor hypoxia in vivo.</p

Transcriptional profile of the homologous recombination machinery and characterization of the EhRAD51 recombinase in response to DNA damage in Entamoeba histolytica

<p>Abstract</p> <p>Background</p> <p>In eukaryotic and prokaryotic cells, homologous recombination is an accurate mechanism to generate genetic diversity, and it is also used to repair DNA double strand-breaks. <it>RAD52 </it>epistasis group genes involved in recombinational DNA repair, including <it>mre11, rad50, nsb1/xrs2, rad51, rad51c/rad57, rad51b/rad55, rad51d, xrcc2, xrcc3, rad52, rad54, rad54b/rdh54 </it>and <it>rad59 </it>genes, have been studied in human and yeast cells. Notably, the RAD51 recombinase catalyses strand transfer between a broken DNA and its undamaged homologous strand, to allow damaged region repair. In protozoan parasites, homologous recombination generating antigenic variation and genomic rearrangements is responsible for virulence variation and drug resistance. However, in <it>Entamoeba histolytica </it>the protozoan parasite responsible for human amoebiasis, DNA repair and homologous recombination mechanisms are still unknown.</p> <p>Results</p> <p>In this paper, we initiated the study of the mechanism for DNA repair by homologous recombination in the primitive eukaryote <it>E. histolytica </it>using UV-C (150 J/m²) irradiated trophozoites. DNA double strand-breaks were evidenced in irradiated cells by TUNEL and comet assays and evaluation of the EhH2AX histone phosphorylation status. In <it>E. histolytica </it>genome, we identified genes homologous to yeast and human RAD52 epistasis group genes involved in DNA double strand-breaks repair by homologous recombination. Interestingly, the <it>E. histolytica </it>RAD52 epistasis group related genes were differentially expressed before and after UV-C treatment. Next, we focused on the characterization of the putative recombinase EhRAD51, which conserves the typical architecture of RECA/RAD51 proteins. Specific antibodies immunodetected EhRAD51 protein in both nuclear and cytoplasmic compartments. Moreover, after DNA damage, EhRAD51 was located as typical nuclear <it>foci</it>-like structures in <it>E. histolytica </it>trophozoites. Purified recombinant EhRAD51 exhibited DNA binding and pairing activities and exchanging reactions between homologous strands <it>in vitro</it>.</p> <p>Conclusion</p> <p><it>E. histolytica </it>genome contains most of the RAD52 epistasis group related genes, which were differentially expressed when DNA double strand-breaks were induced by UV-C irradiation. In response to DNA damage, EhRAD51 protein is overexpressed and relocalized in nuclear <it>foci</it>-like structures. Functional assays confirmed that EhRAD51 is a <it>bonafide </it>recombinase. These data provided the first insights about the potential roles of the <it>E. histolytica </it>RAD52 epistasis group genes and EhRAD51 protein function in DNA damage response of this ancient eukaryotic parasite.</p

Особливості державного регулювання інвестиційно-інноваційної діяльності, в сфері екології

BACKGROUND: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. METHODS: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. RESULTS: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant. In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 1.25; 95% CI, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m(3)), PM10 S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10 K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S. CONCLUSIONS: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important

Psip1/p52 regulates posterior Hoxa genes through activation of lncRNA Hottip

Long noncoding RNAs (lncRNAs) have been implicated in various biological functions including the regulation of gene expression, however, the functionality of lncRNAs is not clearly understood and conflicting conclusions have often been reached when comparing different methods to investigate them. Moreover, little is known about the upstream regulation of lncRNAs. Here we show that the short isoform (p52) of a transcriptional co-activator—PC4 and SF2 interacting protein (Psip1), which is known to be involved in linking transcription to RNA processing, specifically regulates the expression of the lncRNA Hottip–located at the 5’ end of the Hoxa locus. Using both knockdown and knockout approaches we show that Hottip expression is required for activation of the 5’ Hoxa genes (Hoxa13 and Hoxa10/11) and for retaining Mll1 at the 5’ end of Hoxa. Moreover, we demonstrate that artificially inducing Hottip expression is sufficient to activate the 5’ Hoxa genes and that Hottip RNA binds to the 5’ end of Hoxa. By engineering premature transcription termination, we show that it is the Hottip lncRNA molecule itself, not just Hottip transcription that is required to maintains active expression of posterior Hox genes. Our data show a direct role for a lncRNA molecule in regulating the expression of developmentally-regulated mRNA genes in cis