Multiple sources of bias confound functional enrichment analysis of global -omics data

Serious and underappreciated sources of bias mean that extreme caution should be applied when using or interpreting functional enrichment analysis to validate findings from global RNA- or protein-expression analyses

Dysregulation of alternative poly-adenylation as a potential player in Autism Spectrum Disorder

We present here the hypothesis that alternative poly-adenylation (APA) is dysregulated in the brains of individuals affected by Autism Spectrum Disorder (ASD), due to disruptions in the calcium signaling networks. APA, the process of selecting different poly-adenylation sites on the same gene, yielding transcripts with different-length 3′ untranslated regions (UTRs), has been documented in different tissues, stages of development and pathologic conditions. Differential use of poly-adenylation sites has been shown to regulate the function, stability, localization and translation efficiency of target RNAs. However, the role of APA remains rather unexplored in neurodevelopmental conditions. In the human brain, where transcripts have the longest 3′ UTRs and are thus likely to be under more complex post-transcriptional regulation, erratic APA could be particularly detrimental. In the context of ASD, a condition that affects individuals in markedly different ways and whose symptoms exhibit a spectrum of severity, APA dysregulation could be amplified or dampened depending on the individual and the extent of the effect on specific genes would likely vary with genetic and environmental factors. If this hypothesis is correct, dysregulated APA events might be responsible for certain aspects of the phenotypes associated with ASD. Evidence supporting our hypothesis is derived from standard RNA-seq transcriptomic data but we suggest that future experiments should focus on techniques that probe the actual poly-adenylation site (3′ sequencing). To address issues arising from the use of post-mortem tissue and low numbers of heterogeneous samples affected by confounding factors (such as the age, gender and health of the individuals), carefully controlled in vitro systems will be required to model the effect of calcium signaling dysregulation in the ASD brain

A methodology for investigating dust model performance using synergistic EARLINET/AERONET dust concentration retrievals

Systematic measurements of dust concentration profiles at a continental scale were recently made possible by the development of synergistic retrieval algorithms using combined lidar and sun photometer data and the establishment of robust remote-sensing networks in the framework of Aerosols, Clouds, and Trace gases Research Infra-Structure Network (ACTRIS)/European Aerosol Research Lidar Network (EARLINET). We present a methodology for using these capabilities as a tool for examining the performance of dust transport models. The methodology includes considerations for the selection of a suitable data set and appropriate metrics for the exploration of the results. The approach is demonstrated for four regional dust transport models (BSC-DREAM8b v2, NMMB/BSC-DUST, DREAM-ABOL, DREAM8-NMME-MACC) using dust observations performed at 10 ACTRIS/EARLINET stations. The observations, which include coincident multi-wavelength lidar and sun photometer measurements, were processed with the Lidar-Radiometer Inversion Code (LIRIC) to retrieve aerosol concentration profiles. The methodology proposed here shows advantages when compared to traditional evaluation techniques that utilize separately the available measurements such as separating the contribution of dust from other aerosol types on the lidar profiles and avoiding model assumptions related to the conversion of concentration fields to aerosol extinction values. When compared to LIRIC retrievals, the simulated dust vertical structures were found to be in good agreement for all models with correlation values between 0.5 and 0.7 in the 1-6 km range, where most dust is typically observed. The absolute dust concentration was typically underestimated with mean bias values of -40 to -20 mu g m(-3) at 2 km, the altitude of maximum mean concentration. The reported differences among the models found in this comparison indicate the benefit of the systematic use of the proposed approach in future dust model evaluation studies

iGEMS : an integrated model for identification of alternative exon usage events

DNA microarrays and RNAseq are complementary methods for studying RNA molecules. Current computational methods to determine alternative exon usage (AEU) using such data require impractical visual inspection and still yield high false-positive rates. Integrated Gene and Exon Model of Splicing (iGEMS) adapts a gene-level residuals model with a gene size adjusted false discovery rate and exon-level analysis to circumvent these limitations. iGEMS was applied to two new DNA microarray datasets, including the high coverage Human Transcriptome Arrays 2.0 and performance was validated using RT-qPCR. First, AEU was studied in adipocytes treated with (n = 9) or without (n = 8) the anti-diabetes drug, rosiglitazone. iGEMS identified 555 genes with AEU, and robust verification by RT-qPCR (similar to 90%). Second, in a three-way human tissue comparison (muscle, adipose and blood, n = 41) iGEMS identified 4421 genes with at least one AEU event, with excellent RT-qPCR verification (95%, n = 22). Importantly, iGEMS identified a variety of AEU events, including 3'UTR extension, as well as exon inclusion/exclusion impacting on protein kinase and extracellular matrix domains. In conclusion, iGEMS is a robust method for identification of AEU while the variety of exon usage between human tissues is 5-10 times more prevalent than reported by the Genotype-Tissue Expression consortium using RNA sequencing.Peer reviewe

Metabolomic analyses of Leishmania reveal multiple species differences and large differences in amino acid metabolism

Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts

The unprecedented 2017–2018 stratospheric smoke event: decay phase and aerosol properties observed with the EARLINET

Six months of stratospheric aerosol observations with the European Aerosol Research Lidar Network (EARLINET) from August 2017 to January 2018 are presented. The decay phase of an unprecedented, record-breaking stratospheric perturbation caused by wildfire smoke is reported and discussed in terms of geometrical, optical, and microphysical aerosol properties. Enormous amounts of smoke were injected into the upper troposphere and lower stratosphere over fire areas in western Canada on 12 August 2017 during strong thunderstorm–pyrocumulonimbus activity. The stratospheric fire plumes spread over the entire Northern Hemisphere in the following weeks and months. Twenty-eight European lidar stations from northern Norway to southern Portugal and the eastern Mediterranean monitored the strong stratospheric perturbation on a continental scale. The main smoke layer (over central, western, southern, and eastern Europe) was found at heights between 15 and 20 km since September 2017 (about 2 weeks after entering the stratosphere). Thin layers of smoke were detected at heights of up to 22–23 km. The stratospheric aerosol optical thickness at 532 nm decreased from values > 0.25 on 21–23 August 2017 to 0.005–0.03 until 5–10 September and was mainly 0.003–0.004 from October to December 2017 and thus was still significantly above the stratospheric background (0.001–0.002). Stratospheric particle extinction coefficients (532 nm) were as high as 50–200 Mm−1 until the beginning of September and on the order of 1 Mm−1 (0.5–5 Mm−1) from October 2017 until the end of January 2018. The corresponding layer mean particle mass concentration was on the order of 0.05–0.5 µg m−3 over these months. Soot particles (light-absorbing carbonaceous particles) are efficient ice-nucleating particles (INPs) at upper tropospheric (cirrus) temperatures and available to influence cirrus formation when entering the tropopause from above. We estimated INP concentrations of 50–500 L−1 until the first days in September and afterwards 5–50 L−1 until the end of the year 2017 in the lower stratosphere for typical cirrus formation temperatures of −55 ∘C and an ice supersaturation level of 1.15. The measured profiles of the particle linear depolarization ratio indicated a predominance of nonspherical smoke particles. The 532 nm depolarization ratio decreased slowly with time in the main smoke layer from values of 0.15–0.25 (August–September) to values of 0.05–0.10 (October–November) and < 0.05 (December–January). The decrease of the depolarization ratio is consistent with aging of the smoke particles, growing of a coating around the solid black carbon core (aggregates), and thus change of the shape towards a spherical form. We found ascending aerosol layer features over the most southern European stations, especially over the eastern Mediterranean at 32–35∘ N, that ascended from heights of about 18–19 to 22–23 km from the beginning of October to the beginning of December 2017 (about 2 km per month). We discuss several transport and lifting mechanisms that may have had an impact on the found aerosol layering structures

The unprecedented 2017-2018 stratospheric smoke event : Decay phase and aerosol properties observed with the EARLINET

© Author(s) 2019. This open access work is distributed under the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/).Six months of stratospheric aerosol observations with the European Aerosol Research Lidar Network (EARLINET) from August 2017 to January 2018 are presented. The decay phase of an unprecedented, record-breaking stratospheric perturbation caused by wildfire smoke is reported and discussed in terms of geometrical, optical, and microphysical aerosol properties. Enormous amounts of smoke were injected into the upper troposphere and lower stratosphere over fire areas in western Canada on 12 August 2017 during strong thunderstorm-pyrocumulonimbus activity. The stratospheric fire plumes spread over the entire Northern Hemisphere in the following weeks and months. Twenty-eight European lidar stations from northern Norway to southern Portugal and the eastern Mediterranean monitored the strong stratospheric perturbation on a continental scale. The main smoke layer (over central, western, southern, and eastern Europe) was found at heights between 15 and 20 km since September 2017 (about 2 weeks after entering the stratosphere). Thin layers of smoke were detected at heights of up to 22-23 km. The stratospheric aerosol optical thickness at 532 nm decreased from values > 0.25 on 21-23 August 2017 to 0.005-0.03 until 5-10 September and was mainly 0.003-0.004 from October to December 2017 and thus was still significantly above the stratospheric background (0.001-0.002). Stratospheric particle extinction coefficients (532 nm) were as high as 50-200 Mm-1 until the beginning of September and on the order of 1 Mm-1 (0.5- 5 Mm-1) from October 2017 until the end of January 2018. The corresponding layer mean particle mass concentration was on the order of 0.05-0.5 μg m-3 over these months. Soot particles (light-absorbing carbonaceous particles) are efficient ice-nucleating particles (INPs) at upper tropospheric (cirrus) temperatures and available to influence cirrus formation when entering the tropopause from above. We estimated INP concentrations of 50-500 L-1 until the first days in September and afterwards 5-50 L-1 until the end of the year 2017 in the lower stratosphere for typical cirrus formation temperatures of -55 ?C and an ice supersaturation level of 1.15. The measured profiles of the particle linear depolarization ratio indicated a predominance of nonspherical smoke particles. The 532 nm depolarization ratio decreased slowly with time in the main smoke layer from values of 0.15-0.25 (August-September) to values of 0.05-0.10 (October-November) and < 0.05 (December-January). The decrease of the depolarization ratio is consistent with aging of the smoke particles, growing of a coating around the solid black carbon core (aggregates), and thus change of the shape towards a spherical form. We found ascending aerosol layer features over the most southern European stations, especially over the eastern Mediterranean at 32-35? N, that ascended from heights of about 18-19 to 22-23 km from the beginning of October to the beginning of December 2017 (about 2 km per month). We discuss several transport and lifting mechanisms that may have had an impact on the found aerosol layering structures.Peer reviewe

The analysis of factors, barriers and conditions that affect the attractiveness of mining investment in Poland - own research

The mining sector is one of the most important element of economies in the world, having a huge impact on the economic situation in individual countries. The development at any level would be impossible without access to the most important energy resources, chemical, metal or construction. Therefore, the condition and the possibility of the development of the mining sector in each country should be constantly monitored and properly shaped. On the other hand, to ensure the proper stimulation of growth and the inflow of new capital investments are necessary. Consequently, an appropriate level of investment attractiveness is an important issue both in the context of the sector and the entire economy. The article presents the concept of investment attractiveness and the current situation of the mining sector in Poland. A very important part of the paper is also presented the results of the survey of the analysis of factors, barriers and conditions that affect the attractiveness of mining investment in Poland

Order/Disorder and <i>in Situ</i> Oxide Defect Control in the Bixbyite Phase YPrO_3+δ (0 ≤ δ < 0.5)

The YPrO_3+δ system is a nearly ideal model system for the investigation of oxide defect creation and annihilation in oxide ion conductor related phases with potential applications as solid state electrolytes in solid oxide fuel cells. The formation, structure, high temperature reactivity, and magnetic susceptibility of phase pure YPrO_3+δ (0 ≤ δ ≤ 0.46) are reported. The topotactic reduction and oxidation of the YPrO_3+δ system was investigated by powder X-ray <i>in situ</i> diffraction experiments and revealed bixbyite structures (space group: <i>Ia</i>3̅) throughout the series. Combined neutron and X-ray data clearly show oxygen uptake and removal. The research provides a detailed picture of the Y³⁺/Pr³⁺/Pr⁴⁺ sublattice evolution in response to the redox chemistry. Upon oxidation, cation site splitting is observed where the cation in the (¹/₄, ¹/₄, ¹/₄) position migrates along the body diagonal to the (<i>x</i>, <i>x</i>, <i>x</i>) position. Any oxygen in excess of YPrO_3.0 is located in the additional 16<i>c</i> site without depopulating the original 48<i>e</i> site. The <i>in situ</i> X-ray diffraction data and thermal gravimetric analysis have revealed the reversible topotactic redox reactivity at low temperatures (below 425 °C) for all compositions from YPrO₃ to YPrO_3.46. Magnetic susceptibility studies were utilized in order to further confirm praseodymium oxidation states. The linear relation between the cubic unit cell parameter and oxygen content allows for the straightforward determination of oxygen stoichiometry from X-ray diffraction data. The different synthesis strategies reported here are rationalized with the structural details and the reactivity of YPrO_3+δ phases and provide guidelines for the targeted synthesis of these functional materials