Genomic basis of ecological niche divergence among cryptic sister species of non-biting midges

Background: There is a lack of understanding the evolutionary forces driving niche segregation of closely related organisms. In addition, pinpointing the genes driving ecological divergence is a key goal in molecular ecology. Here, larval transcriptome sequences obtained by next-generation-sequencing are used to address these issues in a morphologically cryptic sister species pair of non-biting midges (Chironomus riparius and C. piger). Results: More than eight thousand orthologous open reading frames were screened for interspecific divergence and intraspecific polymorphisms. Despite a small mean sequence divergence of 1.53% between the sister species, 25.1% of 18,115 observed amino acid substitutions were inferred by α statistics to be driven by positive selection. Applying McDonald-Kreitman tests to 715 alignments of gene orthologues identified eleven (1.5%) genes driven by positive selection. Conclusions: Three candidate genes were identified as potentially responsible for the observed niche segregation concerning nitrite concentration, habitat temperature and water conductivity. Additionally, signs of positive selection in the hydrogen sulfide detoxification pathway were detected, providing a new plausible hypothesis for the species’ ecological differentiation. Finally, a divergently selected, nuclear encoded mitochondrial ribosomal protein may contribute to reproductive isolation due to cytonuclear coevolution

Abundance of conserved CRISPR-Cas9 target sites within the highly polymorphic genomes of Anopheles and Aedes mosquitoes.

A number of recent papers report that standing genetic variation in natural populations includes ubiquitous polymorphisms within target sites for Cas9-based gene drive (CGD) and that these "drive resistant alleles" (DRA) preclude the successful application of CGD for managing these populations. Here we report the results of a survey of 1280 genomes of the mosquitoes Anopheles gambiae, An. coluzzii, and Aedes aegypti in which we determine that ~90% of all protein-encoding CGD target genes in natural populations include at least one target site with no DRAs at a frequency of ≥1.0%. We conclude that the abundance of conserved target sites in mosquito genomes and the inherent flexibility in CGD design obviates the concern that DRAs present in the standing genetic variation of mosquito populations will be detrimental to the deployment of this technology for population modification strategies

Retroviral Vectors: Post Entry Events and Genomic Alterations

The curative potential of retroviral vectors for somatic gene therapy has been demonstrated impressively in several clinical trials leading to sustained long-term correction of the underlying genetic defect. Preclinical studies and clinical monitoring of gene modified hematopoietic stem and progenitor cells in patients have shown that biologically relevant vector induced side effects, ranging from in vitro immortalization to clonal dominance and oncogenesis in vivo, accompany therapeutic efficiency of integrating retroviral gene transfer systems. Most importantly, it has been demonstrated that the genotoxic potential is not identical among all retroviral vector systems designed for clinical application. Large scale viral integration site determination has uncovered significant differences in the target site selection of retrovirus subfamilies influencing the propensity for inducing genetic alterations in the host genome. In this review we will summarize recent insights gained on the mechanisms of insertional mutagenesis based on intrinsic target site selection of different retrovirus families. We will also discuss examples of side effects occurring in ongoing human gene therapy trials and future prospectives in the field

Maximum number of r-edge-colorings such that all copies of Kk are rainbow

We consider a version of the Erdős-Rothschild problem for families of graph patterns. For any fixed k ≥ 3, let r0(k) be the largest integer such that the following holds for all 2 ≤ r ≤ r0(k) and all sufficiently large n: The Turán graph Tk-1(n) is the unique n-vertex graph G with the maximum number of r-edge-colorings such that the edge set of any copy of Kk in G is rainbow. We use the regularity lemma of Szemerédi and linear programming to obtain a lower bound on the value of r0(k). For a more general family P of patterns of Kk, we also prove that, in order to show that the Turán graph Tk-1(n) maximizes the number of P-free r-edge-colorings over n-vertex graphs, it suffices to prove a related stability result

Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo

We treated 10 children with X-linked SCID (SCID-X1) using gammaretrovirus-mediated gene transfer. Those with sufficient follow-up were found to have recovered substantial immunity in the absence of any serious adverse events up to 5 years after treatment. To determine the influence of vector integration on lymphoid reconstitution, we compared retroviral integration sites (RISs) from peripheral blood CD3(+) T lymphocytes of 5 patients taken between 9 and 30 months after transplantation with transduced CD34(+) progenitor cells derived from 1 further patient and I healthy donor. Integration occurred preferentially in gene regions on either side of transcription start sites, was clustered, and correlated with the expression level in CD34(+) progenitors during transduction. In contrast to those in CD34(+) cells, RISs recovered from engrafted CD3(+)T cells were significantly overrepresented within or near genes encoding proteins with kinase or transferase activity or involved in phosphorus metabolism. Although gross patterns of gene expression were unchanged in transduced cells, the divergence of RIS target frequency between transduced progenitor cells and post-thymic T lymphocytes indicates that vector integration influences cell survival, engraftment, or proliferation

Kajian Awal Prospek Bahan Galian Monasit Mengandung U Dan Elemen Asosiasinya Di Semelangan Ketapang, Kalimantan Barat

Daerah Semelangan termasuk dalam cakupan area geologi regional Ketapang. Analisis kadar geokimia contoh sedimen yang menunjukkan bahwa daerah Semelangan, Kecamatan Nanga Tayap, Kabupaten Ketapang teridentifikasi mengandung endapan mineral radioaktif berupa monasit yang mengandung uranium (U) dan unsur tanah jarang (rare earth elements, REE) yang cukup potensial. Keberadaan elemen radioaktif telah teridentifikasi dari hasil analisis granulometri beberapa sampel mineral berat yang mengandung mineral monasit mencapai 63% dan beberapa sampel mengandung butiran zirkon mencapai 40% (dari jumlah butiran), hasil analisis butiran dari contoh batuan terdapat contoh yang mengandung monasit 0,11%. Studi di daerah ini dilakukan dengan melakukan kajian data sekunder dan evaluasi data laboratorium. Kajian mencakup aspek geologi, batuan sumber, perangkap dan interpretasi sebaran plaser monasit mengandung U, Th dan zirkon beserta REE. Tujuan yang ingin diperoleh adalah informasi tentang karakter geologi dan sebaran sumberdaya bahan galian monasit mengandung Th dan U serta REE dalam monasit dan zircon. Batuan sumber bahan galian monasit, berupa granit berumur 77–115 juta (Yura – Kapur Akhir), termasuk tipe S dari kelompok granit alkali yang terbentuk pada fasa pegmatitik (pegmatitic stage) yang terdefrensiasi tingkat lanjut pada suhu 550 – 600°C. Nilai radioaktivitas anomali batuan granit biotit (400 c/s - 9200 c/s) dicirikan kandungan oleh mineral berupa K-felspar, kuarsa dan plagioklas (rasio K-felspar terhadap plagioklas bervariasi dari 80 – 100 berbanding 10) mengandung mineral penyerta berupa thorit, monasit, zirkon dan alanit. Kadar U batuan granit berkisar dari 2,5 ppm- 64,8 ppm. Sebaran lateral sedimen plaser aluvium mengandung monasit menempati dataran dari lembah banjir antar perbukitan, terletak terpisah dari dataran pantai mengikuti pola sebaran batuan granit (sumber monasit). Daerah propek monasit terletak pada dataran lembah banjir dari DAS S. Pawan, DAS S. Tulah dan DAS S. Laur dengan luas total 2.113.500 Ha. Semelangan study area included in the regional geology Ketapang. Geochemical analysis of sediment samples that represented showed that the region Semelangan Ketapang, District Nanga Tayap, Ketapang identified monazite deposite containing radioactive mineral. The monazite minerals containing rare earth element are potential. The presence of radioactive elements have been identified by the analysis granulometry of some pan consentrate samples. They containt of monazite grain mineral to reach 63% and some sample content of zircon grain mineral up to 40% (from total grains), grain analysis of rock samples are samples containing monazite 0.11 %. Activities study in this area is done by studying ecxisting data and laboratory data evaluation, which covering studies geological aspects, source rock, trap and plaser monazite deposits containing U, Th and REE and zircon. The objective is to obtain information about the character of geological and mineral resource distribution of monazite containing Th and U and rare earth elements in monazite and zircon. Source rock of the monazite minerals is a granite with aged 77-15 million (Yura - Late Cretaceous), including the S type granite group that formed in the alkali granite pegmatitic stage, which highly differentiated advanced at a temperature 550-6000°C. The radioactivity anomalous values is 400 c/s – 9200 c/s (biotite granite) with a mineral character of the form K-feldspar, quartz and plagioclase (K-feldspar to plagioclase ratio varies from 80-100 versus 10), containing minerals association such as thorit, monazite, zircon and alanit. The U content in granite rock ranging from 2.5 ppm - 64.8 ppm U. Lateral distribution plaser alluvial sediments contain monazite occupy flood plains of the valley between the hills, is located separately from the coastal plain and following the granite distribution pattern (source monazite). Monazite prospect region lies at the flood plains of the valley catcment area S. Pawan, S. Tulah and S Laur with a total area of 2.1135 million hectares

Molecular Evidence of Lentiviral Vector-Mediated Gene Transfer into Human Self-Renewing, Multi-potent, Long-Term NOD/SCID Repopulating Hematopoietic Cells

A major challenge in gene therapy is to achieve efficient transduction of hematopoietic stem cells (HSC). It has previously been shown that lentiviral vectors (LV) transduce efficiently human cord blood-derived NOD/SCID mouse repopulating cells (SRC). Here we studied the effect of cytokines during the short ex vivo incubation with vector. Although SRC transduction was efficient without stimulation, the presence of cytokines significantly improved it. The treatment did not affect the engraftment level or the SRC frequency, but seemed to enhance SRC susceptibility to LV. SRC transduced in both conditions repopulated primary and secondary recipients, maintaining stable multi-lineage transgene expression. Using linear amplification-mediated PCR, we then analyzed vector integration in the bone marrow and CFC of the engrafted mice to monitor the clonal activity of the transduced SRC in vivo. We showed polyclonal engraftment, multi-lineage differentiation, and propagation to secondary recipients of individual SRC. We observed multiple integrations in most clones. These results provide the first formal demonstration that primitive human HSC with self-renewal and multi-lineage repopulation capacities were transduced by LV. Our findings are relevant for the design of clinical protocols that exploit this system to reach significant engraftment by genetically modified HSC in the absence of in vivo selection or strong conditioning regimens

Moisture origin as a driver of temporal variabilities of the water vapour isotopic composition in the Lena River Delta, Siberia

In the context of the Arctic amplification of climate change affecting the regional atmospheric hydrological cycle, it is crucial to characterize the present-day moisture sources of the Arctic. The isotopic composition is an important tool to enhance our understanding of the drivers of the hydrological cycle due to the different molecular characteristics of water stable isotopes during phase change. This study introduces 2 years of continuous in situ water vapour and precipitation isotopic observations conducted since July 2015 in the eastern Siberian Lena delta at the research station on Samoylov Island. The vapour isotopic signals are dominated by variations at seasonal and synoptic timescales. Diurnal variations of the vapour isotopic signals are masked by synoptic variations, indicating low variations of the amplitude of local sources at the diurnal scale in winter, summer and autumn. Low-amplitude diurnal variations in spring may indicate exchange of moisture between the atmosphere and the snow-covered surface. Moisture source diagnostics based on semi-Lagrangian backward trajectories reveal that different air mass origins have contrasting contributions to the moisture budget of the Lena delta region. At the seasonal scale, the distance from the net moisture sources to the arrival site strongly varies. During the coldest months, no contribution from local secondary evaporation is observed. Variations of the vapour isotopic composition during the cold season on the synoptic timescale are strongly related to moisture source regions and variations in atmospheric transport: warm and isotopically enriched moist air is linked to fast transport from the Atlantic sector, while dry and cold air with isotopically depleted moisture is generally associated with air masses moving slowly over northern Eurasia

Identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model

Background: With the expansion of animal production, parasitic helminths are gaining increasing economic importance. However, application of several established deworming agents can harm treated hosts and environment due to their low specificity. Furthermore, the number of parasite strains showing resistance is growing, while hardly any new anthelminthics are being developed. Here, we present a bioinformatics workflow designed to reduce the time and cost in the development of new strategies against parasites. The workflow includes quantitative transcriptomics and proteomics, 3D structure modeling, binding site prediction, and virtual ligand screening. Its use is demonstrated for Acanthocephala (thorny-headed worms) which are an emerging pest in fish aquaculture. We included three acanthocephalans (Pomphorhynchus laevis, Neoechinorhynchus agilis, Neoechinorhynchus buttnerae) from four fish species (common barbel, European eel, thinlip mullet, tambaqui).Results: The workflow led to eleven highly specific candidate targets in acanthocephalans. The candidate targets showed constant and elevated transcript abundances across definitive and accidental hosts, suggestive of constitutive expression and functional importance. Hence, the impairment of the corresponding proteins should enable specific and effective killing of acanthocephalans. Candidate targets were also highly abundant in the acanthocephalan body wall, through which these gutless parasites take up nutrients. Thus, the candidate targets are likely to be accessible to compounds that are orally administered to fish. Virtual ligand screening led to ten compounds, of which five appeared to be especially promising according to ADMET, GHS, and RO5 criteria: tadalafil, pranazepide, piketoprofen, heliomycin, and the nematicide derquantel.Conclusions: The combination of genomics, transcriptomics, and proteomics led to a broadly applicable procedure for the cost- and time-saving identification of candidate target proteins in parasites. The ligands predicted to bind can now be further evaluated for their suitability in the control of acanthocephalans. The workflow has been deposited at the Galaxy workflow server under the URL tinyurl.com/yx72rda7

An Annotated Draft Genome for Radix auricularia (Gastropoda, Mollusca)

Molluscs are the second most species-rich phylum in the animal kingdom, yet only 11 genomes of this group have been published so far. Here, we present the draft genome sequence of the pulmonate freshwater snail Radix auricularia. Six whole genome shotgun libraries with different layouts were sequenced. The resulting assembly comprises 4,823 scaffolds with a cumulative length of 910 Mb and an overall read coverage of 72×. The assembly contains 94.6% of a metazoan core gene collection, indicating an almost complete coverage of the coding fraction. The discrepancy of ∼690 Mb compared with the estimated genome size of R. auricularia (1.6 Gb) results from a high repeat content of 70% mainly comprising DNA transposons. The annotation of 17,338 protein coding genes was supported by the use of publicly available transcriptome data. This draft will serve as starting point for further genomic and population genetic research in this scientifically important phylum