Environmentally friendly carrageenan-based ionic-liquid driven soft actuators

UID/FIS/04650/2020 UID/QUI/0686/2020 LA/P/0008/2020 PID2019-106099RB-C43/AEI/10.13039/501100011033A naturally derived polymer based on iota carrageenan and different ammonium and imidazolium based ionic liquids (ILs) are used for the development of environmentally friendly soft actuators. The influence of IL content and type and solvent evaporation temperature on the morphological and physico-chemical properties of the materials was evaluated, together with the effect on actuator functional response. Independently of the IL content and type, and the solvent evaporation temperature, a non-porous structure is obtained. The incorporation of the IL within the polymer matrix does not affect the thermal stability but leads to a decrease in the Young modulus for the different IL/carrageenan samples. The highest influence was observed by using the [Ch][DHP] IL at a filler content of 40% w/w with a decrease in the Young modulus from 748 MPa for the neat polymer to 145 MPa for the [Ch][DHP]/carrageenan sample. Furthermore, the ionic conductivity of the samples increases with increasing IL content, with the highest values being 2.9 × 10-6 S cm-1 and 1.2 × 10-6 S cm-1 for the samples with 40% w/w of [Bmim][FeCl4] and [Ch][DHP], respectively. Regarding the soft actuator performance, the maximum displacement was obtained for the [Ch][DHP]/carrageenan sample with an IL content of 40% w/w, showing a maximum displacement of 5.8 mm at a DC applied voltage of 9 V.publishersversionpublishe

Novel transposable elements from Anopheles gambiae

<p>Abstract</p> <p>Background</p> <p>Transposable elements (TEs) are DNA sequences, present in the genome of most eukaryotic organisms that hold the key characteristic of being able to mobilize and increase their copy number within chromosomes. These elements are important for eukaryotic genome structure and evolution and lately have been considered as potential drivers for introducing transgenes into pathogen-transmitting insects as a means to control vector-borne diseases. The aim of this work was to catalog the diversity and abundance of TEs within the <it>Anopheles gambiae </it>genome using the PILER tool and to consolidate a database in the form of a hyperlinked spreadsheet containing detailed and readily available information about the TEs present in the genome of <it>An. gambiae</it>.</p> <p>Results</p> <p>Here we present the spreadsheet named AnoTExcel that constitutes a database with detailed information on most of the repetitive elements present in the genome of the mosquito. Despite previous work on this topic, our approach permitted the identification and characterization both of previously described and novel TEs that are further described in detailed.</p> <p>Conclusions</p> <p>Identification and characterization of TEs in a given genome is important as a way to understand the diversity and evolution of the whole set of TEs present in a given species. This work contributes to a better understanding of the landscape of TEs present in the mosquito genome. It also presents a novel platform for the identification, analysis, and characterization of TEs on sequenced genomes.</p

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Structural organization of ionic liquids embedded in fluorinated polymers

Hybrid materials based on ionic liquids (ILs) and polymers are increasingly being used for the development of smart and multifunctional materials, allowing to tune polymer properties or introduce new ones. Nonetheless, the structural organization of ILs within the polymer matrix is not properly understood. This work reports on the structural organization of different ILs incorporated into polyvinylidene fluoride (PVDF) films. The effect of IL type ([Pmim][TFSI], [Pmpip][TFSI], [Bmim]2[NiCl4] and [Bmim][FeCl4) incorporated into the PVDF matrix on the structural organization was evaluated and correlated to the observed variations in the morphological and physical-chemical properties. [Bmim][FeCl4] and [Bmim]2[NiCl4] leads to highly porous structures and the incorporation of ILs into the polymer matrix increases the electroactive β phase content of PVDF. Different structural organization of the hybrid materials at nanoscale has been found by small-angle neutron scattering experiments. Whereas just single polydisperse objects with average size of about 5 nm have been found in PVDF/[Pmim][TFSI] and PVDF/[Pmpip][TFSI] samples, more complex fractal-like organization of pores are present in PVDF/[Bmim][FeCl4] and PVDF/[Bmim]2[NiCl4]. Thus, IL type influences both the morphology and the electroactive phase of the polymer. Complex fractal-like organization observed for [Bmim][FeCl4] and [Bmim]2[NiCl4] into the PVDF matrix allows a porous morphology, while single polydispersed particles of [Pmpip][TFSI] or [Pmpip][TFSI] into PVDF favors strong ion-dipole interactions between the IL and the polymer matrix, resulting in higher electroactive β phase contents.We thank the Fundação para a Ciência e Tecnologia- FCT, for financial support under the framework of the Strategic Funding UID/FIS/04650/2021, UIDB/50006/2020, UIDP/50006/2020, and LA/P/0008/2020, projects PTDC/FIS-MAC/28157/2017, and PTDC/BTM-MAT/28237/2017 and grants SFRH/BD/145345/2019 (LCF), and SFRH/BPD/121526/2016 (DMC). The authors thank funding by the Spanish State Research Agency (AEI) and the European Regional Development Fund (ERFD) through the project PID2019-106099RB-C43/AEI/ 10.13039/501100011033. and from the Basque Government Industry Department under the ELKARTEK program

Environmentally friendly carrageenan-based ionic-liquid driven soft actuators

Naturally derived polymer based on iota carrageenan and different ammonium and imidazolium based ionic liquids (ILs) are used for the development of environmentally friendly soft actuators. The influence of IL content and type and solvent evaporation temperature on the morphological and physico-chemical properties of the materials was evaluated, together with the effect on actuator functional response. Independently of the IL content, type, and solvent evaporation temperature a non-porous structure is obtained. The incorporation of the IL within the polymer matrix does not affect the thermal stability but leads to a decrease in the Young Modulus for the different IL/carrageenan samples. The highest influence was observed by using the [Ch][DHP] IL at a filler content of 40 w/w % with a decrease in the Young Modulus from 748 MPa for the neat polymer to 145 MPa for the [Ch][DHP]/carrageenan sample. Further, the ionic conductivity of the samples increases with increasing IL content, with the highest values being 2.9×10-6 S/cm and 1.2 ×10-6 S/cm for the samples with 40 w/w % of [Bmim][FeCl4] and [Ch][DHP], respectively. Regarding the soft actuator performance, the maximum displacement was obtained for the [Ch][DHP]/carrageenan sample with an IL content of 40 w/w %, showing a maximum displacement of 5.8 mm at a DC applied voltage of 9 V.Work supported by the Portuguese Foundation for Science and Technology (FCT) under strategic funding UID/FIS/04650/2020, UID/QUI/0686/2020, UIDB/50006/2020 and UIDP/50006/2020, project PTDC/FIS-MAC/28157/2017, and grants SFRH/BD/145345/2019 (LCF), SFRH/BPD/121526/2016 (D.M.C), and Investigator FCT Contract 2020.04028.CEECIND (C.M.C.). The authors thank funding by the Spanish State Research Agency (AEI) and the European Regional Development Fund (ERFD) through the project PID2019-106099RB-C43 / AEI / 10.13039/501100011033. The authors also acknowledge funding from the Basque Government Industry and Education Departments under the ELKARTEK, HAZITEK and PIBA (PIBA-2018-06) programs, respectively. Technical and human support provided by SGIker (UPV/EHU, MICINN, GV/EJ, EGEF and ESF) is gratefully acknowledge

PeSV-Fisher: identification of somatic and non-somatic structural variants using nextgeneration sequencing data

Next-generation sequencing technologies expedited research to develop efficient computational tools for the identification of structural variants (SVs) and their use to study human diseases. As deeper data is obtained, the existence of higher complexity SVs in some genomes becomes more evident, but the detection and definition of most of these complex rearrangements is still in its infancy. The full characterization of SVs is a key aspect for discovering their biological implications. Here we present a pipeline (PeSV-Fisher) for the detection of deletions, gains, intra- and inter-chromosomal translocations, and inversions, at very reasonable computational costs. We further provide comprehensive information on co-localization of SVs in the genome, a crucial aspect for studying their biological consequences. The algorithm uses a combination of methods based on paired-reads and read-depth strategies. PeSV-Fisher has been designed with the aim to facilitate identification of somatic variation, and, as such, it is capable of analysing two or more samples simultaneously, producing a list of non-shared variants between samples. We tested PeSV-Fisher on available sequencing data, and compared its behaviour to that of frequently deployed tools (BreakDancer and VariationHunter). We have also tested this algorithm on our own sequencing data, obtained from a tumour and a normal blood sample of a patient with chronic lymphocytic leukaemia, on which we have also validated the results by targeted re-sequencing of different kinds of predictions. This allowed us to determine confidence parameters that influence the reliability of breakpoint predictions.This work was supported by AGAUR (Generalitat de Catalunya, 2009 SGR 1502) (X.E.); CIBERESP (Instituto de Salud Carlos III) (G.E.); ESGI (European Commission, 262055_ESGI) (R.R., X.E.), ENGAGE (European Commission, ENGAGE_201413), TECHGENE (European Commission, TECHGENE_223143), and GEUVADIS (European Commission, 261123_GEUVADIS) (X.E.); NOVADIS (Ministerio de Ciencia y Technologia, SAF2008-00357) (X.E.); Galicia Government Xunta de Galicia (Spain) through the project number 10PXIB918057 (J.M.C.T.); MAEC-AEC1 Predoctoral Fellowship (Ministerio de Asuntos Exteriores y Cooperación, Spain) (A.M.F.); and Ramón y Cajal position and grant BFU2007-60930 (Ministerio de Educación y Ciencia) (M.C.)

Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research