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1دورية أكاديمية
المؤلفون: Claudia A. Chiriboga, Claudio Bruno, Tina Duong, Dirk Fischer, Eugenio Mercuri, Janbernd Kirschner, Anna Kostera-Pruszczyk, Birgit Jaber, Ksenija Gorni, Heidemarie Kletzl, Imogen Carruthers, Carmen Martin, Francis Warren, Renata S. Scalco, Kathryn R. Wagner, Francesco Muntoni, the JEWELFISH Study Group
المصدر: Neurology and Therapy, Vol 12, Iss 2, Pp 543-557 (2023)
مصطلحات موضوعية: Evrysdi, Pharmacodynamics, Risdiplam, Safety, Spinal muscular atrophy, Neurology. Diseases of the nervous system, RC346-429
الوصف: Abstract Introduction Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier for the treatment of patients with spinal muscular atrophy (SMA). The JEWELFISH study (NCT03032172) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of risdiplam in previously treated pediatric and adult patients with types 1–3 SMA. Here, an analysis was performed after all patients had received at least 1 year of treatment with risdiplam. Methods Patients with a confirmed diagnosis of 5q-autosomal recessive SMA between the ages of 6 months and 60 years were eligible for enrollment. Patients were previously enrolled in the MOONFISH study (NCT02240355) with splicing modifier RG7800 or treated with olesoxime, nusinersen, or onasemnogene abeparvovec. The primary objectives of the JEWELFISH study were to evaluate the safety and tolerability of risdiplam and investigate the PK after 2 years of treatment. Results A total of 174 patients enrolled: MOONFISH study (n = 13), olesoxime (n = 71 patients), nusinersen (n = 76), onasemnogene abeparvovec (n = 14). Most patients (78%) had three SMN2 copies. The median age and weight of patients at enrollment was 14.0 years (1–60 years) and 39.1 kg (9.2–108.9 kg), respectively. About 63% of patients aged 2–60 years had a baseline total score of less than 10 on the Hammersmith Functional Motor Scale–Expanded and 83% had scoliosis. The most common adverse event (AE) was upper respiratory tract infection and pyrexia (30 patients each; 17%). Pneumonia (four patients; 2%) was the most frequently reported serious AE (SAE). The rates of AEs and SAEs per 100 patient-years were lower in the second 6-month period compared with the first. An increase in SMN protein was observed in blood after risdiplam treatment and was comparable across all ages and body weight quartiles. Conclusions The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients.
وصف الملف: electronic resource
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2دورية أكاديمية
المؤلفون: Claudia A. Chiriboga, Claudio Bruno, Tina Duong, Dirk Fischer, Eugenio Mercuri, Janbernd Kirschner, Anna Kostera-Pruszczyk, Birgit Jaber, Ksenija Gorni, Heidemarie Kletzl, Imogen Carruthers, Carmen Martin, Francis Warren, Renata S. Scalco, Kathryn R. Wagner, Francesco Muntoni, the JEWELFISH Study Group
المصدر: Neurology and Therapy, Vol 12, Iss 5, Pp 1799-1801 (2023)
مصطلحات موضوعية: Neurology. Diseases of the nervous system, RC346-429
وصف الملف: electronic resource
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3دورية أكاديمية
المؤلفون: Strehlow, Brian, W, Schuster, Astrid, Francis, Warren, R, Eckford-Soper, Lisa, Kraft, Beate, Mcallen, Rob, Nielsen, Ronni, Mandrup, Susanne, Canfield, Donald, E
المساهمون: La Rochelle Université (ULR), LIttoral ENvironnement et Sociétés (LIENSs), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), University of Southern Denmark (SDU), University College Cork (UCC)
المصدر: ISSN: 2804-3871.
مصطلحات موضوعية: [SDV]Life Sciences [q-bio], [SDE]Environmental Sciences
الوصف: International audience ; Abstract Deoxygenation can be fatal for many marine animals; however, some sponge species are tolerant of hypoxia and anoxia. Indeed, two sponge species, Eurypon sp. 2 and Hymeraphia stellifera, survive seasonal anoxia for months at a time. To understand their tolerance mechanisms, we performed differential gene expression analyses on the sponges, their mitochondria and their microbial symbionts under in situ conditions of normoxia, hypoxia and anoxia. Each species possessed a unique microbiome, but the microbiomes of each species were dominated by a species-specific Thaumarchaeon and a Gammaproteobacterium . Holobiont gene expression was species- and oxygen-level dependent, though there were some shared interspecific responses to deoxygenation. In general, few changes occurred in the expression of sponge metabolic genes as a function of oxygenation level, indicating that they may remain metabolically active under anoxia. However, ATP synthesis genes were significantly upregulated under hypoxia when compared to normoxia, and genes for DNA replication were downregulated. Mitochondrial gene expression was effectively unchanged under both hypoxia and anoxia. Nevertheless, both anoxia and hypoxia caused upregulation of heat shock proteins (HSPs), indicating cellular level adaptations to deoxygenation stress. A meta-analysis demonstrated that sponge transcriptional responses to anoxia were distinct from those displayed by other invertebrates while dormant, and the hypothesis of sponge dormancy under anoxia was not supported. Thaumarchaeota symbionts also upregulated stress response genes in hypoxia, while maintaining expression of oxygen-dependent metabolic pathways under hypoxia and anoxia. Gammaproteobacteria symbionts showed relatively few noteworthy changes in gene expression in response to anoxia but decreased metabolic gene expression in hypoxia. There was no clear evidence of upregulated anaerobic respiration in the transcriptomes of the sponge holobionts under anoxia or hypoxia. The ...
العلاقة: hal-04559632; https://univ-rochelle.hal.science/hal-04559632Test; https://univ-rochelle.hal.science/hal-04559632/documentTest; https://univ-rochelle.hal.science/hal-04559632/file/10_24072_pcjournal_410.pdfTest
الإتاحة: https://doi.org/10.24072/pcjournal.410Test
https://univ-rochelle.hal.science/hal-04559632Test
https://univ-rochelle.hal.science/hal-04559632/documentTest
https://univ-rochelle.hal.science/hal-04559632/file/10_24072_pcjournal_410.pdfTest -
4دورية أكاديمية
المؤلفون: Strehlow, Brian W., Schuster, Astrid, Francis, Warren R., Eckford-Soper, Lisa, Kraft, Beate, McAllen, Rob, Nielsen, Ronni, Mandrup, Susanne, Canfield, Donald E.
وصف الملف: application/pdf; image/vnd.djvu
العلاقة: 10_24072_pcjournal_410; https://peercommunityjournal.org/articles/10.24072/pcjournal.410Test/; oai:centre-mersenne.org:10_24072_pcjournal_410; citation: Peer Community Journal, 4 (2024) p -; rdoi 10.24072/pci.zool.100211; preprint 10.1101/2023.02.27.530229
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5دورية أكاديمية
المؤلفون: Schultz, Darrin T, Eizenga, Jordan M, Corbett-Detig, Russell B, Francis, Warren R, Christianson, Lynne M, Haddock, Steven HD
مصطلحات موضوعية: Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Generic health relevance, Ctenophore, Mitochondria, Mitogenome, Selection, Evolution, Bioinformatics, URF, ORF, Bayesian, Sequencing, Medical and Health Sciences
الوصف: To date, five ctenophore species' mitochondrial genomes have been sequenced, and each contains open reading frames (ORFs) that if translated have no identifiable orthologs. ORFs with no identifiable orthologs are called unidentified reading frames (URFs). If truly protein-coding, ctenophore mitochondrial URFs represent a little understood path in early-diverging metazoan mitochondrial evolution and metabolism. We sequenced and annotated the mitochondrial genomes of three individuals of the beroid ctenophore Beroe forskalii and found that in addition to sharing the same canonical mitochondrial genes as other ctenophores, the B. forskalii mitochondrial genome contains two URFs. These URFs are conserved among the three individuals but not found in other sequenced species. We developed computational tools called pauvre and cuttlery to determine the likelihood that URFs are protein coding. There is evidence that the two URFs are under negative selection, and a novel Bayesian hypothesis test of trinucleotide frequency shows that the URFs are more similar to known coding genes than noncoding intergenic sequence. Protein structure and function prediction of all ctenophore URFs suggests that they all code for transmembrane transport proteins. These findings, along with the presence of URFs in other sequenced ctenophore mitochondrial genomes, suggest that ctenophores may have uncharacterized transmembrane proteins present in their mitochondria.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/3265x4m2Test
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6دورية أكاديمية
المؤلفون: Mark Francis Warren, Jason Ali-Lavroff, Damien Holloway, Teresa Magoga
مصطلحات موضوعية: Uncategorised value
الوصف: Linear elastic fracture mechanics methods provide a more comprehensive representation of crack propagation compared to traditional methods such as the linear damage hypothesis (or SN curve approach). These techniques have been widely adopted in the aerospace industry, however, their usage in the design of marine structures remains limited. The presented research uses full-scale trial data measured onboard a 111 m wavepiercing catamaran to compare the results obtained from linear elastic fracture mechanics and SN curve-based methods. The results reveal significant differences in estimated fatigue life between SN curve-based methods and fracture mechanics methods. These differences are likely due to limitations in the fracture mechanics model during the crack initiation phase. Changes in fracture mechanics parameters also had a significant effect on fatigue life, suggesting that if accuracy is important then material specific parameters are required. Despite the limitations shown, linear elastic fracture mechanics methods have a higher level of tailor-ability when compared to SN curve based methods and could offer benefits in situations such as the tracking of known flaws or in the assessment of changes to vessel configuration, or usage profiles
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7تقرير
المؤلفون: Strehlow, Brian, W, Schuster, Astrid, Francis, Warren, R, Eckford-Soper, Lisa, Kraft, Beate, Mcallen, Rob, Nielsen, Ronni, Mandrup, Susanne, Canfield, Donald, E
المساهمون: LIttoral ENvironnement et Sociétés (LIENSs), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), Nordic Centre of Earth Evolution (NORDCEE), University of Copenhagen = Københavns Universitet (UCPH), University College Cork (UCC), University of Southern Denmark (SDU), This project was funded by Villum Fonden grant no. 16518. B.K. was funded by the Villum Young Investigator Grant 25491.
المصدر: https://univ-rochelle.hal.science/hal-04302251Test ; 2023.
مصطلحات موضوعية: [SDV.BA]Life Sciences [q-bio]/Animal biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
الوصف: Deoxygenation can be fatal for many marine animals; however, some sponge species are tolerant of hypoxia and anoxia. Indeed, two sponge species, Eurypon sp. 2 and Hymeraphia stellifera, survive seasonal anoxia for months at a time. To understand their tolerance mechanisms, we performed differential gene expression analyses on the sponges, their mitochondria and their microbial symbionts under in situ conditions of normoxia, hypoxia and anoxia. Each species possessed a unique microbiome, but the microbiomes of each species were dominated by a species-specific Thaumarchaeon and a Gammaproteobacterium . Holobiont gene expression was species- and oxygen-level dependent, though there were some shared interspecific responses to deoxygenation. In general, few changes occurred in the expression of sponge metabolic genes as a function of oxygenation level, indicating that they may remain metabolically active under anoxia. However, ATP synthesis genes were significantly upregulated under hypoxia when compared to normoxia, and genes for DNA replication were downregulated. Mitochondrial gene expression was effectively unchanged under both hypoxia and anoxia. Nevertheless, both anoxia and hypoxia caused upregulation of heat shock proteins (HSPs), indicating cellular level adaptations to deoxygenation stress. A meta-analysis demonstrated that sponge transcriptional responses to anoxia were distinct from those displayed by other invertebrates while dormant, and the hypothesis of sponge dormancy under anoxia was not supported. Thaumarchaeota symbionts also upregulated stress response genes in hypoxia, while maintaining expression of oxygen-dependent metabolic pathways under hypoxia and anoxia. Gammaproteobacteria symbionts showed relatively few noteworthy changes in gene expression in response to anoxia but decreased metabolic gene expression in hypoxia. There was no clear evidence of upregulated anaerobic respiration in the transcriptomes of the sponge holobionts under anoxia or hypoxia. The tolerance of some sponges ...
العلاقة: hal-04302251; https://univ-rochelle.hal.science/hal-04302251Test; https://univ-rochelle.hal.science/hal-04302251/documentTest; https://univ-rochelle.hal.science/hal-04302251/file/2023.02.27.530229v3.full.pdfTest; BIORXIV: 2023.02.27.530229
الإتاحة: https://doi.org/10.1101/2023.02.27.530229Test
https://univ-rochelle.hal.science/hal-04302251Test
https://univ-rochelle.hal.science/hal-04302251/documentTest
https://univ-rochelle.hal.science/hal-04302251/file/2023.02.27.530229v3.full.pdfTest -
8دورية أكاديمية
المصدر: Strehlow , B W , Schuster , A , Francis , W R & Canfield , D E 2022 , ' Metagenomic data for Halichondria panicea from Illumina and nanopore sequencing and preliminary genome assemblies for the sponge and two microbial symbionts ' , BMC Research Notes , vol. 15 , 135 . https://doi.org/10.1186/s13104-022-06013-3Test
مصطلحات موضوعية: Halichondria panicea, Hologenome, Metagenome, Microbiome, Objective, Porifera, Metagenomics, Nanopore Sequencing, Sequence Analysis, DNA, Microbiota, Animals, Porifera/genetics, High-Throughput Nucleotide Sequencing
الوصف: Objectives: These data were collected to generate a novel reference metagenome for the sponge Halichondria panicea and its microbiome for subsequent differential expression analyses. Data description: These data include raw sequences from four separate sequencing runs of the metagenome of a single individual of Halichondria panicea—one Illumina MiSeq (2 × 300 bp, paired-end) run and three Oxford Nanopore Technologies (ONT) long-read sequencing runs, generating 53.8 and 7.42 Gbp respectively. Comparing assemblies of Illumina, ONT and an Illumina-ONT hybrid revealed the hybrid to be the ‘best’ assembly, comprising 163 Mbp in 63,555 scaffolds (N50: 3084). This assembly, however, was still highly fragmented and only contained 52% of core metazoan genes (with 77.9% partial genes), so it was also not complete. However, this sponge is an emerging model species for field and laboratory work, and there is considerable interest in genomic sequencing of this species. Although the resultant assemblies from the data presented here are suboptimal, this data note can inform future studies by providing an estimated genome size and coverage requirements for future sequencing, sharing additional data to potentially improve other suboptimal assemblies of this species, and outlining potential limitations and pitfalls of the combined Illumina and ONT approach to novel genome sequencing.
وصف الملف: application/pdf
العلاقة: https://portal.findresearcher.sdu.dk/da/publications/10111f64-5973-4ab7-b7f1-7b7cce763510Test
الإتاحة: https://doi.org/10.1186/s13104-022-06013-3Test
https://portal.findresearcher.sdu.dk/da/publications/10111f64-5973-4ab7-b7f1-7b7cce763510Test
https://findresearcher.sdu.dk/ws/files/201744896/s13104_022_06013_3.pdfTest -
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المؤلفون: Wörheide, Gert, Francis, Warren R.
الوصف: Release for Zenodo archiving upon publication ...
العلاقة: https://github.com/PalMuc/2Tethya_genomes/tree/v.1.0.1Test; https://dx.doi.org/10.5281/zenodo.10991740Test
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10دورية أكاديمية
المؤلفون: Haddock, Steven H.D., Christianson, Lynne M., Francis, Warren R., Martini, Séverine, Dunn, Casey W., Pugh, Philip R., Mills, Claudia E., Osborn, Karen J., Seibel, Brad A., Choy, C. Anela, Schnitzler, Christine E., Matsumoto, George I., Messié, Monique, Schultz, Darrin T., Winnikoff, Jacob R., Powers, Meghan L., Gasca, Rebeca, Browne, William E., Johnsen, Sönke, Schlining, Kyra L., von Thun, Susan, Erwin, Benjamin E., Ryan, Joseph F., Thuesen, Erik V.
المصدر: Oceanography, 2017 Dec 01. 30(4), 38-47.
الوصول الحر: https://www.jstor.org/stable/26367624Test
النص الكامل