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1.
Wellcome Open Res ; 8: 192, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37351546

RESUMO

We present a genome assembly from an individual male Pheosia gnoma (the Lesser Swallow Prominent; Arthropoda; Insecta; Lepidoptera; Notodontidae). The genome sequence is 271.3 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 17.0 kilobases in length. Gene annotation of this assembly on Ensembl identified 11,628 protein coding genes.

2.
Mol Cancer Res ; 21(5): 411-427, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36669126

RESUMO

The nuclear deubiquitylase BRCA1-associated protein 1 (BAP1) is frequently inactivated in malignant pleural mesothelioma (MPM) and germline BAP1 mutation predisposes to cancers including MPM. To explore the influence on cell physiology and drug sensitivity, we sequentially edited a predisposition mutation (w-) and a promoter trap (KO) into human mesothelial cells. BAP1w-/KO MeT5A cells express less BAP1 protein and phenocopy key aspects of BAP1 loss in MPM. Stable isotope labeling with amino acids in cell culture-mass spectrometry revealed evidence of metabolic adaptation, with concomitant alteration of cellular metabolites. In MeT5A, BAP1 deficiency reduces glycolytic enzyme levels but increases enzymes involved in the tricarboxylic acid cycle and anaplerotic pathways. Notably both argininosuccinate synthase 1 (ASS1), essential for cellular synthesis of arginine, and its substrate aspartate, are elevated in BAP1w-/KO MeT5A cells. Likewise, ASS1 expression is higher in BAP1-altered MPM cell lines, and inversely correlates with BAP1 in The Cancer Genome Atlas MESO dataset. Elevated ASS1 is also evident by IHC staining in epithelioid MPM lacking nuclear BAP1 expression, with improved survival among patients with BAP1-negative/ASS1-expressing tumors. Alterations in arginine metabolism may sensitize cells to metabolic drugs and we find that BAP1-negative/ASS1-expressing MPM cell lines are more sensitive to ASS1 inhibition, although not to inhibition of purine synthesis by mizoribine. Importantly, BAP1w-/KO MeT5A become desensitized to arginine deprivation by pegylated arginine deiminase (ADI-PEG20), phenocopying BAP1-negative/ASS1-expressing MPM cell lines. IMPLICATIONS: Our data reveal an interrelationship between BAP1 and arginine metabolism, providing a potential means of identifying patients with epithelioid MPM likely to benefit from ADI-PEG20.


Assuntos
Mesotelioma Maligno , Mesotelioma , Humanos , Argininossuccinato Sintase/genética , Argininossuccinato Sintase/metabolismo , Ubiquitina Tiolesterase/genética , Aminoácidos , Arginina/metabolismo , Mesotelioma/tratamento farmacológico , Mesotelioma/genética , Linhagem Celular Tumoral , Proteínas Supressoras de Tumor/genética
3.
Wellcome Open Res ; 8: 219, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38903245

RESUMO

We present a genome assembly from an individual male Hedya salicella (the White-backed Marble; Arthropoda; Insecta; Lepidoptera; Tortricidae). The genome sequence is 742.3 megabases in span. Most of the assembly is scaffolded into 25 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 16.3 kilobases in length. Gene annotation of this assembly on Ensembl identified 11,961 protein coding genes.

4.
Wellcome Open Res ; 7: 288, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37767014

RESUMO

We present a genome assembly from an individual male Adalia bipunctata (the two-spot ladybird; Arthropoda; Insecta; Coleoptera; Coccinellidae). The genome sequence is 475 megabases in span. Most of the assembly (94.87%) is scaffolded into 11 chromosomal pseudomolecules, with the X and Y sex chromosomes assembled. The complete mitochondrial genome was also assembled and is 21.2 kilobases in length. Gene annotation of this assembly in Ensembl identified 13,611 protein coding genes.

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