Richard D. Kelly

Ceralasertib plus durvalumab in Ras mutant and Ras wild type advanced non-small cell lung cancer: Two cohorts of the phase II platform National Lung Matrix Trial

Gary Middleton, Richard Buchanan, Joshua Savage, Joe De La Mata Chicharro et autres

PURPOSE: Pre-clinical data suggests that ceralasertib, a potent ATR inhibitor, might reverse resistance to anti-PD-(L)1 in KRAS mutant lung adenocarcinoma (LUAD). Activity of ceralasertib/durvalumab was, therefore, assessed in two prospective, parallel immune checkpoint blockade (ICB)-resistant cohorts, one harbouring KRAS mutations (J1), the …

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Sex specific effects of a high fat diet on metabolism, cognition, and pathology in the Tg-SwDI mouse model of Alzheimer’s disease

Shelby Sabourin, Christina A. Thrasher, Rachel M. Smith, Kasey Belanger-Mayer et autres

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in the US, with over 80% of affected individuals experiencing comorbid metabolic disease. Along with age and sex, metabolic syndrome and prediabetes are known risk factors for developing dementia and AD, highlighting …

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Additional file 1 of Loss of ovarian hormones is detrimental in early disease stages of mouse models of Alzheimer’s disease and multi-etiology dementia

Charly Abi-Ghanem, Alex K. Opiela, Aaron S. Paul, McKenzie L. Comito et autres

Additional file 1.

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Additional file 1 of Loss of ovarian hormones is detrimental in early disease stages of mouse models of Alzheimer’s disease and multi-etiology dementia

Charly Abi-Ghanem, Alex K. Opiela, Aaron S. Paul, McKenzie L. Comito et autres

Additional file 1.

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Loss of ovarian hormones is detrimental in early disease stages of mouse models of Alzheimer’s disease and multi-etiology dementia

Charly Abi‐Ghanem, Alex K. Opiela, Aaron S. Paul, Hao Li et autres

BACKGROUND: Up to 80% of Alzheimer's disease (AD) patients suffer from brain vascular damage resulting in multi-etiology dementia (MED). Sex is a well-known risk factor for dementia; out of three AD patients two are women. 17β-estradiol, a predominant ovarian hormone in woman …

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Sex Specific Effects of a High Fat Diet on Metabolism, Cognition, and Pathology in the Tg-SwDI Mouse Model of Alzheimer’s Disease

Shelby Sabourin, Christina A Thrasher, Rachel M. Smith, Kasey M Belanger‐Mayer et autres

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The 7SK small nuclear ribonucleoprotein links the cell responses to transcription and replication stress by promoting replication fork reversal and homologous recombination

Akhil Bowry, Claire Wilson, Richard D. Kelly, RJ Wilkins et autres

Abstract The 7SK-small nuclear ribonucleoprotein complex (7SK-snRNP) plays a crucial role in the response to transcription stress, releasing positive transcription elongation factor P-TEFb to sustain RNA polymerase II activity when transcription is blocked. Many conditions that block transcription also block DNA replication, …

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Human RNase H2 upregulation counteracts oncogene- and chemotherapy-induced replication stress

RJ Wilkins, Siobhan A. Plass, Claire Wilson, Richard D. Kelly et autres

RNase H2 is a heterotrimeric endoribonuclease that resolves RNA:DNA hybrids and genome-embedded ribonucleotides, which are implicated in DNA replication stress and cancer development. Protein and/or mRNA levels of individual RNase H2 subunits are elevated in some cancers, but little is known about …

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Interactions between menopause and high‐fat diet on cognition and pathology in a mouse model of Alzheimer's disease

Charly Abi‐Ghanem, Richard D. Kelly, Emily Groom, Caitlin G. Valerian et autres

INTRODUCTION: Post-menopausal women constitute about two-thirds of those with Alzheimer's disease (AD). Menopause increases dementia risk by heightening the likelihood of metabolic disease, a well-known risk factor for dementia. We aimed to determine the effects of menopause and high-fat diet (HF) on …

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Human RNase H2 upregulation counteracts oncogene- and chemotherapy-induced replication stress

RJ Wilkins, Siobhan A. Plass, Claire Wilson, Richard D. Kelly et autres

Abstract RNase H2 is a heterotrimeric endoribonuclease that resolves RNA:DNA hybrids and genome-embedded ribonucleotides, which are implicated in DNA replication stress and cancer development. Protein and/or mRNA levels of individual RNase H2 subunits are elevated in some cancers, but little is known …

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The histone demethylase KDM5 has insulator activity in the brain

Matanel Yheskel, Melissa Castiglione, Richard D. Kelly, Simone Sidoli et autres

Abstract KDM5 family proteins are best known for their demethylation of the promoter proximal chromatin mark H3K4me3. KDM5-regulated transcription is critical in the brain, with variants in the X-linked paralog KDM5C causing the intellectual disability (ID) disorder Claes-Jensen syndrome. Although the demethylase …

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Effects of menopause in a mouse model of Alzheimer’s disease and comorbid metabolic disease

Charly Abi‐Ghanem, Abigail E. Salinero, Richard D. Kelly, Krystyna A. Rybka et autres

Abstract Background About two‐thirds of those with Alzheimer’s disease (AD) are women, most of whom are post‐menopausal. Menopause accelerates the risk for dementia by increasing the risk for metabolic, cardiovascular, and cerebrovascular diseases. Mid‐life metabolic disease (e.g. obesity, diabetes, or prediabetes) is …

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